scholarly journals Risk of myocardial infarction among people living with HIV: an updated systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e025874 ◽  
Author(s):  
Oghenowede Eyawo ◽  
Gwenyth Brockman ◽  
Charles H Goldsmith ◽  
Mark W Hull ◽  
Scott A Lear ◽  
...  

ObjectiveCardiovascular disease (CVD) is one of the leading non-AIDS-defining causes of death among HIV-positive (HIV+) individuals. However, the evidence surrounding specific components of CVD risk remains inconclusive. We conducted a systematic review and meta-analysis to synthesise the available evidence and establish the risk of myocardial infarction (MI) among HIV+ compared with uninfected individuals. We also examined MI risk within subgroups of HIV+ individuals according to exposure to combination antiretroviral therapy (ART), ART class/regimen, CD4 cell count and plasma viral load (pVL) levels.DesignSystematic review and meta-analysis.Data sourcesWe searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews until 18 July 2018. Furthermore, we scanned recent HIV conference abstracts (CROI, IAS/AIDS) and bibliographies of relevant articles.Eligibility criteriaOriginal studies published after December 1999 and reporting comparative data relating to the rate of MI among HIV+ individuals were included.Data extraction and synthesisTwo reviewers working in duplicate, independently extracted data. Data were pooled using random-effects meta-analysis and reported as relative risk (RR) with 95% CI.ResultsThirty-two of the 8130 identified records were included in the review. The pooled RR suggests that HIV+ individuals have a greater risk of MI compared with uninfected individuals (RR: 1.73; 95% CI 1.44 to 2.08). Depending on risk stratification, there was moderate variation according to ART uptake (RR, ART-treated=1.80; 95% CI 1.17 to 2.77; ART-untreated HIV+ individuals: 1.25; 95% CI 0.93 to 1.67, both relative to uninfected individuals). We found low CD4 count, high pVL and certain ART characteristics including cumulative ART exposure, any/cumulative use of protease inhibitors as a class, and exposure to specific ART drugs (eg, abacavir) to be importantly associated with a greater MI risk.ConclusionsOur results indicate that HIV infection, low CD4, high pVL, cumulative ART use in general including certain exposure to specific ART class/regimen are associated with increased risk of MI. The association with cumulative ART may be an index of the duration of HIV infection with its attendant inflammation, and not entirely the effect of cumulative exposure to ART per se.PROSPERO registration numberCRD42014012977.

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e019468 ◽  
Author(s):  
Bongani Brian Nkambule ◽  
Zibusiso Mkandla ◽  
Tinashe Mutize ◽  
Phiwayinkosi Vusi Dludla

IntroductionThe incidence of cardiovascular disease (CVD) is now at least threefold higher in HIV-infected patients as compared with the general population. Although platelet activation and reactivity are implicated in the development of CVDs in HIV-infected patients, its precise role remains inconclusive. We aim to assess the association between platelet activation and selected cardiovascular risk factors in HIV-1-infected individuals on highly active antiretroviral treatment (HAART).MethodsThis will be a systematic review and meta-analysis of published studies evaluating the association between platelet activation and CVD risk factors in HAART-treated adults. The search strategy will include medical subject headings words for MEDLINE, and this will be adapted to Embase search headings (Emtree) terms for the EMBASE database. The search will cover literature published between 1 January 1996 to 30 April 2017. Studies will be independently screened by two reviewers using predefined criteria. Relevant eligible full texts will be screened; data will be extracted, and a qualitative synthesis will be conducted. Data extraction will be performed using Review Manager V.5.3. To assess the quality and strengths of evidence across selected studies, the Grading of Recommendations Assessment Development and Evaluation approach will be used. The Cochran’s Q statistic and the I2statistics will be used to analyse statistical heterogeneity between studies. If included studies show high levels of homogeneity, a random effects meta-analysis will be performed using R statistical software.Ethics and disseminationThis will be a review of existing studies and will not require ethical approval. The findings will be disseminated through peer-reviewed publication and presented at local and international conferences. An emerging patient management dilemma is that of the increased incidence of CVD in people living with HIV on HAART. This review may inform treatment and cardiovascular risk stratification of HIV-infected patients at increased risk of developing CVD.PROSPERO registration numberCRD42017062393.


BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e052341
Author(s):  
Fanny Villoz ◽  
Christina Lyko ◽  
Cinzia Del Giovane ◽  
Nicolas Rodondi ◽  
Manuel R Blum

IntroductionStatin-associated muscle symptoms (SAMSs) are a major clinical issue in the primary and secondary prevention of cardiovascular events. Current guidelines advise various approaches mainly based on expert opinion. We will lead a systematic review and meta-analysis to explore the tolerability and acceptability and effectiveness of statin-based therapy management of patients with a history of SAMS. We aim to provide evidence on the tolerability and different strategies of statin-based management of patients with a history of SAMS.Methods and analysisWe will conduct a systematic review of randomised controlled trials (RCTs) and non-randomised studies with a control group. We will search in Data sources MEDLINE, EMBASE, Cochrane Central Register of Controlled Clinical Trials, Scopus, Clinicaltrials.gov and Proquest from inception until April 2021. Two independent reviewers will carry out the study selection based on eligibility criteria. We will extract data following a standard data collection form. The reviewers will use the Cochrane Collaboration’s tools and Newcastle-Ottawa Scale to appraise the study risk of bias. Our primary outcome will be tolerability and our secondary outcomes will be acceptability and effectiveness. We will conduct a qualitative analysis of all included studies. In addition, if sufficient and homogeneous data are available, we will conduct quantitative analysis. We will synthesise dichotomous data using OR with 95% CI and continuous outcomes by using mean difference or standardised mean difference (with 95% CI). We will determine heterogeneity visually with forest plots and quantitatively with I2 and Q-test. We will summarise the confidence in the quantitative estimate by using Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationAs a systematic review of literature without collection of new clinical data, there will be no requirement for ethical approval. We will disseminate findings through peer-reviewed publications.PROSPERO registration numberCRD42020202619.


BMJ Open ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. e020183
Author(s):  
Adolf Kofi Awua ◽  
Edna Dzifa Doe

IntroductionFor a country that lacks a national cervical cancer screening/prevention programme, there is the need to assess the volume of country-specific information, and the status of research on HPV and cervical cancer, in order to provide evidence that will inform policy and further research. The aim of this protocol is to plan an intended systematic review, which is to identify research gaps, prevent unnecessary duplication of work and enable collaboration.Methods and analysisThis protocol, developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols statement and registered by PROSPERO (CRD42017075583), will apply a 13-point eligibility criteria to screening and selecting peer-reviewed research articles and grey literature. These will be obtained from searches in databases, including, among others, those of the National Centre for Biotechnology Information, Cochrane Central Register of Controlled Trials, Google Scholar and the digital collections database of research publications of Universities in Ghana. Collected data will be aggregated and summarised according to emerging themes and simple descriptive statistics.Ethics and disseminationThe study will use publicly available data and will not identify authors of the publication by name. In light of these and as has been indicted, research ethics clearance is not required for evidence syntheses in such reviews. The review will be published in peer-reviewed scientific journals and presented at local and internal conferences as the opportunity becomes available.PROSPERO registration numberCRD42017075583.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Batchelor ◽  
D Liu ◽  
J Bloom ◽  
S Noaman ◽  
W Chan

Abstract Background Morphine analgesia may affect absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of peri-procedural intravenous (IV) morphine administration on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is not well defined. Purpose To conduct a systematic review and meta-analysis exploring clinical outcomes with peri-procedural IV morphine in patients undergoing PPCI for STEMI. Methods Analysis of the electronic databases MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI IV morphine use with myocardial infarction (MI) and mortality. Primary and secondary outcomes were in-hospital or 30-day MI and all-cause mortality respectively. Results Eleven studies (1 randomised controlled trial; 10 cohort studies) were included for systematic review. Five studies, including 3,748 patients were included in meta-analysis of the primary outcome. Of 3,748 patients, 2,239 were treated concurrently with ticagrelor, 1,256 treated with clopidogrel and 253 with prasugrel. As shown in the Figure, there was a trend towards increased risk of myocardial infarction with IV morphine (odds ratio 1.88; 95% CI 0.87–4.09, I2 0%). Across seven studies and 6585 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70, 95% CI 0.40–1.23, I2 19%). Figure 1. MI in hospital or at 30 days Conclusion Based on current literature, evidence of an association between IV morphine and myocardial infarction in patients undergoing PPCI for STEMI is limited by observational methodology and conflicting results. There is no evidence of an association between intravenous peri-procedural morphine and mortality. Clinical trial evidence with strong documentation of adverse events data is required to demonstrate association or causality. Acknowledgement/Funding None


2020 ◽  
Vol 45 (2) ◽  
pp. 429-442
Author(s):  
Carla Hope ◽  
John-Joe Reilly ◽  
Gareth Griffiths ◽  
Jon Lund ◽  
David Humes

Abstract Background Attrition within surgical training is a challenge. In the USA, attrition rates are as high as 20–26%. The factors predicting attrition are not well known. The aim of this systematic review is to identify factors that influence attrition or performance during surgical training. Method The review was performed in line with PRISMA guidelines and registered with the Open Science Framework (OSF). Medline, EMBASE, PubMed and the Cochrane Central Register of Controlled Trials were searched for articles. Risk of bias was assessed using the Newcastle–Ottawa scale. Pooled estimates were calculated using random effects meta-analyses in STATA version 15 (Stata Corp Ltd). A sensitivity analysis was performed including only multi-institutional studies. Results The searches identified 3486 articles, of which 31 were included, comprising 17,407 residents. Fifteen studies were based on multi-institutional data and 16 on single-institutional data. Twenty-nine of the studies are based on US residents. The pooled estimate for overall attrition was 17% (95% CI 14–20%). Women had a significantly higher pooled attrition than men (24% vs 16%, p < 0.001). Some studies reported Hispanic residents had a higher attrition rate than non-Hispanic residents. There was no increased risk of attrition with age, marital or parental status. Factors reported to affect performance were non-white ethnicity and faculty assessment of clinical performance. Childrearing was not associated with performance. Conclusion Female gender is associated with higher attrition in general surgical residency. Longitudinal studies of contemporary surgical cohorts are needed to investigate the complex multi-factorial reasons for failing to complete surgical residency.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Huijuan Zheng ◽  
Junping Wei ◽  
Liansheng Wang ◽  
Qiuhong Wang ◽  
Jing Zhao ◽  
...  

Low selenium status is associated with increased risk of Graves’ disease (GD). While several trials have discussed the efficacy of selenium supplementation for thyroid function, in GD patients, the effectiveness of selenium intake as adjuvant therapy remains unclear. In this systematic review and meta-analysis, we aimed to determine the efficacy of selenium supplementation on thyroid function in GD patients. Two reviewers searched PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and four Chinese databases for studies published up to October 31, 2017. RCTs comparing the effect of selenium supplementation on thyroid hyperfunction in GD patients on antithyroid medication to placebo were included. Serum free thyroxine (FT4), free triiodothyronine (FT3), thyrotrophic hormone receptor antibody (TRAb), and thyroid-stimulating hormone (TSH) levels were assessed. Ten trials involving 796 patients were included. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 9 months of supplementation and compared to placebo administration. Selenium supplementation significantly decreased FT4 (WMD=-0.86 [confidence interval (CI)-1.20 to -0.53]; p=0.756; I2=0.0%) and FT3 (WMD=-0.34 [CI-0.66 to -0.02]; p=0.719; I2=0.0%) levels at 3 months, compared to placebo administration; these findings were consistent at 6 but not 9 months. TSH levels were more elevated in the group of patients taking selenium than in the control group at 3 and 6, but not 9 months. TRAb levels decreased at 6 but not 9 months. At 6 months, patients on selenium supplementation were more likely than controls to show improved thyroid function; however, the effect disappeared at 9 months. Whether these effects correlate with clinically relevant measures remains to be demonstrated.


BMJ ◽  
2020 ◽  
pp. l7078 ◽  
Author(s):  
Joshua D Wallach ◽  
Kun Wang ◽  
Audrey D Zhang ◽  
Deanna Cheng ◽  
Holly K Grossetta Nardini ◽  
...  

AbstractObjectivesTo conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in mind: to clarify uncertainties about the cardiovascular risk of rosiglitazone; to determine whether different analytical approaches are likely to alter the conclusions of adverse event meta-analyses; and to inform efforts to promote clinical trial transparency and data sharing.DesignSystematic review and meta-analysis of randomized controlled trials.Data sourcesGlaxoSmithKline’s (GSK’s) ClinicalStudyDataRequest.com for individual patient level data (IPD) and GSK’s Study Register platforms, MEDLINE, PubMed, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, Scopus, and ClinicalTrials.gov from inception to January 2019 for summary level data.Eligibility criteria for selecting studiesRandomized, controlled, phase II-IV clinical trials that compared rosiglitazone with any control for at least 24 weeks in adults.Data extraction and synthesisFor analyses of trials for which IPD were available, a composite outcome of acute myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death was examined. These four events were examined independently as secondary analyses. For analyses including trials for which IPD were not available, myocardial infarction and cardiovascular related death were examined, which were determined from summary level data. Multiple meta-analyses were conducted that accounted for trials with zero events in one or both arms with two different continuity corrections (0.5 constant and treatment arm) to calculate odds ratios and risk ratios with 95% confidence intervals.Results33 eligible trials were identified from ClinicalStudyDataRequest.com for which IPD were available (21 156 patients). Additionally, 103 trials for which IPD were not available were included in the meta-analyses for myocardial infarction (23 683 patients), and 103 trials for which IPD were not available contributed to the meta-analyses for cardiovascular related death (22 772 patients). Among 29 trials for which IPD were available and that were included in previous meta-analyses using GSK’s summary level data, more myocardial infarction events were identified by using IPD instead of summary level data for 26 trials, and fewer cardiovascular related deaths for five trials. When analyses were limited to trials for which IPD were available, and a constant continuity correction of 0.5 and a random effects model were used to account for trials with zero events in only one arm, patients treated with rosiglitazone had a 33% increased risk of a composite event compared with controls (odds ratio 1.33, 95% confidence interval 1.09 to 1.61; rosiglitazone population: 274 events among 11 837 patients; control population: 219 events among 9319 patients). The odds ratios for myocardial infarction, heart failure, cardiovascular related death, and non-cardiovascular related death were 1.17 (0.92 to 1.51), 1.54 (1.14 to 2.09), 1.15 (0.55 to 2.41), and 1.18 (0.60 to 2.30), respectively. For analyses including trials for which IPD were not available, odds ratios for myocardial infarction and cardiovascular related death were attenuated (1.09, 0.88 to 1.35, and 1.12, 0.72 to 1.74, respectively). Results were broadly consistent when analyses were repeated using trials with zero events across both arms and either of the two continuity corrections was used.ConclusionsThe results suggest that rosiglitazone is associated with an increased cardiovascular risk, especially for heart failure events. Although increased risk of myocardial infarction was observed across analyses, the strength of the evidence varied and effect estimates were attenuated when summary level data were used in addition to IPD. Because more myocardial infarctions and fewer cardiovascular related deaths were reported in the IPD than in the summary level data, sharing IPD might be necessary when performing meta-analyses focused on safety.Systematic review registrationOSF Home https://osf.io/4yvp2/.


2019 ◽  
Vol 5 (1) ◽  
pp. e000501 ◽  
Author(s):  
Manuel Trinidad-Fernandez ◽  
Manuel Gonzalez-Sanchez ◽  
Antonio I Cuesta-Vargas

ObjectiveTo assess whether Functional Movement Screen (FMS) score is associated with subsequent injuries in healthy sportspeople.DesignSystematic review and meta-analysis.Data sourcesThe following electronic databases were searched to December 2017: Medline, PubMed, PsycINFO, SPORTDiscus, Cumulative Index of Nursing and Allied Health Literature, Scopus, Embase, and Physiotherapy Evidence Database.Eligibility criteria for selecting studiesEligibility criteria included (1) prospective cohort studies that examined the association between FMS score (≤14/21) and subsequent injuries, (2) a sample of healthy and active participants without restrictions in gender or age, and (3) the OR was the effect size and the main outcome.ResultsThirteen studies met the criteria for the systematic review and 12 were included in the meta-analysis. In 5 of the 12 studies, and among female athletes in 1 study, FMS score ≤14 out of 21 points was associated with subsequent injuries. The overall OR of the selected studies in the meta-analysis was 1.86 (95% CI 1.32 to 2.61) and showed substantial heterogeneity (I2=70%).Summary/ConclusionWhether or not a low FMS score ≤14 out of 21 points is associated with increased risk of injury is unclear. The heterogeneity of the study populations (type of athletes, age and sport exposure) and the definition of injury used in the studies make it difficult to synthesise the evidence and draw definitive conclusions.Trial registration numberCRD42015015579.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16053-e16053 ◽  
Author(s):  
Carlos Alberto Lopez ◽  
Elham Azimi-Nekoo ◽  
Su Yun Chung ◽  
James Newman ◽  
Janice Shen ◽  
...  

e16053 Background: Fluoropyrimidines such as 5-FU and capecitabine are known to be cardiotoxic drugs. TAS-102 (trifluridine-tipiracil) is a novel oral fluoropyrimidine that was recently FDA approved to treat gastric and colon cancer. However, the incidence of cardiac related events of TAS-102 is not fully ascertained. We performed a meta-analysis and systematic review to determine the incidence of cardiotoxic events associated with TAS-102. Methods: We performed a literature search through PubMed, Embase, and Web of Science to identify any publications in any language up to December 31st, 2019 where TAS-102 (and equivalent terms such as “trifluridine-tipiracil” and “Lonsurf”) was used. These were then manually reviewed to identify any publications reporting cardiac events. Randomized controlled trials (RCTs) were included for meta-analysis to determine the incidence of cardiotoxic events, which were summarized as pooled odds ratios (OR) when compared to placebo. Non-randomized, non-controlled clinical trials (phase I and phase II studies) were included in the systematic review but excluded from the pooled OR calculation. Results: 869 publications were identified in the initial literature search, of which 17 trials (3 Phase III studies, 6 Phase II studies, and 8 phase I studies) met inclusion criteria. A total of 1,877 patients among 4 RCTs were included in the meta-analysis. Compared with placebo, TAS-102 did not increase the risk of myocardial infarction (OR 1.97 95% CI [0.22-17.89]), hypertension (OR 0.73 95% CI [0.37, 1.44]), palpitations (OR 1.51 95% CI [0.30, 7.56]), cardio-pulmonary arrest (OR 0.83 95% CI [0.11-6.32]), or syncope (OR 1.50 95% CI [0.06-37.14]). Among the 1,252 patients receiving TAS-102, the overall incidence of cardiovascular events was low, with hypertension being the most common side effect (21 events), followed by palpitations (6 events), cardiopulmonary arrest (2 events), and myocardial infarction (3 events), though there was no statistically significant increased risk compared to placebo. No deaths were reported. Conclusions: Unlike other fluoropyrimidines, TAS-102 appears to be a cardiogentle drug, with no increased risk of cardiac events compared to placebo. Since fluoropyrimidines remain the backbone of treatment for gastrointestinal malignancies, TAS-102 can offer an alternative to patients who developed cardiotoxicities from other agents. Prospective studies with consideration of cardiac risk factors are required.


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