scholarly journals Effectiveness and safety of glibenclamide for stroke: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e043585
Author(s):  
Lihong Wen ◽  
Bin Huang ◽  
Rong Tu ◽  
Kunzhen Wan ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Random Effect ◽  
Indirect Evidence ◽  
Fixed Effect Model ◽  
Risk Of Bias ◽  
Assessment Instrument ◽  
Cochrane Library ◽  
Published Data ◽  
China National Knowledge Infrastructure

IntroductionDespite the continuous improvement in modern medical treatment, stroke is still a leading cause of death and disability worldwide. How to effectively improve the survival rate and reduce disability in patients who had a stroke has become the focus of many investigations. Recent findings concerning the benefits of glibenclamide as a neuroprotective drug have initiated a new area for prospective studies on the effects of sulfonylureas. Given the high mortality and disability associated with stroke, it is essential to weigh the benefits of neuroprotective drugs against their safety. Therefore, the objective of the current study is to conduct a systematic review using meta-analysis to assess the benefits and safety of glibenclamide as a neuroprotective drug.Methods and analysisThis study will analyse randomised clinical trials (RCTs) and observational studies published up to 31 December 2020 and include direct or indirect evidence. Studies will be retrieved by searching PubMed, EMBASE, Web of Science, the Cochrane Library and China National Knowledge Infrastructure (CNKI) and WanFang Databases. The outcomes of this study will be mortality, scores from the Modified Rankin Scale and the occurrence of hypoglycaemic events. The risk of bias will be assessed using the Cochrane risk of bias assessment instrument for RCTs. A random-effect/fixed-effect model will be used to summarise the estimates of the mean difference/risk ratio using a 95% CI.Ethics and disseminationThis meta-analysis is a secondary research project, which is based on previously published data. Therefore, ethical approval and informed consent were not required for this meta-analysis. The results of this study will be submitted to a peer-reviewed journal for publication.PROSPERO registration numberCRD42020144674.

scholarly journals Prevalence and factors for food allergy in different populations from different regions: A protocol for a systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261092
Author(s):  
Hua Feng ◽  
Xiujuan Xiong ◽  
Zhuo Chen ◽  
Qunying Xu ◽  
Zhongwei Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Food Allergy ◽  
Publication Bias ◽  
Meta Analysis ◽  
Fixed Effect Model ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Factors Associated ◽  
Different Populations ◽  
Funnel Plots

Background To determine the prevalence of food allergy (FA) and factors associated with these occurrences in different populations from different regions. Materials and methods The literature search will be conducted via Pubmed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Vip and Wanfang databases. Ratio rate (RR), odds ratio (OR) and 95% confidence intervals (CIs) will be adopted to evaluate prevalence and factors for FA in different populations from different regions. When the heterogeneity is small (I2<50%), the fixed effect model will be analyzed, otherwise, random effects model analysis will be performed. When the heterogeneity is large (I2≥50%), Meta regression will be used to explore the sources of inter-study heterogeneity. When the heterogeneity is large (I2≥50%) and the results are statistically significant (P<0.05), subgroup analysis will be analyzed based on age, gender, race/region, literature quality and other factors. Funnel plots will be used to reflect reporting bias and the Begg’s test will be used to test the symmetry of the funnel plots. When publication bias occurs, “cut-and-fill” method will be adopted to adjust publication bias. And sensitivity analysis will be performed for all outcome indicators. Discussion This meta-analysis will evaluate the prevalence of FA and factors associated with these occurrences in different populations from different regions on the basis of existing evidences. Our study may be crucial to analyze similarities and differences regarding FA between different individuals from diverse regions and eventually define preventive or diagnostic approaches specifically tailored to certain populations and regions. Systematic review registration OSF registration number: 10.17605/OSF.IO/VQXU9

scholarly journals Immunonutrition for traumatic brain injury in children and adolescents: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e037014
Author(s):  
Rong Peng ◽  
Hailong Li ◽  
Lijun Yang ◽  
Xinwei Chen ◽  
Linan Zeng ◽  
...  
Keyword(s):  
Systematic Review ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Evaluation Method ◽  
Clinical Decision Making ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Published Data ◽  
Pool Data

IntroductionTraumatic brain injury (TBI) is the leading cause of paediatric trauma death and disability worldwide. The ‘Guidelines for the Management of Severe Traumatic Brain Injury (Fourth Edition)’ recommend that nutritional goals should be achieved within 5–7 days of injury. Immune-enhancing nutrition or immunonutrition, referring to the addition of specialised nutrients, including glutamine, alanine, omega-3 fatty acids and nucleotides, to standard nutrition formulas, may improve surgical outcomes in the perioperative period. However, the role of immune-enhancing nutritional supplements for patients with paediatric TBI remains unclear. We will conduct a systematic review to determine the efficacy and safety of immunonutrition for patients with paediatric TBI and provide evidence for clinical decision-making.Methods and analysisStudies reporting immune-enhancing nutrition treatments for patients with paediatric TBI will be included. Outcomes of interest include the length of hospital stay, wound infections, all-cause mortality, non-wound infection, including pneumonia, urinary tract infection and bacteraemia, and the reports adverse events. Duration of follow-up has no restriction. Primary studies consisting of randomised controlled trials (RCTs) and non-RCTs will be eligible for this review, and only studies published in English will be included. We will search the Medline, Embase and Cochrane Library databases from their inception dates to January 2020. We will also search clinicaltrials.gov and the WHO International Clinical Trials Registry Platform for additional information. Two reviewers will independently select studies and extract data. Risk-of-bias will be assessed with tools based on the Cochrane risk-of-bias criteria and Newcastle-Ottawa Quality Assessment Scale. A meta-analysis will be used to pool data when there are sufficient studies with homogeneity. Heterogeneity of the estimates across studies will be assessed; if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method will be applied to assess the level of evidence obtained from this systematic review.Ethics and disseminationThe proposed systematic review and meta-analysis will be based on published data, and thus ethical approval is not required. The results of this review will be published.PROSPERO registration numberCRD42020154814.

scholarly journals Effect of music intervention on mental health in patients with diabetes mellitus: protocol for a systematic review and meta-analysis of randomizsed controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e036268
Author(s):  
Lin-yue Zhou ◽  
Yuan Zhang ◽  
Yuan Tian ◽  
Xiaoxu Fu ◽  
Li-zhen Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mental Disorders ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Published Data ◽  
Controlled Trials ◽  
Music Intervention ◽  
Patients With Diabetes

IntroductionAbout 463 million adults aged 20–79 have diabetes globally. Mental disorders often exist in patients with diabetes as comorbidities, which can lead to aggravation of the diseases, increased difficulties in treatment, as well as elevated mortality rates. Music intervention has been applied in the treatment of comorbidities for 12 years now, but there are still no recommendations due to the lack of evidence. Thus, a meta-analysis is necessary to evaluate the effect of music intervention in treating mental disorders of patients with diabetes.Methods and analysisWe will search the following nine online electronic databases from their inception until March 2020: PubMed, Web of Science, Embase, EBSCO, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database (VIP) and Chinese Biomedical and Medical Database. We also plan to search other relevant resources, including grey literature and the reference lists of relevant publications. Only randomised controlled trials of music intervention to treat depression or anxiety in patients with diabetes will be involved. The primary outcomes include the depression score and anxiety score measured on certain scales, and the secondary outcome is safety. Data extraction will be independently implemented by two researchers. The risk of bias will be evaluated through the Cochrane Collaboration’s Risk of Bias tool. Eventually, all the data will be analysed via the Review Manager V.5.3 software.Ethics and disseminationThis meta-analysis will provide information about applying music intervention to treat depression or anxiety in patients with diabetes. No ethical approval is required because this meta-analysis is based on published data. The results of this systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019146439

scholarly journals Comparison of ventilatory modes to facilitate liberation from mechanical ventilation: protocol for a systematic review and network meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030407 ◽  
Author(s):  
Kimberley A Lewis ◽  
Dipayan Chaudhuri ◽  
Gordon Guyatt ◽  
Karen E A Burns ◽  
Karen Bosma ◽  
...  
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Meta Analysis ◽  
Invasive Mechanical Ventilation ◽  
Random Effect ◽  
Risk Of Bias ◽  
Evaluation Methodology ◽  
Cochrane Library ◽  
Alternative Mode ◽  
Mechanical Ventilation Duration

IntroductionTimely liberation from invasive mechanical ventilation is important to reduce the risk of ventilator-associated complications. Once a patient is deemed ready to tolerate a mode of partial ventilator assist, clinicians can use one of multiple ventilatory modes. Despite multiple trials, controversy regarding the optimal ventilator mode to facilitate liberation remains. Herein, we report the protocol for a systematic review and network meta-analysis comparing modes of ventilation to facilitate the liberation of a patient from invasive mechanical ventilation.Methods and analysisWe will search MEDLINE, EMBASE, PubMed, the Cochrane Library from inception to April 2019 for randomised trials that report on critically ill adults who have undergone invasive mechanical ventilation for at least 24 hours and have received any mode of assisted invasive mechanical ventilation compared with an alternative mode of assisted ventilation. Outcomes of interest will include: mortality, weaning success, weaning duration, duration of mechanical ventilation, duration of stay in the acute care setting and adverse events. Two reviewers will independently screen in two stages, first titles and abstracts, and then full texts, to identify eligible studies. Independently and in duplicate, two investigators will extract all data, and assess risk of bias in all eligible studies using the Modified Cochrane Risk of Bias tool. Reviewers will resolve disagreement by discussion and consultation with a third reviewer as necessary. Using a frequentist framework, we will perform random-effect network meta-analysis, including all ventilator modes in the same model. We will calculate direct and indirect estimates of treatment effect using a node-splitting procedure and report effect estimates using OR and 95% CI. We will assess certainty in effect estimates using Grading of Recommendations Assessment, Development and Evaluation methodology.Ethics and disseminationResearch ethics board approval is not necessary. The results will be disseminated through publication in a peer-reviewed journals.PROSPERO registration numberCRD42019137786

scholarly journals Integrated management of type 2 diabetes and gestational diabetes within multi-morbidity conditions in Africa: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. e023684
Author(s):  
Jean Claude Mutabazi ◽  
Mahmoud M Werfalli ◽  
Angeli Rawat ◽  
Ezekiel Musa ◽  
Shane A Norris ◽  
...  
Keyword(s):  
Systematic Review ◽  
Type 2 Diabetes ◽  
Gestational Diabetes ◽  
Integrated Management ◽  
Meta Analysis ◽  
Cochrane Collaboration ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Published Data

IntroductionMulti-morbidity, defined as the co-existence of more than one chronic condition in one person, has been increasing due to comorbid non-communicable and infectious chronic diseases (CNCICDs). Type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) incidences within the CNCICDs conditions are increasing and overwhelming already weak and under-resourced healthcare systems in Africa. There is then an urgent need for the integrated management of CNCICDs. We aim to review the integrated management of T2D and GDM within multi-morbidity conditions in Africa.MethodsStudies that have assessed the integrated management of T2D and GDM within multi-morbidity conditions in Africa will be considered based on the Population, Intervention, Comparator and Outcome method: population (adult diagnosed with T2D and GDM, who also have other diseases, non-communicable diseases (NCDs) and infectious, in public primary and secondary healthcare facilities in Africa); Intervention (integrated management of T2D and GDM, also suffering from other diseases in Africa), Comparator (Unintegrated management of T2D and GDM in Africa) and Outcomes (integrated management of T2D and GDM in Africa). The following databases Cochrane Library, MEDLINE, PubMed and SCOPUS, the WHO International Clinical Trials Registry Platform, among others will be searched. Two reviewers (JCM and MW) will independently screen, select eligible studies and extract data. Discrepancies will be resolved by consensus or by a discussion with the third author (AR). Quality of included studies will be assessed using both the newly developed tool, ‘the Cochrane Collaboration Risk of Bias Tool’ and ‘Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I)”. A narrative synthesis of extracted data and meta-analysis, if necessary will be conducted and then reported according to the preferred reporting items for systematic review and meta-analysis.Ethics consideration and disseminationBy only using the published data, there is no ethics approval required for this study. This systematic review will be included in JCM’s PhD thesis and its findings will also be disseminated through peer-reviewed publication and conference presentation.PROSPERO registration numberCRD42016046630.

scholarly journals Non-pharmacological interventions for treating sexual dysfunction in postpartum women: a systematic review protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e028660
Author(s):  
Michelly Nóbrega Monteiro ◽  
Kleyton Santos Medeiros ◽  
Iaponira Vidal ◽  
Ivete Matias ◽  
Ricardo Ney Cobucci ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sexual Dysfunction ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Sexual Problems ◽  
Cochrane Library ◽  
Published Data ◽  
Postpartum Women ◽  
Cochrane Central Register ◽  
Pharmacological Interventions

IntroductionSexual dysfunction in the postpartum period is a very common and relevant clinical problem, which has a significant adverse impact on the health of women. We aim to analyse the efficacy and safety of non-pharmacological interventions for treating sexual dysfunction in postpartum women. Our review aims to provide accurate data for effective policy-making and improve our understanding of the treatment of postpartum sexual dysfunction with non-pharmacological therapies.Methods and analysisThe Cochrane Central Register of Controlled Trials in The Cochrane Library, clinicaltrials.gov, Medline/PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), LILACS (Literatura Latino-americana e do Caribe em Ciências da Saúde) and Embase will be used to search for articles dated from database inception to July 2019. Randomised controlled clinical trials and large prospective cohorts with control groups using non-pharmacological treatments for sexual dysfunction in postpartum women will be included. Sexual problems are directly linked to sexual dysfunction; thus, the primary outcome will be the absolute number or percentage of sexual issues in each treatment group. The secondary outcomes will be assessed by decreased sexual problems, such as lack of lubrication, decreased libido and difficulty reaching orgasm. Three reviewers will independently select trials and extract data from the original publications. The citations will be screened independently by reviewers in duplicate. The risk of bias of the included studies will be assessed according to the Cochrane risk of bias tool. Data synthesis will be performed using Review Manager (RevMan) software V.5.2.3. In the event that a meta-analysis is possible, we will assess the heterogeneity across the studies by computing the I2statistic.Ethics and disseminationAs the design of this study includes a review of published data, the need to obtain ethical approval was waived by our institutional review committee. We intend to publish the findings of this systematic review in a peer-reviewed journal.PROSPERO registration numberCRD42018103077.

scholarly journals Is acupuncture effective for knee osteoarthritis? A protocol for a systematic review and meta-analysis

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e052270
Author(s):  
Chuan-Yang Liu ◽  
Jian-Feng Tu ◽  
Myeong Soo Lee ◽  
Ling-Yu Qi ◽  
Fang-Ting Yu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Knee Osteoarthritis ◽  
Evidence Synthesis ◽  
Meta Analysis ◽  
Demographic Data ◽  
Risk Of Bias ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
China National Knowledge Infrastructure ◽  
Best Evidence Synthesis

IntroductionKnee osteoarthritis (KOA) is one of the leading causes of disability. The effectiveness of acupuncture for treating KOA remains controversial. This protocol describes the method of a systematic review and meta-analysis evaluating the effectiveness and safety of acupuncture for treating KOA.Methods and analysisFour English databases (PubMed, Embase, Cochrane Library databases and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Database for Chinese Technical Periodicals, and Wanfang) will be searched from the database inception to 1 September 2021. All randomised controlled trials related to acupuncture for KOA will be included. Extracted data will include publication details, basic information, demographic data, intervention details and patient outcomes. The primary outcome will be pain intensity. Risk of bias will be assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Article selection, data extraction and risk of bias assessment will be performed in duplicate by two independent reviewers. If the meta-analysis is precluded, we will conduct a descriptive synthesis using a best-evidence synthesis approach. The strength of recommendations and quality of evidence will be assessed using the Grading of Recommendations Assessment Development and Evaluation working group methodology.Ethics and disseminationEthics approval is not required because individual patient data are not included. This protocol was registered in the international Prospective Register of Systematic Reviews on 25 February 2021. The systematic review and meta-analysis will be submitted for publication in a peer-reviewed journal. The findings will also be disseminated through conference presentations.Trial registration numberCRD42021232177.

scholarly journals Effectiveness of non-pharmacological interventions for reducing postpartum fatigue: a systematic review protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e051136
Author(s):  
Jialu Qian ◽  
Shiwen Sun ◽  
Lu Liu ◽  
Xiaoyan Yu
Keyword(s):  
Systematic Review ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Published Data ◽  
Controlled Trials ◽  
Pharmacological Interventions ◽  
Randomised Controlled ◽  
Postpartum Fatigue

IntroductionPostpartum fatigue is a common symptom among new mothers after their pregnancy. It has a considerable negative impact on women’s functional and mental status as well as the development of babies. Identifying effective interventions to prevent or reduce postpartum fatigue is meaningful to improve the quality of life and avoid adverse outcomes of this vulnerable population. This systematic review aims to synthesise non-pharmacological evidence and evaluate the effectiveness of interventions for reducing postpartum fatigue among puerperas.Methods and analysisThis review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will systematically search the Cochrane Library, PubMed, Embase, Web of Science, PsycINFO, CINAHL and ProQuest databases to identify clinical trials implementing non-pharmacological interventions conducted during 0–78 weeks postpartum for fatigue reduction. An additional search of OpenGrey will be conducted to identify grey literature. The search will be performed on 30 March 2021 without restrictions on time and language. Two independent reviewers will be responsible for study selection, data extraction and study quality assessment. The Cochrane risk-of-bias tool will be adopted to evaluate the risk biases of the included randomised controlled trials, and the Risk of Bias in Non-randomised Studies of Interventions will be applied to evaluate non-randomised controlled trials. Any disagreements will be referred to a third reviewer to reach a consensus. Findings will be qualitatively synthesised, and a meta-analysis will be conducted for the statistical combination if outcome data are sufficient and available.Ethics and disseminationThis systematic review will not involve the collection of primary data and will be based on published data. Therefore, ethics approval is not required. The final findings will be disseminated through peer-reviewed journals and academic conferences.PROSPERO registration numberCRD42021234869

scholarly journals Effectiveness and feasibility of telerehabilitation in patients with COVID-19: a protocol for a systematic review and meta-analysis

BMJ Open ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. e058932
Author(s):  
Abubeker Alebachew Seid ◽  
Setognal Birara Aychiluhm ◽  
Ahmed Adem Mohammed
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Mean Difference ◽  
Cochrane Library ◽  
P Value ◽  
Published Data ◽  
Respiratory Rehabilitation

IntroductionRespiratory rehabilitation is the use of exercise, education, and behavioural interventions to alleviate symptoms and improve quality of life. Recent studies highlight that respiratory rehabilitation is effective and safe for patients with COVID-19. We aim to evaluate the effectiveness and feasibility of respiratory telerehabilitation on patients infected with COVID-19 by conducting a systematic review and meta-analysis.Methods and analysisPubMed, Web of Science, Science Direct, Physiotherapy Evidence Database, Google Scholar and Cochrane Library databases will be searched from inception to the end of November 2021. Randomised controlled trials investigating the effectiveness of telerehabilitation in the management of COVID-19 will be included. The primary outcomes will be functional capacity, cardiopulmonary exercise tests and quality of life. Secondary outcomes will include anxiety/depression level, sleep quality, mortality rate, completion rate, reason for withdrawal, adverse events, service satisfaction, cost-effectiveness and other potential factors. Two reviewers will independently screen and extract data and perform quality assessment of included studies. The Cochrane risk of bias tool will be used to assess risk of bias. Review Manager V.5.4 (Cochrane Collaboration) software will be used for statistical analysis. Heterogeneity will be analysed using I² statistics. Mean difference or standardised mean difference with 95% CI and p value will be used to calculate treatment effect for outcome variables.Ethics and disseminationEthical approval is not required because this systematic review and meta-analysis is based on previously published data. Final result will be published in peer-reviewed journal and presented at relevant conferences and events.PROSPERO registration numberCRD42021287975.

scholarly journals Effectiveness of Nutritional Education for Obese Older Adults With Frailty: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 401-401
Author(s):  
Yue-Heng Yin ◽  
Liu Yat Justina
Keyword(s):  
Systematic Review ◽  
Physical Function ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Well Being ◽  
Risk Of Bias ◽  
Cochrane Library ◽  
Nutritional Education ◽  
Hand Search ◽  
Education Interventions

Abstract Obesity has been shown to intensify the decline of physical function and lead to frailty. Nutrition is an important method in managing obesity and frailty, while seldom reviews have ever explored the effects of nutritional education interventions. We conducted a systematic review (PROSPERO: CRD42019142403) to explore the effectiveness of nutritional education interventions in managing body composition and physio-psychosocial parameters related to frailty. Randomized controlled trials and quasi-experimental studies were searched in CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, PubMed and Scopus from 2001 to 2019. Hand search for the reference lists of included papers was conducted as well. We assessed the quality of included studies by Cochrane risk of bias tool. Meta-analyses and narrative synthesis were used to analyse the data. Two studies with low risk of bias were screened from 180 articles, which involved 177 older people with an average age of 69.69±4.08 years old. The results showed that nutritional education was significantly effective in reducing body weight and fat mass than exercises, and it was beneficial to enhancing physical function and psychosocial well-being. But the effects of nutritional education in increasing muscle strength were not better than exercises. The combined effects of nutritional education and exercises were superior than either exercises or nutritional education interventions solely in preventing the loss of lean mass and bone marrow density, and in improving physical function. Due to limited numbers of relevant studies, the strong evidence of effectiveness of nutritional education interventions on reversing frailty is still lacking.

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