1016/22, 11:21 AM hilpsewerd york ac.ukiprosparalcisplay_record.php?RacordiO=357116 NIHR | Aeielite PROSPERO fetes International prospective register of systematic reviews Clinical trials for muscle quality in older adults: a systematic review and meta- analysis ‘Sho Hatanaka, Hiroyuki Oka, Ko Matsudaira, Yutaka Watanabe, Michiyo Kawamura, Rei Otsuka, Kaori Kinoshita, Kanae Furuya, Jiagi LU, Yosuke Osuka, Takahisa Ohta To enable PROSPERO to focus on COVID-19 submissions, this registration record has undergone basic automated checks for eligibility and is published exactly as submitted. PROSPERO has never provided peer review, and usual checking by the PROSPERO team does not endorse content. Therefore, automatically published records should be treated as any other PROSPERO registration. Further detail is provided here. Citation Sho Hatanaka, Hiroyuki Oka, Ko Matsudaira, Yutaka Watanabe, Michiyo Kawamura, Rei Otsuka, Kaori Kinoshita, Kanae Furuya, Jiagi Li, Yosuke Osuka, Takahisa Ohta. Clinical trials for muscle quality in older adults: a systematic review and meta-analysis. PROSPERO 2022 CRD42022357116 Available from’ https:/www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022357 116 Review question 1. What type of intervention was provided? 2. As compared to the control program, how do the intervention programs affect muscle quality? Searches Sources: PubMed, Cochrane Library, Web of Science, Ichushi Search dates: 6 September 2022 Language: English Publication period: From inception to August 2022 Types of study to be included We will include randomized controlled trials to assess the effects of the interventions. Condition or domain being studied Effects of various interventions on morphological and neuromuscular muscle quality in older adults. Participants/population Inclusion: Older men and/or women aged 260 years, regardless of health conditions (e.g., healthy, hospitalized, sarcopenic). Exclusion: Population that does not include adults aged 260 years at all. Studies comparing older and younger adults. Intervention(s), exposure(s) Inclusion: Any intervention (.g., exercise, nutrition, medication) or combination of interventions for = 8 weeks, 451016/22, 11:21 AM hilpsewerd york ac.ukiprosparalcisplay_record.php?RacordiO=357116 Exclusion: Within-subject studies (e.g., right leg assigned to intervention with the left leg as control). Studies in which acute effects were observed. Comparator(s)/control Inclusion: Group randomized to no intervention, placebo, or program with the lowest impact on muscle quality (e.g., stretching). Exclusion: None. Main outcome(s) Changes in morphological (e.g., muscle fat infitration, cellular membrane integrity) and neuromuscular (eg., specific tension) muscle quality from baseline to follow-up(s). Morphological muscle quality should be measured by ultrasound, computed tomography, magnetic resonance imaging, dual-energy X-ray absorptiometry, or bioelectrical impedance analysis. Neuromuscular muscle quality should be expressed as muscle strength or function measurement (e.g., peak power test) divided by muscle size measurement (e.g., muscle thickness, cross-sectional area, Volume) from ultrasound, computed tomography, magnetic resonance imaging, dual-energy X-ray absorptiometry, or bioelectrical impedance analysis. Measures of effect Standardized mean difference. Additional outcome(s) Adverse events. Data extraction (selection and coding) Study selection: All studies included in the search will be screened after removing duplicates. Primary screening will be conducted on titles and abstracts to determine whether the study is a randomized controlled trial study that included participants aged 260 years. Studies that cannot be determined will be retained for secondary screening, Primary screening will be conducted by seven reviewers. Two groups (three reviewers each) will judge each study separately. Any disagreement will be resolved by the remaining reviewer. These decisions will be managed using a software tool (Rayan; https:/www.rayyan ai). Secondary screening will be performed for full-text articles. Studies with duplicate data will be excluded. When the full-text is not available, the authors will be contacted and the article will be excluded if it cannot be confirmed. Studies with poorly defined or measured muscle quality will also excluded. Three reviewers will be assigned for secondary screening, Two reviewers will screen separately. Any disagreement will be resolved by the third reviewer. Data extraction: Study characteristics and information on interventions and outcomes will be extracted and accumulated Study characteristics will include publication information, participant characteristics, and the main outcome of the study itself. Information about the intervention will include components of the intervention (e.g., protein supplementation), quantitative information (e.g., nutritional intake), qualitative information (e.g., instructional content), program delivery, and compliance (e.g., attendance rates), Information about outcomes will be the index of muscle quality, the method of measuring muscle quality, the direction and significance of the results, the mean and standard deviation before and after the intervention duration, and adverse events. IFunreported data are needed, we will contact the authors for confirmation. Items that cannot be confirmed will be treated as missing. Extraction will be performed separately by two reviewers, and disagreements will be resolved by consensus between all reviewers. The extracted data will be recorded in an Excel spreadsheet Risk of bias (quality) assessment hitpsiwwncrd.york.2c.ukiprosperoldsplay_record.ph?RecordlO=357116ore, 14:21 AM hitps:ivwwerd york a.uk/prospero/sisplay_record php?RecordID=357116 A revised version of the Cochrane risk-of-bias tool for randomized trials will be used to assess the risk of bias at the outcome level. The tool consists of the overall risk of bias and five domains to assess the characteristics of the studies: randomization process, deviations from intended interventions, missing outcome data, outcome measurement, and selection of the reported result. Overall risk of bias is expressed as “low risk of bias” (the study is judged to be at low risk of bias for all domains), “some concerns" (The study is judged to raise some concems in at least one domain, but not to be at high risk of bias for any domain), or “high risk of bias’(The study is judged to be at high risk of bias in at least one domain, or the study is judged to have some concems for multiple domains in a way that substantially lowers confidence in the result). The results for the overall and each domain will be reported with the synthesized results. In total, three reviewers will be involved in the quality assessment. Two reviewers will independently assess the quality of the studies, Disagreements between reviewers will be resolved by a thitd reviewer. Strategy for data synthesis A table summarizing characteristics about studies, subjects and interventions will be created. In addition, quantitative variables and effect size (Hedges' g) of the interventions will be extracted and calculated for analysis. A random-effects meta-analysis will be performed with the effect size of muscle quality as the dependent variable when sufficient data are available, Statistical heterogeneity of the dataset will be determined using Cochran's Q test (P-value threshold:0.1) and I? (>50%). The inclusion of studies with some concer or a high risk of bias will be determined using sensitivity analysis. Publication bias will be assessed using funnel plots and Egger's test (p-value threshold: 0.1). Analysis of subgroups or subsets When sufficient extracted data have been gathered for subgroup analysis, it should be based on the following characteristics: sex, health status, presence or absence of weight loss, and nature of the intervention. In addition, a meta-togression analysis will be performed with effect size as the dependent variable and the heterogeneity factor as the independent variable. Contact details for further information Sho Hatanaka hatanaka@tmig.or.p Organisational affiliation of the review Tokyo Metropolitan Institute of Gerontology hittps://www.tmig.or jp/index. htm! Review team members and their organisational affiliations Dr Sho Hatanaka, Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology Dr Hiroyuki Oka. Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, the University of Tokyo Hospital Dr Ko Matsudaira, Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, the University of Tokyo Hospital Dr Yutaka Watanabe. Gerodontology, Department of Oral Health Science, Faculty of Dental Medicine, Hokkaido University Ms Michiyo Kawamura, Medical Sciences Group, Research Support Division, Hokkaido University Library Dr Rei Otsuka. Department of Epidemiology of Aging, Center for Gerontology and Social Science, Research Institute, National Center for Geriatrics and Gerontology Dr Kaori Kinoshita. Department of Frailty Research, Center for Gerontology and Social Science, Research Institute, National Center for Geriatrics and Gerontology Dr Kanae Furuya. Department of Epidemiology of Aging, Center for Gerontology and Social Science, Research Institute, National Center for Geriatrics and Gerontology Dr Jiagi Li. Department of Frailty Research, Center for Gerontology and Social Science, Research Institute,1016/22, 11:21 AM hilpsewerd york ac.ukiprosparalcisplay_record.php?RacordiO=357116 National Center for Geriatrics and Gerontology Dr Yosuke Osuka, Research Team for Promoting Independence and Mental Health, Tokyo Metropolitan Institute of Gerontology Dr Takahisa Ohta. Integrated Research Initiative for Living Well with Dementia, Tokyo Metropolitan Institute of Gerontology ‘Type and method of review Intervention, Meta-analysis, Systematic review Anticipated or actual start date 31 August 2022 (01 March 2023, Funding sources/sponsors Japan Agency for Medical Research and Development Grant number(s) State the funder, grant or award number and the date of award Ref 22dk0110048h0001 Conflicts of interest HO has applied for a patent in Japan for a muscle diagnostic program and a method of analyzing ultrasound images (application No: Patent Application 2019-027884). Yes Language English Country Japan Stage of review Review Ongoing Subject index terms status Subject indexing assigned by CRD ‘Subject index terms Aged; Humans; Muscle Strength; Muscle, Skeletal Date of registration in PROSPERO ‘11 September 2022 Date of first submission 31 August 2022 Stage of review at time of this submission The review has not started 461016/22, 11:21 AM hilpsewerd york ac.ukiprosparalcisplay_record.php?RacordiO=357116 Stage Started Completed Preliminary searches No No Piloting of the study selection process No No Formal screening of search results against eligibility criteria No No Data extraction No No Risk of bias (qu ) assessment No No Data analysis, No No The record owner confirms that the information they have supplied for this submission is accurate and complete and they understand that deliberate provision of inaccurate information or omission of data may be construed as scientific misconduct. The record owner confirms that they will update the status of the review when it is completed and will add publication details in due course. Versions 11 September 2022 14 September 2022 PROSPERO ‘This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO, The registrant confirms that the information supplied for this submission is acourate and complete. CRD bears no responsibilty or ability for the content ofthis registration record, any associated files or external websites. hitpsiwwn.crd.york.2c.ukiprosperoldsplay_record.php?RecordlO=357116