Personalised future prescribing using pharmacogenomics: A resumé of a joint Royal College of Physicians / British Pharmacological Society working party report.

There is rapidly growing recognition of the important contribution of individually carried genetic factors to drug response variation (pharmacogenomics) for an increasingly wide range of drugs and of the resulting implications for healthcare across multiple specialisms. This concise overview of the March 2022 joint report of the Royal College of Physicians and the British Pharmacological Society on this topic outlines its coverage of aspects of scientific rationale (with examples), the so far largely unmet need for planned, systematic implementation and training within the UK NHS, and the key forward strategies required. They include a centrally funded, well defined developmental service design with implementation priorities, clinical decision support, clear clinical governance and ongoing research, public and patient engagement, and agreed, updated education and training packages.

Health risk appraisal in older people 7: long-acting benzodiazepine use in community-dwelling older adults in London: is it related to physical or psychological factors?

Aim To investigate whether the use of long-acting benzodiazepines, in individuals aged 65 and over is mediated by physical or psychological factors. BACKGROUND: Long-acting benzodiazepine consumption among older people has implications for mortality, morbidity and cost-effective prescribing. Two models explain benzodiazepine use in this age group, one linked to physical illness and disability and one to psychological factors. METHODS: Secondary analysis of baseline data from a study of 1059 community-dwelling non-disabled people aged 65 years and over recruited from three general practices in London. For this analysis, use of long-acting benzodiazepines was defined as any self-reported use of diazepam or nitrazepam in the last four weeks. Associations between demographic factors, health service use, and physical and psychological characteristics and benzodiazepine use were investigated. Findings The prevalence of benzodiazepine use in this sample was 3.3% (35/1059). In univariate analyses, benzodiazepine use was associated with female gender, low income, high consultation rates, physical factors (medication for arthritis or joint pain, polypharmacy, difficulties in instrumental activities of daily living, recent pain) and psychological factors (poor self-perceived health, social isolation, and symptoms of anxiety or agitation). In a multivariate logistic regression analysis only two factors retained statistically significant independent associations with benzodiazepine use: receiving only the state pension (OR=4.0, 95% CI: 1.70, 9.80) and pain in the past four weeks (OR=3.79, 95% CI: 1.36, 10.54).

Interdisciplinary management of hip fracture.

Hip fracture is a prevalent age-associated occurrence incorporating both medical and surgical need and a major challenge to public health and NHS resources. Effective management requires coordinated collaboration across specialties, professions and services. This concise guideline focuses on interdisciplinary aspects of hip fracture management abstracted from National Institute for Health and Care Excellence (NICE) clinical guideline (CG124), including the concept and implementation of the Hip Fracture Programme, detection and management of comorbidity and delirium, optimal analgesia, timing of surgery, multidisciplinary mobilisation, rehabilitation and hospital discharge. The recently updated National Hip Fracture Database report and NICE quality standard are potential drivers for progress.

Effect of health risk assessment and counselling on health behaviour and survival in older people: a pragmatic randomised trial.

BACKGROUND: Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS: This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS: This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

Assessment and prevention of falls in older people--concise guidance.

Falls in later life are a major health issue, both in terms of their injurious consequences and their significance as a diagnostic marker. Cost-effective measures for their assessment and prevention are well documented but insufficiently implemented. This Concise Guideline comprises a distillation of recommendations for the assessment and prevention of falls in older people based on Clinical Guideline 161 (incorporating CG21) published by the National Institute of Health and Care Excellence (NICE) in 2013. The recommendations are intended to provide both generalists and specialists with an overview of practical strategies for clinical case and/or risk ascertainment and intervention, and for referral and service implementation across the primary-secondary care interface and within the hospital setting. Recommendations abstracted verbatim from the Guideline are highlighted. Explanatory or supporting comment is given as appropriate.

Risk factors for depressed mood amongst a community dwelling older age population in England: cross-sectional survey data from the PRO-AGE study.

BACKGROUND: The Quality and Outcomes Framework in the United Kingdom (UK) National Health Service previously highlighted case finding of depression amongst patients with diabetes or coronary heart disease. However, depression in older people remains under-recognized. Comprehensive data for analyses of the association of depression in older age with other health and functional measures, and demographic factors from community populations within England, are lacking. METHODS: Secondary analyses of cross-sectional baseline survey data from the England arm of a randomised controlled trial of health risk appraisal for older people in Europe; PRO-AGE study. Data from 1085 community-dwelling non-disabled people aged 65 years or more from three group practices in suburban London contributed to this study. Depressed mood was ascertained from the 5-item Mental Health Inventory Screening test. Exploratory multivariable logistic regression was used to identify the strongest associations of depressed mood with a previous diagnosis of a specified physical/mental health condition, health and functional measures, and demographic factors. RESULTS: Depressed mood occurred in 14% (155/1085) of participants. A previous diagnoses of depression (OR 3.39; P < 0.001) and poor vision as determined from a Visual Function Questionnaire (OR 2.37; P = 0.001) were amongst the strongest factors associated with depressed mood that were independent of functional impairment, other co-morbidities, and demographic factors. A subgroup analyses on those without a previous diagnosis of depression also indicated that within this group, poor vision (OR 2.51; P = 0.002) was amongst the strongest independent factors associated with depressed mood. CONCLUSIONS: Previous case-finding strategies in primary care focussed on heart disease and diabetes but health-related conditions other than coronary heart disease and diabetes are also associated with an increased risk for depression. Complex issues of multi-morbidity occur within aging populations. 'Risk' factors that appeared stronger than those, such as, diabetes and coronary heart disease that until recently prompted for screening in the UK due to the QOF, were identified, and independent of other morbidities associated with depressed mood. From the health and functional factors investigated, amongst the strongest factors associated with depressed mood was poor vision. Consideration to case finding for depressed mood among older people with visual impairment might be justified.

Health risk appraisal in older people 6: factors associated with self-reported poor vision and uptake of eye tests in older people.

BACKGROUND: Although free eye testing is available in the UK from a nation-wide network of optometrists, there is evidence of unrecognised, tractable vision loss amongst older people. A recent review identified this unmet need as a priority for further investigation, highlighting the need to understand public perceptions of eye services and barriers to service access and utilisation. This paper aims to identify risk factors for (1) having poor vision and (2) not having had an eyesight check among community-dwelling older people without an established ophthalmological diagnosis. METHODS: Secondary analysis of self-reported data from the ProAge trial. 1792 people without a known ophthalmological diagnosis were recruited from three group practices in London. RESULTS: Almost two in ten people in this population of older individuals without known ophthalmological diagnoses had self-reported vision loss, and more than a third of them had not had an eye test in the previous twelve months. In this sample, those with limited education, depressed mood, need for help with instrumental and basic activities of daily living (IADLs and BADLs), and subjective memory complaints were at increased risk of fair or poor self-reported vision. Individuals with basic education only were at increased risk for not having had an eye test in the previous 12 months (OR 1.52, 95% CI 1.17-1.98 p=0.002), as were those with no, or only one chronic condition (OR 1.850, 95% CI 1.382-2.477, p<0.001). CONCLUSIONS: Self-reported poor vision in older people without ophthalmological diagnoses is associated with other functional losses, with no or only one chronic condition, and with depression. This pattern of disorders may be the basis for case finding in general practice. Low educational attainment is an independent determinant of not having had eye tests, as well as a factor associated with undiagnosed vision loss. There are other factors, not identified in this study, which determine uptake of eye testing in those with self-reported vision loss. Further exploration is needed to identify these factors and lead towards effective case finding.

Health risk appraisal for older people 4: case finding for hypertension, hyperlipidaemia and diabetes mellitus in older people in English general practice before the introduction of the Quality and Outcomes Framework.

BACKGROUND: Early intervention can help to reduce the burden of disability in the older population, but many do not access preventive care. There is uncertainty over what factors influence case finding in older patients in general practice. AIM: To explore factors associated with case finding for hypertension, hyperlipidaemia and diabetes mellitus in older patients. METHOD: Two thousand four hundred and ninety-one patients aged 65 years and above were recruited from three large practices in suburban London before the introduction of the Quality and Outcomes Framework (QOF) completed a questionnaire on health, functional status, health behaviours and preventive care. FINDINGS: Those not reporting heart disease, diabetes or hypertension were included in a secondary data analysis to explore factors influencing uptake of preventive care measures. Approximately one-third denied having had a blood pressure check in the previous year. They were more likely to have had little contact with doctors and to have an unhealthy lifestyle (smoking and a high-fat diet). One-third reported a cholesterol test in the previous five years. Cholesterol measurement was reported more often by men and those with a high body mass index. Those with unhealthy lifestyles (smoking and high-fat diet), those who had only received the state pension and those who limited their activities because of a fear of falling were less likely to report cholesterol measurement. About 10% reported a fasting blood glucose measurement and were more likely to consult more often and have more medications, but they were less likely to have a high-fat diet. Preventive care uptake was associated with frequent contacts with doctors, but overall the uptake of preventive care was low. Older people with healthier lifestyles were more likely to have primary preventative care interventions. These findings provide a baseline against which the effect of the QOF on the care of older people can be measured in future studies.

Prevention and management of hip fracture in older patients.

The average age at hip fracture is 83 for women and 84 for men, with about 80% of cases in women. The 30% mortality and 20% new institutionalisation rates at 12 months reflect the high prevalence of comorbidity and to some extent suboptimal management at the time of the fracture. With timely intervention and better clinical management many fractures can be prevented and when they do occur their human and economic costs can be greatly reduced. Fragility fractures occur in those with demonstrable osteoporosis or osteopaenia and/or risk factors. The goal of prevention is to identify and treat those at risk UK clinicians lack a single universally endorsed, decision support resource. The prudent strategy is to become familiar with all three available risk measures, introduce fracture risk assessment into routine practice, and allow clinical judgement to prevail in cases of doubt (perhaps, especially in very elderly people, more often in the direction of intervention). The classical signs after a fall by an older person, of severe pain, shortening and external rotation of the affected limb, and loss of mobility, should result in immediate and rapid transfer to hospital. It is not rare in the case of intracapsular fractures for mobility to be deceptively maintained on a moderately or minimally painful hip.

Health risk appraisal for older people 5: self-efficacy in patient-doctor interactions.

OBJECTIVE: Enhancing self-efficacy is central to programmes promoting self-care and self-management. However, little is known about older people's self-efficacy in doctor-patient interactions. This paper investigates lifestyle, medical and demographic factors associated with self-efficacy in doctor-patient interactions in older people in general practice. METHODS: A cross-sectional analysis of data from a randomised controlled trial of older people was conducted in a health risk appraisal study in London. Self-efficacy was measured using the Perceived Efficacy in Patient-Physician Interactions Questionnaire. RESULTS: Older people with higher self-efficacy were significantly more likely to report having had recent preventive care measures such as recent blood pressure measurement and influenza immunisation. Women were less likely to have higher self-efficacy than men. Older people were significantly less likely to have high self-efficacy if they reported having poor memory, low mood, limited activities due to fear of falling, basic education, difficulties with at least one activity of daily living, reduced physical activity, living alone, or risk of social isolation. CONCLUSION: A third of people had low self-efficacy in doctor-patient interactions. They appear to be a vulnerable group. Low self-efficacy in interactions with doctors may be a symptom or a characteristic of older people who experience social isolation and depression. Policies that depend on enhancing self-care and self-management need to consider the large number of older people with low self-efficacy in using medical services, and understanding characteristics in older people associated with lower confidence in doctor-patient interactions may be useful in clinical practice and research.

A randomized trial of effects of health risk appraisal combined with group sessions or home visits on preventive behaviors in older adults.

BACKGROUND: To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany. METHODS: Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse). RESULTS: Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement. CONCLUSIONS: HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior.

The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET).

BACKGROUND: fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications. DESIGN: the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo-controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial. SETTING: HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia. SUBJECTS: all participants were > or =80 years of age and hypertensive. METHODS: participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture. RESULTS: there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498). CONCLUSIONS: despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate.

Association of depression with subsequent mortality, cardiovascular morbidity and incident dementia in people aged 80 and over and suffering from hypertension. Data from the Hypertension in the Very Elderly Trial (HYVET).

BACKGROUND: depression is common in elderly people and may be associated with increased cardiovascular risk and incident dementia. METHOD: participants in the Hypertension in the Very Elderly Trial (HYVET) completed a depression screening instrument, the Geriatric Depression Score (GDS), at baseline and annually. We examined the association of GDS score with incident stroke, mortality and dementia using Cox proportional hazards models (hazard ratios, HR and 95% confidence intervals, CI) adjusted for treatment group and other potential confounders. RESULTS: 2,656 HYVET participants completed the GDS. The mean follow-up was 2.1 years. A GDS score > or =6 was associated with increased risks of all-cause (HR 1.8, 95% CI 1.4-2.3) and cardiovascular mortality (HR 2.10, 95% CI 1.5-3.0), all stroke (HR 1.8, 95% CI 1.2-2.8) and all cardiovascular events (HR 1.6, 95% CI 1.2-2.1). Risk of incident dementia also tended to be increased (HR 1.28, 95% CI 0.95-1.73). Each additional GDS point at baseline also gave rise to a significantly increased risk of fatal and non-fatal cardiovascular events, all-cause mortality and dementia. CONCLUSION: there was a strong association between baseline depression scores and later fatal and non-fatal cardiovascular endpoints over a mean follow-up of 2 years in a hypertensive very elderly group. The mechanism of this association warrants further study.

Cardiovascular and biochemical risk factors for incident dementia in the Hypertension in the Very Elderly Trial.

OBJECTIVES: Several cardiovascular and biochemical factors including hypertension have been associated with cognitive decline and dementia, although both epidemiological and intervention evidence is mixed with the majority of studies examining those in midlife or younger elderly and the recent Hypertension in the Very Elderly Trial showing no significant association between blood pressure lowering and incident dementia. It has also been suggested that risk factors may differ in the very elderly. The aim of these analyses was to examine the impact of baseline cardiovascular and biochemical factors upon incident dementia and cognitive decline in a very elderly hypertensive group. METHODS: Participants of the Hypertension in the Very Elderly Trial were aged at least 80 years and hypertensive. Cognitive function was assessed at baseline and annually with diagnostic information collected for dementia and relationships between baseline total and high-density lipoprotein cholesterol, creatinine, glucose, haemoglobin, heart failure, atrial fibrillation, diabetes, previous stroke and later dementia/cognitive decline were examined. RESULTS: There were 3336 participants with longitudinal cognitive function data. In multivariate analyses higher creatinine was associated with a lower risk of incident dementia and cognitive decline. Higher total and lower high-density lipoprotein cholesterol were associated with lower risk of cognitive decline. Other variables were not significant. CONCLUSIONS: In very elderly hypertensive patients heart failure, diabetes, atrial fibrillation, prior stroke, glucose and haemoglobin levels did not demonstrate a relationship with cognitive decline or dementia. Higher creatinine (excluding moderate renal impairment) was associated with a lower risk of dementia and cognitive decline. The findings for total and high-density lipoprotein cholesterol add to the varied literature in this area and together these findings may add weight to the suggestion that risk factor profiles differ in the very elderly.

The impact of educational level on oral health-related quality of life in older people in London.

There are socioeconomic inequalities in oral health, but the relationship between education and oral health-related quality of life (OHRQoL) among older adults has not been adequately studied. This study assessed whether there is an educational gradient in OHRQoL among older people in London. We employed secondary analysis of baseline data (n = 1,090) from a randomized controlled trial of health-risk appraisal on community-dwelling non-disabled people 65 yr of age and older, registered with three group medical practices in suburban London. Multiple linear regressions were used to analyze the association between OHRQoL [measured using the Geriatric Oral Health Assessment Index (GOHAI)] and education, adjusted for age, gender, pension status, and denture wearing. Overall, 30.6% reported low levels of OHRQoL. Eating discomfort was the most frequent problem (24% reported 'often/always'), while concerns about appearance were also prevalent. Significant variations in OHRQoL existed between socioeconomic groups. In adjusted analyses, there was a clear education gradient in OHRQoL, with worse perceptions at each lower level of education. Low educational level has an independent negative impact on OHRQoL in older people, which is not explained by differences in income or in denture wearing between educational groups. Policies targeting lower educated groups should be complemented with whole-population strategies for the reduction of oral health inequalities.

The relationship between pain intensity and severity and depression in older people: exploratory study.

BACKGROUND: Pain and depression are known to be associated in later life, and both have a negative effect on physical performance both separately and in combination. The nature of the relationships between pain intensity and depression in elderly persons experiencing pain is less clear. The objectives of this study were to explore which factors are associated with depressed mood in older people experiencing pain, and to test the hypothesis that older people experiencing pain are at risk of depressed mood according to the severity or frequency of their pain. In addition we explored whether other potentially modifiable factors might increase the risk of depressed mood in these persons. METHODS: The study is a secondary analysis of baseline data for four hundred and six community-dwelling non-disabled people aged 65 and over registered with three group practices in suburban London who had experienced pain in the past 4 weeks. Intensity and frequency of pain was measured using 24 item Geriatric Pain Measure (GPM) and the presence of depressive symptoms using the 5 item Mental Health Inventory. Risk for social isolation was measured using the 6 item Lubben Social Network scale and instrumental activities of daily living (IADL) were also measured. RESULTS: Overall 76 (19%) had depressed mood. Pain frequency and severity were not statistically significantly associated with depressed mood in this population. In multivariate analyses, significant predictors of the presence of depressive symptoms were difficulties with basic ADLs (OR 2.8, 95% CI 1.1.7.8), risk for social isolation (OR 4.1, 95% CI 1.8-9.3), and basic education only (OR 2.2, 95% CI 1.1-4.4). CONCLUSION: Older people experiencing pain are also likely to experience depression. Among those experiencing pain, social network and functional status seem to be more important predictors of depressive symptoms than the severity of pain. Further studies should evaluate whether improvement of social network and functional status might reduce depressive symptoms in older patients.