Abstract 12138: Angiotensin Blockade Reduces Aortic Dilatation in Patients With Marfan Syndrome: A Meta-Analysis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Partha Sardar ◽  
Amartya Kundu ◽  
Omosalewa Adenikinju ◽  
Gerald Pekler ◽  
Saurav Chatterjee ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Aortic Root ◽  
Meta Analysis ◽  
Conclusive Evidence ◽  
Sensitivity Analyses ◽  
Current Evidence ◽  
Cochrane Central Register ◽  
Aortic Dilatation ◽  
Observation Study ◽  
Aortic Root Dilatation

Introduction: Recently few studies evaluated the effects of ACE/ARB in patients with Marfan syndrome. However, as majority of the studies were small and mainly pilot studies, conclusive evidence of benefit with ACE/ARB in this scenario is still pending. The objective of the present meta-analysis was to evaluate the effect of ACE/ARB on the progression of aortic root dilatation in patients with Marfan syndrome. Hypothesis: Treatment with ACE/ARBs is effective for the prevention of aortic-root enlargement in patients with Marfan syndrome. Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Clinical Trials from the inception to April 30, 2013. The main outcome of the present analysis was the change in aortic root diameter with ACE/ABR therapy compared to control. The random effects model of DerSimonian and Laird was used. Results: Four studies were included in the final analysis; three studies were randomized trial and one was observation study. ACE/ARB significantly reduced enlargement of aortic root diameters compared to control; mean difference of -0.97 (95% confidence interval, -1.42 to -0.52; P<0.0001). Consistent benefit of ACE/ARB was observed in all sub-group and sensitivity analyses; against beta blocker, against placebo, in adult patients, with only ARB, analysis with the results from only RCTs. Conclusions: This is the first meta-analysis indicating a beneficial effect of ACE/ARB treatment on aortic root dilatation in patients with Marfan Syndrome. Current evidence supports the use of ARB, specially losartan for this indication.

scholarly journals Losartan for Preventing Aortic Root Dilatation in Patients with Marfan Syndrome: A Meta-Analysis of Randomized Trials

2019 ◽  
Vol 8 (2) ◽  
pp. 365-372 ◽  
Author(s):  
Ayman Elbadawi ◽  
Mohamed A. Omer ◽  
Islam Y. Elgendy ◽  
Ahmed Abuzaid ◽  
Ahmed H. Mohamed ◽  
...  
Keyword(s):  
Marfan Syndrome ◽  
Aortic Root ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Aortic Root Dilatation

Abstract 15146: Updated Meta-Analysis of Role of Angiotensin Blockade in Reducing Aortic Dilatation in Patients With Marfan Syndrome

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Amartya Kundu ◽  
Partha Sardar ◽  
Saurav Chatterjee ◽  
Wilbert S Aronow ◽  
Linda Pape
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Marfan Syndrome ◽  
Aortic Root ◽  
Meta Analysis ◽  
Significant Benefit ◽  
Converting Enzyme ◽  
Aortic Root Dilatation ◽  
Receptor Blockers ◽  
Angiotensin Blockade

Introduction: Patients with Marfan Syndrome have an increased risk of sudden death due to aortic dissection, mostly preceded by aortic dilatation.There has been considerable interest in evaluating the role of angiotensin blockade with Angiotensin Converting Enzyme (ACE) inhibitors or Angiotensin Receptor Blockers (ARB) on reducing the progression of aortic root dilatation in these patients. While earlier studies showed considerable benefit with ACE/ARB, recently large scale Randomized Control Trials showed conflicting results. The purpose of this meta-analysis was to assess the role of angiotensin blockade in reducing the rate of aortic root dilatation in patients with Marfan Syndrome. Methods: We searched PubMed, EMBASE, and Cochrane Central Register of Clinical Trials from the inception to May 30, 2015 using the terms “Marfan syndrome”, “angiotensin converting enzyme inhibitors” and “angiotensin II-receptor blockers”. Data was extracted using standardized protocol.The main outcome of the present analysis was the change in aortic root diameter with ACE/ABR therapy compared to control. The random effects model of DerSimonian and Laird was used. The statistical analysis was done in line with recommendations from the Cochrane Collaboration using Review Manager (RevMan) version 5.3. Results: Six studies enrolling a total of 1252 patients were included in the final analysis. Five were randomized controlled trials and one was an observation study. Analysis showed that there was no significant benefit with ACE/ARB in reducing aortic root dilatation rate compared to control [Mean Difference of -0.24 ; 95 % CI -0.36 to -0.13, P < 0.00001]. Conclusion: Based on the results of this meta analysis which includes data from the most recent trials, there is no significant benefit with ACE/ARB treatment on reducing the rate of aortic root dilatation in patients with Marfan Syndrome.

scholarly journals Conditional power of antidepressant network meta-analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lisa Holper
Keyword(s):  
Meta Analysis ◽  
Indirect Evidence ◽  
Dropout Rate ◽  
Conclusive Evidence ◽  
Effect Sizes ◽  
Current Evidence ◽  
Hamilton Depression Scale ◽  
Conditional Power ◽  
Sample Sizes ◽  
Antidepressant Treatments

Abstract Background Conditional power of network meta-analysis (NMA) can support the planning of randomized controlled trials (RCTs) assessing medical interventions. Conditional power is the probability that updating existing inconclusive evidence in NMA with additional trial(s) will result in conclusive evidence, given assumptions regarding trial design, anticipated effect sizes, or event probabilities. Methods The present work aimed to estimate conditional power for potential future trials on antidepressant treatments. Existing evidence was based on a published network of 502 RCTs conducted between 1979-2018 assessing acute antidepressant treatment in major depressive disorder (MDD). Primary outcomes were efficacy in terms of the symptom change on the Hamilton Depression Scale (HAMD) and tolerability in terms of the dropout rate due to adverse events. The network compares 21 antidepressants consisting of 231 relative treatment comparisons, 164 (efficacy) and 127 (tolerability) of which are currently assumed to have inconclusive evidence. Results Required sample sizes to achieve new conclusive evidence with at least 80% conditional power were estimated to range between N = 894 - 4190 (efficacy) and N = 521 - 1246 (tolerability). Otherwise, sample sizes ranging between N = 49 - 485 (efficacy) and N = 40 - 320 (tolerability) may require stopping for futility based on a boundary at 20% conditional power. Optimizing trial designs by considering multiple trials that contribute both direct and indirect evidence, anticipating alternative effect sizes or alternative event probabilities, may increase conditional power but required sample sizes remain high. Antidepressants having the greatest conditional power associated with smallest required sample sizes were identified as those on which current evidence is low, i.e., clomipramine, levomilnacipran, milnacipran, nefazodone, and vilazodone, with respect to both outcomes. Conclusions The present results suggest that conditional power to achieve new conclusive evidence in ongoing or future trials on antidepressant treatments is low. Limiting the use of the presented conditional power analysis are primarily due to the estimated large sample sizes which would be required in future trials as well as due to the well-known small effect sizes in antidepressant treatments. These findings may inform researchers and decision-makers regarding the clinical relevance and justification of research in ongoing or future antidepressant RCTs in MDD.

scholarly journals Interventional radiology versus operative management for splenic injuries: a study protocol for a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e028172
Author(s):  
Masahiro Kashiura ◽  
Noritaka Yada ◽  
Kazuma Yamakawa
Keyword(s):  
Systematic Review ◽  
Interventional Radiology ◽  
Meta Analysis ◽  
Operative Management ◽  
Sensitivity Analyses ◽  
Definitive Treatment ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Statistical Heterogeneity ◽  
Non Operative Management

IntroductionOver the past decades, the treatment for blunt splenic injuries has shifted from operative to non-operative management. Interventional radiology such as splenic arterial embolisation generally increases the success rate of non-operative management. However, the type of intervention, such as the first definitive treatment for haemostasis (interventional radiology or surgery) in blunt splenic injuries is unclear. Therefore, we aim to clarify whether interventional radiology improves mortality in patients with blunt splenic trauma compared with operative management by conducting a systematic review and meta-analysis.Methods and analysisWe will search the following electronic bibliographic databases to retrieve relevant articles for the literature review: Medline, Embase and the Cochrane Central Register of Controlled Trials. We will include controlled trials and observational studies published until September 2018. We will screen search results, assess the study population, extract data and assess the risk of bias. Two review authors will extract data independently, and discrepancies will be identified and resolved through a discussion with a third author where necessary. Data from eligible studies will be pooled using a random-effects meta-analysis. Statistical heterogeneity will be assessed by using the Mantel-Haenszel χ² test and the I² statistic, and any observed heterogeneity will be quantified using the I² statistic. We will conduct sensitivity analyses according to several factors relevant for the heterogeneity.Ethics and disseminationOur study does not require ethical approval as it is based on the findings of previously published articles. This systematic review will provide guidance on selecting a method for haemostasis of splenic injuries and may also identify knowledge gaps that could direct further research in the field. Results will be disseminated through publication in a peer-reviewed journal and presentations at relevant conferences.PROSPERO registration numberCRD42018108304.

scholarly journals Association between thyroid disorders and COVID-19: a protocol for a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Soraya Doustmohammadian ◽  
Azam Doustmohammadian ◽  
Marjan Momeni
Keyword(s):  
Assessment Tool ◽  
Heart Diseases ◽  
Data Extraction ◽  
Meta Analysis ◽  
Current Evidence ◽  
Thyroid Disorders ◽  
Cochrane Central Register ◽  
Cochrane Reviews ◽  
Increased Risk ◽  
Review Team

Abstract Background The novel coronavirus (COVID-19) epidemic initially appeared in Wuhan, Hubei Province, China, on 31 December 2019 and was spread rapidly worldwide. Most underlying diseases reported with COVID-19 patients are diabetes, hypertension, coronary heart diseases, and cerebrovascular disease. We do not know whether individuals with thyroid disease are at increased risk of COVID-19 infection. Methods Two experienced researchers will conduct an electronic search of the databases including PubMed/MEDLINE, the Cochrane Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ProQuest, for articles published since October 2019. Clinical trials and observational studies will be included. Studies will be screened after de-duplication. A standardized data extraction form will be developed through discussions with the review team and will be revised after piloting. An appropriate risk of bias assessment tool will be used to assess the quality of studies. Two independent reviewers will assess the eligibility, extraction of detailed information, and quality assessment of studies. The results will be pooled for meta-analysis, subgroup analysis and/or descriptive analysis based on the included data conditions. Conclusion Results of this study will provide current evidence on the association of COVID-19 diseases with any thyroid disorders such as hypothyroidism, thyrotoxicosis, and thyroid cancer with or without radioiodine therapy. Findings will be disseminated in peer-reviewed publications and conference presentations. Trial registration PROSPERO registration number: CRD42020184289. https://www.crd.york.ac.uk/PROSPERO/#recordDetails

scholarly journals Comparative Efficacy of Pharmacological and Nonpharmacological Interventions for Acne Vulgaris: A Network Meta-Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Qingyang Shi ◽  
Lizi Tan ◽  
Zhe Chen ◽  
Long Ge ◽  
Xiaoyan Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Physical Symptoms ◽  
Current Evidence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Comparative Efficacy ◽  
Inflammatory Lesions ◽  
Randomized Controlled

Acne has several effects on physical symptoms, but the main impacts are on the quality of life, which can be improved by treatment. There are several acne treatments but less evidence comparing their relative efficacy. Thus, we assessed the comparative efficacy of pharmacological and nonpharmacological interventions for acne. We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to April 2019, to include randomized controlled trials for acne that compared topical antibiotics (TA), benzoyl peroxide (BPO), topical retinoids (TR), oral antibiotics (OA), lasers, light devices including LED device (LED), photodynamic therapy (PDT), and intense pulsed light, chemical peels (CP), miscellaneous therapies or complementary and alternative medicine (MTCAM), or their combinations. We performed Bayesian network meta-analysis with random effects for all treatments compared with placebo and each other. Mean differences (MDs) of lesions count and risk ratios of adverse events with their 95% credible intervals (CrIs) were calculated, and all interventions were ranked by the Surface Under the Cumulative Ranking (SUCRA) values. Additional frequentist additive network meta-analysis was performed to detect the robustness of results and potential interaction effects. Sensitivity analyses were carried out with different priors, and metaregression was to adjust for nine potential effect modifiers. In the result, seventy-three randomized controlled trials (27,745 patients with mild to moderate acne), comparing 30 grouped intervention categories, were included with low to moderate risk of bias. For adverse effects, OA had more risk in combination treatment with others. For noninflammatory lesions reduction, seventeen interventions had significant differences comparing with placebo and three interventions (TR+BPO: MD = −21.89, 95%CrI [−28.97, −14.76]; TR+BPO+MTCAM: −22.48 [−34.13, −10.70]; TA+BPO+CP: −20.63 [−33.97, −7.13]) were superior to others with 94, 94, and 91% SUCRA values, respectively. For inflammatory lesions reduction, nineteen interventions were significantly better than placebo, and three interventions (TR+BPO: MD = −12.13, 95%CrI [−18.41, −5.80]; TR+BPO+MTCAM: −13.21 [−.39, −3.04]; LED: −11.30 [−18.34, −4.42]) were superior to others (SUCRA: 81, 81, and 77%, respectively). In summary of noninflammatory and inflammatory lesions results, TR+BPO and TA+BPO were the best options compared to others. The frequentist model showed similar results as above. In summary, current evidence supports the suggestion that TR+BPO and TA+BPO are the best options for mild to moderate acne. LED is another option for inflammatory lesions when drug resistance occurs. All the combinations involved with OA showed more risk of adverse events than others. However, the evidence of this study should be cautiously used due to the limitations.

PIK3CA Mutations and Their Impact on Survival Outcomes of Patients with Cervical Cancer: A Systematic Review

2020 ◽  
Vol 64 (6) ◽  
pp. 547-555
Author(s):  
Vasilios Pergialiotis ◽  
Christina Nikolaou ◽  
Dimitrios Haidopoulos ◽  
Maximos Frountzas ◽  
Nikolaos Thomakos ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
Cancer Progression ◽  
Meta Analysis ◽  
Current Evidence ◽  
Survival Outcomes ◽  
Cochrane Central Register ◽  
Wild Type ◽  
Pik3ca Mutations ◽  
The Impact

<b><i>Introduction:</i></b> Several studies have implicated the PIK3/AKT pathway in the pathophysiology of cancer progression as its activation seems to be aberrant in several forms of cancer. The purpose of the present systematic review is to evaluate the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer. <b><i>Methods:</i></b> We used the Medline (1966–2020), Scopus (2004–2020), ClinicalTrials.gov (2008–2020), EMBASE (1980–2020), Cochrane Central Register of Controlled Trials (CENTRAL) (1999–2020), and Google Scholar (2004–2020) databases in our primary search along with the reference lists of electronically retrieved full-text papers. Statistical meta-analysis was performed with the RevMan 5.3 software. <b><i>Results:</i></b> Overall, 12 articles were included in the present study that comprised 2,196 women with cervical cancer. Of those, 3 studies did not report significant differences in survival outcomes among patients with mutated versus wild-type PIK3CA tumors, 5 studies reported decreased survival outcomes, and 3 studies revealed increased survival rates. The meta-analysis revealed that patients with the mutated PIK3CA genotypes had worse overall survival compared to patients with wild-type PIK3CA (HR 2.31; 95% CI: 1.51, 3.55; 95% PI: 0.54, 9.96; data from 3 studies) and the same was observed in the case of DFS rates (HR 1.82; 95% CI: 1.47, 2.25; 95% PI: 1.29, 2.56; data from 4 studies). <b><i>Conclusion:</i></b> Current evidence concerning the impact of PIK3CA mutations on survival outcomes of patients with cervical cancer is inconclusive, although the majority of included studies support a potential negative effect, primarily among those with squamous cell carcinoma tumors.

scholarly journals Novel pathogenic SMAD2 variants in five families with arterial aneurysm and dissection: further delineation of the phenotype

2018 ◽  
Vol 56 (4) ◽  
pp. 220-227 ◽  
Author(s):  
Elyssa Cannaerts ◽  
Marlies Kempers ◽  
Alessandra Maugeri ◽  
Carlo Marcelis ◽  
Thatjana Gardeitchik ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Aortic Root ◽  
Transforming Growth Factor ◽  
Premature Stop Codon ◽  
Missense Variant ◽  
Artery Dissection ◽  
Aortic Dilatation ◽  
Arterial Aneurysm ◽  
Missense Variants ◽  
Aortic Root Dilatation

BackgroundMissense variants in SMAD2, encoding a key transcriptional regulator of transforming growth factor beta signalling, were recently reported to cause arterial aneurysmal disease.ObjectivesThe aims of the study were to identify the genetic disease cause in families with aortic/arterial aneurysmal disease and to further define SMAD2 genotype–phenotype correlations.Methods and resultsUsing gene panel sequencing, we identified a SMAD2 nonsense variant and four SMAD2 missense variants, all affecting highly conserved amino acids in the MH2 domain. The premature stop codon (c.612dup; p.(Asn205*)) was identified in a marfanoid patient with aortic root dilatation and in his affected father. A p.(Asn318Lys) missense variant was found in a Marfan syndrome (MFS)-like case who presented with aortic root aneurysm and in her affected daughter with marfanoid features and mild aortic dilatation. In a man clinically diagnosed with Loeys-Dietz syndrome (LDS) that presents with aortic root dilatation and marked tortuosity of the neck vessels, another missense variant, p.(Ser397Tyr), was identified. This variant was also found in his affected daughter with hypertelorism and arterial tortuosity, as well as his affected mother. The third missense variant, p.(Asn361Thr), was discovered in a man presenting with coronary artery dissection. Variant genotyping in three unaffected family members confirmed its absence. The last missense variant, p.(Ser467Leu), was identified in a man with significant cardiovascular and connective tissue involvement.ConclusionTaken together, our data suggest that heterozygous loss-of-function SMAD2 variants can cause a wide spectrum of autosomal dominant aortic and arterial aneurysmal disease, combined with connective tissue findings reminiscent of MFS and LDS.

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