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Background: Few studies have explored the activity levels of hospitalised older people and the intra-daily activity patterns in this group have not been described., Aims: To describe the quantity and daily pattern of physical activity among hospitalised older people using two accelerometers: the ankle-worn StepWatch Activity Monitor (SAM), and the wrist-worn GENEActiv., Methods: This cross-sectional observational study was conducted on the acute medical wards for older people in one UK hospital., Inclusion Criteria: participants aged ≥ 70 years, and able to mobilise prior to admission. Participants wore both devices for up to seven consecutive days, or until hospital discharge, whichever was sooner. Intra-daily activity levels were analysed hourly over each 24 h period., Results: 38 participants (mean age 87.8 years, SD 4.8) had their activity levels measured using both devices. The SAM median daily step count was 600 (IQR 240-1427). Intra-daily activity analysis showed two peak periods of ambulatory activity between 9 am-11 am and 6 pm-7 pm. With physical activity defined as ≥ 12 milli-g (GENEActiv), the median time spent above this cut-off point was 4.2 h. 62% of this activity time was only sustained for 1-5 min. Acceptability of both devices was high overall, but the wrist-worn device (96%) was more acceptable to patients than the ankle-worn device (83%)., Conclusion: Activity levels of these hospitalised older people were very low. Most physical activity was sustained over short periods. The intra-daily pattern of activity is an interesting finding which can help clinicians implement time-specific interventions to address the important issue of sedentary behaviour.

Introduction: The loss of mitochondrial function and content have been implicated in sarcopenia although they have been little studied in the very old, the group in which sarcopenia is most common. In this pilot study, our aim was to determine if mitochondrial respiratory chain function and content are preserved among healthy 85-year-olds., Methods: We recruited 19 participants (11 female) through their general practitioner and assessed their medical history, functional status and self-reported physical activity. We identified sarcopenia using grip strength, Timed Up-and-Go and bioimpedance analysis. We assessed mitochondrial respiratory chain function using phosphorous magnetic resonance spectroscopy, estimating τ 1/2 PCr, the recovery half-time of phosphocreatine in the calf muscles following a bout of aerobic exercise. We performed a biopsy of the vastus lateralis muscle and assessed mitochondrial respiratory chain content by measuring levels of subunits of complex I and IV of the respiratory chain, expressed as Z-scores relative to that in young controls., Results: Participants had a median (IQR) of 2 (1,3) long-term conditions, reported regular aerobic physical activity, and one participant (5.3%) had sarcopenia. Sixteen participants completed the magnetic resonance protocol and the mean (SD) τ 1/2 PCr of 35.6 (11.3) seconds was in keeping with preserved mitochondrial function. Seven participants underwent muscle biopsy and the mean fibre Z-scores were -0.7 (0.7) and -0.2 (0.4) for complexes I and IV, respectively, suggesting preserved content of mitochondrial respiratory chain enzymes., Conclusion: Muscle mitochondrial respiratory chain function and content are preserved in a sample of active, well-functioning 85-year-olds, among whom sarcopenia was uncommon. The results from this study will help inform future work examining the association between muscle mitochondrial deficiency and sarcopenia., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Current evidence that links "healthier" dietary patterns to better measured physical performance is mainly from older populations; little is known about the role of earlier diet. We examined adult diet quality in relation to physical performance at age 60-64 years., Methods: Diet quality was defined using principal component analysis of dietary data collected at age 36, 43, 53, and 60-64. Throughout adulthood, diets of higher quality were characterized by higher consumption of fruit, vegetables, and wholegrain bread. Diet quality scores calculated at each age indicated compliance with this pattern. Physical performance was assessed using chair rise, timed-up-and-go, and standing balance tests at age 60-64. The analysis sample included 969 men and women., Results: In gender-adjusted analyses, higher diet quality at each age was associated with better measured physical performance (all p < .01 for each test), although some associations were attenuated after adjustment for covariates. Diet quality scores were highly correlated in adulthood (0.44 ≤ r ≤ 0.67). However, conditional models showed that higher diet quality at age 60-64 (than expected from scores at younger ages), was associated with faster chair rise speed and with longer standing balance time (adjusted: 0.08 [95% CI: 0.02, 0.15] and 0.07 [0.01, 0.14] SD increase in chair rise speed and balance time, respectively, per SD increase in conditional diet quality; both p < .05)., Conclusions: Higher diet quality across adulthood is associated with better physical performance in older age. Current diet quality may be particularly important for physical performance, suggesting potential for improvements in diet in early older age.

Background: Poor performance in physical tests such as grip strength and walking speed is a risk factor for disability in old age, although whether such measures improve the discrimination of clinical prediction models when traditional clinical risk factors are already known is not clear. The prevalence of disability in mid-life is relatively low and hence screening in this age group may present an opportunity for early identification of those at increased future risk who may benefit most from preventative interventions., Methods: Data were drawn from two waves of the Medical Research Council National Survey of Health and Development. We examined whether several chronic conditions, poor health behaviours and lower scores on three measures of physical performance (grip strength, chair rise speed and standing balance time) at age 53 were associated with self-reported mobility and/or personal care disability at age 69. We used the area under the curve statistic (AUC) to assess model discrimination., Results: At age 69, 44% (826/1855) of participants reported mobility and/or personal care disability. Our final clinical prediction model included sex, knee osteoarthritis, taking 2+ medications, smoking, increased BMI and poor performance in all three physical tests, with an AUC of 0.740 compared with 0.708 for a model which did not include the performance measures., Conclusion: Measures of physical performance in midlife improve discrimination in clinical prediction models for disability over 16 years. Importantly, these and similar measures are also potential targets of future diet, exercise and pharmacological intervention in mid-life., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Regular physical activity (PA) is associated with reduced risk of the development and progression of musculoskeletal, metabolic and vascular disease. However, PA declines with age and this can contribute to multiple adverse outcomes. The aims of this study were to describe the relationship between accelerometer-determined PA, body composition and sarcopenia (the loss of muscle mass and function with age). Seven-day PA was measured using the GENEactiv accelerometer among 32 men and 99 women aged 74-84 years who participated in the Hertfordshire Sarcopenia Study. We measured mean daily acceleration and minutes/day spent in non-sedentary and moderate-to-vigorous physical activity (MVPA) levels. Body composition was measured by dual-energy X-ray absorptiometry, muscle strength by grip dynamometry and function by gait speed. Sarcopenia was defined according to the EWGSOP diagnostic algorithm. Men and women spent a median (inter-quartile range) of 138.8 (82, 217) and 186 (122, 240) minutes/day engaging in non-sedentary activity but only 14.3 (1.8, 30.2) and 9.5 (2.1, 18.6) min in MVPA, respectively. Higher levels of PA were associated with reduced adiposity, faster walking speed and decreased risk of sarcopenia. For example, a standard deviation (SD) increase in mean daily acceleration was associated with an increase in walking speed of 0.25 (95% CI 0.05, 0.45) SDs and a reduction in the risk of sarcopenia of 35% (95% CI 1, 57%) in fully adjusted analyses. PA was not associated with hand grip strength. Community-dwelling older adults in this study were largely sedentary but there was evidence that higher levels of activity were associated with reduced adiposity and improved function. PA at all intensity levels in later life may help maintain physical function and protect against sarcopenia.

Objective: In patients with mitochondrial DNA (mtDNA) maintenance disorders and with aging, mtDNA deletions sporadically form and clonally expand within individual muscle fibers, causing respiratory chain deficiency. This study aimed to identify the sub-cellular origin and potential mechanisms underlying this process., Methods: Serial skeletal muscle cryosections from patients with multiple mtDNA deletions were subjected to subcellular immunofluorescent, histochemical, and genetic analysis., Results: We report respiratory chain-deficient perinuclear foci containing mtDNA deletions, which show local elevations of both mitochondrial mass and mtDNA copy number. These subcellular foci of respiratory chain deficiency are associated with a local increase in mitochondrial biogenesis and unfolded protein response signaling pathways. We also find that the commonly reported segmental pattern of mitochondrial deficiency is consistent with the three-dimensional organization of the human skeletal muscle mitochondrial network., Interpretation: We propose that mtDNA deletions first exceed the biochemical threshold causing biochemical deficiency in focal regions adjacent to the myonuclei, and induce mitochondrial biogenesis before spreading across the muscle fiber. These subcellular resolution data provide new insights into the possible origin of mitochondrial respiratory chain deficiency in mitochondrial myopathy. Ann Neurol 2018;84:289-301., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Objective: To explore the association between ethnicity, sociodemographic, health, and lifestyle factors, and physical performance (PP) in ethnically diverse community-dwelling older adults from one geographic area. Method: We used multivariable linear regression to identify factors associated with upper (grip strength [GS], arm curls [AC]) and lower (chair stands [CS]) body strength and mobility (gait speed [GSp]) in 577 older adults (mean age 74 ± 8; 104 African American, 142 Afro-Caribbean, 123 Hispanic, and 208 European American) from South Florida. Results: Worse mental health was negatively associated with CS in African Americans and AC in Hispanics. Older age and higher body mass index (BMI) was associated with slower GSp in all except in Hispanics. Higher physical activity was associated with higher upper body strength in Hispanics and better mobility in African Americans and Afro-Caribbeans, but not in European Americans. Conclusion: Studies with large multiethnic cohorts are needed to further our understanding of ethnic differences in PP, which will help in tailoring interventions and recognizing unmet needs for health and social services., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A loss of muscle mass occurs as a consequence of a range of chronic and acute diseases as well as in older age. This wasting results from an imbalance of protein synthesis and degradation with a reduction in synthesis and resistance to anabolic stimulation often reported features. Ribosomes are required for protein synthesis, so changes in the control of ribosome synthesis are potential contributors to muscle wasting. MicroRNAs (miRNAs) are known regulators of muscle phenotype and have been shown to modulate components of the protein synthetic pathway. One miRNA that is predicted to target a number of components of protein synthetic pathway is miR-424-5p, which is elevated in the quadriceps of patients with chronic obstructive pulmonary disease (COPD)., Methods: Targets of miR-424-5p were identified by Argonaute2 pull down, and the effects of the miRNA on RNA and protein expression were determined by quantitative polymerase chain reaction and western blotting in muscle cells in vitro. Protein synthesis was determined by puromycin incorporation in vitro. The miRNA was over-expressed in the tibialis anterior muscle of mice by electroporation and the effects quantified. Finally, quadriceps expression of the miRNA was determined by quantitative polymerase chain reaction in patients with COPD and intensive care unit (ICU)-acquired weakness and in patients undergoing aortic surgery as well as in individuals from the Hertfordshire Sarcopenia Study., Results: Pull-down assays showed that miR-424-5p bound to messenger RNAs encoding proteins associated with muscle protein synthesis. The most highly enriched messenger RNAs encoded proteins required for the Pol I RNA pre-initiation complex required for ribosomal RNA (rRNA) transcription, (PolR1A and upstream binding transcription factor). In vitro, miR-424-5p reduced the expression of these RNAs, reduced rRNA levels, and inhibited protein synthesis. In mice, over-expression of miR-322 (rodent miR-424 orthologue) caused fibre atrophy and reduced upstream binding transcription factor expression and rRNA levels. In humans, elevated miR-424-5p associated with markers of disease severity in COPD (FEV 1 %), in patients undergoing aortic surgery (LVEF%), and in patients with ICU-acquired weakness (days in ICU). In patients undergoing aortic surgery, preoperative miR-424-5p expression in skeletal muscle was associated with muscle loss over the following 7 days., Conclusions: These data suggest that miR-424-5p regulates rRNA synthesis by inhibiting Pol I pre-initiation complex formation. Increased miR-424-5p expression in patients with conditions associated with muscle wasting is likely to contribute to the inhibition of protein synthesis and loss of muscle mass., (© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Low grip strength in older inpatients is associated with poor healthcare outcomes including longer length of stay and mortality. Measuring grip strength is simple and inexpensive. However, it is not routinely used in clinical practice. We aimed to evaluate the implementation of grip strength measurement into routine clinical practice., Methods: This implementation study was a mixed methods study based in five acute medical wards for older people in one UK hospital. Intervention design and implementation evaluation were based on Normalization Process Theory (NPT). A training program was developed and delivered to enable staff to measure grip strength and use a care plan for patients with low grip strength. Routine implementation and monitoring was assessed using the "implementation outcome variables" proposed by WHO: adoption, coverage, acceptability, fidelity, and costs analysis. Enablers and barriers of implementation were identified., Results: One hundred fifty-five nursing staff were trained, 63% in just 3 weeks. Adoption and monthly coverage of grip strength measurement varied between 25 and 80% patients across wards. 81% of female patients and 75% of male patients assessed had low grip strength (< 27 kg for men and < 16 kg for women). Staff and patients found grip measurement easy, cheap and potentially beneficial in identifying high-risk patients. The total cost of implementation across five wards over 12 months was less than £2302. Using NPT, interviews identified enablers and barriers. Enablers included: highly motivated ward champions, managerial support, engagement strategies, shared commitment, and integration into staff and ward daily routines. Barriers included lack of managerial and staff support, and high turnover of staff, managers and champions., Conclusions: Training a large number of nurses to routinely implement grip strength measurement of older patients was feasible, acceptable and inexpensive. Champions' motivation, managerial support, and shared staff commitment were important for the uptake and normalisation of grip strength measurement. A high percentage of older patients were identified to be at risk of poor healthcare outcomes and would benefit from nutritional and exercise interventions. Measuring grip strength in these patients could provide an opportunity to identify those with normal grip strength for fast tracking through admission to discharge thereby reducing length of stay., Trial Registration: Clinicaltrials.gov NCTO2447445 . Registered May 18, 2015.

Objectives: To investigate the associations between objective and subjective measures of oral health and incident physical frailty., Design: Cross-sectional and longitudinal study with 3 years of follow-up using data from the British Regional Heart Study., Setting: General practices in 24 British towns., Participants: Community-dwelling men aged 71 to 92 (N = 1,622)., Measurements: Objective assessments of oral health included tooth count and periodontal disease. Self-reported oral health measures included overall self-rated oral health; dry mouth symptoms; sensitivity to hot, cold, and sweet; and perceived difficulty eating. Frailty was defined using the Fried phenotype as having 3 or more of weight loss, grip strength, exhaustion, slow walking speed, and low physical activity. Incident frailty was assessed after 3 years of follow-up in 2014., Results: Three hundred three (19%) men were frail at baseline (aged 71-92). Having fewer than 21 teeth, complete tooth loss, fair to poor self-rated oral health, difficulty eating, dry mouth, and more oral health problems were associated with greater likelihood of being frail. Of 1,284 men followed for 3 years, 107 (10%) became frail. The risk of incident frailty was higher in participants who were edentulous (odds ratio (OR) = 1.90, 95% confidence interval (CI) = 1.03-3.52); had 3 or more dry mouth symptoms (OR = 2.03, 95% CI = 1.18-3.48); and had 1 (OR = 2.34, 95% CI = 1.18-4.64), 2 (OR = 2.30, 95% CI = 1.09-4.84), or 3 or more (OR = 2.72, 95% CI = 1.11-6.64) oral health problems after adjustment for age, smoking, social class, history of cardiovascular disease or diabetes mellitus, and medications related to dry mouth., Conclusion: The presence of oral health problems was associated with greater risks of being frail and developing frailty in older age. The identification and management of poor oral health in older people could be important in preventing frailty., (© 2017 The Authors The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.)

The population of older adults aged 85 years and over (the very old) is growing rapidly in many societies because of increases in life expectancy and reduced mortality at older ages. In 2016, 27.3 million very old adults were living in the European Union, and in the UK, 2.4% of the population (1.6 million) were aged 85 and over. Very old age is associated with increased risks of malnutrition, multimorbidity, and disability. Diet (nutrition) is a modifiable risk factor for multiple age-related conditions, including sarcopenia and functional decline. Dietary characteristics and nutrient intakes of the very old have been investigated in several European studies of ageing to better understand their nutritional requirements, which may differ from those in the young-old. However, there is a major gap in regard to evidence for the role of dietary patterns, protein, vitamin D and other nutrients for the maintenance of physical and cognitive functioning in later life. The Newcastle 85+ Study, UK and the Life and Living in Advanced Age, New Zealand are unique studies involving single birth cohorts which aim to assess health trajectories in very old adults and their biological, social and environmental influences, including nutrition. In this review, we have updated the latest findings in nutritional epidemiology with results from these studies, concentrating on the diet-physical functioning relationship., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Background: The assessment of physical activity levels of hospitalised older people requires accurate and reliable measures. Physical activities that older people in hospital commonly engage in include exercises and walking. Measurement of physical activity levels of older inpatients is essential to evaluate the impact of interventions to improve physical activity levels and to determine associations between physical activity in hospital and other health-related outcome measures., Objective: To determine which measures are used to measure physical activity of older people in hospital, and to describe their properties and applications., Method: A systematic review of four databases: Medline, Embase, CINAHL and AMED was conducted for papers published from 1996 to 2016. Inclusion criteria were participants aged ≥ 65 years and studies which included measures of physical activity in the acute medical inpatient setting. Studies which specifically assessed the activity levels of surgical patients or patients with neurological conditions such as stroke or brain injury were excluded. All study designs were included in the review., Results: 18 studies were included from 127 articles selected for full review. 15 studies used objective measures to measure the physical activity of older inpatients: 11 studies used accelerometers and four used direct systematic observations. Seven accelerometers were identified including the StepWatch Activity Monitor, activPAL, GENEActiv, Kenz Lifecorder EX, Actiwatch-L, Tractivity and AugmenTech Inc. Pittsburgh accelerometer. Three studies used a subjective measure (interviews with nurses and patients) to classify patients into low, intermediate and high mobility groups. The StepWatch Activity Monitor was reported to be most accurate at step-counting in patients with slow gait speed or altered gait. The activPAL was reported to be highly accurate at classifying postures., Conclusion: Physical activity levels of older inpatients can be measured using accelerometers. The accuracy of the accelerometers varies between devices and population-specific validation studies are needed to determine their suitability in measuring physical activity levels of hospitalised older people. Subjective measures are less accurate but can be a practical way of measuring physical activity in a larger group of patients., Competing Interests: The authors do not have any conflicts of interest

Introduction: Low physical capability predicts mortality, perhaps by association with co-morbidity. However, few studies include participants <70years old with lower co-morbidity burdens compared to older adults. We examined relationships between usual walking speed (UWS), timed chair stands speed, grip strength, standing balance and all-cause mortality in 8477 participants aged 48-92years enrolled in the European Prospective Investigation of Cancer-Norfolk study., Methods: Participants (55.1% female) were followed up for 6.0 years (inter-quartile range 4.6, 7.5). Associations were examined using Cox proportional hazards regression by age-group (<70years versus ≥70years) and then in the whole cohort adjusted for age, sex, anthropometry, history of diabetes/stroke/myocardial infarction/cancer, smoking, alcohol intake, socioeconomic status, television viewing time and physical activity., Results: Age and sex adjusted associations were similar in younger and older participants (P interaction all >0.05) and those with lower physical capability had higher mortality risk. For example, in those <70years old hazard ratios (95% confidence interval) for mortality in the third, second and lowest sex-specific quartiles of UWS compared to the highest were 1.21 (0.75, 1.96), 2.11 (1.35, 3.28) and 2.91 (1.84, 4.62) and in participants ≥70years old were 1.19 (0.73, 1.95), 2.09 (1.35, 3.24) and 2.64 (1.73, 4.02) respectively. In the whole cohort, strong associations between all physical capability tests and mortality persisted after multivariable adjustment and after excluding participants with co-morbidity., Conclusions: Physical capability was independently predictive of future mortality risk with similar associations in late mid-life, when co-morbidity burden is lower, as at older age., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent guidance by the National Institute for Health and Care Excellence (NICE) focuses on the management of people with multimorbidity, including Parkinson's disease (PD). To date there has been little exploration of this in neurodegenerative diseases. This study aimed to explore the associations between multimorbidity, motor severity and quality of life (QoL) in early PD. Regression analyses determined whether multimorbidity was significantly associated with disease severity and QoL. Multimorbidity was a small but significant predictor of QoL in people with incident PD, but not motor severity, suggesting that they may benefit from a tailored multidisciplinary approach to care.

Background: Recruitment rates of older people in epidemiological studies, although relatively higher than in clinical trials, have declined in recent years. This study aimed to explore motivating factors and concerns among older participants in an intensive epidemiological study (Hertfordshire Sarcopenia Study - HSS) and identify those that could aid future recruitment to epidemiological studies and clinical trials., Methods: Participants of the HSS fasted overnight and travelled several hours each way to the research facility at an English hospital for extensive diet/lifestyle questionnaires and investigations to assess muscle including blood tests and a muscle biopsy. We conducted semi-structured interviews with 13 participants (ten women) at the research facility in May-October 2015. The interviews were audio-taped, transcribed verbatim, coded and analysed thematically by three researchers., Results: We identified personal motives for participation (potential health benefit for self and family; curiosity; comparing own fitness to others; socialising). Altruistic motives (benefit for other people; belief in importance of research) were also important. Participants voiced a number of external motives related to the study uniqueness, organisation and safety record; family support; and just 'being asked'. Anxiety about the biopsy and travel distance were the only concerns and were alleviated by smooth and efficient running of the study., Conclusions: Personal and altruistic reasons were important motivators for these older people to participate in demanding, intensive research. They valued belonging to a birth cohort with previous research experience, but personal contact with the research team before and after consent provided reassurance, aided recruitment to HSS and could be readily replicated by other researchers. Any fears or concerns related to certain aspects of a demanding, intensive study should ideally be explored at an early visit to establish a good relationship with the research team.

Objective: to investigate the associations between initial level and rate of change in grip strength (GS) and all-cause mortality in very old adults (≥85 years) over a 9.6-year follow-up., Methods: prospective mortality data from 845 participants in the Newcastle 85+ Study were analysed for survival in relation to GS (kg, baseline and 5-year mean change) using Cox proportional hazards models., Results: during the follow-up, 636 (75.3%) participants died. Higher baseline GS was associated with a decreased risk of mortality in all participants [hazard ratio (HR) = 0.95, 95% confidence interval (CI): 0.93-0.98, P < 0.001], men (HR = 0.97, 95% CI: 0.95-0.99, P = 0.009) and women (HR = 0.96, 95% CI: 0.94-0.99, P = 0.007) after adjustment for health, lifestyle and anthropometric factors. Overall GS slope had a downward trajectory and was determined in 602 participants: 451 experienced constant decline (negative slope) and 151 had increasing GS (positive slope) over time. Men and women with a negative slope had a 16 and 33% increased risk of mortality, respectively, with every kg/year decline in GS (P ≤ 0.005), and participants with a positive slope had a 31% decreased risk of mortality (P = 0.03) irrespective of baseline GS and key covariates., Conclusion: higher baseline GS and 5-year increase in GS were protective of mortality, whilst GS decline was associated with an increased risk of mortality in the very old over 9.6 years, especially in women. These results add to the biological and clinical importance of GS as a powerful predictor of long-term survival in late life., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Identifying frailty is key to providing appropriate treatment for older people at high risk of adverse health outcomes. Screening tools proposed for primary care often involve additional workload. The electronic Frailty Index (eFI) has the potential to overcome this issue., Aim: To assess the feasibility and acceptability of using the eFI in primary care., Design and Setting: Pilot study in one suburban primary care practice in southern England in 2016., Method: Use of the eFI on the primary care TPP SystmOne database was explained to staff at the practice where a comprehensive geriatric assessment (CGA) clinic was being trialled. The practice data manager ran an eFI report for all patients ( n = 6670). Date of birth was used to identify patients aged ≥75 years ( n = 589). The eFI was determined for patients attending the CGA clinic ( n = 18)., Results: Practice staff ran the eFI reports in 5 minutes, which they reported was feasible and acceptable. The eFI range was 0.03 to 0.61 (mean 0.23) for all patients aged ≥75 years (mean 83 years, range 75 to 102 years). For CGA patients (mean 82 years, range 75 to 94 years) the eFI range was 0.19 to 0.53 (mean 0.33). Importantly, the eFI scores identified almost 12% of patients aged ≥75 years in this practice to have severe frailty., Conclusion: It was feasible and acceptable to use the eFI in this pilot study. A higher mean eFI in the CGA patients demonstrated construct validity for frailty identification. Practice staff recognised the potential for the eFI to identify the top 2% of vulnerable patients for avoiding unplanned admissions., (© British Journal of General Practice 2017.)

The concept of multimorbidity has attracted growing interest over recent years, and more latterly with the publication of specific guidelines on multimorbidity by the National Institute for Health and Care Excellence (NICE). Increasingly it is recognised that this is of particular relevance to practitioners caring for older adults, where multimorbidity may be more complex due to the overlap of physical and mental health disorders, frailty and polypharmacy. The overlap of frailty and multimorbidity in particular is likely to be due to the widespread health deficit accumulation, leading in some cases to functional impairment. The NICE guidelines identify 'target groups' who may benefit from a tailored approach to care that takes their multimorbidity into account, and make a number of research recommendations. Management includes a proactive individualised assessment and care plan, which improves quality of life by reducing treatment burden, adverse events, and unplanned or uncoordinated care., (© The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Various operational definitions have been proposed to assess the frailty condition among older individuals. Our objective was to assess how practitioners measure the geriatric syndrome of frailty in their daily routine., Methods: An online survey was sent to national geriatric societies affiliated to the European Union Geriatric Medicine Society (EUGMS) and to members of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)., Results: A total of 388 clinicians from 44 countries answered to the survey. Most of them were medical doctors (93%), and their primary field of practice was geriatrics (83%). Two hundred and five clinicians (52.8%) always assessed frailty in their daily practice, 38.1% reported to "sometimes" measure it, and 9.1% never assess it. A substantial proportion of clinicians (64.9%) diagnose frailty using more than one instrument. The most widely used tool was the gait speed test, adopted by 43.8% of the clinicians, followed by clinical frailty scale (34.3%), the SPPB test (30.2%), the frailty phenotype (26.8%) and the frailty index (16.8%)., Conclusion: A variety of tools is used to assess frailty of older patients in clinical practice highlighting the need for standardisation and guidelines.

Objective: To explore influences on diet in a group of community-dwelling older adults in the UK., Design: Data were collected through focus group discussions with older people; discussions were audio-recorded, transcribed verbatim and transcripts analysed thematically., Setting: Hertfordshire, UK., Subjects: Participants were sampled purposively from the Hertfordshire Cohort Study, focusing on those whose diets had been assessed at two time points: 1998-2001 and 2011., Results: Ninety-two adults participated (47 % women; 74-83 years) and eleven focus groups were held. A number of age-related factors were identified that were linked to food choices, including lifelong food experiences, retirement, bereavement and medical conditions, as well as environmental factors (such as transport). There appeared to be variability in how individuals responded to these influences, indicating that other underlying factors may mediate the effects of age-related factors on diet. Discussions about 'keeping going', being motivated to 'not give up', not wanting to be perceived as 'old', as well as examples of resilience and coping strategies, suggest the importance of mediating psychological factors. In addition, discussion about social activities and isolation, community spirit and loneliness, indicated the importance of social engagement as an influence on diet., Conclusions: Interventions to promote healthier diets in older age should take account of underlying psychological and social factors that influence diet, which may mediate the effects of age-related factors.

Background: Falls are a major cause of disability, morbidity and mortality in older persons, but have been under researched in developing countries., Objective: To describe challenges encountered in a community-based study on falls in a multi-ethnic population aged ≥65 years in a low-income setting., Methods: The study was conducted in four stages: A pilot study (n=105) to establish a sample size for the survey. An equipment validation study (n=118) to use for fall risk determination. A cross-sectional baseline (n=837) and a 12-month follow-up survey (n=632) to establish prevalence and risk factors for falls., Results: Prevalence rate of 26.4% (95% CI 23.5-29.5%) and risk factors for recurrent falls: previous falls, self-reported poor mobility and dizziness were established. Adaptations to the gold standard prospective fall research study design were employed: 1) to gain access to the study population in three selected suburbs, 2) to perform assessments in a non-standardised setting, 3) to address subjects' poverty and low literacy levels, and high attrition of subjects and field workers., Conclusion: Studies on falls in the older population of low- to middle-income countries have methodological challenges. Adaptive strategies used in the Cape Town study and the research experience reported may be instructive for investigators planning similar studies in such settings.

Objective: Older patients who are at risk of poor healthcare outcomes should be recognised early during hospital admission to allow appropriate interventions. It is unclear whether routinely collected data can identify high-risk patients. The aim of this study was to define current practice with regard to the identification of older patients at high risk of poor healthcare outcomes on admission to hospital., Results: Interviews/focus groups were conducted to establish the views of 22 healthcare staff across five acute medicine for older people wards in one hospital including seven nurses, four dieticians, seven doctors, and four therapists. In addition, a random sample of 60 patients' clinical records were reviewed to characterise the older patients, identify risk assessments performed routinely on admission, and describe usual care. We found that staff relied on their clinical judgment to identify high risk patients which was influenced by a number of factors such as reasons for admission, staff familiarity with patients, patients' general condition, visible frailty, and patients' ability to manage at home. "Therapy assessment" and patients' engagement with therapy were also reported to be important in recognising high-risk patients. However, staff recognised that making clinical judgments was often difficult and that it might occur several days after admission potentially delaying specific interventions. Routine risk assessments carried out on admission to identify single healthcare needs included risk of malnutrition (completed for 85% patients), falls risk (95%), moving and handling assessments (85%), and pressure ulcer risk assessments (88%). These were not used collectively to highlight patients at risk of poor healthcare outcomes. Thus, patients at risk of poor healthcare outcomes were not explicitly identified on admission using routinely collected data. There is a need for an early identification of these patients using a valid measure alongside staff clinical judgment to allow timely interventions to improve healthcare outcomes.

Musculoskeletal ageing is a major public health concern owing to demographic shifts in the population. Sarcopenia, generally defined as the age-related loss of muscle mass and function, is associated with considerable risk of falls, loss of independence in older adults and hospitalization with poorer health outcomes. This condition is therefore associated with increased morbidity and health care costs. As with bone mass, muscle mass and strength increase during late adolescence and early adulthood, but begin to decline substantially from ∼50 years of age. Sarcopenia is characterized by many features, which include loss of muscle mass, altered muscle composition, infiltration with fat and fibrous tissue and alterations in innervation. A better understanding of these factors might help us to develop strategies that target these effects. To date, however, methodological challenges and controversies regarding how best to define the condition, in addition to uncertainty about what outcome measures to consider, have delayed research into possible therapeutic options. Most pharmacological agents investigated to date are hormonal, although new developments have seen the emergence of agents that target myostatin signalling to increase muscle mass. In this review we consider the current approaching for defining sarcopenia and discuss its epidemiology, pathogenesis, and potential therapeutic opportunities.

Background: weak hand grip strength in later life is a risk factor for disability, morbidity and mortality and is central to definitions of sarcopenia and frailty. It is unclear whether rate of change in grip strength adds to level of grip strength as a risk factor for poor ageing outcomes., Methods: study participants were 292 community-dwelling men and women whose grip strength was measured during the 1994/5 (average age 67) and 2003/5 (average age 76) phases of the Hertfordshire Ageing Study, UK. Individual rate of change in grip strength was estimated using a residual change method. Mortality was followed-up to 2011 (42 men and 21 women died)., Results: average grip strengths in 2003/5 were 38.4 kg (standard deviation [SD] = 8.1) and 23.7 kg (SD = 6.6) for men and women respectively. Average annualised rates of change in grip strength (2003/5 minus 1994/5) were modest owing to a healthy-participant effect (men: -0.12 kg/y, SD = 0.71; women: 0.08 kg/y, SD = 0.54) but varied widely. Mortality risk varied according to level and rate of change in grip strength (P = 0.03); death rates per 100 person years of follow-up were 6.7 (95% CI: 4.6, 9.6) among participants who lost grip over time and had low grip in 2003/5, in contrast with 0.8 (95% CI: 0.1, 5.8) among participants whose grip changed little over time and remained high in 2003/5., Conclusions: levels of grip strength in later life should be considered in conjunction with estimates of change in grip strength identified by repeat measurement over time. Normative data for longitudinal change in grip strength are required., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Mixed reports exist about the role of 25-hydroxyvitamin D (25(OH)D) in muscle ageing and there are few prospective studies involving the very old (aged ≥ 85) who are at highest risk of low 25(OH)D, loss of muscle mass and strength, and physical performance decline. In the Newcastle 85+ Study ( n = 845), we aimed to determine the association between 25(OH)D season-specific quartiles (hereafter SQ1-SQ4), grip strength (GS) and physical performance decline (Timed Up-and-Go Test, TUG) over 5 years using mixed models. In the time-only models with linear and quadratic slopes, SQ1 and SQ4 of 25(OH)D were associated with weaker GS initially in men (SQ1: β (SE) = -2.56 (0.96); SQ4: -2.16 (1.06)) and women (SQ1: -1.10 (0.52); SQ4: -1.28 (0.50)) (all p ≤ 0.04). In the fully adjusted models, only men in SQ1 had a significant annual decline in GS of 1.41 kg which accelerated over time (-0.40 (0.1)), (both p ≤ 0.003) compared with those in combined middle quartiles. Only women in SQ1 and SQ4 of 25(OH)D had worse TUG times initially, but the rate of TUG decline was not affected. Low baseline 25(OH)D may contribute to muscle strength decline in the very old and particularly in men.

Sarcopenia of age is prevalent and costly and proven pharmacological interventions are currently lacking. The pathophysiology of sarcopenia is incompletely understood but appears to involve multiple pathways, including inflammation, hormonal dysregulation, impaired regeneration, mitochondrial dysfunction and denervation. There are several ways in which we might select potential pharmacological interventions for testing in clinical trials. These include a 'bottom-up' approach using basic science to elucidate the molecular processes involved and identify potential targets from this knowledge-a strategy that has led to the development of myostatin inhibitors. A 'top-down' approach might use observational data to examine the association between physical function and use of certain medications, such as the association between angiotensin-converting enzyme inhibitors with slower decline in physical function. Once a pharmacological intervention has been proposed, efficacy must be demonstrated in this complex multi-morbid population. Both muscle mass and muscle function need to be measured as outcomes, but these outcomes require large sample sizes and sufficient follow-up to detect change. Biomarkers that can predict the response of sarcopenia to intervention after a short time would greatly assist our ability to select candidate interventions in short proof-of-concept trials. Further development of trial methods is required to accelerate progress in this important area of medicine for older people.

Introduction: Recognition that an older person has sarcopenia is important because this condition is linked to a range of adverse outcomes. Sarcopenia becomes increasingly common with age, and yet there are few data concerning its descriptive epidemiology in the very old (aged 85 years and above). Our aims were to describe risk factors for sarcopenia and estimate its prevalence and incidence in a British sample of the very old., Methods: We used data from two waves (2006/07 and 2009/10) of the Newcastle 85+ Study, a cohort born in 1921 and registered with a Newcastle/North Tyneside general practice. We assessed sarcopenia status using the European Working Group on Sarcopenia in Older People (EWGSOP) definition. Grip strength was measured using a Takei digital dynamometer (Takei Scientific Instruments Ltd., Niigata, Japan), gait speed was calculated from the Timed Up and Go test, and lean mass was estimated using a Tanita-305 body fat analyzer. We used logistic regression to examine associations between risk factors for prevalent sarcopenia at baseline and incident sarcopenia at follow-up., Results: European Working Group on Sarcopenia in Older People sarcopenia was present in 21% of participants at baseline [149/719 participants, mean age 85.5 (0.4) years]. Many participants had either slow gait speed or weak grip strength (74.3%), and hence measurement of muscle mass was frequently indicated by the EWGSOP definition. Incidence data were available for 302 participants, and the incident rate was 3.7 cases per 100 person years at risk. Low Standardized Mini-Mental State Examination, lower occupational social class, and shorter duration of education were associated with sarcopenia at baseline, while low muscle mass was associated with incident sarcopenia. Low body mass index (BMI) was a risk factor for both in a graded fashion, with each unit decrease associated with increased odds of prevalent [odds ratio (OR) 1.29, 95% confidence interval (CI): 1.21, 1.37] and incident (OR 1.20, 95% CI: 1.08, 1.33) sarcopenia., Conclusions: To our knowledge, this is the first study to describe prevalence and incidence of EWGSOP sarcopenia in the very old. Low BMI was a risk factor for both current and future sarcopenia; indeed, there was some evidence that low BMI may be a reasonable proxy for low lean mass. Overall, the high prevalence of sarcopenia among the very old suggests that this group should be a focus for future research., (© 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Objectives The aim of this study was to characterize the descriptive epidemiology of insomnia in midlife and explore the relative importance of different occupational risk factors for insomnia among older workers. Methods A questionnaire was mailed to all adults aged 50-64 years registered with 24 English general practices. Insomnia was defined as having at least one of four problems with sleep severely in the past three months. Subjects were also asked about employment conditions, feelings concerning work, and their health. Associations were assessed by logistic regression and population attributable fractions (PAF) calculated. Results Analysis was based on 8067 respondents (5470 in paid work), 18.8% of whom reported insomnia. It was more common among women, smokers, obese individuals, those living alone, and those in financial hardship, and less prevalent among the educated, those in South-East England, and those with friendships and leisure-time pursuits. Occupational risk factors included unemployment, shift working, lack of control and support at work, job insecurity, job dissatisfaction and several of its determinants (lacking a sense of achievement, feeling unappreciated, having difficult work colleagues, feeling unfairly criticized). Population burden of insomnia was associated more strongly with difficulties in coping with work demands, job insecurity, difficult colleagues, and lack of friendships at work [population attributable fraction (PAF) 15-33%] than shift work and lack of autonomy or support (PAF 5-7%). It was strongly associated with seven measures of poorer self-assessed health. Conclusions Employment policies aimed at tackling insomnia among older workers may benefit from focusing particularly on job-person fit, job security and relationships in the workplace.

Background: There is evidence that the personality traits conscientiousness, extraversion and neuroticism are associated with health behaviours and with risk of various health outcomes. We hypothesised that people who are lower in conscientiousness or extraversion or higher in neuroticism may be at greater risk of frailty in later life., Methods: We used general linear models to examine the prospective relation between personality, assessed using the Midlife Development Inventory, and change in frailty, modelled by a frailty index, in 5314 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing., Results: Men and women with higher levels of neuroticism or lower levels of extraversion or conscientiousness had an increased frailty index score at follow-up. After adjustment for potential confounding or mediating variables, including frailty index score at baseline, the frailty index score at follow-up-which potentially ranges from 0 to 1-was higher by 0.035 (95 % confidence interval 0.018, 0.052) for a standard deviation increase in neuroticism and lower by 0.061 (0.031, 0.091) or 0.045 (0.020, 0.071) for a standard deviation increase in extraversion or conscientiousness, respectively. There was some evidence that the association between extraversion and frailty may be due to reverse causation whereby poorer health affected responses to items in the personality inventory., Conclusions: Higher levels of neuroticism or lower levels of conscientiousness or extraversion may be risk factors for the onset or progression of frailty. Future studies need to replicate these observations in other populations and explore the mechanisms underlying these associations., Competing Interests: Compliance with Ethical Standards Authors’ Statement of Conflict of Interest and Adherence to Ethical Standards Authors Catharine R Gale, Rene Mottus, Ian J Deary, Cyrus Cooper and Avan Aihie Sayer declare that they have no conflict of interest. Ethical approval for the English Longitudinal Study of Ageing was obtained from the Multicentre Research and Ethics Committee. Participants gave written informed consent. Procedures complied with the Helsinki Declaration of 1975 as revised in 2000.

Background: Malnutrition is common in hospital inpatients and is associated with increased morbidity and mortality. Insufficient assistance at mealtimes can contribute to this and therefore trained volunteer mealtime assistants may be of benefit., Objectives: To identify and review the current evidence for the impact of trained volunteer mealtime assistants on dietary intake and satisfaction with mealtime care in adult hospital inpatients., Methods: A systematic search of Medline, Embase and CINAHL was conducted to identify relevant articles. Articles of any methodology were considered. Quality assessment and data extraction were carried out by two reviewers independently., Participants: Participants were inpatients in a hospital setting, including rehabilitation units. Participants in long term care facilities were excluded., Intervention: Articles that examined the effect of trained volunteer mealtime assistants on nutritional outcomes or satisfaction with mealtime care were included., Results: 5576 articles were identified, of which 14 were included in the review. Nine were small research studies and five were quality improvement initiatives. The quality of eight studies was moderate, with one study being of lower quality. Eight articles reported dietary intake and seven demonstrated an improvement, with protein intakes at volunteer mealtimes increasing by 4.3g-10.1g and energy intakes by 44-105kcal. Ten articles reported positive staff, patient and volunteer feedback. No adverse events were reported., Conclusion: There is evidence from small studies and improvement projects that trained volunteer mealtime assistants are safe and improve satisfaction with mealtime care in hospital inpatients, although evidence for an effect on dietary intake was less consistent. Larger studies with robust methodology are required to confirm this., Competing Interests: None

Objective: Malnutrition among older hospital inpatients is common and is associated with poor clinical outcomes. Time-pressured staff may struggle to provide mealtime assistance. This study aimed to evaluate the impact of trained volunteer mealtime assistants on the dietary intake of older inpatients., Design: Quasi-experimental two year pre and post- test study of the introduction of volunteer mealtime assistants to one acute medical female ward, with contemporaneous comparison with a control ward., Setting: Two acute medical female wards in a university hospital in England., Participants: Female acute medical inpatients aged 70 years and over who were not tube fed, nil by mouth, terminally ill or being nursed in a side room., Intervention: The introduction of volunteer mealtime assistants to one ward to help patients during weekday lunchtimes in the intervention year., Measurements: Patients' background and clinical characteristics were assessed; 24-hour records were completed for individual patients to document dietary intake in both years on the two wards., Results: A total of 407 patients, mean (SD) age 87.5 (5.4) years, were studied over the two-year period; the majority (57%) needed mealtime assistance and up to 50% were confused. Patients' clinical characteristics did not differ between wards in the observational or intervention years. Throughout the intervention year volunteers provided mealtime assistance on weekday lunchtimes on the intervention ward only. Daily energy (median 1039 kcal; IQR 709, 1414) and protein (median 38.9 g: IQR 26.6, 54.0) intakes were very low (n=407). No differences in dietary intake were found between the wards in the observational or intervention years, or in a pre-post-test comparison of patients on the intervention ward. Data were therefore combined for further analysis to explore influences on dietary intake. In a multivariate model, the only independent predictor of energy intake was the feeding assistance required by patients; greater need for help was associated with lower energy intake (P<0.001). Independent predictors of protein intake were the feeding assistance given (P<0.001) and use of sip feeds; sip feed users had slightly higher protein intakes (P=0.014)., Conclusions: Trained volunteers were able to deliver mealtime assistance on a large scale in an effective and sustainable manner, with the potential to release time for nursing staff to complete other clinical tasks. The study participants had a low median intake of energy and protein highlighting the importance of patient factors associated with acute illness; a stratified approach including oral and parenteral nutritional supplementation may be required for some acutely unwell patients. The level of mealtime assistance required was the factor most strongly associated with patients' poor intake of energy and protein and may be a useful simple indicator of patients at risk of poor nutrition., Competing Interests: None declared.

Objective: To evaluate the use of a short questionnaire to assess diet quality in older adults., Design: Cross-sectional study., Setting: Hertfordshire, UK., Participants: 3217 community-dwelling older adults (59-73 years)., Measurements: Diet was assessed using an administered food frequency questionnaire (FFQ); two measures of diet quality were defined by calculating participants' 'prudent diet' scores, firstly from a principal component analysis of the data from the full FFQ (129 items) and, secondly, from a short version of the FFQ (including 24 indicator foods). Scores calculated from the full and short FFQ were compared with nutrient intake and blood concentrations of vitamin C and lipids., Results: Prudent diet scores calculated from the full FFQ and short FFQ were highly correlated (0.912 in men, 0.904 in women). The pattern of associations between nutrient intake (full FFQ) and diet scores calculated using the short and full FFQs were very similar, both for men and women. Prudent diet scores calculated from the full and short FFQs also showed comparable patterns of association with blood measurements: in men and women, both scores were positively associated with plasma vitamin C concentration and serum HDL; in women, an inverse association with serum triglycerides was also observed., Conclusions: A short food-based questionnaire provides useful information about the diet quality of older adults. This simple tool does not require nutrient analysis, and has the potential to be of value to non-specialist researchers., Competing Interests: No author has a conflict of interest.

Aims and Objectives: To review current evidence for the use of volunteers to mobilise older acute medical in-patients., Background: Immobility in hospital is associated with poor healthcare outcomes in older people, but maintaining mobility is frequently compromised due to time pressures experienced by clinical staff. Volunteers are established in many hospitals, usually involved in indirect patient care. Recent evidence suggests that trained mealtime volunteers had a positive impact on patients and hospital staff. It is unclear whether volunteers can help older inpatients to mobilise., Design: Systematic review., Methods: We searched Cochrane, Medline, Embase, CINAHL, AMED and Google databases using MeSH headings and keywords within six key themes: inpatients, older, mobility/exercise, delirium, falls and volunteers. Full texts of relevant articles were retrieved and reference lists reviewed., Results: Of the 2428 articles that were identified, two scientific studies and three reports on quality improvement initiatives were included in the final review. One study included volunteer assisted mobilisation as part of a delirium prevention intervention (HELP). The second study has not reported yet (MOVE ON). The contribution of volunteers in both is unclear. Three quality improvement initiatives trained volunteers to help mobilise patients. They were not formally evaluated but report positive effects of the volunteers on patient and staff satisfaction., Conclusions: This review has identified a lack of scientific evidence for the use of volunteers in mobilising older medical inpatients, but quality improvement initiatives suggest that volunteers can be employed in this role with reports of staff and patient satisfaction: this is an area for further development and evaluation., Relevance to Clinical Practice: This review outlines the evidence for the involvement of volunteers in maintaining patients' mobility, identifies mobilisation protocols that have been used, the need to train volunteers and for formal evaluation of volunteers in this role. Prospero registration number: CRD42014010388., (© 2016 John Wiley & Sons Ltd.)

Sarcopenia and frailty are important conditions that become increasingly prevalent with age. Sarcopenia is the loss of muscle mass and function, and frailty can be defined as multi-system impairment associated with increased vulnerability to stressors. There is overlap between the two conditions, especially in terms of the physical aspects of the frailty phenotype: low grip strength, gait speed and muscle mass. These measures have been associated with a wide range of ageing outcomes and can be assessed in the clinical setting. In terms of intervention, there is evidence for the benefit of resistance exercise programmes, although these may not always be feasible. Considerable research into the use of medicines, both existing and new, as well as dietary supplements is ongoing. Finally in order to prevent or delay the development of these conditions, an additional approach is to consider aetiological factors operating across the life course., (© Royal College of Physicians 2016. All rights reserved.)

Background: Weak grip strength (GS) is a key component of sarcopenia and frailty and a powerful predictor of mortality, morbidity and disability. Despite increasing interest in understanding GS across the lifespan, little is known about GS decline in the very old (aged ≥85). We examined trajectories of GS in very old adults and identified the determinants., Methods: GS (kg) was measured four times over 5 years in 319 men and 526 women participating in the Newcastle 85+ Study. A weak GS sub-cohort was identified as having strength of ≤27 kg (men), and ≤16 kg (women) at baseline and follow-up. Mixed models were used to establish trajectories of GS and associated factors in all participants, men and women, and in those with weak GS., Results: Men's mean grip strength was 24.42 (SD = 6.77) kg, and women's 13.23 (4.42) kg (p<0.001) at baseline, with mean absolute change of -5.27 (4.90) kg and -3.14 (3.41), respectively (p<0.001) by 5-year follow-up. In the time-only mixed model, men experienced linear annual decline in GS of -1.13 (0.8) kg (β (SE), p<0.001), whilst women's decline although slower, accelerated by -0.06 (0.02) kg (p = 0.01) over time. In the saturated model, higher baseline physical activity, height, fat-free mass, better self-rated health, and not having arthritis in hand(s) were associated with stronger GS initially in both sexes. Annual GS decline in men and participants with weak GS who were highly physically active was slower by 0.95 and 0.52 kg, respectively compared with inactive counterparts., Conclusion: Grip strength decline in the very old followed linear (men) and curvilinear (women) trends. High levels of physical activity were protective of GS loss in men (but not in women) and in those with weak GS. Thus maintaining muscle strength in later life is important to reduce the morbidity and mortality in the very old., Competing Interests: We have the following interest: The Newcastle 85+ Study was partly funded by Unilever Corporate Research. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Objectives: Demographic changes are requiring people to work longer. Labour force participation might be promoted by tackling sources of job dissatisfaction. We aimed to describe the epidemiology of job dissatisfaction in older British workers, to explore which perceptions of work contribute most importantly, and to assess possible impacts on health., Methods: Participants aged 50-64 years were recruited from 24 English general practices. At baseline, those currently in work (N=5437) reported on their demographic and employment circumstances, overall job satisfaction, perceptions of their work that might contribute to dissatisfaction, and their general health, mood and well-being. Associations of job dissatisfaction with risk factors and potential health outcomes were assessed cross-sectionally by logistic regression, and the potential contributions of different negative perceptions to overall dissatisfaction were summarised by population attributable fractions (PAFs)., Results: Job dissatisfaction was more common among men, below age 60 years, those living in London and the South East, in the more educated and in those working for larger employers. The main contributors to job dissatisfaction among employees were feeling unappreciated and/or lacking a sense of achievement (PAF 55-56%), while in the self-employed, job insecurity was the leading contributor (PAF 79%). Job dissatisfaction was associated with all of the adverse health outcomes examined (ORs of 3-5), as were most of the negative perceptions of work that contributed to overall dissatisfaction., Conclusions: Employment policies aimed at improving job satisfaction in older workers may benefit from focussing particularly on relationships in the workplace, fairness, job security and instilling a sense of achievement., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Handgrip strength is a non-invasive marker of muscle strength, and low grip strength in hospital inpatients is associated with poor healthcare outcomes including longer length of stay, increased functional limitations, and mortality. Measuring grip strength is simple and inexpensive. However, grip strength measurement is not routinely used in clinical practice. The aim of this study is to evaluate the feasibility of implementing grip strength measurement into routine clinical practice., Methods/design: This feasibility study is a mixed methods design combining qualitative, quantitative, and economic elements and is based on the acute medical wards for older people in one hospital. The study consists of three phases: phase 1 will define current baseline practice for the identification of inpatients at high risk of poor healthcare outcomes, their nutrition, and mobility care through interviews and focus groups with staff as well as a review of patients' clinical records. Phase 2 will focus on the feasibility of developing and implementing a training programme using Normalisation Process Theory to enable nursing and medical staff to measure and interpret grip strength values. Following the training, grip strength will be measured routinely for older patients as part of admission procedures with the use of a care plan for those with low grip strength. Finally, phase 3 will evaluate the acceptability of grip strength measurement, its adoption, coverage, and basic costs using interviews and focus groups with staff and patients, and re-examination of clinical records., Discussion: The results of this study will inform the translation of grip strength measurement from a research tool into clinical practice to improve the identification of older inpatients at risk of poor healthcare outcomes., Trial Registration: Clinicaltrials.gov NCTO2447445.

Background: Several regions of the genome have shown to be associated with COPD in genome-wide association studies of common variants., Objective: To determine rare and potentially functional single nucleotide polymorphisms (SNPs) associated with the risk of COPD and severity of airflow limitation., Methods: 3226 current or former smokers of European ancestry with lung function measures indicative of Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 COPD or worse were genotyped using an exome array. An analysis of risk of COPD was carried out using ever smoking controls (n=4784). Associations with %predicted FEV1 were tested in cases. We followed-up signals of interest (p<10(-5)) in independent samples from a subset of the UK Biobank population and also undertook a more powerful discovery study by meta-analysing the exome array data and UK Biobank data for variants represented on both arrays., Results: Among the associated variants were two in regions previously unreported for COPD; a low frequency non-synonymous SNP in MOCS3 (rs7269297, pdiscovery=3.08×10(-6), preplication=0.019) and a rare SNP in IFIT3, which emerged in the meta-analysis (rs140549288, pmeta=8.56×10(-6)). In the meta-analysis of % predicted FEV1 in cases, the strongest association was shown for a splice variant in a previously unreported region, SERPINA12 (rs140198372, pmeta=5.72×10(-6)). We also confirmed previously reported associations with COPD risk at MMP12, HHIP, GPR126 and CHRNA5. No associations in novel regions reached a stringent exome-wide significance threshold (p<3.7×10(-7))., Conclusions: This study identified several associations with the risk of COPD and severity of airflow limitation, including novel regions MOCS3, IFIT3 and SERPINA12, which warrant further study., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Loss of muscle mass and strength is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD) that limits their quality of life and has prognostic implications but does not affect everyone equally. To identify mechanisms that may contribute to the susceptibility to a low muscle mass, we investigated microRNA (miRNA) expression, methylation status, and regeneration in quadriceps muscle from COPD patients and the effect of miRNAs on myoblast proliferation in vitro. The relationships of miRNA expression with muscle mass and strength was also determined in a group of healthy older men., Methods: We identified miRNAs associated with a low fat-free mass (FFM) phenotype in a small group of patients with COPD using a PCR screen of 750 miRNAs. The expression of two differentially expressed miRNAs (miR-675 and miR-519a) was determined in an expanded group of COPD patients and their associations with FFM and strength identified. The association of these miRNAs with FFM and strength was also explored in a group of healthy community-dwelling older men. As the expression of the miRNAs associated with FFM could be regulated by methylation, the relative methylation of the H19 ICR was determined. Furthermore, the proportion of myofibres with centralized nuclei, as a marker of muscle regeneration, in the muscle of COPD patients was identified by immunofluorescence., Results: Imprinted miRNAs (miR-675 and from a cluster, C19MC which includes miR-519a) were differentially expressed in the quadriceps of patients with a low fat-free mass index (FFMI) compared to those with a normal FFMI. In larger cohorts, miR-675 and its host gene (H19) were higher in patients with a low FFMI and strength. The association of miR-519a expression with FFMI was present in male patients with severe COPD. Similar associations of miR expression with lean mass and strength were not observed in healthy community dwelling older men participating in the Hertfordshire Sarcopenia Study. Relative methylation of the H19 ICR was reduced in COPD patients with muscle weakness but was not associated with FFM. In vitro, miR-675 inhibited myoblast proliferation and patients with a low FFMI had fewer centralized nuclei suggesting miR-675 represses regeneration., Conclusions: The data suggest that increased expression of miR-675/H19 and altered methylation of the H19 imprinting control region are associated with a low FFMI in patients with COPD but not in healthy community dwelling older men suggesting that epigenetic control of this loci may contribute to a susceptibility to a low FFMI.

Background: The UK population is ageing; improved understanding of risk factors for hospital admission is required. Linkage of the Hertfordshire Cohort Study (HCS) with Hospital Episode Statistics (HES) data has created a multiple-failure survival dataset detailing the characteristics of 2,997 individuals at baseline (1998-2004, average age 66 years) and their hospital admissions (regarded as 'failure events') over a 10 year follow-up. Analysis of risk factors using logistic regression or time to first event Cox modelling wastes information as an individual's admissions after their first are disregarded. Sophisticated analysis techniques are established to examine risk factors for admission in such datasets but are not commonly implemented., Methods: We review analysis techniques for multiple-failure survival datasets (logistic regression; time to first event Cox modelling; and the Andersen and Gill [AG] and Prentice, Williams and Peterson Total Time [PWP-TT] multiple-failure models), outline their implementation in Stata, and compare their results in an analysis of housing tenure (a marker of socioeconomic position) as a risk factor for different types of hospital admission (any; emergency; elective; >7 days). The AG and PWP-TT models include full admissions histories in the analysis of risk factors for admission and account for within-subject correlation of failure times. The PWP-TT model is also stratified on the number of previous failure events, allowing an individual's baseline risk of admission to increase with their number of previous admissions., Results: All models yielded broadly similar results: not owner-occupying one's home was associated with increased risk of hospital admission. Estimated effect sizes were smaller from the PWP-TT model in comparison with other models owing to it having accounted for an increase in risk of admission with number of previous admissions. For example, hazard ratios [HR] from time to first event Cox models were 1.67(95 % CI: 1.36,2.04) and 1.63(95 % CI:1.36,1.95) for not owner-occupying one's home in relation to risk of emergency admission or death among women and men respectively; corresponding HRs from the PWP-TT model were 1.34(95 % CI:1.15,1.56) for women and 1.23(95 % CI:1.07,1.41) for men., Conclusion: The PWP-TT model may be implemented using routine statistical software and is recommended for the analysis of multiple-failure survival datasets which detail repeated hospital admissions among older people.

Background: Several recessive Mendelian disorders are common in Europeans, including cystic fibrosis (CFTR), medium-chain-acyl-Co-A-dehydrogenase deficiency (ACADM), phenylketonuria (PAH) and alpha 1-antitrypsin deficiency (SERPINA1)., Methods: In a multicohort study of >19,000 older individuals, we investigated the relevant phenotypes in heterozygotes for these genes: lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC)) for CFTR and SERPINA1; cognitive measures for ACADM and PAH; and physical capability for ACADM, PAH and SERPINA1., Results: Findings were mostly negative but lung function in SERPINA1 (protease inhibitor (PI) Z allele, rs28929474) showed enhanced FEV1 and FVC (0.13 z-score increase in FEV1 (p=1.7 × 10(-5)) and 0.16 z-score increase in FVC (p=5.2 × 10(-8))) in PI-MZ individuals. Height adjustment (a known, strong correlate of FEV1 and FVC) revealed strong positive height associations of the Z allele (1.50 cm increase in height (p=3.6 × 10(-10)))., Conclusions: The PI-MZ rare (2%) SNP effect is nearly four times greater than the 'top' common height SNP in HMGA2. However, height only partially attenuates the SERPINA1-FEV1 or FVC association (around 50%) and vice versa. Height SNP variants have recently been shown to be positively selected collectively in North versus South Europeans, while the Z allele high frequency is localised to North Europe. Although PI-ZZ is clinically disadvantageous to lung function, PI-MZ increases both height and respiratory function; potentially a balanced polymorphism. Partial blockade of PI could conceivably form part of a future poly-therapeutic approach in very short children. The notion that elastase inhibition should benefit patients with chronic obstructive pulmonary disease may also merit re-evaluation. PI is already a therapeutic target: our findings invite a reconsideration of the optimum level in respiratory care and novel pathway potential for development of agents for the management of growth disorders., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people., Methods: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking ≥ 4 h/day; lifting ≥ 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders., Results: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength., Conclusions: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Healthy diet has been associated with better muscle strength and physical performance in cross-sectional studies of older adults but the effect of dietary patterns (DP) on subsequent decline, particularly in the very old (aged 85+), has not been determined., Objective: We investigated the association between previously established DP and decline in muscle strength and physical performance in the very old., Design: 791 participants (61.8% women) from the Newcastle 85+ Study were followed-up for change in hand grip strength (HGS) and Timed Up-and Go (TUG) test over 5 years (four waves 1.5 years apart). Mixed models were used to determine the effects of DP on muscle strength and physical performance in the entire cohort and separately by sex., Results: Previously we have established three DP that varied in intake of red meats, potato, gravy and butter and differed with key health and social factors. HGS declined linearly by 1.59 kgF in men and 1.08 kgF in women (both p<0.001), and TUG slowed by 0.13 log10-transformed seconds (log10-s) in men and 0.11 log10-s in women per wave after adjusting for important covariates (both p<0.001), and also showed a nonlinear change (p<0.001). Men in DP1 ('High Red Meat') had worse overall HGS (β = -1.70, p = 0.05), but men in DP3 ('High Butter') had a steeper decline (β = -0.63, p = 0.05) than men in DP2 ('Low Meat'). Men in DP1 and women in DP3 also had overall slower TUG than those in DP2 (β = 0.08, p = 0.001 and β = 0.06, p = 0.01, respectively), but similar rate of decline after adjusting for sociodemographic, lifestyle, health, and functioning factors. The results for HGS and TUG were not affected by participants' cognitive status., Conclusions: DP high in red meats, potato and gravy (DP1), or butter (DP3) may adversely affect muscle strength and physical performance in later life, independently of important covariates and cognitive status.

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard., Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region., Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of -0.85 SDs (95% CI: -0.94, -0.76)., Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing regions., (© The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Rates of hospital admission are increasing, particularly among older people. Poor health behaviours cluster but their combined impact on risk of hospital admission among older people in the UK is unknown., Methods: 2997 community-dwelling men and women (aged 59-73) participated in the Hertfordshire Cohort Study (HCS). We scored (from 0 to 4) number of poor health behaviours engaged in at baseline (1998-2004) out of: current smoking, high weekly alcohol, low customary physical activity and poor diet. We linked HCS with Hospital Episode Statistics and mortality data to 31/03/2010 and analysed associations between the score and risk of different types of hospital admission: any; elective; emergency; long stay (>7 days); 30-day readmission (any, or emergency)., Results: 32%, 40%, 20% and 7% of men engaged in 0, 1, 2 and 3/4 poor health behaviours; corresponding percentages for women 51%, 38%, 9%, 2%. 75% of men (69% women) experienced at least one hospital admission. Among men and women, increased number of poor health behaviours was strongly associated (p<0.01) with greater risk of long stay and emergency admissions, and 30-day emergency readmissions. Hazard ratios (HRs) for emergency admission for 3/4 poor health behaviours in comparison with none were: men, 1.37 (95% CI 1.11 to 1.69); women, 1.84 (95% CI 1.22 to 2.77). Associations were unaltered by adjustment for age, body mass index and comorbidity., Conclusions: Clustered poor health behaviours are associated with increased risk of hospital admission among older people in the UK. Lifecourse interventions to reduce number of poor health behaviours could have substantial beneficial impact on health and use of healthcare in later life., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Hip fracture is the most significant complication of osteoporosis in terms of mortality, long-term disability and decreased quality of life. In the recent years, different techniques have been developed to assess lower limb strength and ultimately fracture risk. Here we examine relationships between two measures of lower limb bone geometry and strength; proximal femoral geometry and tibial peripheral quantitative computed tomography. We studied a sample of 431 women and 488 men aged in the range 59-71 years. The hip structural analysis (HSA) programme was employed to measure the structural geometry of the left hip for each DXA scan obtained using a Hologic QDR 4500 instrument while pQCT measurements of the tibia were obtained using a Stratec 2000 instrument in the same population. We observed strong sex differences in proximal femoral geometry at the narrow neck, intertrochanteric and femoral shaft regions. There were significant (p < 0.001) associations between pQCT-derived measures of bone geometry (tibial width; endocortical diameter and cortical thickness) and bone strength (strength strain index) with each corresponding HSA variable (all p < 0.001) in both men and women. These results demonstrate strong correlations between two different methods of assessment of lower limb bone strength: HSA and pQCT. Validation in prospective cohorts to study associations of each with incident fracture is now indicated.

Objectives: Poor appetite is commonly reported by older people but is rarely measured. The Simplified Nutritional Appetite Questionnaire (SNAQ) was validated to predict weight loss in community dwelling older adults but has been little used in hospitals. We evaluated it in older women on admission to hospital and examined associations with healthcare outcomes., Design: Longitudinal observational with follow-up at six months., Setting: Female acute Medicine for Older People wards at a University hospital in England., Participants: 179 female inpatients., Measurements: Age, weight, Body Mass Index (BMI), grip strength, SNAQ, Barthel Index Score, Mini Mental State Examination (MMSE), Geriatric Depression Scale: Short Form (GDS-SF), Malnutrition Universal Screening Tool (MUST), category of domicile and receipt of care were measured soon after admission and repeated at six month follow-up. The length of hospital stay (LOS), hospital acquired infection, readmissions and deaths by follow-up were recorded., Results: 179 female participants mean age 87 (SD 4.7) years were recruited. 42% of participants had a low SNAQ score (<14, indicating poor appetite). A low SNAQ score was associated with an increased risk of hospital acquired infection (OR 3.53; 95% CI: 1.48, 8.41; p=0.004) and with risk of death (HR 2.29; 95% CI: 1.12, 4.68; p = 0.023) by follow-up., Conclusion: Poor appetite was common among the older hospitalised women studied, and was associated with higher risk of poor healthcare outcomes.

Unlabelled: Clustering of factors linked with poor bone health is common in older adults and is associated with lower bone density and increased fracture risk in women., Purpose: Many factors are associated with bone mineral density, which in turn is strongly linked with risk of fragility fracture. We assessed how commonly clustering of risk factors occurs and related such clustering to bone mineral density in a population of older community-dwelling men and women., Method: This is a cross-sectional study with 498 men and 498 women aged 59 to 72 years, who were participants in the Hertfordshire Cohort Study, in whom incident fracture was recorded. Physical activity, diet quality, history of prior fracture, family history of fracture, cigarette and alcohol consumption and comorbidities were obtained through baseline questionnaire. Measurements of grip strength and bone mineral density of the lumbar spine and total femur were also taken., Results: Clustering of risk factors was common, with over 30% having two or more. In women, a graded association between the number of risk factors and low bone density was seen, and strong relationships were also seen between the number of risk factors and incident fracture; women with three or more risk factors had an adjusted hazard ratio (HR) of incident fracture of 5.98 (1.67, 21.43; p = 0.006) compared to women with no risk factors; women with two risk factors had an adjusted HR of 2.97 (1.14, 7.74; p = 0.03) and those with one, 2.28 (0.90, 5.75; p = 0.08)., Conclusion: Clustering of risk factors for poor bone health is common in community-dwelling older adults and is associated with increased risk of fracture and adverse bone health in women., Competing Interests: Compliance with ethical standards The East and North Hertfordshire Ethical Committees granted ethical approval for the study, and all participants gave written informed consent. Conflicts of interest Elaine Dennison has received speaker fees from Lilly; Cyrus Cooper has received consultancy fees/honoraria from Servier, Eli Lilly, Merck, Amgen, Novartis and Medtronic. Jean Zhang, Karen Jameson, Avan Aihie Sayer and Sian Robinson declare that they have no conflict of interest. Funding The Hertfordshire Cohort Study is funded by grants from the Medical Research Council and Arthritis Research UK.