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 &lt;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. </p

Acceptability and feasibility of magnetic femoral nerve stimulation in older, functionally impaired patients

Abstract Objective Magnetic femoral nerve stimulation to test muscle function has been largely unexplored in older people. We assessed acceptability, feasibility, along with reproducibility and correlation with other physical function measures. Results Study 1 recruited older people with sarcopenia. Stimulation was performed at baseline and 2 weeks along with six minute walk (6MW), maximum voluntary quadriceps contraction, short physical performance battery and grip strength. Acceptability was measured using visual analog scales. Study 2 used baseline data from a trial of older people. We correlated stimulation results with 6MW, maximal voluntary contraction and muscle mass. Maximum quadriceps twitch tension was measured in both studies, evoked using biphasic magnetic stimulation of the femoral nerve. In study 1 (n = 12), magnetic stimulation was well tolerated with mean discomfort rating of 9% (range 0–40%) on a visual analog scale. Reproducibility was poor (intraclass correlation coefficient 0.06; p = 0.44). Study 2 (n = 64) showed only weak to moderate correlations for maximum quadriceps twitch tension with other measures of physical function (6 minute walk test r = 0.24, p = 0.06; maximal voluntary contraction r = 0.26; p = 0.04). We conclude that magnetic femoral nerve stimulation is acceptable and feasible but poorly reproducible in older, functionally impaired people

Validation of the AX3 triaxial accelerometer in older functionally impaired people

Background: Studying physical activity (PA) trends in older populations and potential interventions for increasing PA is important, as PA is a factor in many age-related health outcomes such as chronic disease, premature mortality, physical function, and injuries from falls[1]. Objective measures of PA provide valuable information regarding the functional impact that ageing and chronic disease states may have on a patient’s life. Aims: The purpose of this study was to test the validity of the AX3 PA monitor in an older population, to investigate if the AX3 is a valid measure of distinct types or levels of activity in older people with a spectrum of mobility. Methods: Validity of the AX3 PA monitor was tested using the RT3 as a means of cross validating the AX3. Study participants wore both the AX3 and the RT3 accelerometers, positioned on their non-dominant side, while completing a series of standardised everyday activities. Results: Although overall correlation was high (r&gt;0.8) between the RT3 and lower-limb mounted AX3 counts, the correlation between the two devices was much stronger for walking activity than for any of the non-walking activities. Discussion: Activity counts at all lower limb positions for the AX3 and RT3 were highly correlated. Correlation between wrist-mounted AX3 counts and lower limb AX3 counts was only moderate, and worsened when walking aids were in use. Conclusions: The results of this study indicate that the AX3 monitor is a valid tool, which might be used to objectively measure walking activity in older, functionally impaired adults; a welcome finding for this under-researched area

Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain:A Proof‐of‐Concept Trial

Objective: To determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life. Methods: This parallel-group, randomized, placebo-controlled, double-blind trial randomized community-dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between-group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5-domain (EQ-5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed-model regression, adjusting for baseline values of test variables. Results: A total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12-week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) - 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI -0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI -0.7, 0.8]; P = 0.98), or EQ-5D 3L score (0.04 points [95% CI -0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C-telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident. Conclusion: Spironolactone did not improve symptoms, physical function, or health-related quality of life in older people with knee OA

Association between objectively measured physical activity and opioid, hypnotic, or anticholinergic medication use in older people – data from the Physical Activity Cohort Scotland study

Background: Centrally acting medications cause cognitive slowing and incoordination, which could reduce older people’s physical activity levels. This association has not been studied previously.Objectives: To examine the association between opioid, hypnotic and anticholinergic medication, and objectively measured physical activity, in a cohort of older people.Methods: We used data from the Physical Activity Cohort Scotland, a representative cohort of community-dwelling older people aged 65 and over who were assessed at baseline and again 2-3 years later. Objective physical activity was measured using Stayhealthy RT3 accelerometers over 7 days. Baseline medication use (opioid use, hypnotic use, modified anticholinergic risk score [mARS]) was obtained from linked, routinely collected community prescribing records. Cross-sectional and longitudinal associations between baseline medication use and both baseline activity and change in activity over time were analysed using unadjusted and adjusted linear regression models.Results: 310 participants were included in the analysis; mean age 77 (SD 7) years. No association was seen between baseline use of any medication class and baseline physical activity levels in unadjusted or adjusted models. For change in activity over time, there was no difference between users and non-users of hypnotics or opioids. Higher anticholinergic burden was associated with a steeper decline in activity over the follow up period (mARS=0: -7051 counts/24h/yr; mARS=1-2 -15942 counts/24h/yr; mARS&gt;=3 -19544 counts/24h/yr; p=0.03) and this remained robust to multiple adjustments.Conclusion: Anticholinergic burden is associated with greater decline in objectively measured physical activity over time in older people, a finding not seen with hypnotic or opioid use

Leucine and ACE inhibitors as therapies for sarcopenia (LACE trial): study protocol for a randomised controlled trial

Background: Sarcopenia (the age-related loss of muscle mass and function) is a major contributor to loss of mobility, falls, loss of independence, morbidity and mortality in older people. Although resistance training is effective in preventing and reversing sarcopenia, many older people are sedentary and either cannot or do not want to exercise. This trial examines the efficacy of supplementation with the amino acid leucine and/or angiotensin converting enzyme inhibition to potentially improve muscle mass and function in people with sarcopenia. Promising preliminary data exist from small studies for both interventions, but neither has yet been tested in adequately powered randomised trials in patients with sarcopenia. Methods: Leucine and ACE inhibitors in sarcopenia (LACE) is a multicentre, masked, placebo-controlled, 2 × 2 factorial randomised trial evaluating the efficacy of leucine and perindopril (angiotensin converting enzyme inhibitor (ACEi)) in patients with sarcopenia. The trial will recruit 440 patients from primary and secondary care services across the UK. Male and female patients aged 70 years and over with sarcopenia as defined by the European Working Group on Sarcopenia (based on low total skeletal muscle mass on bioimpedance analysis and either low gait speed or low handgrip strength) will be eligible for participation. Participants will be excluded if they have a contraindication to, or are already taking, an ACEi, angiotensin receptor blocker or leucine. The primary clinical outcome for the trial is the between-group difference in the Short Physical Performance Battery score at all points between baseline and 12 months. Secondary outcomes include appendicular muscle mass measured using dual-energy X-ray absorptiometry, muscle strength, activities of daily living, quality of life, activity using pedometer step counts and falls. Participants, clinical teams, outcomes assessors and trial analysts are masked to treatment allocation. A panel of biomarkers including microRNAs, neurohormones, genetic polymorphisms and markers of inflammation relevant to muscle pathophysiology will be measured to explore predictors of response and further elucidate mechanisms underlying sarcopenia. Participants will receive a total of 12 months of either perindopril or placebo and either leucine or placebo. Discussion: The results will provide the first robust test of the overall clinical and cost-effectiveness of these novel therapies for older patients with sarcopenia. Trial registration: ISRCTN, ISRCTN90094835. Registered on 18 February 2015

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

A feasibility study of a theory-based intervention to improve appropriate polypharmacy for older people in primary care

Background: A general practitioner (GP)-targeted intervention aimed at improving the prescribing of appropriate polypharmacy for older people was previously developed using a systematic, theory-based approach based on the UK Medical Research Council’s complex intervention framework. The primary intervention component comprised a video demonstration of a GP prescribing appropriate polypharmacy during a consultation with an older patient. The video was delivered to GPs online and included feedback emphasising the positive outcomes of performing the behaviour. As a complementary intervention component, patients were invited to scheduled medication review consultations with GPs. This study aimed to test the feasibility of the intervention and study procedures (recruitment, data collection). Methods: GPs from two general practices were given access to the video, and reception staff scheduled consultations with older patients receiving polypharmacy (≥4 medicines). Primary feasibility study outcomes were the usability and acceptability of the intervention to GPs. Feedback was collected from GP and patient participants using structured questionnaires. Clinical data were also extracted from recruited patients’ medical records (baseline and 1 month post-consultation). The feasibility of applying validated assessment of prescribing appropriateness (STOPP/ START criteria, Medication Appropriateness Index) and medication regimen complexity (Medication Regimen Complexity Index) to these data was investigated. Data analysis was descriptive, providing an overview of participants’ feedback and clinical assessment findings. Results: Four GPs and ten patients were recruited across two practices. The intervention was considered usable and acceptable by GPs. Some reservations were expressed by GPs as to whether the video truly reflected resource and time pressures encountered in the general practice working environment. Patient feedback on the scheduled consultations was positive. Patients welcomed the opportunity to have their medications reviewed. Due to the short time to follow-up and a lack of detailed clinical information in patient records, it was not feasible to detect any prescribing changes or to apply the assessment tools to patients’ clinical data. Conclusion: The findings will help to further refine the intervention and study procedures (including time to follow-up) which will be tested in a randomised pilot study that will inform the design of a definitive trial to evaluate the intervention’s effectiveness

Effect of Angiotensin System Inhibitors on Physical Performance in Older People - A Systematic Review and Meta-Analysis

Objective: Preclinical and observational data suggest that angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be able to improve physical performance in older people via direct and indirect effects on skeletal muscle. We aimed to summarize current evidence from randomised controlled trials in this area. Design: Systematic review and meta-analysis. Setting and Participants: Randomized controlled trials enrolling older people, comparing ACEi or ARB to placebo, usual care or another antihypertensive agent, with outcome data on measures of physical performance. Methods: We searched multiple electronic databases without language restriction between inception and the end of February 2020. Trials were excluded if the mean age of participants was <65 years or treatment was targeting specific diseases known to affect muscle function (for example heart failure). Data were sought on measures of endurance and strength. Standardized mean difference (SMD) treatment effects were calculated using random-effects models with RevMan software. Results: Eight trials (952 participants) were included. Six trials tested ACEi, 2 trials tested ARBs. The mean age of participants ranged from 66 to 79 years, and the duration of treatment ranged from 2 months to 1 year. Trials recruited healthy older people and people with functional impairment; no trials specifically targeted older people with sarcopenia. Risk of bias for all trials was low to moderate. No significant effect was seen on endurance outcomes [6 trials, SMD 0.04 (95% CI –0.22 to 0.29); P =.77; I2 = 53%], strength outcomes [6 trials, SMD –0.02 (95% CI –0.18 to 0.14), P =.83, I2 = 21%] or the short physical performance battery [3 trials, SMD –0.04 (95% CI –0.19 to 0.11), P =.60, I2 = 0%]. No evidence of publication bias was evident on inspection of funnel plots. Conclusions and Implications: Existing evidence does not support the use of ACE inhibitors or angiotensin receptor blockers as a single intervention to improve physical performance in older people

Development of an intervention to improve appropriate polypharmacy in older people in primary care using a theory-based method

BACKGROUND: It is advocated that interventions to improve clinical practice should be developed using a systematic approach and intervention development methods should be reported. However, previous interventions aimed at ensuring that older people receive appropriate polypharmacy have lacked details on their development. This study formed part of a multiphase research project which aimed to develop an intervention to improve appropriate polypharmacy in older people in primary care. METHODS: The target behaviours for the intervention were prescribing and dispensing of appropriate polypharmacy to older patients by general practitioners (GPs) and community pharmacists. Intervention development followed a systematic approach, including previous mapping of behaviour change techniques (BCTs) to key domains from the Theoretical Domains Framework that were perceived by GPs and pharmacists to influence the target behaviours. Draft interventions were developed to operationalise selected BCTs through team discussion. Selection of an intervention for feasibility testing was guided by a subset of the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria. RESULTS: Three draft interventions comprising selected BCTs were developed, targeting patients, pharmacists and GPs, respectively. Following assessment of each intervention using a subset of the APEASE criteria (affordability, practicability, acceptability), the GP-targeted intervention was selected for feasibility testing. This intervention will involve a demonstration of the behaviour and will be delivered as an online video. The video demonstrating how GPs can prescribe appropriate polypharmacy during a typical consultation with an older patient will also demonstrate salience of consequences (feedback emphasising the positive outcomes of performing the behaviour). Action plans and prompts/cues will be used as complementary intervention components. The intervention is designed to facilitate the prescribing of appropriate polypharmacy in routine practice. CONCLUSION: A GP-targeted intervention to improve appropriate polypharmacy in older people has been developed using a systematic approach. Intervention content has been specified using an established taxonomy of BCTs and selected to maximise feasibility. The results of a future feasibility study will help to determine if the theory-based intervention requires further refinement before progressing to a larger scale randomised evaluation