CDK 4/6 inhibitors (CDKi) + endocrine therapy (ET) in ER-positive metastatic breast cancer (mBC) patients according ET sensitivity: A systematic review and meta-analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12532-e12532
Author(s):  
Michela Piezzo ◽  
Maria Riemma ◽  
Daniela Cianniello ◽  
Roberta Caputo ◽  
Giuseppina Fusco ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Random Effect ◽  
Objective Response ◽  
Random Effect Model ◽  
Metastatic Breast ◽  
Pooled Analysis ◽  
P Value ◽  
Er Positive ◽  
Resistant Group ◽  
Metastatic Sites

e12532 Background: Addition of CDKi to ET in ER-positive mBC has proven effective in improving both progression-freesurvival (PFS) and Objective Response Rate (ORR). However, no randomized clinical trial (RCT) has so far shown a significant increase of Overall Survival (OS). We carried out a metanalysis of all RTCs to better characterize the efficacy of CDK4/6i in some relevant subgroups, with particular reference to OS. Methods: Literature search of main databases was carried out up to 08 Dec 2018. Hazard ratios (HRs) for PFS and OS and risk ratios (RRs) for ORR were extracted/calculated for each trial and then pooled by using both fixed and random effect model. Confidence intervals (CIs) at 95% were calculated for each statistics. Kaplan-Meier meta-curves were generated by pooling data of all trials, among ET sensitive and ET resistant pts. Results: Eight RCTs were included accounting for a total of 4580 pts, 2802 receiving a CDKi (palbociclib, ribociclib or abemaciclib) in association with ET (NSAI, tamoxifene or fulvestrant) and 1778 receiving ET alone or plus placebo. Pooled analysis of HRs showed a significant improvement in PFS, regardless ET sensitivity, disease site, number of metastatic sites and treatment free interval. Analysis of OS included 3 RCTs with a total of 1243 pts and showed a statistically significant improvement of OS (HR 0.769 [95% CI 0.638, 0.926], p-value 0.006). Pooled estimate for RR showed higher ORR in CDK 4/6 arm both in ET sensitive (RR 1.35 [95% CI 1.19, 1.52]) and ET resistant group (RR 2.19 [95% CI 1.66, 2.89]). Similarly, pts with measurable disease showed a RR of 1.34 (95% CI 1.20, 1.50) in ET sensitive group and 2.26 (95% CI 1.72, 2.96) in ET resistant group. Pooled survival curves showed an absolute benefit in PFS, both in ET sensitive (median PFS: NR vs 15 months) and ET resistant (median PFS: 19.2 vs 8.9 months). Conclusions: Our findings suggest that addition of CDKi to ET improve clinical outcome in terms of PFS, ORR and OS, irrespective of pts/tumor characteristics.

Meta-analysis of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy versus endocrine therapy alone on progression-free survival (PFS) and overall survival (OS) for metastatic breast cancer (MBC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1060-1060
Author(s):  
Ranju Kunwor ◽  
Ramkaji Baniya ◽  
Maysa M. Abu-Khalaf
Keyword(s):  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Pooled Analysis ◽  
Cochrane Library ◽  
Hormone Receptor Positive

1060 Background: CDK 4/6 inhibitors with Endocrine therapy (ET) are the preferred first line treatment for Hormone Receptor positive and Human Epidermal Growth factor receptor 2 negative (HR+/HER2-) MBC. Over the last few years multiple trials have shown benefit in PFS. Only two studies evaluating Ribociclib and Abemaciclib showed an OS benefit while no statistically significant OS benefit has been reported in any of the studies evaluating Palbociclib raising the possibility that this benefit may be drug specific rather than applicable to all CDK 4/6 Inhibitors. This updated meta-analysis of randomized controlled trials (RCTs) aims to assess the PFS and OS of all three CDK 4/6 inhibitors in HR+/HER2- MBC. Methods: We performed a systematic search for RCTs using Cochrane Library, PubMed, Embase, and Web of Science. Only the phase II and III RCTs comparing CKD 4/6 inhibitors plus ET with ET alone were eligible for this meta-analysis. The pooled analysis of Hazard Ratio (HR) was performed with Review Manager 5.3 using random effect model. Results: A total of 8 RCTs including 4338 patients with HR+/HER2- MBC were included in this meta-analysis (table). The pooled HR for PFS was 0.55 (95% confidence interval (CI), 0.50-0.59; P < .00001) and the pooled HR for OS was 0.75 (95% CI, 0.68-0.84; P < .00001). Conclusions: The result of our meta-analysis confirms the previously reported PFS benefit from CDK 4/6 inhibitors plus ET and shows an OS benefit when including RCTs of all 3 CDK 4/6 inhibitors for the treatment of HR+/HER2- MBC. [Table: see text]

scholarly journals Progression free survival and overall survival of CDK 4/6 inhibitors plus endocrine therapy in metastatic breast cancer: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Michela Piezzo ◽  
Paolo Chiodini ◽  
Maria Riemma ◽  
Stefania Cocco ◽  
Roberta Caputo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Visceral Metastases ◽  
Metastatic Sites

Abstract PURPOSE: The introduction of CDK4/6 inhibitors plus endocrine therapy (ET) represents the most relevant advance in the management of HR-positive/HER2-negative metastatic breast cancer. We carried out a meta-analysis of randomized controlled trials (RCTs) with the aims of better characterising the efficacy of CDK4/6 inhibitors in some relevant subgroups and of testing heterogeneity between different compounds with particular focus on their ability to improve OS. METHODS: We performed a systematic literature search to identify phase II/III RCTs of CDK4/6 inhibitors plus ET in AI-sensitive and AI-resistant patients. Pooled estimates of HRs were computed for PFS, OS and ORR analysis, by using both a fixed and random effect model. Predefined subgroup analyses were performed to better understand treatment effect concerning specific patients’ characteristics. Pooled survival curves were generated by pooling the data of all trials. RESULTS: 8 RCTs were included. Adding a CDK4/6 inhibitors to ET is beneficial in terms of PFS irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the TFI. The addition of CDK4/6 inhibitors significantly improves OS in AI-sensitive (HR 0.75, 95%CI [0.63-0.89]) and AI-resistant patients (HR 0.77, 95%CI [0.67-0.89]). Pooled data from each single drug show that Palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68-1.02]). CONCLUSION: Our meta-analysis confirms the efficacy of CDK4/6 inhibitors overall and in major patients subgroups, supporting the use of CDK4/6 inhibitors plus ET as standard treatment for most HR+ MBC patients.

scholarly journals Comparative efficacy between ketamine, memantine, riluzole and d-cycloserine in patients diagnosed with drug resistant depression: a meta-analysis

2019 ◽  
Vol 8 (6) ◽  
pp. 1132
Author(s):  
Nishita H. Darji ◽  
Devang A. Rana ◽  
Supriya D. Malhotra
Keyword(s):  
Rating Scale ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Fixed Effect ◽  
P Value ◽  
Drug Resistant ◽  
Effect Model ◽  
Resistant Depression ◽  
Glutamate Modulators

Background: Glutamate modulators are having immense potential and are newer entities for treating drug resistant depression. The objectives were to generate statistical evidence on basis of existing data of ketamine, memantine, riluzole and d-cycloserine in resistant depression.Methods: A total of 14 RCTs following PRISMA guidelines and matching inclusion and exclusion criteria were collected of ketamine (5), memantine (3), riluzole (2) and d-cycloserine (4) vs placebo in drug resistant depression. Only RCTs with primary diagnosis of drug resistant depression (Previously on two standard antidepressant therapy) were included. Studies with treatment response rate, 50% reduction in total score of the depression rating scale-Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale or Beck Depression Inventory was chosen as clinical outcome measure. RevMan 5.3 software was used for the analysis.Results: In ketamine group using random effect model SMD was 2.122 (95% CI 0.659-3.584). P-value was statistically significant (random effect p <0.005 and in fixed effect <0.001). In memantine group, using random effect model -0.963 was SMD and (95% CI -1.958-0.0324). P-value was <0.001, significant in fixed effect. In riluzole group, SMD was -0.564 with (95% CI -3.927-2.799) in random effect. P-value was 0.741. In d-cycloserine group SMD was 0.316 with (95% CI -1.252-1.885) in random effect. P-value was 0.690.Conclusions: Ketamine showed best efficacy followed by memantine. Riluzole and DCS as such have no efficacy although its acts by same glutamate pathway. More molecular based research is required in use of glutamate modulators in resistant depression.

scholarly journals Immunosuppressants in Liver Transplant Recipients With Coronavirus Disease 2019: Capability or Catastrophe?—A Systematic Review and Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Dipesh Kumar Yadav ◽  
Vishnu Prasad Adhikari ◽  
Qi Ling ◽  
Tingbo Liang
Keyword(s):  
Liver Transplant ◽  
Immunosuppressive Therapy ◽  
Meta Analysis ◽  
Severe Disease ◽  
Random Effect ◽  
Random Effect Model ◽  
Mammalian Target Of Rapamycin ◽  
Calcineurin Inhibitors ◽  
Pooled Analysis ◽  
Organ Rejection

Background: The probable impact of a maintenance immunosuppressant (IS) on liver transplant (LT) recipients with coronavirus disease 2019 (COVID-19) remains unexplored. Our specific aim was to approximate the prognosis of LT recipients with COVID-19 on the standard maintenance IS.Method: We searched separate databases for the qualified studies in between December 2019 and June 25, 2021. Ultimately, a meta-analysis was carried out using a fixed-effect or random-effect model based on the heterogeneity.Results: In a total of eight studies and 509 LT recipients with COVID-19, the pooled rates of severity and mortality during all the combined immunosuppressive therapies were 22.4 and 19.5%, respectively. Our study sufficiently showed that an immunosuppressive therapy in LT recipients with COVID-19 was significantly associated with a non-severe COVID-19 [odds ratio (OR): 11.49, 95% CI: 4.17–31.65; p &lt; 0.001] and the survival of the patients (OR: 17.64, 95% CI: 12.85–24.22; p &lt; 0.001). Moreover, mammalian target of rapamycin inhibitor (mTORi) typically had the lowest rate of severity and mortality compared to other ISs such as calcineurin inhibitors (CNIs), steroids, and antimetabolites, i.e., severity (13.5 vs. 21.1, 24.7, and 26.3%) and mortality (8.3 vs. 15, 17.2, and 12.1%), respectively. Contrary to the general opinions, our meta-analysis showed comorbidities such as diabetes, hypertension, cardiopulmonary disorders, chronic kidney disease (CKD), age &gt;60, the duration of LT to the diagnosis of COVID-19, primary disease for LT, and obesity were not significantly associated with the severity and mortality in LT recipients with COVID-19 under an immunosuppressive therapy. However, our pooled analysis found that LT recipients with COVID-19 and without comorbidities have a less severe disease and low mortality rate compared to those with both COVID-19 and comorbidities.Conclusions: In conclusion, LT recipients with COVID-19 undergoing immunosuppressive therapies are not significantly associated with the severity and mortality. Therefore, taking the risk of organ rejection into a key consideration, a complete withdrawal of the IS may not be wise. However, mycophenolate mofetil (MMF) might be discontinued or replaced from an immunosuppressive regimen with the CNIs- or mTORis-based immunosuppressive therapy in some selected LT recipients with COVID-19, depending upon the severity of the disease.

scholarly journals Toxoplasmosis infection among pregnant women in Africa: A systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254209
Author(s):  
Tamirat Tesfaye Dasa ◽  
Teshome Gensa Geta ◽  
Ayalnesh Zemene Yalew ◽  
Rahel Mezemir Abebe ◽  
Henna Umer Kele
Keyword(s):  
Systematic Review ◽  
Pregnant Women ◽  
Democratic Republic Of Congo ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Congenital Toxoplasmosis ◽  
Protozoan Parasite ◽  
P Value ◽  
Toxoplasma Infection

The epidemiology of toxoplasmosis in pregnancy is a major issue in public health. Toxoplasmosis is caused by the protozoan parasite. Toxoplasma parasite is at high risk for life-threatening diseases during pregnancy. Congenital toxoplasmosis results from a maternal infection acquired during gestation. Therefore, this systematic review and meta-analysis was aimed to determine the seropositive prevalence of toxoplasmosis infection among pregnant women who attended antenatal care in a health facility in Africa. A systematic review and meta-analysis of published and unpublished studies were included. Databases such as MEDLINE, PubMed, EMBASE, CINAHL, Web of Science, African Journals Online were used with relevant search terms. The quality of the articles was critically evaluated using the tool of the Joanna Briggs Institute. Data were extracted on Microsoft word 2016. Meta-analysis was conducted using STATA 14 software. The heterogeneity and publication bias were assessed using the I2 statistics and Egger’s test, respectively. Forest plots were used to present the pooled prevalence and odds ratio with a 95% confidence interval of meta-analysis using the random effect model. In total, 23 studies comprising 7,579 pregnant women across ten countries in Africa were included in this meta-analysis. The overall prevalence of seropositive toxoplasmosis among pregnant women in Africa was 51.01% (95% CI; 37.66, 64.34). The heterogeneity test showed that heterogeneity was high, I2 = 99.6%, P-value < 0.001. The variables responsible for the source of heterogeneity were included from Cameroon, the Democratic Republic of Congo, and Ethiopia. Overall prevalence of toxoplasmosis in Africa showed that more than one-half of pregnant women were infected. The risk of acquiring toxoplasmosis infection during pregnancy is high; hence, preventive measures to avoid exposure of pregnant women to Toxoplasma infection should be strictly applied.

A systematic and meta-analysis study on the prevalence of tuberculosis and relative risk factors for prisoners in Iran

2021 ◽  
Vol 21 ◽  
Author(s):  
Sedigheh Taherpour ◽  
Mojtaba Mousavi Bazzaz ◽  
Hamidreza Naderi ◽  
Saeed Samarghandian ◽  
Alireza Amirabadizadeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Random Model ◽  
Health Interventions ◽  
P Value ◽  
Analysis Study ◽  
Effect Model ◽  
Related Risk

Introduction: This study aimed to evaluate the incidence of Tuberculosis (TB) among prisoners in Iran, by performing a systematic and meta-analysis study on the related articles. Methodology: Scopus, Iran doc, Cochrane, Pubmed, Medline, Embase and Iran Medex, Magiran, SID, Google Scholar, and EBSCO were searched. After quality assessment of the articles, a fixed or random model, as appropriate, was used to pool the results in a meta-analysis. Heterogeneity between the studies was assessed using I-square and Q-test. Results: The overall sample size of included studies was 19562 that 64 of them were with TB. The highest prevalence of tuberculosis was related to the study of Rasht, 517 in 100,000 but the lowest rate was related to the study of Sought Khorasan, 25 in 100,000. The ES of the random effect model is 0.003 (95% CI, 0.001-0.005) and p-value <0.0001. The Higgins’ I2 of all studies is 86.55%, and the p-value of the Cochrane Q statistics is <0.001, indicating that there is heterogeneity. Based on the Egger regression plot (t=2.18, p = 0.08, CI 95%: -0.001, 0.005) no publication bias existed. Conclusion: The frequency of TB among the prisoners in Iran was low. Due to important limitations in this study, it is not possible to indicate the exact prevalence of TB among prisoners in Iran and compare this with the general population. More studies are needed to assess the related risk factor for designing health interventions plan to decrease the incidence rate of TB among prisoners.

scholarly journals Comparison of Rifabutin-Based Versus Rifampin-Based Regimens for the Treatment of Mycobacterium avium Complex: A meta-Analysis Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Bahareh Hajikhani ◽  
Mohammad Javad Nasiri ◽  
Brian C. Adkinson ◽  
Taher Azimi ◽  
Farima Khalili ◽  
...  
Keyword(s):  
Publication Bias ◽  
Mycobacterium Avium ◽  
Mycobacterium Avium Complex ◽  
Meta Analysis ◽  
Treatment Success ◽  
Random Effect ◽  
Random Effect Model ◽  
P Value ◽  
Double Blind ◽  
Similar Treatment

Background: The incidence of Mycobacterium avium complex (MAC) increases as immunosuppressed conditions become more common. MAC's standard treatment regimen includes a macrolide, ethambutol, and a rifamycin, among which rifampin and rifabutin are the most commonly used. Although current guidelines recommend initial therapy for MAC with rifampin, it has been theorized to be less efficacious than rifabutin.Methods: We reviewed the relevant scientific literature published up to February 18, 2020. Statistical analyses were performed with Comprehensive Meta-Analysis Software Version 2.0 (Biostat, Englewood, NJ). The pooled frequency with 95% confidence intervals (CI) was assessed using a random-effect model. We considered P &lt;0.05 as statistically significant for publication bias.Results: After reviewing 3665 records, we identified 24 studies that satisfied the inclusion criteria. Among these studies, 8 had rifabutin in their regimens (rifabutin group) and 16 had rifampin in their regimens (rifampin group). The estimated pooled treatment success rate was found to be 54.7% (95% CI 41.0-67.0%) in rifabutin groups and 67.5% (95% CI 55.7-77.4%) in rifampin groups. There was no evidence of publication bias among the included studies (Egger’s test p-value was 0.7).Conclusion: In this study, it was shown that in comparison to Rifabutin, rifampin has similar treatment success rates in treating MAC. In order to determine the exact preference of each of these drugs, double-blind clinical trial studies are recommended.

scholarly journals Inflammatory markers in Covid-19 Patients: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Golnaz Vaseghi ◽  
Marjan Mansourian ◽  
Raheleh Karimi ◽  
Kiyan Heshmat-Ghahdarijani ◽  
Paria Rouhi ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
P Value ◽  
Chi Square ◽  
Effect Model ◽  
Chi Square Test ◽  
History Of ◽  
The Mean

AbstractIntroductionDiagnosis of COVID-19 is based on clinical manifestation, history of exposure, positive findings on chest CT and laboratory tests. It has been shown that inflammation plays a role in pathogenesis of COVID-19.MethodWe used the necessary transformations to convert the median and IQR to mean and SD Random-effect model using Der Simonian, and Laird methods was used if heterogeneity between studies was significant, the homogeneity among studies was assessed with I2 Statistic, values above 50%, and for the chi-square test, P-values <0.1 was supposed statistically significantResultsTwelve studies were included in the analysis that all of which were conducted in China in the year 2020. The result of combining 12 articles with 772 participants showed that the pooled estimate of the mean of lymphocyte with 95% CI was (Mean: 1.01; 95% CI (0.76-1.26); p-value<0.001). About WBC the pooled result of 9 studies with 402 participants was (Mean: 5.11; 95% CI (3.90-6.32); p-value<0.001) Also the pooled mean estimate of 9 studies with 513 patients for the ratio of Neutrophil/lymphocyte was (Mean: 3.62; 95% CI (1.48-5.77); p-value=0.001). The pooled mean from the combination of 7 studies with 521 patients on CRP was (Mean: 28.75; 95% CI (8.04-49.46).ConclusionInflammatory Markers increase in patients with Covid-19, which can be a good indicator to find patients.

scholarly journals Risk of cardiovascular malformations after exposure to paroxetine in pregnancy: meta-analysis

2013 ◽  
Vol 37 (6) ◽  
pp. 198-203 ◽  
Author(s):  
Nitesh Painuly ◽  
Ritu Painuly ◽  
Reinhard Heun ◽  
Pratap Sharan
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
First Trimester ◽  
Pooled Analysis ◽  
Cardiovascular Malformations ◽  
Effect Model ◽  
Cardiovascular Defects ◽  
First Trimester Of Pregnancy

Aims and methodTo examine the association between the use of paroxetine during pregnancy and the risk of cardiovascular defects in the newborn. A systematic review of nine electronic databases was carried out and bibliographies were hand-searched for other relevant articles. Inclusion criteria for studies were the use of selective serotonin reuptake inhibitors in the first trimester of pregnancy, with separate data available for paroxetine and cardiovascular defects in newborn babies. A random-effect model was used to combine the data.ResultsA total of 11 studies were included in the analysis, concerning 4515 offspring who were exposed to paroxetine in the first trimester and 1 469 302 controls. In pooled analysis, paroxetine in the first trimester of pregnancy was slightly, but significantly, associated with a risk of cardiovascular malformations in the offspring (relative risk= 1.25, 95% CI 1.01–1.54). Separate analyses of case-control and cohort studies made this difference non-significant.Clinical implicationsThis meta-analysis supports current guidelines advising not to use paroxetine in early pregnancy.

scholarly journals Microbleeds in Alzheimer’s Disease: A Neuropsychological Overview and Meta-Analysis

2016 ◽  
Vol 43 (6) ◽  
pp. 753-759 ◽  
Author(s):  
Amir A. Sepehry ◽  
Alexander Rauscher ◽  
Ging-Yuek Hsiung ◽  
Donna J. Lang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Degrees Of Freedom ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
High Sensitivity ◽  
P Value ◽  
Cross Sectional ◽  
Small Effect Size

AbstractThe current literature on the role of brain microbleeds (MB) on the neuropsychological outcomes of Alzheimer’s disease (AD) is heterogeneous. We therefore meta-analytically examined the neuropsychological literature pertaining to MBs in AD. Using a priori selected criteria, studies with cross-sectional neuropsychological assessment on MBs and AD were reviewed. Six of 122 studies met selection criteria and provided neuropsychological data on either AD with MB and without MB, or in contrast to healthy controls. The global neuropsychological difference between AD with MB and AD without MB based on random effect model was nonsignificant, heterogeneous, and small (Effect Size =−0.155; 95% confidence interval =−0.465 to 0.155; p value =0.326; Heterogenity: Q-value =12.744; degrees of freedom =5; p =0.026; I2 =61%). The contribution of MBs to cognitive deficits in AD remains unclear. Future studies of MB in AD should strive to use standardized neuroimaging techniques with high sensitivity for MB, a common standard for MB definition, and neuropsychological tests sensitive for detecting subtle cognitive impairment.

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