scholarly journals The Cardiovascular Risks of Fostamatinib in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuehong Chen ◽  
Huan Liu ◽  
Yupeng Huang ◽  
Sang Lin ◽  
Geng Yin ◽  
...  

Objective: This systematic review and meta-analysis is aimed at assessing the risks of cardiovascular adverse events in patients with rheumatoid arthritis (RA) who have been treated with fostamatinib.Methods: The electronic databases of OVID Medline, OVID EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify studies that reported cardiovascular events or hypertension in RA patients treated with fostamatinib. Two reviewers separately and simultaneously screened the retrieved studies based on study selection criteria, collected data and performed methodological quality assessments. The effect size of meta-analysis was estimated by the Peto odds ratio (OR) or relative risk (RR) with 95% confidence intervals (95%CI). Funnel plot was used to estimate publication bias and sensitivity analysis was performed to test the robustness of the results.Results: A total of 12 trials composed of 5,618 participants with low to moderate risk of bias were included. In comparison to the placebo, the use of fostamatinib was found to elevate the risk of hypertension (RR=3.82, 95%CI 2.88–5.05) but was not associated with the risks of all-cause death (Peto OR=0.16, 95%CI 0.02–1.24), major adverse cardiovascular events (Peto OR=1.24, 95%CI 0.26–5.97), pulmonary heart disease and disease of pulmonary circulation (Peto OR=1.23, 95%CI 0.13–11.87), in addition to other forms of heart disease (Peto OR=1.96, 95%CI 0.72–5.38). Furthermore, sensitivity analysis showed no significant change in effective trends and no publication bias was found.Conclusion: Fostamatinib is associated with increased risk of hypertension; however, no increased risks of cardiovascular events were observed. Further well-planned cohort studies with large study populations and longer follow-up times are needed to elucidate the outcomes.Systematic Review Registration: [PROSPERO], identifier [CRD42020198217].

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
I Giacchetta ◽  
M Chiavarini ◽  
G Naldini ◽  
R Fabiani

Abstract Background The probability of developing invasive cutaneous malignant melanoma (CMM) is higher in women than in men up until the age of 49. Several studies investigated the association between hormonal factors and CMM. The aim of this systematic review and meta-analysis is to summarize the evidence on the association between Oral Contraceptives (OC) and the risk of CMM. Methods This review and meta-analysis follow the PRISMA guidelines. A systematic literature search was conducted on Medline and Web of Science until December 2019. Studies were eligible if reported a risk estimate for the association between OC and CMM. Heterogeneity testing was performed using Cochran's Q and I2 statistics. Publication bias was assessed by Egger's test and Begg's test. Meta-analysis was performed using random effect model. Results The results of the pooled analysis of all 32 studies showed no significant association between OC and the risk of CMM (OR 1.02; 95% CI 0.94-1.11; I2=39.32%, p = 0.013). The stratified analyses by study design found no significant association between OC and the risk of CMM neither in the 18 case-control studies (OR 1.02; 95% CI 0.87-1.21; I2=56.91%, p = 0.002) nor in the 14 cohort studies (OR 1.04; 95% CI 0.98-1.11; I2=0.00%, p = 0.557). No significant publication bias could be detected by Egger's test or Begg's test. Conclusions This meta-analysis of available literature suggests no significant association between OC and the risk of developing CMM. Further investigations are needed to evaluate the possible relationship of OC use and other hormonal factors potentially contributing to the increased risk of CMM in women during their reproductive years. Key messages Oral contraceptives (OC) do not significantly contribute to the risk of Cutaneous Malignant Melanoma (CMM). Further studies are needed to investigate the potential role of other hormonal factors in the increased probability of developing CMM in women during their reproductive years.


Author(s):  
Farzane Saeidifard ◽  
Jose R Medina Inojosa ◽  
Colin P West ◽  
Thomas P Olson ◽  
Virend K Somers ◽  
...  

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.


Author(s):  
BibiAsma Syed ◽  
Mashael Alshafai ◽  
Karam Turk-Adawi

Background: Hemoglobinopathies are among the most common inherited genetic diseases. The World Health Organization estimates that at least 5% of the world’s population are carriers for hemoglobinopathies (2.9% for thalassemia and 2.3% for sickle cell disease). Programs like premarital screening (PMS) have been developed in most Middle East countries on a mandatory basis to reduce atrisk marriages by providing counseling after a confirmed “genetic carrier” state for hemoglobinopathies. Aim/Objective: The aim of this systematic review and meta-analysis was to estimate the prevalence of atrisk marriages globally and see the variation by region, income level, ethnicity, study period, implementation year of PMS program, study design and consanguinity proportion. Methods: Different databases such as PubMed, Science Direct, and Scopus were searched systematically by using key terms and MeSH Terms. Studies from Google Scholar and reference lists of studies were also collected, and the author extracted all relevant data. Two reviewers independently conducted quality assessment by using Hoy et al (2012) risk of bias tool. Quality effects model (QEM) was used due to considerable heterogeneity observed between studies. Subgroup analysis and sensitivity analysis were also performed for assessing the causes of heterogeneity. Results: A total of 15 studies were included in this meta-analysis. The overall pooled prevalence of at-risk marriages among total couples at-risk was 64% (95% CI: 49%- 78%). Estimates of several subgroups were found to be different as compared to the overall pooled estimate. Funnel plot and Doi plot indicated the presence of publication bias. Sensitivity analysis including only studies with low risk led to a pooled estimate of 52% (CI: 46%, 57%) and indicated absence of publication bias. Conclusion and recommendations: The pooled estimates varied widely and there was a substantial heterogeneity among studies, therefore, there is a need for more well-designed studies across different countries. Moreover, the importance of the quality of counseling sessions should be stressed and combined with efforts in other community sectors, such as high schools where students can attain high knowledge regarding genetic diseases before the age of marriage.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
John A. Cuenca ◽  
Javier Balda ◽  
Ana Palacio ◽  
Larry Young ◽  
Michael H. Pillinger ◽  
...  

Background. Febuxostat is approved in the United States for the management of hyperuricemia in patients with gout. In November 2017 the FDA released a warning alert on a possible link between febuxostat and cardiovascular disease (CVD) reported in a single clinical trial. Objective. To conduct a systematic review and meta-analysis and assess the risk of major adverse cardiovascular events (MACE) in patients receiving febuxostat compared to a control group. Methods. We searched the MEDLINE and EMBASE database for studies published up until March 2018. We included randomized clinical trials (RCTs) that compared febuxostat to control groups including placebo and allopurinol. We calculated the pooled relative risk (RR) of MACE and cardiovascular disease (CVD) mortality with the corresponding 95% confidence intervals (CI). Results. Our search yielded 374 potentially relevant studies. Among the 25 RCTs included in the systematic review, 10 qualified for the meta-analysis. Among the 14,402 subjects included, the median age was 54 years (IQR 52-67) and 90% were male (IQR 82-96); 8602 received febuxostat, 5118 allopurinol, and 643 placebo. The pooled RR of MACE for febuxostat was 0.9; 95% CI 0.6-1.5 (p= 0.96) compared to the control. The RR of CV-related death for febuxostat was 1.29; 95% CI 1.01-1.66 (p=0.03). Conclusions. Compared with other SU-lowering treatments, febuxostat does not increase or decrease the risk of cardiovascular disease but may increase the risk of CVD death. More RCTs measuring cardiovascular safety as a primary outcome are needed to adequately evaluate the risk of CVD with febuxostat.


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.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Zhenliu Zhu ◽  
Fengying Zhang ◽  
Yunxia Liu ◽  
Shuqin Yang ◽  
Chunting Li ◽  
...  

Until now, the relationship of obstructive sleep apnoea (OSA) with diabetic retinopathy (DR) was controversial. This meta-analysis was performed to obtain definitive conclusion on this topic. Relevant articles were searched on databases of Pubmed, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The articles were selected according to inclusion and exclusion criteria. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of OSA with risk of DR.I2andPvalue were used to assess the presence of heterogeneity.I2≥ 50% orP<0.05indicated significant heterogeneity. Sensitivity analysis was performed to evaluate the robustness of pooled results. Begg’s funnel plot and Egger’s regression analysis were adopted to assess publication bias. 6 eligible studies were selected in the present meta-analysis. The pooled results indicated that OSA was significantly associated with increased risk of DR (OR = 2.01, 95% CI = 1.49–2.72). Subgroup analysis based on type of diabetes mellitus suggested that OSA was related to DR in both Type 1 and Type 2 diabetes mellitus. Sensitivity analysis demonstrated that pooled results were robust. No significant publication bias was observed (P=0.128). The results indicate that OSA is related to increased risk of DR.


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.


Stroke ◽  
2020 ◽  
Vol 51 (2) ◽  
pp. 387-394 ◽  
Author(s):  
Luciano A. Sposato ◽  
Melody Lam ◽  
Britney Allen ◽  
Salimah Z. Shariff ◽  
Gustavo Saposnik ◽  
...  

Background and Purpose— Stroke risk is sex-specific, but little is known about sex differences of poststroke major adverse cardiovascular events (MACEs). Stroke-related brain damage causes autonomic dysfunction and inflammation, sometimes resulting in cardiac complications. Sex-specific cardiovascular susceptibility to stroke without the confounding effect of preexisting heart disease constitutes an unexplored field because previous studies focusing on sex differences in poststroke MACE have not excluded patients with known cardiovascular comorbidities. We therefore investigated sex-specific risks of incident MACE in a heart disease-free population-based cohort of patients with first-ever ischemic stroke and propensity-matched individuals without stroke. Methods— We included Ontario residents ≥66 years, without known cardiovascular comorbidities, with first-ever ischemic stroke between 2002 and 2012 and propensity-matched individuals without stroke. We investigated the 1-year risk of incident MACE (acute coronary syndrome, myocardial infarction, incident coronary artery disease, coronary revascularization procedures, incident heart failure, or cardiovascular death) separately for females and males. For estimating cause-specific adjusted hazard ratios, we adjusted Cox models for variables with weighted standardized differences >0.10 or those known to influence MACE risk. Results— We included 93 627 subjects without known cardiovascular comorbidities; 21 931 with first-ever ischemic stroke and 71 696 propensity-matched subjects without stroke. Groups were well-balanced on propensity-matching variables. There were 53 476 women (12 421 with and 41 055 without ischemic stroke) and 40 151 men (9510 with and 30 641 without ischemic stroke). First-ever ischemic stroke was associated with increased risk of incident MACE in both sexes. The risk was time-dependent, highest within 30 days (women: adjusted hazard ratio, 25.1 [95% CI, 19.3–32.6]; men: aHR, 23.4 [95% CI, 17.2–31.9]) and decreasing but remaining significant between 31 and 90 days (women: aHR, 4.8 [95% CI, 3.8–6.0]; men: aHR, 4.2 [95% CI, 3.3–5.4]), and 91 to 365 days (aHR, 2.1 [95% CI, 1.8–2.3]; men: aHR, 2.0 [95% CI, 1.7–2.3]). Conclusions— In this large population-based study, ischemic stroke was independently associated with increased risk of incident MACE in both sexes.


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