Referral to the NHS Diabetes Prevention Programme and conversion from nondiabetic hyperglycaemia to type 2 diabetes mellitus in England: A matched cohort analysis.

BACKGROUND: The NHS Diabetes Prevention Programme (NDPP) is a behaviour change programme for adults who are at risk of developing type 2 diabetes mellitus (T2DM): people with raised blood glucose levels, but not in the diabetic range, diagnosed with nondiabetic hyperglycaemia (NDH). We examined the association between referral to the programme and reducing conversion of NDH to T2DM. METHODS AND FINDINGS: Cohort study of patients attending primary care in England using clinical Practice Research Datalink data from 1 April 2016 (NDPP introduction) to 31 March 2020 was used. To minimise confounding, we matched patients referred to the programme in referring practices to patients in nonreferring practices. Patients were matched based on age (≥3 years), sex, and ≥365 days of NDH diagnosis. Random-effects parametric survival models evaluated the intervention, controlling for numerous covariates. Our primary analysis was selected a priori: complete case analysis, 1-to-1 practice matching, up to 5 controls sampled with replacement. Various sensitivity analyses were conducted, including multiple imputation approaches. Analysis was adjusted for age (at index date), sex, time from NDH diagnosis to index date, BMI, HbA1c, total serum cholesterol, systolic blood pressure, diastolic blood pressure, prescription of metformin, smoking status, socioeconomic status, a diagnosis of depression, and comorbidities. A total of 18,470 patients referred to NDPP were matched to 51,331 patients not referred to NDPP in the main analysis. Mean follow-up from referral was 482.0 (SD = 317.3) and 472.4 (SD = 309.1) days, for referred to NDPP and not referred to NDPP, respectively. Baseline characteristics in the 2 groups were similar, except referred to NDPP were more likely to have higher BMI and be ever-smokers. The adjusted HR for referred to NDPP, compared to not referred to NDPP, was 0.80 (95% CI: 0.73 to 0.87) (p < 0.001). The probability of not converting to T2DM at 36 months since referral was 87.3% (95% CI: 86.5% to 88.2%) for referred to NDPP and 84.6% (95% CI: 83.9% to 85.4%) for not referred to NDPP. Associations were broadly consistent in the sensitivity analyses, but often smaller in magnitude. As this is an observational study, we cannot conclusively address causality. Other limitations include the inclusion of controls from the other 3 UK countries, data not allowing the evaluation of the association between attendance (rather than referral) and conversion. CONCLUSIONS: The NDPP was associated with reduced conversion rates from NDH to T2DM. Although we observed smaller associations with risk reduction, compared to what has been observed in RCTs, this is unsurprising since we examined the impact of referral, rather than attendance or completion of the intervention.

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age: Cohort Study Using Electronic Health Records.

BACKGROUND: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. METHODS: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ≤5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. RESULTS: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40-6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30-7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. CONCLUSIONS: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Inception and deprescribing of statins in people aged over 80 years: cohort study.

Objective: statin use over the age of 80 years is weakly evidence-based. This study aimed to estimate rates of statin inception and deprescribing by frailty level in people aged 80 years or older. Methods: a cohort of 212,566 participants aged ≥80 years was sampled from the UK Clinical Practice Research Datalink. Statin inception was defined as a first-ever prescription in a non-statin user; deprescribing was defined as a last ever statin prescription more than 6 months before the end of participant records. Rates were estimated in a time-to-event framework allowing for mortality as a competing risk. Co-variates were age, gender, frailty category and prevention type. Results: prevalent statin use increased from 2001-5 (9.9%) to 2011-15 (49.3%). Inception of statins in never-users was low overall at 2.4% per year (95% confidence interval (CI) 2.2-2.6%) and declined with age. Deprescribing of statins in current users occurred at a rate of 5.6% (95% CI 5.4-5.9%) per year overall and increased with age, reaching 17.8% per year (95% CI 6.7-28.9%) among centenarians. Deprescribing was slightly higher for primary prevention (6.5% per year) than secondary prevention (5.2% per year) indications (P < 0.001). Deprescribing increased with frailty level being 5.0% per year in 'fit' participants and 7.1% in 'severe' frailty (P < 0.001). Conclusions: statin use has increased in the over 80s but deprescribing is common and increases with age and frailty level. These paradoxical findings highlight a need for better evidence to inform statin use and discontinuation for people aged ≥80 years.

Frailty and bone health in European men.

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.

Chronic widespread pain is associated with worsening frailty in European men.

BACKGROUND: we hypothesised that chronic widespread pain (CWP), by acting as a potential stressor, may predispose to the development of, or worsening, frailty. SETTING: longitudinal analysis within the European Male Ageing Study (EMAS). PARTICIPANTS: a total of 2,736 community-dwelling men aged 40-79. METHODS: subjects completed a pain questionnaire and shaded a manikin, with the presence of CWP defined using the American College of Rheumatology criteria. Physical activity, smoking, alcohol consumption and depression were measured. Repeat assessments took place a median of 4.3 years later. A frailty index (FI) was used, with frail defined as an FI >0.35. The association between CWP at baseline and the new occurrence of frailty was examined using logistic regression; the association between CWP at baseline and change in FI was examined using negative binomial regression. RESULTS: at baseline, 218 (8.3%) men reported CWP. Of the 2,631 men who were defined as non-frail at baseline, 112 (4.3%) were frail at follow-up; their mean FI was 0.12 (SD 0.1) at baseline and 0.15 (SD 0.1) at follow-up, with a mean change of 0.03 (SD 0.08) P ≤ 0.001. Among men who were non-frail at baseline, those with CWP were significantly more likely to develop frailty. After adjustment for age and centre, compared with those with no pain, those with CWP at baseline had a 70% higher FI at follow-up; these associations remained significant after further adjustment for smoking, body mass index, depression, physical activity and FI at baseline. CONCLUSION: the presence of CWP is associated with an increased risk of frailty in older European men.

Association of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone with mortality among middle-aged and older European men.

BACKGROUND: vitamin D deficiency has been associated with an increased risk of mortality, but whether this relationship is causal or linked to co-existent comorbidity and adverse life factors remains uncertain. Our objective was to determine whether endogenous 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D) and parathyroid hormone (PTH) levels predicted all-cause, cardiovascular and cancer mortality independently of health and lifestyle factors. SETTING: : prospective cohort analysis within the European Male Ageing Study. PARTICIPANTS: : 2,816 community-dwelling men aged 40-79 years at baseline. METHODS: : Cox regression was used to examine the association of all-cause mortality with 25(OH)D, 1,25(OH)2D and PTH; cardiovascular and cancer mortality were modelled using competing-risks regression. Results were expressed as hazard ratios (HR) and 95% confidence intervals (CIs) for Cox models; sub-hazard ratios (SHR) and 95% CIs for competing-risks models. RESULTS: : a total of 187 men died during a median of 4.3 years of follow-up. Serum levels of 25(OH)D (per 1 SD decrease: HR = 1.45; 95% CI = 1.16, 1.81) and 1,25(OH)2D (per 1 SD decrease: HR = 1.20; 95% CI = 1.00, 1.44) were associated with an increased risk of all-cause mortality after adjusting for age, centre, smoking, self-reported morbidities, physical activity and functional performance. Only levels of 25(OH)D <25 nmol/l predicted cancer mortality (SHR = 3.33; 95% CI = 1.38, 8.04). CONCLUSION: : lower 25(OH)D and 1,25(OH)2D levels independently predicted all-cause mortality in middle-aged and older European men. Associations with cancer mortality were only observed among men with very low levels of 25(OH)D. These associations were only partially explained by the range of adverse health and lifestyle factors measured here.

The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men.

BACKGROUND: the link between the vitamin D endocrine axis and frailty remains undefined, with few studies examining the joint effect of vitamin D and parathyroid hormone (PTH) levels. Our objective was to determine the association of frailty with serum 25-hydroxyvitamin D (25(OH)D) and PTH. SETTING: cross-sectional analysis within the European Male Ageing Study (EMAS). PARTICIPANTS: a total of 1,504 community-dwelling men aged 60-79 years. METHODS: frailty was classified using a frailty phenotype (FP) and frailty index (FI). The association of frailty with 25(OH)D and PTH was examined using multinomial logistic regression; individual FP criteria with 25(OH)D and PTH using binary logistic regression. Results were expressed as relative odds ratios (ROR) and 95% confidence intervals (CIs) for multinomial; odds ratios (OR) and 95% CIs for binary models. RESULTS: using the FP, 5.0% of subjects were classified as frail and 36.6% as prefrail. Lower levels of 25(OH)D were associated with being prefrail (per 1 SD decrease: ROR = 1.45; 95% CI: 1.26-1.67) and frail (ROR = 1.89; 95% CI: 1.30-2.76), after adjusting for age, centre and health and lifestyle confounders (robust group = base category). Higher levels of PTH were associated with being frail after adjustment for confounders (per 1 SD increase: ROR = 1.24; 95% CI: 1.01-1.52). Comparable results were found using the FI. Among the five FP criteria only sarcopenia was not associated with 25(OH)D levels, while only weakness was associated with PTH. CONCLUSION: lower 25(OH)D and higher PTH levels were positively associated with frailty in older men. Prospective data would enable the temporal nature of this relationship to be explored further.

Investigating the impact of distance on the use of primary care extended hours.

INTRODUCTION: Poor access to general practice services has been attributed to increasing pressure on the health system more widely and low satisfaction among patients. Recent initiatives in England have sought to expand access by the provision of appointments in the evening and at weekends. Services are provided using a hub model. NHS national targets mandate extended opening hours as a mechanism for increasing access to primary care, based on the assumption that unmet need is caused by a lack of appointments at the right time. However, research has shown that other factors affect access to healthcare and it may not simply be appointment availability that limits an individual's ability to access general practice services. OBJECTIVES: To determine whether distance and deprivation impact on the uptake of extended hours GP services that use a hub practice model. METHODS: We linked a dataset (N = 25,408) concerning extended access appointments covering 158 general practice surgeries in four Clinical Commissioning Groups (CCGs) to the General Practice Patient Survey (GPPS) survey, deprivation statistics and primary care registration data. We used negative binomial regression to estimate associations between distance and deprivation on the uptake of extended hours GP services in the Greater Manchester City Region. Distance was defined as a straight line between the extended hours provider location and the patient's home practice, the English Indices of Multiple Deprivation were used to determine area deprivation based upon the home practice, and familiarity was defined as whether the patient's home practice provided an extended hours service. RESULTS: The number of uses of the extended hours service at a GP practice level was associated with distance. After allowing for distance, the number of uses of the service for hub practices was higher than for non-hub practices. Deprivation was not associated with rates of use. CONCLUSION: The results indicate geographic inequity in the extended hours service. There may be many patients with unmet need for whom the extension of hours via a hub and spoke model does not address barriers to access. Findings may help to inform the choice of hub practices when designing an extended access service. Providers should consider initiatives to improve access for those patients located in practices furthest away from hub practices. This is particularly of importance in the context of closing health inequality gaps.

Epidemiology and determinants of non-diabetic hyperglycaemia and its conversion to type 2 diabetes mellitus, 2000-2015: cohort population study using UK electronic health records.

OBJECTIVES: To study the characteristics of UK individuals identified with non-diabetic hyperglycaemia (NDH) and their conversion rates to type 2 diabetes mellitus (T2DM) from 2000 to 2015, using the Clinical Practice Research Datalink. DESIGN: Cohort study. SETTINGS: UK primary Care Practices. PARTICIPANTS: Electronic health records identified 14 272 participants with NDH, from 2000 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Baseline characteristics and conversion trends from NDH to T2DM were explored. Cox proportional hazards models evaluated predictors of conversion. RESULTS: Crude conversion was 4% within 6 months of NDH diagnosis, 7% annually, 13% within 2 years, 17% within 3 years and 23% within 5 years. However, 1-year conversion fell from 8% in 2000 to 4% in 2014. Individuals aged 45-54 were at the highest risk of developing T2DM (HR 1.20, 95% CI 1.15 to 1.25- compared with those aged 18-44), and the risk reduced with older age. A body mass index (BMI) above 30 kg/m2 was strongly associated with conversion (HR 2.02, 95% CI 1.92 to 2.13-compared with those with a normal BMI). Depression (HR 1.10, 95% CI 1.07 to 1.13), smoking (HR 1.07, 95% CI 1.03 to 1.11-compared with non-smokers) or residing in the most deprived areas (HR 1.17, 95% CI 1.11 to 1.24-compared with residents of the most affluent areas) was modestly associated with conversion. CONCLUSION: Although the rate of conversion from NDH to T2DM fell between 2010 and 2015, this is likely due to changes over time in the cut-off points for defining NDH, and more people of lower diabetes risk being diagnosed with NDH over time. People aged 45-54, smokers, depressed, with high BMI and more deprived are at increased risk of conversion to T2DM.

Importance of Frailty for Association of Antipsychotic Drug Use With Risk of Fracture: Cohort Study Using Electronic Health Records.

OBJECTIVE: To evaluate association of first- or second-generation antipsychotic (AP) drugs with fracture risk at different levels of frailty over the age of 80 years. DESIGN: Population-based cohort study. SETTING AND PARTICIPANTS: United Kingdom Clinical Practice Research Datalink including 153,304 patients aged 80 years and older between 2006 and 2015. METHODS: Rates of fracture and adjusted rate ratios (RR) were estimated by AP drug exposure category, adjusting for age, sex, frailty, number of deficits, and dementia diagnosis. RESULTS: Data were analyzed for 165,726 treatment episodes (153,304 patients; 61.3% women; mean age 83 years; 21,365 fractures; 681,221.1 person-years of follow-up). AP exposure was associated with increasing age, frailty, and dementia diagnosis. After adjusting for frailty and covariates, first-generation AP exposure was associated with risk of any fracture, RR 1.24 (95% confidence interval 1.07-1.43, P = .003). Second-generation AP exposure was associated with femur fracture (RR 1.41, 1.22-1.64, P < .001) but less strongly with any fracture (RR 1.12, 1.01-1.24, P = .033). Fracture incidence increased with frailty level. The number of person-years of first-generation AP treatment associated with 1 additional fracture at any site was 75 (42-257) for severely frail patients but 187 (95% confidence interval 104-640) for 'fit' patients. For second-generation AP, 1 additional femur fracture might result from 173 (111-323) person-years treatment in severe frailty but 365 (234-681) person-years treatment for 'fit' patients. CONCLUSIONS AND IMPLICATIONS: Frail patients are more likely to receive AP drug treatment, but their absolute risk of AP-associated fracture is substantially greater than for nonfrail patients.

Trajectory of Total Cholesterol in the Last Years of Life Over Age 80 Years: Cohort Study of 99,758 Participants.

Background: Epidemiological studies suggest that lower total cholesterol (TC) may be associated with higher mortality. This study aimed to evaluate whether a decline in TC before death might account for the association of TC with mortality over age 80 years. Methods: Cohort study using primary care electronic health records of 99,758 participants aged 80-105 years from the UK Clinical Practice Research Datalink. Hazard ratios for all-cause mortality were adjusted for age, gender, frailty, comorbidity, blood pressure, and smoking. Fractional polynomial models were fitted to evaluate longitudinal trends in TC before death or end-of-study. Adjusted odds ratios were estimated using generalized estimating equations. Results: There were 63,630 women and 36,128 men, mean age 86 years, with 29,200 deaths. There were 41,164 treated with statins at cohort entry. Compared with TC values of 4.5-5.4 mmol/L, TC values <3.0 mmol/L were associated with higher mortality (statin treated hazard ratios 1.53, 95% confidence interval 1.43-1.64, p < .001; not treated, 1.41, 1.29-1.54, p < .001). A secular decline in TC values accelerated in the last 2 years of life. In the last quarter of follow-up, the adjusted odds of TC < 3.0 mmol/L for those who died, compared with surviving participants, were 3.33 (2.84-3.91, p < .001) for untreated and 1.88 (1.68-2.11, p < .001) for statin-treated participants. Conclusions: TC values show a terminal decline in the last years of life. Reverse causation may contribute to the association of lower TC with higher mortality in nonrandomized studies.

Incidence and mortality of fractures by frailty level over 80 years of age: cohort study using UK electronic health records.

OBJECTIVE: This study aimed to estimate the association of frailty with incidence and mortality of fractures at different sites in people aged over 80 years. DESIGN: Cohort study. SETTING: UK family practices from 2001 to 2014. PARTICIPANTS: 265 195 registered participants aged 80 years and older. MEASUREMENTS: Frailty status classified into 'fit', 'mild', 'moderate' and 'severe' frailty. Fractures, classified into non-fragility and fragility, including fractures of femur, pelvis, shoulder and upper arm, and forearm/wrist. Incidence of fracture, and mortality within 90 days and 1 year, were estimated. RESULTS: There were 28 643 fractures including: non-fragility fractures, 9101; femur, 12 501; pelvis, 2172; shoulder and upper arm, 4965; and forearm/wrist, 6315. The incidence of each fracture type was higher in women and increased with frailty category (femur, severe frailty compared with 'fit', incidence rate ratio (IRR) 2.4, 95% CI 2.3 to 2.6). Fractures of the femur (95-99 years compared with 80-84 years, IRR 2.7, 95% CI 2.6 to 2.9) and pelvis (IRR 2.9, 95% CI 2.5 to 3.3) were strongly associated with age but non-fragility and forearm fractures were not. Mortality within 90 days was greatest for femur fracture (adjusted HR, compared with forearm fracture 4.3, 95% CI 3.7 to 5.1). Mortality was higher in men and increased with age (HR 5.3, 95% CI 4.3 to 6.5 in those over 100 years compared with 80-84 years) but was less strongly associated with frailty category. Similar associations with fractures were seen at 1-year mortality. CONCLUSIONS: The incidence of fractures at all sites was higher in women and strongly associated with advancing frailty status, while the risk of mortality after a fracture was greater in men and was associated with age rather than frailty category.

Declining blood pressure and intensification of blood pressure management among people over 80 years: cohort study using electronic health records.

BACKGROUND: Management of high blood pressure (BP) in people over 80 years is controversial, but there is limited information available concerning the uptake of hypertension treatment at this age. OBJECTIVE: To evaluate use of antihypertensive drugs and changes in SBP and DBP from 2001 to 2014 in men and women aged 80 years and over. METHODS: Cohort study using primary care electronic health records of 265 225 participants from the UK Clinical Practice Research Datalink. Records of BP and antihypertensive medications were analysed. Linear trends were estimated by frailty category in multiple regression models. RESULTS: Data were analysed for 116 401 men and 148 824 women. The proportion with BP recorded increased from 51% in 2001 to 78% in 2014. The proportion of patients prescribed antihypertensive medications increased from 64 to 76%. Mean SBP declined from 150 (SD 20) mmHg in 2001 to 135 (16) mmHg in 2014. In 'fit' participants, the decline in SBP was 12.4 (95% confidence interval 11.9-13.0) mmHg/decade in those treated for hypertension and 8.5 (7.8-9.1) mmHg in those not treated. The decline in SBP was smaller as frailty increased. The proportion of all participants with BP less than 140/90 mmHg increased from 14 to 44% in the study period. CONCLUSION: In octogenarians, BP treatment has intensified between 2001 and 2014. BP values have declined in both treated and untreated participants, with a substantial increase in the proportion achieving conventional BP targets.

Longitudinal Trends in Hypertension Management and Mortality Among Octogenarians: Prospective Cohort Study.

The role of hypertension management among octogenarians is controversial. In this long-term follow-up (>10 years) study, we estimated trends in hypertension prevalence, awareness, treatment, and control among octogenarians, and evaluated the relationship of systolic blood pressure (SBP) ranges with mortality. Data were based on the English Longitudinal Study of Ageing (ELSA). Outcome measures were hypertension prevalence, awareness, treatment and control, and cardiovascular disease, and all-cause mortality events. Participants were separated into 8 categories of SBP values (<110, 110-119, 120-129, 130-139, 140-149, 150-159, 160-169, and >169 mm Hg). Among 2692 octogenarians, mean SBP levels declined from 147 mm Hg in 1998/2000 to 134 mm Hg in 2012/2013. The decline was of lower magnitude in the 50 to 79 years old subgroup (n=22007). Hypertension prevalence and awareness were 40% and 13%, respectively, higher among octogenarians than the 50 to 79 years of age subgroup, but hypertension treatment rates were similar (≈90%). Around 47% of the treated octogenarians achieved conventional BP targets (<140/90 mm Hg), increasing to 59% when assessed against revised targets (<150/90 mm Hg). All-cause mortality rates were higher (hazard ratio, 1.55; 95% confidence interval, 0.89-2.72) at lower extremes of SBP values (<110 mm Hg). The lowest cardiovascular disease and all-cause mortality risk among treated octogenarians was observed for an SBP range of 140 to 149 mm Hg (1.04, 0.60-1.78) and 160 to 169 mm Hg (0.78, 0.51-1.21). An increasing trend in hypertension awareness and treatment was observed in a large sample of community-dwelling octogenarians. The results do not support the view that more stringent BP targets may be associated with lower mortality.

The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS).

Few studies have directly compared the ability of the most commonly used models of frailty to predict mortality among community-dwelling individuals. Here, we used a frailty index (FI), frailty phenotype (FP), and FRAIL scale (FS) to predict mortality in the EMAS. Participants were aged 40-79 years (n=2929) at baseline and 6.6% (n=193) died over a median 4.3 years of follow-up. The FI was generated from 39 deficits, including self-reported health, morbidities, functional performance and psychological assessments. The FP and FS consisted of five phenotypic criteria and both categorized individuals as robust when they had 0 criteria, prefrail as 1-2 criteria and frail as 3+ criteria. The mean FI increased linearly with age (r(2)=0.21) and in Cox regression models adjusted for age, center, smoking and partner status the hazard ratio (HR) for death for each unit increase of the FI was 1.49. Men who were prefrail or frail by either the FP or FS definitions, had a significantly increased risk of death compared to their robust counterparts. Compared to robust men, those who were FP frail at baseline had a HR for death of 3.84, while those who were FS frail had a HR of 3.87. All three frailty models significantly predicted future mortality among community-dwelling, middle-aged and older European men after adjusting for potential confounders. Our data suggest that the choice of frailty model may not be of paramount importance when predicting future risk of death, enabling flexibility in the approach used.

Frailty and sexual health in older European men.

BACKGROUND: There has been little research on how late-life frailty interrelates with sexual health. Our objective was to examine the association of frailty with sexual functioning and satisfaction among older men. METHODS: The study population consisted of 1,504 men aged 60 to 79 years, participating in the European Male Aging Study. Self-report questionnaires measured overall sexual functioning, sexual function-related distress, and erectile dysfunction. Frailty status was defined using a phenotype (FP) or index (FI). Associations between frailty and sexual function were explored using regression models. RESULTS: Based on the frailty phenotype, 5% of men were classified as frail, and the mean frailty index was 0.18 (SD = 0.12). Frailty was associated with decreasing overall sexual functioning and increasing sexual function-related distress in multiple linear regressions adjusted for age, smoking, alcohol consumption, living arrangements, comorbidities, and depression. Frailty was also associated with an increased odds of erectile dysfunction after adjustment for the same confounders: odds ratio = 1.99 (95% confidence interval = 1.14, 3.48) and 4.08 (95% confidence interval = 2.63, 6.36) for frailty phenotype and frailty index, respectively. CONCLUSIONS: Frailty was associated with impaired overall sexual functioning, sexual function-related distress, and erectile dysfunction. Individuals assessed for frailty-related deficits may also benefit from an appraisal of sexual health as an important aspect of well-being and quality of life.

Low testosterone in ageing men: a modifiable risk factor for frailty?

There is substantial interest in the role of testosterone (T) in male ageing. Studies suggest that low T may be a risk factor for frailty, the vulnerable health status that occurs at advanced ages. However, T deficiency is relatively rare in ageing men and, importantly, is linked to modifiable risk factors including body weight and concurrent illnesses. These observations shift the focus away from hormone replacement and towards potential preventative strategies to help maintain T levels in ageing men. Furthermore, the effects of T on physical function remain inconsistent, and studies examining the safety of T treatment in ageing males raise concerns. Further research may usefully focus on novel pro-anabolic pharmaceutical agents, which together with other interventions will allow for optimal management of frailty.