Comparative safety of the sodium glucose co-transporter 2 (SGLT2) inhibitors: a systematic review and meta-analysis

ObjectiveTo estimate the association between the use of sodium glucose co-transporter-2 (SGLT2) inhibitors and postmarket harms as identified by drug regulatory agencies.DesignWe conducted a systematic review and meta-analysis of randomised controlled trials (RCT). Six large databases were searched from inception to May 2018. Random effects models were used to estimate pooled relative risks (RRs).InterventionSGLT2 inhibitors, compared with placebo or active comparators.Primary outcomesAcute kidney injury (AKI), diabetic ketoacidosis (DKA), urinary tract infections (UTI), bone fractures and lower limb amputations.ResultsWe screened 2418 citations of which 109 were included. Most studies included one of four SGLT2 inhibitors, dapagliflozin, canagliflozin, empagliflozin and ipragliflozin. When compared with placebo, SGLT2 inhibitors were found to be significantly protective against AKI (RR=0.59; 95% CI 0.39 to 0.89; I2=0.0%), while no difference was found for DKA (RR 0.66; 95% CI 0.30 to 1.45, I2=0.0%), UTI (RR 1.02; 95% CI 0.95 to 1.09, I2=0.0%) or bone fracture (RR 0.87; 95% CI 0.69 to 1.09, I2=1.3%). Three studies reported on amputation, with one finding a significant increase risk. No increased risk for either outcome was found when compared with active controls. Subgroup analysis did show an increased risk of UTI with dapagliflozin only (RR 1.21; 95% CI 1.02 to 1.43, I2=0.0%), but no other analysis supported an increased risk of AKI, DKA, UTI or fracture.ConclusionsCurrent evidence from RCTs does not suggest an increased risk of harm with SGLT2 inhibitors as a class over placebo or active comparators with respect to AKI, DKA, UTI or fracture. However, wide CIs for many comparisons suggest limited precision, and therefore clinically important adverse events cannot be ruled out. Dapagliflozin, appears to independently increase the risk of UTI, although the mechanism for this intraclass variation in risk is unclear.PROSPERO registration numberCRD42016038715.

Download Full-text

Diaphragmatic herniation after esophagogastric surgery: systematic review and meta-analysis

Langenbeck s Archives of Surgery ◽

10.1007/s00423-021-02214-9 ◽

2021 ◽

Author(s):

Davide Bona ◽

Francesca Lombardo ◽

Kazuhide Matsushima ◽

Marta Cavalli ◽

Valerio Panizzo ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Treatment Algorithm ◽

Pulmonary Complications ◽

Morbidity And Mortality ◽

Current Evidence ◽

Esophageal Hiatus ◽

Pooled Prevalence ◽

Increased Risk ◽

Esophagogastric Surgery

Abstract Introduction The anatomy of the esophageal hiatus is altered during esophagogastric surgery with an increased risk of postoperative hiatus hernia (HH). The purpose of this article was to examine the current evidence on the surgical management and outcomes associated with HH after esophagogastric surgery for cancer. Materials and methods Systematic review and meta-analysis. Web of Science, PubMed, and EMBASE data sets were consulted. Results Twenty-seven studies were included for a total of 404 patients requiring surgical treatment for HH after esophagogastric surgery. The age of the patients ranged from 35 to 85 years, and the majority were males (82.3%). Abdominal pain, nausea/vomiting, and dyspnea were the commonly reported symptoms. An emergency repair was required in 51.5%, while a minimally invasive repair was performed in 48.5%. Simple suture cruroplasty and mesh reinforced repair were performed in 65% and 35% of patients, respectively. The duration between the index procedure and HH repair ranged from 3 to 144 months, with the majority (67%) occurring within 24 months. The estimated pooled prevalence rates of pulmonary complications, anastomotic leak, overall morbidity, and mortality were 14.1% (95% CI = 8.0–22.0%), 1.4% (95% CI = 0.8–2.2%), 35% (95% CI = 20.0–54.0%), and 5.0% (95% CI = 3.0–8.0%), respectively. The postoperative follow-up ranged from 1 to 110 months (mean = 24) and the pooled prevalence of HH recurrence was 16% (95% CI = 13.0–21.6%). Conclusions Current evidence reporting data for HH after esophagogastric surgery is narrow. The overall postoperative pulmonary complications, overall morbidity, and mortality are 14%, 35%, and 5%, respectively. Additional studies are required to define indications and treatment algorithm and evaluate the best technique for crural repair at the index operation in an attempt to minimize the risk of HH.

Download Full-text

Comparing Interventions Aimed at Improving Influenza Vaccination Coverage Among Vulnerable Populations: A Systematic Review and Meta-Analysis Protocol

10.1101/2021.03.08.21253172 ◽

2021 ◽

Author(s):

Pei Chen Wu ◽

Lyn McPherson ◽

Stephen B Lambert ◽

Peter Wnukowski-Mtonga ◽

Nicholas G Lennox ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Random Effects Models ◽

Vaccination Rates ◽

Concurrent Control ◽

Vaccination Recommendations ◽

Increased Risk ◽

Improvement Interventions ◽

High Risk Populations ◽

Quality Improvement Interventions

ABSTRACTBackgroundInfluenza is a major contributor to global disease burden. Vaccination recommendations specifically target populations at increased risk of serious influenza sequelae. The aim of this study is to conduct a systematic review and meta-analysis to evaluate the effectiveness of different quality improvement interventions to increase vaccination rates in high-risk populations.MethodsRandomized and nonrandomized studies with concurrent control groups will be identified. Interventions to increase vaccination rates will be categorized by strategy type. Overall intervention effects will be calculated using random effects models. Study quality will be assessed using a modified Cochrane Risk of Bias tool.

Download Full-text

Pregnancy-related complications and incidence of atrial fibrillation: a systematic review and meta-analysis

EP Europace ◽

10.1093/europace/euab116.145 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

T Al Bahhawi ◽

A Aqeeli ◽

S L Harrison ◽

D A Lane ◽

I Buchan ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Cohort Studies ◽

Observational Studies ◽

Large Scale ◽

Data Extraction ◽

Meta Analysis ◽

Significant Heterogeneity ◽

Random Effects Models ◽

Increased Risk

Abstract Funding Acknowledgements Type of funding sources: None. Background Pregnancy-related complications have been previously associated with incident cardiovascular disease. However, data are scarce on the association between pregnancy-related complications and incident atrial fibrillation (AF). This systematic review examines associations between pregnancy-related complications and incident AF. Methods A systematic search of the literature utilising MEDLINE and EMBASE (Ovid) was conducted from 1990 to 6 April 2020. Observational studies examining the association between pregnancy-related complications including hypertensive disorders of pregnancy (HDP), gestational diabetes, placental abruption, preterm birth, low birth weight, small-for-gestational-age and stillbirth, and incidence of AF were included. Screening and data extraction were conducted independently by two reviewers. Inverse-variance random-effects models were used to pool hazard ratios. Results: Six observational studies met the inclusion criteria one case-control study and five retrospective cohort studies, with four studies eligible for meta-analysis. Sample sizes ranged from 1,839-1,303,365. Mean/median follow-up for the cohort studies ranged from 7-36 years. Most studies reported an increased risk of incident AF associated with pregnancy-related complications. The pooled summary statistic from four studies reflected a greater risk of incident AF for HDP (hazard ratio (HR) 1.47, 95% confidence intervals (CI) 1.18-1.84; I2 = 84%) and from three studies for pre-eclampsia (HR 1.71, 95% CI 1.41-2.06; I2 = 64%; Figure). Conclusions The results of this review suggest that pregnancy-related complications particularly pre-eclampsia appear to be associated with higher risk of incident AF. The small number of included studies and the significant heterogeneity in the pooled results suggest further large-scale prospective studies are required to confirm the association between pregnancy-related complications and AF. Abstract Figure.

Download Full-text

Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis

PLoS Medicine ◽

10.1371/journal.pmed.1002983 ◽

2019 ◽

Vol 16 (12) ◽

pp. e1002983 ◽

Cited By ~ 20

Author(s):

Jan Menne ◽

Eva Dumann ◽

Hermann Haller ◽

Bernhard M. W. Schmidt

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Meta Analysis ◽

Kidney Injury ◽

Sglt2 Inhibitors

Download Full-text

Adiposity and the risk of rheumatoid arthritis: a systematic review and meta-analysis of cohort studies

Scientific Reports ◽

10.1038/s41598-020-71676-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Tomoya Ohno ◽

Dagfinn Aune ◽

Alicia K. Heath

Keyword(s):

Rheumatoid Arthritis ◽

Systematic Review ◽

Waist Circumference ◽

Cohort Studies ◽

Meta Analysis ◽

Case Control Studies ◽

Rheumatoid Arthritis Risk ◽

Random Effects Models ◽

Relative Risks ◽

Meta Analyses

Abstract Several studies have investigated associations between overweight/obesity and risk of developing rheumatoid arthritis, however, the evidence is not entirely consistent, and previous meta-analyses mainly included case–control studies, which can be affected by various biases. We therefore conducted a systematic review and meta-analysis of cohort studies on adiposity and risk of rheumatoid arthritis. Relevant studies were identified by searching PubMed and Embase databases. Random effects models were used to estimate summary relative risks (RRs) and 95% confidence intervals (CIs) for rheumatoid arthritis in relation to different measures of adiposity. Thirteen cohort studies (10 publications) were included. The summary RR per 5 kg/m2 increase in body mass index (BMI) was 1.11 (95% CI 1.05–1.18, I2 = 50%), but the association was restricted to women (1.15, 95% CI 1.08–1.21, I2 = 17%) and not observed in men (0.89, 95% CI 0.73–1.09, I2 = 58%). The summary RR per 5 kg/m2 increment in BMI at age 18 years was 1.17 (95% CI 1.01–1.36, I2 = 26%, n = 3), and per 10 cm increase in waist circumference was 1.13 (95% CI 1.02–1.25, I2 = 44%, n = 2). Higher BMI in middle age, BMI at age 18 years, and waist circumference were associated with increased rheumatoid arthritis risk, suggesting adiposity could be targeted for primary prevention.

Download Full-text

Aspirin and fracture risk: a systematic review and exploratory meta-analysis of observational studies

BMJ Open ◽

10.1136/bmjopen-2018-026876 ◽

2020 ◽

Vol 10 (2) ◽

pp. e026876 ◽

Cited By ~ 2

Author(s):

A L Barker ◽

Sze-Ee Soh ◽

Kerrie M Sanders ◽

Julie Pasco ◽

Sundeep Khosla ◽

...

Keyword(s):

Systematic Review ◽

Fracture Risk ◽

Observational Studies ◽

Meta Analysis ◽

Large Population ◽

Mineral Density ◽

Random Effects Models ◽

Manual Search ◽

Relative Risks ◽

Hip Bmd

ObjectivesThis review provides insights into the potential for aspirin to preserve bone mineral density (BMD) and reduce fracture risk, building knowledge of the risk-benefit profile of aspirin.MethodsWe conducted a systematic review and exploratory meta-analysis of observational studies. Electronic searches of MEDLINE and Embase, and a manual search of bibliographies was undertaken for studies published to 28 March 2018. Studies were included if: participants were men or women aged ≥18 years; the exposure of interest was aspirin; and relative risks, ORs and 95% CIs for the risk of fracture or difference (percentage or absolute) in BMD (measured by dual energy X-ray absorptiometry) between aspirin users and non-users were presented. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklists for observational studies. Pooled ORs for any fracture and standardised mean differences (SMDs) for BMD outcomes were calculated using random-effects models.ResultsTwelve studies met the inclusion criteria and were included in the meta-analysis. Aspirin use was associated with a 17% lower odds for any fracture (OR 0.83, 95% CI 0.70 to 0.99; I2=71%; six studies; n=511 390). Aspirin was associated with a higher total hip BMD for women (SMD 0.03, 95% CI −0.02 to 0.07; I2=0%; three studies; n=9686) and men (SMD 0.06, 95% CI −0.02 to 0.13, I2=0%; two studies; n=4137) although these associations were not significant. Similar results were observed for lumbar spine BMD in women (SMD 0.03, 95% CI −0.03 to 0.09; I2=34%; four studies; n=11 330) and men (SMD 0.08; 95% CI −0.01 to 0.18; one study; n=432).ConclusionsWhile the benefits of reduced fracture risk and higher BMD from aspirin use may be modest for individuals, if confirmed in prospective controlled trials, they may confer a large population benefit given the common use of aspirin in older people.

Download Full-text

Hypertension and the risk of endometrial cancer: a systematic review and meta-analysis of case-control and cohort studies

Scientific Reports ◽

10.1038/srep44808 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 24

Author(s):

Dagfinn Aune ◽

Abhijit Sen ◽

Lars J. Vatten

Keyword(s):

Systematic Review ◽

Endometrial Cancer ◽

Cohort Studies ◽

Contraceptive Use ◽

Meta Analysis ◽

Case Control ◽

Adjusted Relative Risk ◽

Case Control Studies ◽

Relative Risks ◽

Increased Risk

Abstract A history of hypertension has been associated with increased risk of endometrial cancer in several studies, but the results have not been consistent. We conducted a systematic review and meta-analysis of case-control and cohort studies to clarify the association between hypertension and endometrial cancer risk. PubMed and Embase databases were searched up to 27th of February 2016. Prospective and case-control studies which reported adjusted relative risk estimates and 95% confidence intervals of endometrial cancer associated with a hypertension diagnosis were included. Summary relative risks were estimated using a random effects model. Nineteen case-control studies and 6 cohort studies were included. The summary RR was 1.61 (95% CI: 1.41–1.85, I2 = 86%) for all studies, 1.73 (95% CI: 1.45–2.06, I2 = 89%) for case-control studies and 1.32 (95% CI: 1.12–1.56, I2 = 47%) for cohort studies. The association between hypertension and endometrial cancer was weaker, but still significant, among studies with adjustment for smoking, BMI, oral contraceptive use, and parity, compared to studies without such adjustment. This meta-analysis suggest an increased risk of endometrial cancer among patients with hypertension, however, further studies with more comprehensive adjustments for confounders are warranted to clarify the association.

Download Full-text

Childhood maltreatment and adult suicidality: a comprehensive systematic review with meta-analysis

Psychological Medicine ◽

10.1017/s0033291718003823 ◽

2019 ◽

Vol 49 (07) ◽

pp. 1057-1078 ◽

Cited By ~ 33

Author(s):

Ioannis Angelakis ◽

Emma Louise Gillespie ◽

Maria Panagioti

Keyword(s):

Systematic Review ◽

Childhood Abuse ◽

Childhood Maltreatment ◽

Emotional Abuse ◽

Suicide Attempts ◽

Meta Analysis ◽

Current Evidence ◽

Bibliographic Databases ◽

Increased Risk ◽

Different Types

AbstractThis comprehensive systematic review and meta-analysis aims to quantify the association between different types of childhood maltreatment and suicidality. We searched five bibliographic databases, including Medline, PsychINFO, Embase, Web of Science and CINAHL, until January 2018. Random-effects meta-analysis was employed followed by univariable and multivariable meta-regressions. Heterogeneity was quantified using theI2statistic and formal publication bias tests were undertaken. The methodological quality of the studies was critically appraised and accounted in the meta-regression analyses. Data from 68 studies based onn= 261.660 adults were pooled. All different types of childhood maltreatment including sexual abuse [odds ratio (OR) 3.17, 95% confidence interval (CI) 2.76–3.64], physical abuse (OR 2.52, 95% CI 2.09–3.04) and emotional abuse (OR 2.49, 95% CI 1.64–3.77) were associated with two- to three-fold increased risk for suicide attempts. Similar results were found for the association between childhood maltreatment and suicidal ideation. Complex childhood abuse was associated with a particularly high risk for suicide attempts in adults (OR 5.18, 95% CI 2.52–10.63). Variations across the studies in terms of demographic and clinical characteristics of the participants and other core methodological factors did not affect the findings of the main analyses. We conclude that there is solid evidence that childhood maltreatment is associated with increased odds for suicidality in adults. The main outstanding challenge is to better understand the mechanisms which underpin the development of suicidality in people exposed to childhood maltreatment because current evidence is scarce.

Download Full-text

Relation between Age-Related Macular Degeneration and Cardiovascular Events and Mortality: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2016/8212063 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 11

Author(s):

Jie Wang ◽

Yangjing Xue ◽

Saroj Thapa ◽

Luping Wang ◽

Jifei Tang ◽

...

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Macular Degeneration ◽

Cardiovascular Events ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Relative Risks ◽

Age Related ◽

Increased Risk ◽

All Cause Mortality

Data on the association between age-related macular degeneration (AMD) and cardiovascular disease and mortality are conflicting. The purpose of this report is to conduct a systematic review to better understand the role of AMD as a risk factor for CVD events and mortality. We searched Medline (Ovid) and Embase (Ovid) for trials published from 1980 to 2015. We included 20 cohort studies that reported relative risks with 95% confidence intervals for the association of AMD and cardiovascular events and mortality, involving 29,964,334 participants. In a random-effects model, the adjusted RR (95% confidence interval [CI]) associated with AMD was 1.08 (1.00–1.117) for all-cause mortality (8 studies) and 1.18 (0.98–1.43) for cardiovascular disease mortality (5 studies). The pooled RR (95% CI) was 1.17 (0.94–1.45) for coronary heart disease (CHD; 3 studies) and 1.13 (0.93–1.36) for stroke (8 studies). Findings from this systematic review support that AMD is associated with increased risk of all-cause mortality. The evidence that AMD predicts incident CVD events or CVD mortality remains inclusive and warrants further study in the future.

Download Full-text

Current evidence for anesthesia management during endovascular stroke therapy: updated systematic review and meta-analysis

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2018-013916 ◽

2018 ◽

Vol 11 (2) ◽

pp. 107-113 ◽

Cited By ~ 4

Author(s):

Nitin Goyal ◽

Konark Malhotra ◽

Muhammad F Ishfaq ◽

Georgios Tsivgoulis ◽

Christopher Nickele ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Meta Analysis ◽

Anesthetic Management ◽

Functional Independence ◽

Sensitivity Analyses ◽

Current Evidence ◽

Vessel Occlusion ◽

Random Effects Models ◽

Randomized Studies

IntroductionDebate continues about the optimal anesthetic management for patients undergoing endovascular treatment (ET) of acute ischemic stroke due to emergent large vessel occlusion.ObjectiveTo compare, using current evidence, the clinical outcomes and procedural characteristics among patients undergoing general anesthesia (GA) and local or monitored anesthesia (non-GA).MethodsWe performed a systematic review and meta-analysis of all available studies that involved the use of stent retrievers for ET (stentriever group). Additionally, we included studies that were published in 2015 and later, and compared the clinical outcomes among the studies using stentrievers or no stentrievers (pre-stentriever group). Outcome variables included functional independence (FI; modified Rankin Scale scores of 0–2), symptomatic hemorrhage, mortality, procedure duration, and vascular and respiratory complications. We calculated pooled odds ratios and 95% CIs using random-effects models.ResultsSixteen studies (three randomized controlled clinical trials (RCTs) and 13 non-randomized studies) were identified comprising 5836 patients. Although non-GA was associated with higher odds of 3-month FI (OR=1.57; 95% CI 1.17 to 2.10; P=0.003) and lower odds of 3-month mortality (OR=0.62; 95% CI 0.47 to 0.82; P=0.0006, substantial heterogeneity was noted across included trials. Sensitivity analyses of RCTs showed that non-GA was inversely associated with FI (OR=0.55; 95% CI 0.34 to 0.89; P=0.01; I2=15%), while no association was noted with mortality (OR=1.36; 95% CI 0.79 to 2.34; P=0.27; I2=0%).ConclusionOur updated meta-analysis demonstrates favorable results with non-GA, probably owing to inclusion of non-randomized studies. Recent single-center RCTs indicate that GA is associated with higher odds of FI at 3 months, while other outcomes are similar between the two groups.

Download Full-text