Comparison of poly(ADP-ribose) polymerase inhibitors (PARPi's) as maintenance therapy for platinum-sensitive ovarian cancer: Systematic review and network meta-analysis.

e18070 Background: Over the past decade, 3 PARPi's (olaparib, niraparib and rucaparib) have been approved by the FDA as maintenance therapy for recurrent ovarian cancer. However, thus far, no trial compared the 3 approved PARPi's in the overall population, in patients with BRCA mutations (BRCAm), or in those with wild-type BRCA (BRCAwt). Methods: We performed a systematic review and identified relevant literature from Embase, Pubmed and Cochrane Library. To be included in the analysis, studies had to be phase 2 or 3 randomized controlled trials (RCT) of platinum-sensitive recurrent or newly diagnosed ovarian cancer, randomized to placebo or PARPi as maintenance therapy and where complete or partial response was documented. A frequentist network meta-analysis was used for indirect comparisons between the different PARPi's to assess superiority in terms of progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, 6 RCTs involving 2,770 patients, were included in the network meta-analysis. Results from the indirect comparisons revealed no statistically significant differences between the 3 different PARPi's with respect to OS. PFS results demonstrated a nonsignificant trend supporting superiority for niraparib in all patients as well as in BRCAm patients (Table). Only 2 studies reported OS results for niraparib and none reported OS results for rucaparib. Niraparib showed a statistically significant increased risk for all grade thrombocytopenia and neutropenia. Conclusions: Our analysis demonstrates no statistically significant differences between the 3 PARPi’s in any of the analyzed groups, and a trend supporting PFS superiority for niraparib in all patients and in BRCAm patients, while having greater risk for thrombocytopenia and neutropenia. Additional OS results are pending from current studies, and would be useful for elucidating the relative roles of the different PARPi's in platinum-sensitive ovarian cancer. [Table: see text]

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Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis

Cancers ◽

10.3390/cancers12103026 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3026

Author(s):

Amos Stemmer ◽

Inbal Shafran ◽

Salomon M. Stemmer ◽

Daliah Tsoref

Keyword(s):

Ovarian Cancer ◽

Maintenance Therapy ◽

Randomized Clinical Trials ◽

Meta Analysis ◽

Progression Free Survival ◽

Wild Type ◽

Brca Mutations ◽

Increased Risk ◽

Significant Difference ◽

Indirect Comparisons

Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.

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Abstract WP165: Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis

Stroke ◽

10.1161/str.47.suppl_1.wp165 ◽

2016 ◽

Vol 47 (suppl_1) ◽

Author(s):

Ajay Gupta ◽

Ashley Giambrone ◽

Gino Gialdini ◽

Caitlin B Finn ◽

Diana Delgado ◽

...

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Strong Predictor ◽

Brain Infarction ◽

Meta Analysis ◽

Relevant Literature ◽

Large Population ◽

Cochrane Library ◽

Increased Risk ◽

Silent Brain Infarction

Introduction: Silent brain infarction (SBI) on magnetic resonance imaging (MRI) is relatively frequently detected but of uncertain clinical significance. Hypothesis: We hypothesized that a pooled estimate from all relevant published and unpublished sources will demonstrate SBI to be an independent risk factor for future stroke. Methods: We performed a systematic review and meta-analysis to summarize the association between MRI-defined SBI and future stroke. We searched for relevant literature in Ovid MEDLINE, Ovid Embase, and the Cochrane Library Database from inception to April 3, 2015. All cohort studies involving adults with MRI detection of SBI who were subsequently followed for incident clinically-defined stroke were eligible. Study data and quality assessment was recorded in duplicate with disagreements in data extraction resolved by a third reader. Results: We studied 14,764 subjects from 13 studies with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% CI 2.24-3.86, P<0.0001; Q=39.649, P<0.0001, Figure Panel A). In the 8 studies of 10,427 subjects providing cardiovascular risk factor-adjusted hazard ratios (HR), SBI was an independent predictor of incident stroke (HR of 2.08 [95% CI 1.69-2.56, P<0.0001, Figure Panel B]; Q=8.99, P=0.253). In a subgroup analysis pooling 9,483 stroke-free individuals from large population-based studies, SBI was present in ∼18% of participants and remained a strong predictor of future stroke (HR 2.06 [95% CI 1.64-2.59], p<0.01). A potential limitation of the existing literature was that MRI techniques for detecting SBI were variable across studies and were detected using older generation MRI equipment. Conclusion: SBI is present in approximately 1 in 5 stroke-free older adults and is associated with 2-fold increased risk of future stroke.

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Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies

Journal of Translational Medicine ◽

10.1186/s12967-021-02878-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Kei Hayashida ◽

Ryosuke Takegawa ◽

Muhammad Shoaib ◽

Tomoaki Aoki ◽

Rishabh C. Choudhary ◽

...

Keyword(s):

Systematic Review ◽

Reperfusion Injury ◽

Animal Studies ◽

Ischemia Reperfusion Injury ◽

Myocardial Dysfunction ◽

Ischemia Reperfusion ◽

Meta Analysis ◽

Relevant Literature ◽

Human Studies ◽

Cochrane Library

Abstract Background Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. Methods We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. Results Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI–associated myocardial dysfunction after cardiac surgery. Conclusion The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

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EXPRESS: Stroke risk following traumatic brain injury: systematic review and meta-analysis

International Journal of Stroke ◽

10.1177/17474930211004277 ◽

2021 ◽

pp. 174749302110042

Author(s):

Grace Mary Turner ◽

Christel McMullan ◽

Olalekan Lee Aiyegbusi ◽

Danai Bem ◽

Tom Marshall ◽

...

Keyword(s):

Systematic Review ◽

Stroke Risk ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Cochrane Library ◽

Control Group ◽

Large Sample Size ◽

Hazard Ratios ◽

Increased Risk ◽

The Cochrane Library

Aims To investigate the association between TBI and stroke risk. Summary of review We undertook a systematic review of MEDLINE, EMBASE, CINAHL, and The Cochrane Library from inception to 4th December 2020. We used random-effects meta-analysis to pool hazard ratios (HR) for studies which reported stroke risk post-TBI compared to controls. Searches identified 10,501 records; 58 full texts were assessed for eligibility and 18 met the inclusion criteria. The review included a large sample size of 2,606,379 participants from four countries. Six studies included a non-TBI control group, all found TBI patients had significantly increased risk of stroke compared to controls (pooled HR 1.86; 95% CI 1.46-2.37). Findings suggest stroke risk may be highest in the first four months post-TBI, but remains significant up to five years post-TBI. TBI appears to be associated with increased stroke risk regardless of severity or subtype of TBI. There was some evidence to suggest an association between reduced stroke risk post-TBI and Vitamin K antagonists and statins, but increased stroke risk with certain classes of antidepressants. Conclusion TBI is an independent risk factor for stroke, regardless of TBI severity or type. Post-TBI review and management of risk factors for stroke may be warranted.

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Executive functions in children with heart disease: a systematic review and meta-analysis

Cardiology in the Young ◽

10.1017/s1047951121001074 ◽

2021 ◽

pp. 1-9

Author(s):

William M. Jackson ◽

Nicholas Davis ◽

Johanna Calderon ◽

Jennifer J. Lee ◽

Nicole Feirsen ◽

...

Keyword(s):

Systematic Review ◽

Executive Functions ◽

Data Extraction ◽

Meta Analysis ◽

Executive Dysfunction ◽

Cochrane Library ◽

Planning Problem ◽

Healthy Controls ◽

Cross Sectional ◽

Increased Risk

Abstract Context: People with CHD are at increased risk for executive functioning deficits. Meta-analyses of these measures in CHD patients compared to healthy controls have not been reported. Objective: To examine differences in executive functions in individuals with CHD compared to healthy controls. Data sources: We performed a systematic review of publications from 1 January, 1986 to 15 June, 2020 indexed in PubMed, CINAHL, EMBASE, PsycInfo, Web of Science, and the Cochrane Library. Study selection: Inclusion criteria were (1) studies containing at least one executive function measure; (2) participants were over the age of three. Data extraction: Data extraction and quality assessment were performed independently by two authors. We used a shifting unit-of-analysis approach and pooled data using a random effects model. Results: The search yielded 61,217 results. Twenty-eight studies met criteria. A total of 7789 people with CHD were compared with 8187 healthy controls. We found the following standardised mean differences: −0.628 (−0.726, −0.531) for cognitive flexibility and set shifting, −0.469 (−0.606, −0.333) for inhibition, −0.369 (−0.466, −0.273) for working memory, −0.334 (−0.546, −0.121) for planning/problem solving, −0.361 (−0.576, −0.147) for summary measures, and −0.444 (−0.614, −0.274) for reporter-based measures (p < 0.001). Limitations: Our analysis consisted of cross-sectional and observational studies. We could not quantify the effect of collinearity. Conclusions: Individuals with CHD appear to have at least moderate deficits in executive functions. Given the growing population of people with CHD, more attention should be devoted to identifying executive dysfunction in this vulnerable group.

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The association between XRCC3 rs1799794 polymorphism and cancer risk: a meta-analysis of 34 case–control studies

BMC Medical Genomics ◽

10.1186/s12920-021-00965-4 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Weiqing Liu ◽

Shumin Ma ◽

Lei Liang ◽

Zhiyong Kou ◽

Hongbin Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Thyroid Cancer ◽

Cancer Risk ◽

Large Scale ◽

Meta Analysis ◽

Cochrane Library ◽

Cancer Type ◽

Increased Risk ◽

Risk Of Cancer

Abstract Background Studies on the XRCC3 rs1799794 polymorphism show that this polymorphism is involved in a variety of cancers, but its specific relationships or effects are not consistent. The purpose of this meta-analysis was to investigate the association between rs1799794 polymorphism and susceptibility to cancer. Methods PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies through June 11, 2019. All analyses were performed with Stata 14.0. Subgroup analyses were performed by cancer type, ethnicity, source of control, and detection method. A total of 37 studies with 23,537 cases and 30,649 controls were included in this meta-analysis. Results XRCC3 rs1799794 increased cancer risk in the dominant model and heterozygous model (GG + AG vs. AA: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 1.00–1.08, P = 0.051; AG vs. AA: OR = 1.05, 95% CI = 1.00–1.01, P = 0.015). The existence of rs1799794 increased the risk of breast cancer and thyroid cancer, but reduced the risk of ovarian cancer. In addition, rs1799794 increased the risk of cancer in the Caucasian population. Conclusion This meta-analysis confirms that XRCC3 rs1799794 is related to cancer risk, especially increased risk for breast cancer and thyroid cancer and reduced risk for ovarian cancer. However, well-designed large-scale studies are required to further evaluate the results.

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Safety and efficacy of mycophenolate mofetil in treating neuromyelitis optica spectrum disorders: a protocol for systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-040371 ◽

2020 ◽

Vol 10 (11) ◽

pp. e040371

Author(s):

Mengyu Han ◽

Luqi Nong ◽

Ziqiang Liu ◽

You Chen ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Mycophenolate Mofetil ◽

Neuromyelitis Optica ◽

Meta Analysis ◽

Grey Literature ◽

Relevant Literature ◽

Biomedical Literature ◽

Cochrane Library ◽

Neuromyelitis Optica Spectrum Disorders ◽

Spectrum Disorders

IntroductionNeuromyelitis optica spectrum disorders (NMOSD) is an inflammatory and heterogeneous astrocyte disorder of the central nervous system with the characteristic of higher incidence in women and Asian people. Most patients with NMOSD have a course of recurrence and remission that is prone to cause paralysis and blindness. Several studies have confirmed the efficacy and promising prospect of mycophenolate mofetil (MMF) in the treatment of NMOSD. Yet its therapeutic effect and safety are controversial. Although there has been two published literature that is relevant to the topic of this study, both of them have certain defects, and they can only provide answers about the efficacy or safety of MMF in the treatment of NMOSD from partial perspectives or conclusions. This research aims to perform a direct and comprehensive systematic review and meta-analysis to evaluate MMF’s effectiveness and safety in treating NMOSD.Methods and analysisThis systematic review will cover all comparative researches, from randomised controlled trials to cohort studies, and case–control study. A relevant literature search will be conducted in PubMed, Web of Science, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database and Chinese Biomedical Literature Database from their inception to 31 June 2020. We will also search registers of clinical trials, potential grey literature and abstracts from conferences. There are no limits on language and publication status. The reporting quality and risk of bias will be assessed by two researchers independently. Expanded Disability Status Scales and annualised relapse rate will be evaluated as the primary outcome. The secondary outcomes will consist of the frequency and severity of adverse events, best-corrected visual acuity, relapse-free rate and time to the next attack. A meta-analysis will be performed using RevMan V.5.3 software provided by the Cochrane Collaboration and Stata V.12.0.Ethics and disseminationBecause the data used for this systematic review will be exclusively extracted from published studies, ethical approval and informed consent of patients will not be required. The systematic review will be published in a peer-reviewed journal, presented at conferences and will be shared on social media platforms.PROSPERO registration numberCRD42020164179.

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Prevalence of Syphilis among Pregnant Women in Sub-Saharan Africa: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2019/4562385 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Siraj Hussen ◽

Birkneh Tilahun Tadesse

Keyword(s):

Systematic Review ◽

Pregnant Women ◽

Screening Program ◽

Meta Analysis ◽

Relevant Literature ◽

Sub Saharan Africa ◽

Cochrane Library ◽

Forest Plot ◽

Pooled Prevalence ◽

Sub Saharan

Objective. Syphilis is one of the most imperative STIs, caused by the spirochete Treponema pallidum. During pregnancy it is associated with disastrous health outcomes in the newborn. In sub-Saharan Africa, study findings on the prevalence of syphilis among pregnant women are highly dispersed and inconsistent. The aim of the current review is to conduct a systematic review and meta-analysis of syphilis in sub-Saharan Africa among pregnant women. Design. Systematic review and meta-analysis. Data Sources. Databases including MEDLINE, PubMed, Cochrane Library, Google Scholar, and HINARI and reference lists of previous prevalence studies were systematically searched for relevant literature from January 1999 to November 2018. Results were presented in forest plot, tables, and figures. Random-effects model was used for the meta-analysis. For the purpose of this review, a case of syphilis was defined as positive treponemal or nontreponemal tests among pregnant women. Data Extraction. Our search gave a total of 262 citations from all searched databases. Of these, 44 studies fulfilling the inclusion criteria and comprising 175,546 subjects were finally included. Results. The pooled prevalence of syphilis among pregnant women in sub-Saharan Africa was 2.9% (95%CI: 2.4%-3.4%). East and Southern African regions had a higher syphilis prevalence among pregnant women (3.2%, 95% CI: 2.3%-4.2% and 3.6%, 95%CI: 2.0%-5.1%, respectively) than the sub-Saharan African pooled prevalence. The prevalence of syphilis among pregnant women in most parts of the region seemed to have decreased over the past 20 years except for the East African region. However, prevalence did not significantly differ by region and time period. Conclusion. This review showed a high prevalence of syphilis in sub-Saharan Africa among pregnant women. The evidence suggests strengthening the screening program during pregnancy as part of the care package during antenatal care visits. Programs focusing on primary prevention of syphilis in women should also be strengthened.

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Cerebrovascular Complications After Upper Extremity Access for Complex Aortic Interventions: A Systematic Review and Meta-Analysis

CardioVascular and Interventional Radiology ◽

10.1007/s00270-019-02330-6 ◽

2019 ◽

Vol 43 (2) ◽

pp. 186-195 ◽

Cited By ~ 6

Author(s):

Max M. Meertens ◽

Charlotte C. Lemmens ◽

Gustavo S. Oderich ◽

Geert W. H. Schurink ◽

Barend M. E. Mees

Keyword(s):

Systematic Review ◽

Endovascular Treatment ◽

Upper Extremity ◽

Meta Analysis ◽

Aortic Aneurysms ◽

Cochrane Library ◽

Cerebrovascular Event ◽

Cerebrovascular Complications ◽

Increased Risk ◽

Aortic Interventions

Abstract Purpose The purpose of this study was to review the risk of developing cerebrovascular complications from upper extremity access during endovascular treatment of complex aortic aneurysms. Methods A systematic review and meta-analysis were conducted according to the PRISMA guideline. An electronic search of the public domains Medline (PubMed), Embase (Ovid), Web of Science and Cochrane Library was performed to identify studies related to the treatment of aortic aneurysms involving upper extremity access. Meta-analysis was used to compare the rate of cerebrovascular event after left, right and bilateral upper extremity access. Results are presented as relative risk (RR) and 95% confidence intervals (CIs). Results Thirteen studies including 1276 patients with complex endovascular treatment of aortic aneurysms using upper extremity access were included in the systematic review. Left upper extremity access (UEA) was used in 1028 procedures, right access in 148 and bilateral access in 100 procedures. The rate of cerebrovascular complications for patients treated through left UEA was 1.7%, through right UEA 4% and through bilateral UEA 5%. In the meta-analysis, we included seven studies involving 645 patients treated with a left upper extremity access, 87 patients through a right and 100 patients through a bilateral upper extremity access. Patients, who underwent right-sided (RR 5.01, 95% CI 1.51–16.58, P = 0.008) or bilateral UEA (RR 4.57, 95% CI 1.23–17.04, P = 0.02), had a significantly increased risk of cerebrovascular events compared to those who had a left-sided approach. Conclusion Left upper extremity access is associated with a significantly lower rate of cerebrovascular complications as compared to right or bilateral upper extremity access.

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Effect of Early Intravenous Immunoglobulin Therapy in Kawasaki Disease: A Systematic Review and Meta-Analysis

Frontiers in Pediatrics ◽

10.3389/fped.2020.593435 ◽

2020 ◽

Vol 8 ◽

Author(s):

Fan Yan ◽

Huayong Zhang ◽

Ruihua Xiong ◽

Xingfeng Cheng ◽

Yang Chen ◽

...

Keyword(s):

Systematic Review ◽

Kawasaki Disease ◽

Intravenous Immunoglobulin ◽

Meta Analysis ◽

The United States ◽

Cochrane Library ◽

Ivig Treatment ◽

Intravenous Immunoglobulin Therapy ◽

Increased Risk ◽

Significant Difference

Background: In the latest 2017 American Heart Association guidelines for Kawasaki disease (KD), there are no recommendations regarding the early administration of intravenous immunoglobulin (IVIG). Therefore, the purpose of this systematic review and meta-analysis was to investigate the effects of early IVIG therapy on KD.Methods: We searched databases including the PubMed, Medline, the Cochrane Library, and the Clinicaltrials.gov website until July 2019.Results: Fourteen studies involving a total of 70,396 patients were included. Early treatment with IVIG can lead to an increased risk of IVIG unresponsiveness [OR 2.24; 95% CI (1.76, 2.84); P = 0.000]. In contrast to the studies performed in Japan [OR 1.27; 95% CI (0.98, 1.64); P = 0.074] that found no significant difference in coronary artery lesions (CAL) development, studies conducted in China [OR 0.73; 95% CI (0.66, 0.80); P = 0.000] and the United States [OR 0.50; 95% CI (0.38, 0.66); P = 0.000] showed a reduced risk in the occurrence of CAL with early IVIG treatment.Conclusions: At present, the evidence does not support the treatment with IVIG in the early stage of the onset of KD. But, early IVIG treatment could be a protective factor against the development of CAL, which needs to be further clarified.

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