Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

INTRODUCTION: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor. These variants have been rarely studied in older people or people with sarcopenia. METHODS: We performed a post hoc sub-study of the Leucine and ACE (LACE) inhibitor trial, which enrolled 145 participants aged ≥70 years with low grip strength and low gait speed. Participants' blood samples were genotyped for rs179972 using TaqMan and rs5810761 by amplification through Hotstar Taq. Genotypes were compared with outcomes of physical performance and body composition measures. RESULTS: Data from 136 individuals were included in the analysis. For rs1799722 the genotype frequency (TT: 17, CC: 48, CT: 71) remained in Hardy-Weinberg Equilibrium (HWE p = 0.248). There was no difference between the genotypes for six-Minute Walk Distance (6MWD) or Short Physical Performance Battery (SPPB). Men with the TT genotype had a significantly greater 6MWD than other genotypes (TT 400m vs CT 310m vs CC 314m, p = 0.027), and greater leg muscle mass (TT 17.59kg vs CT 15.04kg vs CC 15.65kg, p = 0.007). For rs5810761, the genotype frequency (-9-9: 31, +9+9: 43, -9+9: 60) remained in HWE (p = 0.269). The +9+9 genotype was associated with a significant change in SPPB score at 12 months (-9-9 0 vs -9+9 0 vs +9+9-1, p<0.001), suggesting an improvement. In men, the -9-9 genotype was associated with lower arm fat (-9-9 2.39kg vs -9+9 2.72kg vs +9+9 2.76kg, p = 0.019). CONCLUSION: In men, the rs1799722 TT genotype was associated with longer 6MWD and greater leg muscle mass, while the rs5810761 -9-9 genotype was associated with lower arm fat mass.

The use of natural language processing for the identification of ageing syndromes including sarcopenia, frailty and falls in electronic healthcare records: a systematic review.

BACKGROUND: Recording and coding of ageing syndromes in hospital records is known to be suboptimal. Natural Language Processing algorithms may be useful to identify diagnoses in electronic healthcare records to improve the recording and coding of these ageing syndromes, but the feasibility and diagnostic accuracy of such algorithms are unclear. METHODS: We conducted a systematic review according to a predefined protocol and in line with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Searches were run from the inception of each database to the end of September 2023 in PubMed, Medline, Embase, CINAHL, ACM digital library, IEEE Xplore and Scopus. Eligible studies were identified via independent review of search results by two coauthors and data extracted from each study to identify the computational method, source of text, testing strategy and performance metrics. Data were synthesised narratively by ageing syndrome and computational method in line with the Studies Without Meta-analysis guidelines. RESULTS: From 1030 titles screened, 22 studies were eligible for inclusion. One study focussed on identifying sarcopenia, one frailty, twelve falls, five delirium, five dementia and four incontinence. Sensitivity (57.1%-100%) of algorithms compared with a reference standard was reported in 20 studies, and specificity (84.0%-100%) was reported in only 12 studies. Study design quality was variable with results relevant to diagnostic accuracy not always reported, and few studies undertaking external validation of algorithms. CONCLUSIONS: Current evidence suggests that Natural Language Processing algorithms can identify ageing syndromes in electronic health records. However, algorithms require testing in rigorously designed diagnostic accuracy studies with appropriate metrics reported.

Nutritional Screening, Initial Management and Referral for Older People with Sarcopenia or Frailty - Results from a UK-Wide Survey.

Objectives: We surveyed healthcare staff working with older people to understand current practice in nutrition screening, initial management and referral for older people with sarcopenia and frailty. Methods: We conducted a UK-wide web-based survey of staff working with older people in both hospital and community settings. Surveys were distributed through professional organisation e-mail lists and social media channels. Descriptive data were generated from categorical responses and inductive thematic analysis was applied to free-text responses. Results: Data were analysed from 169 respondents (110 hospital, 59 community), representing 99 healthcare organisations. 91 (83%) hospital respondents and 24 (41%) community respondents reported that nutrition screening was performed on all patients with sarcopenia or frailty. The Malnutrition Universal Screening Tool was most commonly used to trigger referral to dietetics teams, but there was considerable variation in management before referral, referral thresholds and referral pathways. Themes derived from free-text responses included the need for training, issues of responsibility and ownership, inadequate resources (time, staff and equipment) and ineffective or inefficient processes for referral and management. Conclusions: Current UK nutritional care for older people with sarcopenia and frailty is heterogeneous. There are opportunities for better tools, processes, training and resources to improve current practice and pathways.

Improving care for patients with multiple long-term conditions admitted to hospital: challenges and potential solutions.

Increasing numbers of people live with multiple long-term conditions. These people are more likely to be admitted to hospital, experience adverse outcomes and receive poorer quality care than those with a single condition. Hospitals remain organised around a model of single-organ, disease-specific care which is not equipped to meet the needs of people living with multiple long-term conditions. This article considers these challenges and explores potential solutions. These include different service models to provide holistic, multidisciplinary inpatient and outpatient care across specialty boundaries, training a workforce to deliver high-quality hospital care for people living with multiple long-term conditions, and developing technological, financial and cultural enablers of change. Considerably more research is required to fully appreciate the shared risk factors, underlying mechanisms, patterns and consequences of multiple long-term conditions. This is essential to design and deliver better structures and processes of hospital care for people living with multiple long-term conditions.

The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS).

IMPORTANCE: Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. OBJECTIVE: The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. DESIGN: The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. RESULTS: 107 participants (mean age: 54 ± 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. CONCLUSION AND RELEVANCE: The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.

Rising to the challenge of defining and operationalising multimorbidity in a UK hospital setting: the ADMISSION research collaborative.

PURPOSE: Greater transparency and consistency when defining multimorbidity in different settings is needed. We aimed to: (1) adapt published principles that can guide the selection of long-term conditions for inclusion in research studies of multimorbidity in hospitals; (2) apply these principles and identify a list of long-term conditions; (3) operationalise this list by mapping it to International Classification of Diseases 10th revision (ICD-10) codes. METHODS: Review by independent assessors and ratification by an interdisciplinary programme management group. RESULTS: Agreement was reached that when defining multimorbidity in hospitals for research purposes all conditions must meet the following four criteria: (1) medical diagnosis; (2) typically present for ≥ 12 months; (3) at least one of currently active; permanent in effect; requiring current treatment, care or therapy; requiring surveillance; remitting-relapsing and requiring ongoing treatment or care, and; (4) lead to at least one of: significantly increased risk of death; significantly reduced quality of life; frailty or physical disability; significantly worsened mental health; significantly increased treatment burden (indicated by an increased risk of hospital admission or increased length of hospital stay). Application of these principles to two existing lists of conditions led to the selection of 60 conditions that can be used when defining multimorbidity for research focused on hospitalised patients. ICD-10 codes were identified for each of these conditions to ensure consistency in their operationalisation. CONCLUSIONS: This work contributes to achieving the goal of greater transparency and consistency in the approach to the study of multimorbidity, with a specific focus on the UK hospital setting.

A silver bullet for ageing medicine?: clinical relevance of T-cell checkpoint receptors in normal human ageing.

Immunosenescence describes dysregulation of the immune system with ageing manifested in both the innate and adaptive immunity, including changes in T-cell checkpoint signaling. Through complex and nuanced process, T-cells lose excitatory signaling pathways and upregulate their inhibitory signaling, leading to ineffective immune responses that contribute to the formation of the ageing phenotype. Here we expand on the expression, function, and clinical potential of targeting the T-cell checkpoint signaling in age and highlight interventions offering the most benefits to older adults' health. Notably, modifications in vaccination such as with mTOR inhibitors show immediate clinical relevance and good tolerability. Other proposed treatments, including therapies with monoclonal antibodies fail to show clinical efficacy or tolerability needed for implementation at present. Although T-cell co-signaling fits a valuable niche for translational scientists to manage immunosenescence, future study would benefit from the inclusion of older adults with multiple long-term conditions and polypharmacy, ensuring better applicability to actual patients seen in clinical settings.

How far back do we need to look to capture diagnoses in electronic health records? A retrospective observational study of hospital electronic health record data.

OBJECTIVES: Analysis of routinely collected electronic health data is a key tool for long-term condition research and practice for hospitalised patients. This requires accurate and complete ascertainment of a broad range of diagnoses, something not always recorded on an admission document at a single point in time. This study aimed to ascertain how far back in time electronic hospital records need to be interrogated to capture long-term condition diagnoses. DESIGN: Retrospective observational study of routinely collected hospital electronic health record data. SETTING: Queen Elizabeth Hospital Birmingham (UK)-linked data held by the PIONEER acute care data hub. PARTICIPANTS: Patients whose first recorded admission for chronic obstructive pulmonary disease (COPD) exacerbation (n=560) or acute stroke (n=2142) was between January and December 2018 and who had a minimum of 10 years of data prior to the index date. OUTCOME MEASURES: We identified the most common International Classification of Diseases version 10-coded diagnoses received by patients with COPD and acute stroke separately. For each diagnosis, we derived the number of patients with the diagnosis recorded at least once over the full 10-year lookback period, and then compared this with shorter lookback periods from 1 year to 9 years prior to the index admission. RESULTS: Seven of the top 10 most common diagnoses in the COPD dataset reached >90% completeness by 6 years of lookback. Atrial fibrillation and diabetes were >90% coded with 2-3 years of lookback, but hypertension and asthma completeness continued to rise all the way out to 10 years of lookback. For stroke, 4 of the top 10 reached 90% completeness by 5 years of lookback; angina pectoris was >90% coded at 7 years and previous transient ischaemic attack completeness continued to rise out to 10 years of lookback. CONCLUSION: A 7-year lookback captures most, but not all, common diagnoses. Lookback duration should be tailored to the conditions being studied.

Myoprotective whole foods, muscle health and sarcopenia in older adults.

PURPOSE OF REVIEW: Sarcopenia increases in prevalence at older ages and may be exacerbated by poor diet. Whole foods rich in specific nutrients may be myoprotective and mitigate the risk of sarcopenia. Here we review recent evidence published from observational and intervention studies regarding myoprotective foods and explore their benefit for the prevention and/or treatment of sarcopenia in older adults. RECENT FINDINGS: We found limited new evidence for the role of whole foods in sarcopenia and sarcopenia components (muscle mass, strength, physical performance). There was some evidence for higher consumption of protein-rich foods (milk and dairy) being beneficial for muscle strength in observational and intervention studies. Higher consumption of antioxidant-rich foods (fruit and vegetables) was associated with better physical performance and lower odds of sarcopenia in observational studies. Evidence for other protein- and antioxidant-rich foods were inconsistent or lacking. There remains a clear need for intervention studies designed to identify the role of whole foods for the treatment of sarcopenia. SUMMARY: Although evidence for myoprotective roles of dairy, fruit and vegetables is emerging from observational studies, higher level evidence from intervention studies is needed for these foods to be recommended in diets of older adults to prevent and/or treat sarcopenia.

Experiences of hospital care for people with multiple long-term conditions: a scoping review of qualitative research.

BACKGROUND: Multiple long-term conditions-the co-existence of two or more chronic health conditions in an individual-present an increasing challenge to populations and healthcare systems worldwide. This challenge is keenly felt in hospital settings where care is oriented around specialist provision for single conditions. The aim of this scoping review was to identify and summarise published qualitative research on the experiences of hospital care for people living with multiple long-term conditions, their informal caregivers and healthcare professionals. METHODS: We undertook a scoping review, following established guidelines, of primary qualitative research on experiences of hospital care for people living with multiple long-term conditions published in peer-reviewed journals between Jan 2010 and June 2022. We conducted systematic electronic searches of MEDLINE, CINAHL, PsycInfo, Proquest Social Science Premium, Web of Science, Scopus and Embase, supplemented by citation tracking. Studies were selected for inclusion by two reviewers using an independent screening process. Data extraction included study populations, study design, findings and author conclusions. We took a narrative approach to reporting the findings. RESULTS: Of 8002 titles and abstracts screened, 54 papers reporting findings from 41 studies conducted in 14 countries were identified as eligible for inclusion. The perspectives of people living with multiple long-term conditions (21 studies), informal caregivers (n = 13) and healthcare professionals (n = 27) were represented, with 15 studies reporting experiences of more than one group. Findings included poor service integration and lack of person-centred care, limited confidence of healthcare professionals to treat conditions outside of their specialty, and time pressures leading to hurried care transitions. Few studies explored inequities in experiences of hospital care. CONCLUSIONS: Qualitative research evidence on the experiences of hospital care for multiple long-term conditions illuminates a tension between the desire to provide and receive person-centred care and time pressures inherent within a target-driven system focussed on increasing specialisation, reduced inpatient provision and accelerated journeys through the care system. A move towards more integrated models of care may enable the needs of people living with multiple long-term conditions to be better met. Future research should address how social circumstances shape experiences of care.

Determining the feasibility of characterising cellular senescence in human skeletal muscle and exploring associations with muscle morphology and physical function at different ages: findings from the MASS_Lifecourse Study.

Cellular senescence may be associated with morphological changes in skeletal muscle and changes in physical function with age although there have been few human studies. We aimed to determine the feasibility of characterising cellular senescence in skeletal muscle and explored sex-specific associations between markers of cellular senescence, muscle morphology, and physical function in participants from the MASS_Lifecourse Study. Senescence markers (p16, TAF (Telomere-Associated DNA Damage Foci), HMGB1 (High Mobility Group Box 1), and Lamin B1) and morphological characteristics (fibre size, number, fibrosis, and centrally nucleated fibres) were assessed in muscle biopsies from 40 men and women (age range 47-84) using spatially-resolved methods (immunohistochemistry, immunofluorescence, and RNA and fluorescence in situ hybridisation). The associations between senescence, morphology, and physical function (muscle strength, mass, and physical performance) at different ages were explored. We found that most senescence markers and morphological characteristics were weakly associated with age in men but more strongly, although non-significantly, associated with age in women. Associations between senescence markers, morphology, and physical function were also stronger in women for HMGB1 and grip strength (r = 0.52); TAF, BMI, and muscle mass (r > 0.4); Lamin B1 and fibrosis (r = - 0.5); fibre size and muscle mass (r ≥ 0.4); and gait speed (r = - 0.5). However, these associations were non-significant. In conclusion, we have demonstrated that it is feasible to characterise cellular senescence in human skeletal muscle and to explore associations with morphology and physical function in women and men of different ages. The findings require replication in larger studies.

Why are older adults living with the complexity of multiple long-term conditions, frailty and a recent deterioration in health under-served by research? A narrative synthesis review of the literature.

Older adults living with the complexity of multiple long-term conditions (MLTC), frailty and a recent deterioration in health are under-served by research. As a result, current treatment guidelines are often based on data from studies of younger and less frail participants, and often single disease focused. The aims of this review were (i) to identify why older adults living with the complexity of MLTC, frailty and a recent deterioration in health are under-served by research and (ii) to identify strategies for increasing their recruitment and retention. Although a range of factors have been suggested to affect the participation of older adults with MLTC and frailty in research, this review shows that much less is known about the inclusion of older adults living with the complexity of MLTC, frailty and a recent deterioration in health. Researchers should focus on strategies that minimise participation burden for these patients, maintaining an adaptive and flexible approach, to increase their recruitment and retention. Future research should include qualitative interviews to provide further insights into how best to design and conduct research to suit the needs of this population group.

Spotlight on the academic multidisciplinary team: proposals from the 3rd NIHR Newcastle BRC Academic Geriatric Medicine Workshop.

High-quality care for older people is best delivered by multidisciplinary teams involving a range of professions. Similarly, if research evidence is to effectively inform practice, it needs to be designed and executed by teams that are both multidisciplinary and multiprofessional. Here, we summarise the discussions from a 1-day workshop convened by the National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre in Spring 2021, which focussed on multidisciplinary academic teams. Barriers to success include small numbers of clinical academic researchers across all professions focussing on older people, and lack of career pathways, role models and support for non-medical clinical researchers. The workshop identified strengths in the tradition of multidisciplinary working in the care of older people, research questions that lend themselves naturally to multidisciplinary working, increasing interest from funders in multidisciplinary research, and untapped opportunities for greater commercial engagement. Initiatives to improve engagement of students and trainees, mentorship, career pathways, networking across research centres and possibly developing a national School of Older People's Care Research are all ways that we can ensure the growth of multidisciplinary research to best serve older people's health and social care in the future.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

BACKGROUND: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.g., the activin/myostatin signalling pathway) are hypothesised to contribute to the development of sarcopenia. METHODS: We compared regional body composition measured by DXA with genotypes for two polymorphisms (rs10783486, minor allele frequency (MAF) = 0.26 and rs2854464, MAF = 0.26) in the activin 1B receptor (ACVR1B) determined by PCR in a cross-sectional analysis of DNA from 110 older individuals with sarcopenia from the LACE trial. RESULTS: Neither muscle mass nor strength showed any significant associations with either genotype in this cohort. Initial analysis of rs10783486 showed that males with the AA/AG genotype were taller than GG males (174±7cm vs 170±5cm, p = 0.023) and had higher arm fat mass, (median higher by 15%, p = 0.008), and leg fat mass (median higher by 14%, p = 0.042). After correcting for height, arm fat mass remained significantly higher (median higher by 4% padj = 0.024). No associations (adjusted or unadjusted) were seen in females. Similar analysis of the rs2854464 allele showed a similar pattern with the presence of the minor allele (GG/AG) being associated with greater height (GG/AG = 174±7 cm vs AA = 170 ±5cm, p = 0.017) and greater arm fat mass (median higher by 16%, p = 0.023). Again, the difference in arm fat remained after correction for height. No similar associations were seen in females analysed alone. CONCLUSION: These data suggest that polymorphic variation in the ACVR1B locus could be associated with body composition in older males. The activin/myostatin pathway might offer a novel potential target to prevent fat accumulation in older individuals.

Hallmarks of ageing in human skeletal muscle and implications for understanding the pathophysiology of sarcopenia in women and men.

Ageing is a complex biological process associated with increased morbidity and mortality. Nine classic, interdependent hallmarks of ageing have been proposed involving genetic and biochemical pathways that collectively influence ageing trajectories and susceptibility to pathology in humans. Ageing skeletal muscle undergoes profound morphological and physiological changes associated with loss of strength, mass, and function, a condition known as sarcopenia. The aetiology of sarcopenia is complex and whilst research in this area is growing rapidly, there is a relative paucity of human studies, particularly in older women. Here, we evaluate how the nine classic hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication contribute to skeletal muscle ageing and the pathophysiology of sarcopenia. We also highlight five novel hallmarks of particular significance to skeletal muscle ageing: inflammation, neural dysfunction, extracellular matrix dysfunction, reduced vascular perfusion, and ionic dyshomeostasis, and discuss how the classic and novel hallmarks are interconnected. Their clinical relevance and translational potential are also considered.

Attitudes and barriers to resistance exercise training for older adults living with multiple long-term conditions, frailty, and a recent deterioration in health: qualitative findings from the Lifestyle in Later Life - Older People's Medicine (LiLL-OPM) study.

BACKGROUND: Many older adults live with the combination of multiple long-term conditions (MLTC) and frailty and are at increased risk of a deterioration in health requiring interaction with healthcare services. Low skeletal muscle strength is observed in individuals living with MLTC and is central to physical frailty. Resistance exercise (RE) is the best available treatment for improving muscle strength, but little is known about the attitudes and barriers to RE in this group of older adults. This study therefore aimed to explore the knowledge of and attitudes towards RE, as well as the barriers and enabling factors, in older adults living with MLTC, frailty and a recent deterioration in health. METHODS: Fourteen participants aged 69-92 years (10 women) from the Lifestyle in Later Life - Older People's Medicine (LiLL-OPM) study were recruited from an Older People's Medicine Day Unit in Newcastle, UK. Participants were invited to take part in a semi-structured interview exploring their knowledge and attitudes as well as barriers and enabling factors to RE. Data were analysed using thematic analysis. RESULTS: The analysis generated three themes (1) a lack of awareness and understanding of RE, (2) a self-perceived inability to perform RE; physical and psychological barriers and (3) willingness to perform RE under expert guidance. There was a general lack of awareness and understanding of RE, with most participants having never heard of the term and being unaware of its potential benefits. When RE was described, participants stated that they would be willing to try RE, but it was apparent that an individualised approach underpinned by expert guidance would be required to support engagement. CONCLUSIONS: Older adults living with MLTC, frailty and a recent deterioration in health lack awareness and understanding of RE. Despite a range of barriers, this group appear willing to engage in RE if they are appropriately supported. There is a need to co-design and deliver effective strategies, including education, to raise awareness and understanding of RE, as well as promote engagement in RE, in this group of older adults.

Comparing associations of handgrip strength and chair stand performance with all-cause mortality-implications for defining probable sarcopenia: the Tromsø Study 2015-2020.

BACKGROUND: Widely adopted criteria suggest using either low handgrip strength or poor chair stand performance to identify probable sarcopenia. However, there are limited direct comparisons of these measures in relation to important clinical endpoints. We aimed to compare associations between these two measures of probable sarcopenia and all-cause mortality. METHODS: Analyses included 7838 community-dwelling participants (55% women) aged 40-84 years from the seventh survey of the Tromsø Study (2015-2016), with handgrip strength assessed using a Jamar + Digital Dynamometer and a five-repetition chair stand test (5-CST) also undertaken. We generated sex-specific T-scores and categorised these as "not low", "low", and "very low" handgrip strength or 5-CST performance. Cox Proportional Hazard regression models were used to investigate associations between these two categorised performance scores and time to death (up to November 2020 ascertained from the Norwegian Cause of Death registry), adjusted for potential confounders including lifestyle factors and specific diseases. RESULTS: A total of 233 deaths occurred (median follow-up 4.7 years) with 1- and 5-year mortality rates at 3.1 (95% confidence interval [CI] 2.1, 4.6) and 6.3 (95% CI 5.5, 7.2) per 1000 person-years, respectively. There was poor agreement between the handgrip strength and 5-CST categories for men (Cohen's kappa [κ] = 0.19) or women (κ = 0.20). Fully adjusted models including handgrip strength and 5-CST performance mutually adjusted for each other, showed higher mortality rates among participants with low (hazard ratio [HR] 1.22, 95% CI 0.87, 1.71) and very low (HR 1.68, 95% CI 1.02, 2.75) handgrip strength compared with the not low category. Similar associations, although stronger, were seen for low (HR 1.88, 95% CI 1.38, 2.56) and very low (HR 2.64, 95% CI 1.73, 4.03) 5-CST performance compared with the not low category. CONCLUSIONS: We found poor agreement between T-score categories for handgrip strength and 5-CST performance and independent associations with mortality. Our findings suggest that these tests identify different people at risk when case-finding probable sarcopenia. As discussions on an international consensus for sarcopenia definitions proceed, testing both handgrip strength and chair stand performance should be recommended rather than viewing these as interchangeable assessments.

Mapping inpatient care pathways for patients with COPD: an observational study using routinely collected electronic hospital record data.

Introduction: Respiratory specialist ward care is associated with better outcomes for patients with COPD exacerbations. We assessed patient pathways and associated factors for people admitted to hospital with COPD exacerbations. Methods: We analysed routinely collected electronic health data for patients admitted with COPD exacerbation in 2018 to Queen Elizabeth Hospital, Birmingham, UK. We extracted data on demographics, deprivation index, Elixhauser comorbidities, ward moves, length of stay, and in-hospital and 1-year mortality. We compared care pathways with recommended care pathways (transition from initial assessment area to respiratory wards or discharge). We used Markov state transition models to derive probabilities of following recommended pathways for patient subgroups. Results: Of 42 555 patients with unplanned admissions during 2018, 571 patients were admitted at least once with an exacerbation of COPD. The mean±sd age was 51±11 years; 313 (55%) were women, 337 (59%) lived in the most deprived neighbourhoods and 45 (9%) were from non-white ethnic backgrounds. 428 (75.0%) had ≥4 comorbidities. Age >70 years was associated with higher in-hospital and 1-year mortality, more places of care (wards) and longer length of stay; having ≥4 comorbidities was associated with higher mortality and longer length of stay. Older age was associated with a significantly lower probability of following a recommended pathway (>70 years: 0.514, 95% CI 0.458-0.571; ≤70 years: 0.636, 95% CI 0.572-0.696; p=0.004). Conclusions: Only older age was associated with a lower chance of following recommended hospital pathways of care. Such analyses could help refine appropriate care pathways for patients with COPD exacerbations.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

BACKGROUND: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result. Polymorphic variation in the ACE promoter (I/D alleles) has been associated with differences in ACE activity and muscle physiology in a range of clinical conditions. This aim of this analysis was to determine whether I/D polymorphic variation is associated with muscle mass, strength, in sarcopenia or contributed to the lack of response to treatment in the LACE study. METHODS: Sarcopenic individuals were recruited into a 2x2 factorial multicentre double-blind study of the effects of perindopril and/or leucine versus placebo on physical performance and muscle mass. DNA extracted from blood samples (n = 130 72 women and 58 men) was genotyped by PCR for the ACE I/D polymorphism. Genotypes were then compared with body composition measured by DXA, hand grip and quadriceps strength before and after 12 months' treatment with leucine and/or perindopril in a cross-sectional analysis of the influence of genotype on these variables. RESULTS: Allele frequencies for the normal UK population were extracted from 13 previous studies (I = 0.473, D = 0.527). In the LACE cohort the D allele was over-represented (I = 0.412, D = 0.588, p = 0.046). This over-representation was present in men (I = 0.353, D = 0.647, p = 0.010) but not women (I = 0.458, D = 0.532, p = 0.708). In men but not women, individuals with the I allele had greater leg strength (II/ID = 18.00 kg (14.50, 21.60) vs DD = 13.20 kg (10.50, 15.90), p = 0.028). Over the 12 months individuals with the DD genotype increased in quadriceps strength but those with the II or ID genotype did not. Perindopril did not increase muscle strength or mass in any polymorphism group relative to placebo. CONCLUSION: Our results suggest that although ACE genotype was not associated with response to ACE inhibitor therapy in the LACE trial population, sarcopenic men with the ACE DD genotype may be weaker than those with the ACE I/D or II genotype.