SECTION 6 Old age medicine

6.1 Ageing and clinical medicine 511

6.1 Ageing and clinical medicine 511

6.1 Ageing and clinical medicine Claire Steves and Neil Pendleton ESSENTIALS In 2017 there were, for the first time, more people older than 65 years than children under the age of 5 years. Despite the recent exponential increase in human lifespan, health-​span has not kept pace, and variability between countries in healthy lifespan exceeds that of life expectancy. The increase in morbidity as people age is largely explained by loss of physiological reserve capacity in multiple systems simul- taneously, which is termed frailty. Recent evidence suggests that different heritable (intrinsic factors) factors drive the ageing of dif- ferent organ systems, but diverse systems share environmental (or extrinsic) drivers. Ageing is associated with macromolecular changes (molecular damage); changes in nutrient sensing, metabolism, and metabolic signalling; senescence in stem cells; altered intercellular commu- nication, in particular changes associated with inflammaging; and changes in circadian rhythms and the hypothalamo-​pituitary-​ adrenal axis. We need to better understand these processes to meet the challenge set by extension in lifespan and achieve healthy ageing and reduction in age-​associated disease. Introduction Population ageing has seen unprecedented changes in human demographics across the world. Estimates are that in 2017 people older than 65  years will outnumber under 5-​year-​olds and, by 2050, more than a fifth of the world population will be over 60  years (Fig. 6.1.1). However, despite this recent exponential increase in human lifespan, health-​span has not kept pace, and variability between countries in healthy lifespan exceeds that of life expectancy (Fig. 6.1.2). The increase in morbidity is largely explained by loss of physiological reserve capacity in multiple sys- tems simultaneously, resulting in reduced resistance to stressors. This has been characterized as frailty, a multidimensional state which predicts adverse health events and mortality. Ageing and frailty are separate concepts. Any attempt to look at the mechanisms underpinning ageing must consider the relation- ship between time-​dependent functional decline despite optimal conditions—​‘intrinsic ageing’—​and the real-​life development of frailty syndromes, which may more reflect inactivity, stress, and exposure—​‘stressed ageing’. The extension in lifespan we have seen sets a new challenge to investigate the potential for healthy ageing and reduction in age-​associated disease. Heritability studies in twins show that population variance in frailty and many diseases of old age arise largely due to a combination of heritable effects (shared more by monozygotic twins) and environmental effects unique to individuals, which include stochastic variations. Few genetic links to longevity or frailty have been established in humans, which is likely to be due to a large number of small effects under the threshold of detection. Notable exceptions are the APOE genotype, and the INK4a-​INK4b locus. Studies in mammals have identified various interesting targets that appear to prolong life and re- duce disability—​in particular the target of rapamycin (TOR) pathway, and insulin or insulin-​like growth factor 1 signalling system, discussed next. Recent evidence suggests that different heritable (intrinsic factors) factors drive the ageing of different organ systems, but diverse systems share environmental (or ex- trinsic) drivers. All branches of clinical medicine are seeing increases both in older adult patients and in the combinations of co​morbidities in the context of whole system ageing, due in part to common risk factors (Fig. 6.1.3). An appreciation of gerontology is therefore relevant for all physicians. A more collaborative approach between those working on chronic diseases such as cardiovascular disease, cancer, and dementia with underlying processes of ageing is needed. This chapter aims to provide clinicians with concise description of the interplay between human ageing and age-​related diseases. In add- ition, new potential therapeutic avenues for age-​related disease are arising from research into ageing in model animals and humans, and these are also discussed in this chapter. Macromolecular changes Molecular damage underpins most models of ageing, and some have conceptualized ageing as a consequence of an imbalance be- tween molecular damage and repair. Experimental biogerontology

512 Section 6  Old age medicine Age <5 Age 65+ 20% 15% 10% 5% 0% 1950 1960 1970 1980 1990 2000 2010 2020 2030 2040 2050 Fig. 6.1.1  Young children and older people as a percentage of Global Population 1950–​2050. From United Nations World Population Prospects, the 2010 Revision. Available at http://​esa.un.ord/​ unpd.wpp. (a) 20 24 22 20 18 16 14 12 10 8 HLYs at 50 years of age (years) 24 22 20 18 16 14 12 10 8 HLYs at 50 years of age (years) 22 24 26 28 30 32 Men (c) Men Women (b) Women NL GR MT DK LE HLYs LE HLYs BE LU PT SI CZ SK HU EE LT LV PL FR CY AT DE FI ES IE SE IT UK EE LT SK LV HU PT DE FI CY AT SI CZ BE IE NL SE GR UK PL MT DK LU ES FR IT 28 30 32 LE at 50 years of age (years) 34 36 14.53 18.42 15.92 14.77 23.64 9.05 12.86 18.01 13.56 19.78 10.78 18.91 20.63 11.02 11.49 17.99 21.68 20.21 16.48 14.90 12.28 15.34 19.16 20.22 19.74 33.70 33.39 32.86 30.72 31.94 30.52 34.15 35.37 33.41 33.02 29.40 33.24 35.31 29.32 29.90 33.60 32.74 33.28 31.23 32.92 29.96 32.44 35.02 34.05 32.69 15.66 18.66 13.71 16.26 24.12 10.42 13.87 19.74 13.55 20.81 11.39 20.17 20.86 12.74 11.86 18.16 22.58 20.40 20.16 12.67 13.07 17.25 18.62 20.31 20.78 Austria (AT) Belgium (BE) Cyprus (CY) Czech Republic (CZ) Denmark (DK) Estonia (EE) Finland (FI) France (FR) Germany (DE) Greece (GR) Hungary (HU) Ireland (IE) Italy (IT) Latvia (LV) Lithuania (LT) Luxembourg (LU) Malta (MT) Netherlands (NL) Poland (PL) Portugal (PT) Slovakia (SK) Slovenia (SI) Spain (ES) Sweden (SE) UK (UK) 29.08 28.67 29.52 25.61 28.30 22.42 28.48 29.57 28.96 29.43 22.72 29.50 30.37 21.31 21.74 28.78 29.07 29.14 24.62 28.12 23.68 26.81 29.48 30.28 29.46 Fig. 6.1.2  Inequalities in healthy life years in the 25 countries of the European Union in 2005, showing life expectancy (LE) and healthy life years (HLYs) at 50 years of age for all EU countries. HLYs, healthy life years; LE, life expectancy. (a) and (b) show scatter graphs for men and women, respectively. (C) Data for scatter graphs. From Jagger C, et al. (2008). Inequalities in healthy life years in the 25 countries of the European Union in 2005: a cross-​national meta-​regression analysis. Lancet, 372, 2124–​31, with permission from Elsevier.

6.1  Ageing and clinical medicine 513 has shown that damage to DNA, protein, lipids, and other molecules is associated with ageing in simple organisms, but it is not yet clear how the accumulation of molecular damage relates to age-​related disease and frailty in humans. Understanding the types and consequences of macromol- ecular damage associated with ageing will open up possibilities of intervening to redress the balance in favour of repair. However, protein, DNA, lipids, or other molecules do not function in isola- tion. Taking a network or systems approach allows integration of data across multiple levels of molecular change. This more holistic approach in biological gerontology has clear parallels with practice in clinical gerontology. One of the oldest theories in line with the damage/​repair balance has been the Free Radical/​Oxidative Stress Theory of Ageing, which postulated that oxidation damage decreased cellular func- tion resulting in reduction in system adaptability and an increase in development of pathology. However, it is becoming apparent that this theory is at least incomplete—​conflicting evidence comes from experimental models manipulating antioxidant enzyme systems, comparative studies in species which are naturally long-​lived, and age-​related disease and mortality in humans. Contradictions may be explained in part by the principle of hormesis—​that submaximal stress may actually be healthy. Genomic instability In DNA, damage has many forms, from point mutations to chromosomal gains and losses, and these changes accumulate with age and can manifest in age-​related cancer and cellular senescence, and link to pathological changes seen with age. Likewise loss of telomere length has long been associated with age. These protective caps of chromosomes shorten at each cell division, but can be rebuilt by repair enzymes in many cell types. Termination leads to replicative senescence and has been linked to diseases such as cancer. Whether telomere length acts as a marker or is a driver itself is not clear. Some evidence for the importance of DNA damage in ageing comes from progeroid genetic syndromes, which are characterized by some features of premature ageing. For example, loss of function of an acute thrombocytopenic purpura (ATP) dependent helicase in Werner’s syndrome leads to defects in DNA double strand breaks and enhanced telomere attrition, with the cellular consequences of increased cell death and senescence. Epigenetics Epigenetics can be considered operationally as a mitotically heritable feature or phenotype resulting from changes to the chromosome without alterations in DNA sequence. This involves changes in chromatin (DNA methylation and histone structure), transcription mechanisms, and non​coding ribonucleic acid (RNA). This is how molecular scientists can explain substantial differences in lifespan of animals such as worker ants and bees, versus the queen, who has the same genetic library, but differing reference systems. Recent research in epigenetics has identified some mechanisms underpinning intrinsic ageing. The Sirtuins family hold an im- portant role in age-​related diseases and organism lifespan. These are histone deacetylases and ADP-​ribosyltransferases which ap- pear to have a role in regulating genomic stability. Their effect on chromatin regulation demonstrates linkage between ageing and reproducible modifiers such as caloric restriction and exercise. The Sirtuins and specifically SIRT-​1 have been implicated in models of Alzheimer’s disease and diabetes mellitus. Using agents with direct effects on Sirtuins may mimic the positive ageing effect of calorie restriction. Organs/Systems Glucose intolerance Immune system dysfunction Sarcopenia Adiposity Endocrine system dysfunction Nervous system dysfunction Cardiovascular system dysfunction Renal dysfunction Respiratory system dysfunction Cells Genomic instability Mitochondria dysfunction Telomere attrition Cellular senescence Epigenetic alterations Loss of proteostasis Deregulated nutrient sensing Stem cell exhaustion Altered intercellular communication Organism Homeostasis breakdown with increased risk of failure Fig. 6.1.3  A hierarchical model of ageing from cells to organism. From Wu IC, et al. (2015). Biomedicine (Taipei), 5(1), 1.

514 Section 6  Old age medicine While at present there is no direct evidence that alterations in DNA methylation can extend animal lifespan, Horvath’s clock—​a combination of 353 methylation markers—​can pre- dict human age within four years, with a Pearson’s correlation coefficient of 0.96. As such it is currently the best biomarker for age. However, it is not yet clear whether this clock is helpful as a marker of age-​related morbidity, or whether the clock measures a biological process relevant to the variation in human lifespan. Epigenetics is thus seen as a exciting area of basic science re- search, translating the unrealized potential of the genome to understand mechanisms playing a role in human age-​related dis- ease. Such new insights may suggest targets for intervention. Modification in protein structure Maintenance of normal protein structure is a prerequisite of normal cellular function. Collectively the interactive network of functional proteins is called the proteome. Stressors constantly perturb the status quo by damaging proteins, resulting in aggregation. The cellular mechanism which monitors and manages the potentially damaging molecular aggregates of toxic material or misfolded proteins is called the proteostasis network. However, even within normal function, protein structural modifications need to occur to allow transport and assembly for correct function, with the resultant opportunity for damage in the form of altered conformational states. It is likely that this is why the complex system of proteostasis, with its chaperones and proteases, evolved. This network is both local and systemic. The ubiquitin-​based proteosome system is a key player in the management of cellular misfolded proteins, in which linkage of ubiquitin to the protein acts as signal for destruction. Although molecular chaperones such as ubiquitin can act by altering misfolding errors, their effects on damaged proteins is more di- verse. Chaperone molecules can also act as buffers to mutation-​ encoded abnormal protein structure. Ageing leads to greater levels of protein damage requiring management, but it also af- fects the efficiency of proteostasis. In this ‘Proteotoxicity’ model, damage can result in both enzymatic dysfunction and aggrega- tion, as is observed in several age-​related conditions such as car- diovascular, neurodegenerative disease, and cancer (Fig. 6.1.4). Proteosome management includes organelles, with mito- chondria being a key example. Mitochondria have a central role in cellular energy systems and generate reactive oxygen species. Delivering this function exposes these organelles to constant damage. In turn damaged mitochondria must be disaggregated and removed. Failure to adequately manage outputs from damaged mitochondria is seen with increasing age, and also in specific age-​ associated diseases such as Parkinson’s disease. While we understand the importance of individual proteins and the proteosome to healthy cell function, we know very little about systemic effects within organs or systems. We have some evidence of systemic effect of lifestyle via high fat intake, which can tip the balance in cellular proteostatic function leading to excess damaged aggregates. This can then lead to organ dysfunc- tion, disease phenotypes, and ageing. Autophagosome Heat shock Lysosome Chaperone-mediated autophagy Proteasomal degradation Unfolded protein Chaperone-mediated folding Refolded protein HSP HSF-1 Ageing Aggregation Oxidative stress Folded protein ER stress Hsc70 UbUbUbUb Macroautophagy Fig. 6.1.4  Age-​associated loss of proteostasis after stressors leading to accumulation/​aggregation driven toxicity.
ER stress, endoplasmic reticulum stress. From López-​Otín C, et al. (2013). The hallmarks of aging. Cell, 153(6), 1194–​217, with permission from Elsevier.

6.1  Ageing and clinical medicine 515 Nutrient sensing, metabolism, and metabolic signalling The close relationship between metabolic processes and ageing has been understood for decades. Specifically the effect of caloric re- striction on extension of lifespan has been demonstrated across species. These findings probably extend to primates: a study fol- lowing rhesus monkeys for 20 years in Wisconsin showed a sig- nificant improvement in lifespan on limiting monkeys to consume 70% of their own ad libitum diet (Fig. 6.1.5). Also, and crucially, they showed improvements in multiple ageing-​related diseases including diabetes, cancer, cardiovascular disease, and brain atrophy. The problem in translating these findings to humans is that it is unlikely, in a food-​rich era, that the general population will will- ingly restrict their diet to 30% less than ‘they would like’. Research into the mechanisms of energy restriction is important to deter- mine the most efficacious and acceptable means, and to identify ways to therapeutically ‘highjack’ the pathways involved. In add- ition, dissemination of knowledge of how caloric restriction works may help people to ‘own the idea’ and be more willing to take it on board in their lifestyle. The mechanistic effects of caloric restriction Metabolism is an essential process to the production of fuel energy, structural synthesis, growth, and reproduction. Core pathways such as glycolysis and fatty acid oxidation are altered in ageing and relatively spared in animal models of caloric re- striction. Diverse animal models have shown that a critical enzyme complex in metabolic signalling is the mammalian target of rapamycin complex 1 (mTORC1), which is activated in states of nutrient excess or by growth factors. The mTORC1 complex drives anabolic processes, building energy stores and macromolecular synthesis. Its actions have been studied using the inhibitor rapamycin, which was initially developed as an immunosuppressive agent. Several hypothetical mechan- isms for its life-​extending properties have been identified. One is the reduction of protein synthesis, resulting in lower burden on proteostatic systems. The mTORC1 complex inhibits cellular autophagy, including macroautophagy of older proteins and or- ganelles. Rapamycin increases this activity, which has important cell survival consequences. The adenosine monophosphate (AMP) dependant protein kinase (AMPK) is the reciprocal complex to mTOCR1 activation, re- sulting in catabolic adenosine triphosphate (ATP) generation and energy repletion in times of nutrient deprivation. A well-​known antidiabetic drug, metformin, is an indirect AMPK activator and has been used to explore the mechanism increasing the cellular AMP/​ADP ratio. Its use results in reduced mortality in many spe- cies, including man. Functionally it inhibits mTORC1 activity and promotes macroautophagy. These two key complexes in metabolic regulation altered by either rapamycin or metformin result in con- sequential effects on lifespan, but it is not yet known whether this comes with reduction in age-​associated pathology, with the excep- tion of metformin in diabetes mellitus, although this may not be due to this effect. Another relevant system is the nicotinamide adenine dinucleo- tide (NAD) coenzyme which, via redox reaction, forms redu- cing agent NADPH. NAD can also donate ADP ribose to poly ADP ribose polymerases (PARP) that are involved in DNA re- pair. Pharmacological agents focused on PARP molecules are currently being trialled in certain cancers. NAD also acts as a substrate for the Sirtuin family of protein deacetylases. Ageing reduces the activity of some Sirtuins, but caloric restriction can prevent this ageing decline in SIRT-​1 and SIRT-​3. The SIRT-​1 ac- tivator reservatrol has been a controversial agent in the study of ageing. It may act by increasing mitochondrial genesis, activating AMPK and increasing NAD levels, thereby demonstrating a link between these systems. The reservatrol lifespan extension in animal models seems to be mediated by reducing the negative effects of a high fat diet. The benefits of caloric restriction have led to studies examining limitation in specific nutritional components (Fig. 6.1.6). Not all behave similarly, and diets that predominantly restrict pro- tein may be much more efficacious than those which are high in protein, yet low in calories. The mechanisms that underlie these food-​type specific effects on longevity are currently under inves- tigation, and both the mTOR pathway and reduction in reactive oxygen species formation may be relevant. Futile cycles A counterintuitive observation in cellular metabolism is so-​called futile cycling. This is a process where two pathways flow in opposite directions, resulting in apparently useless energy transfer and en- ergy wastage through heat production. Some of these futile cyc- ling processes are increased with ageing, including the glycerol/​ free fatty acid cycle. The hydrolysation of triglycerides to free fatty acids can be used to generate ATP, while these free fatty acids can also be used to regenerate triglycerides. A connection with mol- ecules associated with ageing is present by virtue of this process delivering NAD levels required for PARP and sirtuin function. A further futile cycle-​related mechanism is uncoupling in mito- chondria, whereby there is loss of energy through incomplete coup- ling of ATP generation by oxidative phosphorylation. The resultant reactive oxygen species can damage cellular components and lead to an ageing phenotypic change, depending on their location. Age-related mortality (a) (b) Age (years) Percent survival 10 20 0 40 80 100 60 15 20 25 30 35 All-cause mortality Age (years) Percent survival 10 20 0 40 80 100 60 15 20 25 30 35 Control CR Control CR Fig. 6.1.5  Mortality curves in rhesus monkeys with sustained caloric restriction. CR, caloric restriction. Reproduced from Colman RJ, et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201–20​4.

516 Section 6  Old age medicine This observation connects the futile cycle process with the Free Radical/​Oxidative Stress Theory of Ageing. Senescence in stem cells There is currently substantial interest in research focused on the regenerative potential of stem cells, largely to repair degeneration of tissue associated with ageing. A challenge to this is the decline associated with ageing on stem cell functionality. There is considerable diversity of stem cell activity in normal tissues in an adult. Stem cells in some organs (e.g. the skin and blood) retain life long regeneration potential, whereas in others (such as neurological tissue) regeneration is limited. Data on Sirtuins and cancer suppressor genes in stem cells currently suggests that stem cells are generally more resistant to genetic damage. Nevertheless, quiescent stem cells accumulate other mo- lecular damage which may contribute to tissue ageing through impairing the stem cells’ productivity, or passing defects on to their cell progeny in older organs (Fig. 6.1.7). This could lead to tissue degeneration and may limit the potential to re-​activate stem cells in older organ systems. Reactivation of stem cells depends on their interaction with the local and systemic environment, which may be altered in aged or- gans, for example, by chronic inflammation. In organs that have limited intrinsic stem cell activity (e.g. brain and heart), trans- plantation holds more promise than activation. Parabiotic experi- ments, linking young and old animals (see next), show that old stem cells can be rejuvenated when exposed to circulating factors present in young animals. Considering all these data it is clear that stem cell therapy, whether using endogenous or implanted sources, presents potentially major opportunities to deal with the effects of ageing on human organs that lead to conditions such as arthritis and sarcopenia. They offer particular potential in diseases of organs with cellular loss and limited regenerative potential, such as the neurodegenerative con- ditions Parkinson’s and Alzheimer’s diseases. Insights from parabiosis There has been recent rejuvenation of interest into experiments joining young and old animals in the search for circulating fac- tors in younger animals with the ability to combat certain aspects of ageing. In such experiments, two genetically identical or inbred animals (most notably mice) of different ages have their circulations surgically linked (heterochronic parabiosis). Follow-​on screening for proteins in the blood of these mice have identified circulating factors which may be pro-​ageing or antiageing, in particular, for muscle tissues (the Wnt and TGF​β signalling pathways and oxy- tocin), and in stem cells (chemokines CCL11/​Eotaxin impeding neurogenesis in the hippocampus and subventricular tissue). Replication by different groups and in different species, as in all studies, is important to be certain if these effects are likely to be robust in humans. There are also concerns that factors stimulating stem cells (in particular) have the potential side effect of tumori- genesis. Nevertheless, in the study of potential circulating factors, parabiotic or serum transplant methodology could be extended, for example, by genetically altering one animal of a same aged pair in relation to the pathway of interest. Altered intercellular communication Inflammaging and immunosenesence The observation that ageing is accompanied with a chronic low-​ grade inflammatory state has been referred to as inflammaging (Fig. 6.1.8). This occurs in the absence of overt infection and is as- sociated with increased risk of mortality. This active inflammatory Control Caloric restriction Shift in energy metabolism Normal energy metabolism Decreased rate of ageing Longevity Morbidity & mortality Normal ageing Cellular damage dysfunction and loss Master regulators Fig. 6.1.6  Caloric restriction-​induced reprogramming of energy metabolism leading to reduced rate of ageing. From Anderson RM, et al. (2009). Caloric restriction and aging: studies in mice and monkeys. Toxicologic Pathology, 37(1), 47–​51. Loss of lineage specificity Progeny Stem cells ? YOUNG OLD Depletion due to loss of self-renewal Depletion due to senescence Malignant transformation Fig. 6.1.7  Decline in stem cell function with age. From Liu L and Rando TA (2011). Manifestations and mechanisms of stem cell aging. J Cell Biol., 193(2), 257–​66. © 2011 Liu and Rando, available under the Creative Commons BY-​NC-​SA 3.0 license.

6.1  Ageing and clinical medicine 517 state is evidenced in epidemiological studies by elevation of C-​ reactive protein (CRP) and interleukin 6 (IL6) levels. Although theoretically this observation may suggest a causal association with reduction in functional level, body composition changes, im- mune and organ function, this has yet to be proven. Nevertheless, inflammaging has the potential to offer interventions that may alter the morbidity associated with increased age, with transla- tional opportunities using existing agents. When either tissue damage or invasion by a foreign pathogen takes place, acute inflammation is an essential response to repair and management of the potential harmful consequences. Chronic inflammation, characterized by low level persistent activity in the immune system, has negative consequences leading to tissue damage and degeneration. There are several potential mechanisms by which this occurs. One is the production of reactive molecules by leukocytes which attack tissue cellular components. Both im- mune and other cells types that are damaged in this process can produce cytokines which amplify the inflammation. Inflammation leads to modification of anabolic signalling via insulin-​like growth factor and other similar molecules, aimed at protein synthesis. These mechanisms interact and lead to state of chronically in- flamed tissues in older adults. Further stimuli of immune function include the increased cellular molecular debris, such as damaged part-​organelles, peroxidized lipids, and glycated proteins, that result from increased production and inadequate elimination seen with ageing. An example of this is the damaged components of mitochondria, which being believed to be of bacterial origin are potentially potent stimuli to inflammation. Cellular senescence occurs in response to stress and damage, with senescent cells accumulating in older tissues. Persistent senescence leads to production of a collection of pro-​ inflammatory cytokines which comprise the senescence-​associated secretary phenotype (SASP). The immune system itself also under- goes immunosenesence, which leads to a mild increase in innate im- munity and a reduction in adaptive immunity, possibly enhanced by inactive infections such as cytomegalovirus (CMV) where T-​cell resources are expended. There is also an increased activity in the co- agulation system in aged animals and humans, leading to vascular pathology which also activates the immune system. Although we understand that increased active circulating in- flammatory molecules are associated with poor health and survival, we should consider whether this is through contributing to increased age-​related diseases. Core to the ageing immune phenotype are IL6 and tumour necrosis factor. These molecules, by interacting with cell surface receptors, activate transcription factors for multiple regulatory genes like nuclear factor kappa-β (NF-​kβ), which regulates most genes implicated in the senescence-​ associated secretary phenotype. NF-​kβ also directly drives several phenotypes associated with ageing, such as neurodegeneration and atherosclerosis. These observations provide potential common pathways from biological ageing to disease morbidity associated with older age. There is evidence for this in diseases such as cancer and vas- cular disease, in which inflammatory cytokines and senescence-​ associated secretary phenotypes are implicated. Complementary evidence for this comes from murine models where restoration of ‘young’ circulating inflammatory systemic factors can limit age-​ associated tissue changes. Examples include using whole ‘young serum’ to enhance muscle stem cells and maintaining comparable levels of circulating gonadotrophin-​releasing hormone to reverse ageing in muscle, brain, and skin of older animals. Immune ageing may not always be detrimental, but could be an adaptation that can optimize maintenance and repair. A relevant observation that supports a positive view of inflammaging is that long-​lived humans, centenarians, have high levels of circulating Il6 and hypercoagulability. This is in the face of a delay in the onset of many age-​associated diseases such as cardiovascular disease or cancer. This contradiction needs explanation, but possibly relates to differing genotypic sensitivities to pro-​inflammatory cytokines, or that inflammaging can be in a state of balanced activity within long-​lived adults. The substantial evidence that inflammation is important both in ageing and disease development prompts the obvious question as to whether modifying the process improves health. The non-​ steroidal anti-​inflammatory drug aspirin is the most widely used cardiovascular prevention intervention, acting at cardiac, cerebral, and systemic sites. There is observational evidence that it is asso- ciated with lower risk of several cancers seen in later life. Further evidence of prevention of mortality associated with inflammaging is the effect of exercise, which modifies chronic inflammation. The microbiome With the advent of genetic sequencing technology, a new area of re- search has sprung up investigating the health effects of the compos- ition of the human microbiome on health. Evidence is mounting that the gut microbiome, in particular, influences host metabolism Antigenic load and environmental free radicals Immune activation and tissue damage Inflammation & repair Oxidative metabolism Reactive oxygen species Further release of pro- inflammatory cytokines Remodelling and Inflammaging Fig. 6.1.8  The cycle of inflammaging. From Baylis D, et al. (2013). Understanding how we age: insights into inflammaging. Longev Healthspan, 2(1), 8.

518 Section 6  Old age medicine and the innate and adaptive immune system. This may have par- ticular relevance in inflammaging and frailty. Our gut, with an astounding surface area of about 32 square metres, is the largest interface with the external world, and contains 70% of the body’s lymphocytes. The gut microbiome has more than 150 times the genetic po- tential of the human genome by virtue of the trillions of micro- organisms, which are highly variable between people, yet stable in individuals. Age and frailty are both associated with alternations in the microbiota, which is likely to be a dynamic combination of host habitability, diet, and microbial effects. The identification of several classes of anti-​inflammatory commensal bacteria has ig- nited an interest in whether the microbiota of older subjects can be manipulated—​especially by diet—​to reduce systemic inflamma- tory levels and ensuing consequences. In conclusion, inflammaging is an important focus to the inter- play between ageing and chronic disease. Further understanding of the balance between positive features of immune response to harmful stimuli and the damaging effect of chronic low level in- flammation is needed. Translation of knowledge of the basic mech- anism of inflammaging to prevent age-​associated multimorbidity has been enhanced by the development of agents for organ-​specific inflammatory diseases. The well characterized health benefits of a balanced diet and adequate exercise may act through modulating the inflammatory system. Further insight into the mechanisms at play will enable more specific interventions, which may be more palatable and feasible on a population scale. Circadian rhythms, the hypothalmo-​pituitary-​adrenal axis, and ageing Mammals have clock genes that regulate an intrinsic cell cycle, most of these being transcription factors affecting gene expression. These clocks run on a 24-​hour cycle affecting the time-​dependant and location-​dependant cellular processes seen in cells from dif- ferent tissues. Epidemiological evidence indicates that perturbation of sleep-​ activity cycles in humans (e.g. through shift work) is associated with detrimental effects in many ageing related diseases and life- span. Epidemiological evidence also supports circadian clock influence on disease processes, such as cardiovascular event rela- tionships to time of day (Fig. 6.1.9). Experimental models suggest alteration in circadian rhythms can reduce lifespan, for example, in mice. The Sirtuins have con- nection with the clock genes of circadian cycles. SIRT-​1 expression Nutrition Circadian Clock Shift-work/nutritional disturbance/ clock gene mutation etc Circadian harmony/ homeostasis Circadian desynchrony Predictive/reactive synchrony Anabolism/ Catabolism Repair Metabolic dysregulation ROS Cell death Impaired repair Damage accumulation Combat Avoid Gating Metabolic homeostasis Promote healthy ageing Accelerates ageing and Age-related pathologies Disturbed homeostasis Predictive/reactive desynchrony Fig. 6.1.9  A schematic representation of the role of clocks in cellular tasks impacting cellular homeostasis and consequently affecting healthy ageing. From Bednářová A, et al. (2013). Nature’s timepiece—​Molecular coordination of metabolism and its impact on aging. Int J Mol Sci, 14(2), 3026–​49.

6.1  Ageing and clinical medicine 519 declines with increasing age and is associated with both length- ening of the circadian rhythm and inability to adapt to this cycle. The hypothalamus is responsible for regulating physiologic func- tions such as temperature regulation, thirst, hunger, sleep, mood, sex drive, and the release of other hormones within the body. There is a central clock located within the suprachiasmic nucleus of the hypo- thalamus which functions to maintain synergy of cellular clocks across the mammalian body. Light/​dark cycles influence the central clock signal, resulting in dissemination of day cycle effects on periph- eral cells. A major function of the clock gene transcription is to regu- late metabolic processes involved in glucose and lipid homeostasis. An additional hypothalamus-​mediated effect on lifespan is through nuclear factor-​kappaB (NF-​kB), inhibition of which in the mouse hypothalamus results in lifespan extension via modifying its inflammatory mediating effect. There is also direct impairment of neurogenesis and poor metabolic regulation resulting from NF-​ kB suppression of gonadotrophin-​releasing hormone. Following on the inflammaging theme, alterations in the gut microbial me- tabolism, in part mediated by dietary changes associated with shift work, provide another mechanism for circadian rhythms to impact inflammation and thereby alter the cause of ageing and lifespan-​ limiting morbidities such as metabolic or cardiovascular disease. The hypothalamus and circadian rhythm effects on lifespan and age-​associated pathological developments provide linkage to metabolic signalling. These may be an important target for the generation of interventions that result in systemic effect on age-​ associated disease and healthy longevity. Stress and ageing—​a synthesis between extrinsic and intrinsic factors Stress has an interesting and complex relationship with ageing. This is because stress can be considered in a variety of ways, from cellular injury arising from intrinsic factors to whole organism psychological and social stressors. Additionally stress can be biologically harmful (toxic stress) or physiologically beneficial (hormetic stress), leading to beneficial changes in cellular systems. First, we need to consider stress with a multilevel approach. In simple multicellular organisms stress focuses on clear physical agents such as heat, radiation, and reactive oxygen species. In hu- mans, ‘extrinsic’ stress, such as psychological and social challenges, may also contribute. Such stressors have been associated with sys- temic neuro-​hormonal and immune activation. The integration of diverse forms of stress in humans results in a more variable effect of stress across similar stressors, making estimation of the effects more complex. When considering stress we need to synthesize the laboratory level evidence of physical agents with systemic more complex social adversities to try to understand how these play out in human ageing. This is important as significant epidemiological data show evidence for an association between chronic stress and diseases. At a molecular cellular level much of our understanding of the effects of stress comes from simple organisms. An example of this is the work showing that ‘intrinsic’ genetic variation in the nematode Caenorhabditis elegans leads to significant variability both in life- span and resistance to harmful agents such as heat, heavy metals, and oxidative stress. Work on mechanisms behind this multiple stress resistance model show that molecular chaperones such as Heat Shock Factor-​1 are associated with protein homeostasis, redu- cing accumulation of harmful insoluble molecules. Added to this are observations that short-​term controlled exposure to stressful events, such as heat, can increase lifespan in nematodes and flies (hormesis). The effect of short-​term stressors include activation of genes involved in metabolic control. Thus, stress can be bene- ficial in these simple models, controlling for extent and period of exposure, and where other challenges to survival are eliminated. In models of higher level organisms, including humans, the story is more complex. Examples of a stress resistant or resilient phenotype come from research on psychological stressors in which not all individuals in situations of adversity suffer the same nega- tive consequences. Psychological research points to cognitive pro- cesses and social resources mediating the difference in outcome to stressors. What is not understood is whether these abilities are translated into resistance to cellular stresses. The harmful effect of ‘extrinsic’ stress on human health is far better appreciated. There is epidemiological evidence that adverse life events, including those in childhood, lead to higher risk of disease and mortality. The effects of prenatal stress has also been linked to later human health, as set out in the Barker hypothesis of the Developmental Origins of Disease. This process may func- tion though epigenetic alterations which can be transgenerational. Unlike simple organism research, in human studies, attempts to identify mechanisms mediating association between stressors and age-​associated disease are more challenging, but markers such as systemic inflammation, gene expression profile, and telomere changes have been identified. If we accept that stress has both positive and negative effects on ageing morbidity, then we can consider how we might intervene. Some consider that exercise is an example of a physiological and metabolic stress, acting possibly by free radical production and re- duction in inflammation, which has beneficial aspects for ageing. Alternatively, physical inactivity prevalent in modern society may constitute the ‘stressed’ state, especially considering the far greater population levels of physical activity in our evolutional history. We need to better understand both whether hormetic stress benefits ageing, and the mechanisms that underpin resilient pheno- types. This may include the integration of evidence-​based interven- tions such as exercise into models aimed at reducing stress-​related age-​associated poor health. Conclusion A connected systems-​level knowledge of ageing underpins many clinical and population health challenges of ageing, such as cancer, cardiovascular, and neurodegeneration (Fig. 6.1.10). Ageing, and age-​related diseases within different organ systems and multimorbidity should not be considered in isolation, but rather as components of whole systems’ ageing, with many sys- tems sharing extrinsic factors in particular. This is why clinicians specializing in ageing use a comprehensive approach to the frail older patient, who generally presents with non​specific problems such as falls, delirium, and immobility. Another reason for such an approach is the appreciation of how evidence-​based health promo- tion/​disuse prevention interventions, such as exercise, nutrition,

520 Section 6  Old age medicine and positive lifestyle choices, improve health and well-​being. These can be used to develop or refine how we practice personalized medicine in an ageing world. FURTHER READING Fontana L, Partridge L (2015). Promoting health and longevity through diet:  from model organisms to humans. Cell, 161,
106–​18. Franceschi C, Campisi J (2014). Chronic inflammation (inflammaging) and its potential contribution to age-​associated diseases. J Gerontol A Biol Sci Med Sci, 69 Suppl 1, S4–​9. Global Health and Ageing (2011). WHO and National Institute Ageing. NIH Publication no. 11–​7737 October 2011. He S, Sharpless NE (2017). Senescence in health and disease. Cell, 169(6), 1000–11. Kundu P, Blacher E, Elinav E, Pettersson S (2017). Our gut microbiome: the evolving inner self. Cell, 171(7), 1481–93. López-​Otín C, et  al. (2013). The hallmarks of aging. Cell, 153, 1194–​217. Moskalev AA, et al. (2014). Genetics and epigenetics of aging and longevity. Cell Cycle, 13, 1063–​77. Niccoli T, Partridge L (2012). Ageing as a risk factor for disease. Curr Biol, 22, R741–​52. Special Issue. Why we age (2015). Science, 350, Dec 4. HERITABLE GENETIC AND EPIGENETIC FACTORS EXCESSIVE LIFE STRESS PHYSICAL INACTIVITY Changes in HPA axis Senescence Inflammaging Changes in nutrient sensing Molecular damage INTRINSIC AGEING CALORIC EXCESS EXTRINSIC FACTORS Fig. 6.1.10  Schematic of ageing, indicating possible interactions between extrinsic factors, mechanisms of ageing, and intrinsic factors driving molecular ageing. HPA Axis, hypothalamic-​pituitary-​adrenal axis.

6.10 Neurodegenerative disorders in older people 6

6.10 Neurodegenerative disorders in older people 601

ESSENTIALS Neurodegenerative disorders are associated with a progressive loss of structure and function of neurones that leads to neuronal death. Their aetiology combines ageing, genetic susceptibility, and risk factors including environmental exposure, balanced against protective factors. They present with varying combinations of progressive cognitive, emotional, motor, autonomic and periph- eral symptoms, and clinical signs. Neurodegenerative conditions are all likely to have a preclinical prodromal period, followed by slow initial decline during which there is clinical presentation, followed by a further steady decline and an eventual accelerated decline. The rate of progression of these disorders varies greatly, but they are all inevitably progressive, currently have no cure, and require symptomatic treatment. This chapter focuses on the clinical presentation, diagnosis, and management of Parkinson’s disease as perhaps the best example of an age-​related neurodegenerative condition. It explains the par- ticular challenges of the disease in the context of ageing, the use of the multidisciplinary team, and the management of the non​motor symptoms. Introduction Neurodegenerative disorders are associated with a progressive loss of structure and function of neurones that leads to neuronal death. They present with varying combinations of progressive cognitive, emotional, motor, autonomic, and peripheral symp- toms and clinical signs. These conditions include Alzheimer’s dis- ease (AD), Parkinson’s disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia (FTD). The aetiology of neurodegenerative disorders combines ageing, genetic susceptibility, and risk factors including environmental ex- posure, balanced against protective factors. Pathologically, neurodegenerative disorders all exhibit abnor- malities of protein handling, leading to the intracellular depos- ition of abnormal proteins in a variety of patterns associated with distinct patterns of cell loss. The deposition of proteins gives rise to pathological markers such as the Lewy body, due to α-synuclein protein (e.g. PD), or plaques and tangles due to Tau protein (e.g. AD). The conditions can be divided according to the predominant protein deposition into α-​synucleinopathies (PD, dementia with Lewy bodies, and multiple system atrophy) and tauopathies (AD, progressive supranuclear palsy, corticobasal degeneration, and frontotemporal dementia). Cell death is the culmination of a cascade of complex processes. Many of these processes parallel the changes which occur in ageing, although the detailed pattern differs. Pathologically some of these conditions are interrelated such that the presence of one increases the risk of the development of another. There is often mixed degen- erative pathology combined independently with vascular disease, which may contribute to cognitive and physical decline. This can be seen, for example, in the pathological overlap between PD and AD transitioning through PD dementia and dementia with Lewy bodies with increasing AD pathology (Fig. 6.10.1). 6.10 Neurodegenerative disorders in older people John Hindle AD DLB Vascular PD PDD Limbic and cortical Lewy bodies Fig. 6.10.1  Neuropathological overlap in neurodegenerative disease in older people. AD, Alzheimer’ disease; DLB, dementia with Lewy bodies; PD, Parkinson’s disease; PDD, Parkinson’s disease dementia.

602 Section 6  Old age medicine Neurodegenerative conditions are all likely to have a preclinical prodromal period, followed by slow initial decline during which there is clinical presentation, followed by a further steady decline and an eventual accelerated decline (Fig. 6.10.2). The rate of pro- gression of these disorders varies greatly, but they are all inevit- ably progressive, currently have no cure, and require symptomatic treatment. This chapter focuses on the clinical presentation, diagnosis, and management of PD as perhaps the best example of an age-​related neurodegenerative condition. It explains the particular challenges of PD in the context of ageing, the use of the multidisciplinary team, and the management of the non​motor symptoms. Each section highlights where symptoms and management strategies are also applicable to other neurodegenerative disease of older people. For further discussion of neurodegenerative disorders, see chapters on movement disorders (24.7.1–​4), inherited neurodegenerative disorders (24.17), higher cerebral function (24.4.1–​2), and neuro- psychiatric disorders (26.5.3). Parkinson’s disease and ageing Aetiology The specific aetiology of PD is not known, hence the term idio- pathic. In general, the earlier the onset of PD the more likely it is to be associated with genetic abnormalities, although an abnormality of the Leucine Rich Repeat kinase 2 (LRRK-​2) gene may be associated with a few late onset cases. In future it is likely that susceptibility genes will be identified that predis- pose to late onset PD. Several environmental risk factors have been identified, including rural living, exposure to pesticides and herbicides, and well water drinking. Other factors may be protective, including use of non​steroidal drugs, drinking coffee, and smoking. Age is still, however, the largest risk factor for the development of PD. Epidemiology Parkinson’s disease is largely a disease of older age, with the mean age of onset in the early 70s, and an incidence of around 11 cases of PD and 17 cases of parkinsonism per 100 000 popula- tion per year. Age-​adjusted prevalence in the United Kingdom is around 150–​200 per 100 000 population (compared with c.1000 per 100 000 for AD). The pattern of increasing prevalence with age is remarkably similar across most European and Western countries. Pathogenesis Pathologically, PD is characterized by the formation of Lewy bodies and a distinct pattern of cell loss. The pathogenesis consists of a cascade of events leading to cell death. It is now recognized that the spread of pathology may occur through transmission of abnor- mally folded proteins across the synapse commencing in the brain- stem and spreading to the cortex, as described in Chapter 24.7.2. The very earliest changes occur in the vagal nucleus and in the ol- factory bulb, the latter being associated with loss of sense of smell. Brainstem pathology may produce autonomic dysfunction, and limbic involvement may produce mood changes. Extension of pathology to the cortex and hippocampus may lead to cognitive changes and dementia. Despite the presence of significant path- ology, even in the early stages of PD, the brain adopts compensatory mechanisms that delay the clinical presentation. In older people the reduced reserve brought about through ageing and associated pathologies such as vascular disease, overwhelms these compensa- tory mechanisms leading to a relatively earlier clinical decline than would be caused by PD-​specific pathology alone. Clinical features The diagnosis of PD or other neurodegenerative disorders should be confirmed by a specialist, either a neurologist or geriatrician, although it is still revised later in about 10% of cases. The clinical symptoms and signs can be divided into motor and non​motor fea- tures, with the latter being increasingly important in older age. The characteristic motor phenotype includes bradykinesia, rigidity, tremor, and the loss of postural reflexes. Non​motor symptoms in- clude anosmia, neuropsychiatric problems, autonomic dysfunc- tion, sleep disturbances, gastrointestinal, and bladder problems. Prodromal symptoms including depression, anxiety, anosmia, restless legs, and sleep behaviour disorder may precede the onset of the typical motor syndrome. Motor signs and symptoms The onset of motor symptoms may be subtle, and these are easily missed or mistaken for age-​related changes by the patient or doctor. All of the motor symptoms are characteristically asymmetrical. Bradykinesia is a fatigable slowing of movement and alteration of its rhythm and amplitude. It may be associated with slowness of axial movements, giving difficulty turning in bed. Reduced facial movement and slowness of expression may lead to a mask-​like face. Rigidity is typically irregular through passive movement and is termed cogwheel. There is also background continuous rigidity de- scribed as lead-​pipe rigidity. The tremor of PD is usually a rhythmic rest tremor of around 4–​7 cycles per second, but some patients may also have this tremor on sustained posture. Hand tremor often emerges when walking. The gait characteristically has a delay in ini- tiation, hesitancy and shortening of stride length, the use of extra steps to turn round, and associated loss of arms swing and stooping. The gait pattern needs to be differentiated from the hesitant gait often seen in older people who have developed a fear of falling. A very marked stoop on standing, which disappears on lying down, can sometimes develop due to a spinal dystonia known as camptocormia. This may be associated with other spinal pathology or myopathy. An early onset sideways stoop, often called the Pisa syndrome, is more characteristic of multiple system atrophy. Minimal decline-prodromal period Symptom onset Diagnosis Steady decline Accelerated decline Susceptibility Time/age Function Fig. 6.10.2  Common neurodegeneration disease model.

6.10  Neurodegenerative disorders in older people 603 Postural instability may be present, even on diagnosis, particu- larly in older people. Absence of other neurological signs supports a diagnosis of PD, but coincidental neurological signs such as brisk reflexes or extensor plantar responses are common in older people. With disease progression motor signs become bilateral, as- sociated with increased axial rigidity, postural changes, instability, and falls. Abnormal movements in the form of dyskinesia associated with medication are more prevalent in younger onset PD, and when they occur in older age they are usually less severe. The motor symptoms of PD may worsen in periods of intercurrent illness or following major procedures or anaesthesia. Other disorders of movement Cerebellar dysfunction is common in multiple system atrophy, and when present the condition is termed multiple system atrophy-​C in contrast to multiple system atrophy-​P which has predominant parkinsonism. Myoclonic jerks can be present as a late phenom- enon in PD and AD, but commonly develop earlier in dementia with Lewy bodies and corticobasal degeneration. Dystonia can occur related to fluctuations in drug response in PD. Unilateral dystonia is a common feature in corticobasal degeneration. Differential diagnosis Ageing Mild parkinsonian signs can occur sporadically in a few very elderly people without an established neurological disorder. They can be distinguished by symmetrical signs, an absence of rest tremor, and a lack of response to dopaminergic therapy. They may reduce functional capacity and are associated with increased likelihood of mild cognitive impairment. These signs are likely to be multifactorial in origin, including age-​associated decline in dopaminergic activity, deep white matter disease, and ‘incidental’ Lewy body pathology (not amounting to PD) that can also be present without clinical signs and symptoms. Ageing can also be associated with axial impairment of gait and postural control, sometimes called age-​related gait disturbance (Table 6.10.1). Drug-​induced Parkinsonism Increasing age is associated with increasing sensitivity to side effects of dopamine blocking agents, producing drug-​induced parkinsonism. It is more common in women and in those with a family history of PD and affective disorders. Symptoms may come on within a few weeks of commencement of the causal agent in 50% of cases, but others may take many years to develop. Drug-​induced parkinsonism has less tremor and is more likely to be symmetrical. When there is marked asymmetry it may be due to an unmasking of subclinical PD, which then progresses in the typical pattern. The commonest agents causing drug-​induced parkinsonism are given in Table 6.10.2. If possible, withdrawal of the causal drug should be considered, although this must be done very slowly to avoid precipitating a tardive movement disorder (dyskinesia or dystonia). In 60% of cases improvement will occur within two months, but it may take much longer. Essential tremor Essential tremor is more common with increasing age and is associated with symmetrical postural tremor at higher fre- quency (8–​12  hz) than in PD. There may be a family history and response to alcohol. Differentiation from PD can some- times be difficult because some people with PD will have a noticeable postural tremor. β-blockers are the most effective treatment for postural tremor, with improvement occurring in over 50%, although intolerance of, and contraindications to, the use of β-blockers are more common in older patients. Other agents including primidone, other anticonvulsants and benzodiazepines are more likely to cause side effects in older people. Other dementias An early presentation of dementia, prior to the onset of motor symptoms, may be due to dementia with Lewy bodies, which is now thought to be part of a spectrum that includes PD. Dementia with Lewy bodies is particularly associated with fluctuating cognition, visual hallucinations, language difficul- ties, and marked sensitivity to dopamine blocking drugs. The motor signs are similar to PD. There may be some response to L-​dopa, but doses need to be kept extremely low to avoid ex- acerbation of hallucinations. Autonomic problems, particularly orthostatic hypotension, are common in dementia with Lewy bodies. Frontotemporal dementia mainly affects those under the age of 65 years and usually presents with behavioural changes and/​ or disturbances of language and memory. AD can have associated parkinsonism leading to diagnostic confusion. The parkinsonism may be due to the development of associated Lewy body pathology. Vascular parkinsonism Cerebrovascular disease, in particular deep white matter changes, increases with age and may be associated with parkin- sonism. This typically affects the lower body, producing pre- dominant gait symptoms and postural instability. Small steps with a rapid cadence give a characteristic ‘marche à petits pas’. Table 6.10.1  Differentiating age-​related motor changes from Parkinson’s disease (PD) Parkinson’s disease Mild parkinsonian signs ‘Age-​related’
gait disturbance Tremor Rest Absent in 90% Absent Rigidity Typical cogwheel or lead pipe Variable Musculoskeletal Bradykinesia Typical with fatigue Variable General slowness Gait and balance disturbance Late Early Axial impairment gait and posture Symmetry Asymmetrical Symmetrical Symmetrical Dementia risk Increased Slightly increased Age-​related L-​dopa response Good Poor None

604 Section 6  Old age medicine Occasionally, acute vascular lesions of the basal ganglia can give rise to asymmetrical parkinsonism. Although vascular parkinsonism is characterized by a relatively poor response to L-​dopa, some patients with vascular parkinsonism, particu- larly those with lesions close to the nigrostriatal pathway, may respond to L-​dopa. Multisystem degenerations Other multisystem degenerations may occur in older people. These conditions have a more rapid progression requiring com- plex multidisciplinary management and early palliative care. Progressive supranuclear palsy is associated with early falls and injury, planning difficulties, vertical gaze palsies, swallowing dif- ficulties, and poor response to L-​dopa. People with progressive supranuclear palsy also show difficulty suppressing ongoing move- ment, such as continuing clapping when asked to clap three times (applause sign). Multiple system atrophy, although usually presenting at an earlier age than PD or progressive supranuclear palsy, can occur in older age and is associated particularly with autonomic dysfunc- tion, cerebellar symptoms, and a more rapid progression. Urinary symptoms are particularly common at onset. Initially, these are commonly urgency, frequency, and incontinence, but voiding problems may develop later. Corticobasal degeneration may present with marked asym- metry of motor signs including dystonia, myoclonus and limbs moving outside voluntary control (alien limb phenomenon), asso- ciated with cognitive impairment and dyspraxia. It may also pre- sent with dementia. The condition is probably underdiagnosed, with the persistent asymmetry leading to misdiagnosis as vas- cular disease or stroke. The differentiating features of the neurodegenerative conditions are given in Table 6.10.3. Investigations There is no single diagnostic test for PD since it is a clinical diagnosis. Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain are not recommended routinely, but in older patients it is more common to find coincidental vascular and deep white matter changes. An isotope brain scan highlighting dopamine nerve terminals (ioflupane iodine-​123 injection—​DaTscan) may help differentiate degenerative parkin- sonism from essential tremor or drug-​induced parkinsonism (see Chapter 24.7.2). Treatment Multidisciplinary treatment Anyone with suspected PD should be referred for specialist assess- ment, enabling access to a specialist multidisciplinary team. Early referral should be considered to a PD nurse specialist, physiother- apist, occupational therapist, speech and language therapist, and later possible referrals may include dietician, psychologist, and psychiatrist (Table 6.10.4). Drug treatment Older people tend to be more sensitive to the cognitive and psychi- atric side effects of PD drugs treatments (Table 6.10.5). The focus of drug therapy for motor dysfunction in older people with PD is L-​dopa (plus dopamine decarboxylase inhibitor, e.g. carbidopa in Co-​careldopa or benserazide in Co-​beneldopa). There is no reason to delay initiation of L-​dopa in older people. The starting dose is smaller in older than younger patients, with more gradual incre- ments and regular monitoring of response. Anticholinergic drugs should be avoided since they may cause hallucinations and cognitive decline. In older patients who de- velop wearing off from the response to L-​dopa there is benefit from adjunctive therapy, such as addition of a monoamine oxidase B inhibitor (rasagiline, selegiline), catechol-​O-​methyltransferase inhibitor (entacapone) or small doses of a direct acting dopamine agonist (ropinirole, rotigotine, pramipexole). Patients may still benefit from the use of more complex ther- apies such as subcutaneous apomorphine or intrajejunal L-​dopa. Patients over the age of 70 years are much less likely to be suitable for brain stimulation. Other degenerative Parkinsonisms do not respond well to drug treatment. Management of falls Falls are common in PD, particularly with increasing stage of the disease and ageing, and may occur in 50% over a three-​month period. They may occur even in moderate disease, affect quality of life and increase fracture risk (Table 6.10.6). Falls occur very early in the course of progressive supranuclear palsy. Table 6.10.2  Agents causing drug-​induced parkinsonism Drugs commonly causing parkinsonism Drug less commonly causing parkinsonism Drug rarely causing parkinsonism Drug type/​ usage Examples Drug type/​ usage Examples Drug type/​ usage Examples Typical Neuroleptics Chlorpromazine Trifluoperazine Flupentixol Haloperidol Pimozide Sulpiride Atypical Neuroleptics Aripiprazole Amisulpiride Olanzapine Risperidone Atypical neuroleptics Clozapine Quetiapine Antiemetic Metoclopramide Anticonvulsants Sodium valproate Antidepressants Paroxetine Vestibular sedative Prochloperazine Antiarrhythmic Amiodarone Dopamine depleters Tetrabenazine Travel sickness Cinnarazine Anticonvulsants Lamotrigine

6.10  Neurodegenerative disorders in older people 605 Table 6.10.3  Features of neurodegenerative conditions Synucleinopathies Tauopathies Other PD DLB MSA AD PSP CBD FTD ET Common age of onset 60–​70

65 50–​60 65 70 variable 45–​65 All ages Pathological marker Lewy bodies Lewy bodies Glial cytoplasmic inclusion bodies, gliosis Plaques and tangles Tangles Tangles Pick bodies Variable Clinical motor Extrapyramidal Asymmetrical parkinsonism, tremor common Symmetrical parkinsonism Symmetrical parkinsonism in MSA-​P Late onset parkinsonism Symmetrical parkinsonism in PSP-​P Marked asymmetrical parkinsonism Late: overlap with PSP or CBD None Gait Slow, short stride, reduced arm swing, narrow base, stoop, falls late Slow, short stride, reduced arm swing Slow, short stride, reduced arm swing, narrow base, marked stoop, ataxia, syncope causing falls Normal Upright posture, wide base, motor recklessness, early falls Marked asymmetrical reduced arm swing and dystonia Late changes Normal Other movements Occasional myoclonic jerks, dystonia Myoclonic jerks common Cerebellar dysfunction Myoclonic jerks late onset Applause sign Alien limb, myoclonic jerks, dystonia Late abnormal movements None Gaze palsy None None Horizontal > vertical None Vertical > horizontal Horizontal = vertical None or overlap with PSP None Clinical neuropsychiatric Cognition Dementia late Dementia at presentation Dementia rare Dementia at presentation Planning problems early Variable: dyspraxia, language problems Dementia at presentation, language problems Normal Behaviour Hallucinations later Hallucinations early. Challenging behaviour Normal Hallucinations late Challenging behaviour Reckless behaviour in some Variable Early behavioural and personality changes Normal Other problematic non​motor features Wide variety Autonomic Autonomic predominate Variable Apathy, swallow problems Variable Aphasia, None Treatment Drugs L-​dopa good response Some response to L-​dopa but doses kept low Poor response to L-​dopa Poor response to L-​dopa Poor response to L-​dopa Poor response to L-​dopa Poor response to L-​dopa β-​block MDT priorities Motor function then all non​motor symptoms Mental health Autonomic impairment Mental health Falls, swallow problems Mental health, motor symptoms Mental health Tremor Prognosis:
survival Normal to slight reduction Reduced 10 yr Reduced 6 yr 6 yr 8 yr Normal AD, Alzheimer’s disease; CBD, corticobasal degeneration; ET, essential tremor; FTD, frontotemporal dementia; DLB, Lewy body dementia; MDT, multidisciplinary team; MSA, multiple system atrophy; PD, Parkinson’s disease; PSP, progressive supranuclear palsy.

606 Section 6  Old age medicine It is important to monitor risk of falls in older people with PD (Table 6.10.7). Those at risk should be screened for fracture risk using a standard fracture risk calculator (e.g. Q-​Fracture) and treated accordingly. Interventions also include ensuring good motor control and avoidance of ‘off’ periods, a reduction in dys- kinesia, and avoiding postural hypotension. The standard strength and balance exercise approaches to prevention may be insufficient, and there is some evidence for the use of specialized physiotherapy utilizing cueing strategies, cognitive strategies, environmental changes, and assistive devices. A full multidisciplinary assessment is vital in the management of falls in PD and is particularly im- portant in progressive supranuclear palsy. Non​motor signs and symptoms The number and severity of non​motor symptoms increases both with age and disease progression. Non​motor symptoms, particu- larly mental health symptoms, significantly impact quality of life and need special consideration in older people. Many of the non​motor symptoms arise secondary to autonomic dysfunction, including constipation, urinary symptoms, orthostatic hypoten- sion and sweating (Table 6.10.7). Table 6.10.4  The multidisciplinary team (MDT) referral and roles Team member Referral Some of the key roles of team members General practitioner Initiates referral Early recognition, referral, continuity of care, prescribing and medicines management, managing co​morbidity, link with primary healthcare team Specialist doctor (geriatrician or neurologist) At diagnosis Diagnosis, drug treatment, symptom management, coordination of MDT, education and information, research Specialist nurse At diagnosis Assessment of needs, communication, symptom management, medicines management, support and counselling, education, integration of the service, managing case load, independent prescribing Physiotherapist At diagnosis and active review Monitor and identification of rehabilitation priorities, exercise programme, restoration and compensation of function Occupational therapist Early referral after diagnosis Patient and carer centred assessment, development of goals, address physical and psychosocial problems, enhance participation in everyday activities and self-​care Speech and language therapist Early referral after diagnosis Improvement of vocal loudness and pitch range, optimize intelligibility, effective communication, assistive technologies, assess and manage swallowing Dietician Nutrition and weight loss Nutritional screening, advice on weight, review fluid and fibre intake, avoidance of constipation, dietary advice, altered texture of food, food supplements Psychologist Cognition, management of neuropsychiatric symptoms Assessment of cognition, mood and neuropsychiatric symptoms, diagnosis of cognitive impairment, cognitive therapies for cognitive impairment and mood Social worker When care needs increase Non​medical care needs, advice about services and eligibility, coordination of service providers, advice about care provision Pharmacist Prescription of drug treatments Advice about medications and potential interactions or contraindications, dispense medications, medication reviews, independent prescribing Voluntary body support group Throughout the disease Information and support for patients, carers, and liaison with MDT Table 6.10.5  Drug treatment: do’s and don’ts for motor symptoms in the older patient Do Do not • Start with L-​dopa: low dose, slow titration • Prescribe anticholinergics • Consider increased dose and frequency of L-​dopa for motor fluctuations • Suddenly stop treatments • Consider adjunctive drugs; COMT, MAOB, or cautious use of dopamine agonist, for motor fluctuations • Consider apomorphine or intrajejunal L-​dopa for advanced treatment • Consider the use of acetylcholinesterase inhibitors for dementia • Ensure patients admitted to hospital get medications on time COMT, catechol-​O-​methyltransferase inhibitors; MAOB, Monoamine oxidase B inhibitors. Table 6.10.6  Falls in PD and other neurodegenerative conditions Factors contributing to increasing falls risk in patients with PD Clinical predictors of falls Non​specific PD-​specific • Increasing age • Increasing motor severity • Presence of a previous fall in the last year • Cognitive impairment • Axial rigidity • Evidence of freezing of gait in the last month • Polypharmacy • Freezing of gait • Reduced self-​selected gait (less than 1.0 m/​second) • Sarcopenia • Motor
fluctuations • Slow timed up and go test
(e.g. taking longer than
12 seconds) • Joint disease • Postural changes • Cardiac • Side effects of PD medications • Visual impairment
and hearing
loss • Autonomic impairment • Co-​morbidities • Cognitive
changes

6.10  Neurodegenerative disorders in older people 607 Olfaction This is the most common non​motor symptom, occurring eventu- ally in up to 90% of patients. There is a deficit in detection, iden- tification, and discrimination of different smells. Patients do not often complain of loss of smell, but this is picked up on direct ques- tioning. Loss of smell may, however, also occur with ageing and with other neurodegenerative conditions. There is no treatment for olfactory deficit. Gastrointestinal problems Swallowing problems are very common in late PD and particu- larly prevalent in multiple system atrophy and progressive supra- nuclear palsy. Patients have difficulty forming and manipulating a bolus of food, and there is slowness and poor coordination of transmission of the bolus to the pharynx, which can be worsened through poor dental hygiene or poorly fitting dentures. Along with oesophageal dysmotility this can give rise to an experience of dysphagia. There may be reduced frequency of swallowing and this may be associated with dribbling of saliva in over 50% of patients. There is slowing of gastric emptying and of small-​bowel transit time, resulting in a feeling of fullness and reduced desire to eat. Altered motility and transit time may affect both nutrient and drug absorption. Constipation is almost a universal feature in clinical PD and may precede the onset by very many years (Table 6.10.8). Faecal im- paction can lead to spurious diarrhoea due to overflow of liquid colonic contents around the obstruction. There is an increased risk of sigmoid volvulus and, in the presence of impaction, an increased risk of colonic rupture. Referral to a speech therapist is key to management of speech and swallowing problems, including dribbling. It is important to assess swallowing in all patients with advancing PD and other Table 6.10.7  Treatment of non​motor symptoms and signs Symptom or sign Onset Treatment Drugs Non​pharmacological Dribbling Later Oral glycopyrrolate Avoid other anticholinergics Botox to salivary glands SALT referral Swallowing problems Later (earlier in PSP and MSA) No specific treatment SALT referral Constipationa Early or before PD symptoms Macrogol laxatives (movicol, laxido) Improve dopaminergic therapy Adequate fluid and fibre intake Improve mobility Abdominal massage Urinary urgency Later in PD, earlier in MSA Avoid oxybutinin Consider tolterodine, trospium, or solifenacin Intermittent self-​catheterization for retention (MSA) Orthostatic hypotension Usually later (early in MSA) Midodrine Fludrocortisone (Pyridostigmine, droxydopa, desmopressin) Avoid sudden postural changes, excessive vagal tone, or vasodilatation. Consider graduated stockings Restless legs Early or before PD symptoms Dopamine agonists Lifestyle advice: less tea, coffee, alcohol, appropriate exercise, sleep hygiene Rapid eye movement sleep behaviour disorder Can be early or before PD symptoms and throughout disease Clonazepam, melatonin Sleep hygiene, review sleeping arrangements Sweating Usually later Possible oral glycopyrrolate Topical antiperspirant often not effective Suitable clothing and environment Depression Can be early or before PD symptoms and throughout disease SSRI antidepressants. Avoid tricyclic antidepressants Exercise, peer support, group therapy, cognitive therapy Anxiety Can be early or before PD symptoms and throughout disease SSRI antidepressants (those licensed for anxiety) Exercise, peer support, group therapy, cognitive therapy, relaxation Psychosis Illusions and visual experiences common in first 5 years—​full psychosis later Reduction in PD drugs Atypical antipsychotics Acetylcholinesterase inhibitor Counselling patients and carer Dementia Mild cognitive impairment common early in older people Dementia later Acetylcholinesterase inhibitor Memantine Multidisciplinary support, liaison with psychiatry a Notes—​see Table 6.10.8. MSA, multiple system atrophy; PD, Parkinson’s disease; SALT, speech and language therapist; SSRI, selective serotonin reuptake inhibitor. Table 6.10.8  Constipation in PD and related conditions Causes Mechanisms • Changes in the neural plexus of
the colon • Colonic dysmotility • Autonomic changes • Anorectal dysfunction • Reduced mobility • A combination of the two • Reduced fluid intake • Poor diet

608 Section 6  Old age medicine neurodegenerative conditions because of the risk of aspiration. The speech therapist will teach compensatory strategies to patients to reduce dribbling and to aid swallowing. In cases with problematic dribbling the use of Botulinum toxin A or B to the parotid and saliva glands can be considered. Anticholinergics are limited by side effects and increased confusion in older people with PD, hence use of sublingual atropine or topical hyoscine should be avoided. There is limited evidence for oral glycopyrrolate (which does not cross the blood brain barrier) and some interest in ipratropium bromide, and the unlicensed use of glycopyrrolate 1–​2 mg twice to three times per day can be considered under specialist supervision. L-​dopa possibly improves the volitional phase of swallowing. In acutely ill cases short-​term enteric feeding might be required. For longer term management, there needs to be consideration and discussion about the potential benefits and burdens of enteral feeding in those with severe swallowing difficulties in late stage disease. Delayed gastric emptying may be helped by advice about meal size and content, and the use of liquid L-​dopa. There is no specific management available for the delay in small-​bowel transit time. Colonic dysmotility may be helped by increasing fibre and fluid intake and use of osmotic laxatives (macrogol). It is important to ensure regular rather than intermittent use of laxatives to avoid constipation with overflow diarrhoea, although laxatives may ex- acerbate anorectal dysfunction, which may be helped by improve- ment in dopaminergic therapy. It is also important to assess nutritional state and consider re- ferral to a dietician. Appetite may be reduced and food enjoyment changed due to loss of smell. Altering the overall volume and con- sistency of food is likely to reduce food adequacy unless specific adjustments and/​or supplements are provided. Urogenital symptoms Sexual dysfunction is common in PD, which is associated with loss of libido and erectile dysfunction. The cause of sexual dysfunction is due to combination of autonomic impairment, mood changes, psychosocial changes, co​morbidity, and (in men) age-​related tes- tosterone deficiency. Urinary symptoms are common with increasing age but are more prevalent in PD, where they affect up to half of all patients. Symptoms of bladder overactivity include frequency and urgency of micturition. A weak detrusor combined with sphincter dysfunc- tion causes hesitancy and a weak stream of urine. Dysfunction of the sphincter and pelvic floor muscles exacerbate all symptoms. In older men, symptoms commonly overlap with prostatism. Urinary symptoms early in the course of parkinsonism raises the suspicion of the diagnosis of multiple system atrophy, particularly if there is post-​voidal residual volume greater than 100 ml. The nature of and cause of sexual dysfunction in older people should be explored through a specialist clinic. The role of androgen or oestrogen replacement in older people is unclear. For erectile dysfunction, the use of phosphodiesterase inhibitors such as sildenafil can be considered, although they may cause hypotension. In cases of detrusor overactivity, urgency, and frequency, anti- cholinergic drugs that are less likely to cross the blood brain barrier should be considered, such as tolterodine, trospium, or solifenacin. Drugs such as oxybutynin are more likely to cross the blood brain barrier and should be avoided in older people due to their tendency to cause confusion. For patients who have not responded to, or are not suitable for, anticholinergics, the β-​3 agonist mirabegron or bladder wall botulinum toxin may also be considered. The results of prostatic surgery and effects on continence in older men with PD are unpredictable. Intermittent self-​catheterization may be needed in multiple system atrophy. Cardiovascular symptoms Cardiovascular autonomic dysfunction is common as PD advances, is present early in multiple system atrophy, and is very common in dementia with Lewy bodies. Symptoms include dizziness and light-​headedness, falls, loss of confidence when walking, fatigue, and feeling muddled or confused. Patients may also experience pain over the shoulders and into the neck (coat hanger pain), and even angina like pain. Postprandial dizziness is also common. It is important to monitor blood pressure regularly because orthostatic (postural) hypotension may occur in half PD patients. It should be checked after lying for up to 10 minutes (or sitting if this is not feasible), and then on standing at one and again at three minutes. A drop in systolic blood pressure of greater than 20 mm Hg or to below 100 mm Hg, or a drop of 10 mm diastolic, is considered ab- normal. Orthostatic hypotension may be associated with cognitive impairment and dementia. Patients with PD and particularly de- mentia with Lewy bodies may develop neurovascular instability, with associated fluctuations in blood pressure and carotid sinus sensitivity, leading to syncope. The simplest assessment for cardiovascular autonomic dys- function is 24-​hour blood pressure monitoring, which will show a reversal of the normal diurnal variation in blood pressure with daytime hypotension interspersed with periods of marked hyper- tension when recumbent or at night. The investigation and man- agement of syncope is considered in more detail in Chapters 6.8 and 16.2.2. Tilt table testing may be undertaken with or without glyceryl trinitrate (GTN) provocation, but detailed tests of auto- nomic function are not normally undertaken in daily practice. Practical management of symptoms includes non​pharmaco- logical interventions as the first line. While drugs may increase standing systolic blood pressure, they may also increase postural blood pressure drop and exacerbate recumbent and nocturnal hypertension. There is little evidence that treatments affect symp- toms, functional ability, or quality of life. The most commonly used drug is fludrocortisone, whose most likely side effect is oedema. The sympathomimetic vasoconstrictor midodrine may be used under specialist supervision with the last dose given in late after- noon to avoid exacerbating night-​time hypertension. Other drugs such as pyridostigmine, droxydopa, or desmopressin are restricted to clinical trials. Sleep disorders Sleep disorders may precede the motor symptoms of PD, ultimately affecting over 50% of patients, and they are also common in de- mentia with Lewy bodies and multiple system atrophy. Daytime sleepiness is common in PD, may be more common with increasing age, and is increased by the use of dopaminergic drugs, particularly direct acting agonists. These symptoms are important since they may affect safety, particularly with driving. The use of modafinil may be considered if other causes of sleepiness have been excluded. Rapid eye movement sleep behaviour disorder may also precede

6.10  Neurodegenerative disorders in older people 609 PD, dementia with Lewy bodies, and multiple system atrophy. In this condition the normal atonia seen in rapid eye movement sleep is lost, allowing the person to move and shout in sleep, which can be problematic during aggressive dreams. It is important to distin- guish this from night-​time hallucinations. Good daytime control of symptoms and control of motor symp- toms in the evening and overnight will enhance sleep quality. The use of long acting L-​dopa last thing at night may help night-​ time symptoms. Continued use of night-​time sedation should be avoided due to possible increased risk of falls. Direct acting dopa- mine agonists may be associated particularly with daytime sleepi- ness and should be reduced carefully where this occurs, especially when causing sudden onset of sleepiness. The effects on driving should be reviewed. Rapid eye movement sleep behaviour disorder may benefit from the use of 0.5–​1 mg of clonazepam at night. Thermo-​regulation Peripheral autonomic dysfunction linked with hypothalamic dopa- mine deficiency is associated with abnormalities of temperature control. This presents with bouts of sweating in over 60% people with PD and may be associated with motor fluctuation. Patients may be noted to have fluctuation in temperature when monitored in hospital. The sweating affects the whole body and is therefore not amenable to local control with antiperspirants. Good control of motor function is the mainstay of treatment. Unlicensed specialist use of the oral glycopyrrolate may be considered. Respiratory problems The ultimate cause of death in many people with PD is broncho- pneumonia and it is suspected that respiratory dysfunction in Parkinson’s may predispose to this condition, along with an in- creased risk of aspiration due to swallowing difficulties. There may be a combined obstructive and restrictive pattern, which often goes unrecognized. Stridor may be a feature of multiple system atrophy. It is important to ensure good motor control, promote physical activity, facilitate good sitting posture, recognize the risk of aspir- ation, ensure care during anaesthesia, and consider pulmonary rehabilitation. Pain Pain is a common symptom and is often unrecognized. It may be due to abnormal central pain mechanisms, neuropathy, dystonia, dyskinesia, and musculoskeletal problems. Shoulder pain can be a presenting feature of PD. Good control of motor function and attention to posture and musculoskeletal symptoms is important. The usual pain pathway should be followed, and patients may need the support of specialist pain services. Neuropsychiatric problems In many ways the maintenance of mental health in PD and other neurodegenerative conditions may be more important than the physical state, since neuropsychiatric problems adversely affect quality of life. Depression and dementia are associated with in- creased mortality. The risk of developing dementia in PD is considerably higher than that of age-​matched controls, affecting over 80% of patients in the long term. Dementia is associated with spread of pathology into cortical areas, often associated with an increasing burden of AD and vascular pathology associated with a significant cholin- ergic deficiency. Subtle cognitive impairment may be detected early on in the disease, particularly in older patients. Cognitive impair- ment in PD particularly affects planning or executive function, visuospatial function and attention, rather than memory functions (non​amnestic dementia), whereas in AD the dementia affects pref- erentially memory (amnestic dementia). Dementia and (particu- larly) dyspraxia can be early features of corticobasal degeneration. Dopaminergic medication may help improve cognition in early disease but later may have an adverse effect. Management of de- mentia in PD is similar to the principles involved in the management of other forms of dementia, supported by a specialist multidiscip- linary team with mental health expertise. Acetylcholinesterase in- hibitors such as rivastigmine should be considered under specialist guidance, following pulse and electrocardiogram screening to avoid cardiovascular complications. Memantine may be considered for those intolerant of acetylcholinesterase inhibitors. Although there is great interest in the possible use of non​pharmacological interventions, evidence is currently lacking. Psychosis Hallucinations occur in up to 50% of people with PD and are very common in dementia with Lewy bodies. Drug treatment adds to the effects of visual disturbances, changes in sleep, cognitive impair- ment and effects of light and shadows to precipitate hallucinations (Fig. 6.10.3). Hallucinations may be visual, usually of animals or people, but occasionally may also be auditory. They may be associ- ated with the secondary development of delusions. People with PD are also prone to delirium, particularly during acute illness, with hallucinations as part of this. An explanation of the nature of the experiences to the patient and carer can often alleviate concerns about hallucinations. Consider gradual reduction of dopaminergic drugs under the supervision of a specialist, particularly focusing on drugs most likely to precipi- tate hallucinations such as anticholinergic drugs or direct acting dopamine agonists (Fig. 6.10.4). It is, however, important to avoid sudden reduction of dopaminergic treatment as this may be asso- ciated with development of hyperpyrexia. Achieving a balance be- tween the benefits of motor control with the risk of hallucinations Brain neurochemical abnormalities Visual dysfunction Environment PD medications Cortical pathology PD psychosis Brainstem/ sleep dysfuntion Fig. 6.10.3  Aetiology of psychosis in Parkinson’s disease (PD).

610 Section 6  Old age medicine will be impacted by individual patient tolerance of symptoms. In the presence of cognitive impairment acetylcholinesterase inhibi- tors may reduce hallucinations. Occasionally low-​dose atypical neuroleptics may need to be considered, such as short-​term use of quetiapine or specialist use of clozapine. Mood Depression and anxiety are common in PD and other neuro­ degenerative conditions and may affect 50% of patients. Anxiety may be associated with motor fluctuation. Depression is often under-​recognized, particularly in older patients. Dopaminergic therapy should be optimized to reduce motor fluctuations. Non​pharmacological interventions including anx- iety management and cognitive approaches should be considered. Selective serotonin reuptake inhibitors antidepressants may be considered in appropriate cases, but tricyclic antidepressants are usually avoided. There is a potential interaction between se- lective serotonin reuptake inhibitors and tricyclic antidepressants with monoamine oxidase B (MAOB) inhibitors, which can cause hyperpyrexia. Prognosis All neurodegenerative conditions are progressive:  no treatment available can modify disease progression, but treatment can sig- nificantly improve quality of life. Progression is usually slow, al- though multiple system atrophy, progressive supranuclear palsy, and (occasionally) dementia with Lewy bodies can progress more rapidly. The final stages of PD, AD, and dementia with Lewy bodies are remarkably similar, with a combination of dementia, psychosis, immobility due to parkinsonism and a requirement for compre- hensive personal and nursing care. Palliative care As neurodegenerative conditions advance it is important to rec- ognize the palliative needs of patients and the support required for carers. Advanced care planning decisions related to complex interventions such as enteric feeding or life-​support may need to be considered, and this needs to be done earlier in the more ac- celerated course of progressive supranuclear palsy, multiple system atrophy, and corticobasal degeneration. With the development of increasingly severe motor disability, non​motor problems such as dysphagia, and dementia, the focus of treatment should be on sup- portive care with the minimization of aggressive treatments and interventions. Management should be focused on comfort and quality of life. Many people in the advanced stages of disease may require nursing at home or in a nursing home. Although clinic attendance becomes impossible, ongoing involvement of clinical staff with relevant expertise remains necessary. Close liaison with specialist palliative care services should be considered. Areas of future research In future there will be a greater concentration on research into the relationship between ageing and neurodegeneration and the pre- clinical prodromal periods of all these conditions, since it is hoped that early preventative intervention will reduce progression. There will be an increased understanding of the contribution of risk fac- tors and susceptibility genes to the aetiology of neurodegenerative conditions in older people, perhaps allowing preventative strat- egies for those at risk of the conditions. It is clear that these con- ditions are extremely complex and the prospect of a single cure for each is unrealistic, but it is more likely that a better understanding of the conditions will lead to a variety of individualized preventa- tive and treatment strategies. FURTHER READING Aarsland D, et al. (2007). The effect of age of onset of PD on risk of dementia. J Neurol, 254, 38–​45. Berg D, et al. (2014). Time to redefine PD? Introductory statement of the MDS Task Force on the definition of Parkinson’s disease. Mov Disord, 29, 454–​62. Burn DJ (2010). The treatment of cognitive impairment associated with Parkinson’s disease. Brain Pathol, 20, 672–​8. Campbell N, et al. (2009). The cognitive impact of anticholinergics: a clinical review. Clin Interv Aging, 4, 225–​33. Chaudhuri KR, Healy D, Schapira AHV (2006). The non-​motor symptoms of Parkinson’s disease:  diagnosis and management. Lancet Neurol, 5, 235–​45. Emre M, et al. (2004). Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med, 351, 2509–​18. Halliday G, et al. (2008). The progression of pathology in longitudin- ally followed patients with Parkinson’s disease. Acta Neuropathol, 115, 409–​15. Hawkes CH (2008). Parkinson’s disease and aging: same or different process? Mov Disord, 23, 47–​53. Hindle JV (2010). Ageing, neurodegeneration and Parkinson’s dis- ease. Age Ageing, 39, 156–​61. Jenner P, et al. (2013). Parkinson’s disease—​the debate on the clin- ical phenomenology, aetiology, pathology and pathogenesis. J Parkinsons Dis, 3, 1–​11. Kalra S, Grosset DG, Benamer HT (2010). Differentiating vascular parkinsonism from idiopathic Parkinson’s disease: a systematic review. Mov Disord, 25, 149–​56. Mattson MP, Magnus T (2006). Ageing and neuronal vulnerability. Nat Rev Neurosci, 7, 278–​94. McKeith IG, et al. (2005). Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology, 65, 1863–​72. Anticholinergics Tricyclics Amantidine Dopamine agonists Apomorphine Other antidepressants COMT MAOB L-dopa Fig. 6.10.4  Stepwise drug adjustment and withdrawal in psychosis in PD.

6.10  Neurodegenerative disorders in older people 611 Mosimann UP, et al. (2006). Characteristics of visual hallucinations in Parkinson disease dementia and dementia with lewy bodies. Am J Geriatr Psychiatry, 14, 153–​60. Muzerengi S, Clarke CE (2015). Initial drug treatment in Parkinson’s disease. BMJ, 351, h4669. National Institute for Health and Clinical Excellence (NICE) (2017). Parkinson’s disease in adults. [NG71]. https://www.nice.org.uk/ guidance/ng71 Petrou M, et al. (2015). Amyloid deposition in Parkinson’s disease and cognitive impairment: a systematic review. Mov Disord, 30, 928–​35. Playfer J, Hindle J (eds). Parkinson’s disease in the older patient, 2nd edition. Radcliffe, Oxford. Scottish Intercollegiate Guideline Network (2010). Diagnosis and pharmacological management of Parkinson’s disease. Guideline No. 113. Shin HW, Chung SJ (2012). Drug-​induced parkinsonism. J Clin Neurol (Seoul, Korea), 8, 15–​21. Srivanitchapoom P, et al. (2014). Drooling in Parkinson’s disease:
a review. Parkinsonism Relat Disord, 20, 1109–​18. Yarnall A, Rochester L, Burn DJ (2011). The interplay of cholinergic function, attention, and falls in Parkinson’s disease. Mov Disord, 26, 2496–​503. Zijlmans JCM, et al. (2004). The L-​dopa response in vascular parkin- sonism. J Neurol Neurosurg Psychiatry, 75, 545–​7.

6.11 Promotion of dignity in the life and death of

6.11 Promotion of dignity in the life and death of older patients 612

ESSENTIALS Respect for the dignity of patients is a traditional part of medical codes. Dignified care is key to a holistic person-​centred approach, with participation of the individual, communication, and respect. Nurses and doctors recognize lack of dignity in depersonalized care, treating the person as an object, humiliation, abuse, and invisibility. Older people regard dignity as critically important in their care. This relates to issues around privacy, courteousness, respect for the individual, and consideration about choices related to care, and to respect for cultural or religious needs. Assuring dignity requires the sensitive addressing of basic needs and the promotion of inclusivity and participation, with recognition that even in the presence of some impairment of cognition the wishes and views of the patient remain central to decision-​making. Elder abuse can be defined as a single or repeated act or lack of appropriate action, occurring within any relationship where there is an expectation of trust, which causes harm or distress to an older person. These acts may be through neglect, or physical or psycho- logical abuse, or sexual assault. The precise prevalence of abuse is uncertain, but it occurs sufficiently frequently that all clinicians who come into contact with older people are likely to encounter it. Recognizing when people enter the last year of their life is im- portant to achieve the right focus of care for older people. The rate of functional decline, measured as deteriorating performance status, is the most reliable indicator of prognosis in patients with ad- vanced illness, regardless of diagnosis. A diagnosis of dying should prompt timely appropriate discussions with patient (when possible) and family members, with explanation of the transition of the goals of care from ‘cure’ to ‘maintaining comfort’. Anticipatory care plan- ning is key to ensuring that patients live and die in the manner that they wish. Dignity A philosophical perspective Philosophically the concept of dignity dates to at least the time of Aristotle (384–​322 BC), who linked it to a sense of being worthy of respect; he regarded it as the desired state between an excess of servility and of self-​importance. Subsequently, Kant in the 18th century defined dignity as that quality possessed by things which have value but cannot be traded, and which are above price. For Kant, the concept of dignity related to the human character- istics of rationality and autonomy. Although Kant referred to the ‘intrinsic value’ of humans, this is linked in his writing to the possession of autonomy. More recent philosophers have also identified autonomy as an important factor in dignity, for example, describing a foolish choice as having the potential to cause the individual to lack dignity. The concept of autonomy as central to dignity is challenged by others, who see it as one of the values but not the only value important in dignity, and who recognize the importance of dignity even when autonomy is lacking. A well-​reported example of the tension which can arise be- tween dignity and autonomy is the case (which occurred as recently as the 1990s) of the French dwarf who was paid to be thrown in a drinking game. The local town council ruled that this was an insult to human dignity, but the dwarf in question appealed against the judgement saying they had deprived him of his livelihood and he ought to be allowed to make autonomous decisions for himself. The following concepts of dignity have been described which are helpful in considering dignity in the context of healthcare. Nordenfelt describes intrinsic and contingent value, and divides the latter into four varieties of dignity (Box 6.11.1). 6.11 Promotion of dignity in the life and death of older patients Eileen Burns and Claire Scampion Box 6.11.1  Dignity • The dignity of Menschenwurde—​the dignity all humans have simply by virtue of being human. • Dignity of merit—​dignity of ‘office holding’, or as a consequence of having earned merit, for example, a hereditary monarch. • Dignity of moral stature—​dignity based on the actions or omissions of an individual, for example, a local community leader. • Dignity of personal identity—​related to concepts of self-​respect, integrity, autonomy, and inclusion. This can be taken away when someone is insulted or humiliated, for example, a school child sent to stand in the corner.

6.11  Promotion of dignity in the life and death of older patients 613 The meaning of dignity in a healthcare setting Actions of others can be seen to either enhance or reduce another’s dignity. In the context of a care setting, the relationship may in- clude one party (e.g. the doctor or nurse) holding a position of dominance. Dignity can be respected or violated in many ways, due to acts or omissions of staff (Box 6.11.2). Professional views of what constitutes undignified care accord with these views: nurses and doctors recognize lack of dignity in depersonalized care, treating the person as an object, humiliation, abuse, and invisibility. Dignified care is key to a holistic person-​ centred approach, with participation of the individual, communi- cation, and respect. The role of dignity in the code of conduct of doctors
and other healthcare professionals Respect for the dignity of patients is a traditional part of medical and nursing codes. The Hippocratic oath requires those who swear it to respect those who require treatment, regardless of gender or status, and to do so with justice (Box 6.11.3 and Fig. 6.11.1). In many medical schools, updated versions of the Hippocratic oath are sworn, including vows not to alter one’s practice on the basis of the patient’s race, nationality, religion, sex, socioeconomic standing, or sexual orientation. Others include assurances of the physician’s accountability to his or her patients, protection of patients’ autonomy, and informed consent or assistance with decision-​making. Both the UK Royal College of Nursing and the International Nursing Code emphasize the respect of the dignity of the individual in their care as a core quality of the nurse. Views of older people and their families about dignity in healthcare Within the healthcare context, the concepts of ‘Menchenwurde’ (i.e. respect for all humans as a consequence of their humanity) identifies that we should treat the unconscious, demented, or de- lirious patient in the same way as any other patient with respect, tolerance, and empathy. Older people regard dignity as critically important in their care. Although philosophers may struggle to define the term, patients and their relatives are clear that in the context of a healthcare envir- onment it relates to issues around privacy, courteousness, respect for the individual, and consideration about choices related to care, and to respect for cultural or religious needs (Box 6.11.4). Box 6.11.2  A taxonomy of possible transgressions of dignity • Not being seen: when someone is disregarded or unheard—​the pa- tient calling for the nurse; the relative trying to catch the eye of the doctor. • Being seen, but only as member of a group (e.g. as a woman, an old person, and so on). Group membership can be a source of pride, but if the treatment of the group is disadvantageous (e.g. delayed attention to a referral from a ‘geriatrics’ ward), then the dignity of the individual is diminished. • Injuries to dignity from violations of personal space: if permission is not gained there is substantial risk of violation to dignity in the healthcare setting. An example may be the disregard for a wish for privacy in the areas of washing, dressing, or using a toilet. • Humiliation: in this setting, dignity is injured by the singling out of a subject for criticism. An inappropriate response from healthcare staff to a delirious patient or one who has suffered an episode of incontin- ence can easily be perceived as humiliation. Box 6.11.3  The Hippocratic oath ‘ . . . Whatever houses I may visit, I will come for the benefit of the sick, remaining free of all intentional injustice, of all mischief and in particular of sexual relations with both female and male persons, be they free or slaves . . . ’ (translated from the Greek by Edelstein L. The Hippocratic oath: Text, translation and interpretation. In: Temkin O, Temkin CL, eds. Ancient medicine: Selected papers of Ludwig Edelstein. Baltimore: Johns Hopkins University Press, 1967:
3-​64. Reprinted by permission of Johns Hopkins University Press.) Fig. 6.11.1  Fragment of the Hippocratic oath on papyrus from the
3rd century. Wellcome Library, London. Box 6.11.4  Issues highlighted by patient and carers after hospital discharge in the United Kingdom • Being treated as an individual • Help with eating and drinking • Help with toileting • Privacy in care: keeping curtains closed, private rooms, informa- tion being kept private • Being addressed appropriately by staff (avoidance of inappro- priate use of endearments such as ‘love’, ‘dear’) • Maintaining respectable appearance—​attention to clothing, grooming • Stimulation—​this was especially a concern for care home residents or those living alone in their own home

614 Section 6  Old age medicine The challenge to dignity in the care of older people in the acute hospital Research into the experience of care in acute hospitals has iden- tified several possible barriers to the provision of dignified care (Box 6.11.5). The view that hospitals are not the right places for older people fails to recognize that older people are the main users of healthcare. Thus, the physical environment, staff skills, and education and or- ganizational processes are often not aligned to the needs of the older people using the hospital facilities. For people with dementia, appropriately designed environ- ments can: • promote independence • reduce the incidence of agitation and challenging behaviour and the prescription of antipsychotic medication • improve nutrition and hydration • increase engagement in meaningful activities • encourage greater carer involvement • improve staff morale, recruitment, and retention Careful ward design with attention to colour coding of bays, ad- equate clear signage, safe walking spaces, and communal areas can enhance dignity. Adequate room for equipment required for care (such as hoists), gender-​specific washing and toileting facilities, all promote dignity in care. Other factors important to the promotion of dignity are staff education about specific aspects of care of older people including those with dementia, and the engendering of a culture which values and promotes courteous and respectful communication and inter- actions with patients. A  focus on ‘targets’ may have unintended consequences that make dignified care more difficult to achieve. These may include: • Frequent ward moves in order to allow access for new patients presenting to hospital, or because of ‘specialty bed’ requirements, with loss of the development of a relationship between staff and patients, central to personal care. • A blanket policy of the use of isolation rooms with the aim of re- ducing risk of infection, without recognition that the risk of falls is increased by the use of side rooms, nor with a recognition of the risk of lack of access to stimulation and to care when needed. Dignity and safety may be compromised if an individual assess- ment of risk and benefit is not made. • Financial targets may restrict staffing levels and ‘skill mix’, ren- dering the provision of timely and appropriate care difficult. If staff cannot meet the needs of patients—​especially around eating and drinking, washing, dressing, and toileting—​dignity is compromised. ‘Seeing the person’ as an individual includes respectful commu- nication, promotion of privacy and of autonomy, and of a sense of control. It requires the sensitive addressing of basic needs such as nutrition, elimination, and personal hygiene, and the promo- tion of inclusivity and participation by providing information and enhancing communication to support decision-​making, with recognition that even in the presence of some impairment of cognition, the wishes and views of the patient remain central to decision-​making. Elder abuse Elder abuse was first described in 1975, and general clinical aware- ness of this problem has grown since that time. Although the early research was derived from populations in the Western world, data from around the globe has indicated that it is a worldwide problem. The most widely used definition of elder abuse comes from the World Health Organization: ‘A single or repeated act or lack of appropriate action, occurring within any relationship where there is an expectation of trust which causes harm or distress to an older person.’ The person in a relationship of trust with the older person may be a family member, friend, or neighbour, or a paid (‘formal’) care- giver, including both health and social care workers. Types of elder abuse include as follows: • Physical abuse including acts done with the intention causing physical pain or injury. These may include assault, hitting, slap- ping, pushing, burning or scalding, misuse of medication, and restraint. • Psychological abuse, defined as acts done with the intention of causing emotional pain, including emotional abuse, threats of harm or abandonment, deprivation of contact, humiliation, blaming, controlling, intimidation, coercion, harassment, verbal abuse, isolation, or unreasonable withdrawal of services or sup- port networks. • Sexual assault, including rape, indecent exposure, sexual harassment, inappropriate looking or touching, sexual teasing or innuendo, sexual photography, subjection to pornography or witnessing sexual acts, indecent exposure or sexual assault, or sexual acts to which the person has not consented or was pressured into consenting. • Financial abuse, including misappropriation of the older person’s money or property, including theft, fraud, coercion in relation to a person’s financial affairs or arrangements including in connec- tion with wills, property, inheritance, or financial transactions (e.g. loans) or the misuse or misappropriation of property, pos- sessions, or benefits. • Neglect, or the failure of a designated carer to meet the needs of the dependent older person, including ignoring medical, emo- tional, or physical care needs, failure to provide access to appro- priate healthcare and support, the withholding of the necessities of life such as medication, adequate nutrition, and heating. Estimates of the prevalence of elder abuse have been difficult as definitions used in the past have varied, and as surveys tend to under-​report due to the tendency of abuse to be hidden. A further Box 6.11.5  Challenges to provision of dignified care by hospital staff • The view that an acute hospital is not the right place for older people • Attention paid to those factors on which a hospital’s success is seen to rest, which may have unintended consequences on dignity in care • ‘Seeing the person’: person-​centred, not task-​driven care

6.11  Promotion of dignity in the life and death of older patients 615 confounding factor is the higher rate of abuse among those with dementia or depression; both of these populations are less likely to be able to respond to surveys. Not all studies have used the same definition of abuse. With these caveats, the rates reported are shown in Table 6.11.1. While the precise prevalence of various forms of abuse is un- certain, the phenomenon occurs sufficiently frequently that all clinicians who come into contact with older people are likely to en- counter it in their routine practice. It is noteworthy that the preva- lence of abuse identified in surveys far exceeds that reported to adult protection services, indicating that the vast majority of abuse goes unreported, using statutory procedures. Abuse of older people can occur in several environments; within their own home, a care home, or an acute hospital setting. The term ‘institutional abuse’ has been used to describe abuse that is the re- sult of organizational action or inaction, for example, as the result of inappropriate policies, poor staff training, and education. So risk factors arise across several domains (Box 6.11.6). Evidence on the role of physical (rather than mental) infirmity as a risk factor for receiving abuse is conflicting. Older people who suffer one form of abuse may be subject to other forms: for ex- ample, those subject to physical abuse are likely also to be abused financially. In some cases the pattern of elder abuse is a continu- ation of an abusive relationship that antedates old age. Cases also occur when a previously abusive male partner is abused by his female partner when he is old, frail, and no longer the dominant partner. Cultural differences may influence perception of what consti- tutes abuse: for example, the use of physical restraints is regarded as acceptable in some healthcare systems and regarded as unaccept- able in others; in some cultures there is an expectation that family members may act as a proxy for the views of the older person, re- gardless of their capacity to make decisions, whereas others would regard this as an abuse of autonomy. Identification of abuse Doctors, nurses, and other medical personnel can play a vital role in assisting elder abuse victims. Studies have shown that elderly individuals, on average, make 14 visits per year to a primary or secondary care physician, and therefore opportunities for earlier recognition of abuse may be currently unidentified. Although there has been an increase in awareness of elder abuse over the years, physicians tend to only report 2% of elder abuse cases. Reasons for lack of reporting by physicians include a failure to recognize signs of abuse, lack of current knowledge concerning laws on elder abuse, concern about the possible reaction of the abuser, and the impact on the relationship with the older pa- tient. Other concerns include anxiety about possible court ap- pearances, actual or anticipated lack of cooperation from elderly patients or families, and a perception of lack of time or reim- bursement for time. Education is clearly important to equip clinicians to identify the signs of possible abuse. A  European undergraduate curriculum for geriatric medicine, devised using a modified Delphi technique (with agreement between representatives of 29 countries) includes elder abuse. However, a survey of UK medical schools indicated that this topic was not taught in 35% of schools, and it was exam- ined in only 29%. Clinical assessment of the person at risk of abuse There are no validated screening tools recommended for routine use to detect elder abuse. Clinicians are required to be aware of risk factors and alert to indications of possible abuse. Although abuse can occur in situations with none of the risk factors listed in Box 6.11.6, the presence of one or more risk factors should heighten awareness. There are few specific diagnostic signs, as bruising, fractures, la- cerations, burns, and head injuries can happen either as a conse- quence of falls or accidental injury or of abuse. These may be noted in an initial assessment while beginning to take the history and establish rapport. Weight loss is common in those with frailty as well as in neglect. Medication non​adherence may be an innocent misunderstanding or intentional over-​ or undertreatment. Although the issues in history and examination are listed sep- arately in Box 6.11.7, in practice the overall picture is built grad- ually, in an iterative manner, reacting to observations made. This may not be completed at one session, but if a patient is thought Table 6.11.1  Prevalence of reported abuse by type Type of abuse Percentage Abuse (all forms) within the preceding month (community dwelling elderly people) 6% Physical abuse within the previous year (within their relationship, elderly couples) 6% Significant psychological abuse within the previous year (disabled older adults) 25% Family carers reporting physical abuse towards care recipients with dementia within the previous year 5% Care home staff admitting perpetrating significant psychological abuse 16% Rates of abuse reported to adult protection services 1–​2% Box 6.11.6  Risk factors for abuse • Living with others (rather than alone), with increased risk of conflict and friction. This applies for all forms of abuse except financial, which is commoner in those living alone. • Dementia: people with dementia are at higher risk of abuse. The mechanism is thought to be through the increased stress found among carers of dementia patients. Sleep disturbance or behavioural disturbance (especially if aggression or violence occurs) may be a trigger. • Social isolation: the victim is more likely to be isolated from friends and family (apart from their caregiver) than non​victims. Isolation can lead to an increase in stress in the caregiver and abusive behav- iours can be hidden in the absence of others who might otherwise intervene. • Mental illness (especially depression) in the caregiver is more common than in non​abusing caregivers. Alcohol abuse in the abuser is also associated with an increased risk of abuse. • Financial reliance of some caregivers on the dependent person is another factor more commonly seen in abusers. This may prevent a care-​giving son or daughter from leaving home, or may result in attempts by the caregiver to extract money from the victim.

616 Section 6  Old age medicine to be at ongoing risk, then early action may be necessary. A team approach is vital. A thorough assessment with investigation as to the cause of any abnormalities identified is required. Victims will commonly be ashamed that they have been abused and a sensitive approach is essential. If abuse seems likely, then the history should include the nature, frequency, severity, and context of the abuse. Responding to definite or suspected abuse This will depend on the situation (Box 6.11.8). Immediate treat- ment to injuries is a priority, though it may be appropriate to obtain photographic evidence. Where a criminal offence is suspected, then forensic evidence collection is a priority. If a criminal offence has been committed or is suspected, the police should be informed. Actions which may constitute crim- inal offences are assault (physical or psychological), sexual assault and rape, theft, fraud, or other forms of financial exploitation, and some forms of discrimination such as on the grounds of race or gender. In cases of alleged criminal offences the responsibility for initiating prosecution is with the state (the police force or public prosecution service). Agencies such as health, social care, and police services need to work together to ensure a properly coordinated joint investigation takes place, minimizing distress that results from repeated interviewing. The older person’s emotional, physical, intellectual, and mental capacity in relation to self determination and consent, and any intimidation, misuse of authority, or undue influence, must be as- sessed. Assessment of ‘capacity’ with regard to decision-​making about abuse is the key to action. Careful assessment is required if an older person chooses to make decisions which place them at risk of being abused or neglected. People are assumed to have capacity to make their own decisions. Barriers to decision-​making (e.g. sensory deficits or communication difficulties) must be addressed to maximize the opportunity of the elder to participate fully in decisions about their care. If someone has capacity and declines assistance, this limits the help that he or she may be given, but action may be required to protect others who are at risk of harm. Outcome for victims of abuse Victims of abuse are more likely to experience adverse outcomes compared with non​abused elders with a similar burden of co​morbidities. They are more likely to die, to be admitted to a care home, and to suffer from depression than their peers. Admission to hospital is commoner in those whose abuse has been reported to adult protection services, compared with others with similar burden of co​morbidities but not subject to abuse. Prevention of recurrent abuse A carer who experiences unintentional or intentional harm from the adult they are supporting, or a carer who unintentionally harms or neglects the adult for whom they are caring, may need a careful assessment to establish whether the risk of future abuse can be mitigated by provision of treatment, training, or support. An understanding of the factors that led to abuse may allow a remedial course of action. This might include additional support if carer strain is implicated, support for abstention from alcohol, treatment of depression, or support and treatment in managing ag- gression in patients with dementia. Dignity at the end of life Recognition of the patient reaching the end of life In economically developed countries, increasingly ageing popu­ lations mean that more people are dying over the age of 85, hence Box 6.11.7  Clinical assessment History • Anticipate:  being aware of risk factors and heightened attention to signs which may suggest abuse or neglect • Seek to establish trust and speak in private with the subject • Notice if the carer seems reluctant to facilitate or ‘allow’ this privacy (as the carer may be the abuser) • Enquire directly about any episodes of abuse (physical, emotional, sexual (if indications that this may have occurred) or financial), but using simple words and questions (e.g. ‘do you feel afraid or anxious when you are being helped ... is there anything happening to you at home that you wish was different?’) • Elicit explanation from a carer (possible abuser) for any suspicious findings or allegations, but do this sensitively and avoid ‘acting the policeman’ • If any other informants are available elicit their observations Examination • Note signs of psychological distress • Note general state of hygiene and cleanliness • Examine for signs of dehydration • Note any skin lesions (bruises, lacerations, and so on) and any pressure injury • Note any evidence of traumatic alopecia, and bruises or welts, espe- cially if in an unusual shape or pattern • Rectal or vaginal bleeding or evidence of sexually transmitted infection • Trauma to the wrists or ankles may indicate the use of physical re- straints; glove or stocking distribution scalding may indicate immer- sion burns. Identify symptoms or signs of depression and evidence of dementia (using a formal cognitive test) Box 6.11.8  What happens when an allegation of abuse has been made? • investigation of the complaint • assessment and care planning for the vulnerable person who has been abused • consideration of criminal proceedings • action by employers, such as suspension, disciplinary proceedings, use of complaints and grievance procedures, and action to remove the perpetrator from the professional register • arrangements for treatment or care of the abuser if appropriate, con- sideration of the implications relating to regulation, inspection, and contract monitoring

6.11  Promotion of dignity in the life and death of older patients 617 patterns of disease at the end of life are changing. The World Health Organization considers palliative care for older people to be an ur- gent public health priority. In countries where palliative care is better established, the focus has been on cancer. But in these countries, older people are now more likely to die with multiple co​morbidities, including frailty and dementia, in which palliative care needs are less easily defined. The summative effect may be much greater than might be expected from the individual components, with resultant complexity of presentation and need. Thus recognition of the ter- minal phase of illness can be particularly challenging. Recognizing when people enter the last year of their life is im- portant to achieve the right focus of care for older people. While most people will opt for the offer of investigation and disease-​ orientated treatments where potential for recovery is reasonable, it is the healthcare professional’s role to identify those clinical situ- ations where the patient would likely benefit from a change in the goal of their treatment to supportive and palliative care. This recognition facilitates communication with patients and families and enables the implementation of anticipatory care plan- ning. It allows assessment of future needs and appropriate align- ment of care with patient wishes. For those patients who would prefer to avoid futile and aggressive interventions, which might be burdensome, and include hospital admissions, forward planning allows prioritization of appropriate care in the patient’s preferred place. Many people do not die at home, although most would wish to. In England, most deaths occur in an NHS hospital. Recognizing when people are approaching the end of their life is difficult, and healthcare professionals tend to err towards an op- timistic prognosis. Identifying those who are unlikely to survive more than 12 months is very often more difficult than identifying those who have reached the last days of life. These days, most people die when they are old, and older people are more likely than young to acquire a serious and disabling progressive illness that gradually interferes more with their daily activities until death. Individuals vary, but three trajectory patterns have been described (Box 6.11.9). Trajectory 3 is more common in older patients, particularly those aged over 85 with multimorbidity, dementia, and frailty. One-​quarter of people over 85 have dementia. The end stages of dementia can last two or three years and there may be an absence of a terminal phase, or—​because there is only slight acceleration of the trajectory of functional loss as death approaches—​the point at which a patient enters this terminal phase may be very difficult to recognize. The coexistence of other factors may result in typ- ical late stage features, such as swallowing difficulties, appearing earlier. These patients on trajectory 3 may benefit from inclusion of a palliative approach to their care before they reach a terminal phase, although involvement of specialist palliative care is un- common, as it is also for patients on illness trajectory 2. The stra- tegic need for these groups is to incorporate the end-​of-​life care approaches and necessary palliative treatment skills in primary and community services and medical specialties such as geriatric medicine. It is very difficult to predict prognosis in frail older popula- tions. Disease specific prognostic tools are of limited usefulness because they are insufficiently accurate in predicting survival of patients with multimorbidity. Conversely, the rate of func- tional decline, measured as deteriorating performance status, is strongly correlated with prognosis in patients with advanced illness, regardless of diagnosis. Thus monitoring the patient over a period of time will provide an insight into the momentum of decline, and this is likely to provide the most accurate estimate of prognosis. This period of observation also allows for recogni- tion and treatment of reversible causes of deterioration. Broadly speaking, patients observed to have a monthly or weekly deterior- ation are likely to have a prognosis measured in months or weeks. Those who are deteriorating daily are likely to have a prognosis measured in days. In the United Kingdom, the National Gold Standards Framework uses general prognostic indicators of decline alongside clinical features specific to advanced single organ diseases, such as heart failure, to identify patients at the end of life. For those on illness tra- jectory 3 with multimorbidity, general prognostic indicators may be more useful (Box 6.11.10). For those patients identified as reaching end of life, it is im- portant to recognize their transition to the actively dying phase of their illness in order to facilitate a ‘good death’. Diagnosing dying may be difficult when based on subjective assessment of clinical decline over time, particularly when done by individual professionals and therefore dependent on continuity of care. But signs and symptoms of impending death can often be rec- ognized and then should be communicated to the patient and their family. Remember that however much this seems like a natural pro- gression to the healthcare professional, the actuality of death may still come as a shock to both the patient and their family despite great age, frailty, and multiple co​morbidities. It may be Box 6.11.9  Illness trajectories at the end of life Trajectory 1 is most commonly seen in cancer and describes a short period of reasonably predictable, rapid decline over weeks or months. Where palliative care services exist, this is the group that has been well-​catered for. Trajectory 2 is associated with organ failure, for example, chronic obstructive pulmonary disease or heart failure. Typically, these pa- tients experience long-​term progressive limitations with intermittent periods of crisis often requiring hospitalization. Each crisis has the potential to result in death, but often does not, with the recovery being not easily predictable and often incomplete. Trajectory 3 describes an extended period often over a few years of ‘prolonged dwindling’ in which there is general deterioration on a background of poor baseline physical and/​or cognitive function. This decline may be interjected by periods of ill-​health requiring hospitalization (e.g. for pneumonia or fractured neck of femur, with resultant acute deterioration in baseline function). Box 6.11.10  General prognostic indicators of decline towards end of life 1 Deteriorating functional status. Limited self-​care; in bed/​chair more than 50% of the day 2 Progressive weight loss (more than 10%) in the last six months 3 Two or more unplanned admissions in the last six months, or sentinel event (serious fall, bereavement, transfer to a nursing home) 4 Increasing care requirement or nursing home residency

618 Section 6  Old age medicine appropriate to give a trial of treatment (e.g. antibiotics) if it is thought that the cause of deterioration could be reversible and the diagnosis of dying is in doubt. This should be reviewed regularly, and further intervention should be stopped if there are ongoing signs of deterioration despite treatment. Communicating this ambiguity is important for the support of staff as well as for pa- tients and families. In the last days of life, patients may become increasingly drowsy with an acute deterioration in functional status, becoming bed­ bound and semi-​comatose as death approaches. Interest in food/​ fluids diminishes; there may be increasing difficulties with swal- lowing and consequently taking oral medication is compromised. Poor cardiac output may result in mottled skin, cold peripheries, and reduced urine output. Poor cerebral perfusion may precipi- tate a terminal delirium with agitation or restlessness. With a re- duced level of consciousness, the patient may be unable to clear upper airway secretions and develop noisy gurgling respirations. Towards the last few hours of life, Cheyne–​Stokes respirations with apnoeic episodes may occur. A diagnosis of dying should prompt a timely, frank discus- sion with family members and an explanation of the transition of the goals of care from ‘cure’ to ‘maintaining comfort’. It is important that all the healthcare staff involved understand that the patient is dying and focus their goals of care appropriately in order to facilitate well-​coordinated end-​of-​life care that meets the patient’s physical, psychosocial, and spiritual needs. This should be considered a positive change to achieve ‘dignity in death’. A  medication review should be undertaken, stopping those that do not provide symptomatic benefit and prescribing ‘as required’ medications for symptom relief. For example, mor- phine may be prescribed for pain or breathlessness and mouth care administered to prevent discomfort from a sore mouth (see Chapter 6.7). Anticipatory care planning In patients who are identified as nearing end of life, anticipa- tory care planning is key to ensuring that they live and die in the manner that they wish. Care at the end of life is often provided by multidisciplinary teams from health and social care and the vol- untary sector. Planning ahead enables optimum coordination to facilitate timely adaptations of care to meet the changing needs of the patient. Anticipatory care planning is the process of decision-​making with regards to future care that can come into effect when the patient no longer has capacity. It is not unusual for very sick elderly patients to present when they no longer have capacity and without any formal advance care plans. However, it may be possible to plan for care in potential future situations (e.g. ad- missions to hospital), guided by best interests and discussions with family, taking into account the patient’s previous beliefs and behaviours. An advance care plan must be freely made without coercion while the individual still has mental capacity. It cannot be used to request a specific medical intervention or refuse basic care such as food or water by mouth. In the United Kingdom, antici- patory care planning takes on three main forms as described in Box 6.11.11: although things may differ slightly elsewhere, the basic principles apply. An advance decision to refuse treatment may be invalid if the patient had withdrawn their refusal while they still had capacity, or the patient has behaved in a way that was inconsistent with the de- cision while suggesting that they might have changed their mind. Alternatively, it would be invalid if the patient had subsequently appointed a surrogate decision maker and given them authority to make decisions with regards to the treatments covered in the ad- vance decision. An advance decision to refuse treatment would not be applic- able if the proposed treatment and/​or the circumstances differ to that specified, or if the circumstances have changed such that there are reasonable grounds to believe that this would have af- fected their decision had they known about it while they still had capacity; for example, if a new disease-​modifying treatment has become available. In the event of an advance decision to refuse treatment being invalid or not applicable, a best interests deci- sion should be made with consideration to the wishes set out within it. Anticipatory care planning empowers patients to have input into their current and future care. It allows respect for patient au- tonomy and preparation for the possibility of loss of capacity in the future. There is evidence that it results in less aggressive med- ical care and fewer hospital admissions. In patients who are re- ceiving hospice care in the United Kingdom, 10% of patients who have undertaken anticipatory care planning die in hospital, com- pared to 25% of those patients who have not. The ability of family Box 6.11.11  The three main forms of anticipatory care planning 1 Advance statements. These are documented statements of pref- erences, wishes, beliefs, and values regarding future care. They may relate to medical treatments and/​or non​medical aspects of care. An advance statement is not legally binding, but should be used when the patient no longer has capacity to guide management when a best interests decision is being made. 2 Advance decision to refuse treatment (ADRT). This is a legally binding document in which a patient states a clear refusal of a particular treatment if they no longer have capacity in the future. It is preferable, but not required, that the patient gives specific cir- cumstances in which they would refuse the specific treatment because this will reduce ambiguity and guide clinicians in whether an ADRT is valid and applicable. An ADRT for life-​sustaining treat- ment should be signed and witnessed, and if valid then should be adhered to. 3 Lasting power of attorney (LPA). This allows patients to nominate a person (attorney) who they want to act as a surrogate decision-​ maker should they lack capacity in the future. In the United Kingdom, these are divided into two types; ‘property and financial affairs’ and ‘health and welfare’. If there are concerns that the attorney is not making decisions in the patient’s best interests, then their decisions can be challenged.

6.11  Promotion of dignity in the life and death of older patients 619 members to cope with bereavement is directly influenced by how prepared they are for the death of their relative and anticipatory care planning can reduce the incidence of anxiety, depression, and post-​traumatic stress in surviving relatives. FURTHER READING Boland B, Burnage J, Chowhan H (2013). Safeguarding adults at risk of harm. BMJ, 346, f2716. Boyd K, Murray SA (2010). Recognising and managing key transi- tions in end of life care. BMJ, 314, c4863. British Medical Association (2011). Safeguarding vulnerable adults—
a tool kit for general practitioners. BMA. http://bma. org.uk/-/ media/Files/PDFs/Practical%20advice%20at%20work/Ethics/ safeguarding vulnerableadults.pdf Christakis NA, Lamont EB (2000). Extent and determinants of error in doctors’ prognoses in terminally ill patients: prospective cohort study. BMJ, 320, 469–​72. Coventry PA, et al. (2005). Prediction of appropriate timing of pal- liative care for older adults with non-​malignant life-​threatening disease: a systematic review. Age Aging, 34, 218–​27. Department of Health (2008). End of life care strategy: promoting high quality care for all adults at the end of life. Department of Health, London. Kennedy C, et al. (2014). Diagnosing dying: an integrative literature review. BMJ Support Palliat Care, 4, 263–​70. Lau F, et al. (2009). Using the palliative performance scale to provide meaningful survival estimates. J Pain Symptom Manage, 38, 134–​44. Lynn J, Adamson DM (2003). Living Well at the End of Life: Adapting Health Care to Serious Chronic Illness in Old Age. RAND Corporation, Santa Monica, CA. https://​www.rand.org/​pubs/​white_​papers/​ WP137.html Mullick A, Martin J, Sallnow L (2013). An introduction to advance care planning in practice. BMJ, 347, f6064. Murray SA, et  al. (2005). Illness trajectories and palliative care. BMJ, 330, 10071011. National Audit Office (2008). End of life care. National Audit Office, London. National Gold Standards Framework Centre England (2008). Prognostic Indicator Guidance Paper 2008. https://www. goldstandardsframework.org.uk Royal College of Physicians (2009). Advance Care Planning: Concise Evidence-​based Guidelines. https://​www.rcplondon.ac.uk/​guidelines-​ policy/​advance-​care-​planning Tad W, Bayer T, Dieppe P (2002). Dignity in health care: Reality or
rhetoric. Reviews in Clinical Gerontology, 12(1), 1–4. Woolhead G, Calnan M, Dieppe P, Tadd W (2004). Dignity in older age: what do older people in the United Kingdom think?, Age and Ageing, 33(2), 165–70. World Health Organization (WHO) (2011). Palliative care for older people: better practices. World Health Organization, Geneva, Switzerland.

SECTION 7 Pain and palliative care Section editor: Bee Wee 7.1 Introduction to palliative care   623 Susan Salt 7.2 Pain management   629 Marie Fallon 7.3 Symptoms other than pain   634 Regina McQuillan 7.4 Care of the dying person   639 Suzanne Kite and Adam Hurlow

6.2 Frailty and sarcopenia 521

6.2 Frailty and sarcopenia 521

6.2 Frailty and sarcopenia Andrew Clegg and Harnish Patel ESSENTIALS Sarcopenia and frailty are inter-​related expressions of ageing which identify people at risk of important adverse health events such as falls, disability, and mortality, and the consequent health and social care needs such as hospitalization or care home admission. Sarcopenia is the progressive and generalized loss of skeletal muscle mass and function with age. It has a complex aetiology involving neurohormonal, immunological and nutritional mechan- isms, and is a core component of frailty, which is characterized by reduced biological reserves across a range of physiological systems that increase vulnerability to adverse outcomes following minor stressor events. Detection of frailty should be an essential part of assessment of older people, and the Clinical Frailty Scale is a simple tool based on comprehensive geriatric assessment that enables assignment of a frailty category based on clinical judgement. Adverse trajectories of sarcopenia and frailty can potentially be modified through targeted treatment and multifactorial interven- tions. There is robust evidence to support the use of exercise inter- ventions for older people with sarcopenia and frailty. Introduction The populations of all the world’s countries are ageing. This world- wide increase in life expectancy is remarkable, and should be cele- brated, but living into old age has profound implications for health and well-​being. Sarcopenia and frailty are inter-​related conditions that are common and problematic expressions of ageing. They identify people at risk of a range of important adverse health events such as falls, disability, and mortality, and the consequent health and social care needs such as hospitalization or care home admis- sion. The impact of sarcopenia and frailty extends beyond geriatric medicine across primary care, secondary care, and social services. There is accumulating evidence that the adverse trajectories of sarcopenia and frailty can potentially be modified through tar- geted treatment and multifactorial interventions. Sarcopenia is a muscle disease characterized by poorer muscle strength, loss of skeletal muscle quantity and quality and poorer physical function. Sarcopenia is a core component of frailty, a con- dition characterized by reduced biological reserves across a range of physiological systems, which increase vulnerability to adverse outcomes following minor stressor events. A  unifying feature of sarcopenia and frailty is loss of physical function, which adversely im- pacts the ability to sustain independence in daily living. This in turn leads to reduced social interactions and psychological well-​being. In this chapter we will review the epidemiology, consequences, pathogenesis, diagnosis, and management of sarcopenia and frailty, and consider the how the relationship between them may help better targeting of interventions and holistic care. Sarcopenia Sarcopenia is associated with adverse individual physical and metabolic changes contributing to morbidity, disability, impaired quality of life, and mortality. The health and socioeconomic impli- cations of sarcopenia are considerable: the annual healthcare cost of sarcopenia in the United States has been estimated at $18.5bil- lion. Sarcopenia is now recognized as a disease specific to muscle and has been assigned an official ICD-10-CM diagnosis code. Skeletal muscle comprises approximately 40% of total body mass. It therefore constitutes one of the largest organ systems of the body, playing an essential role in both physical and metabolic func- tioning, including locomotion, thermoregulation, and metabolism of glucose and amino acids. Muscle is a reservoir for proteins and energy that can be utilized in periods of stress or undernutrition; for example, use of amino acids for the synthesis of antibodies and for gluconeogenesis. Reduced muscle mass may therefore help ex- plain the lower metabolic adaptation and immunological response to disease in hospitalized or institutionalized older people. Aetiology—​a life-​course approach Although traditionally associated with the ageing process, the devel- opment of sarcopenia is recognized to begin earlier in life and that the sarcopenic phenotype we recognize in later life is a consequence of adverse muscle changes that accumulate throughout the life-course. In humans, muscle development occurs in stages, beginning at 6

522 Section 6  Old age medicine weeks of gestation until the total number of fibres is set at approxi- mately 24 weeks. Any subsequent increase in muscle bulk occurs by hypertrophy as evidenced by an increase in fibre cross-​sectional area, and not by hyperplasia, so the number of muscle fibres formed prenatally influences the potential for postnatal hypertrophy. Muscle fibre development is determined by muscle use, nutrient availability, and the action of hormones and growth factors that affect regulatory and structurally important myogenesis-​related genes. Muscle mass increases during childhood until adult muscle cross-​sectional areas are reached shortly after puberty, then remain relatively constant in early adulthood until the decline from the late 40s. On average, men have greater muscle mass and strength than women at any given point in the life course. Between the ages of 20 and 80 years, total lean body mass declines by approximately 18% in males and by 27% in females. The resulting health of muscle is a func- tion of the peak attained in early life and the extrinsic and intrinsic changes operating through middle years into old age (Fig. 6.2.1). Pathogenesis At a cellular level, skeletal muscle (Fig. 6.2.2) is continuously remod- elled in response to workload, tension, growth factors, nutrition, and hormones. These factors affect the dynamic balance between muscle fibre protein synthesis and breakdown. Multiple cell signalling pathways mediate the environmental and cellular cues that impact myofibre size through synthesis or degradation. Skeletal muscle is composed of multiple bundles of fascicles sur- rounded by the epimysium Fig. 6.2.2a and 6.2.2b. Each fascicle is bound by the perimysium and is composed of bundles of muscle fibres bound by the endomysium. Each muscle fibre is surrounded by the sarcolemma Fig. 6.2.2c and 6.2.2d. Multiple nuclei reside on the periphery of the fibre under the sarcolemma, while mitochon- dria reside within interfibrilar spaces. Each myofibril is composed of thick myosin and thin actin filaments that form the contractile elements of the muscle and are responsible for the light and dark striations characteristic of skeletal muscle. Proposed mechanisms for the age-​related decline in muscle mass and strength (Table 6.2.1) include a decrease in physical activity/​ sedentary lifestyle, undernutrition, hormonal changes, inflamma- tion, oxidative stress, and denervation. For example, the IGF-​I/​ AKT/​mTOR pathways promote protein synthesis and the mainten- ance of skeletal muscle mass, while catabolic pathways can involve activation of NFkB (nuclear factor kB) by inflammatory mediators including TNF (tumour necrosis factor) and IL-​6 (interleukin 6). Downstream effects of NFkB activation include up regulation of the E3 ubiquitin ligases MAFbx (atrogin-​1) and MURF-​1 that are in- volved in muscle atrophic processes. In sarcopenic muscle the rate of muscle injury (from normal con- traction) exceeds that of repair and regeneration. These effects are a consequence of decreased satellite cell (muscle stem cell) prolif- erative capability and renewal, with added effects of altered inter and intracellular environments favouring catabolism mediated by decrease in growth factors such as circulating insulin, growth hormone, and testosterone and muscle-​specific IGF-​1 levels. Furthermore, production of reactive oxygen species and oxidative stress can lead to mitochondrial DNA damage and a progressive de- cline in mitochondrial function and therefore to energy depletion. Ageing muscles are also characterized by a continuous neuro- pathic cycle of denervation and reinnervation, giving rise to larger, inefficient motor units. The main causes include loss of alpha-​ motoneurones within the central nervous system, withdrawal of nerve terminals from the neuromuscular junctions, and axonal sprouting from remaining neurons. Ultimately, remodelling of skeletal muscle tissue through neuro- pathic and neurohormonal and inflammatory pathways leads to a reduction in muscle cross-​sectional area, volume, and reduced rate of force generation. There are fewer type I  oxidative, slow twitch, and type II glycolytic, fast twitch myofibres, and predom- inantly type II fibre atrophy. The loss of type II fibres, which have relatively more satellite cells, is associated with decreased strength and ability to generate power. The concomitant increase in non-​ contractile material within the fascicles affect muscle quality and lead further to impaired muscle function. In combination, these processes lead to the reduced muscle functional performance. The force generated per unit muscle area is affected by the fibre myosin content, innervation, and increase in connective tissue fat content. Clinical impact of reduced skeletal muscle mass and strength Skeletal muscle strength is determined, in part, by muscle mass, which is a function of myofibre size and number (Fig. 6.2.2). Reduced skeletal muscle mass has been associated with increased functional impairment and disability in both men and women. However, muscle strength and function are more predictive of morbidity and mor- tality than muscle mass alone and this is reflected in recent diagnostic algorithms for sarcopenia. Grip strength is a simple, reliable, and valid proxy measure of body strength, and has good correlation with lower limb physical performance. Low grip strength of community-​ dwelling older people is associated with morbidity including falls, in- creased rate of transition into disability, and premature mortality. In male patients on admission to hospital, lower grip strength was asso- ciated with slower recovery and lower likelihood of discharge to usual residence following a period of inpatient rehabilitation. Slower gait speed has been associated with risk of future dis- ability, falls, institutionalization and death, and is therefore suitable for inclusion in diagnostic algorithms for sarcopenia. Other phys- ical performance measures include chair rise time, time taken to complete five sit to stand actions, and standing balance (the time for sustaining balance on one leg). These objectively measurable variables have been associated with higher risk of all-​cause mor- tality in older people. Gait speed requires intact coordination, Age Range of muscle mass and strength between individuals Growth and development to maximize peak Maintaining peak Minimizing loss Muscle mass and strenght Adult life Early life Older life Fig. 6.2.1  A life-​course approach to sarcopenia.

6.2  Frailty and sarcopenia 523 neural control and joint control, and thus may not be practical in all contexts, when grip strength may be more feasible and have better predictive value. Measures of sarcopenia in practice Measuring muscle strength Grip strength, measured using hand-​held dynamometry, has gained wide acceptance as a reliable and valid measure of muscle strength across healthcare settings. Other modalities include knee extensor power and isometric knee strength and quadriceps torque measurement, but these require static and bulky equipment which may not be appropriate in large-​scale epidemiological studies or routine clinical practice. Measuring muscle mass The commonest approach to measuring muscle mass is through dual-​energy X-​ray absorptiometry (DXA) and bioimpedance scan- ning (BIA), although gold standard modalities include computed tomography (CT) and magnetic resonance imaging (MRI). As muscle mass is correlated with body size, this value can be adjusted for body size using weight or body mass index (BMI). Commonly, the index usually calculated is the appendicular lean mass (ALM)— the muscle mass of the four limbs—expressed as a function of the patient’s height squared, ALM/ht2. Skeletal muscle (a) (b) (c) (d) Epimysium Muscle fascicles Perimysium Endomysium Muscle fibres Mitochondrion Sarcolemma Myofibril Thick (myosin) filament Z disc Z disc I band I band M line A band sarcomere H zone Dark A band Thin (actin) filament Light I band Nucleus Muscle fibre Muscle fascicle Fig. 6.2.2  Anatomical organization of skeletal muscle. (a) Skeletal muscle is contiguous with tendons that connect muscle to bone. Skeletal muscle consists of several hundred to thousands of muscle fibres arranged within fascicles, connective tissue, blood vessels, nerve fibres and is covered externally by the epimysium. (b) Fascicles consist of bundles of fibres separate from the rest of the muscle by connective tissue and are surrounded by the perimysium. (c) An individual muscle fibre is an elongated, multinucleated cell that has a characteristic striated appearance and is covered by the endomysium. An individual fibre is composed of several bundles of myofibrils. Mitochondria reside within the sarcolemma in between the myofibrils and provide energy for muscle contraction through the generation of ATP. (d) Myofibrils constitute the contractile units termed sarcomeres that are arranged end to end. A myofibril is composed of the contractile proteins actin and myosin that overlap to form the dark A bands. Approximation of the sarcomeres in series leads to myofibrillar contraction; the A bands stay the same width but the Z discs move closer together and the I bands shorten. Adapted from OpenStax Anatomy and Physiology. © 18 May 2016 OpenStax, licensed under a Creative Commons Attribution License 4.0 license.

524 Section 6  Old age medicine Measuring physical performance Physical performance measures can be obtained by measuring gait speed alone, or through a well-​characterized battery of measurements encompassing gait speed, standing balance, and chair rise time (collect- ively known as the Short Physical Performance Battery (SPPB)). Use of questionnaires to measure physical function Based on physical performance parameters, the SARC-​F question- naire was developed to predict poor muscle function (Table 6.2.2). It is based on five questions based on: • ability to rise from a chair • ability to walk assisted or unassisted • ability to climb stairs • ability to carry heavy loads (strength) • number of falls A score of ≥4 (scale 0–​10) suggests that the subject is symptom- atic of sarcopenia. The questionnaire has excellent specificity but poor sensitivity for sarcopenia based on consensus criteria (see next), is useful in its predictive power for four-​year physical limi- tation, and may be useful for case finding in clinical practice. Definition and case finding Sarcopenia, can occur primarily due to the ageing process (pri- mary sarcopenia) but can also occur secondary to systemic illness or other interactive factors such as inactivity or malnutrition. For example, in clinical practice, falls, slower gait speed, difficulty rising from a chair, weight loss or muscle wasting should highlight the need for further diagnostic evaluation. The SARC-F question- naire can help elicit self-report from patients who may be symp- tomatic of sarcopenia. Recent definitions of sarcopenia emphasize the ascertainment of muscle strength, followed by measures of muscle quantity and/or quality followed by measures of physical performance. Notable diagnostic criteria with algorithms include those proposed by the European Working Group on Sarcopenia in Older People 2018 (EWGSOP2) (Fig. 6.2.3), the older International Working Group (IWG) on Sarcopenia, the Foundation for the National Health Institutes of Health (FNIH) Sarcopenia Project, and the Asian Working Group for Sarcopenia (AWGS). The EWGSOP2 definition use normative reference values for young healthy adults where possible with cut-off points usually set at –2 or –2.5 standard deviations compared to a mean refer- ence values. Sarcopenia is probable when low muscle strength is present (grip <27 kg for men, <16 kg for women) or time taken to compete five chair rises is greater than 15 seconds. A diagnosis of sarcopenia is confirmed by the presence of low muscle quantity de- fined for example as ALM/ht2 <7.0 kg/m2 for men and <6.0 kg/m2
for women) (Fig. 6.2.3). If these parameters are accompanied by poorer objective physical performance measures e.g. gait speed ≤0.8 m/s, then sarcopenia is considered severe. The International Working Group on Sarcopenia also advocate the measurement to impaired physical performance in addition to slow walk speed as a prelude to measuring muscle mass. The Foundation for the National Health Institutes of Health sarcopenia project was designed to iden- tify clinically relevant cut points of low muscle mass and strength based on their association with impaired mobility. These were grip strength less than 26 kg for men and less than 16 kg for women, and ALM adjusted for BMI under 0.789 kg/m2 for men and under 0.512 kg/m2 for women. The Asian Working Group for Sarcopenia diag- nostic algorithm, relevant criteria include gait speed under 0.8 m/s, ALM/ht2 under 7.0 kg/m2 in men, and under 5.4 kg/m2 in women, and grip strength less than 26 kg for men or 18 kg for women. There has been excellent progress in defining and implementing diagnostic criteria for sarcopenia case finding over the past decade. However it would be helpful for both observational and intervention studies to have agreement on global diagnostic criteria for sarcopenia based on cut off values from skeletal muscle mass indices, grip strength, and walking speed, accounting for gender and culture differences. Table 6.2.1  Anatomical and biochemical changes in ageing muscle Anatomical changes Reduced structural integrity of the myofilaments Reduction in total myofibre number Reduced number and size of type II fibres Decreased muscle mass and cross-​sectional area Infiltration of fat and connective tissue Decrease in number of motor neurons, increase in size of motor units Accumulation of non​contractile proteins Decreased blood flow Biochemical changes Decreased myosin heavy chain synthesis Reduced global muscle protein synthesis Increased oxidative stress Decline in mitochondrial activity Table 6.2.2  The SARC-​F questionnaire for sarcopenia Score Strength How much difficulty do you have in lifting and carrying 10 pounds? None 0 Some 1 A lot or unable 2 Assistance in walking How much difficulty do you have walking across a room? None 0 Some 1 A lot, use aids, or unable 2 Rise from a chair How much difficulty do you have transferring from a chair or bed None 0 Some 1 A lot or unable without help 2 Climb stairs How much difficulty do you have climbing a flight of ten stairs None 0 Some 1 A lot or unable 2 Falls How many times have you fallen in the last year none 0 1–​3 falls 1 4 or more 2 0 = best, 10 = worst, 0–​3 healthy, ≥4 is symptomatic for sarcopenia

6.2  Frailty and sarcopenia 525 Frailty As we age, the cells and tissues of our bodies accumulate damage, which causes gradual loss of physiological reserve. Sarcopenia is a core component of frailty, indicating loss of physiological reserve in the skeletal muscle system, and has been proposed as a key mechanism in the development of frailty (Fig. 6.2.4). However, in frailty, the gradual decline in reserve is accelerated and accumulates alongside skeletal muscle across multiple systems, including the brain, immune, endo- crine, cardiorespiratory, renal, and haematological systems. This accelerated decline across multiple systems can lead to failure of homeostatic mechanisms, which leads to vulnerability to adverse outcomes following minor stressor events. Evidence suggests that it is the total loss of physiological reserve across multiple systems that is important, rather than loss of reserve in any particular system, and sarcopenia is a core component of this multiple system idea. Epidemiology Frailty is common in older age, with prevalence estimates of 10% in the over 65 population, rising to between a quarter and a half of people aged over 85. Higher prevalence rates of frailty in older people has been reported in people living in Southern Europe, older African Americans, and Hispanic populations. There is ac- cumulating evidence of an association between frailty and health inequalities. The prevalence of frailty, and associated outcomes, are strongly linked to national economic indicators—​in higher income countries, the prevalence of frailty is lower, and those with frailty live longer. Furthermore, there is evidence for an association be- tween frailty and measures of social vulnerability, including level of social deprivation. Aetiology—​a life-​course approach Ageing is considered to result from the lifelong accumulation of unrepaired molecular and cellular damage. This damage is inher- ently random and is caused by multiple mechanisms that are regu- lated by a complex maintenance and repair network. Oxidative DNA damage and shortening of telomeres (specialized structures situated at the ends of human chromosomes that help protect the chromosome from enzymatic damage during replication) are thought to be important mechanisms. Interestingly, an association SARC-F or clinical suspicion FIND CASES ASSESS CONFIRM SEVERITY No sarcopenia; rescreen later No sarcopenia; rescreen later Sarcopenia probable* In clinical practice, this is enough to trigger assessment of causes and start intervention Muscle quantity or quality DXA; BIA, CT, MRI Sarcopenia confirmed Sarcopenia severe Physical Performance Gait speed, SPPB, TUG, 400m walk Muscle strength Grip strength, Chair stand test NEGATIVE NORMAL NORMAL LOW LOW POSITIVE OR PRESENT LOW Fig. 6.2.3  Sarcopenia: European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for case-finding, making a diagnosis and quantifying severity in practice. The steps of the pathway area described in stages Find-Assess-Confirm-Severity or F-A-C-S.

526 Section 6  Old age medicine has been reported between oxidative DNA damage and frailty, al- though no association between telomere shortening and frailty has been demonstrated. A life-​course approach to frailty is worth considering because if the situation in old age is the consequence of accelerated loss of biological reserves across multiple systems over a lifetime, then there may be potential benefit from identifying markers and mech- anisms with a view to modifying the relevant processes. For ex- ample, there is evidence for a partially hierarchical development of frailty. One large longitudinal study has identified that weakness tends to be the first sign of frailty, and that weakness, slow walking speed, and low physical activity typically precede weight loss and exhaustion. The presence of weight loss and exhaustion may iden- tify people at especially high risk of rapid decline. The presence of weakness as an early sign of impending frailty is consistent with life-​course evidence in sarcopenia which indicates that the decline in muscle mass and strength is observed in midlife. Identification of sarcopenia may therefore be an especially useful method of identifying people at increased risk of later life frailty. Pathogenesis Frailty is best understood as a multisystem disorder, with per- haps both independent and linked mechanisms operating across organ or physiological systems. Furthermore, accumulating dysregulation across multiple systems can subsequently adversely affect systems previously functioning at a normal level, accelerating Ageing Chronic low-grade inflammation, depletion of endogenous antioxidant defence systems, decrease in motor unit number vs FRAILTY Neuropathic and hormonal changes, anorexia of ageing, protein intake, co-morbid illness, sedentary lifestyle IL-6, TNF, ROS IGF-1 and steroid hormones, dennervation Myofibre protein catabolism Myofibre regeneration Type I and II myofibre number, Type II fibre atrophy, decrease in muscle quality SARCOPENIA Strength, power and endurance Difficulty with weight bearing tasks, falls and fractures, increased fatigue and inability to exercise Satellite cell activation/proliferative capacity Myofibre protein synthesis and anabolism Fig. 6.2.4  Sarcopenia as a component of frailty.

6.2  Frailty and sarcopenia 527 the development and progression of frailty. This is relevant not only for improved understanding of the condition, but also because a key implication of loss of reserve across multiple systems is that thera- peutic replacement of any single system is unlikely to ameliorate the abnormal health state of frailty. A schematic representation of this concept of the pathogenesis of frailty is shown in Fig. 6.2.5. Endocrine system During ageing, a decline is observed in production of growth hor- mone, insulin-​like growth factors, oestradiol, testosterone, and dehydroepiandrosterone sulphate, a major sex steroid precursor. Alongside this decline, there is a rise in production of cortisol. These changes may promote a shift to a state of increased catab- olism, leading to loss of muscle mass, anorexia, weight loss, and reduced energy expenditure—​cardinal clinical features of frailty. Insulin-​like growth factors (IGFs) are a family of small pep- tides that increase anabolic activity in many cells. Promotion of neuronal plasticity and increased skeletal muscle strength are con- sidered to be particularly important effects. The principal IGFs are IGF-​1, IGF-​2, and insulin. IGF-​1 is synthesized in the liver in response to circulating growth hormone, secretion of which is regulated by the hypothalamic-​pituitary axis. A range of growth factors and hormones also stimulate local synthesis of IGF-​1 by neurons, muscle cells, and white blood cells. The local autocrine and paracrine actions of IGF-​1 are considered to be important for the promotion of neuronal plasticity and increased skeletal muscle strength. Insulin-​like growth factors promote neuronal survival by inhibiting apoptosis and can increase learning and memory in hu- mans. Primary neuronal changes in the hippocampus and hypo- thalamus may affect the IGF pathway, resulting in a predisposition for accelerated neuronal death and a consequent deterioration in physiological function. There is evidence that IGFs may play an important role in frailty. A 2004 cross-​sectional study including 51 older partici- pants reported significantly lower levels of IGF-​1 in those who were identified as frail, compared to age-​matched controls. An inverse correlation between IGF-​1 and IL-​6 levels was observed, identifying a potential relationship between IGF-​1 and the frail immune system. A 2009 cross-​sectional study involving 696 older women from the US Women’s Health and Aging Study identi- fied a significant correlation between white blood cell counts and IGF-​1. Brain The ageing brain is characterized by changes to the structure and function of neurons and supporting cells. Changes to hippocampal neurons may be particularly important in frailty, as these cells are involved in homeostatic control of the inflammatory response and implicated in cognitive problems commonly associated with frailty, including dementia. Microglial cells are the resident im- mune cells of the brain and may also be important: they have been implicated in the pathogenesis of delirium, which is independently associated with frailty. The hypothalamus receives and integrates multiple afferent in- puts from diverse regions of the brain to coordinate the organ- ismal response to stress and inflammation, partly through the control of glucocorticoid secretion. Basal glucocorticoid secretion is necessary for the normal function of many cells and levels are increased in response to virtually any stress, including physical and psychological stress, or the presence of inflammation, to pro- vide the altered physiological requirements that promote survival. Peripheral cytokines such as IL-​1 and IL-​6 that are released in re- sponse to stress and inflammation have both direct and indirect effects on the hypothalamus to promote glucocorticoid secretion. Circulating glucocorticoids are subsequently sensed by the hippo- campus, which suppresses hypothalamic stimulation of gluco- corticoid production in a negative feedback loop. Uncontrolled inflammation has the potential to cause cellular damage, and a functional glucocorticoid system is an important component of the homeostatic regulation of local and systemic inflammation. The loss of hippocampal neurons that is observed in both normal ageing and Alzheimer’s dementia may impair the homeostatic control of the glucocorticoid system, with the consequence of uncontrolled inflammation and increased cel- lular damage, promoting organismal ageing. Loss of homeostatic control of the glucocorticoid system may itself promote further neurodegeneration, as chronically elevated levels of glucocortic- oids have been hypothesized to increase hippocampal neuronal damage. The loss of hippocampal neurons that is observed in both normal ageing and Alzheimer’s dementia may therefore pro- mote a spiral of accelerated neuronal damage through impair- ment of the glucocorticoid negative feedback loop, uncontrolled inflammation, and neurotoxic effects of chronically elevated glucocorticoid levels. Genetic factors Epigenetic mechanisms Environmental factors Cumulative molecular & cellular damage Physical activity Nutritional factors STRESS Falls Delirium Fluctuating disability Increased care needs Admission to hospital Admission to long-term care FRAILTY Reduced physiological reserve Brain Endocrine Immune Skeletal muscle Cardiovascular Respiratory Renal Fig. 6.2.5  Schematic representation of frailty.

528 Section 6  Old age medicine A recent cross-​sectional study involving 214 female participants reported that frailty, measured using the phenotype model, was inde- pendently associated with chronically elevated diurnal cortisol levels. Evidence indicates that glucocorticoids may play an important role in the pathophysiolgy of delirium, alongside alterations to microglial cell structure and function. This is likely to be partly related to the role of glucorticoids in homeostatic control of the in- flammatory response, but also potentially via a direct role on cere- bral glucocorticoid receptors. This is supported by the observation that high doses of glucocorticoids can precipitate acute deficits in attention and memory—​core clinical features of delirium. Immune system Ageing is associated with changes to immune stem cells, T-​lymphocyte production, B-​lymphocyte response, and reduced phagocytic activity of neutrophils and macrophages. These changes can precipitate an abnormal inflammatory response to stressor events such as infection or surgical procedures, which may help explain the accelerated catab- olism of skeletal muscle and adipose tissue that is observed when an older person with frailty is challenged by an acute illness. Nutrition The synthesis of muscle fibres requires adequate protein substrates. Physiological changes in the gastrointestinal system with age dic- tate that older people eat less, have early satiety, lose their sense of taste, and have a blunted anabolic response to ingested proteins. Collectively, anorexia of ageing leads to impaired muscle mass and performance. In addition, older people require more protein to counteract the inflammatory and catabolic effects of coexistent co​morbidities and their exacerbations. Diagnosis Detection of frailty should be an essential part of assessment of older people because dimensions of frailty may be amenable to interven- tions. Failure to detect frailty potentially exposes patients to conven- tional interventions that may not be beneficial, and indeed could be harmful. Conversely, excluding fit older people from interventions from which they may benefit on the basis of age alone is unacceptable. Gold standard models The two established international models of frailty are the pheno- type model and the cumulative deficit model. The phenotype model developed by the Fried group identifies frailty by the pres- ence of at least three of five physical characteristics: weight loss; exhaustion; low energy expenditure; slow walking speed; and low handgrip strength. The cumulative deficit model developed by Rockwood and colleagues identifies frailty on the basis of the accu- mulation of a range of ‘deficits’, which can be symptoms, sensory deficits, clinical signs, diseases, disabilities, and abnormal labora- tory test results. Despite the distinct conceptual bases of these ap- proaches, convergence in performance has been demonstrated, which provides support for the notion of frailty as a unified con- struct. Although well-​validated in large international epidemio- logical studies, the two gold standard models are more suited to a research setting, as the time required to complete the assessments limits use in day-​to-​day clinical practice. Clinical assessment Identification of frailty in clinical practice is frequently based on comprehensive geriatric assessment (CGA). This is a process to identify an older person’s medical, functional, social and psy- chological capacity, and limitations to enable a plan for ongoing care. The Clinical Frailty Scale (CFS) is a simple tool based on CGA that enables assignment of a frailty category based on clin- ical judgement. There are seven Clinical Frailty Scale categories ranging from one (fit) to seven (severe frailty), and increasing CFS frailty has been demonstrated to have excellent predictive validity for adverse outcomes of care home admission and mortality. Simple tools to identify frailty There are a range of simple assessments and questionnaires avail- able to identify frailty in routine clinical practice. Gait speed A gait speed of less than 0.8 m/​s (taking more than five seconds to walk 4 m) is a reliable method of identifying frailty. At this cutpoint, both sensitivity (0.99) and specificity (0.64) are high, compared to the phenotype model as research standard. Timed-​up-​and-​go test This assesses how long it takes a person to stand up from a chair, walk 3 m, turn around, and walk back again. A time exceeding 10 seconds can be used to identify the likely presence of frailty. This demonstrates excellent discrimination for identifying frailty (AUC = 0.87), but is less able to discriminate fit people from either prefrail or frail people (AUC = 0.73). PRISMA 7 questionnaire The PRISMA 7 questionnaire screens for frailty using seven ques- tions and is suitable for postal completion/self report. A score of 3 or greater can be used to identify frailty (Box 6.2.1). Other validated tests that are suitable for use in day to day clin- ical practice include the FRAIL tool and the Edmonton Frail Scale. This multidimensional assessment instrument is less comprehen- sive than a full CGA but includes the timed-​up-​and-​go test, and a test for cognitive impairment. It is quick to administer (less than five minutes) and is valid, reliable, and feasible for routine use by trained non​geriatricians. Box 6.2.1  PRISMA 7 questionnaire 1 Are you more than 85 years? Yes = 1 point 2 Male? Yes = 1 point 3 In general, do you have any health problems that require you to limit your activities? Yes = 1 point 4 Do you need someone to help you on a regular basis? Yes = 1 point 5 In general, do you have any health problems that require you to stay at home? Yes = 1 point 6 In case of need, can you count on someone close to you? Yes = 1 point 7 Do you regularly use a stick, walker, or wheelchair to get about? Yes = 1 point

6.2  Frailty and sarcopenia 529 Use of routine data to identify frailty The cumulative deficit frailty index identifies frailty on the basis of the accumulation of a range of deficits, which are multiple patient characteristics including clinical signs, symptoms, and disease states. Electronic health records use clinical codes to categorize and log multiple patient characteristics, including symptoms, signs, la- boratory test results, diseases, disabilities, and information about social circumstances. They therefore provide a potentially simple yet powerful mechanism for identifying cumulative deficits to recog- nize and characterize frailty as part of routine care. As the data are collected routinely, there would be minimal resource implications involved in generating a frailty index using electronic health records. An electronic frailty index (eFI) has been developed and val- idated using routine data from over 900 000 UK primary care patients, and is now available in primary care settings. The eFI identifies older people with mild, moderate, and severe frailty, with robust predictive validity for outcomes of mortality, hospitaliza- tion and care home admission, and good discrimination for these outcomes. More widespread use of the eFI may promote a shift from the currently prevalent reactive approach to frailty to a more proactive primary care model that could enable deployment of a range of interventions, described later on in this chapter. Treatment of sarcopenia and frailty A  multidimensional approach to frailty may include promoting regular physical activity, exercise, medication reviews, social network supports, home adaptations, carer support, and nutritional optimiza- tion. The ultimate treatment goal for an older person with sarcopenia and consequent frailty is to improve physical function, maintain in- dependence, and well-​being. Published diagnostic algorithms for sarcopenia are useful for case finding and established outcome meas- ures can be used when designing intervention trials. For example, the ability to walk a defined distance, gait speed, and grip strength are valid outcome measures given their predictive ability of future dis- ability, hospitalization, mortality, and healthcare expenditure. Exercise programmes Evidence supports the use of progressive resistance exercise (exercise against an increasing external load) as well as endurance based exercise for treatment of sarcopenia. Both modalities have positive effects on muscle strength and physical function with reduction in disability and systemic inflammation. There is evidence that targeted home-​based or group-​based exercise interventions may also improve mobility and functional outcomes for older people with frailty, although those with severe frailty may gain less benefit. Identification of sarcopenia alongside frailty may therefore be an attractive method of improving targeting of exercise programmes to those most likely to gain benefit. Nutrition Current recommendations for protein intake in older people to maintain homeostatsis is 1–​1.2  g protein/​body weight (kg) per day. Observational evidence suggests protein, specifically essential amino acids (e.g. leucine), stimulate muscle protein synthesis more than non​essential amino acids. Protein supplements vary in their composition and evidence from trials is at present inconsistent to develop evidence based recommendations for protein supplemen- tation in sarcopenia. Vitamin D Polymorphisms in vitamin D receptors have been associated with muscle function. Vitamin D supplementation has been shown to have a positive impact on global muscle strength but not mass in older people, and may be beneficial in deficiency states. UK NICE guidance recommends increasing availability of vitamin D sup- plements for older people, particularly those with frailty as an especially high risk group for deficiency. Expert consensus recom- mendations support intake of at least 800 IU/​d of vitamin D and calcium intake of 1000 mg/​day for postmenopausal women for the prevention of age-​related deterioration in musculoskeletal health. Primary care interventions Personalized care planning Measurement of quality of primary care has historically focused on preventive and disease-​specific care processes. Similarly, out- come measurement has focused on disease-​specific indicators. Disease-​specific processes and outcomes are less relevant for older people with frailty, who frequently have multiple co​existing con- ditions and different personal priorities. An alternative approach to providing better care for older people with frailty is to identify a patient’s individual health goals across a range of dimensions. This is the purpose of personalized care planning, which is at the core of international models of long-​term condition manage- ment, for example, the Chronic Care Model and the World Health Organization (WHO) model. A medication review should be undertaken as part of person- alized care planning. Certain medications are associated with in- creased risk of falls and delirium in older people with frailty (e.g. benzodiazepines, opiate analgesia) and should be avoided, or doses reduced, where possible. Palliative care Frailty has been identified as the most common condition leading to death in older age, yet advance care planning discussions are not routinely initiated in people with severe frailty. Routine rec- ognition and severity grading of frailty would enable appropriate advance care planning discussions for people with severe frailty, including involvement of palliative care teams for those with ad- vanced frailty who may be entering the terminal phase of life. Possible targets for pharmacological treatment Observational studies have indicated potential beneficial effects of testosterone on muscle mass and function related to its ana- bolic functions and satellite cell stimulatory activity. However,

530 Section 6  Old age medicine randomized controlled trials have not demonstrated benefit be- cause effects on skeletal muscle appear to be offset by adverse cardiovascular outcomes. Trials of testosterone are presently underway, which should provide some guidance on target popula- tions, effective dosing regimens, duration of treatment to improve muscle mass and strength, but also to reduce the risk of harmful side effects. Growth hormone supplementation was also thought to have promising therapeutic effects, but a multitude of studies have shown more harm than benefit in older people. While it may in- crease muscle mass, it does not increase muscle strength or func- tional performance. Side effects include arthralgia, paraesthesiae, fatigue, and carpal tunnel syndrome. More importantly, growth hormone supplementation has been associated with mortality in some observational human studies. Interest in selective androgen receptor modulators, which are androgen receptor ligands that display selective activation of androgen signalling in target tissues, stems from the observed anabolic effect of testosterone. Early phase II trials are underway, but in the longer term trials will be needed on their safety and efficacy in improving physical function in older people with sarcopenia. Myostatin is a member of the TGF​β superfamily. It acts as a nega- tive regulator of skeletal muscle and is upregulated in many muscle wasting disorders, hence myostatin and its receptor, activin type IIb, are attractive targets for therapy, and myostatin receptor anti- bodies are currently under development with the focus on older people with lower lean mass. The anticipated outcomes would need to include sustained positive effect on muscle function. Bimagrumab, an activin type II receptor antagonist that blocks the effect of myostatin, GDF-​11, and activin, has been shown to im- prove six-​minute walk distance by 52 metres compared with pla- cebo, as well as to increase thigh muscle volume, in a small scale trial of 11 patients with spontaneous inclusion body myositis. Clinical trials of potential therapeutic effects in older people with sarcopenia and frailty are awaited. Other drugs that may have beneficial effects on muscle func- tion include the angiotensin converting enzyme inhibitors (ACEi). Improvement in six-​metre walk test has been seen with the use of perindopril in older persons with functional impairment, but did not show synergistic effects with exercise training. However, a re- cent meta-​analysis of four trials concluded that ACEi did not im- prove walk distance or age-​related strength decline in older people. Clinical trials are ongoing. The role of pharmacological agents in frailty is likely to be mainly focused on long-​term treatment, due to the length of time required for beneficial effects to be observed at a biological level, and for these benefits to translate into clinically meaningful outcomes. However, the role of rapid acting agents to augment the blunted recovery responses in older people with frailty may also represent an attractive option for pharmacological treatment. Other aspects Frailty in hospital and specialist settings Frailty is an independent predictor of adverse outcomes across set- tings, and decision-​making and treatments for older people with frailty in these areas should be structured around a personalized, holistic, goal-​orientated approach to care. There is robust evidence that the provision of inpatient comprehensive geriatric assessment on specialist elderly care wards for older people with frailty im- proves rates of discharge home, improves cognitive and functional outcomes, and reduces mortality compared to provision of usual care on general medical wards. The recognition of frailty as a risk factor for adverse outcomes has led to the establishment of specialist orthogeriatric care based on the principles of comprehensive geriatric assessment for older people admitted to hospital with hip fracture, which has led to im- proved outcomes for this group. Evidence indicates that outcomes may also be improved for patients undergoing elective surgical procedures. Frailty is prevalent in many other specialist settings, including oncology, cardiology, and respiratory medicine. For example, over 50% of older people with cancer have frailty or prefrailty and are at increased risk of chemotherapy intolerance, surgical complica- tions, and mortality. However, it is not yet usual practice to iden- tify the presence of frailty as part of routine cancer care to inform decision-​making based around an individualized balance of risk and benefit (see Chapter 6.6). Impact of sarcopenia and frailty on health and
social care systems Frailty is independently associated with increased risk of falls, de- lirium, disability, dementia, hospitalization, and care home admis- sion, all of which are outcomes that have considerable implications for health and social care services. It is therefore unsurprising that older people with frailty are majority users for many health and social care services. However, systems of care have historically been organized around single illnesses more typically found in younger people. Internationally, health and social care systems need to better meet the needs of older people with frailty and their carers. Integrated care is an approach that seeks to improve quality of care by ensuring that services are well coordinated around individ- uals’ needs. A key principle of integrated care is to identify services and user groups where the potential benefits from an integrated approach are greatest. Older people with frailty frequently need to move between services and organizations. They are therefore particularly susceptible to the effects of multiple assessments, de- lays, or the simple abandonment that are characteristics of poorly integrated services. Successful models of integrated care that de- liver improved quality of care for older people with frailty and demonstrate better outcomes at lower cost have been identified internationally. FURTHER READING Cesari M, et al. (2015). Pharmacological interventions in frailty and sarcopenia: report by the International Conference on Frailty and Sarcopenia Research Task Force. J Frailty Aging, 4, 114–​20. Chen LK, et al. (2014). Sarcopenia in Asia: consensus report of the Asian Working Group for Sarcopenia. J Am Med Dir Assoc, 15, 95–​101. Clegg A, et al. (2012). Do home-​based exercise interventions improve outcomes for frail older people? Findings from a systematic review. Rev Clin Gerontol, 22, 68–​78.

6.2  Frailty and sarcopenia 531 Clegg A, et al. (2013). Frailty in elderly people. Lancet, 381, 752–​62. Collard RM, et  al. (2012). Prevalence of frailty in community-​ dwelling older persons: a systematic review. J Am Geriatr Soc,
60, 1487–​92. Cooper R, Kuh D, Hardy R (2010). Objectively measured phys- ical capability levels and mortality: systematic review and meta-​ analysis. BMJ, 341, c4467. Cruz-​Jentoft AJ, et al. (2018). Sarcopenia: revised European con- sensus on definition and diagnosis. Age and Ageing, doi: 10.1093/ ageing/afy169. Ellis G, et al. (2011). Comprehensive geriatric assessment for older adults admitted to hospital:  meta-​analysis of randomised con- trolled trials. BMJ, 343, d6553. Fielding RA, et al. (2011). Sarcopenia: an undiagnosed condition in older adults:  current consensus definition:  prevalence, etiology, and consequences. International working group on sarcopenia.
J Am Med Dir Assoc, 12, 249–​56. Rockwood K, et al. (2005). A global clinical measure of fitness and frailty in elderly people. CMAJ, 173, 489–​95. Rockwood K, Andrew M, Mitnitski A (2007). A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci, 62, 738–​43. Shaw SC, Dennison EM, Cooper C (2017). Epidemiology of Sarcopenia: determinants throughout the lifecourse. Calcif Tissue Int, 101(3), 229–47. Studenski SA, et al. (2014). The FNIH sarcopenia project: rationale, study description, conference recommendations, and final esti- mates. J Gerontol A Biol Sci Med Sci, 69, 547–​58. Valenzuela T (2012). Efficacy of progressive resistance training inter- ventions in older adults in nursing homes: a systematic review.
J Am Med Dir Assoc, 13, 418–​28. Woo J, Leung J, Morley JE (2014). Validating the SARC-​F: a suitable community screening tool for sarcopenia? J Am Med Dir Assoc, 15, 630–​4.

6.3 Optimizing well- being into old age 532

6.3 Optimizing well- being into old age 532

ESSENTIALS Healthy ageing, well-​being in later life, quality of life, and disability-​ free life are ideas that drive policy and practice in our ageing
society. Their meanings overlap in sometimes confusing ways, but there is consensus that the postponement or containment of dis- ability is a necessary but insufficient precondition of healthy ageing and the optimization of well-​being in later life. Psychological fac- tors like self-​efficacy and sense of coherence also seem necessary for healthy ageing, but may be difficult to work with for many clin- icians trained in a more medical model of healthy ageing. Primary promotion of healthy ageing through the avoidance of disability has had some success, especially through its impact on cardiovascular disease, but we have much to learn about influencing diet and physical activity across the life course for well-​being in later life. Secondary promotion of healthy ageing using either highly fo- cused interventions like exercise classes or complex, multicompo­ nent interventions that match the complexity and heterogeneity of the ageing population, has been studied for decades. Experimental studies have been mostly negative, but more recent trials are sug- gesting that disability can be postponed or reduced. We are coming closer to understanding how best to promote healthy ageing and promote well-​being in later life. We may make faster progress if we understand that many older people consider themselves to have aged successfully, even if their doctors do not, and adopt a ‘humility of perspective’. Background ‘Healthy ageing’ and optimizing well-​being in later life are similar aspirations. According to the World Health Organization re- port of 2015, healthy ageing is the process of developing and maintaining the functional ability that enables well-​being in older age. Functional ability comprises the health related attributes that enable people to be and to do what they have reason to value. It is made up of the individual’s intrinsic capacity (i.e. a composite of all the physical and mental capacities of the individual) and environ- mental and social factors, and their inter-​relationships. Well-​being is an idea that is similarly subjective, functional, and social. Measurement of quality of life can capture both features of both healthy ageing and well-​being, while the trait of dispositional optimism—​the tendency to expect positive outcomes across a var- iety of life domains—​may underpin both states. Most men and women, in all age groups, rate their well-​being and mental well-​being positively. Bowling points out that self-​ rated health, mental health symptoms, long-​standing illness, and social support are the main drivers of overall well-​being in all age groups. Mental health symptoms, long-​standing illness, and social support are the main drivers of mental well-​being. In multivariable models, those who reported no long-​standing illness had, in comparison with others, almost twice the odds of good, rather than not good, overall well-​being, and over three times the odds of good, rather than not good, mental well-​being. This asso- ciation with long-​standing illness is only part of the story. People aged 65 years and over are more likely than younger people to define well-​being as being able to continue to do the things they had always done. Thus it may be the absence of impediments to chosen activities, rather than the absence of illnesses, that really matters. The preservation of functional ability is, then, a good intermediate goal for those wanting to promote healthy ageing and well-​being. The impact on well-​being of impairments of functional ability, such as being continent and mobile, depends on personality fac- tors like resilience, dispositional optimism, and sense of coherence, plus life stresses experienced by the individual. While approving the sentiments behind healthy ageing and optimizing well-​being, doctors and nurses working in the community may struggle to see their immediate relevance to clinical practice, especially given the brief encounters that are typical of primary care. This uncertainty about having an effect on well-​being is understandable given the lack of simple and effective interventions for many common prob- lems (physical, psychological, and social) of later life. Depression in later life is so closely bound up with disability that they are difficult to unravel, while therapies for both are disappointing. Loneliness and social isolation seem largely intractable, despite efforts to relieve them. While all of these factors may seem difficult for practitioners to change, this chapter attempts to counter the pessimistic conclusion that promotion of well-​being in later life is not core business for 6.3 Optimizing well-​being into old age Steve Iliffe

6.3  Optimizing well-being into old age 533 primary care or those caring for older patients in secondary care. On the contrary, encounters between doctors and their patients are, over time, a potentially powerful lever for changing attitudes and behaviour in ways that optimize well-​being in later life. We start with describing the public health tasks that are required over a person’s life course, then focus on the effects that case-​finding and both simple and complex interventions can have on older people’s well-​being. Finally, there is a cautionary note about the risks to well-​being of medical over-​reach. Primary promotion of physical and mental health and well-​being into old age While the World Health Organization (WHO) perspective cap- tures the overarching themes, operationalizing healthy or suc- cessful ageing in later life has proved more difficult. Depp and Jeste’s 2006 review of peer-​reviewed reports of studies of adults over age 60 that included an operationalized definition of ‘successful’ ageing identified 28 studies with 29 different definitions. The mean reported proportion of ‘successful agers’ was 35.8% (standard de- viation:  19.8) but varied widely (interquartile range:  31%). The definitions contained multiple components, although 26 of the 29 agreed that disability and loss of physical functioning were im- portant determinants of well-​being. The most frequent statistically significant correlates of the various definitions of successful ageing were age itself, not smoking, and absence of disability, arthritis, and diabetes. Moderate correlations were found for greater phys- ical activity, more social contacts, better self-​rated health, absence of depression and cognitive impairment, and fewer medical condi- tions. Surprisingly, in this review, gender, income, education, and marital status generally did not relate to successful ageing. A focused review of eight studies by Peel and colleagues noted that the terms ‘healthy’ or ‘successful’ ageing dominated the lit- erature about multidimensional functioning in older age. Studies published between 1985 and 2003 that reported statistical associ- ations between baseline determinants and healthy ageing outcome were identified from a systematic search of medical, psychological, sociological, and gerontological databases. Modifiable risk factors among the behavioural determinants included smoking status, physical activity level, body mass index, diet, alcohol use, and health practices. The authors argued that, on the basis of these findings, effective healthy ageing policies should enhance op- portunities for modification of lifestyle risk factors across the life span. The contribution that physicians, particularly those in primary care, can make to ‘healthy ageing’ thus includes modification of risk factors for unhealthy ageing in younger adults. Here there has been some success. Between 1981 and 2000, coronary heart disease (CHD) mortality in the United Kingdom fell by 62% in men and 45% in women. Studies based on cohorts and prediction models suggested that falls in the prevalence of cigarette smoking and a reduction in population blood pressure levels were important con- tributors to this decline. However, the decline in non​high-​density lipoprotein (HDL) cholesterol levels has been small, there has been no appreciable improvement in physical activity levels, along with an increase in adiposity and obesity. Rising levels of physical in- activity and obesity (and type 2 diabetes) have undermined rather than enhanced declines in CHD mortality. Developing effective responses to these negative trends will involve primary care prac- titioners, supported by colleagues working in hospitals, exploring how to change behaviour and reinforce public health messages. Inevitably, this will have some impact on healthy ageing—​the con- tinuation of what we want to do. A similar pattern may be occurring in ageing as in heart disease, but with a mixed outcome. More people may be living longer, but trajectories of disablement and frailty may not be changing (see Chapter 6.1). In a study from the English Longitudinal Study of Ageing (ELSA), levels of frailty were higher in recent compared with earlier cohorts, especially in the most deprived groups of older people. This may reflect the increased survival of frail indi- viduals, which results in poorer people spending additional years of life in a frail state. This is a contentious view, and other studies show a different picture. For example, in Europe the proportion of older people with disabilities appears to be decreasing, as does their need for help. Longitudinal analyses of disability prevalence and the need for help show this beneficial trend across birth co- horts, independent of age, study, or region. Either way, if ‘healthy ageing’ is determined in mid-​life, attention should be paid to risk factors that currently appear most resistant to change: physical ac- tivity and nutrition. Promoting physical activity If physicians, particularly primary care practitioners, were asked to focus their public health efforts on one change that would en- hance well-​being in later life, it should probably be falls preven- tion, through promotion of physical activity. Physical inactivity increases overall mortality and the risk of many diseases including chronic venous disease (CVD) and diabetes. Regular physical ac- tivity over the life course can reduce the risk of hip fracture by up to 50%. Much of this benefit is thought to be due to a reduction in falls. Falls are common in people aged 65 years and older and can have serious consequences, including injury, pain, impaired function, loss of confidence in carrying out everyday activities, loss of independence and autonomy, and death. There is evidence that interventions providing some forms of exercise may be effective in preventing falls among older people, and that healthcare costs could be reduced if the number of falls was reduced. Promoting habitual physical activity is therefore an important public health approach to the prevention of frailty, falls, and fractures, and to the promotion of well-​being. The pathophysiology, risk assessment, and prevention of falls and fragility fractures are discussed in de- tail in Chapter 6.8. The Department of Health in England advises adults to perform at least 30 minutes of at least moderate intensity physical activity on five or more days weekly, in at least 10 minute bouts, for op- timum health benefits. The full set of recommendations from the English Department of Health is shown in Box 6.3.1. Box 6.3.2 shows the recommendations for physical activity promotion in primary care, from the UK National Institute for Health and Care Excellence (NICE). However, objective assessment of physical activity using accel- erometers in a subsample of the Health Survey for England found that only 5% of men and 4% of women aged 35–​64 years, and 5% men and 0% of women aged 65 years or more, achieved the recom- mended levels.

534 Section 6  Old age medicine Walking is the commonest form of physical activity in adults and should be promoted as a near perfect exercise as it has the lowest risk of harm. However, engagement of inactive people in physical activity is still problematic. A Cochrane review of 17 randomized controlled trials reported moderate positive short-​ term increases in physical activity. Exercise interventions appear to be effective in the short and mid-​term, at least in middle age, but uptake of exercise programmes is low and attrition is high. The best approaches to promoting physical activity are still un- clear, although an intervention by practice nurses in the over 60–​75 age group shows promise. There is much to be done to understand how to alter motivation to exercise, to incentivize continuation of higher levels of activity, and to make physical activity habitual. Getting nutrition right We are only now beginning to understand how important diet is to healthy ageing, aside from the risks of obesity and diabetes. Sarcopenia (the progressive loss of muscle mass and strength with ageing) is a major cause of disability in older people. Potentially modifiable influences on sarcopenia include physical inactivity, increasing body fatness, and inadequate intake of dietary en- ergy and protein. Evidence from prospective cohort studies has suggested that lower intake of protein, vitamins C, D, and E, and whole grains are associated with increased risk of mobility limitation. There is increasing interest in examining dietary patterns rather than single nutrients, on the assumption that an intervention that aims to improve overall diet quality may be more successful than a single nutrient intervention. Adherence to a Mediterranean diet (characterized by a high intake of fruits and vegetable, and mod- erate intake of olive oil) is associated with a slower decline of mo- bility in older people. In contrast, a Westernized dietary pattern with high intake of refined bread, dairy products, and red and pro- cessed meat, and low consumption of fruits and vegetables, is as- sociated in older people with weight loss and slow walking speed. Conversion of this understanding into a public health message that primary care practitioners and other physicians can reinforce in face-​to-​face encounters, and into community initiatives that they can endorse and support, is urgently needed. Mental health and well-​being Healthy ageing is not simply about the maintenance of physical or mental health, but also about maximizing psychological re- sources, especially self-​efficacy and resilience. In Bowling’s study of the relative predictive ability of independent biomedical, psy- chological, and social models of successful ageing, only the base- line psychological model (perceived self-​efficacy and optimism) had a statistically significant effect on later successful ageing, measured using a quality of life tool. One conclusion from this study was that adding years to life and life to years may require two distinct and different approaches, one physical and the other psychological. Huppert’s review of mental capital and well-​being emphasized the effect of early environmental factors on mental well-​being, as well as social circumstances, but concluded that individuals’ learned actions and attitudes may have a greater influence. This does not help doctors, who can rightly point out their inability to change the past; but this misses the point, which is to preserve and enhance well-​being and encourage positive attitudes and behav- iours over the life course, starting anytime. Self-​efficacy and reli- ance can still be nurtured in later life, as seen in self-​management programmes for long-​term conditions. Biomedical models emphasize the absence of disease and good physical and mental functioning as signs of successful ageing, while psychosocial models emphasize life satisfaction, social functioning, and participation, or psychological resources. Lay views about successful ageing are important for testing the val- idity of existing models and measures, if they are to have any rele- vance to the population they are applied to. There is little point in developing policy goals if older people do not regard them as relevant. Despite the codification of practice into algorithms, care pathways, and protocols, there remains space in medical encoun- ters for honest (if brief) conversations about how people perceive their ageing. Bowling and Dieppe remind us that there is ample evidence that many elderly people regard themselves as happy and well, even in the presence of disease or disability. Doctors should be aware that many older people consider themselves to have aged successfully, even if medical models do not. Health professionals need to respect the values and attitudes of each elderly person who asks for help, ra- ther than imposing their medical model on to their patients’ lives. Or, as Callahan and colleagues put it, we should adopt ‘humility of perspective’. Box 6.3.1  UK Physical Activity Guidelines—​weekly recommendations for older people • At least 150 min of moderate intensity aerobic activity, or at least 75 min of vigorous intensity aerobic activity, or an equivalent combination. • Aerobic activity should be performed in bouts of at least 10 min duration. • For additional health benefits, undertake up to 300 min of mod- erate intensity or 150 min of vigorous intensity aerobic activity, or an equivalent combination. • Those at risk of falls should do balance exercise on two or more days. • Muscle-​strengthening activities should be done on two or more days. • Avoid prolonged periods of sitting in the day. • If older adults are unable to do the recommended amounts of phys- ical activity due to health conditions, they should be as physically active as they are able. Source: Department of Health (2011). Box 6.3.2  NICE recommendations for physical activity promotion in primary care NICE recommendations for promoting physical activity • identifying adults who are inactive • delivering brief advice • following up brief advice • incorporating brief advice in commissioning • systems to support brief advice • information and training to support brief advice Source data from Physical activity: brief advice for adults in primary care, NICE Guidelines, May 2013.

6.3  Optimizing well-being into old age 535 Secondary promotion: Screening and case-​finding in primary care Primary care practitioners and other physicians wanting to en- hance the well-​being of their older patients have two choices. They can focus on one high profile determinant of well-​being, or they can opt for more complex, multicomponent interventions. The dis- cussion of public health interventions, as just mentioned, might lead to physical activity promotion being chosen in preference to the less understood topic of nutrition. Complex interventions, on the other hand, are attractive because conceptually they match the complexity of well-​being and so fit with the biopsychosocial model that underpins primary care. Focused interventions Practitioners wanting to prevent falls as a simple way to enhance well-​being can do so by screening all their older patients—​say 65 and over—​using a single question (‘Have you fallen in the last year?’), followed with a more complex assessment for those who respond positively. Those with a history of falls and risk factors for future falls can then be offered a place on a specialist-​run falls ex- ercise programme. Most will benefit in that they will be at lower risk of falling, will feel subjectively fitter, and may enjoy the social interaction of the programme; a few may conclude that the best way to avoid falling is to avoid moving. An alternative is to offer all those aged 65 and over (apart from those who are dying or have medical disorders that would exclude them from exercise) the chance to join a local physical activity pro- gramme, as in the ProAct65 + trial. This large trial, based in general practice, is described in the case study (Box 6.3.3). This approach to physical activity promotion is practical, man- ageable, and affordable. It recruits older people who need to ex- ercise more, uses exercise instructors who are readily available, and relies on easily accessible local amenities. The uptake—​about 10% of those invited—​does not overwhelm the service; since indi- viduals’ readiness to increase physical activity levels will change, recruitment of cohorts of the willing could, over time, allow a large proportion of the older population to participate. Complex multicomponent interventions If well-​being is complex, then attempts to increase it should logic- ally match its complexity. The belief that searching for hidden but correctable disabilities among the older population will result in less disability, improved quality of life, and greater well-​being is an intellectually attractive one, well worth testing in randomized controlled trials. Several such trials took place in the 1980s in the United Kingdom, Denmark, and the United States, and there is much to learn from their histories. Different trials used very dif- ferent interventions and outcome measures, but there are some common outcomes, as shown in Box 6.3.4. These early studies explored the best ways to provide anticipa- tory care for older people, and acknowledged the iatrogenic risks of treating unimportant abnormalities, and of medicalizing old age. Brief, non​intrusive strategies for predicting functional problems during routine consultations were sought and tested in random- ized controlled trials. The preoccupation of doctors with disease Box 6.3.3  Case study of the ProAct65+trial This trial randomized those who were interested in joining into either an exercise class (based on the Falls Management Exercise programme—​ FaME), or home-​based exercise (the Otago Exercise Programme—​OEP), or usual care, for 24 weeks. The open invitation resulted in a partici- pant group who were more physically active than average for their peer group, with higher than average quality of life scores and positive atti- tudes to exercise, but who were below population norms on the Timed Up and Go tests, functional reach, and 30 second chair rise. The self-​ selection of participants for the study did not include the most sedentary (who would have been the most likely to benefit), but did allow those who needed to improve their functional abilities to gain the chance to exercise more. The exercise class (FaME) arm had a greater proportion of participants reporting weekly moderately vigorous physical activity at or above the target level compared to treatment as usual, while the home exercise (OEP) arm did not. Participation in exercise classes, in the FaME arm, re- sulted in increased self-​reported physical activity, and reduced inactivity, which persisted for 12  months after the end of the intervention. The proportion of FaME participants who achieved 150 or more minutes of moderate to vigorous physical activity (MVPA) per week rose from 40% at baseline to 54% at the end of intervention, and 49% a year after the classes ended. The proportion of FaME participants who reported no MVPA/​week fell from 29% at baseline to 15% a year after closure of the intervention. There was no statistically significant difference in the number of falls between FaME, OEP, and the control arm during the intervention phase, so the exercise programme did not increase risks of falling (which can happen). Unlike some other studies of case-​finding for falls prevention, in the 12 months after the close of the intervention phase there was a statistically significant reduction in falls in the FaME arm compared with treatment as usual (OR -​0.4, 95% CI -​0.720, -​0.103, p = 0.009). However, the ProAct65 + interventions were designed to promote physical activity for its broad benefits, rather than a narrow objective of reducing falls, and this may explain its success in reducing falls. FaME costs between £218 and £269 per participant, and the cost of each extra person exercising at or above target was £1739.93 at 2011 prices. We need to understand more about attrition and the timing of re- inforcement programmes—​the effects on physical activity and falls wear off—​but nonetheless the ProAct65 + model could be implemented in pri- mary care, with likely gains to the well-​being of older participants. Box 6.3.4  Outcomes in community-​based health promotion trials for older people, up to 1990 • A  rise in morale among elderly people involved in screening programmes. • Referrals to all agencies tended to increase, including to specialist medical care in some studies. • A reduction in inpatient stay in some studies, possibly through early intervention in disease processes. • Increased inpatient rates through a greater use of respite care. • Reduction in mortality in some trials, perhaps for the same reason that inpatient stays declined, but not in all. • No improvement in older people’s functional ability, and general practitioner workload only decreased in situations where alternative services were organized to bypass existing primary care services.

536 Section 6  Old age medicine to the detriment of its social consequences, the failure to take into account the adaptive powers of older people, and the tendency to underestimate the burden borne by carers, were all identified as major obstacles to progress in developing more effective primary care for older people. Medical and social problems overlapped in ways that were often puzzling to clinicians, screening led to an increase in referrals to other agencies, but without clear evidence of benefit in many instances, and with variations in referral rates determined as much by the referrer as by the patient’s problems. Finally, at-​risk groups proved harder to identify than anticipated, for more pathological events occurred outside the expected at risk groups than in them. The generation of general practitioners and nurses that did this work introduced important ideas about how ageing in its organic, social, and psychological dimensions affected people’s health, how essential multidisciplinary teamwork was to providing appro- priate care for ill older people, and ultimately how networking with community-​based agencies was a more useful model than referral to specialist care. To this we can add the awareness that unmet need is more complex than it appears at first sight, with multiple reasons why needs may not be met, some of which may not be tractable. Despite these findings, the UK government introduced the ‘75 and over checks’—​essentially a multicomponent screening programme—​into British primary care in 1990. The UK Medical Research Council funded a trial which, launched after the intro- duction of the screening policy, compared universal versus tar- geted assessments and management by primary care teams versus a multidisciplinary geriatric assessment team. The results suggest that population screening did not produce health gain, and that primary care teams and multidisciplinary geriatric assessment produced similar outcomes. Chronic disease management If whole population screening was finally accepted as inappro- priate, targeted screening with intensive management of identified problems was seen as a logical alternative. In the United Kingdom this was implemented as nurse-​led chronic disease management for older people with complex co​morbidities who made frequent use of hospital services. The evidence base for this approach was arguably as weak as that for 75 and over screening in 1990. In par- ticular, we should note that chronic disease management remains problematic as a model of care, with evidence of limited effect- iveness, reliance on traditional forms of patient education, poor linkages to primary care, and reliance on referrals rather than population-​based approaches. There is also some discussion about whether chronic disease management is wanted by patients, par- ticularly older people who may feel that their independence and autonomy is threatened by an intrusive care system. Finally, there is a question of how to identify those who are likely to need high levels of care, for there is no linear and unambiguous link between the presence of a condition that can be labelled chronic and the need for health or social care. Despite these negative experiences, research into complex inter- ventions continued in many countries. A systematic review of 15 trials of preventive home visits carried out up to 2000 showed no clear evidence functional improvement. The England arm of the ProAge trial (2000–​2002) showed no change in health risk behav- iours or functioning following intervention. The picture began to change after 2000. Educational professionals doing preventive home visits in Denmark did appear to improve older people’s func- tional mobility. Similarly, nurse-​led case management in Spain did appear to show positive effects on functional ability, caregiver burden, and satisfaction. Reviews of more recent studies have dem- onstrated some potential to alter behaviours and promote inde- pendent living, but it is unclear which intervention components contribute to effectiveness. It appears that we are slowly developing methods of working with older people that do alter their ability to function, and (we presume) their sense of well-​being. Nevertheless, effect sizes are mostly small and there is much still to be done to identify and engage with those most likely to benefit, and to refine interventions. Negative experiences still accumulate; recent pri- mary care interventions designed for frail older people in several European countries failed to show a beneficial effect on disability. To continue to develop this work in the community, and to make interventions usable in primary care, we need a focused, brief as- sessment which takes into account the individual circumstances of the older patient in two ways. First, by emphasizing the ‘person-​ disease management approach’ that requires tailoring of clin- ical responses, and that is a strength of primary care. Second, by promoting goal-​oriented medical practice that permits the older patient to state what outcomes matter most to them; this is an in- tuitively plausible approach, although the evidence base for it is as yet thin. Preventive care and older people: 
Two cautionary notes We need to be cautious about how we promote well-​being, for two reasons. One is that prevention, in this case of disability, can do harm. The second is that well-​being may alter the way we think and act as we get older, potentially with negative consequences for ourselves and others. Tinetti argues that we are unwittingly subjecting older adults to a wide array of preventive treatments that have no or marginal benefit, or even impart unintended harm. Most people receiving preventive treatments will never experience the outcome regard- less of treatment. Recommendations for preventive interventions should take into account the likelihood of benefit and harm, re- membering also that the presence of one disease may lessen the effect on well-​being of preventing another disease or harm. Her argument was a response to a modelling study of preventing end-​stage renal disease in older people. Evidence of effectiveness gained from trials of preventive interventions in younger adults was applied to populations of those aged 70 and over. The re- ductions in relative risk of developing end stage renal disease in younger adults ranged from 25% to 56%, depending on baseline risk. When extrapolated to older people (who have a higher base- line risk), treatment effects of these sizes yield Numbers Needed to Treat (NNT) values greater than 100 for most; those at highest risk would have an NNT value around 16, and those at lowest risk an NNT value of around 2500. Another example is the prevention of stroke by treatment of hypertension and hyperlipidaemia in the oldest old. At over 80 years of age, hypertension is no longer a risk factor for stroke and cholesterol level has little effect, al- though it has a small impact when all cardiovascular endpoints

6.3  Optimizing well-being into old age 537 are aggregated. Treatment of hypertension and hyperlipidaemia is largely irrelevant in frail older people, and has only modest benefits in stroke reduction in the non​frail. However, stroke re- duction is not the only important outcome, and patient thresh- olds for discontinuing statins may be high because they are seen as effective in preventing serious and likely problems which will have a deleterious impact on well-​being. No-​one can be opposed to ‘well-​being’, but we can be wary of it. As European countries become happier, they become relatively less healthy (in the medium term). Countries with higher well-​being tend to spend less on healthcare. Life satisfaction may not be asso- ciated with healthy behaviour, but with consumption (eat, drink, and be merry!), and happiness may reduce perceptions of need for healthcare, resulting in delayed help-​seeking. Conclusions Healthy ageing and well-​being are facets of a complex subject that is bedevilled by boundary problems and paradoxes. Health in later life is the outcome of the interplay between biological, lifestyle, and social factors over a long period of time, an interplay which helps to explain the heterogeneity of older populations that is obvious to most doctors and other healthcare workers. Increasing physical activity and acquiring a healthy diet are the priorities if we apply a public health perspective to optimizing well-​being through pri- mary care. While control of hypertension and cardiovascular risk factors has had an effect on disability, there is much work to be done in developing effective primary promotion approaches across the life course. Secondary promotion in later life uses clinical interven- tions with older people that are either focused or complex and multicomponent. Falls prevention is an example of the former and could be readily implemented in primary care as either two-​stage case-​finding, or through community-​based exercise programmes. The history of complex interventions is long and mostly negative, but there are signs that community-​based interventions are begin- ning to improve functional ability, although the effect sizes in trials are usually modest. There are many reasons why older people will not or cannot adopt all the activities that promote healthy ageing and well-​being, a lesson already learned in primary care. Humility of perspective may help us to make faster progress. FURTHER READING Beaudart C, et  al. (2014). Sarcopenia:  burden and challenges for public health. Arch Public Health, 72, 45. Beswick AD, et al. (2008). Complex interventions to improve phys- ical function and maintain independent living in elderly people: a systematic review and meta-​analysis. Lancet, 371, 725–​35. Bowling, A (2007). Aspirations for older age in the 21st century: what is successful ageing? Int J Aging Human Dev, 64, 263–​97. Bowling A, Dieppe P (2005). What is successful ageing and who should define it? Br Med J, 331, 1548–​51. Byatt K (2014). Overenthusiastic stroke risk factor modification in the over-​80s: are we being disingenuous to ourselves, and to our oldest patients? Evid Based Med, 19, 121–​2. Callahan CM, McHorney CA, Mulrow CD (2003). Successful aging and the humility of perspective. Ann Intern Med, 139, 38990. Chief Medical Officer (2004). At least five a week: evidence on the im- pact of physical activity and its relationship to health. Department of Health, London. Craig R, Mindell J, Hirani Ve (2009). Health Survey for England 2008. Volume 1: Physical Activity and Fitness and Volume 2: Methods and Documentation. The NHS Information Centre, London. www. ic.nhs.uk/​pubs/​hse08physicalactivity De Lepeleire J, Heyrman J (2003). Is everyone with a chronic disease also chronically ill? Arch Public Health, 61, 161–​76. Depp CA, Jeste DV (2006). Definitions and predictors of successful aging: a comprehensive review of larger quantitative studies. Am J Geriatr Psychiatry, 14, 6–​20. Elkan R, et al. (2001). Effectiveness of home-​based support for older people: systematic review and meta-​analysis. BMJ, 323, 719–​24B. Fletcher A, et al. (2004). Population-​based multidimensional assess- ment of older people in UK general practice: a cluster randomised factorial trial. Lancet, 364, 1667–​77. Frost H, Haw HJ, Frank J (2011). Promoting Health & Well-​being in Later Life:  Interventions in Primary Care and Community Settings. Scottish Collaboration for Public Health Research and Policy, Chief Scientist Office, Scottish Government. https://​www. SCPHRP.ac.uk Gillespie LD, et al. (2012). Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev, 12, CD007146. Gopinath B, et al. (2014). Adherence to dietary guidelines positively affects quality of life and functional status of older adults. J Acad Nutr Diet, 114, 220–​9. Harris T, et al. (2015). A primary care nurse-​delivered walking inter- vention in older adults: PACE (pedometer accelerometer consult- ation evaluation)-​Lift cluster randomised controlled trial. PLoS Med, 12, e1001783. Hillsdon M, et  al. (2005). The effectiveness of public health inter- ventions for increasing physical activity among adults: a review of reviews. Health Development Agency, London. Huppert FA (2008). Mental capital and well-​being:  making the most of ourselves in the 21st century. State-​of-​science review. Psychological well-​being: evidence regarding its causes and conse- quences. SR-​X2. Government Office for Science Foresight project, National Institute for Health & Clinical Excellence, London. Iliffe S, et al. (2014). Multicentre cluster randomised trial comparing a community group exercise programme with home-​based exer- cise with usual care for people aged 65 and over in primary care. Health Technol Assess, 18 vii–​xxvii, 1–​10. Laybourne AH, Biggs S, Martin F (2008). Falls exercise intervention & reduced falls rate: always in the patient’s interest? Age Ageing, 37, 10–​13. Marshall A, et  al. (2015). Cohort differences in the levels and tractories of frailty among older people in England. J Epidemiol Community Health, 69, 316–​21. Martinez-​Reig M, et  al. (2014). Nutrtional risk, nutritional status and incident disability in older adults. The FRADEA Study. J Nutr Health Aging, 18, 27076. McClure R, et al. (2005). Population-​based interventions for the pre- vention of fall-​related injuries in older people. Cochrane Database Syst Rev, 1, CD004441. Metzelthin S, et al. (2013). Effectiveness of an interdisciplinary pri- mary care approach to reduce disability in community dwelling frail older people BMJ, 347, f5264.

538 Section 6  Old age medicine Milaneschi Y, Tanaka T, Ferrucci L (2010). Nutritional determinants of mobility. Curr Opin Clin Nutr Metab Care, 13, 625–​9. National Institute of Clinical Evidence (NICE) (2004). Guidelines 21:
Falls:  the assessment and prevention of falls in older people. London. National Institute of Clinical Evidence (NICE) (2013). Falls in
older people:  assessing risk and prevention. NICE guidelines [CG161]. O’Hare A, et al. (2014). Interpreting treatment effects from clinical trials in the context of real-​world risk information. JAMA Intern Med, 174, 391–​7. Ogilvie D, et al. (2007). Interventions to promote walking: systematic review. BMJ, 334, 1204. Peel NM, McClure RJ, Bartlett HP (2005). Behavioral determinants of healthy aging. Am J Prev Med, 28, 298–​304. Stuck AE, et al. (1993). Effects of a comprehensive geriatric assess- ment on survival, residence and function; a meta-​analysis of controlled trials. Lancet, 342, 1032–​6. Tappenden P, et  al. (2012). The clinical effectiveness and cost-​ effectiveness of home-​based, nurse-​led health promotion for older people: a systematic review. Health Technol Assess, 16, 1–​72. Tinetti M (2014). The gap between clinical trials and the real world: extrapolating treatment effects from younger to older adults. JAMA Intern Med, 174, 397–​8. van Haastregt JC, et al. (2000). Effects of preventive home visits to elderly people living in the community: a systematic review. BMJ, 320, 754–​8. World Health Organization (2015). World Report on Ageing and Health 2015. http://​www.who.int/​ageing/​events/​world-​report-​2015-​ launch/​en/

6.4 Older people and urgent care 539

6.4 Older people and urgent care 539

ESSENTIALS Older people, especially those with frailty, are increasingly be- coming the main users of urgent care services, despite efforts to promote care at home; this is a global issue. Older people with frailty will usually present with non​specific presentations, multiple morbidities, functional decline, and differ- ential challenge (those most in need are least able to access the services they require): a constellation that challenges the traditional paradigm of urgent care responses. Comprehensive geriatric assessment is a useful evidence-​based, overarching framework to guide assessment and management of older people with frailty presenting with crises. Geriatric teams should be excellent at delivering comprehensive geriatric assess- ment, but all clinicians throughout the health and social care system need to be able to apply its principles. For older people with frailty, patient/​family-​derived, value-​driven goals of care are more important than protocol-​driven standards of care. Effective management of older people presenting with frailty syndromes requires a specific set of competencies that can be taught and learnt, but changing clinicians’ routine behaviours can be difficult. Rapid comprehensive geriatric assessment in urgent care set- tings, supported by robust early supported discharge services, can improve outcomes for patients and for services. The clinical response needs to be supported by a systems-​based approach that integrates governance, information and risk sharing, underpinned by stable leadership and a shared common vision. Introduction A general overview of acute hospital care for older people is pro- vided in Chapter 6.5. This chapter will focus specifically upon care for older people in emergency departments and acute medical units (AMUs) (i.e. the first 72 hours of a hospital stay), and the interface with community services. This chapter contains a combination of theory and evidence, supported by clinical vignettes. These have been condensed in the sections on developing a framework and on ‘bringing it all to- gether’ that focus upon clinical issues. The epidemiology of crises in older people Urgent care is increasingly synonymous with older peoples’ care in Organisation for Economic Co-​operation and Development (OECD) countries, especially in Europe, which has 23 of 25 of the world’s ‘oldest’ countries. Many countries in Asia are catching up on the ageing demographic, especially in the Far East. The United Nations uses a cut-​off of age of over 60 years to define ‘old’, but being older varies according to country; for example in sub-​ Saharan Africa, the World Health Organization (WHO) suggests the age of 50–​55 be considered old. Although this ageing of the hospital population is the case for the United Kingdom (UK), it has a lower rate than most OECD coun- tries, at 87% of the average. But admission rates are increasing sig- nificantly. Over the 11-​year period from 2001/​02 to 2012/​13, there was a rise of 26% per 1000 older people. Rates increased steadily with age, just 10% for the 65–​69 age group but 50% for the 90 plus age group. In contrast, the total number of bed days following emergency admissions of people aged 65 plus has fallen as a result of reduced length of hospital stays. At least in the United Kingdom, there has been considerable debate about these changes. Increased numbers of older people alone does not explain it as there has also been a rise in the age-​ standardized rates of admission. There is no simple explanation. The reality is likely a combination of the old population being older, with the associated greater morbidity requiring acute care, but also difficulties in coordinating care for these individuals in commu- nity settings. Re-​admission may be common, up to 50% at one year. Policy responses In response to clinical and economic concerns about these rises, in many well-​developed health services internationally there has been a considerable emphasis on identifying the top ‘high resource users’, with a view to providing a ‘wrap-​around’ care solution that, in theory at least, should decrease reliance upon acute hospital based (secondary care) services. Trials of hospital at home have demonstrated at least equivalent outcomes for older people with crises managed in their own homes as opposed to acute hospitals, but for a relatively small population, with careful case selection. 6.4 Older people and urgent care Simon Conroy and Jay Banerjee

540 Section 6  Old age medicine Attempts to upscale the findings from the ‘hospital at home’ trials, in the United Kingdom conceptualized as ‘intermediate care’, have thus far failed to have the desired impact on attenuating acute care use. Perhaps in recognition that the focus on a small number of users in an attempt to reduce the overall burden on acute care has had a limited impact, there has been a move towards ‘proactive care’, again providing holistic assessment and management but in this case focusing upon a broader population, identified on the basis of predicted hospital resource use in the years to follow, rather than incident resource use. The challenges for such schemes, for which robust evidence remains scarce, is upskilling a much broader group of community providers in the management of older people. This will be a significant challenge as the relevant competencies have not been widely promulgated in undergraduate and postgraduate curricula. Additional limitations come from the relative inability of a range of risk prediction tools to identify the population most likely to experience an admission (and hence a population in whom genuine admission prevention might be possible), and at the same time avoid excessive inclusion of those not likely to ex- perience an admission, for whom admission prevention inter- ventions might confer benefit in terms of quality of care, but risk being not cost-​effective. The justification of the focus on hospi- talization use as the main driver of resource use is supported by studies identifying that the bulk of costs in an individual’s care episode over the three months following an acute admis- sion is primarily driven by subsequent hospital use, as opposed to community costs. There is therefore a gap in community capability, in terms of identification, competence, and capacity, in the face of the vol- umes of older people presenting to services which aim to prevent or respond to crises. The implication is that many older people with frailty will continue to access urgent care hospitals, which therefore need to be fully equipped and capable of providing ap- propriate age-​attuned care. In most developed health services, urgent care starts in the emergency department (ED) or acute medical units, hereafter referred collectively to as urgent care settings. However, we need to be aware that currently both admission prevention and admission avoidance approaches are based around a healthcare-​delivery paradigm rather than an improvement in health paradigm. Health, in this context as per the WHO definition of a state of physical, mental, and social well-​being, and not just an absence of disease or infirmity. Evidence-​based interventions for older people with frailty in urgent care settings All too often hospitals are designed to meet the needs of in- dividuals with specific conditions, rather than provide hol- istic care which has been shown to be effective for older people. Unfortunately, there is a limited evidence base to guide service configuration specifically in urgent care settings. Recent reviews focusing upon trials of transitional care models to support frail older people being discharged from emergency departments found no overall impact. So the response is to extrapolate from the existing evidence for comprehensive geriatric assessment (CGA), and apply it in new settings, ideally accompanied by robust service evaluations. This quality improvement approach has evidenced apparent improvements in service level outcome for older people with frailty in urgent care settings in several UK centres; evidence for improved person-​related outcomes from such initiatives have yet to be demonstrated. The key role of frailty Hospitalization of an older person can be a sentinel event that her- alds an intensive period of health and social care service use. This is especially the case for ‘older people with frailty’ (see Chapter 6.2), a distinctive late-​life health state in which apparently minor stressor events are associated with adverse health outcomes. Depending upon definitions, the setting, and local service configuration, about 5–​10% of all emergency department attendees and about 30% of patients in acute medical units are older people with frailty. Although they therefore constitute a minority of the total patients in urgent care settings, they represent a much larger proportion of those at risk of harms and high resource use as they progress from admission into inpatient care. Early identification of frailty is important to maximize the opportunities for reducing harm and optimizing care. Frailty scales exist, but there is limited evidence for their discriminant ability in the urgent care context: although most perform better than chance in predicting a range of poor outcomes, none of them performed adequately for individual clinical decision-​ making, and most perform either poorly or very poorly. When defining a population for intervention in clinical practice, ac- ceptability, and ease of use are important considerations as well as discriminant ability. Perhaps the most practical tool for ur- gent care settlings is the Clinical Frailty Scale (CFS), which is quick simple and easy to use. People with CFS scores of 6–9 are at the greatest risk of harms (delirium, death) as well as longer lengths of stay. Pathways Early identification of frail older people at urgent presentation en- ables targeting for care approaches that can deliver comprehensive geriatric assessment, which is an effective, evidence-​based ap- proach to improve patient outcomes and service efficiency. The aim is to provide specialist care to those most in need, but this is rarely possible for all patients, and in some health services specialist old age services do not exist. There is need, therefore, to upskill general acute care through guidance and pathways that operate at any time of the 24-​hour cycle. Although service structure is less important than what is done, there is a stronger evidence for the effectiveness of dedicated spe- cialist units such acute geriatric units (acute frailty units) than for liaison type services. Treating 13 frail older people using comprehensive geriatric assessment avoids one unnecessary death or admission to resi- dential care at six months, compared with general medical care

6.4  Older people and urgent care 541 for an urgent care episode. To put this in perspective, we need to thrombolyse 17 people with acute ischaemic strokes to avoid one ‘unfavourable’ outcome at the same time as causing 1 death for every 100 treated and one non​fatal bleed for every 20 treated. A  typical frailty (comprehensive geriatric assessment) service will consist of: • A physician with expertise in the care of frail older people—​ usually, but not exclusively, a geriatrician • Physiotherapists and/​or occupational therapists • Nurse specialists that can offer a case management function • Ward and peripatetic teams with skills and expertise in frailty • Staff able to organize complex (and simple) discharge Comprehensive geriatric assessment is a process:
Who does it? Do you need a geriatrician to do comprehensive geriatric assess- ment, or just apply geriatric competencies well? The only logical answer is that it is the application of the competencies that is key, not who applies them. To quote Coni, ‘Geriatrics is too important to be left to geriatricians. We are all geriatricians now, and geriatric medicine should be like a caretaker government—​self-​appointed to instruct others how to do it, and then to preside over its own demise’. But at the heart of this is the difference between knowing and doing: knowledge and skills in managing older people with frailty can be taught, but developing the necessary behaviours is more challenging. More important than the specific roles is the ability of the team to deliver a proportionate, competent assessment, and ongoing management. As a frailty service matures, role boundaries will blur, for example, with emergency physicians proving the diag- nostic element in the emergency department, or single specialty therapists taking responsibility for physical and environmental as- sessments, as opposed to dual (duplicate) assessments. The function of the geriatric team is to provide excellent direct clinical care, which aims to address the needs of at least 70% of frail older people within any given setting, but also to be responsible for education and training of ALL staff that will come into contact with frailty. Where resources permit it seems sensible that conventional comprehensive geriatric assessment (geriatric) services focus their efforts on frail older people. This will mean streaming patients into dedicated services at each stage of the patient journey—​emergency departments, acute medical units, inpatient wards, ‘non​geriatric services’ (see Chapter 6.6) and postacute care. Priorities in the clinical management of older people with frailty General medical care principles apply as much to older people with frailty as anyone else: Early Warning Scores, timely diagnostics, early assertive case management, early goal setting, and so on. For example, an older person with a Modified Early Warning Score (MEWS) of ‘0’ at admission has a very low probability of death (OR 0.14, 95% CI: 0.08–​0.24). Compared to their younger counterparts, presentation is usu- ally more challenging in older people with frailty. Typically, non-​ specific presentations with geriatric syndromes such as falls or delirium may cause diagnostic uncertainty. Communication bar- riers necessitate involvement of carers and families. Coexisting problems including multimorbidity make assess- ment and management complex (see Table 6.4.1). Problem lists are helpful, and in addition to traditional diagnoses should include the range of relevant issues identified by comprehensive geriatric as- sessment. This is achieved most efficiently by coordinated team- work supported by structured but rapid communication, such as frequent brief discussion around marker boards highlighting ac- tions and progress. It can be challenging to carry out a comprehensive geriatric as- sessment in urgent care settings because of constraints of time and place, or because of the priority of urgent medical treatment (e.g. for septic shock) or resuscitation. But even then, elements of comprehensive geriatric assessment are needed, as factors such as mobility, cognition, and patients’ wishes at the end of life have an important impact on clinical management. So challenging as com- prehensive geriatric assessment in urgent care might be to deliver, it is important, and urgent care services must adapt to meet this challenge, just as they have adapted to meet the urgent needs for stroke thrombolysis or coronary angioplasty. Table 6.4.1  Example of the issues to be addressed through comprehensive geriatric assessment (CGA) Presenting complaints—​what matters to the older person Medical Co-​morbid conditions and disease severity, considering current relevance Consider burden of disease Medicines review—​consider the short term risks and benefits of medications (especially antipsychotics, benzodiazepines, antihypertensives, and analgesics) Nutritional status (weight changes, appetite) Psychological Cognition—​is there delirium or dementia or both? Mood and anxiety Fears (especially of falling and dying) Functional ability Basic activities of daily living (dressing, eating, washing, continence) Gait and balance—​testing mobility is an excellent diagnostic tool, as well as being therapeutic Activity/​exercise status (walking distance) Instrumental activities of daily living (housework, driving, shopping) Social circumstances Informal support available from family or friends Social network such a visitors or daytime activities Eligibility for being offered care resources Environment Home comfort, facilities, and safety Use or potential use of telehealth technology, and so on Transport facilities Accessibility to local resources

542 Section 6  Old age medicine Balanced decision-​making Balanced decision-​making should be governed by values more than standards (e.g. standard ‘troponin pathways’ to rule out cardiac disease). Increasingly, values are being conceptualized in terms of person and family centred care, defined as ‘healthcare that estab- lishes a partnership among practitioners, patients, and their fam- ilies (when appropriate) to ensure that decisions respect patients’ wants, needs and preferences, and that patients have the education and support they need to make decisions and participate in their own care’. Specific pitfalls in assessment and management Aside from the ‘philosophy of care’ (holistic assessment, values-​ driven decision-​making), the effective management of older people with frailty requires specific knowledge about presentations in this group. The geriatric syndromes such as falls and delirium, and the risks of hospitalization to patient safety, are discussed in more de- tail in Chapter 6.5. Here we focus on particular considerations in the urgent care setting. Delirium and dementia Dementia and delirium are syndromes: diagnosis depends upon clinical skills. Routine assessment of cognition will identify mod- erate to severe cognitive impairment, but more subtle presenta- tion can be missed. The four-​point Abbreviated Mental Test score (AMT-​4) is quick to complete, and has good correlation with the 10-​point scale but is easier to apply requiring only place, age, date of birth, and year. The detection of cognitive impairment in the emergency department context should always be accompanied by an assessment for delirium. The 4AT is another strong contender that needs more time and knowledge of English. The same is true for the Delirium Triage Screen followed up by the confirmatory brief Confusion Assessment Method. Delirium has acute onset, the course typically over days and weeks. Failed detection in emergency departments is associated with a sevenfold hazard for increased mortality, and is an inde- pendent predictor of hospital length of stay. Symptoms may not only be cognitive: they may be behavioural, psychotic (hallucin- ations, delusions) or mood symptoms with little or absent signs of disorientation or cognitive impairment. For example, symptoms of depression in a delirious individual may be indistinguishable from people suffering from depressive disorder. The key is to sus- pect delirium with any sudden change of mental state or behaviour in older people. Characteristic signs of delirium, which also help distinguish this from dementia, are: • clouding of consciousness • reduced attention and concentration • a fluctuating pattern of symptoms and signs It may not be possible for a clinician in the emergency department to be able to tell whether the cognitive impairment they have de- tected is different from the usual state. Information from carers or third parties is essential and will often hold the key. Both dementia and delirium impact upon treatment, for ex- ample, through raising questions about a person’s capacity to make health and welfare decisions, or practical issues such as concord- ance with therapies. Sepsis Sepsis is a huge challenge in older people with frailty, being both over and underdiagnosed. Sepsis may present with non​specific features, but it is important to focus on objective signs that point to the most probable diagnosis. Fever can be absent in 30% of older people with sepsis, but presence of fever points to bacteraemia in 90% of older people. Volume replacement will be needed in most cases unless fluid overload is evident (remember sacral oedema may be the only sign). In a study of effectiveness of ‘sepsis six’, older people receiving more fluid resuscitation had better survival than the controls. Bundles such as ‘sepsis six’ can be helpful as guides, but have gen- erally not been validated or designed for older people with frailty. Many abnormalities in older people are incidental, best exempli- fied by the ubiquitous ‘dipstick positive urinary tract infection’. The conundrum here is that asymptomatic bacteruria, which com- monly causes positive urine dips, is prevalent (up to 50% of care home residents), and the treatment of positive urinary dips confers no benefit. A clinical diagnosis of urinary tract infection requires the presence of one or more of dysuria, frequency, suprapubic ten- derness, urgency, polyuria, and haematuria in the absence of any other good explanation for the apparent sepsis. Table 6.4.2 illustrates the complexity when applying the sepsis six criteria to a typical older person with frailty, presenting with de- lirium on a background of chronic obstructive pulmonary disease, heart failure, and detrusor instability. Falls and syncope Falls are the commonest single reason for older people to present to urgent care, and they are often due to underlying disease or impair- ment that may be amenable to treatment or modification. Table 6.4.2  Considerations when implementing the sepsis six bundle Deliver high-​flow oxygen • Remember CO2 retention Take blood cultures • Be cautious drawing blood so that delirium related agitation does not result in injury (to patient or staff) • Higher rate of negative blood cultures Administer empiric intravenous antibiotics • Balanced against the risk of C. difficile or antibiotic resistance • Beware ‘sepsis mimics’ (the patient was given antibiotics, so it must be sepsis . . . and for example missing the subdural) Measure serum lactate and send full blood count • Validation studies based in 60-​year-​olds; unclear if prognostic significance holds up in older people with frailty and multiple co​morbidities Start intravenous fluid resuscitation • Important as premorbid dehydration is common, and volume depletion exacerbated by acute illness; • Beware fluid overload—​frequent smaller boluses titrated against clinical response are mandatory Commence accurate urine output measurement • Do not rush to insert urinary catheters: catheter associated sepsis is common, as is subsequent incontinence due to deconditioning of the detrusor muscle • Reducing unnecessary catheterizations improves patient safety. • Bladder scans, weighing incontinence pads, or simply measuring urine volume in continent older people are valid alternatives

6.4  Older people and urgent care 543 Key in urgent care settings is to carefully differentiate between syncopal and non​syncopal falls; this is not always easy because of memory impairment, recall bias, or syncope-​related ante-​ and retrograde amnesia, which is common. All too often, direct witness accounts are not available, meaning that the clinician has to base their judgement on the balance of probabilities. An understanding of cerebral perfusion pressure in older people is important, as minor perturbations can result in syncope or presyncope. While international hypertension guidelines promote a focus on tight blood pressure (BP) control, there is ongoing de- bate about the ideal BP in older people, linked to concerns about perfusion pressure. BP less than 120 systolic in older people, es- pecially where variation with lower troughs is evident, should prompt careful consideration of syncope. It is useful to ask ‘do you remember hitting the floor?’, and not to accept vague assertions such as ‘I must have tripped’ as plausible explanations for the fall. The pattern of injury can also provide clues: facial bruising in particular is highly suspicious of syncope. The presence of syncope should prompt a review of medication and a search for underlying causes, at the very least a 12-​lead electrocardiogram and routine bloods; other tests may be indicated (see Chapter 6.8). This is par- ticularly true in older people with dementia as they may not present with syncope but increasing confusion and slow falls due to ortho- static hypotension. Not all patients with syncope require hospital admission. Where there is a high suspicion of life-​threatening conditions (e.g. severe aortic stenosis, ventricular arrhythmias), admission may be appro- priate. But for most people with syncope there will be a more plaus- ible and more benign explanation, making home-​based care a very reasonable option. Increasingly the use of near-​patient diagnostics, such as echocardiography, are playing a useful role is supporting clinically and goal-​driven driven decision-​making. Injuries Older people presenting with poly-​trauma need to be managed according to advanced trauma and life support (ATLS) principles with special consideration of the fact they do not respond well to prolonged immobilization. Advanced imaging including early computed tomography scanning is important for quick and defini- tive diagnosis, and as an adjunct to clinical assessment. There is an association between increasing age and poor out- come following trauma, although any individual factor or combin- ations fail to predict an unacceptable outcome. Hence it is usually advisable to embark on aggressive therapy, irrespective of age or in- jury, except in the initially moribund individual. Older people who do not respond to this initial resuscitation have adverse outcomes. Responders have a good prognosis, including a complete return to their premorbid state. Pain The use of traditional pain scales can be difficult because of com- munication barriers, such as cognitive impairment. Alternative assessment processes that rely on non​verbal cues may be more useful in some older people. Pain management in people with dementia may be challenging because of co​morbidities, but also because of polypharmacy. The importance of assessing changes in the individual’s normal behaviour patterns as an indicator of increasing stress levels or potential pain cannot be underestimated. The modified Abbey pain scale emphasizes involving the person’s carers/​family. Early, effective pain relief is self-​evidently important, but despite the potential of medications such as opiates to cause drowsiness or confusion, for many patients the net benefit reduces the risk or severity of delirium. Medication While there has been a substantial focus on ‘de-​prescribing’ in older people, driven by guidance such as the STOPP/​START cri- teria and the Anticholinergic Burden Scale urgent care presenta- tions do present an additional opportunity to review medication appropriateness. Consideration should be given as to where a pa- tient is in their life—​their ‘trajectory’—​informed, when possible, by a description of physical and cognitive function over the last year. Some patients will be clearly entering a palliative phase, in which case, is it helpful to continue antiplatelet therapy or anti- coagulants (side effects such as bruising, bleeding, and low-​grade anaemia are common and their impact often underestimated in older people with frailty)? The urgent care presentation heralds the need for a new clinic- ally based balance of risks and benefits, which may be transitory, or may be an opportunity for a longer-​term change. For example, does someone who is bed-​bound really require high dose antianginals if they are no longer exerting themselves? Each de-​prescribing scenario should consider the patient’s values or best interests for- mulations, the rationale for continuing the treatment (how will it help?), and the opportunity costs of continuing prescribing (re- membering that time spent administering medication is time not spent on comfort care). This can be a challenging task, but in- formed by guidance, practice, and clinical supervision, could (and arguably should) be a routine part of urgent care assessments. Any changes and the rationale for the changes should be clearly com- municated to primary care clinicians and to carers. Abuse Abuse is common in older people who, because of their situation or circumstances, are unable to keep themselves safe. The nature of abuse and the fact that it is commonplace makes it critical that it is clearly understood that recognizing and tackling abuse is everyone’s responsibility. The five types of abuse are discussed in more detail in Chapter 6.11. The urgent care setting presents a possibly unique opportunity to recognize the important symptoms or signs of abuse; be alert to this possibility and take time to examine accordingly. Conversely, evidence of good care may also be identified and this is helpful in judging the capability and resilience of carers to support an older person, for example, recently painted nails are generally a good sign. Clinical signs that might suggest abuse are shown in Table 6.4.3: none of these features in isolation should be taken as diagnostic, as all may have alternative explanations, but an accumulating pattern of concerns should alert the clinician to the possibility of abuse. End-​of-​life care and future care planning Remembering that urgent hospitalization of an older person can be a sentinel event that heralds an intensive period of health and social care service use, urgent care clinicians should also ask them- selves if this episode is the start of the end-​of-​life phase. The end of life may be imminent (in which case decision-​making should

544 Section 6  Old age medicine be clearly focused on palliative needs), but might be in the next few months, in which case simply starting the conversation in the urgent care setting might be appropriate, with follow-​up advance/​ future care planning discussions being led by those who know the patient best. Develop a framework From the examples given here, it is clearly apparent that managing older people in urgent care settings can be complex. Unlike patients with single presenting problems, older people will usually present with a range of issues, not just medical, that require addressing in order to achieve an effective management plan. It is not possible to describe every possible scenario; rather, we offer a framework describing overarching principles that can be useful when assessing older people. There are four key points to consider: • Non​specific presentations • Multiple co​morbidities • Functional decline and altered homeostasis • Differential challenge Non​specific presentations Older people with frailty will usually present non​specifically. This means that the textbook clues for diagnosis may not be present. Do not interpret a lack of specificity as a lack of seriousness or urgency. Recognize the non​specific presentations (off legs, falls, immobility, delirium, and so on), and use them as a prompt to switch on your diagnostic antennae to focus upon objective pointers towards a diagnosis. The non​specific presentation itself is a clue; it may be related to a communication barrier (think delirium, dementia, dysphasia, and/​ or sensory impairment). Multiple co​morbidities Do not content yourself with a single system diagnosis; there will usually be multiple active issues, which often interact and com- pete for prioritization. List the active diagnoses and stratify them in order of urgency, as this will help you prioritize those that need addressing now, and those that can wait a few hours, but should not be forgotten. Multiple co​morbidities often bring polypharmacy; use the ur- gent care episode to discern if there are active adverse drug events, or opportunities for de-​prescribing. Functional decline and altered homeostasis Older people with frailty will often have pre-​existing functional impairment, added to which they will often delay presentation with acute illness, either through inherent reticence or reduced access to support, or even neglect by carers. This means that the impact of an acute event will already have started to manifest in terms of functional ability, which could be exacerbated by en- forced bed rest. A period of rehabilitation will often be needed, and increasingly this should be done at home rather than in an institutional setting. Older people with frailty will have altered homeostatic mech- anisms, which means that their reserve is impaired, making them more vulnerable to apparently minor insults, but also altering their responses (e.g. altered drug handling). Remember ‘start low, go slow’ when introducing new drug treatments. Differential challenge Those most in need are least able to access the services they require, which can be due to intrinsic factors, such as cognitive or sensory impairment, or extrinsic factors, such as the lack of age-​attuned services or broader socioeconomic factors. Comprehensive geriatric assessment Comprehensive geriatric assessment offers a useful structure to ensure that a patient’s assessment is holistic, and therefore more likely to result in a management plan that will be successful. When considering a patient, mentally check-​off if you have sought out and identified issues in each of the domains of comprehen- sive geriatric assessment (Table  6.4.1) when formulating your management plan: Medical: Have you got a working primary diagnosis, as well as a list of co​morbidities that are active or important that also require attention? Psychological:  Have you assessed for the presence of delirium, dementia, or depression/​anxiety? These will have a substantial impact upon ongoing management. Functional ability: You may have made a diagnosis, but how will you get the patient ‘clinically stable for transfer’. Being ‘med- ically fit’ is meaningless if the person cannot mobilize to the toilet and back safely. Social circumstances: What support exists? What more is needed to enable a return home? Do you know how to access resources that can help? Environment: Is the home setting conducive to ongoing care needs, or are adaptations required? Do you know how to organize a home hazards review for people who have fallen? Bringing it all together—​a clinical example Consider this fairly typical case scenario (Box 6.4.1) , which dem- onstrates the overarching principles described here in action. Table 6.4.3  Clinical signs to watch out for as possible evidence of abuse Physical • Bruises to parts associated with rough handling, such as upper arms • Poor oral hygiene Psychological • Obstructing the older person’s opportunity to speak • Reticence to speak in front of ‘carers’ Financial or material • Poor state of clothing • Undernutrition Sexual • Bruises to private parts such as introitus or vagina • Sexually transmitted infections Neglect and acts of omission • Late presentation of acute illness • Unwashed body or clothing

6.4  Older people and urgent care 545 Once the initial assessment is complete (in this case taking no more than 1–2 hours in total, using the care home information, near patient testing and hospital systems, and the most important diagnostic tool—​the telephone), a stratified problem list can be for- mulated, as shown in Table 6.4.4. Multiple issues have been identified as probable contributors to the fall. Now that these have been clearly identified they can be individually addressed—​either immediately or over time—​in the clinical management plan (Table 6.4.5). It is important to note that, despite a low Early Warning Score suggesting no need for escal- ation, there is substantial frailty-​related risk. Transfer from urgent care settings To facilitate more detailed assessment in selected older people, the urgent care services will need to have timely access to therapy staff and social services support. These are increasingly being es- tablished under the guise of ‘geriatric emergency medicine’, with service evaluation level evidence of impact. Having undertaken a rapid, holistic assessment of a patient (reflecting the domains of comprehensive geriatric assessment, Table 6.4.1) and established a stratified problem list and treat- ment plan, the next phase of decision-​making should focus upon where is the best place to provide this care. Several ran- domized studies have evaluated geriatric emergency medicine type interventions linking in with community services, but with limited evidence of impact; this is at least partly related to the trials testing undertheorized and underdeveloped inter- ventions. Given the wealth of information about the benefits of comprehensive geriatric assessment, ongoing efforts are re- quired to develop and refine more sophisticated, integrated interventions that enable the delivery of comprehensive geri- atric assessment. Areas of uncertainty, controversy, and
future developments Many older people will have ongoing health issues that need to be addressed, although not necessarily requiring a hospital ad- mission. For such people, timely access to extended scope home services can facilitate early discharge from urgent care; there is ro- bust evidence that such ‘hospital at home services’ can be effective and even save lives. Urgent care services will need to know about how and when to access community services in a timely manner to support early discharge. Box 6.4.1  Emergency case scenario An 89-​year-​old lady, Vera, presents to the emergency department, having been found on floor in her care home; there is no meaningful history from the patient as she is drowsy and not able to recall the event. (NON-​ SPECIFIC PRESENTATION) Past medical history (from the care home information):  ‘recurrent UTI’, Alzheimer’s dementia, hypertension and stroke. (MULTIPLE CO-​ MORBIDITIES, all of which could be contributing to possible delirium) Medications: co-​codamol 30/​500 TT QDS (initiated two months ago following fall and right shoulder injury), bendroflumethiazide 2.5 mg, OD atenolol 50 mg, OD donepezil 10 mg OD, aspirin 75 mg OD, simvastatin 40 mg OD, trimethoprim 100 mg ON. (POLYPHARMACY—​opioids can cause constipation, which can cause urinary retention which can cause UTI; antihypertensives that may contribute to falls risk) A phone call to the care home establishes that she was found on the floor at 4 am, having last been seen in bed at 2 am. Vera was found lying on her right side and had been incontinent of urine. The care home as- sistant reported that she had observed a Vera to have a reduced appetite for last 24 hours, associated with nausea. Vera’s bowels had last opened two days ago. (ENVIRONMENTAL and SOCIAL SUPPORT NETWORKS—​in this case helping with the diagnostic formulation) Vera is usually independently mobile, but requires supervision and prompting to feed herself, wash, and dress. She is occasionally incontinent of urine and wears pads overnight, but continent with bowels. Although usually disorientated, Vera can hold a conversation and answer yes/​ no for simple choices. She has been at the care home for three years. (FUNCTIONAL IMPAIRMENT—​in this case helping establish a baseline and guide treatment aims, as well as identifying a substantial change from baseline that suggests a diagnosis of delirium) Examination findings: clinically dehydrated (jugular venous pressure (JVP) not visible lying flat); lying BP 105/​64; too drowsy to stand; HR 54 bpm regular (confirmed on ECG); neuro-​drowsy and disorientated—​ AMTS 2/​10; resp-​basal crackles (note—​often hypostatic and not always a sign of pulmonary oedema); GI—​abdomen soft, BS present, lower ab- dominal discomfort on palpation; PR—​loaded rectum; urinary—​palpable bladder; joints—​bruised right shoulder, movement preserved in all four limbs, no bony/​ spinal tenderness; no skin sores, nail varnish carefully applied recently. Investigations:  post-​void bladder scan:  710  ml (normal <200  ml) U&E: creatinine 166 micromol/​litre (baseline 72), urine dip not tested (unable to obtain specimen); previous MSU: E. coli resistant to trimetho- prim. CK/​bone/​LFT/​ FBC/​TSH/​haematinics: normal ranges. Computed tomography scan (CT) of head (fall and confusion):  disproportionate hippocampal atrophy and moderate burden of small vessel disease, ma- ture infarct noted right temporal-​parietal lobe. Table 6.4.4  Comprehensive geriatric assessment in practice:
The problem list Multifactorial fall, due to: • Delirium/​dementia • Bradycardia (medications: atenolol/​ donepezil) • Neurological deficit (previous stroke) • Hypotension—​medications and fluid depletion Reduced oral intake due to: • Delirium • Reduced appetite during illness • Constipation • Inaccessible drinks and absence of usual prompts Constipation due to: • Opioids • Reduced mobility, and so on Urinary retention due to: • Constipation/​faecal impaction +/​-​ donepezil causing: • Urinary tract infection (drug resistant) • Acute (mixed pre and postrenal)
kidney injury Polypharmacy • (Opiates/​β-blockade/​thiazide) Hypoactive delirium secondary to issues above

546 Section 6  Old age medicine Key components of an effective early supported discharge service include: • An accurate, holistic clinical management plan that is clearly communicated to community teams in real time. • Capability and capacity in community teams—​services need to be able to respond in real time, accepting referrals 24/​7 that can assure a same or next-​day response. • Competence to be able to deliver the interventions required—​as illustrated with the patient Vera, just discussed; this might include monitoring parenteral fluids, checking bloods, and reviewing medication in addition to usual care issues such as continence care. This may require the development of ‘vertically integrated’ services that can deliver the components of comprehensive geri- atric assessment across the interface. Increasingly community and hospital based teams are blurring the boundaries, through staff ro- tation and shared teaching/​training, to develop such capabilities. • Robust governance and information sharing—​clarity is required over who is responsible for what and when; shared governance systems supported by easy access to shared clinical information and senior clinical support (e.g. through locality based commu- nity geriatricians). Robust assessment of older people with frailty in the first hours of an urgent care episode, combined with early supported discharge has the potential to achieve the nirvana of sooner, faster, better care, potentially at reduced cost, and with better outcomes. FURTHER READING Abbey J, et al. (2004). The Abbey pain scale: a 1-​minute numerical indicator for people with end-​stage dementia. Int J Palliat Nurs, 10, 6–​13. Baztan JJ, et  al. (2009). Effectiveness of acute geriatric units on functional decline, living at home, and case fatality among older patients admitted to hospital for acute medical disorders: meta-​ analysis. BMJ, 338, b50. Carpenter CR, et al. (2015). Risk factors and screening instruments to predict adverse outcomes for undifferentiated older emergency department patients: a systematic review and meta-​analysis. Acad Emerg Med, 22, 1–​21. Cei M, Bartolomei C, Mumoli N (2009). In-​hospital mortality and morbidity of elderly medical patients can be predicted at admis- sion by the Modified Early Warning Score: a prospective study. Int J Clin Pract, 63, 591–​5. Centre for Health Sertvice Economics and Organisation (2014). Understanding Emergency Admissions of Older People. https://​ www.chseo.org.uk/​downloads/​report6-​emergencyadmissions.pdf Conroy SP, et al. (2011). A systematic review of comprehensive geri- atric assessment to improve outcomes for frail older people being rapidly discharged from acute hospital: ‘interface geriatrics’. Age Ageing, 40, 436–​43. Conroy SP, et al. (2014). A controlled evaluation of comprehensive geriatric assessment in the emergency department: the ‘Emergency Frailty Unit’. Age Ageing, 43, 109–​14. Table 6.4.5  Comprehensive geriatric assessment in practice: The clinical management plan Delirium— ​(NON​SPECIFIC PRESENTATION) • Address hydration (consider parenteral fluids given drowsiness and likely lower oral intake), hypoxia, hypothermia, hypotension, and hypoglycaemia • Treat infections—​consider broad spectrum antibiotics given established resistance to many antibiotics (including trimethoprim), pending CSU obtained from in-​out catheter to drain bladder • Consider urinary retention: plan for follow-​up bladder scans rather than insert a catheter • Hold opioids temporarily to facilitate recovery from delirium, but continue paracetamol (NSAIDs contraindicated due to acute kidney injury) (review POLYPHARMACY) Falls risk

• Reduce/​stop β-​blocker as BP low and likely to be contributing to falls risk; will require ongoing monitoring (POLYPHARMACY) • Stop and review later the Bendroflumethazide (or Furosemide) given dehydration and low BP (also limited evidence of benefit from tight BP control in established dementia) (POLYPHARMACY) • Do not stop donepezil (as it is likely to help with delirium recovery), but monitor ECG response to withdrawal of β-​blocker (POLYPHARMACY) • Nurse in an environment less likely to aggravate delirium (reduced noise, low lighting, orientation cues). Later, arrange a home hazards’ review, consider assistive technology such as pressure sensors as several fixed irreversible drivers of falls risks—​stroke, dementia (ENVIRONMENTAL factors) Avoid or treat constipation • Enema for impaction • Add in laxatives as likely to need to restart opioids for shoulder pain (POLYPHARMACY) Reduce risk of dehydration

• Get baseline and then monitor U&Es—​can expect recovery over the next few days assuming above enacted—​re-​test in a few days (HOMEOSTATIC FAILURE) • Frequent offers of oral fluids with recording of cumulative intake (accurate fluid balance is frequently unnecessary or not feasible, but intake can be assessed) • Consider subcutaneous route if oral intake inadequate Consider FUNCTIONAL IMPAIRMENT

• Will require rehabilitation to accompany (not follow) medical treatment—​aim to recover back to baseline status over a period of a week or so • consider ‘hospital at home’ services to support care home staff if patient returns there Consider SOCIAL
NETWORKS/​SUPPORTs

• Consider both their capacity and resilience • Will clearly need support with ADLs whilst delirious—​could this be best provided in the care home, in a familiar environment, with staff empowered by a detailed and holistic management plan? • Contact family to establish patient/​family centred care plan—​what would the patient want in the circumstances? CSU, urethral catheter specimen; ECG, electrocardiogram; NSAIDs, non​steroidal anti-​inflammatory drugs; ADLs, activities of daily living; U&Es, urea and electrolytes.

6.4  Older people and urgent care 547 Dellinger RP, et al. (2008). Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med, 36, 296–​327. Edmans J, et al. (2013). Specialist geriatric medical assessment for pa- tients discharged from hospital acute assessment units: random- ised controlled trial. BMJ, 347, f5874. Elpern E, et al. (2009). Reducing use of indwelling urinary catheters and associated urinary tract infections. Am J Crit Care, 18, 535–​41. Fox MT, et al. (2012). Effectiveness of acute geriatric unit care using acute care for elders components: a systematic review and meta-​ analysis. J Am Geriatr Soc, 60, 2237–​45. Franklin M, et al. (2014). Identifying patient-​level health and social care costs for older adults discharged from acute medical units in England. Age Ageing, 43, 703–​7. Gill TM, et al. (2010). Trajectories of disability in the last year of life. N Engl J Med, 362, 1173–​80. Graf CE, et al. (2012). Can we improve the detection of old patients at higher risk for readmission after an emergency department visit? J Am Geriatr Soc, 60, 1372–​3. Han JH, et al. (2011). Delirium in older emergency department pa- tients: recognition, risk factors, and psychomotor subtypes. Acad Emerg Med, 16, 451–​7. Hippisley-​Cox J, Coupland C (2013). Predicting risk of emergency admission to hospital using primary care data: derivation and validation of QAdmissions score. BMJ Open, 3, e003482. King’s Fund (2001). Variations in Healthcare: The Good, the Bad and the Inexplicable. http://​www.kingsfund.org.uk/​publications/​variations-
​health-​care Lowthian J, et  al. (2015). Discharging older patients from the emergency department effectively: a systematic review and meta-​ analysis. Age Ageing, 44, 761–​70. Marco C, et al. (1995). Fever in geriatric emergency patients: clin- ical features associated with serious illness. Ann Emerg Med, 26, 18–​24. Sager MA, et  al. (1996). Functional outcomes of acute medical
illness and hospitalization in older persons. Arch Intern Med, 156, 645–​52. Shepperd S, et al. (2009). Early discharge hospital at home. Cochrane Database Syst Rev, 1, CD000356. Silvester KM, et al. (2014). Timely care for frail older people referred to hospital improves efficiency and reduces mortality without the need for extra resources. Age Ageing, 43, 472–​7. Wallis SJ, et al. (2015). Association of the clinical frailty scale with hospital outcomes. QJM, 108(12), 943–9.

6.5 Older people in hospital 548

6.5 Older people in hospital 548

ESSENTIALS Older people usually present to hospital because of a crisis: a sudden change in health, function, or circumstances that causes worry, dis- tress, or overwhelms independence or care provision. Crises may relate to the individual, the carer, care systems, or the environment. At the point of presentation it may not be clear which, or what com- bination, of these is responsible. It is necessary to identify all rele- vant factors for hospital care to be effective and efficient. Admission to hospital for an acute illness can have a major nega- tive impact on an older person’s ongoing functional abilities, hence systems of care need to know when to expect and how to manage functional deterioration. For example, an unwell older person may have prolonged bed rest leading to deconditioning and loss of balance or falls; stress, dehydration, malnourishment, and the effects of drugs may cause delirium. Such patients, who account for at least half of hospital inpatients, do not fit the standard ‘acute medical model’ of care, and hospital care systems that fail to take into account their risks and needs increase the chances of poor out- comes and lose efficiency because of unnecessary resource use. Older people need a range of interventions addressing physical and mental health, rehabilitation, social care needs, and family engage- ment. This means that a more comprehensive and flexible approach to care is required, emphasizing a wider range skills and using pro- fessional judgement regarding the most appropriate degree of in- vestigation and treatment. The interface between ‘acute’ and ‘rehabilitation’ is blurred, and much evidence supports the effectiveness of efforts to maintain or restore function beginning very early in the course of an illness (‘re- habilitation starts on admission’). Rehabilitation centres on defining problems in terms of diagnoses and their consequences in terms of organ systems, tasks, and activities in a social and environmental context. Goals are agreed and interventions undertaken at the levels of pathology, impairment, disability, or the environment, and as- sessed for effect, before continuing successive cycles as residual problems are addressed. Hospitals must provide for this rehabili- tation, care planning, and transfer of care to community services where these are separately organized. Some patients do not have the resilience to recover from an acute illness and return to independent living. In this context an individual may become dependent long term, or may experience progressive decline leading to death. Here the clinical approach changes from an emphasis on recovery to support or palliation. Despite efforts to enable people who prefer it to die at home, more die in hospital, and so end-​of-​life care is a core task for hos- pitals. Place of death may be less important than the quality of care delivered. Hospitals should enable high-​quality palliation and the experience of ‘a good death’. Introduction Public health services should be accessible to all regardless of age, sex, diagnosis, or level of disability. Health problems in older people form a large part of the business of many hospitals and there- fore services should be designed and organized with their needs in mind. To achieve this appropriate adjustments are required to the physical environment, staffing expertise and attitudes, and the hospital-​wide cultures and processes. What is an acute hospital for? Hospitals provide multiple functions (see Box 6.5.1). They op- erate within wider health, social and informal care systems, and in varying cultural, professional, political, and financial contexts. Some hospital functions can only be provided in a highly technical environment. Some depend on alternative facilities and staffing groups in primary and community care. Definitions of different facilities may vary between countries. A  subacute or long-​term care facility may be called a hospital in one country, and a nursing home, or intermediate care facility in others. Hospitals provide acute care, but increasingly they must also manage chronic ill-​health, functional limitations, and co​morbid mental health problems, because those are the needs of many of their patients. Hospitals must also consider the impact of ill-​health on family members and carers, and interface with providers of long-​term health and social care. Older people usually present to hospital because of a crisis: a sudden change in health, function, or circumstances that causes 6.5 Older people in hospital Graham Ellis, Alasdair MacLullich, and Rowan Harwood

6.5  Older people in hospital 549 worry, distress, or overwhelms independence or care provision. Crises may relate to the individual (illness or injury), the carer (illness, holidays, carer strain, abuse), care systems (availability or capability of home care or care homes), or the environment (reloca- tion or building work). At the point of presentation it may not be clear which of these is responsible. There are often multiple causes or contributory factors. For hospital care to be effective and effi- cient, it is necessary to identify all relevant factors. Admission to hospital for an acute illness can have a major negative impact on an older person’s ongoing functional abilities. Systems of care need to know when to expect and how to manage functional deterioration. For older people the interface between ‘acute’ and ‘rehabilitation’ is blurred, and much evidence supports the effectiveness of efforts to maintain or restore function begin- ning very early in the course of an illness (‘rehabilitation starts on admission’). Hospitals must provide for this rehabilitation, care planning, and transfer of care to community services where these are separately organized; this process is called discharge (or Transfer of Care) planning. Despite efforts to enable people who prefer it to die at home, more die in hospital, and so end-​of-​life care is a core task for hospitals. Place of death may be less important than the quality of care de- livered. Thus, hospitals should enable high-​quality palliation and the experience of ‘a good death’. Why should modern hospitals adapt to the needs of older adults? Numbers attending and being admitted In developed nations, typically two-​thirds of emergency hospital admissions are of people over 65. In the United Kingdom over the last 10 years there has been a 65% increase in the number of people aged over 75 requiring emergency hospital care, compared to a 31% increase for 15–​59-​year-​olds. Greater numbers of older people are being admitted for emergency surgery, or elective procedures such as joint replacements, urological procedures, or ophthalmic sur- gery. Older people have longer lengths of stay than younger patients. The increased demand is partly due to demographic change (more older people in the population) but is also related to the increasing multimorbidity associated with longer-​lived popu- lations, and changes in older peoples’ expectations and health-​ seeking behaviours. How older patients differ from younger ones ‘If you can still move you are not old’—​Nigerian Proverb Older people differ one from another more than do younger people. Many older people are fit and independent, free from disability and cognitive impairment, and not unlike their younger counterparts. They exercise, socialize, and work much as anyone younger would. They may not feel old and can be resentful of labels such as ‘eld- erly’, ‘frail’, ‘geriatric’ or other perceived pejorative terms. Their illness course and recovery may be unremarkable. Many perform important roles contributing to their families, voluntary organiza- tions, or wider society. Some may be caring for their spouse or much older parents. Others, however, struggle with ordinary daily tasks such as washing, dressing, and walking. They require assistance for the most basic of personal functions. They take longer to recover from acute illness and are more likely to require rehabilitation. These individuals are more likely to need acute hospital admission. These wide differences among older people (Box 6.5.2) neces- sitate a flexible, tailored approach, and evaluation of needs on an individual basis. Older people are prone to deterioration in the face of stressors. Often called frailty, the unifying explanation is of loss of resilience at all levels (cellular, organ, functional and social), reduced physio- logical or homeostatic reserve, and multiple pathologies, making older people prone to injury, illness, and social disruption. Frailty describes a state where patients are vulnerable to acute func- tional decline with challenges that would not present a problem to a younger or more resilient person. This is explored further in Chapter 6.2. The prevalence of multiple co​morbidities increases steeply with age (Fig. 6.5.1) including many acute illnesses as well as chronic, degenerative, and disabling diseases. Complexity increases progressively with the number of diagnoses. Multiple chronic comorbidities are not synonymous with age, frailty, or disability per se, but multiple chronic conditions and social and environ- mental adversity predispose an individual to crises. Likewise, the presence of disability in activities of daily living is not syn- onymous with frailty, but the risk of acquired disability is higher in those who are frail. Frailty, more than age or physiological parameters, best identifies when an older person is at risk of new or worsening disability from an acute illness. Implications for acute hospital care Poor functional outcomes can occur as a consequence of illness, but also as a consequence of treatment or hospital systems. Older Box 6.5.1  Potential functions of a hospital • Emergency medical and surgical care • Elective medical and surgical procedures • Specialist outpatient consultation investigation and treatment • Assessment and management of crises of health or care • Investigation and diagnosis • Rehabilitation • End-​of-​life care • Care planning, decision-​making, transitions to postacute or commu- nity care, care homes, or end-​of-​life care • Education and training • Research Box 6.5.2  How older patients differ • Multiple pathologies • Non​specific presentations • Rapid loss of abilities • Proneness to complications • Need for rehabilitation • Importance of the environment After Grimley-​Evans, J., ‘How are the elderly different?’, in R. L. Kane, J.
Grimley-​Evans, and D. MacFadyen, eds, Improving the health of older people:
a world view, pp. 50–​68. Oxford: Oxford University Press, 1990.

550 Section 6  Old age medicine people are more prone to complications of disease. The risk is in- creased across multiple domains such as adverse drug reactions, surgical wound infections, delirium, malnutrition, falls, pressure sores, venous thromboembolism, hospital-​acquired infections, constipation, and deconditioning. For example, an unwell older person may have prolonged bed rest leading to deconditioning and loss of balance or falls. Stress, dehydration, malnourishment, and the effects of drugs may cause delirium. Hospital care systems that fail to take into account these risks and needs increase the chances of poor outcomes and lose efficiency because of unneces- sary resource use. Treatment plans for an older adult will often include parallel aims such as the treatment of an acute infection, the rehabilitation of functional decline, the palliation of cancer-​related pain and the support for a chronic disease such as diabetes. Implications for the initial assessment of
the older patient Acute illness may present ‘typically’ (as for younger adults), but may also present non​specifically or atypically, for instance with functional deficits such as falls, immobility, delirium and incon- tinence (the ‘geriatric giants’). These atypical presentations may be misunderstood as ‘social’ rather than ‘medical’. On the contrary, these patterns should be recognized as signs of acute illness in the context of frailty, increasing the vulnerability of the patient to poor outcomes including increased early mortality, quicker loss of functional independence, and greater risk of being admitted to a nursing home following hospital care. Identifying degrees of frailty is necessary if patients are to re- ceive targeted interventions to mitigate these risks. There are sev- eral simple tools suitable use in clinical practice, for example, the Clinical Frailty Scale (Fig. 6.5.2). Assessment must include also sensory impairments (vision, hearing) and cognitive state, and systematic description of func- tional ability prior to, and on recovery from, the acute illness. This enables ongoing assessment of progress and is vital in plan- ning future care needs. An example of this is the Barthel Index in Fig. 6.5.3. Practitioners should be careful not to make assumptions and take care to incorporate older adults’ views. Moreover, there may be multiple stakeholders involved including relatives, carers, and services (such as care homes) as well as the patient themselves. Gaining insights from them, as well as understanding their per- spectives and concerns, will enrich the clinical assessment and help future care planning. Importantly, cultural expectations and norms for older adults of different ethnicities may be different from younger adults. Older patients’ needs are not readily addressed by
the traditional model of hospital care Many modern acute hospitals work on the assumption that simple and reliable rapid assessments, leading to defined treatment path- ways with short admissions, optimize outcomes, and maximize efficiency. Much care has a curative focus, and assumes that the individual has mental capacity and is cognitively able and engaged in their own care. Little account is taken of disability or sensory im- pairment. This ‘acute medical model’ of care is well-​suited to single, reversible problems in otherwise well individuals. It may involve a patient in multiple contacts with many new faces. It may require invasive and potentially distressing tests and investigations. It pro- vides high levels of information to patients regarding their con- dition, treatment, and prognosis. It expects patients to withstand prolonged immobility on beds and trolleys, fasting for surgery, or multiple ward moves. This is accepted as the cost of restoring 100 90 80 70 60 50 40 30 20 10 Age group (years) Patients (%) 0 0–4 5–9 10–14 15–19 20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 85+ 0 disorders 2 disorders 3 disorders 4 disorders 5 disorders 6 disorders 7 disorders ≥8 disorders 1 disorder Fig. 6.5.1  Number of chronic disorders by age group. From Barnett K, et al. (2012) Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-​sectional study. Lancet, 380, 37–​43.

6.5  Older people in hospital 551 health. Rehabilitation is the exception rather than a norm, and dis- charge is expected to be straightforward. However, at least half of hospital patients have health needs that do not fit this model. Older people need a range of interventions addressing physical and mental health, rehabilitation, social care needs, and family engagement. This means that a more comprehen- sive and flexible approach to care is required, emphasizing a wider range of skills (such as teamworking, communication, negotiation, and giving comfort) and using professional judgement regarding the most appropriate degree of investigation and treatment. Hospital planning and performance management therefore needs to take systematic notice of diverse population needs, and plan for this provision, taking into account complexities and heterogeneity. Components of healthcare in the acute hospital The goals of acute hospital healthcare can be divided into some fundamental components (Box 6.5.3). These components may be combined (curing a disease may delay death, relieve symptoms, and restore function). Different areas of medical practice use different models to characterize illness and guide management. These are not necessarily incompatible, but emphasize the import- ance of different approaches. Diagnosis remains central to the care of complex older people. Treating the treatable will often be helpful, but palliation, multi- disciplinary management, information giving, counselling and negotiation of goals, restoration of function, and manipula- tion of the physical and social environment assume increased importance. Rehabilitation centres on defining problems in terms of diag- noses and their consequences in terms of organ systems, tasks, and activities in a social and environmental context. Goals are agreed and interventions undertaken at the levels of pathology, impairment, disability, or the environment, and assessed for effect, before continuing successive cycles as residual problems are addressed. Rehabilitation is key to managing disability in old age, but can be limited in progressive disease and mental health problems. The palliative care model also focuses on problems, which are meticulously analysed and treated where possible. There is a 1 Very fit—People who are robust, active, energetic and motivated. These people commonly exercise regularly. They are among the fittest for their age. Clinical Frailty Scale 7 Severely frail—Completely dependent for personal care, from whatever cause (physical or cognitive). Even so, they seem stable and not at high risk of dying (within c.6 months). 8 Very severely frail—Completely dependent, approaching the end of life. Typically, they could not recover even from a minor illness. 9 Terminally ill—Approaching the end of life. This category applies to people with a life expectancy <6 months, who are not otherwise evidently frail. Scoring frailty in people with dementia The degree of frailty corresponds to the degree of dementia. Common symptoms in mild dementia include forgetting the details of a recent event, though still remembering the event itself, repeating the same question/story, and social withdrawal. In moderate dementia, recent memory is very impaired, even though they seemingly can remember their past life events well. They can do personal care with prompting. In severe dementia, they cannot do personal care without help. 2 Well—People who have no active disease symptoms but are less fit than category 1. Often, they exercise or are very active occasionally (e.g. seasonally). 3 Managing well—People whose medical problems are well controlled, but are not regularly active beyond routine walking. 4 Vulnerable—While not dependent on others for daily help, often symptoms limit activities. A common complaint is being ‘slowed up’; and/or being tired during the day. 5 Mildly frail—These people often have more evident slowing, and need help in high order IADLs (finances, transportation, heavy housework, medications). Typically, mild frailty progressively impairs shopping and walking outside alone, meal preparation and housework. 6 Moderately frail—People need help with all outside activities and with keeping house. Inside, they often have problems with stairs and need help with bathing and might need minimal assistance (cuing, standby) with dressing. Fig. 6.5.2  Clinical frailty scale. ©2007–​2009 Version 1.2. All rights reserved. Geriatric Medicine Research, Dalhousie University, Halifax, Canada.

552 Section 6  Old age medicine commitment to open and honest communication, and account taken of psychological, social, and spiritual aspects. Problems are anticipated and advance care plans made. The Recovery Model has its origins in mental healthcare. Positive attributes and abilities are emphasized over the nega- tive. Achievable goals are formulated and risks taken in trying to achieve goals. Failure is accepted. The risk enablement approach identified and acknowledges risks, minimizes them where possible, and then openly decides if residual risks are to be taken, avoided, or compensated for. Person-​centred care represents best practice in dementia, but is applicable for other vulnerable patients. Its precepts are to value the person and those who care for them; to individualize care ac- cording to physical and mental health problems, personality, biog- raphy, values, and preferences; to view problems from the patient’s perspective; and use communication and relationships to enhance Activity Barthel score 0 5 10 15 Independent Independent Independent Independent (including buttons, zips, laces etc.) Can use enema or suppository independently Can control bladder day and night Independent (can get on and off, dress and wipe unassistes) Independent (but may use an aid, e.g. walking stick); ≥50 yards) Walks with little help; ≥50 yards) Minor help or supervision Unable Some help required e.g. needs help cutting, spreading butter etc. Can use a bath tub, shower or take a complete sponge bath unassisted Independent face/hair/ teeth/shaving (implements provided) Needs help but can do at least half unaided Needs help with an enema or suppository Occasional accidents or can not wait for the bed pan/get to the toilet in time Needs some help, but can do some things alone Major help (can sit up alone but needs to be lifted out of bed) Wheelchair independent, including corners; ≥50 yards Needs help or supervision Dependent Dependent Unable, no sitting balance Unable Immobile or <50 yards Dependent Incontinent (or need to be given enemas) Incontinent or catheterized and unable to manage alone Needs help with personal care Feeding Bathing Grooming Dressing Bowels Bladder Toilet use Transfer (bed to chair and back) Mobility (on level surfaces) Stairs Fig. 6.5.3  The Barthel Index of functional status. After Mahoney FI, Barthel D (1965). Functional Evaluation: The Barthel Index. Maryland State Medical Journal, 14, 56–​61. Box 6.5.3  Models of healthcare for older people Prevention Anticipatory intervention in high risk groups Medical Diagnose, treat Rehabilitation Cycle of multiprofessional problem identification, analysis, therapeutic intervention and reassessment, directed at maximizing physical and social functioning Palliative Meticulous management of symptoms, open communication, attention to psychological, social and spiritual aspects, advance care planning Comprehensive geriatric assessment Assessment and management of (acute and chronic) diagnoses, functional, mental, social and environmental dimensions, and planning to address identified needs Person-​centred care Value and respect for personhood, individualized care, empathic understanding, communication and relationships to promote well-​being and reduce distress Recovery model Emphasize hope, set achievable goals, identity positive attributes and abilities, take risks, accept failure Social model Environment and relationships adapted to persons’ abilities

6.5  Older people in hospital 553 well-​being, respect identity and provide comfort, inclusion, and attachment. The social model sees disability as a function of the failure of so- ciety to make adjustments to meet the needs of those with different levels of ability, rather than a defining feature of the individual, and emphasizes the social, legal, cultural, and environment aspects of enablement. The healthcare professional should draw on all of these flexibly and sometimes simultaneously. For geriatricians, the dominant model used is that of ‘comprehensive geriatric assessment’ (CGA) which overlaps with each of these. Comprehensive geriatric assessment Comprehensive geriatric assessment applied to older people with frailty improves clinical outcome (reduces mortality and the need for long-​term care) and reduces the costs of health and social care. The likelihood of multiple overlapping problems necessitates as- sessment across multiple domains to develop a multifaceted thera- peutic plan for recovery and independence. This process is referred to as comprehensive geriatric assessment, or CGA. This term is slightly misleading as it is about more than assessment. It requires an action plan and its delivery as well. Comprehensive geriatric as- sessment is a highly evolved form of ongoing care led by doctors, nurses, and allied health professions (physiotherapy, occupational therapy, speech and language therapy, dietetics) who specialize in looking after older adults with frailty and work as a coordinated team. This may be delivered in a specialist unit or ward, but also by a mobile team in other areas of medicine or surgical care. See Chapter 6.4 for further description. Meta-​analysis of multiple randomized controlled trials dem- onstrated that older people who received comprehensive geriatric assessment were more likely to be alive and in their homes at dis- charge from hospital and at end of follow up (up to 12 months), compared with those who received routine inpatient medical care (Fig. 6.5.4). There are additional benefits from specialist care in terms of reductions in the likelihood of being admitted to resi- dential care. In addition, although not universal, many trials re- ported a reduction in costs associated with comprehensive geriatric assessment care. There are different models of comprehensive geriatric assess- ment. These are broadly similar in that they incorporate specialist coordinated multidisciplinary teams with expertise in the man- agement of older patients. Where they differ tends to be in their acuity or admission criteria. Some acute wards (often called acute care for elders wards, or ACE) admit directly from the emergency department, but typically (in the United Kingdom at least) their admission criteria are based on age alone with the exclusion of cer- tain conditions. Others take patients after 24–​72 hours and are de- signed for patients with frailty syndromes such as falls immobility, delirium, dependence, or risk of admission to institutional care. Still others admit adults later in their hospital journey, perhaps in a less acute facility for rehabilitation when they are more medically stable. Orthogeriatric, surgical liaison, and onco-​geriatric models have successfully applied similar approaches (see Chapter 6.6). In health systems with developed geriatrics services, there is a trend towards earlier and more extensive assessment prior to a decision on admission to hospital, including elder-​friendly emer- gency departments and acute frailty units. These can use referral to community services (‘Hospital at home’) as an alternative to ad- mission in some cases. Rapidly identifying functional impairments or underlying pathology allows earlier commencement of treat- ment and recovery. This has the potential to lead to shorter more productive hospital stays or to more community management of common problems (see Chapter 6.4). If all services treating older patients (including emergency de- partments, surgery and organ-​specialist services) incorporated the principles of comprehensive geriatric assessment, the impact on the health outcomes of this patient group could be significant. Trials of discrete wards provide evidence of greatest benefit (Fig. 6.5.4). The key messages are that specialist-​led, organized, coordinated care with experienced multidisciplinary teams who have control to implement their recommendations and who target the frailer patient are most effective. Standardized valid and reliable assessment scales can be used to assess different domains (Fig. 6.5.5). This means that allied health professionals can describe and quantify a patient’s deficits in a way that is understood and can be reproduced by a separate observer. Assessments must be tailored to the patient group and setting. For example, patients presenting with falls need assessments targeted towards their likely constellation of problems (such as strength and balance), whereas those with delirium will need assessment fo- cusing on their cognition, mood, and behaviour. There are many assessment scales for different domains, including mobility, self care, falls risk, pressure sore risk, nutritional assessments, cogni- tion, and delirium. Success of the comprehensive geriatric assessment approach in- cludes use of protocols of care for the management of key condi- tions, which can be implemented consistently. Some of this may be implicit learning in teams that work regularly together. Some may be more explicitly written protocols of assessment and manage- ment for common conditions such as falls, delirium, or immobility. Linking assessment to individually tailored but flexible interven- tions in real time is a continuous and iterative process, adapting to an individual’s recovery or change in circumstances in order to adapt and maximize recovery. Specialist care versus generalist care Who looks after a patient has two important aspects: 1) ensuring proper access to organ-​specialist or surgical expertise where this is appropriate, which requires an assessment and decision-​making process to take place, and close working between generalist and spe- cialist teams; 2) the need to take a broad overview of all aspects of care, with the authority to co​ordinate and direct care strategically. Evidence suggests that frail older people are best managed by a geriatrician supported by a suitably skilled and resourced multi- disciplinary team, using the comprehensive geriatric assessment approach. However, given the numbers of patients, the available workforce, the need for complex interventions or surgery in older

554 Section 6  Old age medicine people, different healthcare systems, and re-​imbursement mech- anisms, it is likely that many older people will be managed by those who are not specialized in the care of older people. In these circumstances, liaison and consultation models are helpful (see Box 6.5.4). Whether overall care is managed by a geriatrician, an internist, or an organ-​specialist (perhaps relating to the primary working medical diagnosis), they must deliver the aspects of comprehensive geriatric assessment that have been shown to be effective in opti- mizing outcome. Multidisciplinary teams A  team can achieve more than its individual members working alone. Any team needs to be led and coordinated if it is to be ef- fective. Clear leadership is important to focus the team on goals, achieving consensus, and keep to timescales. Meetings frequency should be adequate to keep up with the need for reassessments and adapting treatment plans, being as often as daily in some set- tings. Clear documentation is essential and should centre on the patient’s goals. A patient may wish to return to as near normal life as possible, live at home, and remain independently self-​caring and mobile. The team would identify the obstacles to achieving this, based on comprehensive geriatric assessment, and then plan a menu of interventions to address those aspects which are modifiable. These interventions are likely to be multilateral, addressing symptom relief, specific impairments, task capacity, confidence, and adap- tation strategies. There is usually a hierarchy of importance and timing of these interventions, adjusted in the light of change. Take, for example, mobility improvements aimed at reaching the toilet independently. Interventions may include relief of lower limb pain, repetitive chair based exercise to increase strength, assisted prac- tice performing sit to stand, and temporary provision of a walking aid to enable some independence prior to a fuller recovery. This multilevel approach is an application of the WHO ICF model of disability. Repetitive performance of functional activities is a cornerstone of rehabilitation of older adults, for two reasons. Firstly, because this makes sense to patients as relevant to the life they wish to re- sume living. Secondly, because the complex combinations neces- sary for task performance (e.g. strength of lower and upper limbs, balance, executive function, body-​eye coordination, and so on) cannot be simulated by individual exercises and respond better to composite approaches. Timing matters, and in some cases the team will identify that particular aspects need to addressed first in order to enable progress to build. Goals are reviewed regularly and readjusted at repeated multi- disciplinary team (MDT) meetings to take account of the patient’s Study or Subgroup 1.2.2 Team Subtotal (95% Cl) 2940 2765 83.8% 0.04 Total (95% Cl) 3498 3301 100.0% 0.03 [0.01, 0.05] 1.2.1 Ward Cohen 2002 GEMC (8) 200 346 185 346 10.3% 0.04 [-0.03, 0.12] 2002 Saltvedt 2002 (9) 60 127 55 127 3.8% 0.04 [-0.08, 0.16] 2002 Cohen 2002 UCOP (10) 217 348 185 348 10.3% 0.09 [-0.02, 0.17] 2002 Somme 2010 (11) 11 24 9 21 0.7% 0.03 [-0.26, 0.32] 2010 Goldberg 2013 (12) Total events Heterogeneity: Chi2 = 12.63, df = 11 (P = 0.32); I2 = 13% Test for overall effect: Z = 3.14 (P = 0.002) 146 1769 1548 Total events 310 304 Total events 2079 1852 310 125 290 8.9% 0.04 [-0.04, 0.12] [0.02, 0.07] Subtotal (95% Cl) 558 536 16.2% -0.02 [-0.07, 0.04] 2013 McVey 1989 (13) 64 93 62 92 2.7% 0.01 [-0.12, 0.15] 1989 Winograd 1993 (14) 32 99 36 98 2.9% -0.04 [-0.18, 0.09] 1993 Kircher 2007 (15) 104 150 96 129 4.1% -0.05 [-0.16, 0.05] 2007 Edmans 2013 (16) Heterogeneity: Chi2 = 0.92, df = 3 (P = 0.82); I2 = 0% Test for overall effect: Z = 0.61 (P = 0.54) Heterogeneity: Chi2 = 17.15, df = 15 (P = 0.31); I2 = 13% Test for overall effect: Z = 2.64 (P = 0.008) Test for subgroup differences: Chi2 = 3.39, df = 1 (P = 0.07), I2 = 70.5%
110 216 110 217 6.4% 0.00 [-0.09, 0.10] 2013 CGA Control Risk Difference Risk Difference M-H, Fixed, 95% Cl Events Total Events Total Weight M-H, Fixed, 95% Cl Year 121 190 134 223 6.1% 0.04 [-0.06, 0.13] 2000 Rubenstein 1984 (1) 35 63 22 60 1.8% 0.19 [0.02, 0.36] 1984 Counsell 2000 (7) 474

767 485 764 22.7% -0.02 [-0.07, 0.03] 2000 Applegate 1990 (2) 55

78 43 77 2.3% 0.15 [-0.00, 0.30] 1990 Asplund 2000 (6)
Landefeld 1995 (3) 218 327 194 324 9.7% 0.07 [-0.01, 0.14] 1995 Nikolaus 1999 (4) 114 179 56 93 3.6% 0.03 [-0.09, 0.16] 1999 Nikolaus 1999 plus ESD (5) 118 55 92 3.6% 0.05 [-0.07, 0.18] 1999 Favours control Favours CGA –0.5 –0.25 0.25 0.5 0 181 Fig. 6.5.4  Meta-​analysis of randomized controlled trials of comprehensive geriatric assessment: living at home at the end of follow up (up to 12 months). From Ellis G, et al. (2017) Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database of Systematic Reviews, (9), CD006211.

6.5  Older people in hospital 555 changing progress. It may be necessary to set intermediate goals, which can be part of tempering expectations or overambitious goals. For instance, ‘I want to walk’ may be tempered with ‘let’s work on standing first’. It might become apparent after time that the patient’s initial goals are not possible and so a revised plan is put in place. These changing goals need to be regularly negotiated with patients and their families, particularly where families may play a part in providing ongoing care. Palliative and supportive care Some patients do not have the resilience to recover from an acute illness and return to independent living. In this context an in- dividual may become dependent long term, or may experience progressive decline leading to death. Here the clinical approach changes from an emphasis on recovery to support or palliation (see also Chapter 6.11). Identifying this point is important, but can be difficult and uncertain. A key skill is how to manage the uncertainty, and tread a path between overaggressive medical intervention and nihilism. Repeated hospital admissions, especially with infec- tions, severe weight loss, or in the context of dementia with loss of mobility, continence, swallow, appetite, or communication, are all indicative of a prognosis that may be weeks to months rather than years. Waterlow pressure ulcer prevention/treatment policy Build/weight for height Average Healthy 0 Male A - Has patient Lost Weight recently Yes - Go to B No - Go to C Unsure - Go to C and score 2 B - Weight Loss Score C - patient eating poorly or lack of appetite ‘No’ –0, ‘Yes’ Score = 1 Nutrition score If > 2 refer for nutrition assessment /intervention Continence Complete/ Catheterised 0 1 2 3 Urine Incont. Faecal Incont. Urinary + Faecel Incontinence Mobility Fully Restless/Fidgety Apathetic Restricted Bedbound e.g. Traction e.g. Wheel chair Chairbound 0 1 2 3 4 5 Special risks Tissue malnutrition Terminal cachexia Diabetes, Ms, Cva Motor/sensory Paraplegia (Max of 6) Major surgery or trauma Orthopaedic/Spinal Medication-Cytotoxics, long term/High dose steroids, Anti-Inflammatory Max of 4 Score 10+ At Risk 15+ High Risk 20+ very High Risk On Table > 2 HR# On Table > 6 HR# 4–6 4–6 4–6 5 5 8 Multiple organ failure Single organ failure (Resp, renal, cardiac.) Peripheral vascular Disease Anaemia (Hb < 8)

Scores can be discounted after 48 hours provieded patient is recovering normally

© J Waterlow 1985 Revised 2005* Obtainable from the Nook, Stoke Road. Henlade Taunton Ta3 5LX

15kg = 4 Unsure
= 2 5–10kg = 2 Female 14–49 50–64 65–74 75–80 81+ 1 1 1 2 2 3 4 5 1 1 1 2 3 Tissue Paper Dry Oedematous Clammy, Pyrexia Discoloured Grade1 Broken/Spots Grade 2–4 BMI = 20–24.9 0 Above Average BMI = 25–29.9 1 Obese BMI > 30 2 Below Average BMI > 20 3 BMI = W (kg)/Ht (m)2 Skin type visual risk areas Sex age Malnutrition screening tool (mst) (nutrition vol. 15, no. 6 1999 - australia Fig. 6.5.5  Waterlow Score Risk Prediction Tool. © J. Waterlow 1985, revised 2005. Box 6.5.4  What is a geriatrician? • A physician with a firm foundation in internal medicine, broad gen- eral knowledge, and an understanding of prognosis, but trained to meet the unique healthcare needs of older adults. • Knowledge of ageing and its impact on tissues, organs and systems, and an ability to recognize frailty and its potential consequences. • Ability to investigate and manage frailty syndromes such as confu- sion, immobility, falls, and functional decline. • Additional specialist training in old age psychiatry and palliative care. • Expertise in specific age-​related conditions such as dementia, stroke, Parkinson’s disease, delirium, and fragility fractures. • Generic skills including multidisciplinary leadership and team working, effective communication, understanding of complexity and adaptability. • Compassionate, person-​centred, and patient.

556 Section 6  Old age medicine Palliative care does not mean withdrawal of care, but a refocusing on avoiding distress, improving quality of life, and achieving new goals and priorities. The shift in emphasis from cure and recovery to supportive or palliative care in an acute care setting in hospital can be confusing to staff and patients and families. When open dis- cussion of uncertainty is allied to a combination of the palliative care alongside a trial of ‘curative’ care (a ‘twin track’ approach), this can reduce anxiety. Following open discussion, issues like the continuation or stopping of treatments are simpler, more context-​ oriented, and person-​centred. For those who are leaving hospital with a short life expectancy, this provides an opportunity to review and plan future care needs. This requires an explanation of the likely illness trajectory. Goals (‘what is important now?) and fears should be identified, and the trade-​offs necessary to achieve or avoid them discussed. Families and patients can begin to think about the practical requirements for their care. If a patient or their carers better understand what to expect, they may feel better able to cope with its demands. Crucial to these discussions can be capturing the patient’s wishes. This can be linked to ‘advance care planning’ about what future interventions are, or are not, wanted, and the preferred place of care (or place of death). This might include a discussion about when future hospital admission would, or would not, be appro- priate. Use of advanced care plans to record the patient’s wishes about their future care can reduce subsequent unhelpful hospital- ization, and might include arranging for treatment at home or in a care home in preference. Medications may also be reviewed; for example, to reduce the therapeutic burden of the ‘pill count’ from statins, antithrombotic and antihypertensive drugs may now outweigh the potential bene- fits of the prevention of further vascular events. Some markers have been defined that indicate that the patient may be in the last year of life, but these are not accurate enough to be the sole guide. For instance, in the United Kingdom the ‘Gold Standards Framework’ lays out prognostic indicator guid- ance that can be helpful in identifying stages when a patient may be approaching end-​of-​life care. Safety and risk Frail older people are vulnerable to harm. Recovery from acute illness or injury is often tenuous or uncertain, and equal harm may result from deconditioning, prolonged hospital stays, and restrictive care regimens. The balancing act between enabling recovery and avoiding risk must be tailored to the individual’s circumstances and choices. Older peoples’ priorities go beyond staying alive, or ‘safe’, and restoration of function and autonomy requires the taking of risks. Healthcare-​associated harm is a tragedy. Distinguishing be- tween the inevitable consequences of ill-​health, recognized com- plications, and care-​related mishap or negligence, is not easy. Judgements made, and risks taken, in good faith and for rational reasons, may result in unintended harm. Not all these are neces- sarily causally related to hospital processes, and not all are avoid- able, nor exclusive to hospitals, but they may be. There are considerable political pressures around redu- cing risk. Organizations (including hospitals) are aware of this. Healthcare-​associated harm can result in death, disability, pro- longation of hospital stay, re-​admissions, litigation, and profes- sional censure. This creates tensions as the needs of patients and families may conflict with those of organizations or staff that manage them. Learning from industry and surgical practice has inspired attempts to systematically minimize (or eliminate) risk. Common healthcare-​associated harms in hospitalized older pa- tients are summarized in Box 6.5.5. Many of these overlap with common frailty syndromes, and the same general principles can apply. Thorough assessment, management, communication, and anticipation of common problems are necessary to prevent poor outcomes for vulnerable patients. In general, good multidiscip- linary care is as much about the prevention of harm as the treat- ment of acute illness. Falls Risk of falls in frail hospitalized older people is high. This is be- cause many patents have weakness or hypotension associated with acute illness or immobility. They may make misjudgments or be agitated in association with dementia or delirium or boredom. They may have additional difficulty mobilizing to the toilet, placing them at increased risk. Most falls occur around the bed/​chair space or in toilets, and at times of maximum patient activity rather than at times of low staff presence. Risk can be increased by iatrogenic factors such as drugs and the presence of lines or tubes as irritants or obstacles The relative risk of falls should be assessed, but when caring for older frail patients it can be assumed that all are at risk. Much falls prevention embraces good routine geriatric medical prac- tice:  prompt and accurate diagnosis and treatment of problems (especially delirium), careful drug review, and cautious use of po- tential culprit drugs, checking for hypotension and postural hypo- tension, assessing vision. Appropriate footwear should be worn. Box 6.5.5  Examples of healthcare-​associated harms common in older hospitalized patients • Falls • Pressure sores • Constipation • Hospital-​acquired infections (including Clostridium difficile, norovirus, methicillin-​resistant S.  aureus (MRSA), urinary catheter-​associated, intravascular line-​associated, and surgical wound infections) • Deconditioning • Soft tissue contractures • Venous thromboembolism • Unrecognized acute deterioration • Predictable and unpredictable adverse drug events • Delirium • Depression • Malnutrition • Poor sleep • Loss of autonomy • Disruption of usual support structures (e.g. carer input) • Disorientation to time and place • Discomfort associated with excessive noise or light • Disruption to familiarity and routine • Disruption to caregiver routines and difficulty re-​establishing on discharge

6.5  Older people in hospital 557 Walking aids should be in reach. A continence assessment enables anticipation of those patients whose urgent call may precipitate an unsteady ‘dash’ to the toilet. Reducing the risk of falls has to be balanced against inactivity or boredom. Reluctance to get patients out of bed, discouragement of walking or use of the toilet, or a restrictive or custodial style of care provision with frequent confrontation as patients attempt to do things (‘sit down’) is not an appropriate way to reduce risk. If risk remains high after remediable factors have been corrected, a risk enablement approach should be adopted, that is, to acknow- ledge, minimize, and discuss risk, then decide how far to accept them. The benefits and risks of restraint with bed rails is finely balanced and needs individualized assessment. Although use of electronic aids to alert staff about patients’ movements are increas- ingly popular, evidence for reduction of injurious falls is lacking. Pressure sores Pressure sores are caused by continued pressure of a hard surface against a bony prominence, resulting in ischaemia and breakdown of intervening tissues. The sacrum, trochanters, and heels are the sites at greatest risk. Immobility, loss of sensation, malnutrition, diabetes, peripheral vascular disease, glucocorticosteroid use, and dementia are risk factors. Shearing injuries can also occur. Moisture can also cause maceration and abrasion of skin (‘mois- ture lesions’). Skin damage is graded 1 (non​blanching erythema), 2 (skin break), 3 (subcutaneous tissue loss), 4 (cavity, caused by muscle necrosis). Pressure sores are much less prevalent now, largely due to as- siduous risk assessment and the use of pressure-​relieving mat- tresses. Chairs and wheelchairs also require pressure-​relieving cushions. Patients should be educated and reminded or helped to change position regularly (every half hour). Heel sores are diffi- cult to prevent, although there is a variety of supports and boots available. A mattress alone will not avoid all sores, and many pa- tients require turning (up to two-​hourly) in addition. Judgement must be used over the need for continuing turning overnight, as this disrupts sleep and is unlikely to be continued if the patient returns home. Healing a pressure sore requires relief of pressure, debridement of non​viable tissue, treating of any surrounding cellulitis, dressing to ensure a moist environment, treatment of anaemia, and provi- sion of an adequate diet. Cavity sores require packing so they heal from the bottom and do not close over, and take several months to heal. Venous thromboembolism (VTE) Immobility and age are the biggest risk factors. However, apart from after hip surgery (where there is good evidence for up to four weeks prophylaxis), the evidence for venous thromboembolism prevention in older people is weak, certainly beyond two weeks in hospital. In England, routine assessment of risk is mandated in all acute hospitals. Prophylaxis with low-​dose low molecular weight heparins is reasonable when there is an acute decline in mobility, or limb immobilization, but probably not for those who had limited mobility before the acute illness, or who will never regain their mobility. Importantly, low molecular weight hep- arin (LMWH) injections are painful and are time-​consuming for nurses to administer. Rescue from acute medical deterioration Older people can deteriorate quickly. Vigilance is required to de- tect this. Risk scores, such as the National Early Warning Score (NEWS) in the United Kingdom have been developed to indi- cate patients who are at risk of acute physiological deterioration. However, risk scores have poor specificity in older people (many false positives). In acute settings, high acuity and frailty do not map to the same patients. They are also insensitive to reduced level of arousal, which is a poor prognostic sign. Over-​reaction to risk scores can result in burdensome overobservation, which interferes with sleep and diverts both nursing and medical staff from other activity. This may be appropriate in some cases, but represents an opportunity cost that hard-​pressed systems can ill-​afford. For those rehabilitating, awaiting care transitions, or approaching the end of life, a more individualized approach is required, with opt-​ outs or defined ceilings of response. Delirium Delirium is distressing, and is associated with poor prognosis. Older age, dementia, sensory impairment, and other co​morbidities are important risk factors. It is also common, being present in more than one in five older hospital patients. Cognitive function may not recover fully and the associated mortality is high (40% at six months). Functional recovery after an episode of delirium is often poor. Any medical condition, trauma, or surgery, drug use or drug withdrawal can cause delirium, and cause is often multiple. Infections, adverse drug reactions, metabolic derangements, hyp- oxia, and acute neurological disease are important, and there are also numerous rarer causes that must be sought in cases of persist- ence. Mimics include dementia with Lewy bodies and the step-​wise progression of vascular dementia. Identification requires a high index of suspicion (Box 6.5.6). Mental status impairment should be sought routinely in older pa- tients, and a cognitive collateral history taken for prior cognitive function, time course of decline and change. Assessment of the level of arousal is critical because acute drowsiness is a highly spe- cific (>90%), though not sensitive indicator of delirium. Attention is assessed during history taking, mental state examination, and cognitive assessment. Specific tests include asking the patient to recite the months of the year backwards (or days of the week, if that is too hard). Hallucinations and delusions should be spe- cifically sought; patients often do not volunteer these bewildering Box 6.5.6  Delirium definition and associated features • Acute change in cognition, fluctuating course • Impaired attention • Altered level of arousal • 50% have hallucinations (typically visual) or delusions (typically paranoid) • Emotional features include anxiety (fear), depression, or anger • Psychomotor agitation or withdrawal • Disrupted sleep-​wake cycle, often worse at night • Autonomic features (labile blood pressure, syncope, incontinence)

558 Section 6  Old age medicine and distressing symptoms. Structured tests such as the 4AT (see Fig. 6.5.6) can be useful in routine practice. Core to management is to find the underlying causes or drivers and treat them all, as well as to simultaneously optimize conditions for brain recovery. Agitation can be caused by pain, urinary reten- tion, thirst, constipation, or psychosis, so vigilance in the face of behavioural symptoms is important. Distressing psychotic symptoms or severe anxiety not re- sponding to non​pharmacological methods can be controlled using antipsychotic drugs if needed, or benzodiazepines if the cause is alcohol or drug withdrawal, or in patients with Parkinson’s or Lewy body dementia. These must be subject to regular critical review. Care must be taken to avoid complications such as injury from falls, oversedation, dehydration from poor oral intake, malnutri- tion, or pressure sores. The principles of person-​centred dementia care help (relation- ship building, family involvement, provision of explanation, validation, and comfort). Equally, the physical environment is 4AT Assessment test for delirium & cognitive impairment (label) Patient name: Date of birth: Patient number: Date: Time: Tester: CIRCLE [1] ALERTNESS This includes patients who may be markedly drowsy (eg. difficult to rouse and/or obviously sleepy during assessment) or agitated/hyperactive. Observe the patient. If asleep, attempt to wake with speech or gentle touch on shoulder. Ask the patient to state their name and address to assist rating. Normal (fully alert, but not agitated, throughout assessment) 0 Mild sleepiness for <10 seconds after waking, then normal 0 Clearly abnormal 4 [2] AMT4 Age, date of birth, place (name of the hospital or building), current year. No mistakes 0 1 mistake 1 2 or more mistakes/untestable 2 [3] ATTENTION Ask the patient : “Please tell me the months of the year in backwards order, starting at December.” To assist initial understanding one prompt of “what is the month before December?” is permitted. Months of the year backwards Achieves 7 months or more correctly 0 Starts but scores <7 months/refuses to start 1 Untestable (cannot start because unwell, drowsy, inattentive) 2 [4] ACUTE CHANGE OR FLUCTUATING COURSE Evidence of significant change or fluctuation in: alertness, cognition, other mental function (eg. paranoia, hallucinations) arising over the last 2 weeks and still evident in last 24hrs No 0 Yes 4 4 or above: possible delirium +/- cognitive impairment 1–3: possible cognitive impairment 0: delirium or severe cognitive impairment unlikely (but delirium still possible if [4] information incomplete) 4AT SCORE Fig. 6.5.6  The 4AT delirium screening tool. www.the4at.com

6.5  Older people in hospital 559 important, including quiet, and light. Many acute medical wards are very challenging places for people with delirium. Prevention is more strongly supported by evidence and is there- fore of particular importance. Studies suggest that up to one-​third of delirium can be prevented. Measures include careful drug use, drug review, avoiding anticholinergic, opioids, and benzo- diazepine drugs, avoiding hospital-​acquired infections (in par- ticular urinary catheter-​associated, and aspiration pneumonia). Also important is maintaining hydration, nutrition, sleep, and mobility, detecting and treating pain, and optimizing sensory function where possible. In around 30% of cases, delirium can be very persistent, lasting for many months. Awareness of this is important as this provides a management challenge. As recovery is uncertain, decisions have to be made under conditions of lack of mental capacity that may be temporary, and the pace of recovery does not match the expect- ations of either acute or rehabilitation services. It is important not to make decisions regarding long-​term care or other limiting de- cisions until cognitive recovery has been maximized. Often this will mean that decisions regarding onward care are not made in an acute setting. After the event a debrief and explanation of what occurred can be helpful. Many older people with delirium have little recall of events, but some do. Even after recovery they may be unable to dis- tinguish what was real from what was delusional, may be trauma- tized, or develop post-​traumatic stress disorder. It is also important to communicate with families, explaining delirium’s features and outcomes, as they may also find it upsetting and bewildering, sometimes ascribing the delirium to neglect and sometimes feeling guilt associated with it. Dementia Dementia affects at least a quarter of older people in hospital. Detection is vital for appropriate adjustments to be made to care (Box 6.5.7). However, only 50–​70% of dementia is diagnosed in the United Kingdom, so many patients will have undiagnosed de- mentia. Because delirium or milder acute cognitive impairments commonly complicate dementia in hospitalized patients, detec- tion in such patients is best done by informant history. A tool such as the Informant Questionnaire for Cognitive Decline in the Elderly, validated for use in hospitals, can be helpful. Brief cognitive tests can be useful, but in all cases informant history indicating several months of impaired function is essential. Making a formal diagnosis has enormous implications for pa- tients, and in the short-​term acknowledging the presence of likely ‘cognitive impairment’ to enable immediate adjustments in care to be made, followed by more comprehensive assessment after discharge, is best practice. People with dementia often come to general hospitals because there is a crisis. The relative contributions of physical, mental, and social factors may not be immediately clear. Physical illness is very common, often complicated by superadded delirium. However, if the cause is ‘non​medical’ (not due to physical illness), it is still important to document and make appropriate referrals, such as to mental health or social care services, rather than seeing the patient as not needing care from the healthcare system as a whole. ‘Diagnostic overshadowing’ is the phenomenon of attributing all symptoms to dementia, and is a common pitfall. For instance agi- tation, aggression or shouting may be due to pain, urinary symp- toms, constipation, or delirium, among other possibilities. An understanding of dementia, what promotes wellbeing and living well, and what leads to distress has developed consider- ably over the past 30 years, in particular with the philosophy of person-​centred care. This holds that the experience of dementia is only partly explained by the neurological deficits (amnesia, aphasia agnosia, apraxia, executive dysfunction). In addition, personality, life story, physical and mental health and, (crucially) relationships (the way people relate to you and treat you) are important. Person-​ centred care aims to respect the personhood of the patient with de- mentia, aiming to affirm identity, provide comfort and occupation, and promote inclusion and attachment. Hospitals and hospital systems are often not well-​adapted to meet the needs of people with dementia, although most staff are sympathetic and want to do a good job. An admission to hospital is at a minimum disruptive of familiarity and routine. Continuity both in place and of staff is usually poor as patients are moved from ward to ward, or for investigations. The environment is often busy, noisy, overstimulating, and overwhelming. People who struggle with orientation need help with navigation. Lighting, signage, and way-​finding need to be optimized. All staff need expertise in understanding delirium and dementia, and applying the principles of person-​centred care including non-​ confrontation, diversion (e.g. by engaging in conversation about interests, family, or the past), de-​escalation and threat reduction (e.g. by talking through care or procedures to explain what is hap- pening). Occupation and purposeful activity is important but rarely provided in hospital. This can, however, be an everyday tasks such as dressing or social eating, leisure (games, films) or thera- peutic. Finally, family engagement is especially important; they have information that healthcare professionals need, they need ex- planation and updating, and may want to be involved in hands-​on care such as feeding or occupying. Visiting hours should be liberal or unrestricted. Close integration with mental health professionals is essential, either embedded within older people’s clinical teams or through consultation or liaison services. Close cooperation is also required with community services, such as in accessing previous records, diagnoses and management, and in planning for discharge and fu- ture follow up. General hospital staff can learn appropriate skills and deploy them in a ward environment with the right leadership, expectations, and culture. Care provided in this way also benefits other vulnerable patients, including those with sensory impairments, other mental health problems, or learning disabilities. Box 6.5.7  Diagnosis of dementia • Cognitive history and collateral account of functional decline • Physical and mental state examination • Neuroimaging and other tests (to exclude mimics) • Cognitive testing • Observation of function (e.g. during complex kitchen tasks) • Evolution over time

560 Section 6  Old age medicine Nutrition Nutrition is a further area of vulnerability for older people. Weight loss is a defining feature of frailty. Conversely, obesity is an increasing problem, and this persists into old age, where it is associated with sarcopenia, an important determinant of both functional capacity and metabolic reserve in acute illness. Malnutrition is associated with depression, dementia, meta- bolic disease, cancer, cerebrovascular and other neurological dis- ease, and cardiorespiratory problems. It may also be symptomatic of inadequate or abusive care. Many problems contribute to poor food intake in hospitals, in addition to unsuitable or unpalatable food! Problems include ab- sent, loose or painful teeth, dry mouth or candidiasis, lost or ill-​ fitting dentures, nausea, anorexia, dysphagia, changes in taste and food preference, cognitive problems (forgetting to eat), dyspepsia, and constipation. Dysphagia is often neurogenic due to cerebrovascular disease, neurodegeneration or Parkinson’s disease, and may be decompen- sated by acute illness. The main approach to maintaining nutrition in acute hospital care is prevention or treatment of conditions that contribute to poor intake, attention to food preferences and food consistency, and provision of sufficient human help for those who need it. Social eating (at a table) can help for those who are able, and feeding as- sistants (nurses, or volunteers) are valuable. Use of special diets must be evaluated in the context of the acutely ill person. For in- stance, high fat foods may be better than low fat if they promote palatability, energy intake, and food preference. During an acute illness and injury catabolism predominates and this may lead to weight loss (including muscle), which is often not restored with medical recovery. Nutrition dense supplements are logical, as an efficient way to enhance nutrition in those whose intake is low volume. Muscle mass lost will not be regained without concomitant exercise as well as an appropriate diet. Evidence of benefit is limited in short-​term use or advanced frailty. Nasogastric, gastrostomy, or jejunostomy tube feeding is required in some cases, and can be maintained long term. The main indica- tion is where a potentially reversible problem with swallowing has prevented access to the gut (e.g. acute stroke), or in some postsurgical and critical care situations. Use in frail older people can sometimes be useful, but the balance of potentially small relative benefits against a potentially high procedural risk should be subject to a full, shared decision-​making process with the patient and family. Tube feeding is rarely indicated in advanced dementia and may be traumatic. Care should always be individualized and there are no hard and fast rules. If swallow is vulnerable and tube feeding is not used, it is im- portant to have an open conversation with the patient and family about accepting the potential risks. Some rules for ‘feeding at risk’ or ‘comfort feeding’ can be used to minimize the potential harm. The patient should be alert and sat up. Food should be single consistency, cold rather than hot, and paced so food is placed in the mouth only so fast as each mouthful is cleared. Consistency is important, and fluids may need to be thickened (but do try tasting thickened water or tea; it is quite unpleasant). Speech and language therapists can as- sess and advise. Rapid feeding after a period of starvation or poor nutrition risks Wernicke’s encephalopathy and refeeding syndrome. In such cir- cumstances, high-​dose parenteral B-​vitamins (including thia- mine) should be given, and blood tested for potassium, phosphate, and magnesium. In frailer patients and those with dementia or approaching the end of life, it is important to consider the wider goals of nutrition. Eating should be enjoyable, a focus for social being, and human contact. Oral feeding helps the mouth to stay clean. Social eating (at a table) for those who are well enough is the best means of increasing oral intake in hospital. Moreover meal- times are a key activity for very frail people and can become an important part of the daily routine. Provision should also be made for irregular meals, snacking, finger foods, and flexible meal provision. Immobility and deconditioning Reduction in the ability to walk independently or at all is often the presentation of an acute illness. It is a non​specific presentation that is in itself a core sign of frailty when the acute event is not clearly resulting in a relevant major impairment such as a hemiparesis or lower limb fracture. Eliciting a history of functional change is cru- cial in the initial assessment. This history should be corroborated with carers, family, or others who can describe and quantify the impact of such changes. The aim is to get a thorough, objective understanding of the ex- tent of the problem, its timescale, and potential causes. Examination includes general assessment, such as postural hypotension and breathing, as well as specific assessments of gait, limb function, muscle, joints, or sensory function. The goal is to determine both the causes of the decline and its impact. This will guide the multi- disciplinary team on how best to address recovery through specific treatments and functional rehabilitation, the aim being at least to restore pre-​admission function. The choice to use a walking aid such as a stick or Zimmer frame should be guided by a physiotherapist who would assess the patient’s ability to use the device safely, as well as the potential it may have to reduce the risk of falls. The clear aim should al- ways be to have the patient use the least restrictive form of aid or to continually improve their mobility. Walking inside on a level floor and managing stairs either inside or outside the building represent two different degrees of challenge and often need to be assessed separately. Physical deconditioning after admission to hospital, acute illness, or surgery is the norm in vulnerable older adults (Fig. 6.5.7). It can be rapid and have disproportionate impact. Bedrest is potentially harmful to older patients: early mobilization and socialization are vital in preventing functional decline. After major surgical intervention, for instance, patients may have prolonged admissions with delays in recovery of independence, or they may be prone to complications such as infections or delirium. Prevention of functional decline should therefore be addressed with anticipa- tion in high-​risk surgery or patient groups. Multidisciplinary team involvement can prevent or reverse the process. Failure to address deconditioning can result in unnecessarily persistent disability or dependency, and hospital re-​admission.

6.5  Older people in hospital 561 Summary—​what would an older adult-​centred hospital look like? First and foremost, the hospital will have the corporate ethos that the care of older people is a core priority. The approach and care will be flexible and eclectic, encompassing a mix of goals and models. It will be adapted to the individual patient’s needs and be able where appropriate to incorporate the family in care. Staff will be knowledgeable and skilled in assessing complexity and its impli- cations in frail older people in addition to more traditional skills in managing acute illness. For some patients the health outcomes may inevitably be poor, but with excellent care each patient will have an experience which minimizes distress and gives the best chance of medical recovery and restoration of function or good palliative care as appropriate. The NHS in Scotland and the Royal College of Physicians of London have considered the needs of hospitalized older people in recent reports (Box 6.5.8). Lessons can also be learnt from pallia- tive care and paediatrics, in terms of both environmental design and processes. All aspect of hospital care need examination, including the en- vironment, facilities, signage, staffing skill mix and training, pro- cesses and pathways, risk assessments, management approaches, and family engagement. The hospital environments will be designed to be enriched and facilitating. Visual clutter, which can cause confusion for patients with cognitive impairment, will be simplified. Signage will be clear and use symbols as well as words. Clocks and orientation boards will be visible (and correct). Furniture will be strategically placed to enable mobility and socializing. A day room or dining room will be provided, enabling social eating for those who are able. Ambient noise will be kept to a minimum, especially at night. Light and visual design will take account of the needs of people with visual impairment and will reflect more natural lighting hues to avoid day and night confusion. High contrast colour will be used to help with orientation within wards. Systems and clinicians will be flexible and be able to embrace mul- tiple approaches—​curative, rehabilitative, mental health-​inspired, palliative, or supportive—​and be able to recognize and communi- cate when a change is appropriate. They can live with uncertainty for those patients where their clinical course is unpredictable or fluctuating, and adaptable if their needs change quickly. There will be no unjustified discrimination on the basis of age, disability (or any other characteristic not pertinent to the decision) in access to services. Following a process of shared decision-​making on goals and preferences, there will be access to organ-​specialist investigation and treatment, surgery, rehabilita- tion, and end-​of-​life care. Care will be safe, but this will be balanced against broader goals for the individual and the need to take risks to achieve those goals. Services will not assume that they can deal with the patient as an independent agent who is cognitively intact and able to give their own account, understand their treatments, or agree to complex interventions. Neither will they presume that frail older people are incapable, or have no view on their care. Assessments of commu- nication, understanding and mental capacity will be made, and family or other carers engaged and consulted as appropriate. Hospitals will cater for families with rules that promote inclu- sion, facilitate visiting, and engagement in care. Communication with family members will be proactive and regular. Support services such as mental healthcare, occupational therapy, speech and language therapy, dietetics, or physiotherapy will be responsive and readily available. Teams will meet sufficiently regularly to enable joint working and planning. The hospital will integrate medical and psychiatric services, acute, rehabilitation and palliative care, hospital and community services, and medical and social needs. A programme of purposeful and therapeutic activities will be provided for people operating at all levels of ability, directed by staff capable of identifying their capacities and strengths (e.g. occupa- tional therapists, dedicated staff, or volunteers). Loss of cardiovascular fitness complicates and slows recovery Immobility increases the risk of deep venous thrombosis, joint pain and stiffness, constipation, depression, hypostatic pneumonia, pressure sores, delirium and thus increases the risk of institutionalization Up to 5% loss of muscle strength per day of inactivity Antigravity muscles are affected most with 40% of this loss of strength occurring in the first week of illness or immobility 40% 5% Fig. 6.5.7  The risks of bed rest. Box 6.5.8  Healthcare Improvement Scotland recommendations for older people in hospital 1 Opportunity and assistance to discuss needs and preferences, including those involved in their care 2 Treatment with dignity and respect 3 Involvement in decision-​making 4 Identification of current health needs, predisposing conditions which heighten the risk of healthcare-​associated harm, and the most appropriate place for care to be delivered 5 If frail to have prompt comprehensive geriatric assessment (CGA) and management by a specialist team 6 Drug review and active medicines management 7 Cognitive assessment 8 Identification assessment and treatment for delirium 9 High-​quality care for those with diagnosed or suspected dementia 10 High-​quality care for those with diagnosed or suspected depression 11 Assessment for risk of falls and measures to reduce risk 12 Timely access to rehabilitation services 13 Effective discharge planning, and good communication at transfers of care 14 Support through periods of transition or delays between care environments 15 Cared for by sufficient numbers of knowledgeable and skilled staff

562 Section 6  Old age medicine Staff will be well-​trained and available in appropriate num- bers and skill mix. They will work in teams and feel supported. They will be confident, and use their professional judgement in the service of patients and their families, and will be sup- ported professionally and psychologically. They will have time to communicate, make thorough assessments, and deliver care compassionately. FURTHER READING British Geriatrics Society—​a comprehensive resource with online guidelines, research and educational materials. www.bgs.org.uk Ellis G, et al. (2017). Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database of Systematic Reviews, (9), CD006211. Future Hospital Programme (2013). Caring for Medical Patients: A Report from the Future Hospital Commission to the Royal College of Physicians. September 2013. https://www.the4AT.com Harwood RH (2012). Dementia for the hospital physician. Clin Med, 12, 35–​9. Healthcare Improvement Scotland (2015). Care of Older People in Hospital Standards. June 2015. www.healthcareimprovementscotland.org Oliver D, et al. (2014). Making our health care systems fit for an ageing population. The Kings Fund, London. Pollock K (2015). Is home always the best and preferred place of death? BMJ, 351, h4855. Quinn TJ, et al. (2011). Functional assessment in older people. BMJ, 343, d4681. Tadd W, et al. (2011). Dignity in Practice: An Exploration of the Care of Older Adults in Acute NHS Trusts. NIHR SDO Programme report. http://​ www.netscc.ac.uk/​hsdr/​files/​project/​SDO_​ES_​08-​1819-​218_​V01.pdf

6.6 Supporting older peoples’ care in surgical and

6.6 Supporting older peoples’ care in surgical and oncological services 563

ESSENTIALS The clinical profile of patients presenting for elective and emer- gency surgery and for oncological treatment is changing. Patients are now older and more complex with coexisting multimorbidity and geriatric syndromes. There is increasing recognition of the need to improve the effectiveness, efficiency, and the experience of pa- tients in this vulnerable group. Achieving the best outcomes requires attention to: • Assessment—​with emphasis on multimorbidity, geriatric syn- dromes of frailty and cognitive impairment, and functional status • Quantification of risk—​use of risk prediction tools • Optimization—​modifying the risk profile prior to treatment, including optimization of physiological reserve, organ-​specific pathology, and geriatric syndromes • Shared decision-​making about potential surgical or oncological treatment approaches (or none), based on expert communica- tion of the potential risks, harms, benefits and burdens • Optimal proactive and responsive management throughout the surgical or oncological journey Such wide-​ranging interventions cannot be provided by single specialties, but require collaboration across disciplines and special- ties to ensure delivery of patient-​centred services, relevant educa- tion and training, and a research programme that aims to inform routine clinical practice. Introduction Ageing is associated with an increase in the incidence and preva- lence of degenerative, metabolic, and neoplastic disease. Many of these conditions require surgical or oncological manage- ment, which is generally provided by healthcare professionals other than geriatricians. To ensure the best outcomes for the increasing numbers of older people undergoing surgery or onco- logical intervention, professionals working in these fields re- quire an understanding of geriatric medicine. Additionally, the generalist or medical team may be called upon to support older patients in surgery and oncology who have acute or longer-​term medical issues. They too require an understanding of the specific needs of the older patient in the context of the surgical or onco- logical episode. This includes knowledge of the presence and interaction of age-​related change in physiology, multimorbidity, and geriatric syndromes. It also requires an understanding of the impact of this pathophysiological profile and of social and psychological factors on treatment decisions and optimal clin- ical management before, during, and after any surgical or onco- logical intervention’. The specialist settings: Oncology and surgery The increasing numbers of older people presenting with cancer is explained by demographic change and the age-​related increase in the incidence of many solid organ tumours. However, older people are less likely to be offered oncological treatments than younger people, and those who do undergo treatment are more likely to have dose reduction or premature cessation of treatment courses due to reported toxicities. This may contribute to poorer cancer-related long-term survival in older patients and poorer patient-reported outcomes. Furthermore older people may decline offers of onco- logical treatment, due to widely held belief that increasing age is as- sociated with adverse outcome. However, data suggests that it is not chronological age but physiological decline, multimorbidity, and geriatric syndromes that are the independent predictors of poor outcome. These, of course, are more prevalent among older patients, hence clinical decisions require a working knowledge of these pre- dictors of adverse outcome, when and how to assess, how to modify, how to use information to ensure shared decision-​making, and how to manage the recovery period after oncology treatments. Similarly, despite increased numbers of older people undergoing surgery for degenerative (e.g. joint replacements) or neoplastic conditions (e.g. colorectal cancer), they remain less likely to have equitable access, are more likely to have surgery cancelled, and suffer from an excess of postoperative morbidity, mortality, and functional decline. Rates of postoperative surgical complications remain fairly constant as age increases, but medical complications such as cardiac, respiratory, renal, and neurological impairments 6.6 Supporting older peoples’ care in surgical and oncological services Jugdeep Dhesi and Judith Partridge

564 Section 6  Old age medicine occur more frequently in older patients. These complications ad- versely impact functional recovery, short-​term and longer-​term mortality rates, and healthcare costs. The pathway of surgical and oncological care The patient pathway of care follows a similar pattern in surgery and oncology. There are five key stages for clinicians to consider. Indeed, this is the case for patients of all ages, but in complex older patients each stage can present specific challenges. These stages are: • Assessment—​describing the patient’s clinical and psychosocial profile • Quantification of risk—​using risk prediction tools • Optimization—​modifying the risk profile prior to treatment • Shared decision-​making about potential surgical or oncological treatment approaches (or none), based on expert communication of the potential risks, harms, benefits and burdens • Optimal proactive and responsive management throughout the surgical or oncological journey Assessment—​describing the older patient’s clinical profile The aim of preoperative or pre-​oncological assessment in older people is to identify the nature and degree of factors that may ad- versely impact clinician reported adverse outcomes (e.g. morbidity and mortality) and patient-​reported outcomes (e.g. quality of life, functional deterioration). This can be challenging in a complex older patient. A full history and examination is the starting point and is essential, but rarely sufficient. The findings can be conceptu- alized as follows. Assessment for multimorbidity Multimorbidity, including previously undiagnosed disease, is to be expected in older patients, hence a systematic and standardized approach is needed. Investigations should be guided by the find- ings rather than be ‘routine’. For example, symptoms of recurrent infections suggests the need for screening for diabetes; a history of smoking and shortness of breath, the need for spirometry for chronic obstructive pulmonary disease; and symptoms of cardiac ischaemia, an electrocardiogram and further cardiac investiga- tions for heart disease. Assessment for geriatric syndromes As discussed in other chapters in this section, geriatric syndromes are a group of conditions where ‘symptoms do not result solely from discrete diseases, but instead from accumulated impairments in multiple systems and develop when the accumulated effect of these impairments in multiple domains compromises compensa- tory ability’. The presence of these syndromes is associated with adverse postoperative and oncological treatment outcomes, and as such should be carefully considered. Frailty Frailty is an independent risk factor for adverse postoperative and post-​oncological morbidity, mortality, and institutionaliza- tion. The consensus understanding of the term is a syndrome of decreased physiological reserve across several organ systems such that there is higher risk of adverse clinical and functional out- comes from additional illness, injury, or iatrogenic interventions (see Chapter 6.2). There is, however, no consistency in the diag- nostic tools for frailty used in clinical practice. For example, an- aesthetic studies often use surrogate markers to ‘diagnose’ frailty such as gait velocity or the shuttle walk. These measures may be useful for risk stratification as they do have some predictive power for outcomes in clinical settings, but they do not provide broader information of a multidomain syndrome or any guidance for risk modification. Some surgical subspecialties have developed spe- cialty specific frailty assessments, for example the Comprehensive Assessment for Frailty (CAF) score in cardiac surgery. Similarly, in oncology this has led to the development of the widely used Balducci frailty criteria. Although these tools may be clinically feasible in older surgical and oncological patients, most have not been assessed for their clinimetric properties in these settings. The ideal tool would not only diagnose frailty, be well-​validated, and be clinically feas- ible, but also identify aspects of the frailty syndrome that could be optimized in order to modify risk. To this end the Edmonton Frailty Scale is proving useful, especially as it highlights domains for potential optimization (see Table 6.6.1). These may include nutritional status, mood, polypharmacy, or the introduction of a social support to maintain independence. Emerging evidence sug- gests it is both a practical and translatable tool for use in specialist settings. Cognitive impairment Cognitive impairment is an independent predictor of adverse postoperative and post-​oncological outcomes (morbidity, mor- tality, poor functional outcome) and of increased length of stay. It is under-​recognized in surgical and oncological populations. The purpose of identifying cognitive impairment in these contexts is not limited to making a formal diagnosis of dementia, but add- itionally to provide baseline information to: • alert the clinician to the need to carefully to assess capacity and ability to consent • predict risk of perioperative/​peri-​treatment cognitive syndromes such as delirium • facilitate clear communication of this risk with the patient and their carers, as well as with other healthcare professionals • employ evidence-​based strategies to prevent or manage cognitive decline or delirium • prompt longer-​term follow up with subsequent specialist in- volvement such as a memory clinic assessment One of the reasons for the lack of recognition of cognitive impair- ment in surgical and oncological patients may be the previous paucity of guidance on which patients should be screened for cognitive dysfunction prior to surgery or oncological treatment.

6.6  Supporting older peoples’ care in surgical and oncological services 565 More recent literature suggests routine cognitive screening (e.g. by the dementia questionnaire, 4AT—​see Fig. 6.5.6, in Chapter 6.5) or a clock drawing test should be conducted in all older patients, followed by a more detailed assessment in those highlighted as at high risk. Alternatively, a brief but more detailed assessment (e.g. the Montreal Cognitive Assessment, MoCA) could be em- ployed. The decision as to which approach is most useful should be guided by the likely prevalence of cognitive dysfunction in the specific clinical population in question. For example, in vascular surgical patients the prevalence of cognitive impairment, par- ticularly executive dysfunction, is high and therefore routine use of the MoCA may be advocated, whereas screening using the 4AT may be more appropriate in other surgical populations. Assessment of functional status Poor baseline functional status or high dependency levels predict adverse functional outcome, with longer recovery time and less likelihood of returning to baseline status, hence assessment of functional status is important to: • inform shared decision-​making, including functional deterior- ation as a potential outcome to be considered in addition to the more conventional treatment risks • identify scope for optimization of the individual or their envir- onment before surgery or treatment • employ techniques and ward based enablement strategies to minimize functional deterioration • anticipate the need for support when discharge planning Functional status can be measured using various tools, most of which quantify a patient’s need for help (or not) to complete activ- ities of daily living (ADLs) and instrumental activities of daily living (IADLs), for example, the Barthel Index (see Fig. 6.5.3 in Chapter 6.5). However, within the older surgical or oncological population the use of such tools can be limited by a marked ceiling effect. More de- tailed assessments can be useful, particularly if patients or carers can self-​complete (e.g. Nottingham Extended Activities of Daily Living, NEADL), although the utility of many of these tools have not been thoroughly investigated in these clinical settings. The overall approach to the preparation for surgical or onco­ logical treatment is summarized in Table 6.6.2. Quantification of risk—​use of risk prediction tools in older people Conducting baseline assessments in specialist settings provides information that can be used to quantify risk of adverse clinician reported outcomes such as organ-​specific morbidity and 30-​day mortality. In the surgical setting the most widely accepted and valid- ated tools are the American Society of Anaesthesiologists (ASA), Portsmouth-​Physiology and Operative Severity Score for the enUmeration of Mortality (PPOSSUM), and the Surgical Risk Scale (SRS). Cardiopulmonary exercise testing is also being used to profile individual risk, but is limited to the single domain of cardiopulmonary fitness. In the oncological setting, WHO Table 6.6.1  Using the Edmonton Frailty Scale to address aspects of the frailty syndrome in the surgical or oncological setting Frailty protocol Frailty Domain Specific Aspect of Frailty Modification Compensation Cognition Abnormal clox test Vascular risk factor control Onward referral to memory clinic Assessment of capacity Information provision to patient and carer (diagnosis of cognitive impairment and delrium risk) Functional independence Needs assistance with daily activities Referral to occupational therapist and social worker Pre-​emptive assessment of care needs Social support Has no one to help out at home when required Referral to social worker for therapeutic interventions Arrange home care/​befriending /​day centre/​pendant alarm Medication use Number of medications Review/​rationalize medications Assess/​optimize cognition Provision of dosette box Arrange carer to prompt medications Forgetting to take medications Nutrition Recent weight loss Assess for underlying cause Dietician, speech and language therapy, and occupational therapy Nutritional supplements Highlight to ward/​community dieticiana Mood Self-​reported low mood Liaise with GP, specialist psychiatric services MDT input Access to local services Continence Self-​reported urinary incontinence Medications, exercise strategies,
bladder training regimesa Referral to continence servicea Provision of pads Functional performance TUAG >11 seconds Referral for physiotherapya Provision of walking aids Provision of equipment to assist patients at home (e.g. jar opening devices) a Depending on timeframe to surgical procedure the intervention may consist of highlighting patient to ward team (dietician, therapists) or referral to community teams while awaiting surgery. Clox test, and executive clock drawing test; TUAG, Timed Up And Go test.

566 Section 6  Old age medicine performance status has traditionally been used to help clinicians to describe a patient’s risk profile and to plan treatment. However, many of these tools do not adjust for age or the presence or se- verity of multimorbidity. Furthermore, they have subjective com- ponents, demonstrate a ceiling effect in older patients, and are population based tools, hence their use for predicting individual risk in the older complex patient is limited. There are also many organ-​specific risk prediction tools, for predicting cardiac events, respiratory failure or acute kidney in- jury, but the practical application of these is limited in older people where multimorbidity is common and individuals are at risk of multiple inter-​related medical complications. There are no specific tools to assess risk of functional decline, but there are for postoperative cognitive disorders, in particular for de- lirium. This is because delirium is a well recognized postoperative complication in emergency surgery, vascular surgery, and hip frac- ture surgery. Unfortunately, most of these tools include age, emer- gency surgery, and dementia as primary predictors, and since these are prevalent in the populations we are discussing here, they lack discriminatory power in the older surgical population, limiting their practical application. More recent oncological literature suggests using a combination of objective scores examining multiple domains (e.g. geriatric de- pression scale, mini-​mental status examination, ADL/​IADL, per- formance status, brief fatigue inventory, ASA, POSSUM, ACE27) to assess risk. The intrinsic complexity of such an approach has led to the establishment of onco-​geriatric units that use the comprehensive geriatric assessment (CGA) approach to facilitate risk profiling prior to oncological treatment. Similarly, using com- prehensive geriatric assessment in the preoperative setting may provide a fuller risk profile of a complex older surgical patient. The drawback of this method may be the time and expertise in- volved, also the fact that it does not provide a numerical score of risk, which clinicians and patients often prefer. However, modified versions of the comprehensive geriatric assessment process are in- creasingly considered essential in the specialist settings of surgery and oncology to help inform risk assessment and management. Table 6.6.2 describes how the CGA process can be employed in preoperatively or pre-oncological treatment. Optimization—​modifying the risk profile in
the older patient Better postoperative and post-​oncological treatment outcomes are likely if the patient is as ‘fit as possible’ prior to these interventions. Achieving this level of ‘fitness’ in older patients requires a multi- modal approach to improving physiological status, optimizing coexisting morbidity, and addressing geriatric syndromes. The fol- lowing issues should be considered. Optimization of physiological reserve Short duration exercise therapy has been shown to improve car- diorespiratory status prior to surgery and oncological treatment. Uptake and compliance has been good, even in older populations with new diagnoses of cancer. The evidence suggests both en- durance and high intensity exercise are safe and feasible in older populations, although these studies have not yet shown that im- provement in physiological status results in improved post-​ treatment outcomes. Optimization of organ-​specific pathology There are numerous guidelines informing the optimization and perioperative management of conditions such as diabetes and an- aemia. The aim of such guidance is to reduce the incidence and se- verity of predictable organ-​specific complications (e.g. pneumonia in a patient with chronic obstructive pulmonary disease, acute kidney injury in a patient with known chronic kidney disease, and transfusion rates in a patient with known anaemia). Where no spe- cific perioperative guidance exists, optimization should be based on general guidance for the management of specific diseases. The de- scription of assessment and optimization of individual conditions affecting older patients is beyond the scope of this chapter. Clearly the challenge is how to employ multiple guidelines in an older pa- tient with multimorbidity, where drug therapy for one condition may aggravate another underlying condition (e.g. using β-blockers in ischaemic heart disease aggravating postural hypotension in a patient with Parkinson’s disease on levodopa) and as such requires the expertise of a geriatrician or other generalist. Optimization of geriatric syndromes Optimization of frailty There is emerging evidence for optimization of single aspects of the frailty syndrome using, for example, preoperative exercise or Table 6.6.2  The benefits of a systematic interdisciplinary approach preparing for surgery or oncology treatments Assessment • Physiological reserve • Morbidity (existing and previously undiagnosed) • Frailty • Cognition • Capacity to consent • Patient and carer expectations Optimization • Physiological reserve • Multimorbidity • Frailty • Psychosocial issues • Social support and resources Prediction of postoperative or post-​ treatment risk • Organ-​specific complications • Functional decline • Mortality Medication management • Pharmacological optimization of comorbidities • Reduction of harmful drug-​drug interactions • Anticipate medication related adverse effects (e.g. anticholinergic load and delirium) • Plan for necessary preoperative/​pretreatment cessation of medications (e.g. anticoagulants) • Ensure accurate perioperative/​peritreatment prescription (with alternative formulations if necessary, e.g. of Parkinson’s meds) Anticipate and mitigate changes in functional during and after treatment • Clarify social resources and resilience • Make environmental adaptations proactively • Plan for more complex hospital discharge needs Communication to promote shared decision-​making • Incorporate a broader scope of benefits and risks, including functional change, in discussing treatment decisions • Consideration of alternative options

6.6  Supporting older peoples’ care in surgical and oncological services 567 nutritional support. However, there is no evidence to date to support the hypothesis that preoperative or pretreatment multicomponent interventions can modify the frailty syndrome or impact on postoperative or post-​treatment outcome, other than through the use of CGA. Optimization of cognitive function/​reducing risk
of delirium Dementia specific medications, notably anticholinesterases, can produce improvement in cognition and symptoms of dementia for some patients, but the timescale of response will often preclude this initiation in patients prior to oncological treatments or surgery, and to date there is no clinical trial evidence of impact on the outcomes. There is evidence, however, to suggest that pre-​existing contribu- tors to postoperative cognitive disorders can be modified. Given that delirium is now known to commonly worsen the longer-​term cognitive trajectory, preventing postoperative delirium in those at risk is clearly of importance. Multicomponent interventions for prevention of delirium were initially described in medical populations but have been trans- lated into surgical populations. These interventions include medi- cines optimization (e.g. stopping deliriogenic drugs), treating electrolyte imbalances and disorders such as hypothyroidism, and correcting nutritional deficiencies (e.g. folate deficiency). There is insufficient evidence to support the use of pharmaco- logical agents such as antipsychotics to prevent delirium. Optimization of functional status and potential
hospital-​acquired deconditioning As preoperative/​treatment functional status is predictive of postsurgical/​treatment functional recovery, assessment should prompt a proactive approach to maximizing function prior to surgery or oncological treatment, utilizing multidisciplinary skills. An example may be a patient awaiting elective joint re- placement receiving preoperative strength and balance training from a physiotherapist, pre-​emptive home adaptations from an occupational therapist, and initiation of social support by a social worker either preoperatively or proactively arranged for hospital discharge. Such approaches employed in a structured manner are being used as part of prehabilitation in enhanced recovery programmes in various surgical specialties surgery. Clearly in ur- gent cancer surgery or consideration for oncological treatment, the form of prehabilitation will need to be tailored to the limited time available. Communication and shared decision-​making After assessment, the next phase in the surgical or oncological pathway of care is shared decision-​making. At this stage, the differing expertise of the doctor and the patient should be com- bined to develop a shared care plan. This requires knowledge and good communication skills on the part of the doctor, and the pa- tient must be assessed to have capacity to take part in such a discus- sion. If the patient lacks capacity then the relevant legal framework must be adhered to (e.g. the Mental Capacity Act in the United Kingdom). The doctor should present information on the available treat- ment options, together with the likelihood of benefit or harm for each, and the likely burden of treatment. It is important to con- sider the vocabulary used and the presentation of risk. While healthcare professionals may interpret the term ‘risk’ as a statis- tical probability, many patients assume ‘risk’ implies a bad out- come or harm. Likewise, the word ‘chance’ may be interpreted as throwing of dice. The word ‘likelihood’ can be a more useful term. Some patients may find pictures, tables, or graphs helpful to understand outcome predictions. The patient should be en- couraged to consider this information in terms of their individual goals and what they want the treatment to achieve, for example, a reduction in specific symptoms, avoidance of dependency, or an increase in life expectancy. This discussion, guided by the patient, can result in a decision to: • proceed with the surgical or oncological treatment option • modify the treatment proposed • not proceed with surgery/​oncological treatment, but to employ other treatment options (e.g. symptom control) • inform the management of treatment-​related risks • defer the decision to a future date, at which time further or re- peated information may be requested by the patient, before a shared care plan can be developed Using the same principles as shared decision-​making, pro- active advance care planning should be considered in patients at high risk of postoperative/​treatment morbidity and mortality. This should include a discussion with the patient regarding ‘ceilings of care’. Questions to be considered include whether the patient should be managed in a ward setting only, whether multiorgan support in an intensive care unit would be appro- priate, or whether they should be resuscitated in the event of a cardiorespiratory arrest. Similarly, patients who decline surgery or treatment may then be at risk of premature death due to the underlying surgical pathology. For example, a patient with an ab- dominal aortic aneurysm is at risk of rupture at a time and place where even an urgent surgical response may be unsuccessful. The management of just such a possibility should be discussed and documented. In such cases, the risks of undertaking an emer- gency procedure are even higher than for an elective procedure, and in many situations the patient chooses palliation. This deci- sion will need to be communicated with the primary care team and the family or carers in order to facilitate community-​based palliative treatment. Optimal management of older patients throughout the surgical or oncological
journey Although a proactive approach and pretreatment may reduce the risk of adverse outcome, it is not possible for all risk to be elimin- ated. It is therefore important to plan and establish standardized team approaches to common postoperative or post chemo-​ radiotherapy complications, which are especially common in older people.

568 Section 6  Old age medicine Management of medical complications Postoperative and post-​oncological treatment cardiac (e.g. atrial fibrillation), respiratory (e.g. lower respiratory infection), neuro- logical (e.g. delirium), or other medical complications are more likely in older than younger patients. This is particularly important as older people are less likely to tolerate these complications than younger patients and more likely to have ‘failure to rescue’. Clear management plans based on current guidance should be in place for these predictable complications. These need to be supplemented by education and training for surgical or cancer care staff to en- sure complications are identified early through routine screening, managed in a standardized way according to local protocols, and referred to specialty teams early. Management of geriatric syndromes Cognitive disorders There is scant literature regarding cognitive disorders specific to the oncological setting, but there is an increasing focus on these complications in relation to surgery. The evidence suggests that perioperative cognitive disorders are common and include postoperative delirium, postoperative cognitive dysfunction, and longer-​term cognitive impairment. While the use of such terms implies that they are discreet entities, this is not yet established. Of these conditions, postoperative delirium is the most well described, aided by the clear definition in the Diagnostic and Statistics Manual of Mental Disorders (DSM-​5). In contrast, postoperative cognitive dysfunction and longer-​term cognitive impairment suffer from lack of universally accepted definitions, with variations in the neurocognitive tools used, the time-​point of cognitive assessment, and what constitutes a clinically meaningful postoperative cog- nitive change. Furthermore, many studies have been limited by a failure to preoperatively diagnose existing cognitive impairment, provide a systematic approach to the identification of postoperative delirium, and/​or conduct meaningful longer-​term follow up. In terms of management of postoperative delirium, the mainstay is non​pharmacological with an emphasis on maintaining a sup- portive environment, good nursing care, and de-​escalation strat- egies. For example, with delirium, staff should be aware of delirium in patients who have been identified as at high risk at preassessment, know how to diagnose delirium using tools such as the confusion assessment method, know how to manage delirium or know where to find local guidelines, and be aware of how and when to refer to specialist teams. As with delirium in other settings, there is a role for pharmacological intervention in hyperactive delirium when a patient is a danger to themselves or others, including through the re- fusal of essential investigation or treatment. The use of medications to treat a patient with delirium who lacks capacity should always be considered within the relevant legal framework. Current guid- ance differentiates between using dopamine antagonists for most postoperative delirium, with benzodiazepine usage reserved for de- lirium secondary to alcohol withdrawal, those with movement dis- orders, or those with a prolonged QT interval on electrocardiogram. Impaired functional recovery Management plans should also address less clearly defined complications such as delayed functional recovery, fatigue, or psychological sequelae (anxiety or depression). While evidence describing the trajectory of recovery after surgery or cancer treat- ment is limited, it appears that postsurgical functional limitation can persist for up to six months. Targeting such functional deteri- oration requires a proactive multidisciplinary approach involving early mobilization whenever possible, with removal of obstacles to this such as unreported pain, a care approach which promotes autonomy, mental and physical activity, structured rehabilitation with patient-​centred goals, and proactive planning for new care needs in terms of equipment or carers. As previously highlighted, these needs can often be anticipated and actions taken beforehand, rather than relying on a reactive approach initiated once the com- plication has occurred. Specific consideration in emergency surgery The principles of managing emergency surgical patients are the same as those described for elective surgical patients, with the main difference being the need to tailor management to the shorter timeframe available. The subspecialty of orthogeriatrics provides a good example of the evolution of geriatric medicine provision in emergency surgery. Orthogeriatrics The concept and development of orthogeriatric care started in the United Kingdom in the late 1950s and has evolved to what is now an established evidence-​based approach with NICE guidance. The fundamental principles are: • holistic care that extends beyond the broken bone • multidisciplinary team care delivered by a range of disciplines with appropriate expertise • integrated care in which there is explicit shared ‘ownership’ of the programme, working collaboratively in partnership with shared clinical governance • a long-​term conditions approach incorporating rehabilitation and secondary prevention of fractures by focusing both on falls prevention and bone health Largely depending upon local context and resources, various models of orthogeriatric collaboration have emerged. Initially the focus was on the postoperative phase, but increasingly the evidence supports shared care from the moment of presentation with gains in clinical outcomes to be made by medical intervention from the beginning. The most common models are: • Traditional—​a reactive consultation service with the care led and predominantly delivered by orthopaedic teams. Advice is sought from general medicine, organ-​specific, or geriatric medi- cine teams as required. • Structured support—​the orthopaedic team retain overall re- sponsibility but with scheduled liaison geriatric medicine input (e.g. fixed ward rounds/​multidisciplinary team meetings), some- times starting preoperatively but more commonly not. • Phased care—​orthopaedic teams retain responsibility up to the immediate postoperative period, when geriatric medicine takes over, usually involving patients being transferred to the geriatric

6.6  Supporting older peoples’ care in surgical and oncological services 569 medicine unit once stable. Orthopaedic input is reduced to as and when required. • Shared care model—​here geriatricians and orthopaedic surgeons take joint responsibility and accountability for the care of the pa- tient from admission, supported by a multidisciplinary team and incorporating rehabilitation services. The best results appear to come from collaboration between orthopaedic, anaesthetic, and geriatric medicine teams in the de- sign and delivery of the care pathway. The focus of the surgical team is on making the diagnosis and considering the surgical options. The medical team focuses on ensuring prompt history, examination, risk assessment, immediate management focusing on medical optimization for surgery, and taking a longer-​term view of management of postsurgical recovery. The anaesthetic team reviews the information provided by both the medical and surgical team and uses this to ensure an appropriate strategy for pain management, intraoperative care, and consideration of the need for high-​dependency care in the postoperative period. There is necessarily overlap between these tasks and teams, and all of the healthcare professionals involved should have an under- standing of assessment of capacity to consent, management of delirium, prevention of pressure ulcers, and of consideration for advance care planning. One of the clearest associations from large scale audit and ob- servational studies is the link between timing of surgery and improved outcome. This has resulted in a widespread change in clinical practice, at least in the United Kingdom, where reim- bursement of the provider hospital depends upon surgery being undertaken within 36 hours. Overall the evidence suggests that early surgery does reduce postoperative complications, improve functional outcomes, and reduce mortality, in addition to re- sulting in a shorter hospital stay and therefore lower financial cost. Furthermore, from the patient’s perspective, early surgery to achieve definitive pain control and allow early mobilization is beneficial. There are, however, clinical situations—​probably rele- vant to less than 5% of patients—​where medical optimization prior to surgery is preferable. There are no evidence-​based rules on this, but current consensus suggests that the following clinical issues justify this approach: • Anaemia (Hb <90 g/​litre) • Acute uraemia • Severe electrolyte imbalance (Na <120 or >150 mmol/​litre; K <2.8 or >6.0 mmol/​litre) • Uncontrolled diabetes • Uncontrolled heart failure • Correctable cardiac arrhythmia (e.g. atrial fibrillation with rapid ventricular rate) • Exacerbation of chronic chest or acute chest infection • Severe sepsis • Reversal of iatrogenic or other significant coagulation deficiencies The discovery of a systolic murmur consistent with aortic valve dis- ease is not an uncommon finding in older people, and if clarifica- tion with echocardiography is not rapidly available this can lead to surgical delays, but experienced anaesthetists can judge the poten- tial risk of perioperative hypotension in this situation and adjust their approach accordingly. In the postoperative period, it is essential to focus on reducing risk of medical and functional complications (delirium, pneu- monia, hospital-​acquired deconditioning). Secondary prevention of falls and fracture is discussed in Chapter 6.8. Translating the lessons from orthogeriatric care into other emergency surgical settings The National Hip Fracture Database, in the United Kingdom which was established to describe the hip fracture population, the out- comes, and provide benchmarking data, has successfully raised the profile of hip fracture care. This has resulted in increased use of guidelines and facilitated improvements in quality of care with better outcomes. Lessons learnt from orthogeriatrics are now being translated into other high-​risk emergency surgical populations such as those undergoing emergency laparotomy. The National Emergency Laparotomy Audit (NELA) in the United Kingdom reported that in the emergency general surgical population, 70% of patients were aged over 70 years and had a 25% postoperative mortality rate. Although there is emerging data that the timely involvement of geriatricians can improve outcomes, the organiza- tional component of NELA shows that such care is not yet routine. As with the hip fracture population, it is likely that a combination of evidence-​based direct clinical care and supporting indirect and non​clinical components such as guidelines, pathways, and protocols will be needed to improve outcomes for older people undergoing emergency laparotomy. Furthermore, there are sig- nificant numbers of older patients admitted under other surgical subspecialties, for example, ruptured aneurysms under vascular, haematuria under urology, and skin trauma under plastics, all of whom have high-​risk profiles (multimorbidity, frailty, cognitive impairment). These populations require novel evidence-​based ap- proaches tailored to take into account their specific risk profile, surgery-​specific issues, and clinical pathways. The benefits of novel approaches to surgical
and oncological care for older people The changing demographics and the clinical profile of the surgical and oncological populations has led to the development of novel patient-​centred rather than organ or specialty centred services. Such services bring together the expertise of all healthcare pro- fessionals involved in the surgical or oncological pathway of care. This may include surgeons, anaesthetists, oncologists, and geria- tricians, as well as allied healthcare professionals, and liaison with organ-​specialist physicians. The intended benefits of these novel approaches are to achieve: • targeted and appropriate use of level 2 and 3 care • standardized management of predictable complications • proactive rehabilitation and discharge planning • smoother transitions to community care The anticipated benefits include: • more effective care reflected in clinician-​reported outcomes (morbidity, mortality) • increased efficiency (lower cancellation rates, reduced length of stay)

570 Section 6  Old age medicine • better patient experience and subsequent quality of life • improved functional recovery The development of a multidisciplinary approach encompassing partnerships across clinical specialties, allied health profes- sionals, nurses, and managers, and so on may galvanize better commissioning of services, shared clinical governance ap- proaches, and collaborative research networks. Central to this ap- proach is the embedding of comprehensive geriatric assessment in surgical and cancer services for older people, and this is now promoted by several specialist societies, including the ‘Optimal preoperative assessment of the geriatric surgical patient’ guide- line published collaboratively by the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics Society. The same approach has been advocated by the Society of International Oncogeriatrics for pa- tients with cancer. FURTHER READING Balducci L (2007). Aging, frailty, and chemotherapy. Cancer Control, 14, 7–​12. Bell S, et  al. (2015). Risk of postoperative acute kidney injury
in patients undergoing orthopaedic surgery—​development and validation of a risk score and effect of acute kidney injury on survival: observational cohort study. BMJ, 351, h5639. Braude P, et al. (2016). Perioperative medicine for older patients: how do we deliver quality care? Future Hospital Journal, 3, 33–​6. Gladman JR, Lincoln NB, Adams SA (1993). Use of the extended ADL scale with stroke patients. Age Ageing, 22, 419–​24. Gupta H, et al. (2011). Development and validation of a risk calculator predicting postoperative respiratory failure. Chest, 140, 1207–​15. Inouye SK, et al. (1990). Clarifying confusion: the confusion assess- ment method. A new method for detection of delirium. Ann Intern Med, 113, 941–​8. Lawrence VA, et al. (2004). Functional independence after major ab- dominal surgery in the elderly. J Am Coll Surg, 199, 762–​72. Lee TH, et  al. (1999). Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation, 100, 1043–​9. Lin H, et al. (2016). Frailty and post-​operative outcomes in older sur- gical patients: a systematic review. BMC Geriatr, 16, 157. Marcantonio ER, et al. (2001). Reducing delirium after hip fracture: a randomized trial. J Am Geriatr Soc, 49, 516–​22. Myles PS, et al. (2016). Standardizing end points in perioperative trials:  towards a core and extended outcome set. Br J Anaesth, 116, 586–​9. Nadelson M, Sanders R, Avian M (2014). Perioperative trajectory in adults. Br J Anaesth, 112, 440–​51. National Institute for Health and Care Excellence (NICE). Delirium:  Prevention, Diagnosis and Management. Clinical guideline [CG103]. https://​www.nice.org.uk/​guidance/​cg103?un lid=812382453201667151246 Partridge J, et al. (2014). The impact of pre-​operative comprehensive geriatric assessment on postoperative outcomes in older patients undergoing scheduled surgery: a systematic review. Anaesthesia, 1, 8–​16. Rolfson DB, et al. (2006). Validity and reliability of the Edmonton Frail Scale. Age Ageing, 35, 526–​9. Siddiqi N, et al. (2016). Interventions to prevent delirium in hospital- ised patients, not including those on intensive care units. Cochrane Database Syst Rev, 3, CD005563. Sündermann S, et al. (2011). Comprehensive assessment of frailty for elderly high-​risk patients undergoing cardiac surgery. Eur J Cardiothorac Surg, 39, 33–​7.

6.7 Drugs and prescribing in the older patient 571

6.7 Drugs and prescribing in the older patient 571

ESSENTIALS The use of pharmacological agents is often a central component of medical therapy for older people. Medications can relieve symp- toms, improve function, and prevent illness, but they also have the capacity to inflict great harm. Older people are at particular risk of such harms as a result of impaired homeostatic reserve, of al- tered drug metabolism, the presence of multimorbidity and conse- quent polypharmacy, which increases both exposure to potentially harmful agents and the chance of drug–​drug interactions. The therapeutic priorities for older, frail people may differ when com- pared to younger, robust patients; limited life expectancy means that attempts to prolong life may become relatively less important than the relief of symptoms and avoidance of side effects and medi- cation burden. Prescribing in younger patients, especially those with single dis- eases, is strongly influenced by evidence collected from randomized controlled trials, reflected in disease-​specific guidelines. This ap- proach is much less useful in older patients, when combining guide- lines can lead to contradictory advice in those with multimorbidity, and simply summing the prescribing recommendations from mul- tiple single disease guidelines leads to high medication burdens. Adverse drug events are a major source of ill-​health, and unthinking adherence to disease-​based guidelines is unlikely to provide overall benefit to older people’s health, function, or quality of life. The aim of prescribing for older people is to ensure that prescribing is neither avoided, nor is needlessly excessive, but is appropriate. Appropriate prescribing requires that: • all medicines are prescribed for the purpose of achieving specific therapeutic objectives that have been agreed with the patient • therapeutic objectives are actually being achieved, or there is a reasonable chance they will be achieved in the future • therapy has been optimized to minimize the risk of adverse drug events • the patient is motivated and able to take all medicines as intended The principal risk factors for inappropriate prescribing are polypharmacy related to complex multimorbidity and exposure to multiple prescribers. Tools such as the Screening Tool of Older People’s Prescriptions/​Screening Tool to Alert to Right Treatment criteria can help with identifying and managing inappropriate pre- scribing. Two complementary Cochrane systematic reviews have shown that deprescribing is beneficial in older people. Introduction The use of pharmacological agents is often a central component of medical therapy for older people. Although medications have an important role to play in the relief of symptoms, the improve- ment of function, and the prevention of future illness, such agents also have the capacity to inflict great harm. Older people are at particular risk of such harms—​as a result of impaired homeo- static reserve, of altered drug metabolism, and the presence of multimorbidity and consequent polypharmacy—​increasing both exposure to potentially harmful agents and the chance of drug–​ drug interactions. The therapeutic priorities for older, frail people may differ when compared to younger, robust patients; limited life expectancy means that attempts to prolong life may become rela- tively less important than the relief of symptoms and avoidance of side effects and medication burden. This chapter addresses these issues that make prescribing in older people challenging, discusses the important emerging healthcare hazard of polypharmacy, but also offers advice on key principles of prescribing, deprescribing, and decision-​making to ensure appropriate medication use for older people. Pharmacokinetics and pharmacodynamics in old age The physiological changes seen with ageing impact both the me- tabolism and mechanism of action of drugs. This is particularly salient as multimorbidity in older people is often accompanied by polypharmacy. Despite the advances in drug design, computational pharmacology, and modelling, the current state of knowledge is still a very long way away from understanding the rate, extent, and mechanisms of multidirectional drug–​drug, drug–​food, and drug–​disease interactions in whole-​system biology applicable to older people. Furthermore, inter-​racial differences in the response 6.7 Drugs and prescribing in the older patient Miles Witham, Jacob George, and Denis O’Mahony

572 Section 6  Old age medicine to therapy and the presence of genetic polymorphisms mean that our current understanding of pharmacokinetics in older people is primitive at best. The basic tenets of pharmacokinetics (absorp- tion, distribution, metabolism, and excretion) are discussed here, but the reader is reminded that these are simplistic illustrations of processes that in reality are far more complex in the context of multimorbidity and polypharmacy. Pharmacokinetics There are three important changes that occur with ageing which impact on pharmacokinetics. They are (a) a reduction in total body water (b) a reduction in lean body mass, and (c) a relative increase in total body fat. The implications of these changes will be dis- cussed in the following sections. Absorption Ageing results in certain physiological changes that may affect gastrointestinal absorption of oral drugs. Drugs that are admin- istered through an intravenous or intramuscular are not subject to these effects. Some of the effects of altered absorption are due to: • Reduced gastric acid secretion, secondary to atrophic changes seen in gastric mucosa. This is more pronounced in females due to a relatively smaller overall gastric surface area and parietal cell mass. As a general rule, in an acidic environment such as the stomach, acidic drugs (e.g. phenytoin, aspirin, penicillin) will exist in a non​ionic form and therefore are absorbed at a higher rate than basic drugs (e.g. diazepam, morphine, pethidine), be- cause non​ionic molecules pass more easily through the lipid bilayers in cell membranes than ionized molecules. The reduc- tion in stomach acidity may therefore result in higher levels of absorption of basic drugs than might occur in younger people. Conversely, in the small intestinal environment which is largely basic, drugs that are basic are generally better absorbed. • An overall reduction in small bowel absorptive surface area. This occurs equally in both sexes. This results in the reduced absorption of certain nutrients and minerals such as glucose and iron. • Reduced splanchnic blood flow. • Increased atrophy of the gastrointestinal mucosa, with conse- quently reduced enzymatic activity. An example of significant differences in absorption in older people is levodopa, used in Parkinson’s disease. A  reduction in dopa-​ decarboxylase expression in gastrointestinal mucosa results in a prolonged half-​life (t½) and area under the curve (AUC), but not peak drug concentration (Cmax) nor time to peak drug concen- tration (Tmax) in older patients. It is important to consider these alterations, particularly in people who have had previous gastro- intestinal surgery or require tube feeding via naso-​jejunal or per- cutaneous endoscopic gastrostomy feeding. Older patients are also more likely to have peripheral oedema and therefore transdermal and subcutaneous routes of drug de- livery may also be impaired. The presence of intestinal wall oedema in congestive cardiac failure or hypoalbuminemia may reduce ab- sorption of oral medications (e.g. furosemide). The route of delivery of any drug is therefore a particularly important consideration to make when prescribing for older people. Distribution The key factor that alters drug distribution in older people is in- creased fat in proportion to muscle mass. This therefore increases the volume of distribution (Vd) of lipophilic drugs in relation to body weight while hydrophilic drugs (gentamicin, digoxin, ethanol) have lower Vd and therefore higher plasma concentra- tions, making them more liable to cause toxicity at conventional doses. Despite this, the t½ of hydrophilic drugs is often unchanged as renal/​hepatic clearance is often reduced concomitantly. Lipophilic drugs (e.g. haloperidol, amitriptyline, or diazepam) are sequestered in fatty tissue and released at a slow rate, particu- larly after repeated administration. In starvation or other catabolic states, the rate of release of these drugs may accelerate as fat is used as an energy source. Protein binding of drugs is also altered in frail, older people due to the commonly observed reduction in albumin (which is respon- sible for binding of acidic drugs). Therefore free unbound drug levels of acidic drugs such as warfarin, digoxin, and lorazepam tend to be higher in older, frailer patients. α-​1 acid glycoprotein (A1AG), which binds to basic drugs, is often increased in illnesses. This would, in theory, have the effect of lowering free drug concen- trations of basic drugs such as diazepam and morphine. However, the consequence of these changes is not fully understood as the ef- fects of protein binding on free drug concentrations are also de- pendent on hepatic and renal clearance. Metabolism Drugs are mainly metabolized in the liver via phase I (oxidation, hydrolysis, reduction) and phase II reactions such as glucuronida­ tion (which increases water solubility), acetylation and sulphation (which reduce toxicity). The rate of first pass metabolism is thought to decrease with age. The ability of the liver, via first pass metabolism, to extract drugs from the circulation as well as the rate of hepatic blood flow are the major determinants of hepatic drug clearance. Drugs that have high extraction ratios such as propranolol, nifedipine, and pethidine have a higher risk of toxic effects. Non​steroidal anti-​inflammatory (NSAIDs) and opiates are particularly liable to result in toxicity in older people due to a combination of decreased hepatic metabolism and reduced renal excretion. Polypharmacy may lead to cytochrome P450 (CypP450) inter- actions between inducer and inhibitor drugs, which may lead to complex drug–​drug and drug–​food interactions. Excretion Ageing is associated with reduced renal blood flow, tubular secre- tion, and renal mass. The reduction in muscle mass in older frail people also has an impact on the reliability of serum creatinine as a measure of renal function in older people; alternatives that may be of use include measurement of cystatin C. Current recommenda- tions for drugs mainly excreted via the kidneys are for estimated glomerular filtration rate using the Modified Diet in Renal Disease (MDRD) calculation. The Cockcroft and Gault formula used to calculate creatinine clearance may underestimate renal function in older people compared to eGFR calculated by CKD-​EPI and MDRD equations. Excretion of water-​soluble drugs such as di- goxin, lithium, and NSAIDs are disproportionately affected by a

6.7  Drugs and prescribing in the older patient 573 reduction in renal function and therefore more liable to accumu- late to toxic levels when renal function is reduced. Pharmacodynamics The action of a drug on its intended and unintended targets results in its efficacy and/​or adverse effects. Impaired homeostasis and the presence of multiple chronic diseases, coupled with changes in re- ceptor binding or affinity may either augment or blunt the effect of a drug in older people. An example of this would be the use of anti- cholinergic agents in older men with benign prostatic hypertrophy, which may as a side effect cause urinary retention. There are no hard and fast rules that allow for the prediction of altered pharma- codynamics when prescribing in older people. The following are examples of changes that occur during ageing that have clinical im- plications on drug action: • Increased sensitivity to benzodiazepines, tricyclic antidepressants, anticholinergics due to increased volume of distribution and pro- longed half-​life. • Reduced β-​adrenergic receptor mass and sensitivity, therefore reducing catecholamine responsiveness as well as effectiveness of β-​blocker therapy. • Reduced intravascular volume leading to exaggerated hypoten- sive effect of antihypertensive agents. • Increased vitamin K-​dependent factors (II, VII, IX, X) inhibition by warfarin in older people, despite no age-​related differences in pharmacokinetics of warfarin. Suggested mechanisms include increased intrinsic sensitivity of vitamin K to warfarin in older people and the relative deficiency of vitamin K in older people. The mechanism of action for most of these pharmacodynamic adverse effects is unknown. However, the prescriber should ex- ercise increased caution when prescribing drugs in older people that have a narrow therapeutic index (e.g. theophylline, warfarin, lithium, digoxin, aminoglycoside antibiotics) as fragile compensa- tory homeostatic mechanisms may be quickly overwhelmed due to other seemingly unrelated factors such as pre-​existing condi- tions. The advice in prescribing for older people has always been to gradually up-​titrate to effect—​‘start low and go slow’ as discussed next. There is however a concern that this strategy may result in underdosing and a lack of therapeutic effect and therefore regular review for efficacy as well as side effects is warranted. Pharmacology of drug withdrawal The practice of regular medication review is becoming increasingly important. Polypharmacy is a major cause of illness, as is discussed next in more detail. Patients often accumulate new medications with every admission to hospital and in many instances, courses of treatment intended for a limited time or as a trial end up as chronic repeat prescriptions, increasing the potential for adverse drug events and drug–​drug interactions. Medications are also often commenced to treat the side effects of an existing treatment, rather than switching to another agent (e.g. diuretics prescribed for ankle oedema secondary to a dihydropyridine calcium channel blocker). Abrupt withdrawal and rebound effects are often exaggerated in older people due to reduced homeostatic responsiveness and pre-​ existing disease (e.g. abrupt β-blocker withdrawal and increased frequency of angina). Drug withdrawal may be beneficial—​oral hypoglycaemic agents are often linked with hypoglycaemia in older people who have re- duced oral intake. A study of nursing home residents in Sweden showed that the withdrawal of oral hypoglycaemic agents in older patients with tight glycemic control is safe and reduced the risk of hypoglycaemic attacks. Discussions surrounding issues such as long-​term benefits of therapy versus quality of life, end-​of-​life planning, adherence to therapy, and patient preference ought to occur when consid- eration of additional therapy for older people is made. Once a decision is made to reduce therapy, tapering down doses and stopping one medication at a time is ideal, mirroring the ‘start low and go slow’ approach when starting new medications. Long-​ term use of medications such as benzodiazepines can result in physiological tolerance and dependence. Therefore, monitoring of withdrawal symptoms for central nervous system agents in particular, is crucial. Balancing benefits and harms of prescribing What are the aims of prescribing for older people? The central aim of prescribing for older people is to ensure that prescribing is neither avoided nor is needlessly excessive, but is ap- propriate. Appropriate prescribing requires that: • all medicines are prescribed for the purpose of achieving specific therapeutic objectives that have been agreed with the patient • therapeutic objectives are actually being achieved or there is a reasonable chance they will be achieved in the future • therapy has been optimized to minimize the risk of adverse drug events • the patient is motivated and able to take all medicines as intended A hallmark of older people is heterogeneity, not only of physiology and function, but also of health beliefs and expectations. No two older people are the same, and it is critical that this heterogeneity is embraced when making prescribing decisions. Before rational prescribing decisions can be made, clinicians need to be clear about the aims of prescribing for an individual older person. For some older people who are in robust health with good phys- ical function, the aim desired by both patient and clinician may be prevention of future illness—​and the approach to prescribing may be similar to that adopted in younger patients. However, for many older people, life expectancy may be limited, and the burden of side effects relative to benefit may not be favourable—​either due to a lack of benefit, perceived or actual excessive risk or side effects, or a reluctance to add to an already large burden of medicaliza- tion. Still others may not place a high priority on preventing future disease onset, but would still value interventions that forestall de- compensation of existing illnesses, such as heart failure or chronic obstructive pulmonary disease. Clinicians are not adept at antici- pating patients’ perceptions, for example, of their quality of life, hence asking patients and carers about their views and wishes is essential. Therefore the approach to prescribing might vary—​multiple medications for disease prevention together with medications to relieve multiple symptoms may be desirable in the first instance,

574 Section 6  Old age medicine but perhaps an approach characterized by removal of medications and minimization of intervention in the second instance. The first and most important step in appropriate prescribing for older people is therefore to ascertain their expectations, beliefs, and pref- erences for healthcare intervention. Evidence and guidelines Prescribing in younger patients, especially those with single dis- eases, is strongly influenced by evidence collected from random- ized controlled trials, reflected in disease-​specific guidelines. This approach is much less useful in older patients for several reasons. Firstly, most clinical trial evidence is collected in relatively young patients, often with few co​morbidities and taking few other medi- cations. Ageism—​both overt by using upper age limits in trial proto- cols, and covert, via unnecessarily rigid inclusion and exclusion criteria—​remains a significant barrier to providing trial evidence that is applicable to older people, although some progress has been made in recent years. Harms of medications are often poorly re- ported. Although trial evidence may be applicable to some older people, it is a mistake to assume that the balance of risk and benefit in older people is necessarily the same as that seen in trials involving younger people. Older people are usually at higher absolute risk of adverse disease outcomes, hence the absolute benefit of an interven- tion may be greater. However, limited life expectancy may not pro- vide sufficient opportunity for these benefits to be realized. Furthermore, impaired homeostatic reserve, and interactions with other medications mean that the risk of adverse drug events may be correspondingly higher—​and in some cases this may out- weigh any benefits. Thus trial evidence garnered in younger pa- tients must be interpreted with caution in informing prescribing decisions in older people, and the more dissimilar the older person is to the trial population, the less useful the trial results are likely to be. Lastly, most clinical guidelines are focused on single diseases, but older people suffer from multimorbidity and hence single dis- ease guidelines may be unhelpful. Combining some guidelines leads to contradictory advice in patients with multimorbidity, and simply summing the prescribing recommendations from mul- tiple single disease guidelines leads to high medication burdens. Anticholinergic burden is a particularly important example of this; many medications have anticholinergic side effects (including some antidepressants, antipsychotics, antimuscarinics, but also drugs such as ranitidine). Following individual guidelines can easily re- sult in a high cumulative anticholinergic burden, which is associ- ated with an increased risk of falls, cognitive decline, and mortality. The combination of limited life expectancy and multimorbidity also leads to uncertainty as to whether a given medication inter- vention can change the attributable risk of a given condition in frail, multimorbid patients. A lack of time for an intervention to have an effect (e.g. on death) is one aspect of this uncertainty, but the other issue is whether a reduction in death attributable to a given condition (e.g. heart failure) is simply replaced by a different risk (e.g. death from dementia) with no overall gain in life expect- ancy. To answer this uncertainty requires data from trials in frail patients with multimorbidity, but such trial data are lacking, as just discussed. It cannot be assumed that benefits seen in more robust patients with single diseases will translate into benefits for frail, multimorbid patients. Common prescribing risks in older people Although medication side effects can affect any physiological system, there are certain manifestations of harm that are particularly common in older people, and provide a framework for practice. Such effects may be idiosyncratic (comparatively rare in older people), due to off-​target effects (effects on physiological systems other than that intended), or on-​target (adverse effects as a direct consequence of the intended physiological effect of the drug). An example of the first would be a rash due to antibiotics; an off-​target example would be falls due to the central nervous system effect of antimuscarinic medications used for overactive bladder, and an on-​target effect would be bleeding due to anticoagulants. Table 6.7.1 outlines some key medication side effects seen in older people. Table 6.7.1  Selected examples of common harms from medications in older people Clinical problem Medication classes Falls Opioids Benzodiazepines Neuroleptics Antidepressants H1 blockers Hypoglycaemic agents Drugs with anticholinergic effects Anticholinesterase inhibitors Antihypertensives Digoxin Delirium Opioids Benzodiazepines Neuroleptics Antidepressants Drugs with anticholinergic effects Hypoglycaemic agents Steroids Gastrointestinal bleeding NSAIDs Steroids SSRIs Levo-​dopa Anticoagulants Impaired renal function ACEi/​ARB Aldosterone antagonists Diuretics Aminoglycoside antibiotics Trimethoprim Proton pump inhibitors Electrolyte disturbance ACEi/​ARB Aldosterone antagonists Diuretics Trimethoprim Proton pump inhibitors Laxatives Theophylline β-2 agonists Constipation Opiates Drugs with anticholinergic side effects Oral iron Calcium channel blockers Worsening of
heart failure Steroids NSAIDs Tricyclic antidepressants Non​dihydropyridine calcium channel blockers Thiazolidinediones ACEi, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker; SSRI, selective serotonin uptake inhibitor; NSAIDs, non​steroidal anti-​inflammatory drugs.

6.7  Drugs and prescribing in the older patient 575 Principles of prescribing in older people The following principles can help to ensure that prescribing in older people maximizes effectiveness, minimizes risk, and meets the needs and wishes of the patient: • Make the patient central to the decision-​making process and align prescribing goals with those of the patient. • Start low, go slow. Start with the lowest possible dose of medi- cation, give adequate time for the medication to work, and in- crease doses in small increments. If side effects occur, reduce the dose to the previous step. Similarly, when stopping medications, reduce the dose gradually to avoid withdrawal effects; this is of particular importance where rebound physiological effect may occur (e.g. with β-blockers, benzodiazepines, antidepressants, or proton pump inhibitors). • Review prescribing and prescribing goals regularly. In particular, new symptoms or illnesses, changes in physical function, or life expectancy should prompt review as patient priorities, risks and benefits may all change. • If a medication is no longer indicated, stop it. An example of this is the inappropriate long-​term use of proton pump inhibi- tors; many older people take these medications for years despite having no evidence of oesophagitis, active peptic ulceration, or symptoms. Proton pump inhibitor use has been associated with multiple potential harms including increased risks of osteopor- osis, enteric infections, pneumonia, hyponatraemia, hypomag- nesaemia, and microscopic colitis. • Use single medications for multiple benefits. For example, if a patient has angina and heart failure, use a β-blocker as a first-​line agent, as this will have symptomatic benefit for the angina as well as improving symptoms and prognosis for heart failure. • Avoid treating drug side effects with another medication. An ex- ample here is the aforementioned case of ankle oedema caused by dihydropyridine calcium channel blockers. This common side effect is often treated with diuretic therapy, rather than by stop- ping the offending drug; the consequence is often intravascular volume depletion, orthostatic hypotension, falls, and worsening renal function. • Consider non​pharmacological interventions before adding to medication burden. Such interventions may be at least as ef- ficacious, and may carry considerably less risk. For instance, physiotherapy to improve quadriceps strength is a powerful (and underused) way to improve both pain and function in knee osteoarthritis. A  concept that is useful in managing multimorbidity for some older people is to identify the ‘dominant condition’; that is, the illness that impacts overwhelmingly on a patient’s function and quality of life. Examples include advanced dementia, where severe cognitive impairment has an impact far in excess of virtually any other comorbidity, or severe heart failure. Although this concept can help to clarify the thoughts of both the patient and prescriber, it is sometimes difficult to identify a dominant condition, or to disen- tangle which illnesses are causing which symptoms. In such cases, a multifaceted approach to management is essential. In addition, it is worthwhile to try to select interventions that are least disruptive to the lives of older people. This might mean using once-​daily formulations (which may make supervised administration easier), selecting therapies requiring less moni- toring such as blood tests, or scheduling treatments so that side effects do not interfere with daily life (e.g. timing of diuretic doses). Appropriate and inappropriate prescribing in older people Potentially inappropriate prescribing encompasses the three inter-​related areas of misprescribing, overprescribing, and under­ prescribing. Misprescribing occurs when drugs are introduced that heighten the risk of an adverse drug event. Increased adverse drug event risk may be the result of incorrect dose, incorrect frequency, of inappropriate or suboptimal mode of drug delivery or inappro- priate duration of drug therapy. Misprescribing also includes the introduction of drugs that increase the risk of adverse drug–​drug or drug–​disease interaction to an unacceptable level. Overprescribing refers to drug therapy that has no clear indication but is neverthe- less continued without any valid clinical reason. Underprescribing is the omission of appropriate pharmacotherapy for irrational or ageist reasons, resulting in heightened risk to the patient, for example, the omission of long-​term anticoagulant therapy in an older patient with chronic atrial fibrillation and concurrent risk factors for stroke. Potentially inappropriate prescribing also refers to the use of a drug that: • has the wrong indication • has no indication • has a high risk of an adverse drug event (i.e. adverse drug–​drug or drug–​disease interactions) • is unnecessarily expensive • is prescribed for too short or too long a time period The principal risk factors for inappropriate prescribing are polypharmacy and exposure to multiple prescribers. Complex multimorbidity is the principal driver of polypharmacy; indeed, major polypharmacy (i.e. 10 or more daily prescription drugs), may be viewed as the potentially inappropriate prescribing response to complex multimorbidity that results in heightened risk of ad- verse drug–​drug and drug–​disease interactions. This increased risk of iatrogenic morbidity is now the focus of deprescribing interventions, particularly in frailer multimorbid older people with limited prognosis. Tools such as the Screening Tool of Older People’s Prescriptions/​Screening Tool to Alert to Right Treatment (STOPP/​START) criteria can potentially help with identifying and managing inappropriate prescribing. Potentially inappropriate medications and potential prescribing omissions occur frequently in older people in all clinical settings. Recent studies using both STOPP/​START criteria and Beers cri- teria for the detection of both types of events show that poten- tially inappropriate prescribing is commonplace in primary care, hospital care and particularly in extended nursing care settings (Table 6.7.2). While the literature is generally consistent on the high prevalence of potentially inappropriate medications and potential prescribing omissions in older people, it is less clear how best to attenuate their occurrence. This uncertainty about how to tackle potentially in- appropriate medications may, in part, arise from the lack of clear association between potentially inappropriate medications that are defined by Beers criteria and occurrence of adverse drug events in

576 Section 6  Old age medicine large scale studies in the last decade. In contrast, there is a clear association between STOPP criteria-​defined potentially inappro- priate medications and adverse clinical outcomes, such as adverse drug events, or decline in physical function in older people who are hospitalized with acute illness. STOPP criteria have been used as an intervention in prospective randomized clinical trials in older people with interesting results. STOPP/​START criteria when applied at a single time point to the medication lists of hospitalized acutely ill older people resulted in highly significant improvement in medication appropriate- ness at discharge. The application of STOPP/​START criteria also improved underutilization of medication to a highly significant degree at discharge. Importantly, the marked improvements in medication appropriateness and underutilization were maintained at 6 months’ follow-​up in the intervention population compared to control patients who experienced no significant change throughout the study from randomization to end of follow-​up. The number of patients needed to ‘treat’ with STOPP/​START criteria to produce improvement in medication appropriateness (measured using the Medication Appropriateness Index) was just 3 (absolute risk reduc- tion in inappropriate medication was 35.7%); the number of pa- tients needed to treat (NNT) to produce a reduction in underuse of appropriate medication was 5. In another trial involving 359 older residents of a long-​term care facility in Israel, application of the STOPP/​START criteria at baseline, at 6 and 12 months was compared to standard pharma- ceutical care. Patients in the intervention group experienced significantly lower numbers of daily prescription medicines, sig- nificantly lower monthly prescription costs, and significantly fewer falls compared to control patients. A  further trial involving acutely ill hospitalized older people evaluated the effect of STOPP criteria recommendations made by a specialist inpatient geriatric consultation team to attending physicians to discontinue potentially inappropriate medications in addition to the standard geriatric assessment and advice. Control patients received standard geriatric assessment and advice only. The intervention group had twice as many patients with reduction of potentially inappropriate medications at discharge (39.7%) as the control group (19.3%). A  fourth trial examined the effect of a single application of STOPP/​START criteria to medication lists within 48 hours of hospital admission on incident adverse drug reactions during the index hospitalization in unselected older people with acute un- selected acute illness. Patients under the care of specialist teams, other than Geriatric Medicine, Clinical Pharmacology, Palliative Medicine, and Oncology were eligible for randomization. The re- sults showed a highly significant reduction in incident adverse drugs reactions in the intervention group (12.5%) compared to the control group (23.9%); the absolute risk reduction of 11.4% meant that the number of patients needed to treat to prevent one older patient experiencing a non​trivial incident adverse drug reaction was 9.  In the same study, the median monthly medication cost was significantly lower in the intervention group compared to the control group. In contrast to the randomized controlled trial evidence sup- porting the clinical relevance of STOPP/​START criteria, there is no current trial evidence showing that application of Beers criteria as a clinical intervention results in better clinical outcomes. Other tools (e.g. the Fit fOR The Aged (FORTA) tool) are also being developed and are currently being evaluated in trials. Deprescribing in older people Deprescribing can be defined as ‘the systematic process of identifying and discontinuing drugs in instances in which existing or potential harms outweigh existing or potential benefits within the context of an individual patient’s care goals, current level of functioning, life expectancy, values, and preferences’. A review of 31 studies of drug withdrawal in patients aged 65 years and over concluded that antihypertensive, psychotropic and benzodiazepine medications could be withdrawn safely in 20–​100% of cases. An Australian study of older patients taking antihypertensive medica- tion demonstrated that over one-​third of patients had normal blood pressure one year after discontinuation of antihypertensive therapy. Another study involving community-​based patients on long-​term benzodiazepines showed that an education programme provided and sustained by community pharmacists led to a reduction in benzodiazepine use of over three-​quarters without serious with- drawal problems. Importantly, results in those aged over 80 years and those taking ≥10 daily drugs were no worse than other groups. In two recent complementary Cochrane systematic reviews, deprescribing has been shown to be beneficial in older people. Among frailer older people, deprescribing appeared to be most effective when there was a combination of physician medication review and a proactive palliative approach to pharmacotherapy involving collaboration with patients, their relatives, and primary care physicians. In one study in Israel, applying an algorithm for proactive deprescribing in nursing home residents led to two-​ thirds of patients taking three drugs per patient less without pa- tient detriment. In the same study, one-​year mortality and acute hospitalization rates in intervention patients was approximately half those of control patients. A structured approach to deprescribing has been described as follows:

  1. Full medication reconciliation (i.e. determine all drugs taken by the patient and why).
  2. Estimate overall drug-​related risk in the patient.
  3. Consider each drug as a possible candidate for exclusion on the basis of: (a) Valid indication (b) Being prescribed to counteract the adverse effects of another drug (prescribing cascade) Table 6.7.2  Prevalence of potentially inappropriate medications and potential prescribing omissions in various clinical settings Primary care Hospital Nursing home Potentially inappropriate medication prevalence (STOPP criteria, version 1) 21% 34–​50% 60–​70% Potentially inappropriate medication prevalence (Beers criteria, version 3) 13–​18% 25–​32% 37–​53.4% Potential prescribing omission prevalence
    (START criteria, version 1) 22.7% 57.9% 70%

6.7  Drugs and prescribing in the older patient 577 (c) Actual/​potential harm of a drug exceeding actual/​potential benefit (d) Loss of efficacy or symptoms completely resolved (e) Likelihood to yield benefit during the patient’s estimated re- maining lifespan (f) Overall medication burden 4) Prioritization of drugs to remove from the patient’s prescription. 5) Proceed with and monitor structured drug discontinuation programme, removing one drug at a time and observing for overall improvement or worsening of the patient’s condition. Other interventions for improving prescribing in older people There are several other ways of improving the overall quality of prescribing in older people. These include:

  1. Comprehensive geriatric assessment (CGA), which includes structured scrutiny of older patients’ medications, their mode of delivery and acceptability, and adherence.
  2. Structured pharmacist review of medication with feedback to prescribers. This can occur as an opportunistic review (level 0), can be limited to a technical review to remove unused items or switch to more cost-​effective items (level 1), a review of medi- cations and conditions with patient notes (level 2), or a full re- view with both notes and the patient present (level 3). Given the complexity of prescribing in older people, level 3 reviews are to be preferred.
  3. Clinical decision support software systems with automated screening for adverse drug–​drug and drug–​disease interactions.
  4. Medication adherence interventions. The evidence base to support the overall clinical relevance of comprehensive geriatric assessment is now very strong indeed (see Chapter 6.4). Two recent systematic reviews of the efficacy of comprehensive geriatric assessment in the acute hospital setting concluded that it significantly reduces mortality, nursing home re- quirement, functional dependency, and re-​admission. The positive impact of pharmacist delivered medication review is stronger when it is delivered in the context of multidisciplinary team working. Computerized physician order entry and clinical decision support system approaches to prescribing optimization have been in exist- ence for approximately 20 years with varying efficacy when applied to older patients. The impact of various interventions to improve medication ad- herence in older people has been evaluated by meta-​analysis and systematic review. Several interventions such as medication review, written and verbal patient education, drug regime simplification, drug administration aids, patient-​friendly packaging and label- ling, medication reminders, home visits, and follow-​up have been shown to significantly improve medication adherence. However, the impact of these adherence-​promoting interventions on positive health outcomes and health service utilization is unclear. Conclusion Safe and effective prescribing in older people requires both ex- pert knowledge of drug effects, side effects, and interactions, but also in-​depth knowledge about a patient’s multimorbidity, life ex- pectancy, and their therapeutic agenda. Adverse drug events are a major source of ill-​health, and unthinking adherence to disease-​ based guidelines is unlikely to provide overall benefit to older people’s health, function, or quality of life. Careful consideration of the aims of new prescribing, a cautious approach to uptitration of medication, use of non​pharmacological alternatives, regular re- view, and deprescribing form the basis of a safe and effective ap- proach to prescribing in older people. The use of appropriateness tools such as the STOPP/​START criteria can help to improve the quality of prescribing for older people, and the use of such tools along with comprehensive assessment, decision support software and the expert input of pharmacy staff can help prescribers to navi- gate the often difficult passage between overtreatment and thera- peutic nihilism. FURTHER READING Alldred DP, et  al. (2013). Interventions to optimise prescribing for older people in care homes. Cochrane Database Syst Rev, 2, CD009095. Dumbreck S, et  al. (2015). Drug–​disease and drug–​drug inter- actions:  systematic examination of recommendations in 12 UK national clinical guidelines. BMJ, 350, h949. Ellis G, et al. (2011). Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database Syst Rev, 7, CD006211. Frankenthal D, et al. (2014). Intervention with the screening tool of older persons potentially inappropriate prescriptions/​screening tool to alert doctors to right treatment criteria in elderly residents of a chronic geriatric facility: a randomized clinical trial. J Am Geriatr Soc, 62, 1658–​65. Gallagher PF, O’Connor MN, O’Mahony D (2011). Prevention
    of potentially inappropriate prescribing for elderly patients:  a randomized controlled trial using STOPP/​START criteria. Clin Pharmacol Ther, 89, 845–​54. Habicht DW, Witham MD, McMurdo ME (2008). The under-​ representation of older people in clinical trials: barriers and poten- tial solutions. J Nutr Health Aging, 12, 194–​6. Hughes LD, McMurdo ME, Guthrie B (2013). Guidelines for people not for diseases: the challenges of applying UK clinical guidelines to people with multimorbidity. Age Ageing, 42, 62–​9. Iyer S, et  al. (2008). Medication withdrawal trials in people aged 65 years and older: a systematic review. Drugs Aging, 25, 1021–​31. Kuhn-​Thiel AM, Weiss C, Wehling M (2014). Consensus validation of the FORTA (Fit fOR The Aged) List: a clinical tool for increasing the appropriateness of pharmacotherapy in the elderly. Drugs Aging, 31, 131–​40. Lugtenberg M, et al. (2011). Current guidelines have limited applic- ability to patients with comorbid conditions: a systematic analysis of evidence-​based guidelines. PLoS One, 6, e25987. O’Connor MN, Gallagher P, O’Mahony D (2012). Inappropriate prescribing: criteria, detection and prevention. Drugs Aging, 29, 437–​52. O’Connor MN, et al. (2016). Prevention of hospital-​acquired adverse drug reactions in older people using STOPP/​START criteria:  a cluster randomized controlled trial. J Am Geriatr Soc, 64, 1558–​66. O’Mahony D, O’Sullivan D, Byrne S. STOPP/​START criteria for potentially inappropriate prescribing in older people: version 2.

578 Section 6  Old age medicine Patterson SM, et al. (2012). Interventions to improve the appropriate use of polypharmacy for older people. Cochrane Database Syst Rev, 5, CD008165. Pearlman RA, Uhlmann RF (1988). Quality of life in chronic dis- eases: perceptions of elderly patients. J Gerontol, 43, M25–​M30. Rudolph JL, et al. (2008). The anticholinergic risk scale and anticholin- ergic adverse effects in older persons. Arch Intern Med, 168, 508–​13. Scott IA, et al. (2015). Reducing inappropriate polypharmacy: the process of deprescribing. JAMA Intern Med, 175, 827–​34. Spinewine A, Fialova D, Byrne S (2012). The role of the pharmacist in op- timizing pharmacotherapy in older people. Drugs Aging, 29, 495–​510. Topinkova E, et al. (2012). Evidence-​based strategies for the opti- mization of pharmacotherapy in older people. Drugs Aging, 29, 477–​94. Tosato M, et al. (2014). Potentially inappropriate drug use among hospitalised older adults:  results from the CRIME study. Age Ageing, 43, 767–​73. van der Cammen TJ, et al. (2014). Drug cessation in complex older adults: time for action. Age Ageing, 43, 20–​5. Wilson M, et al. (2015). Prescribing to fit the needs of older people—​ the NHS Scotland Polypharmacy Guidance, 2nd edition. J R Coll Physicians Edinb, 45, 108–​13.

6.8 Falls, faints, and fragility fractures 579

6.8 Falls, faints, and fragility fractures 579

ESSENTIALS Falls and their complications are the fifth leading cause of deaths in older adults. They typically result from the interplay of the envir- onment, co​morbidity, and age-​related changes in postural stability. Recurrent falls can be debilitating in terms of physical consequences and in terms of the psychological impact of fear of falling, resulting in restriction of activity leading to a spiral of deconditioning, further loss of function, low mood, depression, and social isolation. Since some falls can be prevented, all older people in contact with healthcare professionals should be asked routinely whether they have fallen in the past year. Patients reporting single falls should undergo gait and balance assessments to identify those with higher risk who may benefit from a multifactorial falls risk assessment, which is required by those reporting two or more falls, or difficulties with gait and balance, and by any older patient who seeks medical attention as the result of a fall. Management requires a multifactorial approach, directed by the relevant contributors determined in the assessment process. The aim should be to prevent future falls and minimize their consequences, while avoiding imposing restrictions to the point that they negatively impact function, independence, and quality of life. The incidence of syncope is 11 events per 1000 person years over the age of 70 years, and is a differential diagnosis in older adults with unexplained falls. Orthostatic hypotension is a common cause in older people, treatment of which includes elimination of contrib- uting medications when possible, increased salt intake, increased fluid intake, and advice to rise slowly from a seated or lying position. Fragility fractures occur as the result of low energy mechanical forces that under usual circumstances would not result in a fracture, and all patients at risk of falls should undergo a bone health assess- ment and determination of their future risk of major fracture, with treatment of osteoporosis when appropriate. Introduction A fall is defined as ‘an unexpected event in which the participants come to rest on the ground, floor, or lower level’. Falls are common in older adults with one in three adults over the age of 65 years sustaining at least one fall per year, increasing to one in two for the over 80s. The incidence is similar in men and women, but women are more likely to sustain an injury. Falls have significant conse- quences with 2–​5% resulting in fractures, up to 10% serious injury and hospitalization, along with loss of confidence, functional in- dependence, and an associated increased likelihood of a move to institutional care. Falls and their complications are the leading cause of death from injury in adults over 65 years and the fifth leading cause of all deaths in older adults. They also have a considerable economic cost accounting for an estimated £2 billion of healthcare spend in the United Kingdom annually, and $34 billion in the United States in 2013. This chapter will examine the risk factors for falls in older adults and the role of comprehensive assessment and multifactorial interventions to reduce the risk of future falls. This will include evaluation and treatment of orthostatic hypotension and carotid sinus syndrome and their relationship to falls in older adults. The association between falls and fragility fractures will be considered and controversies relating to calcium and vitamin D supplemen- tation and the use of anticoagulants in those at high risk of falling will be discussed. Consequences of falls The consequences of falls range from none or minor injuries to severe such as hip fracture, head trauma, and death due to the in- juries sustained. Recurrent falls can be debilitating both in terms of physical consequences but equally in terms of the psycho- logical impact of fear of falling, resulting in moderate restriction of activity in up to two-​thirds of those affected. Fear of falling following a hip fracture is associated with an increased risk of institutionalization and mortality. Only half of older people who fall can get up unaided, frequently leading to prolonged periods on the ground or a ‘long lie’, which in turn can result in develop- ment of pressure ulcer, rhabodomyolyis, and renal failure, hypo- static pneumonia, and additional loss of function. Older patients will frequently limit their mobility and activity in an effort to minimize their risk of falls, which can result in them dropping 6.8 Falls, faints, and fragility fractures Fiona Kearney and Tahir Masud

580 Section 6  Old age medicine outside activities, hobbies, and social outlets, leading to a spiral of deconditioning, further loss of function, low mood, depression, and social isolation. Risk factors Falls in older adults are rarely due to a single cause (Table 6.8.1). Most result from the interplay of the environment, co​morbidity, and age-​related changes in postural stability. A history of previous falls, particularly two or more falls in the preceding year, is the most powerful predictor of future falls. Other risk factors can be divided into intrinsic and extrinsic. Intrinsic factors include age, gender, disability, and co​morbidity. Extrinsic risk factors largely relate to the domestic and outdoor environments, medications, and mobility aids. The risk of falling increases as the number of risk factors increases. The contribution of individual risk factors varies ac- cording to the population and setting, highlighting the multi- factorial nature of causation. In a systematic review, gait and balance impairments and medications are the most consistent risk factors for falls. Intrinsic risk factors Co-​morbidity An increased incidence of falls has been described in a var- iety of chronic medical conditions including, but not limited to, Parkinson’s disease (PD), stroke, osteoarthritis, ischaemic heart disease, heart failure, chronic obstructive pulmonary disease, de- pression, osteoporosis, and diabetes. The nature of the association is often unclear, but likely reflects the added burden of chronic dis- ease and treatments on the homeostatic mechanisms maintaining postural stability. The risk for falls increases with increasing number of chronic conditions. Cardiac arrhythmias, impaired autoregulation of blood pressure, or hypotension secondary to antihypertensive medications can lead to transient cerebral hypoperfusion and falls. Orthostatic hypotension and syncope are considered in more detail later. Parkinson’s disease has a multifactorial association with falls through the abnormal walking pattern associated with bradykinesia, rigidity, and the characteristic shuffling gait, but also as a consequence of the increased incidence of orthostatic hypotension due to the disease and treatment. There is also a tem- poral relationship between Parkinson’s disease and falls medi- ated by cognitive impairment and executive dysfunction. Patients with stroke have an impaired reaction to loss of balance, in add- ition to motor impairments and the need for mobility aids fol- lowing a stroke. Osteoarthritis is associated with joint deformity and pain that impairs mobility and a person’s ability to negotiate obstacles. Peripheral neuropathy is associated with impaired balance and stability partially explaining the increased risk of falls associated with diabetes. Gait and balance impairments Maintaining postural stability at rest and during the dynamic activity of walking requires the complex integration of sensory and motor information regarding the position of the body rela- tive to the surroundings and the ability to generate forces to control body movement, particularly during times of challenge. Integration of the sensory and motor system occurs at a higher cortical level in the brain. Deficits in any component such as peripheral sensation, proprioception, visual or vestibular func- tion, cognition, muscle coordination or strength can result in increased postural sway and poor balance. Age-​related changes or disorders such as cerebrovascular disease contribute to these deficits. Reduced gait speed and unstable gait are associated with falls. Automated devices now enable evaluation of a vast array of gait parameters, including cadence, step length, and stride to stride consistency. A  small degree of fluctuation is present in normal adults, including healthy older adults, but there are changes in dy- namic gait responses, such as stepping over obstacles. Gait vari- ability is associated with increased falls risk and is altered in frailty and neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Gait can also be considered in broader clinical terms and clas- sified according to where in the neuromuscular network the problem is felt to arise. Using this hierarchical system, a primary gait disorder may be due to a progressive central neurological condition arising in the cerebral cortex (higher level gait dis- order), midbrain, cerebellum, or spinal cord (middle level gait disorder) or peripheral nervous system and/​or the result of a musculoskeletal condition (lower level gait disorder). Common clinical causes and the associated gait features are outlined in Table 6.8.2. Muscle weakness Lower limb muscle weakness of knee extension and ankle dorsifexion in particular is associated with falls. It may arise as a consequence of age-​related changes or wasting of muscle groups due to associated osteoarthritis. Clinically this may present with difficulty standing from a seated position. Table 6.8.1  Risk factors for falls in older adults Intrinsic Extrinsic Female gender Advancing age Co-​morbid conditions • Cardiovascular disease including orthostatic hypotension and syncope • Parkinson’s disease • Stroke • Sensory impairments/​peripheral neuropathy • Osteoarthritis/​rheumatoid arthritis Gait and balance impairment Muscle weakness/​myelopathy Cognitive impairment/​impaired executive function Visual impairment Psychological factors •​ Depression •​ Fear of falling Nutritional deficiencies Home trip hazards Bifocal lenses Medications/​ Polypharmacy Alcohol Mobility aids Inappropriate footwear Institutional care

6.8  Falls, faints, and fragility fractures 581 Cognitive impairment Cognitive impairment at least doubles falls risk. There is a height- ened association in those with poor executive function or decision-​ making skills, because gait is not in fact an automatic motor activity but is a learned complex motor task requiring attention. As an individual’s cognitive capacity declines so too does their cap- acity to adequately allocate attention to walking. Reduced capacity for attention results in an increased risk of falls. This is exemplified by the ‘stops walking when talking’ phenomenon, first reported in 1997, where an individual stops walking when engaged in a sec- ondary attention demanding activity, indicating impaired cap- acity to dual-​task. In fact dual-​task impairment is associated with a fivefold increased risk of falls. Dual-​task impairment is thought to clinically represent the inability to appropriately divide attention between two cognitively demanding tasks, and failure to prioritize upright posture or walking when distracted, leading to increased postural sway and gait variability, in turn leading to falls. Executive function also relates to decision-​making, planning, and judgement, and if impaired, may lead to an individual making unsafe decisions about mobilization such as not waiting for as- sistance due to lack of insight into deficits, forgetting to use mo- bility aids or using them unsafely, or failing to adapt to challenges posed by obstacles, low lighting, or changes in surface. Also, it is interesting to note that declines in gait speed and stability have pre- dicted cognitive decline in older adults. The association may reflect a shared anatomical substrate rather than a causative relationship. Visual impairment Falls are associated with a spectrum of visual impairment. As well as reduced visual acuity, visual field defects, impaired depth perception, and contrast sensitivity are implicated. The common conditions of cataract, macular degeneration, and glaucoma pro- duce one or more of these deficits. Bifocal and varifocal lenses used to compensate for visual acuity impairments are also associated with falls due to their impact on depth perception and contrast sensitivity for obstacles. Cataracts are associated with an increased risk of falls, borne out by the reduction in rate of falls following ex- pedited first cataract surgery. Psychological factors Depression is associated with altered gait dynamics and an in- creased risk of falls. Impaired executive function is thought to me- diate, in part, this relationship between depression and falls. Up to 70% of recent fallers and 40% of people who have not fallen re- port fear of falling. Fear of falling is associated with poorer physical performance, slower gait, and reduced muscle strength, likely due in part to the self-​imposed restriction to activity and function by those with fear of falling. Fear of falling predicts falls at one year making it both a risk factor for and a consequence of falls. Nutritional deficiencies Poor nutrition, evidenced by a low body mass index and reduced muscle mass is associated with falls. Vitamin D deficiency is asso- ciated with muscle weakness and increased postural sway. Extrinsic risk factors Medications and falls Polypharmacy (≥4 drugs) is an independent risk factor for falls. Increasing numbers of medications in addition to recent dose changes are associated with falls, but so too is poor medication Table 6.8.2  Neuromuscular classification of gait disorder Level at which gait abnormality arises Associated conditions Gait features Higher level Cerebrovascular disease and dementia Apraxic gait Difficulty initiating walking Small shuffling steps (‘marche a petit pas’) Occasional freezing and difficulty turning Lacks other typical features of Parkinsonism (tremor and rigidity) Stroke Hemiplegic with circumduction of the hip on affected side Normal pressure hydrocephalus Broad-​based gait Middle level Cerebellar Disease Broad-​based gait Cerebellar ataxia Parkinson’s disease (dopamine deficiency in
basal ganglia) Parkinsonism (cerebrovascular disease or medications) Shuffling festinant gait Small steps Stooped posture Difficulty turning Freezing Spinal cord lesions Multiple sclerosis Paraplegic gait/​Scissoring gait Lower level Peripheral neuropathy Distal weakness Poor dorsiflexion Foot drop Occasionally broad-​based with sensory ataxia and positive Romberg’s test Osteoarthritis Antalgic/​limping gait Myopathy Difficulty climbing stairs or rising from a seated position Myopathic/​waddling gait

582 Section 6  Old age medicine compliance. In particular, drugs affecting the central nervous system and drugs moderating blood pressure or heart rate are most frequently implicated in falls. Antipsychotic medications (odds ratio (OR) of falls 1.6), benzodiazepines (OR 1.6), and antidepressants (OR 1.7) including newer selective serotonin reuptake inhibitors, are the most common drugs associated with falls. People taking two or more psychotropic medications are at an even greater risk of falls. Antihypertensive medications are associated with a 20% increased risk of falls, with stronger associations for vasodilator medications and weaker associations for diuretics and β-blockers. Alcohol An increased risk of falls is associated with excessive alcohol intake but not with alcohol consumption within the recommended limits. Environmental The evidence for environmental factors as an independent pre- dictor of falls is mixed. Hazards such as loose carpets, slippery floors, ill-​fitting footwear, poor lighting, and unsuitable mobility aids are likely most relevant for an individual with relevant in- trinsic risks such as poor sight, balance, or cognition. Institution dwellers Being resident in a care home or similar facility is associated with a threefold increased risk of falls compared to a community-​dwelling older population. Fall rates may be even higher among mobile care home residents as rates decrease among very frail bed-​bound residents unable to rise from a chair unaided. The prevalence of dementia and long-​tem conditions in this group will account for some of the associated increased risk of falls. Presentation Individuals will typically describe the immediate nature of a fall at presentation (trip, slip, ‘legs gave way’, and so on) or present with an injury as the consequence of a fall. Up to 80% of falls that do not result in injury are not reported. This may be due to poor recall and cog- nitive impairment, unwillingness by the individual to be considered frail, or the misconception that falling is a normal part of ageing. Since some falls can be prevented, all older people in contact with healthcare professionals should be asked routinely whether they have fallen in the past year and asked about the frequency, context, and characteristics of the fall(s). Patients reporting single falls should undergo gait and balance assessments to identify those with higher risk who may benefit from a multifactorial falls risk assessment. Patients reporting two or more falls, those who re- port difficulties with gait and balance, and any older patient who seeks medical attention as the result of a fall, are also regarded as at higher risk and require further assessment. Multifactorial assessment History Assessment begins with a comprehensive history eliciting the fre- quency of falls, the circumstances in which the fall(s) occurred, prodromal symptoms, and injuries sustained. Injurious falls are more often associated with loss of consciousness and may point to an underlying cardiac aetiology or diagnosis of syncope. Patients with observed syncope may deny loss of consciousness, but will be generally unable to adequately describe the fall itself. A collateral history should be obtained if available, as up to one-​third of older adults without cognitive impairment will not recall the events surrounding a fall three months later. A  comprehensive review of past medical history and comorbidities may reveal the cause of, or potential contributors to, the fall. Diagnoses and their association with falls are out- lined in Table 6.8.3. Medication review A detailed review of medication and their potential contribution to falls should be completed. Table 6.8.4 lists the common medi- cations associated with falls and the proposed mechanism through which they increase this risk. Physical examination Physical assessment encompassing all major systems is focussed on determining previously undiagnosed problems in addition to evaluating the severity of existing co​morbidity and extent to which Table 6.8.3  Clinical diagnoses and their association with falls System Condition Association with falls Neurological Stroke Gait/​balance/​mobility Muscle strength Visual field defects Central processing/​cognitive impairment Parkinson’s disease Gait/​mobility Orthostatic hypotension Cognition/​executive dysfunction at later stages Multiple sclerosis Gait/​mobility Dementia Impaired decision-​making Gait abnormalities Vision Cataracts Glaucoma Macular degeneration Visual impairment Bifocal lenses Impaired depth perception Vestibular disorders Labyrinthitis Meniere’s disease Balance impairment Dizziness Cardiovascular Syncope Loss of consciousness Orthostatic hypotension Dizziness Loss of consciousness Ischaemic heart disease Arrhythmias Medications Endocrine Diabetes mellitus Sensory neuropathy Visual impairment Hypothyroidism Muscle weakness Musculoskeletal Osteoarthritis Joint pain and deformity Rheumatoid arthritis Joint pain and deformity Urinary Urinary frequency/​ urgency Rushing to the toilet Nocturia Vitamin deficiencies Vitamin B12 deficiency Impaired proprioception Vitamin D deficiency Impaired muscle strength Increased postural sway

6.8  Falls, faints, and fragility fractures 583 it is contributing to falls. Neurological examination should test the central and peripheral nervous system in addition to the cerebellum. An examination of the extremities should assess muscle bulk and function, joint deformities, and sensory neuropathies. Asking a patient to walk will reveal information not only about strength, balance, and muscle function, but also about gait patterns associated with certain conditions outlined in the earlier sections. Nystagmus, if present, should be differentiated as to whether it is likely arising from a central (cerebellar) or peripheral (vestibular) problem. Tests of visual acuity (e.g. Snellen Chart) and an eye examination to ascertain the presence or absence of cataracts should be com- pleted. Some specialized clinical-​based assessments include con- trast sensitivity. Cardiovascular examination should assess heart rate and regu- larity of rhythm, and establish the presence or absence of murmurs that may be associated with syncope, such as severe aortic sten- osis. Lying and standing blood pressures consistent with standard testing protocols (Box 6.8.1) should be completed. Orthostatic hypotension is defined as a symptomatic systolic blood pressure (BP) drop of 20 mm Hg (or to below 100 mm Hg) or a diastolic BP drop of 10 mm Hg within three minutes of standing. A standard test of cognition should be incorporated into falls assessment to assess the degree of cognitive deficit (if there is estab- lished cognitive impairment) and also to identity cognitive impair- ment not recognized prior to the presentation with a fall. Review of footwear, walking aids, and—​for higher-​risk individuals—​the home environment, should also be completed. Several questionnaire type tools are available and used by occu- pational therapists to assess the likely role of home hazards, which may help target limited home visiting capacity on those most likely to benefit. There is evidence that falls can be prevented using a hazard checklist combined with observation in the home environ- ment, specifically by an occupational therapist, to understand and modify the fall risks associated with performance of activities of daily living (ADL). Functional assessment Several functional assessments aim to establish falls risk. While this exemplifies the importance of reliably ascertaining falls risk, it also serves to highlight that there is no single optimal test for this purpose. The Timed Up and Go Test (TUG) is a simple test of strength and mobility that constitutes the time taken for a patient to stand from a seated position without using their arms, walk 3 metres, turn around, and return to the seated position. Reference ranges for average performances within age groups have been established, but definitive cut-​offs have been difficult to define in terms of asso- ciated risk of falls, hence its value lies in its simplicity to perform and as a prompt to additional assessment when very abnormal. Additional specialized assessments are detailed in Table 6.8.5. Most of these require specialist training, with some of them taking up to 45 minutes to complete, limiting their utility outside of a dedicated falls clinic. Investigations Routine blood investigations may identify the possible contribu- tion of intercurrent illness such as infection to the presentation. More chronic issues such as electrolyte disturbances leading to muscle weakness, or anaemia leading to fatigue and dizziness, may also be detected. Vitamin D levels should be measured in older people who are frail, housebound, institutional residents, or members of ethnic groups with darker skin living in cooler cli- mates (e.g. South Asians in United Kingdom). Those individuals with low levels may benefit from vitamin D supplementation. Additional investigations are driven by the history or suspected underlying aetiology, such as electrocardiograms (ECG), echocar- diography, and 24-​hour ECG monitoring if a cardiac arrhythmia or valvular lesions are implicated, or head-​up tilt testing if syncope is suspected. Brain or spinal cord imaging with computed tomog- raphy or magnetic resonance imaging scanning may be indicated if pathology of the central nervous system is suspected, but not routinely. Table 6.8.4  Medications associated with falls Drug Indication Association with falls Antihypertensives Hypertension Hypotension Postural hypotension Diuretics Hypertension Heart failure Postural hypotension Muscle weakness due to electrolyte disturbance Requiring repeated trips to the toilet or rushing to the toilet SSRIs Depression Unknown mechanism; possible postural hypotension Antiarrhythmic Atrial fibrillation Tachyarrhythmia Heart block Cardiac pause Pro-​arrhythmic Benzodiazepines Anxiety Insomnia Sedation Confusion Tricyclic antidepressants Depression Pain Sedation Confusion Postural hypotension Anticholinergics Lower urinary tract symptoms Confusion α-blockers Hypertension Benign prostatic hypertrophy Postural hypotension Antipsychotics Primary psychiatric disorders Depression Behavioural and psychological symptoms of dementia Sedation Confusion Extrapyramidal side effect Sedation Impact on QT interval leading to arrhythmia Opiates Pain Sedation Confusion Box 6.8.1  Protocol for measurement of lying and standing blood pressure Lying and standing blood pressures Patients rest in the supine position for at least five minutes. Blood pres- sure is checked while supine and the patient then stands. Blood pres- sures are repeated at 1 minute, 3 minutes, and 5 minute intervals while standing using a standard sphygmomanometer.

584 Section 6  Old age medicine Investigation and management of syncope Syncope is defined as a transient loss of consciousness due to tran- sient global cerebral hypoperfusion, characterized by rapid onset, short duration and complete (spontaneous) recovery (see also Chapters  16.2.2 and 16.4). Syncope is common in older adults, with an incidence of 11 events per 1000 person years over the age of 70  years, and is a differential diagnosis in older adults with unexplained falls. Key questions in the history include information about pre­ cipitating factors (cough, eating, micturition), posture or position (lying, standing), activity at time of event, the presence of pro- dromal symptoms (dizziness, lightheadedness, nausea), past med- ical history (cardiac disease, arrhythmias, postural hypotension), family history of sudden death, and drug history with particular focus on medications affecting blood pressure, heart rhythm, or QT interval. An eyewitness account, if available, may give key in- formation about the events immediately before (posture change, pallor), the duration of the episode, any associated features (myo- clonic jerks), and the recovery period. Orthostatic hypotension Pathophysiology Orthostatic hypotension (OH) and carotid sinus disease subtypes of neurally mediated syncope will be considered here as they are the commoner explanations in older adults who present with a fall. Orthostatic hypotension may occur as a consequence of impaired vasoconstriction due to chronic impairment of autonomic ac- tivity. The prevalence of orthostatic hypotension is approximately 6% in community-​dwelling older adults, but varies depending on the populations assessed. Impaired ability to increase sys- temic vascular resistance (SVR) in response to orthostatic stress is the most common associated pathophysiological defect. This usually reflects reduced α1-​adrenegic receptor responsiveness in older adults, whereby decreased venous return and stroke volume accompanying orthostasis are not counterbalanced by an increase in systemic vascular resistance, leading to diminished cardiac output, subsequent transient cerebral hypoperfusion, and syncope. Additional mechanisms that can contribute include loss of ar- terial compliance, disturbed cerebral autoregulation, reduced plasma volume secondary to reduced plasma renin activity, and ad- renergic receptor dysfunction. Patients with orthostatic hypoten- sion may present with presyncope occurring for the same reasons but not resulting in loss of consciousness. These patients frequently use terms such as dizziness, lightheadedness, giddiness, or weak- ness to describe their symptoms. Medications are a major contributor to orthostatic hypotension in older adults. Antihypertensive medications and those affecting the cardiovascular system are most frequently implicated, but cen- trally acting medications such as phenothiazines and antidepres- sants may also have a role. Causes of orthostatic hypotension are broadly catergorized as drug-​induced (antihypertensive and vasodilator medications, diuretics, phenothaizines, antidepres- sants and Levodopa), primary autonomic failure (pure autonomic failure, Parkinson’s disease, multiple system atrophy, dementia with Lewy bodies), secondary autonomic failure (diabetes mellitus, amyloidosis, spinal cord injuries, uraemia), or volume depletion (haemorrhage or dehydration). Diagnosis and investigation In order to make diagnostic assessment of orthostatic hypoten- sion more uniform, head-​up tilt testing is increasingly relied upon to confirm an initial clinic diagnosis of orthostatic hypotension. Patients undergo passive posture change on a mechanized table, from a horizontal beginning point to an upright position of ≥60 degrees. When combined with phasic blood pressure assessment using digital artery photoplethysmography, beat to beat blood pressure changes can be captured. It also allows indirect, non-​ invasive calculation of several cardiovascular variables, such as systemic vascular resistance, stroke volume, and cardiac output, Table 6.8.5  Gait and/​or balance assessment tools Scale Description Timed Up and
Go Test •​ Time taken to stand from a seated position without using arms, walk 3 metres, turnaround, and return to the seated position •​ Reference ranges for average performance have been established in meta​ analyses with a mean of 8.1 seconds for 60–​69 ​year ​olds, 9.2 seconds for 70–​79 year ​olds, and 11.3 seconds for 80–​99 ​year ​olds •​ Cut ​offs of 13.5–​15 seconds have distinguished fallers from non ​fallers Physiological Profile Assessment® • Used to determine falls risk in terms of component deficits rather than the result of multiple disease entities •​ Assesses vision (including acuity, contrast sensitivity and depth perception), lower limb strength, proprioception, vibration sense, and muscle strength, reaction time, and body sway Tinetti Scale •​ Assesses 24 domains of gait and balance •​ Increased risk of falls in those with impairments in six or more aspects of the test Berg Balance Scale •​ Assesses static and dynamic balance incorporating functional assessments such as functional reach an 180 ​degree turns •​ Scored out or 56 with scores below 40 indicating an increased risk of falls Dynamic gait index •​ Assesses steady state walking and walking under more challenging tasks •​ Scored out of 24 with scores of <19 indicating increased incidence of falls Functional Reach •​ Requires subjects to raise their arm to shoulder height and then reach as far forward as they can without losing balance, falling forward, or taking a step. Distance of the full reach is then measured •​ Shorter reach with loss of balance is associated with an increased risk of falls Dual-​task gait assessment •​ This is a proxy measure of attentional capacity and ability to divide attention where the subject completes a secondary cognitive task (naming animals or counting backwards in 3 s) while walking •​ Gait dynamics are compared to the reference single task condition •​ Impaired ability to dual ​task is associated with an increased risk of falls in older adults

6.8  Falls, faints, and fragility fractures 585 by means of specifically designed software that analyses the digital artery pressure waveform generated by each digital artery pulse. Administration of sublingual glyceroltrinitrate (GTN) improves the sensitivity of the test. Management of orthostatic hypotension Treatment of confirmed orthostatic hypotension includes elimin- ation of contributing medications when possible, increased salt in- take, increased fluid intake, and advice to rise slowly from a seated or lying position. World class III compression hosiery may help, but its use is often limited by the ability and dexterity of older adults to don the stockings without significant assistance. Physicians and general practitioners should be advised to treat the standing blood pressure only, and to have a low threshold for reduction of antihypertensives if orthostatic hypotension is sus- pected. Many cases will require a balance between prevention of orthostatic hypotension-​related morbidity by avoiding precipitous BP drops, while managing hypertension with a view to prevention of long-​term complications. Medications that raise blood pressure can be tried if conservative management is inadequate to control symptoms. Fludrocortisone and midodrine are the drugs used most commonly in the United Kingdom. Fludrocortisone is a mineralocorticoid and acts as a plasma expander, leading to increased circulating volume and blood pressure. Although used fairly widely in the United Kingdom, the evidence base for its effectiveness is weak. Electrolytes, in par- ticular potassium, should be monitored after initiation of the drug. Midodrine is an α-​agonist leading to increases in blood pressure by increasing vascular tone. At present, it is available on a named ­patient basis only in the United Kingdom, but more widely available throughout the rest of Europe and the United States. Its use should be considered on a case-​by-​case basis by a clinician experienced in its administration. Due to the mechanism of action it has the po- tential to cause hypertension, therefore it is recommended that its use should be limited to patients with resting blood pressure below 130 mm Hg systolic. It should be avoided within four hours of bed- time to minimize potential to exacerbate nocturnal hypertension. Carotid sinus syndrome Definitions and diagnosis Carotid sinus syndrome (CSS), also known as carotid sinus hyper- sensitivity is a form of reflex syncope arising from alterations in autonomic tone due to hypersensitivity of baroreceptors in the carotid reflex arc. There are three subtypes of carotid sinus syn- drome: cardio-​inhibitory carotid sinus syndrome, which is defined as a ventricular pause of more than three seconds following carotid sinus massage; vasodepressor carotid sinus syndrome, which is de- fined as a drop in systolic blood pressure of more than 50 mm Hg following carotid sinus massage; and mixed carotid sinus syn- drome, which has combined features of both. Carotid sinus syndrome is provoked by carotid sinus massage in the resting horizontal position or following head-​up tilt to ≥60 degrees. The carotid pulse anatomically corresponds to the carotid sinus, a concentrated area of baroreceptors. Pressure is applied in a circular motion to the left or right (never together) carotid pulse for five seconds with continuous blood pressure and electrocardio- gram monitoring to assess for a significant BP drop or sinus pause. It is repeated on the opposite side if non​diagnostic, and again on each side in the head-​up tilt position until carotid sinus massage has been performed in all four potential positions, or until a clinically significant abnormality has been demonstrated. Contraindications to carotid sinus massage are stroke within three months or the presence of an unevaluated carotid bruit. The incidence of tran- sient ischaemic attack (TIA) or stroke following carotid sinus mas- sage is 1 in 1000. All patients should have a valid consent process for the procedure with discussion of relevant contraindications and complications. Management A  sinus pause of more than 3 seconds following carotid sinus massage is an indication for a permanent pacemaker (PPM). The treatment of vasodepressor carotid sinus syndrome is similar to the treatment of orthostatic hypotension. In many cases, elim- ination of medications potentiating hypotension will lead to improvement or resolution of the problem. Up to one-​third of older adults with the cardio-​inhibitory subtype of carotid sinus syndrome will continue to fall, even after the insertion of a per- manent pacemaker. This is, in part, due to the coexistence of the cardio-​inhibitory and vasodepressor subtypes of carotid sinus syndrome. Management of falls The management of falls requires a multifactorial approach, which is directed by the relevant contributors determined in the assess- ment process. The aim should be to prevent future falls and min- imize their consequences, while avoiding imposing restrictions to the point that they negatively impact function, independence, and quality of life. Co-​morbid conditions should be optimized, revers- ible conditions treated, visual impairment identified (with referral for specialist input if required), contributing medications reduced or eliminated where possible, physiotherapy-​prescribed strength and balance exercise training commenced, cognition monitored, and the home (or usual) environment reviewed to reduce hazards. Care plans and rehabilitation programmes should be individu- alized and tailored to the needs of the patient and delivered by a multidisciplinary team. The minimum dose of exercise to reduce falls in older adults is 50 hours. A Cochrane review completed in 2012 summarized the evidence for falls prevention strategies and is summarized in Box 6.8.2. The role of cognitive impairment Importantly, most of the trials included in the Cochrane system- atic review excluded older participants with cognitive impairment and therefore the results may not be applicable to this group. In fact, multifactorial interventions similar to those delivered in a non​cognitively impaired population have not been effective in re- ducing falls in older adults with cognitive impairment. Emerging evidence indicates that falls risk can be modified with strength and balance training in older adults with cognitive impairment, but protracted rehabilitation programmes with greater therapist input and supervision are required in comparison to a non​cognitively impaired population.

586 Section 6  Old age medicine Fragility fractures Definition and consequences Fragility fractures occur as the result of low energy mechanical forces that under usual circumstances would not result in a frac- ture. This has been defined by the World Health Organization as a fall from standing height or less. Most occur in the setting of low bone mineral density (osteopenia or osteoporosis), although a third or more of some fragility fractures occur in those without osteoporosis. The commonest sites for fragility fracture are the hip (proximal femur), spine (vertebral) and wrist (distal radius), upper arm (proximal humerus), and pelvis (pubic ramus). Hip fractures have the most serious consequences in terms of both mortality and morbidity, with up to 10% dying within one month and up to a third by one year. A further third of people newly require assistance to walk one year after hip fracture. Specialist orthogeriatric liaison for optimization of care for older adults fol- lowing a hip fracture is an evidence-​based standard of care, which has developed in response to the recognition of the high associated mortality due to medical co​morbidity in this group. This is dis- cussed in Chapter 6.6. Assessment All patients at risk of falls should undergo a bone health assess- ment and determination of their future risk of major fracture. Assessment of bone mineral density (BMD) with dual energy X-​ray absorptiometry (DXA) is the gold standard for diagnosis of osteoporosis. The National Institute for Health and Care Excellence (NICE) in the United Kingdom advise that treat- ment with a bisphosphonate following a low energy hip fracture can be considered in postmenopausal women over the age of 75 years if DXA scanning is deemed clinically inappropriate or unfeasible. Determining future risk of fragility fracture and managing ac- cordingly is central to reducing morbidity and mortality in older adults presenting with falls. There are several tools widely avail- able to estimate 10-​year fracture risk based on an individual’s risk factor profile, of which the Fracture Risk Assessment Tool (FRAX, www.shef.ac.uk.FRAX) and the Q-​Fracture Risk Calculator (www. qfracture.org) are most widely used. FRAX allows estimation of 10-​year probability of hip fracture and major osteoporotic frac- ture using clinical risk factors alone if bone mineral density is not known. It is validated in 11 different cohorts and allows cal- culation of country-​specific thresholds for cost-​effectiveness of osteoporosis treatment. FRAX does not include falls risk in its modelling of fracture risk, but Q-​Fracture does. Despite the es- tablished relationship between low bone mineral density and frac- ture, approximately half of hip fractures occur in women whose bone mineral density is above the threshold for osteoporosis. Assessment of clinical risk factors independent of bone mineral density is therefore important, and this includes consideration of risk of future falls. Treatments Pharmacological treatments for osteoporosis and secondary pre- vention of fragility fractures are considered in Chapter 20.4. Models of care for falls and fracture prevention A comprehensive geriatric assessment underpins the management of people who are prone to falls. There are many models of care that are fashioned according to existing services in different regions and countries. Many are based on the American Geriatrics Society/​ British Geriatrics Society Clinical Practice Guidelines, ‘Prevention of Falls in Older Persons’. For those older people who have a had a fragility fracture, as- sessment of falls and fracture risk is essential, and the Fracture Liaison Service model of care has become an established standard. The aim of such a service is to improve the secondary prevention of fragility fractures by improving the identification and treatment of osteoporosis, but also to reduce the risk of further falls by linking the affected individuals with falls services. A systematic review and meta-​analysis reported different types of Fracture Liaison Service models: some were all-​encompassing and delivered identification, investigation, and initiation of interventions; some delivered iden- tification and investigation, but relied on initiation of interven- tions by the primary care physician; some delivered identification and sent an alert to the primary care physician that further inves- tigations are needed, but relied on the primary care physician to organize those investigations and appropriate interventions; and Box 6.8.2  Summary of the Results of Cochrane Systematic Review: Interventions for preventing falls in older people living in the community Interventions that reduced the rate of falling and risk of falling (Gillespie et al., 2012): • Group and home-​based exercise that included both balance retraining and muscle strengthening components (rate ratio (RaR) 0.71, 95% con- fidence interval (CI) 0 .63–​0.82 for rate of falls and risk ratio (RR) 0.85, 95% CI 0.76–​0.96 for risk of falling) • Tai chi (balance-​based exercise) (RaR 0.72, 95% CI 0.52–​1.00 for rate of falls and RR 0.71, 95% CI 0.57–​0.87 for risk of falling) • Home safety interventions, especially those delivered by an occupa- tional therapist (RaR 0.69, 95% CI 0.55–​0.86 for rate of falls, and RR 0.79, 95% CI 0.70–​0.91 for risk of falling) Interventions that reduced rate of falling but not risk of falling: • Multifactorial interventions including an individualized risk assessment (RaR 0.76, 95% CI 0.67–​0.86) • Pacemaker insertion for people with confirmed cardio-​inhibitory ca- rotid sinus syndrome (RaR 0.73, 95% CI 0.57–​0.93) • Expedited first cataract extraction surgery in women, but not second cataract surgery (RaR 0.66 95% CI 0.45–​0.95) • Gradual withdrawal of psychotropic medications (RaR 0.34, 95% CI 0.16–​0.73) • Antislip shoe devices for icy weather (RaR 0.42, 95% CI 0.22–​0.78) • Podiatry and foot and ankle exercises in people with foot pain (RaR 0.64, 95% CI 0.45–​0.91)

6.8  Falls, faints, and fragility fractures 587 some models provided education to the patient, but did not alert the primary care physician. Special considerations and uncertainties Falls in hospital Inpatient falls are the most commonly reported patient safety inci- dent in UK hospitals. Over 600 inpatient falls are reported per day in acute hospitals in England and Wales, amounting to over 240 000 falls and 2500 hip fractures annually among acute inpatients in this territory (see also Chapter  6.5). The Royal College of Physicians National Audit of Inpatient Falls in 2015 reported a fall rate of 6.63 per 1000 occupied bed days, while in the United States rates of falls in hospitals range from 3.3 to 11.5 falls per 1000 patient days. At one end of the spectrum, inpatient falls can impact negatively on a patient’s function, confidence, recovery time and length of stay: at the more serious extreme they can result in severe harm due to hip fractures, head injury, and even death. Many of the falls risk factors in older adults in hospitals are unchanged compared to those in a general older population. However, the coexistence of acute illness, delirium, cognitive impairment, urinary incontin- ence, sleep disturbance, impaired mobility, new medications, and environment change associated with a hospital stay further amp- lify an individual’s risk of falls. A Cochrane review in 2012 found that, in contrast to multifac- torial interventions to reduce falls in community-​dwelling older adults, there is little conclusive evidence that a similar standard multifactorial approach reduces falls in the acute hospital setting. More recently a plausible ‘6-​Pack’ programme comprising a nine-​ item falls risk assessment with six nursing interventions—​‘falls alert’ sign; supervision of patients in the bathroom; ensuring pa- tients’ walking aids are within reach; establishment of a toileting regime; use of low-​low beds; and use of bed-​chair alarms—​failed to out-​perform standard care in a randomized trial. Identifying the specific risks in potentially vulnerable individ- uals may be a more effective strategy as there is no ‘one size fits all’ assessment to detect reliably those most at risk. The individualized approach takes account of baseline risk factors and the effect of concomitant illness and treatments. There may be a role for multi- factorial interventions, including exercise, in the subacute ward setting where patients have longer lengths of stay. Hip protectors Hip fractures usually result from a fall. Hip protectors are designed to reduce the forces impacting the hip in a sideways fall, thereby lessening the chance for a femoral neck fracture. The protectors are placed or sown on each side of an undergarment. Although some individual trials have confirmed that they can reduce hip fractures, others have shown negative results, probably related to problems with adherence and persistence, with compliance rates generally varying between a third to two-​thirds only. A Cochrane review in 2014 included 19 controlled trials that compared a hip protector intervention group with a control no hip protector group, and found a small but significant 18% reduction in hip fracture risk for people in nursing or residential care settings. However, no beneficial effect was seen in a community-​dwelling setting. Nevertheless, where an older person continues to have re- current falls despite assessment and intervention, hip protectors may be worth considering in individuals who will wear them. Vitamin D controversies Vitamin D deficiency is associated with impaired balance, low bone mineral density, muscle weakness, and increased risk of falls. Serum 25 dihydroxy vitamin D levels of 20 ng/​ml (50 nmoles/​l) to 30 ng/​ml (75nmoles/​l) have been proposed, below which vitamin D levels are thought to be inadequate. Supplementation has been shown to improve muscle strength and balance, thereby reducing falls. Meta-​analyses in older adults with vitamin D deficiency have found that doses of 700–​1000 IU of vitamin D daily reduces the risk of falling by up to 19%. Care home residents have high prevalence of vitamin D defi- ciency and current recommendations are to consider vitamin D supplementations for care home residents without the necessity to confirm deficiency on blood tests. In clinical practice, vitamin D is often co-​administered with calcium supplements as metanalyses have demonstrated the need for both calcium and vitamin D sup- plementation to reduce fracture risk. In 2011 concern was raised about adverse cardiovascular mor- tality in association with calcium supplements. Vitamin D alone has not been found to affect cardiovascular risk, but guidance on the use of calcium and vitamin D in combination, which is most frequently found in clinical practice, remains uncertain. A meta-​ analysis in 2015, looking specifically at reported cardiovascular outcomes in subjects co-​administered calcium and vitamin D, concluded that the guidelines on calcium and vitamin D supple- mentation should not change until randomized controlled trials have been conducted where cardiovascular mortality is the pri- mary outcome measure and findings are adequately adjusted for major confounders. Anticoagulation for atrial fibrillation Atrial fibrillation (AF) affects 4–​8% of people aged over 60, and oral anticoagulation with warfarin, and now the newer direct oral anti- coagulants, is associated with a significant reduction in the risk of stroke and other thromboembolic sequelae. Despite this evidence, the rate of prescription of oral anticoagulants in older adults with AF is as low as 50% of those suitable for the treatment. Concern about the risk of falls and associated severe harm is most frequently cited as the reason for non​prescription. However, the rate of subdural haematoma on oral anticoagulants in older adults with an average risk of stroke is low, with an estimated need for the individual to fall up to 300 times per year for the risk to out- weigh the potential benefits from a thromboembolic viewpoint. The newer direct oral anticoagulants confer benefits to the patient in terms of non​varied dosing, lack of need for repeated blood tests for monitoring, reliable therapeutic effect, and improvement in overall control for patients who have very labile international normalized ratios (INRs) and limited time in the therapeutic range on warfarin. They would seem to offer an alterative in patients deemed at added risk of adverse outcomes due to high INRs, but the current lack of established antidotes for reversal of each direct oral anticoagulants needs to be considered before their prescription in older adults with

588 Section 6  Old age medicine AF. The decision on whether or not to anticoagulate a patient with AF who is at very high risk of falls is an individualized one, taking into account the patient`s frailty, cognitive state, co​morbidities, and (where appropriate) their personal viewpoint. FURTHER READING Barker AL, et  al. (2016). 6-​PACK programme to decrease fall
injuries in acute hospitals:  cluster randomised controlled trial. BMJ, 352, h6781. British Orthopaedic Association (2007). The Care of Patients with Fragility Fracture. http://​www.bgs.org.uk/​index.php?option=com_​ content&view=article&id=338:bluebookfragilityfracture&catid= 47:fallsandbones&Itemid=307 Challoumas D, et al. (2015). Effects of combined vitamin D-​calcium supplements on the cardiovascular system: should we be cautious? Atherosclerosis, 238, 388–​98. Ganda K, et al. (2013). Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-​analysis. Osteoporos Int, 24, 393–​406. Gillespie LD, et al. (2012). Interventions for preventing falls in older people living in the community. Cochrane Database Syst Rev, 2, CD007146. Kanis JA, et al. (2008). FRAX and the assessment of fracture prob- ability in men and women from the UK. Osteoporos Int, 19, 385–​97. Moya A, et al. (2009). Guidelines for the diagnosis and management of syncope (version 2009). Eur Heart J, 30, 2631–​71. Muir SW, et al. (2012). The role of cognitive impairment in fall risk among older adults: a systematic review and meta-​analysis. Age Ageing, 41, 299–​308. National Institute for Health and Care Excellence (NICE) (2012). Osteoporosis:  Assessing the Risk of Fragility Fracture. Clinical guideline [CG146]. https://​www.nice.org.uk/​guidance/​cg146 National Institute for Health and Care Excellence (NICE)
(2013). Falls: Assessment and Prevention of Falls in Older People. Clinical guideline [CG161]. https://​www.nice.org.uk/​guidance/​ cg161 Panel on Prevention of Falls in Older Persons, American Geriatrics Society and British Geriatrics Society (2011). Summary of the
updated American Geriatrics Society/​British Geriatrics Society clinical guideline for prevention of falls in older persons. J Am Geriatr Soc, 59, 148–​57. Shaw FE, et al. (2003). Multifactorial intervention after a fall in older people with cognitive impairment and dementia presenting to
the accident and emergency department: randomised controlled trial. BMJ, 326, 73. Tinetti ME, Speechley M, Ginter SF (1988). Risk factors among elderly persons living in the community. N Engl J Med, 319, 1701–​7. Zarraga IGE, Kron J (2013). Oral anticoagulation in elderly adults with atrial fibrillation: integrating new options with old concepts.
J Am Geriatr Soc, 61, 143–​50. Ziere G, et al. (2006). Polypharmacy and falls in middle age and eld- erly population. Br J Clin Pharmacol, 61, 218–​23.

6.9 Bladder and bowels 589

6.9 Bladder and bowels 589

ESSENTIALS Urinary incontinence Urinary incontinence is not an inevitable consequence of ageing. Its impact on social, psychological, and physical well-​being is com- parable to that of other chronic conditions such as diabetes and dementia. The different types of urinary incontinence are identified on the basis of history (including a bladder diary), clinical examination (par- ticularly abdominal and pelvic), and investigation (including urinary dipstick to check for infection and measurement of post-​void re- sidual volume). Treatment should be based on realistic patient-​related goals and follow the principles of comprehensive geriatric assessment. Depending on the type of incontinence, reduction in caffeine in- take, bladder training, pelvic floor exercises, medication (particu- larly antimuscarinic agents and β-​3 agonists), and (rarely) surgery may be used. Targeted rehabilitation, adaptation of the environ- ment, and the provision of toileting aids and equipment are part of the overall treatment package. Constipation and faecal incontinence Constipation, including symptoms of evacuation difficulty and/​or fewer bowel movements, is a common problem as people age. Risk factors include problems in cognition, mobility, gastrointes- tinal motility, dysautonomia, anorectal dysfunction, and disabling neurologic disorders. A systematic case finding and diagnostic ap- proach is therefore essential. Common precipitants of constipation include low fluid volume intake, acute illness, anticholinergic medi- cations, and iron supplementation. Evidence-​based approaches to treatment include increased fluid intake, increased dietary fibre, physical exercise, and abdominal massage. A systematic stepped approach to laxative treatment starts with well-​established cheaper products before proceeding to more expensive alternatives. Faecal impaction with hard or soft stool can result in overflow diarrhoea, hence the presenting complaint can be misleading. Faecal incontinence is more common in frail individuals but is often assessed inadequately. The cause is often multifactorial. Treatment depends on the cause:  a combination of approaches may be necessary, including avoidance of faecal impaction, instiga- tion of a structured bowel care plan including regular prompted toi- leting, dietary modification, and (in some cases) use of loperamide or similar medications. Urinary incontinence Introduction Urinary incontinence (UI) is the involuntary leakage of urine. Its prevalence increases with age due to age-​related changes in the urinary tract and the functional impact of other co​morbidities on the process of toileting. Urinary incontinence is not, however, an inevitable consequence of ageing. This misconception should be actively challenged by healthcare professionals as it may prevent an individual patient from seeking treatment. The maintenance of continence is associated with many factors. The concept of social continence (i.e. to void in a socially acceptable place at a socially acceptable time) highlights the impact of cogni- tive, physical, and environmental aspects. Urinary incontinence in the older adult should therefore be treated as a ‘geriatric syndrome’ and comprehensive geriatric assessment should be undertaken. This should include an assessment of functional status, environ- ment and a medication review. The impact of urinary incontinence on social, psychological, and physical well-​being is comparable to that of other chronic condi- tions such as epilepsy or a stroke. The frail older adult rarely pre- sents in isolation and the need for assistance with toileting and hygiene can have a considerable impact on the quality of life of the carer too. This associated carer burden can occur in both the home and in the institutional setting. This can lead to negative percep- tions of the older adult by the carer as well as a detrimental effect on the carer’s well-​being. The presence of urinary incontinence in association with other co​morbidities can increase the associated burden of these diseases. It has been consistently shown that treatment of urinary incon- tinence in the older adult is more cost-​effective than containment alone, and that the older adult will benefit from assessment and 6.9 Bladder and bowels Susie Orme and Danielle Harari

590 Section 6  Old age medicine treatment. Such benefits include being able to stay in their domicile of choice, maintenance of their social functioning, and ability to perform instrumental activities of daily living. Epidemiology The prevalence of urinary incontinence is likely to be higher than estimated due to low rates of help seeking behaviour. Defining prevalence by age alone is also unhelpful because of the diversity within the population of over 65’s across the world, and within countries fitter community-​dwelling older people differ signifi- cantly in their functional and cognitive ability from the frailer, in- stitutionalized older population. In 1993, UK MORI showed a lifetime prevalence of urinary incontinence at any age of 6.6% in men and 14% in women. There was a steady increase in incidence with age, with urinary incontinence being more prevalent in women at all ages. The Newcastle Cohort 85+ study in 2009 reported an incidence of severe urinary incontinence (weekly or more) of 21%. Overall the literature would suggest a prevalence of 15–​30% of weekly episodes of urinary incontinence for fitter community-​dwelling older adults, and 50–​80% among those in institutional care. The higher incidence of urinary incontinence among the frailer in- dividuals in institutional care demonstrates the impact of cog- nition, co​morbidities, and functional status on the ability to maintain continence. Aetiology—​maintenance of continence ‘Social continence’ is a learnt skill. We learn as children the need to void in a socially appropriate place and at a socially appropriate time. The ability to do this depends on many factors outside the lower urinary tract. In particular, cognitive function, mobility, and manual dexterity are important. If we consider the stages involved in the maintenance of social continence it is easier to appreciate how any functional impairment may influence the ability of an in- dividual to stay dry. • Recognition of the sensation and need to void—​when we have the initial sensation to void we need to control this urge until a suitable place to void is found. This requires an intact and nor- mally innervated bladder, sphincter, and pelvic floor. We require significant cognitive function and sensory awareness to be able to identify a socially acceptable place. • Ability to communicate the need to toilet—​if assistance is re- quired, the ability to summon and the availability of that assist- ance will influence toileting. This is a particular consideration for those who require help. • Functional motor ability—​ability to get to the toilet quickly enough and sufficient manual dexterity to be able to remove lower body garments and sit on the toilet safely. • Ageing changes affecting voiding—​age-​related changes in the lower urinary tract predispose to greater difficulty maintaining continence. Increased collagen deposition in the urethral and bladder walls result in decreased urethral closing pressure and reduced functional bladder capacity respectively. Prostatic volume increases with age and may affect the voiding stage of micturition. Atrophic vaginitis in postmenopausal women can exacerbate urinary incontinence and increase the tendency towards recurrent urinary tract infections. Ageing reduces the production of antidiuretic hormone by the pituitary, which along with changes in the renal medulla leads to the reduced renal concentrating ability with age. Increased production of atrial natriuretic peptide also occurs. These factors result in the ten- dency to troublesome nocturia associated with nocturnal poly- uria, passing more than one-​third of total voided volume during night-​time hours. • Pathological causes of voiding difficulty—​only this last stage is influenced directly by the lower urinary tract: the features and causes are described next. Clearly environmental and physical factors and intercurrent illnesses may impact on the ability to sequence the stages given here. Addressing these factors may help reduce or prevent incon- tinent episodes. Clinical assessment Clinical history A focused clinical history should include asking about the spe- cific symptoms of lower urinary tract dysfunction. Table 6.9.1 describes the relevant symptoms associated with bladder storage changes and Table 6.9.2 the symptoms during and after mic- turition. Table 6.9.3 describes the clinical types of incontinence based on the clinical features. The duration and severity of the symptoms should be noted, and specific reasons why the patient sought treatment at that time. The history should also include a detailed social history, includ­ ing access to toileting facilities, ability to attend to lower body hygiene, and the need for carers to aid toileting. Obstetric history in women should be noted, including parity, instrumental delivery, and any birth complications. Any history of abdominal or pelvic surgery in both men and women should be recorded. A detailed bowel history including any effect that constipation has on lower urinary tract symptoms (LUTS), and the presence of any coexisting faecal incontinence should be elucidated. A re- cord of pad usage and any financial burden associated with the purchase of pads should be recorded. The impact on the carer and assessment of carer burden should also be sought. Drug history is important as many pharmacological agents can affect lower urinary tract symptoms, as shown in Box 6.9.1. Table 6.9.1  Lower urinary tract symptoms (bladder storage symptoms) Symptom Definition Daytime urinary frequency Increased frequency of micturition during waking hours—​more than patient previously felt was normal, ie associated with bother Nocturia The need to micturate one or more times that interrupts and awakens from sleep Urgency Complaint of a sudden compelling desire to pass urine that is difficult to deter Overactive bladder syndrome (OAB) Urinary urgency with increased frequency and nocturia, with or without urinary incontinence, in
the absence of UTI or other pathology UTI, urinary tract infection.

6.9  Bladder and bowels 591 Bladder diary From the history alone, it can be difficult to ascertain the timing of voids and incontinence episodes. A bladder diary is a useful tool to obtain more reliable information. A gold standard ‘bladder diary’ is completed for three consecutive days and records volumes of fluid and food intake, as well as voided volume, episodes of urinary incontinence, and pad changes. This can be a challenge for a frail, older adult to complete, especially in the presence of cognitive im- pairment or functional needs that require the presence of carer to toilet. However, a useful amount of information can be obtained by recording the number and type of drinks (e.g. ‘mug of tea’), and recording when voids are in the toilet and when incontinence epi- sodes occur. It is better to obtain some indication of the voiding pattern of the patient rather than none. In those with severe cognitive impairment, recordings of the vol- umes of and types of fluid drunk and hourly wet checks by day and night can be helpful in obtaining an underlying diagnosis. Useful materials to document bladder activity can be obtained from the International Consultation on Urological Diseases website. Clinical examination A useful assessment of the patient’s functional and mobility status can be made watching their ability to walk over to the couch and undress for the rest of the examination. A record of body mass index should be made. Abdominal examination for evidence of previous surgery, palpable masses, or faecal impaction should be performed. Examination of the external genitalia should look for signs of Candida infection, contact dermatitis, vaginal atrophy, and skin conditions such as lichen planus. Digital rectal exam- ination (PR) is indicated to check anal tone, the presence of hard stool in the rectum and to perform prostate examination in men. Prolapse may be visible at the introitus. Per vaginal examination should be performed, including asking the patient to cough to demonstrate any prolapse of the vaginal walls and to demonstrate stress incontinence. Cognitive assessment is advised in the frail. The abbreviated mental test score is useful and if less than or equal to 7/​10, pro- ceeding to more detailed assessment may be appropriate. Clinical investigations Urine dip stick +/​-​ mid-​stream urine culture and sensitivity The presence of coexisting urinary tract infection (UTI) can ex- acerbate urinary incontinence, although treatment of UTI alone is rarely sufficient to cure the urinary incontinence. The purpose of the urine dip is also to help exclude ‘red flags’, including the pres- ence of haematuria or significant pyuria in the absence of infection. These would indicate the need for further investigation of the lower urinary tract including ultrasound imaging and cystoscopy. Table 6.9.2  Voiding and post-​micturition symptoms Symptom Definition Hesitancy Complaint of a delay in initiating micturition Slow Stream Complaint of a urinary stream perceived as slower than previously or in comparison to others Straining to void Complaint of the need to make an intensive effort to initiate, maintain, or improve urinary stream Feeling of incomplete bladder emptying Complaint that the bladder does not feel empty after micturition Need to immediately re-​void Complaint that further micturition is necessary soon after passing urine Post-​micturition leakage Complaint of a further involuntary passage of urine following completion of micturition Postural dependent micturition Complaint of having to take up specific postural positions to improve bladder emptying Dysuria Complaint of discomfort during or after micturition. Discomfort may be felt internally or externally (external genitalia) Urinary retention Complaint of the inability to pass urine despite persistent effort Table 6.9.3  Urinary incontinence by type Symptom Abbreviation in text Definition Urinary incontinence UI Involuntary loss of urine Stress urinary incontinence SUI Involuntary loss of urine on physical examination, sneezing,
or coughing Urgency urinary incontinence UUI Involuntary loss of urine associated with urgency Postural urinary incontinence PUI Involuntary loss of urine associated with change of body position Nocturnal enuresis Involuntary loss of urine occurs during sleep Mixed urinary incontinence MUI Involuntary loss of urine associated with urgency and also physical examination, sneezing, or coughing Continuous urinary incontinence CUI Continuous involuntary loss of urine Insensible urinary incontinence IUI Urinary incontinence where patient is unaware of how it occurred Functional urinary incontinence FUI Urinary incontinence due to decreased motivation, initiative, or ability to get to the toilet when the need arises Box 6.9.1  Medications impacting bladder function and continence • Alcohol • α-adrenergic agonists (e.g midodrine, pseudoephedrine) • α-blockers (e.g. doxazosin, tamsulosin) • ACE inhibitors (e.g. ramipril, lisinopril) • Caffeine • Cholinesterase inhibitors (e.g. donepezil, rivastigmine) • Diuretics (e.g. bendrofluazide, furosemide, bumetanide) • Anticholinergic drugs • Oral oestrogen therapies (e.g. hormone replacement therapy, HRT) • Opioids (e.g. codeine, morphine, tramadol) • Sedatives and hypnotics (e.g. benzodiazepines, zopiclone)

592 Section 6  Old age medicine Post-​void residual volume The measurement of post-​void residual volume is a simple non-​ invasive test using ultrasound. There is no agreed cut-​off point to define an acceptable post-​void residual volume, but in the ab- sence of symptoms an amount less than 200  ml is likely to be so. Post-​void residual volume increases in the presence of severe constipation with faecal impaction, also with medications with anticholingeric effects. Both of these causes are common within a frail, older population. Urodynamics Multichannel cystometry (with or without video screening) is no longer recommended for the diagnosis of urinary incontinence, but it may be advisable before surgical intervention is undertaken and should form part of a multidisciplinary team assessment of the patient. Differential diagnosis Table 6.9.4 indicates clinical diagnosis by history, examination, and clinical investigations. The impact of multimorbidity Tables 6.9.5 and 6.9.6 indicate the association of urine incontin- ence with other diseases and the additional disease burden exacer- bated by urinary incontinence. Treatment The aims of treatment should be based on patient-​related goals and follow the principles of comprehensive geriatric assessment. Expectations and priorities of the patient and carer regarding treatment goals can be explored during the initial consultation (e.g. ‘I want to sleep better at night without having to get up and go to the toilet’). Goal settings should be realistic and the patient and carer should be fully informed. Targeted rehabilitation, adap- tation of the environment, and the provision of toileting aids and equipment are part of the overall treatment package. Guidance on assessment and diagnosis with a flow chart illustrating the management of urinary incontinence in frail, older men and women is available from the International Consultation on Urological Diseases. The aim of treatment in the very frail may involve goals of being ‘less wet’ or ‘sleep better at night’ rather than complete dryness. Treatment is always more cost effective than containment alone and is beneficial for both the individual and for the greater healthcare economy. The National Institute for Health and Care Excellence (NICE) have produced evidence-​based and cost-​effective treatment guides specifically with reference to four patient groups. They are as follows; • NICE CG97. Lower urinary tract symptoms in men: Management. https://​www.nice.org.uk/​guidance/​cg97 • NICE CG148. Urinary incontinence in neurological disease: Assessment and management. https://​www.nice.org.uk/​guidance/​ cg148 • NICE CG171. Urinary incontinence in women: Management https://​www.nice.org.uk/​guidance/​cg1471 • NICE TA290. Mirabegron for treating symptoms of overactive bladder https://​www.nice.org.uk/​guidance/​ta290 Specific treatment is related to the subtypes of urinary incontin- ence. The following discussion is an overview of current conserva- tive and pharmacological options. Surgical interventions are not discussed in detail and should be considered only after a multidis- ciplinary team review. Conservative management and lifestyle modification Reduction in caffeine intake while maintaining adequate hydration is effective for the symptoms of overactive bladder. Mixed urinary incontinence should also be treated with reduction in caffeine in- take in the first instance. Teaching the bladder to ‘hold on’ is a useful cognitive behav- ioural therapy technique formally known as bladder training. This is effective in cognitively intact patients, but in cognitively Table 6.9.4  Diagnosis by clinical factors, history, examination, and clinical investigations Diagnosis History Examination and Investigations Treatment Stress UI Leakage on coughing, straining activity Signs of prolapse in women, vaginal atrophy. Bladder diary indicates UI episodes but no frequency Pelvic floor exercises. Adequate fluid intake, caffeine reduction, surgical intervention after MDT. Treat constipation Overactive bladder Urgency. Bothersome frequency. Urgency incontinence, nocturia Multiple small voids + episodes of UI by day and night on bladder diary Pelvic floor exercises, caffeine reduction, bladder retraining, prompted voiding, time voiding, antimuscarinics, β3 agonists, treat constipation, Botulinum toxin, sacral neuromodulation Mixed UI Symptoms of both stress UI and OAB As above Treat predominant symptoms first, pelvic floor exercises, adequate fluid intake, bladder retraining, antimuscarinics, β3 agonists Incontinence associated with incomplete bladder emptying Possible insensible losses, nocturnal incontinence, postural leakage Signs of faecal impaction, possible palpable bladder, raised PVR on ultrasound, episodes of UI by day and night Treat constipation, adjust anticholinergic burden, intermittent or indwelling catheter (patient choice) Nocturia predominant associated with reversed nocturnal diuresis Small volumes by day, multiple voids at night, nocturia, and sleep disturbance Signs of CCF and peripheral oedema may be present, small voids by day on bladder diary, multiple large volume voids at night-​time Adequate fluid intake, caffeine reduction, Loop diuretics taken prior to bedtime (4–​6 hours beforehand if furosemide). Active night-​time toileting CCF, congestive cardiac failure; OAB, overactive bladder syndrome; MDT, multidisciplinary team meeting; PVR, post-​void residual urine volume; UI, urinary incontinence.

6.9  Bladder and bowels 593 impaired patients, time intervals between voiding or intentional toileting after meals can reduce the episodes of urinary incontin- ence in the day time, but is unlikely to make people completely dry. Pelvic floor exercises Pelvic floor exercises are effective in both stress urinary incontinence and mixed urinary incontinence. It is advised that they are taught by a professional, rather than simply by giving the patient a leaflet, and that it is ensured the patient has significant cognition to ensure the instructions are followed correctly. Pelvic floor exercises are effective in women of all ages provided they are performed correctly. Containment products and toileting aids Containment products should be used as an adjunct to definitive diagnosis and treatment of the underlying cause of the urinary in- continence rather than a primary solution. They are, however, ne- cessary if the patient is likely to remain wet due to multifactorial reasons including functional and cognitive status that would stop treatment making them completely dry. Table 6.9.5  Conditions contributing to urinary incontinence Condition Type of incontinence Notes Dementia Urge incontinence Functional incontinence Causes UI by variety of mechanisms: a) Decreased motivation and initiative to go to the toilet b) Social disinhibition c) Decreased executive function d) Immobility or gait disturbance e) Severe autonomic failure (Lewy body dementia) Stroke Urge incontinence Functional incontinence Urinary retention Varying effects on bladder and bowel function, mobility, and functional ability to toilet UI post stroke often improves over time. Uncommon but poor prognostic indicator for those in whom it persists Parkinson’s Functional incontinence Urge incontinence Also autonomic failure in ‘Parkinsons plus’ syndromes Delirium Functional incontinence Urinary retention Delirium can be associated with detrusor underactivity or bladder outflow obstruction causing urinary retention (‘cystocerebral syndrome’) as well as infection causing UI Normal pressure hydrocephalus Urge incontinence Incontinence, gait, and cognitive deficits Potentially reversible with VP shunt Anxiety and depression Functional incontinence Can result from incontinence Less motivation to stay continent Can also cause mildly impaired cognition Arthritis Functional incontinence Urge incontinence Diabetes Functional incontinence Polyuria in poorly controlled DM Peripheral neuropathy Autonomic neuropathy Increased susceptibility to UTI Peripheral oedema (heart failure, venous insufficiency, medications) Nocturia Nocturnal polyuria Nocturnal enuresis Overnight reabsorption of peripheral oedema causing increased circulating volume and increased nocturnal urine production. Increased ANP levels secondary to myocardial stretch from increased circulating volume may also contribute to increased nocturnal urine production Constipation and faecal impaction Combined faecal and urinary incontinence Urge incontinence Urinary retention Outflow tract obstruction causing urge incontinence from detrusor overactivity Straining can result in weakened pelvic floor muscles COPD Stress incontinence Cough can exacerbate stress incontinence ANP, atrial natriuretic peptide; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; UI, urinary incontinence; UTI, urinary tract infection; VP, ventriculoperitoneal. Table 6.9.6  Consequences of bladder dysfunction and urinary incontinence Condition Notes Depression
and anxiety Also reduced quality of life and social isolation Falls and fractures Falls and fractures can result from UI, especially UUI and OAB Nocturia Nocturia can result in daytime sleepiness, and have an adverse effect on cognition. It is associated with an increased falls risk of between 10–​20% with two or more voids per night, as well as an increased fracture risk and nocturnal enuresis Pressure area sores UI is an important feature in the development of pressure area sores, and slows their healing. Can also cause skin rashes and dermatitis Urinary tract infection UTI is associated with chronic urinary retention, as well as indwelling catheters and condom (convene) drainage systems OAB, overactive bladder syndrome; UI, urinary incontinence; UTI, urinary tract infection; UUI, urgency urinary incontinence.

594 Section 6  Old age medicine Many devices and pads are available, although provision and re- imbursement or free availability does vary internationally and (in the United Kingdom) locally. Patient choice should be respected where possible. A  useful website is the ‘Continence Products Advisor’, a collaboration between the International Consultation on Incontinence (ICI) and the International Continence Society. Catheters Indwelling catheters are not a viable long-​term option for urinary incontinence. There is a high risk of catheter associated urinary tract infection, bypassing, and local trauma to the peri-​urethral area. For patients with urinary incontinence associated with in- complete bladder emptying, intermittent catheterization is pref- erable. This can be performed by the patient if cognition and dexterity allows, but if necessary a carer or healthcare professional can be trained to provide the procedure. Catheter valves including ‘flip-​flow valves’ allow a filling and emptying cycle during the daytime if the patient has significant cognition and function to be able to open and close the valve. Either this or a suprapubic catheter is preferable if long-​term cath- eterization is unavoidable. The risks of catheter-​associated UTI are less with suprapubic catheterization, and this has less of an impact on sexual function. Pharmacological treatments Antimuscarinic agents Muscarinic M3 receptors initiate bladder contraction, and there are cholinergic receptors (M1-​M5) at many other sites in the body, including the salivary glands, bowel, and central nervous system. Anticholinergic medication blocking these other sites causes side effects, dry mouth and constipation being the most common. Anticholinergic medication acting centrally can cause central nervous system (CNS) side effects. These drugs enter the central nervous system passively via the blood brain barrier (the higher the degree of lipophilicity the greater the penetration), and they are actively removed via P-​glycoprotein 1 transport (also known as multidrug resistance protein 1, which pumps many foreign substances out of cells), hence an antimuscarinic with a high lipophilicity and a low affinity as pump substrate increases the risk of CNS related side effects including confusion (both acutely and chronically). Oxybutynin is a highly liphophilic antimuscarinic with a low P-​glycoprotein 1 substrate affinity, which is why NICE recommends it not be given to very frail older women. However, all antimuscarinics have the potential to cause confusion, hence initiation of this medica- tion should accompany a medication review that takes into account overall anticholinergic burden. A  high total anticholingeric load may be associated with progressive effects on cognition over time. Estimation of this overall anticholinergic burden of multiple medi- cations can be done with on line support (see further reading). The importance of medication review indicates the need for comprehen- sive geriatric assessment in the treatment as well as the diagnosis of urinary incontinence in the frail older adult. β-​3 agonists β-​3 adrenergic receptors inhibit bladder contractions. β-​3 agonists have been shown to have similar efficacy to antimuscarinics in the treatment of overactive bladder. If other medication the frail older adult is taking means that the anticholinergic load cannot be re- duced, and they would be the first line option for pharmacological treatment for those in whom an antimuscarinic is not tolerated or is contraindicated. α-blockers α-1 adrenergic receptors promote contraction of the bladder neck, urethra, and prostate to enhance bladder outflow resistance, par- ticularly in elderly men with enlarged prostates. α-blockers are the first-​line pharmacological agent for men with bothersome lower urinary tract symptoms if conservative measures are unsuccessful or not appropriate. Desmopressin Patients with nocturnal polyuria may benefit from use of oral or nasal desmopressin (an antidiuretic hormone (ADH) analogue) before bedtime if other medical causes have been excluded and they have not benefitted from other treatments. 5-α reductase inhibitors Androgens cause cellular proliferation, decrease in apoptosis, and promote angiogenesis within the prostate. 5-​α reductase inhibi- tors block the conversion of testosterone to dihydrotestosterone and thereby mitigate the effects of androgens. They are offered to men with bothersome lower urinary tract symptoms and a ­prostate ­estimated to be larger than 30 g or a serum prostate-​specific antigen (PSA) greater than 1.4 ng/​ml. Surgical interventions Detailed description of surgical procedures is beyond the scope of this chapter, but surgical intervention should be considered only after discussion at a multidisciplinary team meeting (MDT). Sacral neuromodulation with an implantable device is a recommended option for intractable overactive bladder. Botulinum toxin is also recommended, but the optimum dosage and interval between treatments is not clear. Because of the risk of retention the patient must be able to perform intermittent self-​catheterization before being accepted for the procedure. Future developments The quality of investigation and management of urinary incontin- ence is suboptimal in most if not all countries, including the English National Health Service (NHS), as evidenced by national audits. Men are generally more reluctant to come forward, and those with lower urinary tract storage symptoms are consistently undertreated. This is likely to be due to concerns regarding the risk of medica- tion induced urinary retention, but studies have shown that the risk has been exaggerated and may be less than 2%. If both storage and voiding problems are present, co​prescription of a selective α-​blocker and an antimuscarinic is recommended. There has been an increased body of evidence in recent years that maintenance of continence is as reliant on central control as it is on the lower urinary tract. As we are beginning to understand the cognitive aspects of maintaining continence, the options for treat- ment will become more diverse and more tailored to the needs of the individual. The challenge of an ageing population within the western world means that the personal, social and economic burden of urinary

6.9  Bladder and bowels 595 incontinence cannot be ignored. The pattern of help-​seeking be- haviour in the ‘baby boomers’ means that we are likely to see an increase in patients presenting for treatment or screening and treatment. Constipation and faecal incontinence Introduction Constipation is a common concern for adults beyond age 60, re- flected by more primary care consultations and increasing laxative use. Older people reporting constipation are more likely to have anxiety, depression, and poor health perception and quality of life. In frail older people, constipation can lead to faecal impaction and incontinence, urinary retention, delirium, and hospital admission. Faecal incontinence is distressing, often leading to embarrassment and social isolation, adding to the risks of poor mental health, dependency, and mortality. It is also a particular challenge to in- formal carers, and may be the ‘final straw’ leading to nursing home admission. Despite all this, both constipation and faecal incontin- ence are under-​reported, in part because many doctors are found to make light of the issues, and offers of high-​quality empathic advice are infrequent. Constipation and faecal incontinence are also costly conditions, particularly on laxatives and community nursing time. National and international guidance have emphasized the importance of identifying treatable causes of faecal incontinence in frail older people, rather than simply offering pads, but in the UK audit shows that professional assessment and care is often lacking, and it is likely that the same applies elsewhere. Definitions Use of standardized definitions such as the Rome III criteria (Table 6.9.7) would help epidemiological estimation of the burden of constipation and faecal incontinence and promote more con- sistent clinical assessment and management. These criteria are symptom-​based. Objective assessment relies on finding faecal loading in the rectum and/​or colon through clinical examination and/​or plain X-​ray. Objective assessment is particularly important in frail older people in whom constipation can be underestimated. Constipation subtypes affecting older people include rectal outlet delay and irritable bowel syndrome with predominant constipa- tion (IBS-​C), identified using standard definitions. The WHO International Consultation on Incontinence defines faecal incontinence as ‘involuntary loss of liquid or solid stool that is a social or hygienic problem’. The frequency, amount of leakage and ‘bother’ are recognized parameters to quantify faecal incon- tinence, but patients have highlighted predictability, awareness, ability to wipe, and burning discomfort as important to them. Aetiology and risk factors Lifestyle factors Greater physical activity such as regular walking makes consti- pation less likely for community-​dwelling older people. Exercise increases colonic propulsive activity. Habitually higher levels of physical activity through adulthood may reduce the likeli- hood of constipation problems in older age. Reduced mobility is the strongest association with heavy laxative use among nursing home residents, with gut transit time in bedridden people as long as three weeks. In the United Kingdom, fibre intake (in wheat bran, vegetables, and fruit) decreases with advancing age, and lower consumption predisposes towards constipation. In Europe, the Mediterranean diet is associated with lower constipation rates. In frail individuals lower food intake leads to constipation and anorexia, thus resulting in a vicious cycle. Low fluid intake in older adults makes symptomatic slow transit constipation more likely. Factors leading to low intake include im- paired thirst sensation, relative renal insensitivity to antidiuretic hormone in response to hypertonicity, access difficulty associated with physical or cognitive impairments, and voluntary fluid re- striction in a misguided attempt to control urinary incontinence. Alcohol consumption may be a preventive factor for constipation. Associations with other conditions and their treatments Half or more of older people with faecal incontinence also have urinary incontinence. Co-​morbidity and physical disability con- tribute as much or more than age in predicting constipation and faecal incontinence. Diarrhoea or loose stool is a strong predictor for faecal incontinence in all settings, but is most common in frail older people. In acutely hospitalized patients, loose/​liquid stool consistency, illness severity, and older age are the strongest predictors of faecal incontinence, while faecal loading, functional disability, loose stools, and cognitive impairment are contributory factors. In nursing home residents, risk factors for constipation include low fluid intake, poor bed mobility, neurodegenerative conditions, polypharmacy, and specific culprit medications. Constipation oc- curs in up to a third of patients receiving enteral nutrition. Products containing fibre are available, but definitive data on their efficacy is lacking. Depression and anxiety are associated with increased self-​ reported constipation and faecal incontinence in older people. A perception of constipation may be a somatic manifestation of psychiatric illness, so not all self reports are confirmed by other features. Table 6.9.7  Definitions of constipation Constipation (Rome III criteria) Symptoms for over six months and two or more of the following symptoms on more than 25% of defecations during the past three months: • Straining • Lumpy or hard stools • Two or less bowel movements per week • Sense of incomplete evacuation • Loose stools not present and insufficient criteria for irritable bowel syndrome (abdominal distension or pain relieved by defecation, passage of mucus) Rectal outlet delay or difficult evacuation • Sensation of anorectal blockage • Need for manual manoeuvres (e.g. pressing in or around the anus to aid evacuation) to facilitate defecations Clinical constipation • Large amount of faeces (hard or soft) in rectum on digital examination and/​or • Faecal loading on abdominal radiograph

596 Section 6  Old age medicine Hypercalcaemia from any cause results in constipation by inducing reversible conduction delay within the extrinsic and in- trinsic gut innervations. Constipation is also a well-​recognized diagnostic feature of hypothyroidism, particularly in older women. Long-​term renal haemodialysis patients have prolonged age-​adjusted gut transit time:  most have bothersome constipa- tion unless treated. The cause is likely multifactorial and may include fluid restriction, low fibre intake, suppression of the defe- cation urge while undergoing dialysis, and co​morbidities such as diabetes. Ion exchange resins, sometimes used to prevent or treat hyperkalaemia, are extremely constipating and on occasion a cause of faecal perforation. Diabetes mellitus Diabetic autonomic neuropathy can result in slow colonic transit and impairment of the gastrocolic reflex, but constipation can occur without neuropathy so other factors are involved. Faecal incontinence may result from anorectal dysfunction or bac- terial overgrowth due to prolonged gut transit, which charac- teristically causes nocturnal diarrhoea. Acute hyperglycaemia can further inhibit anorectal function and colonic peristalsis. Metformin, thiazolidineodiones and the gliptins can also cause loose stools, increasing the risk of faecal incontinence. The α-​glucosidase inhibitor, acarbose, may cause diarrhoea, but it may usefully reduce transit time in diabetic patients with constipation. Neurodegenerative conditions More than half of patients with Parkinson’s disease report consti- pation (Rome criteria), mostly being bothered by it. It may present early, even before motor symptoms. There are several mechan- isms: loss of dopaminergic neurons and increased Lewy bodies in the myenteric plexus prolong colonic transit; pelvic dyssynergia causes rectal outlet delay and prolonged straining. Constipation is often associated with other non​motor symptoms, adversely impacting quality of life. Dihydroxyphenylalanine (DOPA) or dopamine agonists may exacerbate constipation. Botulinum toxin injected into the puborectalis muscle has been used to improve rectal emptying in Parkinson’s disease patients with good effect, though repeat injections every three months are required to main- tain clinical benefit. Dementia predisposes individuals to rectal dysmotility, partly through ignoring the urge to defecate. Constipation may precipi- tate physically aggressive behaviour in those unable to communi- cate the problem. Patients with Parkinson’s disease dementia or Lewy body dementia are more likely than those with Alzheimer’s to suffer constipation, impaction, faecal incontinence, and other autonomic symptoms Constipation affects 60% of those recovering from stroke and in early stages this may be associated with combined rectal outlet delay and slow transit constipation. Faecal incontinence is several-​fold more prevalent in stroke survivors than controls. It may develop months after acute stroke and can be transient, con- sistent with the cause being constipation plus overflow. Later on, faecal incontinence is associated with mobility disability rather than the size or location of the stroke lesion. Weak abdominal and pelvic muscles causing difficulties with evacuation may also contribute. Polypharmacy/​drug side effects Many medications increase the risk of constipation (Box 6.9.2). Drug classes with anticholinergic effects reduce gut smooth muscle contractility and are associated with symptomatic con- stipation in community-​dwelling older people and with faecal incontinence in stroke survivors. Long-​term use may result in chronic megacolon. The tendency to constipation from opiates (oral more than transdermal) can be effectively managed by co​prescribing laxatives or suppositories. The key factor with iron supplements is total elemental iron absorbed. Calcium channel blockers can cause severe constipation by impairing lower gut (particularly rectosigmoid) motility. Non​steroidal anti-​ inflammatory drugs (NSAIDS) promote constipation through prostaglandin inhibition. Association with primary gastrointestinal disorders Suspicion for colorectal cancer should be higher in older adults than younger counterparts with bowel symptoms, including faecal incontinence. As a sole symptom, constipation (≤2 reported bowel movements a week) is associated with a greater risk of colon cancer in older people, hence colonoscopy may be warranted in the ab- sence of other obvious causes. Constipation-​predominant irritable bowel syndrome (IBS-​C) is a prevalent subtype of IBS among older people, with preponder- ance for women. It shares some of the Rome III diagnostic criteria for constipation, but is also associated with lower socioeconomic status, anxiety, depression, and somatization. The pathophysi- ology is distinct from the usual chronic constipation, and the usual laxative-​based treatment approach is less successful. Prokinetic and prosecretory agents may be helpful. Perhaps half of adults aged 60+ in developed countries have left-​sided diverticulosis coli, predominantly associated with inad- equate fibre intake, prolonged gut transit, and straining-​induced high intraluminal pressures. This anatomical change may not cause symptoms. Patients with an episode of acute uncomplicated diverticulitis need treatment as they are at risk of erratic bowel habit, with diarrhoea sometimes alternating with constipation, long-​term abdominal pain, and recurrent acute diverticulitis with fever, systemic upset, and potentially perforation. Epidemiology Systematic reviews examining the prevalence of constipation and faecal incontinence have suffered from the lack of standardiza- tion in definitions, but constipation is clearly a highly prevalent problem for older people. For example, in 2004 it was reported that some 63 million people in North America were affected (Rome III Box 6.9.2  Medications increasing the risk of constipation • Polypharmacy (over five medications) • Anticholinergic drugs and total anticholinergic burden (tricyc- lics, antipsychotics, antihistamines, antiemetics, drugs for detrusor hyperactivity) • Opiates • Iron or calcium supplements • Antacids containing aluminium • Non​steroidal anti-​inflammatories

6.9  Bladder and bowels 597 criteria), with a higher prevalence in those aged 65 plus. Reports of infrequent bowel movements alone (≤2 per week) is no more preva- lent in older than younger people (fewer than 8%), and more than 50% move their bowels daily. However, two-​thirds have persistent straining and over a third report hard stools, and this along with evacuation difficulty contributes to higher rates of self-​reported constipation in older people. Despite laxative use, most surveys find that most care home residents are constipated according to Rome III criteria. Among these frailer individuals, difficult evacu- ation can lead to recurrent rectal impaction and overflow. Faecal impaction was a primary diagnosis in 27% of acutely hos- pitalized geriatric patients admitted over the course of one year in the United Kingdom. Loading is the underlying factor in over half and may be even more for care home residents. In community-​dwelling people age has a significant influence on rates of solid and liquid faecal incontinence. The prevalence varies according to the general health and setting of the study, but is typically 6–​12% for community dwellers aged 65+, and two to threefold higher among the 80+ population. Rates are typically twice or more during acute illness requiring hospitalization, and up to 50% in care homes, but these rates depend on the highly variable casemix and quality of bowel care received. Incidence rates are very much higher for people with dementia. Persisting faecal incontinence is a poor prognostic factor in care home residents. Surveys persistently show that, in contrast with younger women, many older people do not report or seek help with faecal incontinence, prompting the suggestion that screening or a sys- tematic case finding approach may be helpful in primary care services, and is essential in care homes. The quality of assess- ment and response in both settings has been demonstrably poor in surveys or audits, so much remains to be done in education and training. Pathogenesis Colonic function Physiological studies suggest that changes in the lower bowel predisposing towards constipation in older people are not pri- marily age-​related. The extrinsic risk factors discussed previ- ously predominate in the pathophysiology of constipation. The total gut transit time (normally 80% of radio-​opaque markers pass from mouth to anus within five days), colonic motor ac- tivity, and postprandial gastrocolic reflex show no differ- ences between healthy older and younger people. Conversely, older people with chronic constipation have prolonged transit, mainly of the left colon and rectosigmoid. Prolongation is greater in institutionalized or bedridden people. Slow transit results in a cycle of worsening constipation by reducing stool water content (normally 75%), shrinking faecal bulk, reduction in intraluminal pressures, and hence less generation of propa- gating motor complexes and propulsive activity. The changes in the ageing gut that predispose to these developments are shown in Box 6.9.3. Pathological metabolic states may also impact colonic func- tion: hypokalaemia and hypomagnesaemia produce neuronal dys- function that minimizes acetylcholine stimulation of gut smooth muscle and hence prolongs transit through the gut. This may cause acute colonic pseudo-​obstruction. Anorectal function Studies of anorectal function show age-​related changes. In normal defecation, colonic activity propels stool into the rectal ampulla causing distention and reflex relaxation of the smooth muscle of the internal anal sphincter or anal canal. This is followed by reflex contraction of the external anal sphincter and skeletal pelvic floor muscles. On perception of the need to defecate, the external sphincter is voluntarily re- laxed, and evacuation proceeds with assistance from abdom- inal wall muscle contraction. There is an age-​related decline in internal sphincter tone and thickness, particularly in frailer older people, predisposing to faecal incontinence. External anal sphincter and pelvic muscle strength is also reduced, particu- larly in multiparous women, contributing to both faecal incon- tinence and evacuation difficulties. Rectal motility is probably preserved in healthy ageing, but some studies have shown increased anorectal sensitivity thresh- olds and reduced rectal compliance. Table 6.9.8 shows the three manifestations of anorectal dysfunction. The anorectal pathology is multifactorial in older women, including pudendal neuropathy, diabetes, and rectal and vaginal prolapse. Constipation and pro- longed straining may further impair pudendal nerve function. Box 6.9.3  Changes in the ageing gut that predispose to constipation • Reduced number of neurons in the myenteric plexus • Impaired response to direct stimulation leading to intrinsic myenteric dysfunction • Progressive loss of interstitial cells of Cajal in the colon • Increased collagen deposit in left colon leading to altered compli- ance and motility • Reduced amplitude of inhibitory junction potentials and hence in- hibitory nerve input to circular colonic muscle causing segmental motor incoordination • Increased binding of plasma endorphins to gut receptors Table 6.9.8  Patterns of anorectal dysfunction leading to rectal outlet delay Name Pathophysiology Clinical picture Rectal dysmotility Reduced rectal motility and contractions Increased rectal compliance, leading to dilation Impaired rectal sensation, blunting urge to pass stool Chronically, rectal distention required to trigger the defecation reflex Hard or soft stool retention on digital examination of which patient may be unaware Chronic rectal distention leads to relaxation of the internal sphincter and faecal soiling Pelvic floor dyssynergia Paradoxical contraction or failure to relax the pelvic floor and external anal sphincter muscles during defecation Severe and longstanding rectal outlet delay Irritable
bowel syndrome (IBS) Increased rectal tone and reduced compliance Lower pain threshold on distending the rectum Usually constipation-​ predominant in older people Abdominal distention or pain relieved by defecation Passage of mucus, and feeling of incomplete emptying

598 Section 6  Old age medicine Pelvic floor dyssynergia may result from sacral cord ischaemia or impingement impairing parasympathetic outflow. It is also ob- served in Parkinson’s disease. Clinical features and differential diagnosis History For the bowel history, a stool chart (recorded by carers if neces- sary) for one week to document bowel pattern and episodes of faecal incontinence may be helpful. Assessment of stool consist- ency is diagnostically helpful and the Bristol stool chart is suitable (Fig. 6.9.1). A recent history of altered bowel habit should prompt consideration of causes other than or additional to ageing, frailty, or dementia (Box 6.9.4). The main differential diagnoses include gastrointestinal problems—​ diverticulitis (with or without complications such as perforation or fistulae), colon or anorectal cancer, and rectal ischaemia—​and spinal cord disease. IBS-​C should be a diagnosis of exclusion in older people, and only made in those with a long history of IBS symptoms. Abdominal pain developing on a background of chronic consti- pation may herald complications such as impaction with obstruc- tion, stercoral perforation, sigmoid volvulus, or urinary retention. Imaging is necessary to clarify the diagnosis. Faecal incontinence associated with faecal loading usually pre- sents as frequent passive leakage of watery stool, which may mis- lead patients, carers, and healthcare providers into thinking the problem is diarrhoea rather than constipation. Leakage of small amounts with some urgency sensation is more typical of external anal sphincter weakness, whereas leakage without awareness is more typical of internal sphincter dysfunction. Faecal incontin- ence associated with complete formed bowel movements is seen in dementia, although these patients are also prone to faecal incontin- ence from faecal loading. Faecal impaction may present with anorexia, vomiting, and ab- dominal pain, but non​specific deterioration may be the only clue in patients with frailty and/​or dementia. Physical examination Digital rectal examination (DRE) is mandatory. It may reveal hard stool, soft stool (particularly when laxatives are used) or no stool, which does not exclude higher impaction. In impaction, other find- ings may include fever, delirium, abdominal distention, reduced bowel sounds, and tachypneoa caused by diaphragmatic splinting. The sepsis features are thought due to microscopic stercoral ulcer- ations of the colon. A dilated rectum with diminished sensation on DRE and re- tained stool suggests rectal dysmotility. Digital assessment of squeeze and basal tone has been shown to be as sensitive and specific as manometry in discriminating sphincter function be- tween continent and incontinent older patients aged over 50. Easy finger insertion with gaping of the anus on finger removal indicates poor internal sphincter tone, whereas reduced squeeze pressure around the finger when asking the patient to ‘squeeze and pull up’ suggests external sphincter weakness. Absent cutaneous-​anal reflex (gentle scratching of the anal margin should normally induce a visible contraction of the external sphincter) and, in particular, perianal anaesthesia suggests sa- cral cord dysfunction. Proctoscopy can easily be incorporated into bedside or clinic as- sessment. It may reveal internal haemorrhoids, anal fissure, ano- rectal cancer, or other abnormalities. Perineal examination is needed for assessment of faecal incon- tinence and constipation in older women, and may reveal posterior vaginal prolapse (evident when bearing down in the gynecologic position), excessive perineal descent (>4 cm when patient bearing down while lying in the lateral position), or rectal prolapse, though lesser degrees of prolapse may be only evident when the patient strains while sitting or squatting. Urinary retention may be associated with faecal incontinence because of common causation (e.g. spinal cord disease), or may re- sult from faecal loading itself, particularly in women. Investigations Plain abdominal X-​ray can be helpful in evaluating constipation. It may demonstrate complications such as sigmoid volvulus or extraluminal gas due to stercoral perforation or more commonly colonic or rectal faecal loading associated with lower bowel dila- tion. Fluid levels in the large or small bowel suggest advanced obstruction. Acute colonic pseudo-​obstruction is most likely to Separate hard lumps, like nuts (hard to pass) Type 1 Type 2 Type 3 Type 4 Type 5 Type 6 Type 7 Bristol Stool Chart Sausage-shaped but lumpy Like a sausage but with cracks on the surface Like a sausage or snake, smooth and soft Soft blobs with clear-cut edges Fluffy pieces with ragged edges, a mushy stool Watery, no solid pieces, Entirely liquid Fig. 6.9.1  Bristol Stool Scale Chart. From Lewis SJ, Heaton KW (1997). Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol, 32 (9), 920–​4, reprinted by permission of the publisher (Taylor & Francis Ltd, http://​www.tandfonline.com). Box 6.9.4  Symptoms that should promote further assessment and investigations • Abdominal pain • Fever • Rectal bleeding or mucus • Rectal pain • Systemic features such as weight loss and anaemia • Faecal incontinence preceding urinary incontinence in patients with dementia

6.9  Bladder and bowels 599 occur in acutely ill hospitalized frail older people with a history of chronic constipation, and may cause colonic dilation with a caecal diameter of ≥10 cm. Faecal loading in the descending and sigmoid colon, and/​or faeces rather than air in the caecum, correlate well with prolonged transit time. Dilatation of the colon in the absence of acute obstruction points to a neurogenic component to bowel dysfunction and thus identifies patients at risk of recurrent co- lonic impaction. Rectal dilatation (>4 cm) implies dysmotility and evacuation problems. Sigmoidoscopy, colonoscopy, or contrast imaging with enema or computed tomography (CT) may be necessary for investigation in patients with worrying clinical features as outlined. Their safety profile in older patients is good, although preparation may need modification and some patients may merit overnight monitoring. The diagnostic yield of colonoscopy for investigation of constipa- tion without other features is low. Anorectal function tests Management of older people with constipation or faecal incontin- ence is not generally improved by anorectal physiology tests. If con- servative measures are inadequate, then endoanal ultrasound may be helpful is in identifying patients for either surgery (sphincter reconstruction) or biofeedback treatment of pelvic dyssynergia manifest by clinically weak sphincters, preserved sensation, and persistent rectal outlet delay. Treatment As the causes of constipation and faecal incontinence in older people are usually multifactorial, and management is impacted by co​morbidity, functional, and social factors, the comprehensive geriatric assessment approach is necessary. Non​pharmacological approaches These should be the first line of management and for many will be sufficient, but plenty of evidence shows that they are underused, even in primary care or in care homes where the prevalence jus- tifies greater levels of competence than currently seem to exist. Research is lacking as a result of professional disinterest, lack of research funding, and the practical challenges of researching with older frail people. Education of patients and caregivers The scope and approach should be targeted to the individual, with awareness of caregiver needs and challenges. The goals may range from resolution of the constipation or faecal incontinence, or minimizing the impact on quality of life while not abolishing the problem, to the practical issues of dealing with intractable faecal incontinence such as pads, bedsheets, and odour control. One randomized controlled trial with older stroke patients showed that an educational approach resulted in persisting modi- fication of diet and fluid intake to control bowel problems. There is insufficient evidence to establish the impact of individual or popu- lation approaches to increasing dietary fibre. Educating informal caregivers on maintaining faecal continence in patients with de- mentia may increase their knowledge, but the impact on faecal incontinence is unknown. The main components of advice and in- formation are shown in Box 6.9.5 and are best supported by written material of appropriate style and language. Pharmacological treatments for constipation The evidence base for laxative treatments in older people is poor, but there is some randomized controlled trial evidence for efficacy and safety in adults with chronic constipation for osmotic salts, sugars and sugar alcohols, polyethylene glycol (PEG), anthraquinones, diphenolic laxatives, bisacodyl, and sodium picosulphate. Higher quality evidence supports the use of polyethylene glycol, followed by lactulose and psyllium. Newer prokinetic agents show promise, but comparative trials and clarification of potential cardiac adverse effects are needed. The paucity of data showing comparative effectiveness of laxa- tives in clinical practice means that a systematic step-​wise ap- proach is recommended for most patients, starting with the milder and cheaper products. For patients in particular clinical settings with a high risk of serious constipation and potential impaction, starting with the stronger agent such as polyethylene glycol (com- bined if necessary with enemas) should be considered. Unsuccessful prevention or treatment often results from inad- equate assessment, resulting in an inappropriate strategy. Rectal outlet delay often requires a different approach (e.g. enemas or sup- positories) to prolonged transit. Selection and techniques of enema and suppository use in frail older people also requires some ex- pertise. Regular use of phosphate enemas should be avoided in pa- tients with renal impairment as hyperphosphataemia may occur. Tap water enemas are the safest type for regular use, although they take more time. Manual evacuation may be necessary before inser- tion of enemas or suppositories in patients with hard stool rectal impaction. Treatment of faecal incontinence The first step is to identify the underlying cause. The general ap- proach to management of the main causes is shown in Table 6.9.9. Comprehensive geriatric assessment Attitudes and coping strategies affect the impact that bowel prob- lems have on individuals, hence these factors need to be incorp- orated in assessment and management, as well as the physical and social resources upon which they can call for support. This means that a comprehensive geriatric assessment-​based approach is re- quired. Functional faecal incontinence can occur in individuals with normal gut function but with toilet access difficulties due to cogni- tive or functional limitations. The difficulties may include wiping Box 6.9.5  Advice and information for carers of patients with dementia and faecal incontinence • Understanding the range of normal bowel patterns • Maintaining a regular and comfortable bowel habit, with attention to privacy/​dignity • The technique of abdominal massage for constipation • Dietary advice to encourage softer stools and increase fibre and fluid intake • Advice on probiotic supplementation (particularly Bifidobacterium Lactis) • Avoidance of sedentariness and increasing physical activity, eg walking • Sphincter strengthening exercises • Using suppositories to stimulate evacuation

600 Section 6  Old age medicine and adjustment of clothing. Withholding evacuation because of access problems can lead to constipation. The domestic or outdoor environment may need assessment to understand the challenges. Loss of continence along with physical independence is under- mining and distressing. Preservation of privacy and dignity of care is important, particularly in institutional or other ‘public’ settings. FURTHER READING Urinary incontinence Ancelin ML, et al. (2006). Non-​degenerative mild cognitive impair- ment in elderly people and use of anticholinergic drugs: longitu- dinal cohort study. BMJ, 332, 455–​9. Continence Products Advisor (a collaboration between the Inter­ national Consultation on Incontinence (ICI) and the International Continence Society). http://​www.continenceproductadvisor.org Gray SL, et al. (2015). Cumulative use of strong anticholinergic medi- cations and incident dementia. JAMA Intern Med, 175, 401–​7. Haylen BT, et al. (2010). An International Urogynecological Asso­ ciation (IUGA)/​International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn, 29, 4–​20. International Consultation on Urological Diseases (2013). Incontinence, 5th edition. http://www.icud.info/​incontinence.html Mayer T, Haefeli WE, Seidling HM (2015). Different methods, dif- ferent results—​how do available methods link a patient’s anti- cholinergic load with adverse outcomes? Eur J Clin Pharmacol, 71, 1299–​314. National Institute for Health and Care Excellence (NICE) (2010). Lower Urinary Tract Symptoms in Men:  Management. Clinical guideline [CG97]. https://​www.nice.org.uk/​guidance/​cg97 National Institute for Health and Care Excellence (NICE) (2012). Urinary Incontinence in Neurological Disease:  Assessment and Management. Clinical guideline [CG148]. https://​ Available from www.nice.org.uk/​guidance/​cg148 National Institute for Health and Care Excellence (NICE) (2013). Mirabegron for Treating Symptoms of Overactive Bladder. Technology appraisal guidance [TA290]. https://​www.nice.org. uk/​guidance/​ta290 National Institute for Health and Care Excellence (NICE) (2013). Urinary Incontinence in Women: Management. Clinical guideline [CG171]. https://​www.nice.org.uk/​guidance/​cg171 Oelke M, et al. (2015). Appropriateness of oral drugs for long-​term treatment of lower urinary tract symptoms in older persons: re- sults of a systematic literature review and international consensus validation process (LUTS-​FORTA 2014). Age Ageing, 44, 745–​55. Salahudeen MS, Duffull SB, Nishtala PS (2015). Anticholinergic burden quantified by anticholinergic risk scales and adverse out- comes in older people: a systematic review. BMC Geriatr, 15, 31. Villalba-​Moreno AM, et al. (2016). Systematic review on the use of anticholinergic scales in polypathological patients. Arch Gerontol Geriatr, 62, 1–​8. Review. Erratum in: Arch Gerontol Geriatr, 2016 May–​Jun, 64, 178–​80. Constipation and faecal incontinence Akpan A, Gosney MA, Barrett JA (2007). Factors contributing to fecal incontinence in older people and outcome of routine man- agement in home, hospital and nursing home settings. Clin Interv Aging, 2, 139–​455. Costilla VC, Foxx-​Orenstein AE (2014). Constipation in adults: diagnosis and Management. Curr Treat Options Gastroenterol, 12, 310–​21. Edwards NI, Jones D (2001). The prevalence of faecal incontinence in older people living at home. Age Ageing, 30, 503–​17. Harari D, et al. (2014). National audit of continence care: adherence to National Institute for Health and Clinical excellence (NICE) Guidance in older versus younger adults with faecal incontinence. Age Ageing, 43, 785–​93. Koloski NA, et al. (2013). Impact of persistent constipation on health-​ related quality of life and mortality in older community-​dwelling women. Am J Gastroenterol, 108, 1152–​8. Landefeld CS, Bowers BJ, Feld AD (2008). National Institutes of Health state-​of-​the-​science statement:  prevention of fecal and urinary incontinence in adults. Ann Intern Med, 148, 449–​58. Macmillan AK, et al. (2004). The prevalence of fecal incontinence in community-​dwelling adults: a systematic review of the literature. Dis Colon Rectum, 47, 1341–​9. Noisen E, et al. (2014). Constipation prevalence and incidence among medical patients acutely admitted to hospital with a medical con- dition. J Clin Nurs, 23, 2295–​302. Norton C, Thomas L, Hill J (2007). Management of faecal incon- tinence in adults: summary of NICE guidance. Br Med J, 334, 1370–​1. Rayner CK, Horowitz M (2013). Physiology of the ageing gut. Curr Opin Clin Nutr Metab Care, 16, 33–​8. Rey E, et al. (2014). A nation-​wide study of prevalence and risk factors for fecal impaction in nursing homes. PLoS One, 9, e105281. Saga S, et al. (2013). Prevlaence and correlates of fecal incontinence among nursing home residents: a population-​based cross-​sectional study. BMC Geriatr, 13, 87. Schnelle JF, et al. (2002). Translating clinical research into practice: a randomized controlled trial of exercise and incontinence care with nursing home residents. J Am Geriatr Soc, 50, 1476–​83. Table 6.9.9  Management of faecal incontinence Overflow faecal incontinence Aim for avoidance of faecal impaction by use of stimulant and/​or osmotic laxatives Add in regular suppositories and enemas if necessary Faecal incontinence related to frailty and/​or dementia Avoid impaction Carry out a structured bowel care plan including regular prompted toileting Faecal incontinence with loose stools Treat or remove identifiable causes, including medications Increase dietary fibre and reduce potential dietary factors (e.g. dairy products, alcohol, unpeeled fruit) Consider loperamide or similar medications Faecal incontinence with weak anal sphincters Consider suitability for sphincter strengthening exercises and biofeedback approaches