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Journal of Cachexia, Sarcopenia and... Feb 2022Sarcopenia is defined as the loss of muscle mass and strength. Despite the seriousness of this disease, a single diagnostic criterion has not yet been established. Few... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sarcopenia is defined as the loss of muscle mass and strength. Despite the seriousness of this disease, a single diagnostic criterion has not yet been established. Few studies have reported the prevalence of sarcopenia globally, and there is a high level of heterogeneity between studies, stemmed from the diagnostic criteria of sarcopenia and the target population. The aims of this systematic review and meta-analysis were (i) to identify and summarize the diagnostic criteria used to define sarcopenia and severe sarcopenia and (ii) to estimate the global and region-specific prevalence of sarcopenia and severe sarcopenia by sociodemographic factors.
METHODS
Embase, MEDLINE, and Web of Science Core Collections were searched using relevant MeSH terms. The inclusion criteria were cross-sectional or cohort studies in individuals aged ≥18 years, published in English, and with muscle mass measured using dual-energy x-ray absorptiometry, bioelectrical impedance, or computed tomography (CT) scan. For the meta-analysis, studies were stratified by diagnostic criteria (classifications), cut-off points, and instruments to assess muscle mass. If at least three studies reported the same classification, cut-off points, and instrument to measure muscle mass, they were considered suitable for meta-analysis. Following this approach, 6 classifications and 23 subgroups were created. Overall pooled estimates with inverse-variance weights obtained from a random-effects model were estimated using the metaprop command in Stata.
RESULTS
Out of 19 320 studies, 263 were eligible for the narrative synthesis and 151 for meta-analysis (total n = 692 056, mean age: 68.5 years). Using different classifications and cut-off points, the prevalence of sarcopenia varied between 10% and 27% in the studies included for meta-analysis. The highest and lowest prevalence were observed in Oceania and Europe using the European Working Group on Sarcopenia in Older People (EWGSOP) and EWGSOP2, respectively. The prevalence ranged from 8% to 36% in individuals <60 years and from 10% to 27% in ≥60 years. Men had a higher prevalence of sarcopenia using the EWGSOP2 (11% vs. 2%) while it was higher in women using the International Working Group on Sarcopenia (17% vs. 12%). Finally, the prevalence of severe sarcopenia ranged from 2% to 9%.
CONCLUSIONS
The prevalence of sarcopenia and severe sarcopenia varied considerably according to the classification and cut-off point used. Considering the lack of a single diagnostic for sarcopenia, future studies should adhere to current guidelines, which would facilitate the comparison of results between studies and populations across the globe.
Topics: Absorptiometry, Photon; Adolescent; Adult; Aged; Electric Impedance; Female; Hand Strength; Humans; Male; Prevalence; Sarcopenia
PubMed: 34816624
DOI: 10.1002/jcsm.12783 -
BMC Geriatrics Dec 2021We conducted a systematic review and meta-analysis to clarify the effects of different exercise modes (resistance training [RT], whole body vibration training [WBVT],... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted a systematic review and meta-analysis to clarify the effects of different exercise modes (resistance training [RT], whole body vibration training [WBVT], and mixed training [MT, resistance training combined with other exercises such as balance, endurance and aerobic training]) on muscle strength (knee extension strength [KES]) and physical performance (Timed Up and Go [TUG], gait speed [GS] and the Chair Stand [CS]) in older people with sarcopenia.
METHOD
All studies published from January 2010 to March 2021 on the effects of exercise training in older people with sarcopenia were retrieved from 6 electronic databases: Pubmed, Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure (CNKI), and Wanfang Database. Two researchers independently extracted and evaluated studies that met inclusion and exclusion criteria. Pooled analyses for pre- and post- outcome measurements were performed using Review Manager 5.4 with standardized mean differences (SMDs) and fixed-effect models.
RESULT
Twenty-six studies (25 randomized controlled trails [RCTs] and one non-randomized controlled trail) were included in this study with 1191 older people with sarcopenia (mean age 60.6 ± 2.3 to 89.5 ± 4.4). Compared with a control group, RT and MT significantly improved KES (RT, SMD = 1.36, 95% confidence intervals [95% CI]: 0.71 to 2.02, p < 0.0001, I = 72%; MT, SMD = 0.62, 95% CI: 0.29 to 0.95, p = 0.0002, I = 56%) and GS (RT, SMD = 2.01, 95% CI: 1.04 to 2.97, p < 0.0001, I = 84%; MT, SMD = 0.69, 95% CI: 0.29 to 1.09, p = 0.008, I = 81%). WBVT showed no changes in KES (SMD = 0.65, 95% CI: - 0.02 to 1.31, p = 0.06, I = 80%) or GS (SMD = 0.12, 95% CI: - 0.15 to 0.39, p = 0.38, I = 0%). TUG times were significantly improved with all exercise training modes (SMD = -0.66, 95% CI: - 0.94 to - 0.38, p < 0.00001, I = 60%). There were no changes in CS times with any of the exercise training modes (SMD = 0.11, 95% CI: - 0.36 to 0.57, p = 0.65, I = 87%).
CONCLUSIONS
In older people with sarcopenia, KES and GS can be improved by RT and MT, but not by WBVT. All three training modes improved TUG times, but not improved CS times.
Topics: Aged; Humans; Exercise; Muscle Strength; Physical Functional Performance; Randomized Controlled Trials as Topic; Resistance Training; Sarcopenia
PubMed: 34911483
DOI: 10.1186/s12877-021-02642-8 -
Journal of Cachexia, Sarcopenia and... Dec 2021Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still... (Review)
Review
BACKGROUND
Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.
METHODS
A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.
RESULTS
A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.
CONCLUSIONS
Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.
Topics: Aged; Animals; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Humans; Male; Mice; Prebiotics; Sarcopenia; Synbiotics
PubMed: 34523250
DOI: 10.1002/jcsm.12784 -
Ageing Research Reviews Jan 2022Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Physical frailty and sarcopenia show extensive clinical similarities. Whether biomarkers exist that are shared by the two conditions is presently unclear.
METHODS
We conducted a systematic review and meta-analysis of cross-sectional and longitudinal studies that investigated the association of frailty and/or sarcopenia with biomarkers as a primary or secondary outcome in adults aged 60 years and older. Only studies published in English that defined frailty using a validated scale and/or questionnaire and diagnosed sarcopenia according to the presence of muscle atrophy plus dynapenia or low physical function were included. Studies were identified from a systematic search of MEDLINE and SCOPUS databases from inception through August 2020. The quality of reporting of each study was assessed by using the Quality Assessment Tool for Observational Cohort, Cross-Sectional and Case-Control studies of the National Institute of Health. A meta-analysis was conducted when at least three studies investigated the same biomarker in both frailty and sarcopenia. Pooled effect size was calculated based on standard mean differences and random-effect models. Sensitivity analysis was performed based on age and the setting where the study was conducted.
RESULTS
Eighty studies (58 on frailty and 22 on sarcopenia) met the inclusion criteria and were included in the qualitative analysis. Studies on frailty included 33,160 community-dwellers, hospitalized, or institutionalized older adults (60-88 years) from 21 countries. Studies on sarcopenia involved 4904 community-living and institutionalized older adults (68-87.6 years) from 9 countries. Several metabolic, inflammatory, and hematologic markers were found to be shared between the two conditions. Albumin and hemoglobin were negatively associated with both frailty and sarcopenia. Interleukin 6 was associated with frailty and sarcopenia only in people aged < 75. Community-dwelling older adults with frailty and sarcopenia had higher levels of tumor necrosis factor alpha compared with their robust and non-sarcopenic counterparts.
CONCLUSIONS
A set of metabolic, hematologic, and inflammatory biomarkers was found to be shared by frailty and sarcopenia. These findings fill a knowledge gap in the quest of biomarkers for these conditions and provide a rationale for biomarker selection in studies on frailty and sarcopenia.
Topics: Aged; Biomarkers; Cross-Sectional Studies; Frail Elderly; Frailty; Humans; Independent Living; Middle Aged; Sarcopenia
PubMed: 34839041
DOI: 10.1016/j.arr.2021.101530 -
Critical Care (London, England) Jan 2023Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients.
METHODS
We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle-Ottawa Scale.
RESULTS
Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day -1.75% (95% CI -2.05, -1.45) of their rectus femoris thickness or -2.10% (95% CI -3.17, -1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%).
CONCLUSION
On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.
Topics: Adult; Humans; Critical Illness; Intensive Care Units; Muscular Atrophy; Muscle, Skeletal; Muscle Weakness
PubMed: 36597123
DOI: 10.1186/s13054-022-04253-0 -
Nutrition Reviews Jan 2021Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased risk of adverse outcomes such as falls, disability, and death. The... (Meta-Analysis)
Meta-Analysis
CONTEXT
Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased risk of adverse outcomes such as falls, disability, and death. The Belgian Society of Gerontology and Geriatrics has developed evidence-based guidelines for the prevention and treatment of sarcopenia. This umbrella review presents the results of the Working Group on Nutritional Interventions.
OBJECTIVE
The aim of this umbrella review was to provide an evidence-based overview of nutritional interventions targeting sarcopenia or at least 1 of the 3 sarcopenia criteria (ie, muscle mass, muscle strength, or physical performance) in persons aged ≥ 65 years.
DATA SOURCES
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, the PubMed and Web of Science databases were searched for systematic reviews and meta-analyses reporting the effect of nutritional supplementation on sarcopenia or muscle mass, strength, or physical performance.
DATA EXTRACTION
Two authors extracted data on the key characteristics of the reviews, including participants, treatment, and outcomes. Methodological quality of the reviews was assessed using the product A Measurement Tool to Assess Systematic Reviews. Three authors synthesized the extracted data and generated recommendations on the basis of an overall synthesis of the effects of each intervention. Quality of evidence was rated with the Grading of Recommendations Assessment, Development and Evaluation approach.
DATA ANALYSIS
A total of 15 systematic reviews were included. The following supplements were examined: proteins, essential amino acids, leucine, β-hydroxy-β-methylbutyrate, creatine, and multinutrient supplementation (with or without physical exercise). Because of both the low amount and the low to moderate quality of the reviews, the level of evidence supporting most recommendations was low to moderate.
CONCLUSIONS
Best evidence is available to recommend leucine, because it has a significant effect on muscle mass in elderly people with sarcopenia. Protein supplementation on top of resistance training is recommended to increase muscle mass and strength, in particular for obese persons and for ≥ 24 weeks. Effects on sarcopenia as a construct were not reported in the included reviews.
Topics: Aged; Aged, 80 and over; Amino Acids, Essential; Creatine; Dietary Supplements; Exercise; Humans; Leucine; Muscle Strength; Muscle, Skeletal; Physical Functional Performance; Sarcopenia; Valerates
PubMed: 32483625
DOI: 10.1093/nutrit/nuaa011 -
Osteoporosis International : a Journal... Jun 2017This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified.... (Review)
Review
UNLABELLED
This systematic review summarizes the effect of combined exercise and nutrition intervention on muscle mass and muscle function. A total of 37 RCTs were identified. Results indicate that physical exercise has a positive impact on muscle mass and muscle function in subjects aged 65 years and older. However, any interactive effect of dietary supplementation appears to be limited.
INTRODUCTION
In 2013, Denison et al. conducted a systematic review including 17 randomized controlled trials (RCTs) to explore the effect of combined exercise and nutrition intervention to improve muscle mass, muscle strength, or physical performance in older people. They concluded that further studies were needed to provide evidence upon which public health and clinical recommendations could be based. The purpose of the present work was to update the prior systematic review and include studies published up to October 2015.
METHODS
Using the electronic databases MEDLINE and EMBASE, we identified RCTs which assessed the combined effect of exercise training and nutritional supplementation on muscle strength, muscle mass, or physical performance in subjects aged 60 years and over. Study selection and data extraction were performed by two independent reviewers.
RESULTS
The search strategy identified 21 additional RCTs giving a total of 37 RCTs. Studies were heterogeneous in terms of protocols for physical exercise and dietary supplementation (proteins, essential amino acids, creatine, β-hydroxy-β-methylbuthyrate, vitamin D, multi-nutrients, or other). In 79% of the studies (27/34 RCTs), muscle mass increased with exercise but an additional effect of nutrition was only found in 8 RCTs (23.5%). Muscle strength increased in 82.8% of the studies (29/35 RCTs) following exercise intervention, and dietary supplementation showed additional benefits in only a small number of studies (8/35 RCTS, 22.8%). Finally, the majority of studies showed an increase of physical performance following exercise intervention (26/28 RCTs, 92.8%) but interaction with nutrition supplementation was only found in 14.3% of these studies (4/28 RCTs).
CONCLUSION
Physical exercise has a positive impact on muscle mass and muscle function in healthy subjects aged 60 years and older. The biggest effect of exercise intervention, of any type, has been seen on physical performance (gait speed, chair rising test, balance, SPPB test, etc.). We observed huge variations in regard to the dietary supplementation protocols. Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supplementation on muscle function appears limited.
Topics: Amino Acids, Essential; Creatine; Dietary Proteins; Dietary Supplements; Exercise; Exercise Therapy; Humans; Muscle Strength; Sarcopenia; Valerates; Vitamin D
PubMed: 28251287
DOI: 10.1007/s00198-017-3980-9 -
Journal of Cachexia, Sarcopenia and... Jun 2023Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia is an age-related disease and is often accompanied by other diseases. Now, many studies have shown that cardiovascular diseases (CVDs) may raise the incidence rate of sarcopenia. Therefore, the purpose of this study was to conduct a systematic review and meta-analysis to investigate the prevalence of sarcopenia in patients with CVDs compared with the general population, defined as relatively healthy non-hospitalized subjects. The databases of PubMed, Embase, Medline and Web of Science were searched for eligible studies published up to 12 November 2022. Two assessment tools were used to evaluate study quality and the risk of bias. Statistical analysis was conducted using STATA 14.0 and R Version 4.1.2. Thirty-eight out of the 89 629 articles retrieved were included in our review. The prevalence of sarcopenia ranged from 10.1% to 68.9% in patients with CVDs, and the pooled prevalence was 35% (95% confidence interval [95% CI]: 28-42%). The pooled prevalence of sarcopenia was 32% (95% CI: 23-41%) in patients with chronic heart failure (CHF), 61% (95% CI: 49-72%) in patients with acute decompensated heart failure (ADHF), 43% (95% CI: 2-85%) in patients with coronary artery disease, 30% (95% CI: 25-35%) in patients with cardiac arrhythmia (CA), 35% (95% CI: 10-59%) in patients with congenital heart disease and 12% (95% CI: 7-17%) in patients with unclassed CVDs. However, in the general population, the prevalence of sarcopenia varied from 2.9% to 28.6% and the pooled prevalence was 13% (95% CI: 9-17%), suggesting that the prevalence of sarcopenia in patients with CVDs was about twice compared with the general population. The prevalence of sarcopenia was significantly higher only in patients with ADHF, CHF and CA compared with the general population. There is a positive correlation between CVDs and sarcopenia. The prevalence of sarcopenia is higher in patients with CVDs than that in the general population. With global aging, sarcopenia has brought a heavy burden to individuals and society. Therefore, it is important to identify the populations with high-risk or probable sarcopenia in order to do an early intervention, such as exercise, to counteract or slow down the progress of sarcopenia.
Topics: Humans; Cardiovascular Diseases; Sarcopenia; Aging; Heart Failure
PubMed: 37002802
DOI: 10.1002/jcsm.13221 -
Journal of Cachexia, Sarcopenia and... Oct 2020Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria. This review... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia prevalence and its clinical impact are reportedly variable in chronic obstructive pulmonary disease (COPD) due partly to definition criteria. This review aimed to identify the criteria used to diagnose sarcopenia and the prevalence and impact of sarcopenia on health outcomes in people with COPD. This review was registered in PROSPERO (CRD42018092576). Five electronic databases were searched to August 2018 to identify studies related to sarcopenia and COPD. Study quality was assessed using validated instruments matched to study designs. Sarcopenia prevalence was determined using authors' definitions. Comparisons were made between people who did and did not have sarcopenia for pulmonary function, exercise capacity, quality of life, muscle strength, gait speed, physical activity levels, inflammation/oxidative stress, and mortality. Twenty-three studies (70% cross-sectional) from Europe (10), Asia (9), and North and South America (4) involving 9637 participants aged ≥40 years were included (69.5% men). Sarcopenia criteria were typically concordant with recommendations of hEuropean and Asian consensus bodies. Overall sarcopenia prevalence varied from 15.5% [95% confidence interval (CI) 11.8-19.1; combined muscle mass, strength, and/or physical performance criteria] to 34% (95%CI 20.6-47.3; muscle mass criteria alone) (P = 0.009 between subgroups) and was greater in people with more severe [37.6% (95%CI 24.8-50.4)] versus less severe [19.1% (95%CI 10.2-28.0)] lung disease (P = 0.020), but similar between men [41.0% (95%CI 26.2-55.9%)] and women [31.9% (95%CI 7.0-56.8%)] (P = 0.538). People with sarcopenia had lower predicted forced expiratory volume in the first second (mean difference -7.1%; 95%CI -9.0 to -5.1%) and poorer exercise tolerance (standardized mean difference -0.8; 95%CI -1.4 to -0.2) and quality of life (standardized mean difference 0.26; 95%CI 0.2-0.4) compared with those who did not (P < 0.001 for all). No clear relationship was observed between sarcopenia and inflammatory or oxidative stress biomarkers. Incident mortality was unreported in the literature. Sarcopenia is prevalent in a significant proportion of people with COPD and negatively impacts upon important clinical outcomes. Opportunities exist to optimize its early detection and management and to evaluate its impact on mortality in this patient group.
Topics: Cross-Sectional Studies; Female; Hand Strength; Humans; Male; Prevalence; Pulmonary Disease, Chronic Obstructive; Quality of Life; Sarcopenia
PubMed: 32862514
DOI: 10.1002/jcsm.12600 -
Age and Ageing Nov 2014to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus... (Review)
Review
OBJECTIVE
to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).
METHODS
PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.
RESULTS
prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.
CONCLUSION
prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.
Topics: Age Factors; Aged; Aged, 80 and over; Aging; Dietary Supplements; Exercise Therapy; Female; Geriatric Assessment; Humans; Male; Middle Aged; Motor Activity; Muscle Strength; Muscle, Skeletal; Nutrition Assessment; Nutritional Status; Prevalence; Sarcopenia; Treatment Outcome
PubMed: 25241753
DOI: 10.1093/ageing/afu115