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.

Simple approaches to characterising multiple long-term conditions (multimorbidity) and rates of emergency hospital admission: Findings from 495,465 UK Biobank participants.

BACKGROUND: Numerous approaches are used to characterise multiple long-term conditions (MLTC), including counts and indices. Few studies have compared approaches within the same dataset. We aimed to characterise MLTC using simple approaches, and compare their prevalence estimates of MLTC and associations with emergency hospital admission in the UK Biobank. METHODS: We used baseline data from 495,465 participants (age 38-73 years) to characterise MLTC using four approaches: Charlson index (CI), Byles index (BI), count of 43 conditions (CC) and count of body systems affected (BC). We defined MLTC as more than two conditions using CI, BI and CC, and more than two body systems using BC. We categorised scores (incorporating weightings for the indices) from each approach as 0, 1, 2 and 3+. We used linked hospital episode statistics and performed survival analyses to test associations with an endpoint of emergency hospital admission or death over 5 years. RESULTS: The prevalence of MLTC was 44% (BC), 33% (CC), 6% (BI) and 2% (CI). Higher scores using all approaches were associated with greater outcome rates independent of sex and age group. For example, using CC, compared with score 0, score 2 had 1.95 (95% CI: 1.91, 1.99) and a score of 3+ had 3.12 (95% CI: 3.06, 3.18) times greater outcome rates. The discriminant value of all approaches was modest (C-statistics 0.60-0.63). CONCLUSIONS: The counts classified a greater proportion as having MLTC than the indices, highlighting that prevalence estimates of MLTC vary depending on the approach. All approaches had strong statistical associations with emergency hospital admission but a modest ability to identify individuals at risk.

Bayesian borrowing for basket trials with longitudinal outcomes.

Basket trials are a novel clinical trial design in which a single intervention is investigated in multiple patient subgroups, or "baskets." They offer the opportunity to share information between subgroups, potentially increasing power to detect treatment effects. Basket trials offer several advantages over running a series of separate trials, including reduced sample sizes, increased efficiency, and reduced costs. Primarily, basket trials have been undertaken in Phase II oncology settings, but could be a promising design in other areas where a shared underlying biological mechanism drives different diseases. One such area is chronic aging-related diseases. However, trials in this area frequently have longitudinal outcomes, and therefore suitable methods are needed to share information in this setting. In this paper, we extend three Bayesian borrowing methods for a basket design with continuous longitudinal endpoints. We demonstrate our methods on a real-world dataset and in a simulation study where the aim is to detect positive basketwise treatment effects. Methods are compared with standalone analysis of each basket without borrowing. Our results confirm that methods that share information can improve power to detect positive treatment effects and increase precision over independent analysis in many scenarios. In highly heterogeneous scenarios, there is a trade-off between increased power and increased risk of type I errors. Our proposed methods for basket trials with continuous longitudinal outcomes aim to facilitate their applicability in the area of aging related diseases. Choice of method should be made based on trial priorities and the expected basketwise distribution of treatment effects.

Remote collection of physical performance measures for older people: a systematic review.

Remotely collected physical performance measures could improve inclusion of under-served groups in clinical research as well as enabling continuation of research in pandemic conditions. It is unclear whether remote collection is feasible and acceptable to older patients, or whether results are comparable to face-to-face measures. We conducted a systematic review according to a prespecified protocol. We included studies with mean participant age ≥ 60 years, with no language restriction. Studies examining the gait speed, Short Physical Performance Battery, distance walk tests, grip strength, Tinetti score, Berg balance test, sit-to-stand test and timed up and go were included. Reports of feasibility, acceptability, correlation between remote and face-to-face assessments and absolute differences between remote and face-to-face assessments were sought. Data were synthesised using Synthesis Without Meta-analysis methodology; 30 analyses from 17 publications were included. Study size ranged from 10 to 300 participants, with a mean age ranging from 61 to >80 years. Studies included a broad range of participants and conditions. Most studies had a moderate or high risk of bias. Only two studies undertook assessment of acceptability or feasibility, reporting good results. Correlation between face-to-face and remote measures was variable across studies, with no measure showing consistently good correlation. Only nine studies examined the accuracy of remote measures; in six studies, accuracy was rated as good (<5% mean difference between face-to-face and remote measures). There is a lack of robust evidence that remote collection of physical performance measures is acceptable to patients, feasible or provides comparable results to face-to-face measures.

New Horizons in cellular senescence for clinicians.

Cellular senescence has emerged as a fundamental biological mechanism underpinning the ageing process and has been implicated in the pathogenesis of an increasing number of age-related conditions. Cellular senescence is a cell fate originally defined as an irreversible loss of replicative potential although it is now clear that it can be induced by a variety of mechanisms independent of replication and telomere attrition. The drivers include a persistent DNA damage response causing multiple alterations in cellular function. Senescent cells secrete a range of mediators that drive chronic inflammation and can convert other cells to the senescent state-the senescence-associated secretory phenotype. Much research to date has been conducted in animal models, but it is now clear that senescent cells accompany ageing in humans and their presence is an important driver of disease across systems. Proof-of-concept work suggests that preventing or reversing senescence may be a viable strategy to counteract human ageing and age-related disease. Possible interventions include exercise, nutrition and senolytics/senostatic drugs although there are a number of potential limitations to the use of senotherapeutics. These interventions are generally tested for single-organ conditions, but the real power of this approach is the potential to tackle multiple age-related conditions. The litmus test for this exciting new class of therapies, however, will be whether they can improve healthy life expectancy rather than merely extending lifespan. The outcomes measured in clinical studies need to reflect these aims if senotherapeutics are to gain the trust of clinicians, patients and the public.

Including older people in health and social care research: best practice recommendations based on the INCLUDE framework.

BACKGROUND: Older people are often explicitly or implicitly excluded from research, in particular clinical trials. This means that study findings may not be applicable to them, or that older people may not be offered treatments due to an absence of evidence. AIMS: The aim of this work was to develop recommendations to guide all research relevant to older people. METHODS: A diverse stakeholder group identified barriers and solutions to including older people in research. In parallel, a rapid literature review of published papers was undertaken to identify existing papers on the inclusion of older people in research. The findings were synthesised and mapped onto a socio-ecological model. From the synthesis we identified themes that were developed into initial recommendations that were iteratively refined with the stakeholder group. RESULTS: A range of individual, interpersonal, organisational, community and policy factors impact on the inclusion of older people in research. A total of 14 recommendations were developed such as removing upper age limits and comorbidity exclusions, involving older people, advocates and health and social care professionals with expertise in ageing in designing the research, and considering flexible or alternative approaches to data collection to maximise opportunities for participation. We also developed four questions that may guide those developing, reviewing and funding research that is inclusive of older people. CONCLUSION: Our recommendations provide up to date, practical advice on ways to improve the inclusion of older people in health and care research.

Development of a UK core dataset for geriatric medicine research: a position statement and results from a Delphi consensus process.

BACKGROUND: There is lack of standardisation in assessment tools used in geriatric medicine research, which makes pooling of data and cross-study comparisons difficult. METHODS: We conducted a modified Delphi process to establish measures to be included within core and extended datasets for geriatric medicine research in the United Kingdom (UK). This included three complete questionnaire rounds, and one consensus meeting. Participants were selected from attendance at the NIHR Newcastle Biomedical Research Centre meeting, May 2019, and academic geriatric medicine e-mailing lists. Literature review was used to develop the initial questionnaire, with all responses then included in the second questionnaire. The third questionnaire used refined options from the second questionnaire with response ranking. RESULTS: Ninety-eight responses were obtained across all questionnaire rounds (Initial: 19, Second: 21, Third: 58) from experienced and early career researchers in geriatric medicine. The initial questionnaire included 18 questions with short text responses, including one question for responders to suggest additional items. Twenty-six questions were included in the second questionnaire, with 108 within category options. The third questionnaire included three ranking, seven final agreement, and four binary option questions. Results were discussed at the consensus meeting. In our position statement, the final consensus dataset includes six core domains: demographics (age, gender, ethnicity, socioeconomic status), specified morbidities, functional ability (Barthel and/or Nottingham Extended Activities of Daily Living), Clinical Frailty Scale (CFS), cognition, and patient-reported outcome measures (dependent on research question). We also propose how additional variables should be measured within an extended dataset. CONCLUSIONS: Our core and extended datasets represent current consensus opinion of academic geriatric medicine clinicians across the UK. We consider the development and further use of these datasets will strengthen collaboration between researchers and academic institutions.

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.

Feasibility, reliability and safety of self-assessed orthostatic blood pressure at home.

BACKGROUND: A postural blood pressure assessment is required to diagnose Orthostatic Hypotension. With increasing remote consultations, alternative methods of performing postural blood pressure assessment are required. OBJECTIVE: Determine whether postural blood pressure measurement at home, without a clinician, is reliable, feasible and safe. DESIGN: Service improvement project within a falls and syncope service in Northeast England. SUBJECTS: Eligibility criteria: aged ≥60 years; postural blood pressure measurement is indicated and is physically and cognitively able to perform. Exclusion criteria: nursing home residents, attending clinic in person. METHODS: Postural blood pressure measurements were performed in patients' homes under clinical observation. Patient-led assessments were performed independent of the clinician, following written guidance. This was followed by a clinical-led assessment after 10-minute supine rest. OUTCOMES: Agreement between patient and clinician derived postural blood pressure values and diagnosis of Orthostatic Hypotension; intervention safety, feasibility and acceptability. RESULTS: Twenty-eight patients were eligible and 25 participated (mean age 75, median Clinical Frailty Score five).There was 95% agreement (Cohen's kappa 0.90 (0.70, 1.00)) between patient and clinician derived readings to diagnose orthostatic hypotension.Postural systolic blood pressure drop correlated strongly (r = 0.80), with patient derived readings overestimating by 1 (-6, 3) mmHg. Limits of agreement, determined via Bland Altman analysis, were +17 and -20 mmHg, greater than pre-determined maximum clinically important difference (±5 mmHg).Twenty participants performed valid postural blood pressure assessments without clinical assistance. CONCLUSIONS: Patient-led postural blood pressure assessment at home is a reliable, safe and acceptable method for diagnosing Orthostatic Hypotension.

Resistance exercise as a treatment for sarcopenia: prescription and delivery.

Sarcopenia is a generalised skeletal muscle disorder characterised by reduced muscle strength and mass and associated with a range of negative health outcomes. Currently, resistance exercise (RE) is recommended as the first-line treatment for counteracting the deleterious consequences of sarcopenia in older adults. However, whilst there is considerable evidence demonstrating that RE is an effective intervention for improving muscle strength and function in healthy older adults, much less is known about its benefits in older people living with sarcopenia. Furthermore, evidence for its optimal prescription and delivery is very limited and any potential benefits of RE are unlikely to be realised in the absence of an appropriate exercise dose. We provide a summary of the underlying principles of effective RE prescription (specificity, overload and progression) and discuss the main variables (training frequency, exercise selection, exercise intensity, exercise volume and rest periods) that can be manipulated when designing RE programmes. Following this, we propose that an RE programme that consists of two exercise sessions per week and involves a combination of upper- and lower-body exercises performed with a relatively high degree of effort for 1-3 sets of 6-12 repetitions is appropriate as a treatment for sarcopenia. The principles of RE prescription outlined here and the proposed RE programme presented in this paper provide a useful resource for clinicians and exercise practitioners treating older adults with sarcopenia and will also be of value to researchers for standardising approaches to RE interventions in future sarcopenia studies.

Developing a core outcome set for hospital deprescribing trials for older people under the care of a geriatrician.

BACKGROUND: Half of older people are prescribed unnecessary/inappropriate medications that are not routinely deprescribed in hospital hence there is a need for deprescribing trials. We aimed to develop a Core Outcome Set (COS) for deprescribing trials for older people under the care of a geriatrician during hospital admission. METHODS: We developed a list of potentially relevant outcomes from the literature. Using a two-round Delphi survey of stakeholder groups representing older people and carers, hospital clinicians, hospital managers, and ageing/deprescribing researchers, each outcome was scored according to Grading of Recommendations Assessment, Development and Evaluation, followed by two consensus workshops to finalise the COS. RESULTS: Two hundred people completed Round 1 and 114 completed Round 2. Representing all stakeholder groups, 10 people participated in workshop 1 and 10 in workshop 2. Six outcomes were identified as most important, feasible and acceptable to collect in a trial: number of prescribed medicines stopped; number of prescribed medicines with dosage reduced; quality of life; mortality; adverse drug events and number of hospital stays. Three other outcomes were identified as important, but currently too burdensome to collect: number of potentially inappropriate medicines prescribed; burden from medication routine; and medication-related admissions to hospital. CONCLUSIONS: A COS represents the minimum outcomes that should be collected and reported. Whilst uncommon practice for COS development, the value of considering outcome collection feasibility is demonstrated by the removal of three potential outcomes that, if included, may have compromised COS uptake due to challenges with collecting the data.

Performance of the SarQoL quality of life tool in a UK population of older people with probable sarcopenia and implications for use in clinical trials: findings from the SarcNet registry.

BACKGROUND: The Sarcopenia Quality of Life (SarQoL) questionnaire is a disease-specific sarcopenia quality of life tool. We aimed to independently assess SarQoL with a particular focus on its suitability as a clinical trial outcome measure. METHODS: We analysed data from the UK Sarcopenia Network and Registry. Measures of physical performance and lean mass were collected at baseline. SarQoL and the Strength, Assistance, Rise, Climb - Falls (SARC-F) questionnaire (to assess functional ability) were collected at both baseline and six-month follow-up. Global changes in fitness and quality of life at 6 months were elicited on seven-point Likert scales. Internal consistency was assessed using Cronbach's alpha. Responsiveness (Cohen's d and Guyatt coefficients) and minimum clinically important differences were calculated for participants reporting slight improvement or worsening in their global scores. Concurrent validity was assessed by correlating baseline SarQoL scores with measures of physical performance and functional ability. RESULTS: We analysed data from 147 participants, 125 of whom underwent follow up assessment; mean age 78 years; 72 (49%) were women. Internal consistency was good; Cronbach's alpha was 0.944 at baseline and 0.732 at telephone follow-up. Correlation between baseline and follow-up SarQoL was weak (r = 0.27; p = 0.03). The minimum clinically important improvement ranged from 5 to 21 points giving trial sample size estimates of 25-100 participants. SarQoL scores were moderately correlated with handgrip (r = 0.37; p < 0.001), SARC-F (r = - 0.45; p < 0.001), short physical performance battery (r = 0.48; p < 0.001) and 4-m walk speed (r = 0.48; p < 0.001). CONCLUSIONS: SarQoL has acceptable performance in older UK participants with probable sarcopenia and is sufficiently responsive for use in clinical trials for sarcopenia.

The ViKTORIES trial: A randomized, double-blind, placebo-controlled trial of vitamin K supplementation to improve vascular health in kidney transplant recipients.

Premature cardiovascular disease and death with a functioning graft are leading causes of death and graft loss, respectively, in kidney transplant recipients (KTRs). Vascular stiffness and calcification are markers of cardiovascular disease that are prevalent in KTR and associated with subclinical vitamin K deficiency. We performed a single-center, phase II, parallel-group, randomized, double-blind, placebo-controlled trial (ISRCTN22012044) to test whether vitamin K supplementation reduced vascular stiffness (MRI-based aortic distensibility) or calcification (coronary artery calcium score on computed tomography) in KTR over 1 year of treatment. The primary outcome was between-group difference in vascular stiffness (ascending aortic distensibility). KTRs were recruited between September 2017 and June 2018, and randomized 1:1 to vitamin K (menadiol diphosphate 5 mg; n = 45) or placebo (n = 45) thrice weekly. Baseline demographics, clinical history, and immunosuppression regimens were similar between groups. There was no impact of vitamin K on vascular stiffness (treatment effect -0.23 [95% CI -0.75 to 0.29] × 10-3  mmHg-1 ; p = .377), vascular calcification (treatment effect -141 [95% CI - 320 to 38] units; p = .124), nor any other outcome measure. In this heterogeneous cohort of prevalent KTR, vitamin K supplementation did not reduce vascular stiffness or calcification over 1 year. Improving vascular health in KTR is likely to require a multifaceted approach.

Vitamin K and vascular calcification.

PURPOSE OF REVIEW: Vascular calcification is a common and important cardiovascular risk factor in patients with chronic kidney disease (CKD). Recent advances in the understanding of the biology of vascular calcification implicate vitamin K-dependent proteins as important regulators in this process. This review highlights recent key advances in vascular biology, epidemiology, and clinical trials in this rapidly evolving field. RECENT FINDINGS: Vitamin K deficiency is associated with increasing severity of vascular calcification among patients with CKD, but the relationship with cardiovascular disease and mortality is inconsistent. Vitamin K may reduce calcification propensity by improving the activity of vitamin K-dependent calcification inhibitors or by down-regulating components of the innate immune system to reduce inflammation. However, recent randomized controlled trials in patients with diabetes, CKD, renal transplant, and on hemodialysis have failed to demonstrate improvement in vascular calcification or stiffness after vitamin K treatment. SUMMARY: Current evidence does not support a clinically useful role for vitamin K supplementation to prevent or reverse vascular calcification in patients with CKD. Knowledge gaps remain, particularly whether higher doses of vitamin K, longer duration of supplementations, or use a vitamin K as a part of a package of measures to counteract vascular calcification might be effective.

Developing a UK sarcopenia registry: recruitment and baseline characteristics of the SarcNet pilot.

BACKGROUND: sarcopenia registries are a potential method to meet the challenge of recruitment to sarcopenia trials. We tested the feasibility of setting up a UK sarcopenia registry, the feasibility of recruitment methods and sought to characterise the pilot registry population. METHODS: six diverse UK sites took part, with potential participants aged 65 and over approached via mailshots from local primary care practices. Telephone pre-screening using the SARC-F score was followed by in-person screening and baseline visit. Co-morbidities, medications, grip strength, Short Physical Performance Battery, bioimpedance analysis, Geriatric Depression Score, Montreal Cognitive Assessment, Sarcopenia Quality of Life score were performed and permission sought for future recontact. Descriptive statistics for recruitment rates and baseline measures were generated; an embedded randomised trial examined the effect of a University logo on the primary care mailshot on recruitment rates. RESULTS: sixteen practices contributed a total of 3,508 letters. In total, 428 replies were received (12% response rate); 380 underwent telephone pre-screening of whom 215 (57%) were eligible to attend a screening visit; 150 participants were recruited (40% of those pre-screened) with 147 contributing baseline data. No significant difference was seen in response rates between mailshots with and without the logo (between-group difference 1.1% [95% confidence interval -1.0% to 3.4%], P = 0.31). The mean age of enrollees was 78 years; 72 (49%) were women. In total, 138/147 (94%) had probable sarcopenia on European Working Group on Sarcopenia 2019 criteria and 145/147 (98%) agreed to be recontacted about future studies. CONCLUSION: recruitment to a multisite UK sarcopenia registry is feasible, with high levels of consent for recontact.

Developing and evaluating a frailty index for older South Africans-findings from the HAALSI study.

BACKGROUND: despite rapid population ageing, few studies have investigated frailty in older people in sub-Saharan Africa. We tested a cumulative deficit frailty index in a population of older people from rural South Africa. METHODS: analysis of cross-sectional data from the Health and Ageing in Africa: Longitudinal Studies of an INDEPTH Community (HAALSI) study. We used self-reported diagnoses, symptoms, activities of daily living, objective physiological indices and blood tests to calculate a 32-variable cumulative deficit frailty index. We fitted Cox proportional hazards models to test associations between frailty category and all-cause mortality. We tested the discriminant ability of the frailty index to predict one-year mortality alone and in addition to age and sex. RESULTS: in total 3,989 participants were included in the analysis, mean age 61 years (standard deviation 13); 2,175 (54.5%) were women. The median frailty index was 0.13 (interquartile range 0.09-0.19); Using population-specific cutoffs, 557 (14.0%) had moderate frailty and 263 (6.6%) had severe frailty. All-cause mortality risk was related to frailty severity independent of age and sex (hazard ratio per 0.01 increase in frailty index: 1.06 [95% confidence interval 1.04-1.07]). The frailty index alone showed moderate discrimination for one-year mortality: c-statistic 0.68-0.76; combining the frailty index with age and sex improved performance (c-statistic 0.77-0.81). CONCLUSION: frailty measured by cumulative deficits is common and predicts mortality in a rural population of older South Africans. The number of measures needed may limit utility in resource-poor settings.

Barriers and potential solutions in the recruitment and retention of older patients in clinical trials-lessons learned from six large multicentre randomized controlled trials.

BACKGROUND: older people remain underrepresented in clinical trials, and evidence generated in younger populations cannot always be generalized to older patients. OBJECTIVE: to identify key barriers and to discuss solutions to specific issues affecting recruitment and retention of older participants in clinical trials based on experience gained from six current European randomised controlled trials (RCTs) focusing on older people. METHODS: a multidisciplinary group of experts including representatives of the six RCTs held two networking conferences and compiled lists of potential barriers and solutions. Every item was subsequently allocated points by each study team according to how important it was perceived to be for their RCTs. RESULTS: the six RCTs enrolled 7,612 older patients. Key barriers to recruitment were impaired health status, comorbidities and diverse health beliefs including priorities within different cultural systems. All trials had to increase the number of recruitment sites. Other measures felt to be effective included the provision of extra time, communication training for the study staff and a re-design of patient information. Key barriers for retention included the presence of severe comorbidities and the occurrence of adverse events. Long study duration, frequent study visits and difficulties accessing the study site were also mentioned. Solutions felt to be effective included spending more time maintaining close contact with the participants, appropriate measures to show appreciation and reimbursement of travel arrangements. CONCLUSION: recruitment and retention of older patients in trials requires special recognition and a targeted approach. Our results provide scientifically-based practical recommendations for optimizing future studies in this population.

Sarcopenia in Patients Undergoing Lower Limb Bypass Surgery is Associated with Higher Mortality and Major Amputation Rates.

BACKGROUND: Sarcopenia is adversely associated with survival in several diseases. Vasculopathy is often associated with multimorbidity and consequent deconditioning with poor long-term outcomes. This study examined the impact of sarcopenia on clinical outcome in patients with and without critical limb-threatening ischaemia who underwent infrainguinal bypass surgery. METHODS: All patients undergoing infra-inguinal surgical revascularisation in 2016-2018 were retrospectively reviewed. Sarcopenia was defined as a skeletal muscle area at the L3 vertebral level (defined as L3 muscle area < 114cm2 for men or <89.8cm2 for women) on CT angiography. The primary outcome was overall survival by analysed by time to event analysis. Secondary outcomes included ipsilateral major lower-limb amputation, length of hospital stay, myocardial infarction and surgical-site infection. RESULTS: A total of 116 patients with a mean age of 66.9 years were included, with a mean follow-up of 21 months. 14 (12%) of patients were sarcopenic; there were more patients with diabetes (40% vs 7%) in the sarcopenic group, p=0.018. Age, gender, Rutherford grade at presentation, other co-morbidities, other laboratory tests, conduit material and Rutherford grade at presentation were similar in those with and without sarcopenia and were statistically insignificant upon testing. Overall survival was worse for sarcopenic patients (Log Rank P=0.001) and Hazard Ratio for death 5.8; 95%CI 1.8-19.1; P=0.001. Major lower-limb amputation occurred more frequently in patients with sarcopenia (7/14 [50%] vs 23/102 [23%]; P=0.046). There was no difference in other secondary outcomes including rates of graft occlusion, myocardial infarction, surgical site infection and length of stay. Adding SMA measurement to a multivariate generalised linear model including age, sex, diabetes, and haemoglobin improved the AUROC from 0.75-0.85. CONCLUSION: In this cohort of patients undergoing vascular surgery, sarcopenia defined using L3 muscle area was significantly associated with overall mortality and major lower-limb amputation.

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

BACKGROUND: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown. METHODS: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m2). We randomly assigned participants to receive 400 µg oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study. RESULTS: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures. CONCLUSIONS: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com).

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

BACKGROUND: Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance. METHODS: We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo. We recruited community-dwelling participants aged 65 and over with baseline 6-min walk distance of <400 m and no contraindications to magnetic resonance imaging scanning. Outcomes were measured at baseline and 20 weeks. The primary outcome was post-exercise phosphocreatine (PCr) recovery rate measured using 31P magnetic resonance spectroscopy of the calf. Secondary outcomes included 6-min walk distance, short physical performance battery (SPPB), lean body mass measured by bioimpedance, endothelial function and quality of life. RESULTS: In total, 124 participants were randomised, mean age 80 (SD 6) years. A total of 59 (48%) were female, baseline 6-min walk distance was 293 m (SD 80 m) and baseline SPPB was 8.5 (SD 2.0). Allopurinol did not significantly improve PCr recovery rate (treatment effect 0.10 units [95% CI, -0.07 to 0.27], P = 0.25). No significant changes were seen in endothelial function, quality of life, lean body mass or SPPB. Allopurinol improved 6-min walk distance (treatment effect 25 m [95% 4-46, P = 0.02]). This was more pronounced in those with high baseline oxidative stress and urate. CONCLUSION: Allopurinol improved 6-min walk distance but not PCr recovery rate in older people with impaired physical function. Antioxidant strategies to improve muscle function for older people may need to be targeted at subgroups with high baseline oxidative stress.