Optimal management of sarcopenia

Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs

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

The effect of perindopril on postural instability in older people with a history of falls-a randomised controlled trial

Angiotensin converting enzyme inhibitors may improve exercise capacity and muscle function in older people but are often thought to increase falls risk. We investigated the effect of perindopril on postural stability in older people with a history of falls.Design: double-blind, parallel group, placebo-controlled randomised trial.Methods: we recruited people aged &gt;65 years with at least one fall in the previous year. Participants received 4 mg perindopril or placebo daily for 15 weeks. The primary outcome was the between-group difference in force-plate measured anteroposterior (AP) sway at 15 weeks. Secondary outcomes included other measures of postural sway, limits of stability during maximal forward, right and left leaning, blood pressure, muscle strength, 6-min walk distance and falls. The primary outcome was assessed using two-way ANOVA, adjusted for baseline factors.Results: we randomised 80 participants. Mean age was 78.0 (SD 7.4) years; 60 (75%) were female. About 77/80 (96%) completed the trial. At 15 weeks there were no significant between-group differences in AP sway with eyes open (mean difference 0 mm, 95% CI -8 to 7 mm, P = 0.91) or eyes closed (mean difference 2 mm, 95% CI -7 to 12 mm, P = 0.59); no differences in other measures of postural stability, muscle strength or function. About 16/40 (42%) of patients in each group had orthostatic hypotension at follow-up. The median number (IQR) of falls was 1 (0,4) in the perindopril versus 1 (0,2) in the placebo group (P = 0.24).Conclusions: perindopril did not improve postural sway in older people at risk of falls.</p

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

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

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

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

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

Deploying AMT for Scale Versus Scope: A Contingency Approach

Flexibility and efficiency are twin capabilities of advanced manufacturing technologies (AMT). Much research has focused on AMT’s role in bolstering manufacturing flexibility. Meanwhile, AMT’s potential for efficiency is often disregarded, even proscribed by researchers, because that dampens the effect on flexibility. Yet, research shows that practitioners frequently implement AMT to pursue efficiency over flexibility. This problem has not been addressed in the literature. We approach this problem by viewing AMT through a strategic lens and examining AMT at the deployment level. Firms with different strategic goals must deploy AMT differently due to flexibility and efficiency often being opposite ends of a tradeoff. We identify two modes of deployment – AMTScale versus AMTScope – with characteristically different features, which explains AMT’s ability to support opposed strategies. Our unique conceptualization puts into proper perspective the mixed empirical results reported in the literature. Drawing on the contingency theory, we find that firms deploying AMTScope (to support a ‘differentiation’ strategy) derive flexibility, while firms deploying AMTScale (to support a ‘cost-leadership’ strategy) sacrifice flexibility

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