Acceptability, feasibility, and effectiveness of WE-SURF™: a virtual supervised group-based fall prevention exercise program among older adults.

Conducted physically, supervised group-based falls prevention exercise programs have demonstrated effectiveness in reducing the risk of falls among older adults. In this study, we aimed to assess the acceptability, feasibility, and effectiveness of a virtual supervised group-based falls prevention exercise program (WE-SURF™) for community-dwelling older adults at risk of falls. METHOD: A preliminary study utilizing virtual discussions was conducted to assess the acceptability of the program among six older adults. Effectiveness was evaluated in a randomized controlled feasibility study design, comprising 52 participants (mean age: 66.54; SD: 5.16), divided into experimental (n = 26) and control (n = 26) groups. The experimental group engaged in a 6-month WE-SURF™ program, while the control group received standard care along with a fall's prevention education session. Feasibility of the intervention was measured using attendance records, engagement rates from recorded videos, dropouts, attrition reasons, and adverse events. RESULTS: Preliminary findings suggested that WE-SURF™ was acceptable, with further refinements. The study revealed significant intervention effects on timed up and go (TUG) (η2p:0.08; p < 0.05), single leg stance (SLS) (η2p:0.10; p < 0.05), and lower limb muscle strength (η2p:0.09; p < 0.05) tests. No adverse events occurred during the program sessions, and both attendance and engagement rates were high (> 80% and 8/10, respectively) with minimal dropouts (4%). The WE-SURF™ program demonstrated effectiveness in reducing the risk of falls while enhancing muscle strength and balance. CONCLUSION: In conclusion, WE-SURF™ was demonstrated to be an acceptable, feasible, and effective virtual supervised group-based exercise program for fall prevention in community-dwelling older adults at risk of falls. With positive outcomes and favourable participant engagement, WE-SURF™ holds the potential for wider implementation. Further research and scaling-up efforts are recommended to explore its broader applicability. (Registration number: ACTRN 12621001620819).

Case management for integrated care of older people with frailty in community settings.

BACKGROUND: Ageing populations globally have contributed to increasing numbers of people living with frailty, which has significant implications for use of health and care services and costs. The British Geriatrics Society defines frailty as "a distinctive health state related to the ageing process in which multiple body systems gradually lose their inbuilt reserves". This leads to an increased susceptibility to adverse outcomes, such as reduced physical function, poorer quality of life, hospital admissions, and mortality. Case management interventions delivered in community settings are led by a health or social care professional, supported by a multidisciplinary team, and focus on the planning, provision, and co-ordination of care to meet the needs of the individual. Case management is one model of integrated care that has gained traction with policymakers to improve outcomes for populations at high risk of decline in health and well-being. These populations include older people living with frailty, who commonly have complex healthcare and social care needs but can experience poorly co-ordinated care due to fragmented care systems. OBJECTIVES: To assess the effects of case management for integrated care of older people living with frailty compared with usual care. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Health Systems Evidence, and PDQ Evidence and databases from inception to 23 September 2022. We also searched clinical registries and relevant grey literature databases, checked references of included trials and relevant systematic reviews, conducted citation searching of included trials, and contacted topic experts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared case management with standard care in community-dwelling people aged 65 years and older living with frailty. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures recommended by Cochrane and the Effective Practice and Organisation of Care Group. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 20 trials (11,860 participants), all of which took place in high-income countries. Case management interventions in the included trials varied in terms of organisation, delivery, setting, and care providers involved. Most trials included a variety of healthcare and social care professionals, including nurse practitioners, allied healthcare professionals, social workers, geriatricians, physicians, psychologists, and clinical pharmacists. In nine trials, the case management intervention was delivered by nurses only. Follow-up ranged from three to 36 months. We judged most trials at unclear risk of selection and performance bias; this consideration, together with indirectness, justified downgrading the certainty of the evidence to low or moderate. Case management compared to standard care may result in little or no difference in the following outcomes. • Mortality at 12 months' follow-up (7.0% in the intervention group versus 7.5% in the control group; risk ratio (RR) 0.98, 95% confidence interval (CI) 0.84 to 1.15; I2 = 11%; 14 trials, 9924 participants; low-certainty evidence) • Change in place of residence to a nursing home at 12 months' follow-up (9.9% in the intervention group versus 13.4% in the control group; RR 0.73, 95% CI 0.53 to 1.01; I2 = 0%; 4 trials, 1108 participants; low-certainty evidence) • Quality of life at three to 24 months' follow-up (results not pooled; mean differences (MDs) ranged from -6.32 points (95% CI -11.04 to -1.59) to 6.1 points (95% CI -3.92 to 16.12) when reported; 11 trials, 9284 participants; low-certainty evidence) • Serious adverse effects at 12 to 24 months' follow-up (results not pooled; 2 trials, 592 participants; low-certainty evidence) • Change in physical function at three to 24 months' follow-up (results not pooled; MDs ranged from -0.12 points (95% CI -0.93 to 0.68) to 3.4 points (95% CI -2.35 to 9.15) when reported; 16 trials, 10,652 participants; low-certainty evidence) Case management compared to standard care probably results in little or no difference in the following outcomes. • Healthcare utilisation in terms of hospital admission at 12 months' follow-up (32.7% in the intervention group versus 36.0% in the control group; RR 0.91, 95% CI 0.79 to 1.05; I2 = 43%; 6 trials, 2424 participants; moderate-certainty evidence) • Change in costs at six to 36 months' follow-up (results not pooled; 14 trials, 8486 participants; moderate-certainty evidence), which usually included healthcare service costs, intervention costs, and other costs such as informal care. AUTHORS' CONCLUSIONS: We found uncertain evidence regarding whether case management for integrated care of older people with frailty in community settings, compared to standard care, improved patient and service outcomes or reduced costs. There is a need for further research to develop a clear taxonomy of intervention components, to determine the active ingredients that work in case management interventions, and identify how such interventions benefit some people and not others.

How do healthcare providers use national audit data for improvement?

BACKGROUND: Substantial resources are invested by Health Departments worldwide in introducing National Clinical Audits (NCAs). Yet, there is variable evidence on the NCAs' effectiveness and little is known on factors underlying the successful use of NCAs to improve local practice. This study will focus on a single NCA (the National Audit of Inpatient Falls -NAIF 2017) to explore: (i) participants' perspectives on the NCA reports, local feedback characteristics and actions undertaken following the feedback underpinning the effective use of the NCA feedback to improve local practice; (ii) reported changes in local practice following the NCA feedback in England and Wales. METHODS: Front-line staff perspectives were gathered through interviews. An inductive qualitative approach was used. Eighteen participants were purposefully sampled from 7 of the 85 participating hospitals in England and Wales. Analysis was guided by constant comparative techniques. RESULTS: Regarding the NAIF annual report, interviewees valued performance benchmarking with other hospitals, the use of visual representations and the inclusion of case studies and recommendations. Participants stated that feedback should target front-line healthcare professionals, be straightforward and focused, and be delivered through an encouraging and honest discussion. Interviewees highlighted the value of using other relevant data sources alongside NAIF feedback and the importance of continuous data monitoring. Participants reported that engagement of front-line staff in the NAIF and following improvement activities was critical. Leadership, ownership, management support and communication at different organisational levels were perceived as enablers, while staffing level and turnover, and poor quality improvement (QI) skills, were perceived as barriers to improvement. Reported changes in practice included increased awareness and attention to patient safety issues and greater involvement of patients and staff in falls prevention activities. CONCLUSIONS: There is scope to improve the use of NCAs by front-line staff. NCAs should not be seen as isolated interventions but should be fully embedded and integrated into the QI strategic and operational plans of NHS trusts. The use of NCAs could be optimised, but knowledge of them is poor and distributed unevenly across different disciplines. More research is needed to provide guidance on key elements to consider throughout the whole improvement process at different organisational levels.

Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study.

BACKGROUND: The number of individuals recovering from severe COVID-19 is increasing rapidly. However, little is known about physical behaviours that make up the 24-h cycle within these individuals. This study aimed to describe physical behaviours following hospital admission for COVID-19 at eight months post-discharge including associations with acute illness severity and ongoing symptoms. METHODS: One thousand seventy-seven patients with COVID-19 discharged from hospital between March and November 2020 were recruited. Using a 14-day wear protocol, wrist-worn accelerometers were sent to participants after a five-month follow-up assessment. Acute illness severity was assessed by the WHO clinical progression scale, and the severity of ongoing symptoms was assessed using four previously reported data-driven clinical recovery clusters. Two existing control populations of office workers and individuals with type 2 diabetes were comparators. RESULTS: Valid accelerometer data from 253 women and 462 men were included. Women engaged in a mean ± SD of 14.9 ± 14.7 min/day of moderate-to-vigorous physical activity (MVPA), with 12.1 ± 1.7 h/day spent inactive and 7.2 ± 1.1 h/day asleep. The values for men were 21.0 ± 22.3 and 12.6 ± 1.7 h /day and 6.9 ± 1.1 h/day, respectively. Over 60% of women and men did not have any days containing a 30-min bout of MVPA. Variability in sleep timing was approximately 2 h in men and women. More severe acute illness was associated with lower total activity and MVPA in recovery. The very severe recovery cluster was associated with fewer days/week containing continuous bouts of MVPA, longer total sleep time, and higher variability in sleep timing. Patients post-hospitalisation with COVID-19 had lower levels of physical activity, greater sleep variability, and lower sleep efficiency than a similarly aged cohort of office workers or those with type 2 diabetes. CONCLUSIONS: Those recovering from a hospital admission for COVID-19 have low levels of physical activity and disrupted patterns of sleep several months after discharge. Our comparative cohorts indicate that the long-term impact of COVID-19 on physical behaviours is significant.

A coordinated national UK liver transplant program response, prioritizing waitlist recipients with the highest need, provided excellent outcomes during the first wave of the COVID-19 pandemic.

INTRODUCTION: Healthcare provision has been severely affected by COVID-19, with specific challenges in organ transplantation. Here, we describe the coordinated response to, and outcomes during the first wave, across all UK liver transplant (LT) centers. METHODS: Several policy changes affecting the liver transplant processes were agreed upon. These included donor age restrictions and changes to offering. A "high-urgency" (HU) category was established, prioritizing only those with UKELD > 60, HCC reaching transplant criteria, and others likely to die within 90 days. Outcomes were compared with the same period in 2018 and 2019. RESULTS: The retrieval rate for deceased donor livers (71% vs. 54%; P < .0001) and conversion from offer to completed transplant (63% vs. 48%; P < .0001) was significantly higher. Pediatric LT activity was maintained; there was a significant reduction in adult (42%) and total (36%) LT. Almost all adult LT were super-urgent (n = 15) or HU (n = 133). We successfully prioritized those with highest illness severity with no reduction in 90-day patient (P = .89) or graft survival (P = .98). There was a small (5% compared with 3%; P = .0015) increase in deaths or removals from the waitlist, mainly amongst HU cohort. CONCLUSIONS: We successfully prioritized LT recipients in highest need, maintaining excellent outcomes, and waitlist mortality was only marginally increased.

Strong, steady and straight: UK consensus statement on physical activity and exercise for osteoporosis.

Exercise and physical activity can improve bone strength and the risk of falls, which may offer benefits in the prevention and management of osteoporosis. However, uncertainty about the types of exercise that are safe and effective instigates lack of confidence in people with osteoporosis and health professionals. Existing guidelines leave some questions unresolved. This consensus statement aimed to determine the physical activity and exercise needed to optimise bone strength, reduce fall and fracture risk, improve posture and manage vertebral fracture symptoms, while minimising potential risks in people with osteoporosis. The scope of this statement was developed following stakeholder consultation. Meta-analyses were reviewed and where evidence was lacking, individual studies or expert opinion were used to develop recommendations. A multidisciplinary expert group reviewed evidence to make recommendations, by consensus when evidence was not available. Key recommendations are that people with osteoporosis should undertake (1) resistance and impact exercise to maximise bone strength; (2) activities to improve strength and balance to reduce falls; (3) spinal extension exercise to improve posture and potentially reduce risk of falls and vertebral fractures. For safety, we recommend avoiding postures involving a high degree of spinal flexion during exercise or daily life. People with vertebral fracture or multiple low trauma fractures should usually exercise only up to an impact equivalent to brisk walking. Those at risk of falls should start with targeted strength and balance training. Vertebral fracture symptoms may benefit from exercise to reduce pain, improve mobility and quality of life, ideally with specialist advice to encourage return to normal activities. Everyone with osteoporosis may benefit from guidance on adapting postures and movements. There is little evidence that physical activity is associated with significant harm, and the benefits, in general, outweigh the risks.

Bereavement in the Time of COVID-19: Learning from Experiences of those Bereaved as a Result of Deaths in an Acute Hospital Setting in 2020.

The COVID-19 pandemic has resulted in many people experiencing bereavement in challenging circumstances. In April 2020 at a large London Trust, a "Bereavement Welfare Hub" was established to offer support and advice by telephone to relatives and carers of all adults who died as inpatients. Data from BWH call records regarding 809 adults who died at the Trust in March, April and May 2020 were collated. A random selection of 149 call records were examined using thematic analysis. Six themes which influenced the bereavement experiences and grief status of call recipients were identified. These included family and community support, care up to the point of death, communication, care after death and death rituals and customs. Several factors positively and negatively influenced the experiences of people bereaved during the first wave of COVID-19. From these findings, recommendations have been made which have the potential to improve the bereavement experience, particularly during the pandemic era.

Feasibility and efficacy of a multi-factorial intervention to prevent falls in older adults with cognitive impairment living in residential care (ProF-Cog). A feasibility and pilot cluster randomised controlled trial.

BACKGROUND: Falls are common in people with dementia living in residential care. The ProF-Cog intervention was developed to address fall risk factors specific to this population. The aim of this study was to evaluate the safety, acceptability, and feasibility of the intervention and provide an estimate of its efficacy. METHODS: This was a cluster randomised controlled pilot study undertaken in care homes in London, UK. All permanent residents living in participating homes who were not terminally ill were invited to participate. The intervention included an assessment of falls risk factors followed by a tailored intervention which could include dementia care mapping, comprehensive geriatric assessment, occupational therapy input and twice-weekly exercise for 6 months as required to target identified risk factors. The control group received usual care without a falls risk assessment. Standing balance was the primary outcome. This and other outcome measures were collected at baseline and after 6 months. Falls were recorded for this period using incident reports. Changes were analysed using multi-level modelling. Adherence to the interventions, adverse events and trial feasibility were recorded. RESULTS: Nine care homes enrolled in the study with a total 191 participants (51% of those eligible); five homes allocated to the intervention with 103 participants, and four homes to the usual care control group with 88 participants. The intervention was safe with only one reported fall whilst undertaking exercise. Adherence to agreed recommendations on activity and the environment was modest (21 and 45% respectively) and to exercise was poor (41%). Balance scores (score range 0-49) analysed on 100 participants decreased by a mean of 3.9 in the control and 5.1 in the intervention groups, a non-significant difference (p = 0.9). In other measures, both groups declined equally and there was no difference in falls rates (IRR = 1.59 95%, CI 0.67-3.76). CONCLUSION: The intervention was safe but not clinically effective. Poor adherence suggests it was not an acceptable or feasible intervention. TRIAL REGISTRATION: ISRCTN00695885 . Registered 26th March 2013.

Exercise to prevent falls in older adults: an updated systematic review and meta-analysis.

OBJECTIVE: Previous meta-analyses have found that exercise prevents falls in older people. This study aimed to test whether this effect is still present when new trials are added, and it explores whether characteristics of the trial design, sample or intervention are associated with greater fall prevention effects. DESIGN: Update of a systematic review with random effects meta-analysis and meta-regression. DATA SOURCES: Cochrane Library, CINAHL, MEDLINE, EMBASE, PubMed, PEDro and SafetyLit were searched from January 2010 to January 2016. STUDY ELIGIBILITY CRITERIA: We included randomised controlled trials that compared fall rates in older people randomised to receive exercise as a single intervention with fall rates in those randomised to a control group. RESULTS: 99 comparisons from 88 trials with 19 478 participants were available for meta-analysis. Overall, exercise reduced the rate of falls in community-dwelling older people by 21% (pooled rate ratio 0.79, 95% CI 0.73 to 0.85, p<0.001, I2 47%, 69 comparisons) with greater effects seen from exercise programmes that challenged balance and involved more than 3 hours/week of exercise. These variables explained 76% of the between-trial heterogeneity and in combination led to a 39% reduction in falls (incident rate ratio 0.61, 95% CI 0.53 to 0.72, p<0.001). Exercise also had a fall prevention effect in community-dwelling people with Parkinson's disease (pooled rate ratio 0.47, 95% CI 0.30 to 0.73, p=0.001, I2 65%, 6 comparisons) or cognitive impairment (pooled rate ratio 0.55, 95% CI 0.37 to 0.83, p=0.004, I2 21%, 3 comparisons). There was no evidence of a fall prevention effect of exercise in residential care settings or among stroke survivors or people recently discharged from hospital. SUMMARY/CONCLUSIONS: Exercise as a single intervention can prevent falls in community-dwelling older people. Exercise programmes that challenge balance and are of a higher dose have larger effects. The impact of exercise as a single intervention in clinical groups and aged care facility residents requires further investigation, but promising results are evident for people with Parkinson's disease and cognitive impairment.

Measurement of lying and standing blood pressure in hospital.

Measuring lying and standing blood pressure (BP) is an important clinical observation in older hospital inpatients. This is because a drop in BP on standing, known as orthostatic hypotension (OH) is common in older people and in acute illness and, therefore, in hospital patients. OH increases the risk of a fall in hospital. Simple measures such as changes in medication or rehydration can reduce this drop in BP and reduce the risk of falls. In a recent snapshot audit in England and Wales of 179 acute hospitals and 4,846 patients aged 65 years and over admitted with an acute illness, only 16% had a lying and standing BP recorded within 48 hours. A review of the literature showed that existing advice on how to measure and interpret lying and standing BP was often not appropriate for use on the ward with frail and unwell inpatients. An online survey of 275 clinicians' usual practice highlighted variation and the need for clarity and pragmatism. In the light of the survey findings, a clinical guide has been developed on when to measure lying and standing BP, how to measure it and what is considered a significant result.

True cost of care.

In The wake of the shocking abuse of frail and vulnerable care home residents featured in a recent BBC Panorama documentary, the call for solutions is understandable. But, sadly, there are no quick or cheap answers. More inspections, installation of surveillance cameras in residents' rooms and prosecution of abusers might assuage public anger for now, but they are as likely to end abuse as to find a cure for dementia.

How can we improve Comprehensive Geriatric Assessment for older people living with frailty in primary care and community settings? A qualitative study.

OBJECTIVE: With advancing age comes the increasing prevalence of frailty and increased risk of adverse outcomes (eg, hospitalisation). Evidence for comprehensive geriatric assessment (CGA), a multidimensional holistic model of care, is mixed in community settings. Uncertainties remain, such as the key components of CGA, who delivers it, and the use of technology. This study aimed to understand the perspectives, beliefs and experiences, of both older people and health professionals, to improve the current CGA and explore factors that may impact on CGA delivery in community settings. DESIGN: A qualitative interview study was conducted with older people and healthcare professionals (HCPs) identified using a maximum variation strategy. Data were analysed using an abductive analysis approach. The non-adoption, abandonment, scale-up, spread and sustainability framework and the theoretical framework of acceptability guided the categorisation of the codes and identified categories were mapped to the two frameworks. SETTING: England, UK. RESULTS: 27 people were interviewed, constituting 14 older people and 13 HCPs. We identified limitations in the current CGA: a lack of information sharing between different HCPs who deliver CGA; poor communication between older people and their HCPs and a lack of follow-up as part of CGA. When we discussed the potential for CGA to use technology, HCPs and older people varied in their readiness to engage with it. CONCLUSIONS: Viable solutions to address gaps in the current delivery of CGA include the provision of training and support to use digital technology and a designated comprehensive care coordinator. The next stage of this research will use these findings, existing evidence and stakeholder engagement, to develop and refine a model of community-based CGA that can be assessed for feasibility and acceptability.

Development and validation of a fall-related impulsive behaviour scale for residential care.

INTRODUCTION: impulsivity in older people with cognitive impairment has yet to be examined rigorously as a risk factor for falls. The objective of this study was to evaluate the psychometric properties of a new fall-related impulsive behaviour scale (FIBS) for a cognitively impaired population living in residential care. METHODS: one hundred and nine care home residents (84.5 ± 8.3 years) were assessed on the FIBS and a range of behavioural, physical and neuropsychological measures. Participants were then prospectively followed up for falls for 6 months. RESULTS: the internal reliability (Cronbach's α = 0.77) and test-retest reliability (intra-class correlation coefficient = 0.93) of the FIBS were both good. Construct validity was supported by significant correlations between the FIBS and the neuropsychiatric inventory (r = 0.43, P < 0.001), wandering (r = 0.33, P = 0.001) and global cognition (r = -0.2, P = 0.04). Compared with residents with FIBS scores <1, those with FIBS scores of ≥ 1 were nearly three times more likely to fall in the following 6 months, AOR = 2.92 (95% CI: 1.03-8.29). CONCLUSION: the FIBS is a simple, valid and reliable scale for assessing fall-related impulsivity in care home residents and can be recommended for use in this group for both research and clinical purposes.

Group-based exercise interventions for community-dwelling older people in Southeast Asia: A systematic review.

OBJECTIVES: Southeast Asia (SEA) is a rapidly ageing and a diversely populated region that requires strategies to maintain its populations' physical activity and sense of well-being. While the benefits of group exercise programs are known, the characteristics and types of exercises in terms of their effectiveness for physical function and fidelity of the programs have yet to be defined within this population. METHODS: Ovid, MEDLINE, Scopus, PEDro (Physiotherapy Evidence Database), EBSCOHOST, Cochrane library and Open Grey databases were searched to identify relevant studies. Methodological quality was assessed using the PEDro Scale and the Newcastle Ottawa Scale (NOS). Meta-analysis was undertaken when the same outcome measures were reported in a minimum of two studies with appropriate data. (PROSPERO: CRD42020177317). RESULTS: Eleven studies with 900 participants were included, out of which 395 participants were allocated to group exercise programs and 383 completed the program. Culturally adapted Thai dance programs and multicomponent exercise programs were the most-commonly reported group exercises. The Timed Up and Go test (TUG) and attendance rates were the most-frequently reported outcomes. Meta-analysis demonstrated significant improvement in physical function assessed using the Timed Up and Go test (Random effect model -1.27 s, 95% CI -1.65, -0.88, I2 = 74%). In two studies, adherence (81% and 94%) and dropout rates (4% and 19%) were reported. CONCLUSIONS: Group-based exercise programs in Southeast Asia consisting mostly of culturally adapted Thai dance programs and multicomponent exercise programs appear to have positive effects on physical function. However, better descriptions of fidelity, including adherence, are required in future studies.

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.

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.

Prevalence of swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19: the PHOSP-COVID analysis.

OBJECTIVE: Identify prevalence of self-reported swallow, communication, voice and cognitive compromise following hospitalisation for COVID-19. DESIGN: Multicentre prospective observational cohort study using questionnaire data at visit 1 (2-7 months post discharge) and visit 2 (10-14 months post discharge) from hospitalised patients in the UK. Lasso logistic regression analysis was undertaken to identify associations. SETTING: 64 UK acute hospital Trusts. PARTICIPANTS: Adults aged >18 years, discharged from an admissions unit or ward at a UK hospital with COVID-19. MAIN OUTCOME MEASURES: Self-reported swallow, communication, voice and cognitive compromise. RESULTS: Compromised swallowing post intensive care unit (post-ICU) admission was reported in 20% (188/955); 60% with swallow problems received invasive mechanical ventilation and were more likely to have undergone proning (p=0.039). Voice problems were reported in 34% (319/946) post-ICU admission who were more likely to have received invasive (p<0.001) or non-invasive ventilation (p=0.001) and to have been proned (p<0.001). Communication compromise was reported in 23% (527/2275) univariable analysis identified associations with younger age (p<0.001), female sex (p<0.001), social deprivation (p<0.001) and being a healthcare worker (p=0.010). Cognitive issues were reported by 70% (1598/2275), consistent at both visits, at visit 1 respondents were more likely to have higher baseline comorbidities and at visit 2 were associated with greater social deprivation (p<0.001). CONCLUSION: Swallow, communication, voice and cognitive problems were prevalent post hospitalisation for COVID-19, alongside whole system compromise including reduced mobility and overall health scores. Research and testing of rehabilitation interventions are required at pace to explore these issues.

A national pilot of donation after circulatory death (DCD) heart transplantation within the United Kingdom.

BACKGROUND: The United Kingdom (UK) was one of the first countries to pioneer heart transplantation from donation after circulatory death (DCD) donors. To facilitate equity of access to DCD hearts by all UK heart transplant centers and expand the retrieval zone nationwide, a Joint Innovation Fund (JIF) pilot was provided by NHS Blood and Transplant (NHSBT) and NHS England (NHSE). The activity and outcomes of this national DCD heart pilot program are reported. METHODS: This is a national multi-center, retrospective cohort study examining early outcomes of DCD heart transplants performed across 7 heart transplant centers, adult and pediatric, throughout the UK. Hearts were retrieved using the direct procurement and perfusion (DPP) technique by 3 specialist retrieval teams trained in ex-situ normothermic machine perfusion. Outcomes were compared against DCD heart transplants before the national pilot era and against contemporaneous donation after brain death (DBD) heart transplants, and analyzed using Kaplan-Meier analysis, chi-square test, and Wilcoxon's rank-sum. RESULTS: From September 7, 2020 to February 28, 2022, 215 potential DCD hearts were offered of which 98 (46%) were accepted and attended. There were 77 potential donors (36%) which proceeded to death within 2 hours, with 57 (27%) donor hearts successfully retrieved and perfused ex situ and 50 (23%) DCD hearts going on to be transplanted. During this same period, 179 DBD hearts were transplanted. Overall, there was no difference in the 30-day survival rate between DCD and DBD (94% vs 93%) or 90 day survival (90% vs 90%) respectively. There was a higher rate of ECMO use post-DCD heart transplants compared to DBD (40% vs 16%, p = 0.0006), and DCD hearts in the pre pilot era, (17%, p = 0.002). There was no difference in length of ICU stay (9 DCD vs 8 days DBD, p = 0.13) nor hospital stay (28 DCD vs 27 DBD days, p = 0.46). CONCLUSION: During this pilot study, 3 specialist retrieval teams were able to retrieve DCD hearts nationally for all 7 UK heart transplant centers. DCD donors increased overall heart transplantation in the UK by 28% with equivalent early posttransplant survival compared with DBD donors.

Prevalence of physical frailty, including risk factors, up to 1 year after hospitalisation for COVID-19 in the UK: a multicentre, longitudinal cohort study.

Background: The scale of COVID-19 and its well documented long-term sequelae support a need to understand long-term outcomes including frailty. Methods: This prospective cohort study recruited adults who had survived hospitalisation with clinically diagnosed COVID-19 across 35 sites in the UK (PHOSP-COVID). The burden of frailty was objectively measured using Fried's Frailty Phenotype (FFP). The primary outcome was the prevalence of each FFP group-robust (no FFP criteria), pre-frail (one or two FFP criteria) and frail (three or more FFP criteria)-at 5 months and 1 year after discharge from hospital. For inclusion in the primary analysis, participants required complete outcome data for three of the five FFP criteria. Longitudinal changes across frailty domains are reported at 5 months and 1 year post-hospitalisation, along with risk factors for frailty status. Patient-perceived recovery and health-related quality of life (HRQoL) were retrospectively rated for pre-COVID-19 and prospectively rated at the 5 month and 1 year visits. This study is registered with ISRCTN, number ISRCTN10980107. Findings: Between March 5, 2020, and March 31, 2021, 2419 participants were enrolled with FFP data. Mean age was 57.9 (SD 12.6) years, 933 (38.6%) were female, and 429 (17.7%) had received invasive mechanical ventilation. 1785 had measures at both timepoints, of which 240 (13.4%), 1138 (63.8%) and 407 (22.8%) were frail, pre-frail and robust, respectively, at 5 months compared with 123 (6.9%), 1046 (58.6%) and 616 (34.5%) at 1 year. Factors associated with pre-frailty or frailty were invasive mechanical ventilation, older age, female sex, and greater social deprivation. Frail participants had a larger reduction in HRQoL compared with before their COVID-19 illness and were less likely to describe themselves as recovered. Interpretation: Physical frailty and pre-frailty are common following hospitalisation with COVID-19. Improvement in frailty was seen between 5 and 12 months although two-thirds of the population remained pre-frail or frail. This suggests comprehensive assessment and interventions targeting pre-frailty and frailty beyond the initial illness are required. Funding: UK Research and Innovation and National Institute for Health Research.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

BACKGROUND: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. METHODS: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy. RESULTS: We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)]. CONCLUSIONS: Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.