A Systematic Review and Meta-analysis to Determine the Effect of Oral Anticoagulants on Incidence of Dementia in Patients with Atrial Fibrillation

Aims: To assess the effect of oral anticoagulant (OAC) administration on incidence of dementia in patients with atrial fibrillation (AF) with Systematic review and meta-analysis in according with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols. Methods: We systematically searched the electronic databases including Pubmed, Embase, Cochrane library, and ClinicalTrails.gov for relevant articles. The primary outcome was the incidence of dementia. The adjusted risk ratio (RR), odds ratio, or hazard ratio were extracted and pooled by the random-effects models. Subgroup analysis was performed according to the setting observational window. Risk of bias was assessed using the Newcastle-Ottawa Scale, while publication bias was assessed by the Begg’s and Egger’s tests. Results: Nine studies included in this review (2 prospective and 7 retrospective observational studies, including 613,920 patients). The results presented the significant association between OAC therapy and the reduced risk of dementia compared with no treatment (RR [95%CI] =0.72 [0.60, 0.86], I2=97.2%; P =0.000). In the subgroup analysis, the pooled RR became statistically non-significant (including four studies, RR [95%CI] =0.75 [0.51, 1.10], I2=98.8%; P =0.000). There is no significant risk of bias and publication bias. Conclusions: This study indicated the protective effect of OAC therapy for dementia in patients with AF. However, the results are limited because of high heterogeneity, inconsistent direction of effect in subgroup analysis. Further prospective well-designed study is needed with longer follow-up duration in younger patients.

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Subclinical thyroid dysfunction and incident atrial fibrillation - a systematic review and meta-analysis

EP Europace ◽

10.1093/europace/euab116.153 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

H Singh ◽

MZ Shahid ◽

SL Harrison ◽

DA Lane ◽

GYH Lip ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Subgroup Analysis ◽

Subclinical Hypothyroidism ◽

Thyroid Dysfunction ◽

Meta Analysis ◽

Risk Of Bias ◽

Subclinical Hyperthyroidism ◽

Quality Of Evidence

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): This project was supported by the MRes programme in the Institute of Life Course and Medical Sciences at The University of Liverpool. Thyroid hormones can act directly and indirectly on the cardiovascular system and studies have demonstrated associations between overt and subclinical thyroid dysfunction and adverse cardiovascular outcomes including heart failure, myocardial infarction, and coronary heart disease. The aim of this study was to assess the association between subclinical thyroid dysfunction and atrial fibrillation (AF). The protocol was registered on PROSPERO (CRD42020221565). MEDLINE and Scopus were searched from inception to 13th November 2020 for studies investigating subclinical thyroid dysfunction and incident AF. Risk of bias was assessed using the Risk of Bias Assessment Tool (RoBANS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool. Subgroup analysis was performed for post-operative and non-post-operative AF. 5413 records were identified. Nine cohort studies were suitable for inclusion in the systematic review, of which seven studies were included in the meta-analysis. The meta-analysis comprised 595,058 patients. Subclinical hyperthyroidism was associated with a 99% increase in the risk of incident AF (Risk ratio (RR): 1.99; 95% confidence intervals (CI); 1.43 to 2.77; p < 0.0001; I² = 67%). Subclinical hypothyroidism was also associated with a greater risk of AF (RR: 1.24; 95% CI; 1.05 to 1.47; p = 0.01; I² = 65%). Subgroup analysis demonstrated a 76% increase in the risk of post-operative AF in patients with subclinical hypothyroidism compared to euthyroid post-operative patients (RR: 1.76; 95% CI; 1.36 to 2.28; p < 0.0001; I² = 0%). Six studies were rated as low risk of bias and three as medium risk of bias according to the RoBANS tool. The quality of evidence for AF in subclinical hyper- and hypothyroid patients was low. Subclinical hyperthyroidism and subclinical hypothyroidism were associated with a higher risk of incident AF and post-operative AF, respectively. The quality of the current evidence is low and ideally a randomised controlled trial should be conducted to confirm these associations and assess impacts of treatments. Abstract Figure.

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Effects of Quran Recitation on the Reduction of Preoperative Anxiety in Elective Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

10.21203/rs.3.rs-48044/v2 ◽

2020 ◽

Author(s):

Vahideh Zarea Gavgani ◽

Mortaza Ghojazadeh ◽

Fatemeh Sadeghi-Ghyassi ◽

Tahmineh Khodapanah

Keyword(s):

Systematic Review ◽

Publication Bias ◽

Subgroup Analysis ◽

Randomized Clinical Trials ◽

Elective Surgery ◽

Meta Analysis ◽

Preoperative Anxiety ◽

Cochrane Library ◽

Qualitative Synthesis ◽

Inconsistency Index

Abstract Background: Anxiety is a common reaction among patients undergoing surgery. This study aim to assess effectiveness of Quran recitation on reducing the preoperative anxiety.Methods: A systematic review of the citations in the Medline, EMBASE, Cochrane Library, PsycInfo, Arab World Research Source and other relevant databases was performed to collect the data. Randomized clinical trials about the effect of Quran recitation on the reduction of preoperative anxiety in elective surgery were included without any Language and date restriction. Interventions with self-reading/self-recitation were excluded. The Cochran’s Q statistic and the (I2) with 50 percent threshold was used for calculation of the heterogeneity and inconsistency index. Subgroup analysis was conducted based on the type of surgery. The funnel plot has been used to evaluate the possibility of the publication bias.Results:Twelve studies were included in the qualitative synthesis and nine studies included in the quantitative synthesis. Our meta-analysis showed a significant reduction in the anxiety level with Quran recitation. The heterogeneity of the included studies was statistically significant (Q=23.05, I2=65.29, P=0.003). The pooled effect size of the anxiety was d=−8.893; 95% CI=[−10.763 to −7.022] (P < 0.001). The subgroup analysis showed that Quran recitation has a beneficial effect on reducing anxiety in both major and minor surgeries.There was no publication bias (t=0.907, P=0.39) in the studies.Conclusion: Quran recitation can be considered as a non-invasive and peaceful intervention to reduce preoperative anxiety in elective surgery.

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Accurate detection of atrial fibrillation using a smartphone remains uncertain: a systematic review and meta-analysis

European Heart Journal ◽

10.1093/ehjci/ehaa946.3505 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Gill ◽

C Sartini ◽

H.W Uh ◽

N Ghoreishi ◽

V Cardoso ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Publication Bias ◽

Meta Analysis ◽

Current Evidence ◽

Cochrane Library ◽

Small Range ◽

Funding Source ◽

True Value

Abstract Introduction Early diagnosis of atrial fibrillation (AF) is essential to reduce complications such as stroke, and improve patient quality of life. Novel screening techniques using smartphone camera photoplethysmography (PPG) can be used for AF detection, but their clinical applicability remains unclear. Purpose To assess the diagnostic accuracy of smartphone PPG compared to conventional ECG for AF detection. Methods We performed a systematic review of MEDLINE, EMBASE, Cochrane library, and other databases (1980-October 2019), including any study or abstract where smartphone finger-tip PPG was compared with a reference ECG (1, 3 or 12-lead). Outcomes were sensitivity (SE), specificity (SP), positive and negative predictive value (PPV; NPV) and overall accuracy. Bivariate hierarchical random effects meta-analysis was performed for studies with confidence intervals for SE and SP, and funnel plots were used to identify publication bias. Study quality was assessed using the established QUADAS-2 tool by two independent graders. Results 1350 publications were screened, of which 17 studies were included in the systematic review (7 full text publications and 10 abstracts), providing 21 comparisons of accuracy for AF detection. Most studies were based in secondary care and small (range n=33 to 1095), with a total of 5469 participants including 1384 with AF. Only 4 studies were multicentre. Smartphone applications used were Cardiio Rhythm, Fibricheck, Preventicus and Heartbeats, with 7 studies not specifying the tool used. Overall SE and SP for AF detection were high, ranging from 76 to 100%, and 85 to 100% respectively. PPV ranged from 54 to 100% and NPV from 77 to 100%, with overall accuracy between 61 and 99%. The meta-analysis included 12 comparisons from 10 studies (n=2714; 936 with AF). The pooled SE was 93% (95% CI 90–96%) and SP 97% (95% CI 95–99%); Figure 1A. QUADAS-2 assessment demonstrated poor quality of studies overall, with a high or unclear risk of bias in at least one domain for all studies. There was clear evidence of publication bias; Figure 1B. Conclusions PPG offers the potential for large scale, non-invasive, patient-led screening of AF. However, current evidence is limited to biased, low quality studies often with unrealistic results for AF detection. These are insufficient to advise clinicians on the true value of current smartphone PPG technology. Figure 1. Meta-analysis & publication bias Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): BigData@Heart EU/EFPIA IMI 116074.

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

Innovation in Aging ◽

10.1093/geroni/igaa057.1291 ◽

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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Prevalence of retinopathy in prediabetes: protocol for a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-040997 ◽

2021 ◽

Vol 11 (1) ◽

pp. e040997

Author(s):

Varo Kirthi ◽

Paul Nderitu ◽

Uazman Alam ◽

Jennifer Evans ◽

Sarah Nevitt ◽

...

Keyword(s):

Systematic Review ◽

Diabetic Retinopathy ◽

Data Extraction ◽

Meta Analysis ◽

International Diabetes Federation ◽

Current Data ◽

Risk Of Bias ◽

Fundus Photography ◽

Primary Data ◽

Cochrane Library

IntroductionThere is growing evidence of a higher than expected prevalence of retinopathy in prediabetes. This paper presents the protocol of a systematic review and meta-analysis of retinopathy in prediabetes. The aim of the review is to estimate the prevalence of retinopathy in prediabetes and to summarise the current data.Methods and analysisThis protocol is developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines. A comprehensive electronic bibliographic search will be conducted in MEDLINE, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and the Cochrane Library. Eligible studies will report prevalence data for retinopathy on fundus photography in adults with prediabetes. No time restrictions will be placed on the date of publication. Screening for eligible studies and data extraction will be conducted by two reviewers independently, using predefined inclusion criteria and prepiloted data extraction forms. Disagreements between the reviewers will be resolved by discussion, and if required, a third (senior) reviewer will arbitrate.The primary outcome is the prevalence of any standard features of diabetic retinopathy (DR) on fundus photography, as per International Clinical Diabetic Retinopathy Severity Scale (ICDRSS) classification. Secondary outcomes are the prevalence of (1) any retinal microvascular abnormalities on fundus photography that are not standard features of DR as per ICDRSS classification and (2) any macular microvascular abnormalities on fundus photography, including but not limited to the presence of macular exudates, microaneurysms and haemorrhages. Risk of bias for included studies will be assessed using a validated risk of bias tool for prevalence studies. Pooled estimates for the prespecified outcomes of interest will be calculated using random effects meta-analytic techniques. Heterogeneity will be assessed using the I2 statistic.Ethics and disseminationEthical approval is not required as this is a protocol for a systematic review and no primary data are to be collected. Findings will be disseminated through peer-reviewed publications and presentations at national and international meetings including Diabetes UK, European Association for the Study of Diabetes, American Diabetes Association and International Diabetes Federation conferences.PROSPERO registration numberCRD42020184820.

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Effectiveness of Antalgic Therapies in Patients with Vertebral Bone Metastasis: A Protocol for a Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083991 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3991

Author(s):

Antonio Jose Martin-Perez ◽

María Fernández-González ◽

Paula Postigo-Martin ◽

Marc Sampedro Pilegaard ◽

Carolina Fernández-Lao ◽

...

Keyword(s):

Systematic Review ◽

Bone Metastasis ◽

Data Extraction ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Pharmacological Intervention ◽

Vertebral Metastasis ◽

Randomized Controlled Clinical Trials

There is no systematic review that has identified existing studies evaluating the pharmacological and non-pharmacological intervention for pain management in patients with bone metastasis. To fill this gap in the literature, this systematic review with meta-analysis aims to evaluate the effectiveness of different antalgic therapies (pharmacological and non-pharmacological) in the improvement of pain of these patients. To this end, this protocol has been written according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and registered in PROSPERO (CRD42020135762). A systematic search will be carried out in four international databases: Medline (Via PubMed), Web of Science, Cochrane Library and SCOPUS, to select the randomized controlled clinical trials. The Risk of Bias Tool developed by Cochrane will be used to assess the risk of bias and the quality of the identified studies. A narrative synthesis will be used to describe and compare the studies, and after the data extraction, random effects model and a subgroup analyses will be performed according to the type of intervention, if possible. This protocol aims to generate a systematic review that compiles and synthesizes the best and most recent evidence on the treatment of pain derived from vertebral metastasis.

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Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽

10.3390/cancers13122984 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2984

Author(s):

Stepan M. Esagian ◽

Christos D. Kakos ◽

Emmanouil Giorgakis ◽

Lyle Burdine ◽

J. Camilo Barreto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Randomized Controlled Trials ◽

Transarterial Chemoembolization ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Controlled Trials ◽

Curative Intent ◽

Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

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What Types of Exercise Are More Effective in Reducing Obesity and Blood Pressure for Middle-Aged Women? A Systematic Review With Meta-Analysis

Biological Research For Nursing ◽

10.1177/10998004211015424 ◽

2021 ◽

pp. 109980042110154

Author(s):

Seong-Hi Park ◽

Chul-Gyu Kim

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Metabolic Syndrome ◽

Body Weight ◽

Waist Circumference ◽

Meta Analysis ◽

Physical Activities ◽

Risk Of Bias ◽

Cochrane Library ◽

Middle Aged

Background: A systematic review was performed to identify the types of physical activities effective as interventions in preventing metabolic syndrome in middle-aged women. Methods: Electronic databases (MEDLINE, EMBASE, the Cochrane Library, and CINAHL) served as the data sources. Cochrane’s Risk of Bias 2 was applied to assess the risk of bias of the randomized controlled trials. Meta-analyses were performed on selected studies using Review Manager 5.3. Thirty-one trials enrolling 2,202 participants were included. Results: Compared to controls, the effects of physical activity were indicated by pooled mean differences, which were −0.57 kg for body weight, −0.43 kg/m2 for body mass index, −1.63 cm for waist circumference, −4.89 mmHg for systolic blood pressure (BP), and −2.71 mmHg for diastolic BP. The effects were greater on the measurements of waist circumference and BP than on body weight and BMI. The types of physical activities were further analyzed according to sub-groups. Only aerobic exercise did not affect body weight and resistance exercise did not significantly change any results. Contrarily, combined exercises significantly reduced measurements of waist circumference and BP. Conclusion: This review can provide valuable information for research and implementation of measures to prevent metabolic syndrome in middle-aged women.

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Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-85359-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paddy Ssentongo ◽

Emily S. Heilbrunn ◽

Anna E. Ssentongo ◽

Shailesh Advani ◽

Vernon M. Chinchilli ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Significant Risk ◽

Significant Risk Factor ◽

Cochrane Library ◽

Random Effects Models ◽

Beneficial Effects ◽

Risk Of Mortality ◽

Immunodeficiency Syndrome ◽

Hiv Negative

AbstractSusceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the risk of mortality among people living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (PLWHA) is largely unknown. PLWHA are unique due to their altered immune system from their history of chronic HIV infection and their use of antiretroviral therapy, some of which have been used experimentally to treat coronavirus disease 2019 (COVID-19). Therefore, we conducted a systematic review and meta-analysis to assess the epidemiology of SARS-COV-2/HIV coinfection and estimate associated mortality from COVID-19 (Prospero Registration ID: CRD42020187980). PubMed, SCOPUS, OVID and Cochrane Library databases, and medRxiv preprint repositories were searched from January 1, 2020, to December 12, 2020. Data were extracted from studies reporting COVID-19 attack and mortality rates in PLWHA compared to their HIV-negative counterparts. Pooled attack and mortality risks were quantified using random-effects models. We identified 22 studies that included 20,982,498 participants across North America, Africa, Europe, and Asia. The median age was 56 years, and 50% were male. HIV-positive persons had a significantly higher risk of SARS-CoV-2 infection [risk ratio (RR) 1.24, 95% CI 1.05–1.46)] and mortality from COVID-19 (RR 1.78, 95% CI 1.21–2.60) than HIV-negative individuals. The beneficial effects of tenofovir and protease-inhibitors in reducing the risk of SARS-CoV-2 infection and death from COVID-19 in PLWHA remain inconclusive. HIV remains a significant risk factor for acquiring SARS-CoV-2 infection and is associated with a higher risk of mortality from COVID-19. In support of the current Centers for Disease Control and Prevention (CDC) guidelines, persons with HIV need priority consideration for the SARS-CoV-2 vaccine.

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Abstract 20: The Effect of Resistance Training on Survival and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.11.suppl_1.20 ◽

2018 ◽

Vol 11 (suppl_1) ◽

Author(s):

Farzane Saeidifard ◽

Jose R Medina Inojosa ◽

Colin P West ◽

Thomas P Olson ◽

Virend K Somers ◽

...

Keyword(s):

Systematic Review ◽

Heart Disease ◽

Resistance Training ◽

Subgroup Analysis ◽

Cancer Mortality ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Risk Of Bias ◽

Cochrane Central Register ◽

All Cause Mortality

Background: This is the first systematic review and meta-analysis to investigate the effect of resistance training (RT) on survival and other cardiovascular outcomes including ischemic heart disease events and stroke. Methods: An experienced librarian searched databases up to September 25 th , 2017, for randomized trials and cohort studies that evaluated the effect of RT on survival and cardiovascular events in the general population. The databases included Ovid MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. Two investigators conducted the screening process independently and in duplicate. Cochrane tools were used to assess the risk of bias in clinical trials and observational studies. We calculated hazard ratios and 95% confidence intervals using RevMan and fixed and random effect models and had a subgroup analysis based on doses of RT and for the combination of RT and aerobic exercise (AE) vs no exercise. Results: The search identified 1429 studies from which 10 (one randomized trial) met the inclusion criteria, including 338,254 participants with a mean follow up of 8.14 years. The meta-analysis showed that RT, in comparison with no exercises, is associated with 24% lower all-cause mortality and 48% lower mortality when combined with AE. Based on subgroup analysis, performing 1-2 sessions of RT/week is associated with lower all-cause mortality by 28% (HR 0.72, 95% CI 0.66-0.78) whereas > 5 sessions of RT/week has no association with all-cause mortality (HR 0.99, 95% CI 0.76-1.31). Further, RT alone or combined with AE is associated with lower CV mortality compared to no exercise (Figures). Finally, RT alone also showed a borderline association with lower all-cancer mortality. Heterogeneity was present for several comparisons, and subsequent analysis will explore sources of this variability. Using study design-specific Cochrane risk of bias tools, no major sources of bias were identified in the included studies. One cohort study looked at the effect of RT on coronary heart disease events and found 23% risk reduction in men, while no study specifically assessed the effect of RT on cerebrovascular outcomes. Conclusion: RT is associated with lower all-cause, CV and all-cancer mortality. RT appears to have an additive effect when combined with AE.

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