Impaired lower limb muscle mass, quality and function in end stage liver disease: A cross-sectional study.

NEW FINDINGS: What is the central question of this study? To what extent does musculoskeletal impairment occur (i.e., muscle mass, quality and function) in patients with end stage liver disease (ESLD) by comparison to a healthy age/sex-matched control group? What is the main finding and its importance? Muscle mass, quality and function are impaired in patients with ESLD (compared to age/sex matched controls). Importantly, greater impairments were seen in lower limb compared to arm and trunk muscle groups. These findings may suggest that there should be greater consideration of muscle health in functionally relevant lower limb muscle groups. ABSTRACT: Sarcopenia is associated with reduced quality of life and increased mortality in patients with end stage liver disease (ESLD). Historically, sarcopenia identification in ESLD utilised L3 skeletal muscle index (SMI). There are few data on muscle quality and function within lower limb muscle groups with high functional relevance. The aim of this prospective case-control study was to evaluate the quadriceps muscle in patients with ESLD. Muscle mass and quality were evaluated using MRI (quadriceps anatomical cross sectional area (ACSA), quadriceps volume index, L3 SMI, quadriceps intermuscular adipose tissue (IMAT)), mid-arm muscle circumference (MAMC) and ultrasonography (vastus lateralis (VL) thickness and quadriceps ACSA). Muscle strength/function was assessed by handgrip strength, peak quadriceps isokinetic torque and chair rise time. Thirty-nine patients with ESLD (55 years, 61% male, 48% alcoholic related liver disease (ArLD), 71% Child-Pugh B/C) and 18 age/sex-matched healthy control participants (HC) were studied. Quadriceps mass was significantly reduced in ESLD versus HC (-17%), but L3 SMI and MAMC were unchanged. Quadriceps IMAT percentage was increased in ESLD (+103%). Handgrip strength (-15%), peak isokinetic torque (-29%), and chair rise time (+56%) were impaired in ESLD. Ultrasound measures of VL thickness (r = 0.56, r = 0.57, r = 0.42) and quadriceps ACSA (r = 0.98, r = 0.86, r = 0.67) correlated to MRI quadriceps ACSA, quadriceps volume and L3 SMI, respectively. Quadriceps muscle mass, quality, and function were impaired in patients with ESLD, whereas conventional assessments of muscle (L3 SMI and MAMC) highlighted no differences between ESLD and HC. Full evaluation of lower limb muscle health is essential in ESLD in order to accurately assess sarcopenia and target future interventions.

Frailty: Pathophysiology, Theoretical and Operational Definition(s), Impact, Prevalence, Management and Prevention, in an Increasingly Economically Developed and Ageing World.

The world's population is ageing, and most older adults experience a later life burdened with disease and disability. Frailty is a multidimensional and dynamic condition characterized by declines in reserve and function across multiple physiological systems, such that the ability to cope with every day or acute stressors becomes compromised. It is projected to become one of the most serious public health challenges economically developed societies will face in the coming century. This review provides a comprehensive overview of frailty, exploring its pathophysiology, theoretical and operational definition(s), impact, prevalence, management, and prevention, within the context of its emergence as a major public health challenge, in an increasingly economically developed and ageing world. Further, this review discusses the major limitations, deficiencies, and knowledge gaps presently within the field, and future research directions pertinent to the advancement of frailty research and the promotion of healthy longevity among the increasing global population of older adults.

Investigating the impact of fluid status on the ultrasound assessment of muscle quantity and quality in the diagnosis of sarcopenia - a multidimensional cross-sectional study.

BACKGROUND: Sarcopenia is a clinical manifestation of adverse ageing, characterised by progressive loss of muscle mass and function. Diagnosis requires assessment of muscle quantity and quality; ultrasound represents an emerging tool for this. However, ultrasound muscle assessment may be impacted by fluid balance. This is particularly important when assessing for acute sarcopenia in hospitalised patients, where fluid disturbance often occurs. The primary aim of this study was to characterise the impact of fluid status on ultrasound muscle assessment, such that this may be accounted for in sarcopenia diagnostics. METHODS: This Multidimensional Cross-sectional study involved 80 participants, who were inpatients at QEHB, a large UK tertiary centre. Fluid status was evaluated clinically and quantified using Bioelectrical Impedance Analysis (BIA). Muscle quantity was measured using Bilateral Anterior Thigh Thickness (BATT) with Rectus Femoris (RF) echogenicity used to assesses muscle adiposity and hence provide an inverse measure of muscle quality. RESULTS: A significant positive correlation was found between fluid status, measured using BIA, and BATT as a measure of muscle quantity, in males (rs = 0.662, p < 0.001) and females (rs = 0.638, p < 0.001). A significant negative correlation was found between fluid status and RF echogenicity (rs=-0.448, p < 0.001). CONCLUSIONS: These findings demonstrate associations between fluid balance and ultrasound assessment of muscle quantity and quality. Given the emerging use of ultrasound muscle assessment in sarcopenia diagnosis, there is a need to account for this in clinical practice. Future research should focus on the development of a corrective equation allowing assessment of muscle quantity and quality which account for changes in fluid status, hence aiding accurate diagnosis of sarcopenia.

Sarcopenia in chronic liver disease: mechanisms and countermeasures.

Sarcopenia, a condition of low muscle mass, quality, and strength, is commonly found in patients with cirrhosis and is associated with adverse clinical outcomes including reduction in quality of life, increased mortality, and posttransplant complications. In chronic liver disease (CLD), sarcopenia is most commonly defined through the measurement of the skeletal muscle index of the third lumbar spine. A major contributor to sarcopenia in CLD is the imbalance in muscle protein turnover, which likely occurs due to a decrease in muscle protein synthesis and an elevation in muscle protein breakdown. This imbalance is assumed to arise due to several factors including accelerated starvation, hyperammonemia, amino acid deprivation, chronic inflammation, excessive alcohol intake, and physical inactivity. In particular, hyperammonemia is a key mediator of the liver-gut axis and is known to contribute to mitochondrial dysfunction and an increase in myostatin expression. Currently, the use of nutritional interventions such as late-evening snacks, branched-chain amino acid supplementation, and physical activity have been proposed to help the management and treatment of sarcopenia. However, little evidence exists to comprehensively support their use in clinical settings. Several new pharmacological strategies, including myostatin inhibition and the nutraceutical Urolithin A, have recently been proposed to treat age-related sarcopenia and may also be of use in CLD. This review highlights the potential molecular mechanisms contributing to sarcopenia in CLD alongside a discussion of existing and potential new treatment strategies.

Factors associated with electrical stimulation-induced performance fatigability are dependent upon stimulation location.

NEW FINDINGS: What is the central question of this study? How does peripheral nerve stimulation (PNS) compare with neuromuscular electrical stimulation (NMES) used clinically to reduce muscle atrophy? What is the main finding and its importance? NMES resulted in progressive increases in M-wave duration and delay of muscle relaxation throughout a single stimulation protocol, findings not observed with PNS. This suggests PNS recruits from a wider pool of muscle fibres/motor units, providing a more favourable alternative to NMES for rehabilitation intervention. ABSTRACT: Neuromuscular electrical stimulation (NMES) is increasingly viewed as a central tenet to minimise muscle loss during periods of disuse/illness - typically applied directly over a muscle belly. Peripheral nerve stimulation (PNS) is afforded less attention, despite providing a more global contractile stimulus to muscles. We investigated NMES versus PNS in relation to performance fatigability and peripheral contributions to voluntary force capacity. Two fatigue protocols were assessed separately: (1) over-quadriceps NMES and (2) peripheral (femoral) nerve stimulation (PNS). Before and after each session, a maximal voluntary contraction (MVC) was performed to assess force loss. Knee-extensor force was measured throughout to assess contractile function in response to submaximal electrical stimulation, and M-wave features quantified myoelectrical activity. NMES and PNS induced similar voluntary (MVC, NMES: -12 ± 9%, PNS: -10 ± 8%, both P < 0.001) and stimulated (NMES: -45 ± 12%, PNS -27 ± 27%, both P < 0.001) force reductions. Although distinct between protocols, myoelectrical indicators of muscle recruitment (M-wave area and amplitude) and nerve conduction time did not change throughout either protocol. Myoelectrical propagation speed, represented as M-wave duration, and the delay before muscle relaxation began both progressively increased during NMES only (P < 0.05 and P < 0.001, respectively). NMES myoelectrical changes suggested performance fatigability, indicating activation of superficial fibres only, which was not observed with PNS. This suggests PNS recruits a wider pool of muscle fibres and motor units and is a favourable alternative for rehabilitation. Future work should focus on implementing PNS interventions in clinically relevant scenarios such as immobilisation, care homes and critical illness.

Interventions to ameliorate reductions in muscle quantity and function in hospitalised older adults: a systematic review towards acute sarcopenia treatment.

OBJECTIVE: Assimilate evidence for interventions to ameliorate negative changes in physical performance, muscle strength and muscle quantity in hospitalised older adults. METHODS: We searched for articles using MEDLINE, Embase, CINAHL and Cochrane library using terms for randomised controlled trials, older adults, hospitalisation and change in muscle quantity, strength or physical performance. Two independent reviewers extracted data and assessed risk of bias. We calculated standardised mean differences for changes in muscle function/quantity pre- and post-intervention. RESULTS: We identified 9,805 articles; 9,614 were excluded on title/abstract; 147 full texts were excluded. We included 44 studies including 4,522 participants; mean age 79.1. Twenty-seven studies (n = 3,417) involved physical activity interventions; a variety were trialled. Eleven studies involved nutritional interventions (n = 676). One trial involved testosterone (n = 39), two involved Growth Hormone (n = 53), one involved nandrolone (n = 29), and another involved erythropoietin (n = 141). Three studies (n = 206) tested Neuromuscular Electrical Stimulation. Evidence for effectiveness/efficacy was limited. Strongest evidence was for multi-component physical activity interventions. However, all studies exhibited at least some concerns for overall risk of bias, and considering inconsistencies of effect sizes across studies, certainty around true effect sizes is limited. CONCLUSION: There is currently insufficient evidence for effective interventions to ameliorate changes in muscle function/quantity in hospitalised older adults. Multiple interventions have been safely trialled in heterogeneous populations across different settings. Treatment may need to be stratified to individual need. Larger scale studies testing combinations of interventions are warranted. Research aimed at understanding pathophysiology of acute sarcopenia will enable careful risk stratification and targeted interventions.

Muscle quantity and function measurements are acceptable to older adults during and post- hospitalisation: results of a questionnaire-based study.

BACKGROUND: To evaluate the acceptability of handgrip strength, gait speed, quadriceps ultrasound, and Bioelectrical Impedance Analysis (BIA) to older adults conducted during and following hospitalisation. METHODS: Questionnaire-based study conducted upon completion of prospective cohort study, with follow-up in either Queen Elizabeth Hospital Birmingham (QEHB), UK, or participant's own home following recent admission to QEHB. Outcome measures were acceptability as defined by total multi-domain score for each test (maximum score 35), and by frailty status. RESULTS: Forty adults aged 70 years and older admitted for emergency abdominal surgery, elective colorectal surgery, or acute bacterial infections (general medicine) participated. Handgrip strength (median 33, IQR 30-35; p = 0.001), gait speed (median 32, IQR 30-35; p = 0.002), ultrasound quadriceps (median 33, IQR 31-35; p = 0.001), and BIA (median 33.5, IQR 31-35; p = 0.001) were considered highly acceptable. Participants responded positively that they enjoyed participating in these tests, and considered these tests of importance. There was no difference in scores between tests (p = 0.166). Individual total test scores did not differ between patients with and without frailty. Qualitative data are also presented on drivers for research participation. CONCLUSIONS: Handgrip strength, gait speed, ultrasound quadriceps, and BIA are acceptable tests to older adults during and following hospitalisation. Our results may serve as standards when evaluating acceptability of other tests. TRIAL REGISTRATION: Prospectively registered February 2019: https://clinicaltrials.gov/ct2/show/NCT03858192.

Utilising the perspectives of patients with lower-limb osteoarthritis on prescribed physical activity to develop a theoretically informed physiotherapy intervention.

BACKGROUND: Lower-limb osteoarthritis (OA) causes high levels of pain and disability. Physiotherapists are the primary healthcare provider of non-pharmacological treatments, and incorporate strategies to optimise physical activity (PA) to aid patients with lower-limb OA to moderate their clinical symptoms. However, patients with lower-limb OA have low adherence to PA recommendations both during treatment and after discharge. This study aimed to use knowledge of identified barriers and facilitators to physiotherapy prescribed PA (during treatment and post-discharge) to develop a theoretically informed intervention to optimise adherence to PA for patients with lower-limb OA during treatment and post-discharge. METHODS: 1) A purposive sample of 13 patients with lower-limb OA participated in semi-structured interviews following physiotherapy treatment. Inductive analysis identified themes/subthemes reflecting barriers and facilitators to physiotherapist prescribed PA, which were organised deductively according to personal factors, treatment and post-discharge phases. 2) Themes/subthemes were mapped onto the theoretical domains framework (TDF). 3) Behaviour change techniques (BCTs) were coded from the key identified domains and a theoretically informed physiotherapy intervention addressing barriers and using facilitators, was developed. RESULTS: Themes of patient confidence, mind-set, motivation, OA symptoms and PA experiences were primary personal factors that influenced PA adherence; with the TDF domain 'Beliefs about capabilities' most important to target. During treatment, the theme of routine formation was the major driver of personal factors; and primarily influenced by developing a positive physiotherapist-patient relationship. Post-discharge, physical factors, psychosocial factors and ongoing access to resources were important themes influencing PA maintenance. 'Environmental context and resources' and 'social influences' emerged as the key TDF domains to target during treatment and post-discharge. The proposed theoretically informed intervention included 26 BCTs delivered across conceptual phases of adoption, routine formation, and maintenance. CONCLUSION: A theoretically informed physiotherapy intervention was proposed to optimise PA adherence in patients with lower-limb OA. The included BCTs primarily target patients' perceived beliefs about their capabilities, by developing a PA routine during treatment and facilitating appropriate psychosocial support and access to resources for PA maintenance post-discharge. The feasibility of delivering the intervention in clinical practice will now be evaluated.

Optimization of dietary RNA interference delivery to western flower thrips Frankliniella occidentalis and onion thrips Thrips tabaci.

In insect reverse genetics, dietary delivery of interfering RNAs is a practical approach in nonmodel species, such as thrips, whose small size, and feeding behavior restricts the use of other delivery methods. In a laboratory context, an unsuitable diet could confound the interpretation of an RNA interference (RNAi) phenotype, however well-formulated artificial diets can minimize experimental variability, reduce the need for insect handling, and can further be used for roles, such as delivering double-strand RNA (dsRNA)-expressing recombinant bacteria. In this study, artificial diets for oral delivery of dsRNA were developed for two important pest thrips species, western flower thrips (Frankliniella occidentalis) and onion thrips (Thrips tabaci), with the goal of (a) stimulating feeding behavior, (b) supporting optimal growth rates of dsRNA-expressing symbiotic bacteria, and (c) nutritionally supporting the thrips for sufficient periods to observe RNAi phenotypes. The efficacy of artificial diets for ingesting "naked" dsRNA or dsRNA-expressing symbionts and dsRNA delivery via host plant uptake was evaluated. Compared with previously published diet formulations, new combinations based on tryptone, yeast, and soy were superior for enhancing feeding and longevity. However, simply adding "naked" dsRNA to an artificial diet was an unreliable form of RNAi delivery in our hands due to dsRNA degradation. Delivery via host plants was more successful, and the new diet formulation was suitable for symbiont-mediated dsRNA delivery, which we believe is the most convenient approach for large-scale knockdown experiments. This study, therefore, provides alternative methodologies for thrips rearing, dietary RNAi delivery, and insights into the challenges of performing dietary RNAi in nonmodel insects.

Protocol for understanding acute sarcopenia: a cohort study to characterise changes in muscle quantity and physical function in older adults following hospitalisation.

BACKGROUND: Older adults are vulnerable to the effects of acute sarcopenia (acute muscle insufficiency) following hospitalisation. However, this condition remains poorly characterised to date. It is hypothesised that acute sarcopenia arises due to a combination of bed rest and inflammatory surge. This study aims to characterise changes in muscle quantity and function, determining which factors (clinical and biological) are most predictive, and how these relate to change in physical function at 13 weeks. METHODS: This study will include three groups of patients aged 70 years and older; patients undergoing elective colorectal surgery, patients admitted for emergency abdominal surgery, and patients admitted under general medicine with acute bacterial infections. Changes in muscle quantity (Bilateral Anterior Thigh Thickness with ultrasound and bioelectrical impedance analysis) and muscle function (muscle strength, physical performance) within 1 week of hospitalisation or surgery will be characterised, with follow-up of patients at 13 weeks. Physical function will be measured using the Patient Reported Outcome Measures Information System, and the Short Physical Performance Battery (or gait speed alone within 1 week of surgery). DISCUSSION: This study will fully characterise changes in muscle quantity and function in hospitalised older adults and enable risk stratification towards targeted interventions in clinical practice. The results of this study will inform further research involving interventions to ameliorate changes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03858192 ; Prospectively registered 28th February 2019.

Social networks and their influences on nutrient intake, nutritional status and physical function in community-dwelling ethnically diverse older adults: a mixed-methods longitudinal study.

BACKGROUND: The United Kingdom population is ageing and becoming increasingly diverse; thus, it is vital to develop and implement interventions supporting this population shift. Social networks (SN) significantly impact health outcomes in later life, however relatively little is known about SN of community-dwelling ethnically diverse older adults. This study aimed to: 1) profile SN and changes in SN in this population over 8 months; 2) examine associations between SN, dietary intake, nutritional status, and physical function. METHODS: SN were assessed using the Wenger Practitioner Assessment of Network Type. Energy and nutrient intakes were measured using multiple-pass 24-h recalls. The Mini Nutritional Assessment-Short Form (MNA-SF) assessed nutritional status. Physical function was measured using the Short Physical Performance Battery (SPPB) and handgrip strength. Data were collected at baseline and 8-months. Correlation and regression analyses examined relationships between SN, physical function, nutrient intake and nutritional status. Semi-structured interviews were conducted at baseline (n = 92) and follow-up (n = 81) to identify potential influences of SN. Interviews were transcribed verbatim and analysed using directed content analysis. RESULTS: Quantitative data were obtained from 100 participants at baseline and 81 at follow-up. Mean (SD) age was 70.8 (8.1) years (59% male), comprising African/Caribbean (60%), South Asian (34%), and other ethnicities (6%). Five SN typologies were identified under two broad areas: integrated-SN consisting of locally integrated (44%) and wider community (8%); and non-integrated-SN consisting of family dependent (25%), local self-contained (17%), and private restricted (6%). At follow-up, 37% remained in non-integrated networks, 19% transitioned to non-integrated networks, 11% transitioned to, and 33% remained in, integrated networks. Participants within integrated networks at baseline had higher SPPB scores at follow-up. Compared to the private restricted, local self-contained SN significantly predicted zinc, riboflavin and vitamin B6 intakes. Participants remaining in, or transitioning to, non-integrated networks had low MNA-SF scores. Qualitative findings indicate that participants with reductions in SN perceived it as causing poorer physical function and eating behaviours. CONCLUSION: In the present study, integrated SN were associated with higher physical function and nutritional status at 8-month's follow-up. These results can inform the design of interventions to improve social networks, physical function and healthy nutrition within this population.

A novel behavioural INTErvention to REduce Sitting Time in older adults undergoing orthopaedic surgery (INTEREST): results of a randomised-controlled feasibility study.

BACKGROUND: Osteoarthritis is a prevalent condition in older adults that causes many patients to require a hip or knee replacement. Reducing patients' sedentariness prior to surgery may improve physical function and post-operative outcomes. METHODS: We conducted a pragmatic randomised-controlled feasibility study with 2:1 allocation into intervention or usual care groups. The intervention, based on Self-Determination Theory, involved techniques to reduce sedentary behaviour, including motivational interviewing, setting of behavioural goals, and more. The primary outcome was feasibility, assessed using mixed methods. We included exploratory measures to inform a future definitive trial, such as ActivPal3 accelerometry to measure movement, the Short Physical Performance Battery (SPPB), Basic Psychological Needs, and cardiometabolic biomarkers. Assessments were at baseline, 1-week pre-surgery, and 6-week post-surgery. RESULTS: We recruited 35 participants aged ≥ 60 years approximately 8 weeks before hip or knee arthroplasty. Participant uptake rate was 14.2%, and retention rate 85.7%. Participants were very satisfied with the study which was found to be feasible with some modifications. Exploratory within-group comparisons found that the intervention has potential to improve SPPB by 0.71 points from baseline to pre-surgery, a clinically significant increase, and reduce sedentary time by up to 66 min d-1. CONCLUSION: In this older surgical population, it is feasible to use behavioural techniques to displace sedentary time to activity and to conduct a trial spanning the period of surgical intervention. This may improve physical function and surgical outcomes. The INTEREST intervention is now ready for evaluation in a full-scale randomised-controlled trial. REGISTRATION: This trial was registered on Clinicaltrials.gov on 13/11/2018. ID: NCT03740412.

Generalisation and specialisation in hoverfly (Syrphidae) grassland pollen transport networks revealed by DNA metabarcoding.

Pollination by insects is a key ecosystem service and important to wider ecosystem function. Most species-level pollination networks studied have a generalised structure, with plants having several potential pollinators, and pollinators in turn visiting a number of different plant species. This is in apparent contrast to a plant's need for efficient conspecific pollen transfer. The aim of this study was to investigate the structure of pollen transport networks at three levels of biological hierarchy: community, species and individual. We did this using hoverflies in the genus Eristalis, a key group of non-Hymenopteran pollinators. We constructed pollen transport networks using DNA metabarcoding to identify pollen. We captured hoverflies in conservation grasslands in west Wales, UK, removed external pollen loads, sequenced the pollen DNA on the Illumina MiSeq platform using the standard plant barcode rbcL, and matched sequences using a pre-existing plant DNA barcode reference library. We found that Eristalis hoverflies transport pollen from 65 plant taxa, more than previously appreciated. Networks were generalised at the site and species level, suggesting some degree of functional redundancy, and were more generalised in late summer compared to early summer. In contrast, pollen transport at the individual level showed some degree of specialisation. Hoverflies defined as "single-plant visitors" varied from 40% of those captured in early summer to 24% in late summer. Individual hoverflies became more generalised in late summer, possibly in response to an increase in floral resources. Rubus fruticosus agg. and Succisa pratensis were key plant species for hoverflies at our sites Our results contribute to resolving the apparent paradox of how generalised pollinator networks can provide efficient pollination to plant species. Generalised hoverfly pollen transport networks may result from a varied range of short-term specialised feeding bouts by individual insects. The generalisation and functional redundancy of Eristalis pollen transport networks may increase the stability of the pollination service they deliver.

Physical fitness training for stroke patients.

BACKGROUND: Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability. OBJECTIVES: To determine whether fitness training after stroke reduces death, dependence, and disability and to assess the effects of training with regard to adverse events, risk factors, physical fitness, mobility, physical function, quality of life, mood, and cognitive function. Interventions to improve cognitive function have attracted increased attention after being identified as the highest rated research priority for life after stroke. Therefore we have added this class of outcomes to this updated review. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 1: searched February 2015), MEDLINE (1966 to February 2015), EMBASE (1980 to February 2015), CINAHL (1982 to February 2015), SPORTDiscus (1949 to February 2015), and five additional databases (February 2015). We also searched ongoing trials registers, handsearched relevant journals and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 58 trials, involving 2797 participants, which comprised cardiorespiratory interventions (28 trials, 1408 participants), resistance interventions (13 trials, 432 participants), and mixed training interventions (17 trials, 957 participants). Thirteen deaths occurred before the end of the intervention and a further nine before the end of follow-up. No dependence data were reported. Diverse outcome measures restricted pooling of data. Global indices of disability show moderate improvement after cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) 0.19 to 0.84; P value = 0.002) and by a small amount after mixed training (SMD 0.26, 95% CI 0.04 to 0.49; P value = 0.02); benefits at follow-up (i.e. after training had stopped) were unclear. There were too few data to assess the effects of resistance training.Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 6.71 metres per minute, 95% CI 2.73 to 10.69), preferred gait speed (MD 4.28 metres per minute, 95% CI 1.71 to 6.84), and walking capacity (MD 30.29 metres in six minutes, 95% CI 16.19 to 44.39) at the end of the intervention. Mixed training, involving walking, increased preferred walking speed (MD 4.54 metres per minute, 95% CI 0.95 to 8.14), and walking capacity (MD 41.60 metres per six minutes, 95% CI 25.25 to 57.95). Balance scores improved slightly after mixed training (SMD 0.27, 95% CI 0.07 to 0.47). Some mobility benefits also persisted at the end of follow-up. The variability, quality of the included trials, and lack of data prevents conclusions about other outcomes and limits generalisability of the observed results. AUTHORS' CONCLUSIONS: Cardiorespiratory training and, to a lesser extent, mixed training reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve the speed and tolerance of walking; some improvement in balance could also occur. There is insufficient evidence to support the use of resistance training. The effects of training on death and dependence after stroke are still unclear but these outcomes are rarely observed in physical fitness training trials. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription and identify long-term benefits.

Exploratory longitudinal cohort study of associations of fatigue after stroke.

BACKGROUND AND PURPOSE: The pathogenesis of poststroke fatigue is unclear. In this prospective study, we explored whether reduced physical activity might contribute to poststroke fatigue or be a consequence of it. METHODS: Patients with a recent acute stroke were assessed at 1, 6, and 12 months with, Fatigue Assessment Scale (FAS), a fatigue case definition, Hospital Anxiety and Depression Score, sleepiness, quality of life, and accelerometry (ActivPAL). Bivariate analyses determined associations between fatigue and step count at each time point. Multiple linear regression tested whether 1-month step count independently predicted 6- and 12-month FAS. RESULTS: A total of 136 participants (mean age, 72 years; 64% men) attended ≥1 assessment. ActivPAL data were available for 84 (64%), 69 (66%), and 58 (64%) participants at 1, 6, and 12 months, respectively. At 6 and 12 months, a positive fatigue case definition was associated with lower daily step counts (P=0.014 and 0.013, respectively). At 1, 6, and 12 months, higher FAS (more fatigue) was associated with lower step count (P<0.001, 0.01, and 0.007), higher depression (P<0.001), anxiety scores (P<0.001) and sleepiness (P<0.001), and poorer quality of life (P<0.001). Lower daily step count (P<0.002 and 0.006) and greater anxiety (P<0.001 for both) at 1 month independently predicted higher FAS at 6 and 12 months. CONCLUSIONS: Lower step counts at 1 month independently predicted greater FAS for ≤12 months. Physical activity might be a therapeutic target for poststroke fatigue.

Sedentary behavior in the first year after stroke: a longitudinal cohort study with objective measures.

OBJECTIVE: To quantify longitudinal changes in sedentary behavior (ie, nonexercise seated or lying behavior) after stroke to ascertain whether reducing sedentary behavior might be a new therapeutic target. DESIGN: Longitudinal cohort study of patients with acute stroke who were followed over 1 year. SETTING: Acute teaching hospital or outpatient clinic, and the community after discharge. PARTICIPANTS: A convenience sample of patients with acute stroke (N=96; median age, 72y, interquartile range [IQR]=64-80y; 67% men; median National Institute of Health Stroke Scale score=2, IQR=1-3) who were assessed at 1, 6, and 12 months after stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Objective measures of amount and pattern of time spent in sedentary behavior: total sedentary time, weighted median sedentary bout length, and fragmentation index. RESULTS: Stroke survivors were highly sedentary, spending on average 81% of the time per day in sedentary behavior: median=19.9 hours (IQR=18.4-22.1h), 19.1 hours (17.8-20.8h), and 19.3 hours (17.3-20.9h) at 1, 6, and 12 months, respectively. Longitudinal changes in sedentary behavior were estimated using linear mixed effects models. Covariates were age, sex, stroke severity (National Institute of Health Stroke Scale score), physical capacity (6-minute walk distance), and functional independence (Nottingham Extended Activities of Daily Living Questionnaire score). Higher stroke severity and less functional independence were associated cross-sectionally with more sedentary behavior (ß=.11, SE=.05, P=.020 and ß=-.11, SE=.01, P<.001, respectively). Importantly, the pattern of sedentary behavior did not change over the first year after stroke and was independent of functional ability. CONCLUSIONS: Stroke survivors were highly sedentary and remained so a year after stroke independently of their functional ability. Developing interventions to reduce sedentary behavior might be a potential new therapeutic target in stroke rehabilitation.

Testing advances in molecular discrimination among Chinook salmon life histories: evidence from a blind test.

The application of DNA-based markers toward the task of discriminating among alternate salmon runs has evolved in accordance with ongoing genomic developments and increasingly has enabled resolution of which genetic markers associate with important life-history differences. Accurate and efficient identification of the most likely origin for salmon encountered during ocean fisheries, or at salvage from fresh water diversion and monitoring facilities, has far-reaching consequences for improving measures for management, restoration and conservation. Near-real-time provision of high-resolution identity information enables prompt response to changes in encounter rates. We thus continue to develop new tools to provide the greatest statistical power for run identification. As a proof of concept for genetic identification improvements, we conducted simulation and blind tests for 623 known-origin Chinook salmon (Oncorhynchus tshawytscha) to compare and contrast the accuracy of different population sampling baselines and microsatellite loci panels. This test included 35 microsatellite loci (1266 alleles), some known to be associated with specific coding regions of functional significance, such as the circadian rhythm cryptochrome genes, and others not known to be associated with any functional importance. The identification of fall run with unprecedented accuracy was demonstrated. Overall, the top performing panel and baseline (HMSC21) were predicted to have a success rate of 98%, but the blind-test success rate was 84%. Findings for bias or non-bias are discussed to target primary areas for further research and resolution.

Identification of the needs and priorities of older people and stakeholders in rural and urban areas of Santo Andre, Brazil.

BACKGROUND: There are few data reporting the needs and priorities of older adults in Brazil. This hampers the development and/or implementation of policies aimed at older adults to help them age well. The aim of this study was to understand areas of importance, priorities, enablers and obstacles to healthy ageing as identified by older adults and key stakeholders in both urban and rural environments. METHODS: Two locations were selected, one urban and one rural in the municipality of Santo André, in the metropolitan region of São Paulo (SP). Workshops for older adults (>60 y) and stakeholders were conducted separately in each location. The workshops incorporated an iterative process of discussion, prioritisation and ranking of responses, in roundtable groups and in plenary. Areas of commonality and differences between older adult and stakeholder responses were identified by comparing responses between groups as well as mapping obstacles and enablers to healthy ageing identified by older adults, to the priorities identified by stakeholder groups. The socio-ecologic model was used to categorise responses. RESULTS: There were few shared responses between stakeholders and older adults and little overlap between the top ranked responses of urban and rural groups. With respect to areas of importance, both stakeholder groups ranked policies for older people within their top five reponses. Both older adult groups ranked keeping physically and mentally active, and nurturing spirituality. There was a marked lack of congruence between older adults' obstacles and enablers to healthy ageing and stakeholder priorities, in both urban and rural settings. Most responses were located within the Society domain of the socio-ecologic model, although older adults also responded within the Individual/ Relationships domains, particularly in ranking areas of most importance for healthy ageing. CONCLUSIONS: Our results highlight substantial differences between older adults and stakeholders with respect to areas of importance, priorities, enablers and obstacles to healthy ageing, and point to the need for more engagement between those in advocacy and policymaking roles and the older people whose needs they serve.

Frailty progression in adults aged 40 years and older in rural Burkina Faso: a longitudinal, population-based study.

BACKGROUND: Little is known about ageing and frailty progression in low-income settings. We aimed to describe frailty changes over time in individuals living in rural Burkina Faso and to assess which sociodemographic, disability, and multimorbidity factors are associated with frailty progression and mortality. METHODS: This longitudinal, population-based study was conducted at the Nouna Health and Demographic Surveillance Systems (HDSS) site in northwestern Burkina Faso. Eligible participants were aged 40 years or older and had been primarily resident in a household within the HDSS area for at least the past 6 months before the baseline survey and were selected from the 2015 HDSS household census using a stratified random sample of adults living in unique households within the area. Participants were interviewed in their homes in 2018 (baseline), 2021 (follow-up), or both. We derived the Fried frailty score for each participant at each timepoint using data on grip strength, gait speed, self-reported weight loss, self-reported exhaustion, and physical activity, and described changes in frailty status (no frailty, pre-frailty, or frailty) between 2018 and 2021. We used multivariate regression models to assess factors (ie, sex, age, marital status, educational attainment, wealth quintile, WHO Disability Assessment Schedule (WHODAS) score, and multimorbidity) associated with frailty progression (either worsening frailty status or dying, compared with frailty status remaining the same or improving) and with mortality, and developed sequential models: unadjusted, adjusting for sociodemographic factors (sex, age, marital status, educational attainment, and wealth quintile), and adjusting for sociodemographic factors, disability, and multimorbidity. FINDINGS: Between May 25 and July 19, 2018, and between July 1 and Aug 22, 2021, 5952 individuals were invited to participate: 1709 (28·7%) did not consent, 1054 (17·8%) participated in 2018 only and were lost to follow-up, 1214 (20·4%) participated in 2021 only, and 1975 (33·2%) were included in both years or died between years. Of 1967 participants followed up with complete demographic data, 190 (9·7%) were frail or unable to complete the frailty assessment in 2018, compared with 77 (3·9%) in 2021. Between 2018 and 2021, frailty status improved in 567 (28·8%) participants and worsened in 327 (16·6%), and 101 (5·1%) participants died. The relative risk of frailty status worsening or of dying (compared with frailty impRoving or no change) increased with age and WHODAS score, whereas female sex appeared protective. After controlling for all sociodemographic factors, multimorbidity, and WHODAS score, odds of mortality were 1·07 (odds ratio 2·07, 95% CI 1·05-4·09) times higher among pre-frail individuals and 1·1 (2·21, 0·90-5·41) times higher among frail individuals than among non-frail individuals. INTERPRETATION: Frailty status was highly dynamic in this low-income setting and appears to be modifiable. Given the rapid increase in the numbers of older adults in low-income or middle-income countries, understanding the behaviour of frailty in these settings is of high importance for the development of policies and health systems to ensure the maintenance of health and wellbeing in ageing populations. Future work should focus on designing context-appropriate interventions to improve frailty status. FUNDING: Alexander Von Humboldt Foundation, Institute for Global Innovation, University of Birmingham, and Wellcome Trust.

Exploring the priorities of ageing populations in Pakistan, comparing views of older people in Karachi City and Thatta.

As a lower middle-income country, Pakistan faces multiple issues that influence the course of healthy ageing. Although there is some understanding of these issues and the objective health outcomes of people in Pakistan, there is less knowledge on the perceptions, experiences, and priorities of the ageing population and their caretakers (hereafter, "stakeholders"). The aim of the study was to identify the needs and priorities of older adults and stakeholders across both urban and rural locations. We sought to explore the views of two groups of people, older adults and stakeholders on topics including the definition of ageing as well as areas of importance, services available, and barriers to older people living well. Two-day workshops were conducted in one rural city, Thatta and one urban city, Karachi. The workshops were designed using the Nominal Group Technique, which included plenary and roundtable discussions. The responses were ranked through rounds of voting and a consensus priority list was obtained for each topic and group. Responses were categorized using the socio-ecological framework. Responses were compared between stakeholders and older people and between different geographical areas. 24 urban and 26 rural individuals aged over 60 years and 24 urban and 26 rural stakeholders attended the workshops. There were few areas of agreement with respect to both geographical region and participant group. Comparing older adults' definition of ageing, there was no overlap between the top five ranked responses across urban and rural locations. With respect to areas of importance, there was agreement on free health care as well as financial support. In terms of barriers to healthy ageing, only nation-wide inflation was ranked highly by both groups. In addition, there were relatively few areas of congruence between stakeholder and older adult responses, irrespective of location, although engagement with family, adequate nutrition and monetary benefits were responses ranked by both groups as important for healthy ageing. Both groups ranked issues with the pension system and financial difficulties as barriers. When categorized using the socio-ecological model, across all questions, societal factors were prioritized most frequently (32 responses), followed by individual (27), relationship (15), and environment (14). Overcoming barriers to facilitate healthy ageing will require a multi-faceted approach and must incorporate the priorities of older individuals. Our results may serve as a guide for researchers and policymakers for future engagement and to plan interventions for improving the health of the ageing population in Pakistan.