BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

BackgroundBRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers.MethodsPubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test.ResultsA total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (Pheterogeneity = 0.40, for interaction).ConclusionBRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.

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Comparing active immunotherapy efficacy of PD-L1 ≥ 50% NSCLC patients: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21139 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21139-e21139

Author(s):

Yi Hu ◽

Xiaochen Zhao ◽

Yuezong Bai ◽

Longgang Cui ◽

Fan Zhang

Keyword(s):

Systematic Review ◽

Overall Survival ◽

Randomized Controlled Trials ◽

Primary Outcome ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled ◽

The Difference ◽

Nsclc Patients

e21139 Background: Several therapies based on immune checkpoint inhibitors (ICIs) have been approved as the 1L standard of care for PD-L1≥ 50% advanced non-small cell lung cancer (NSCLC). However, little is known about the difference in efficacy between different strategies. We conducted a systematic review and meta-analysis to help clinicians choose more reasonable treatment options. Methods: We searched PubMed, Cochrane library, Embase and major conference proceedings from January 2010 to December 2020 for randomized controlled trials that had available subgroup hazard ratios (HRs) for overall survival according to PD-L1≥ 50%. Only drugs met primary outcome or approved by FDA were included for analysis. The primary outcome was the difference in overall survival (OS). HRs and 95% CI were calculated for the pooled OS using a random-effects model. p<0.05 was considered as statistical difference. Results: A total of 10 randomized controlled trials were included for this meta-analysis. The pooled HR and 95% CI for monotherapy, ICI plus chemotherapy and ICI plus ICI were 0.64 (0.55, 0.74), 0.64 (0.51, 0.79) and 0.70 (0.55, 0.90), respectively. There was no statistical differences between ICI monotherapy and ICI plus chemotherapy (HR 1.00, 95% CI 0.77- 1.30), between ICI monotherapy and ICI plus ICI (HR 0.91, 95% CI 0.69- 1.22) or between ICI plus chemotherapy and ICI plus ICI (HR 0.91, 95% CI 0.66- 1.27). Conclusions: For PD-L1≥ 50% NSCLC patients, active ICI monotherapies showed no different efficacy when compared with ICI combination therapies.

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Adjuvant Transarterial Chemoembolization Following Curative-Intent Hepatectomy Versus Hepatectomy Alone for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cancers ◽

10.3390/cancers13122984 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2984

Author(s):

Stepan M. Esagian ◽

Christos D. Kakos ◽

Emmanouil Giorgakis ◽

Lyle Burdine ◽

J. Camilo Barreto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Randomized Controlled Trials ◽

Transarterial Chemoembolization ◽

Meta Analysis ◽

Risk Of Bias ◽

Cochrane Library ◽

Controlled Trials ◽

Curative Intent ◽

Randomized Controlled

The role of adjuvant transarterial chemoembolization (TACE) for patients with resectable hepatocellular carcinoma (HCC) undergoing hepatectomy is currently unclear. We performed a systematic review of the literature using the MEDLINE, Embase, and Cochrane Library databases. Random-effects meta-analysis was carried out to compare the overall survival (OS) and recurrence-free survival (RFS) of patients with resectable HCC undergoing hepatectomy followed by adjuvant TACE vs. hepatectomy alone in randomized controlled trials (RCTs). The risk of bias was assessed using the Risk of Bias 2.0 tool. Meta-regression analyses were performed to explore the effect of hepatitis B viral status, microvascular invasion, type of resection (anatomic vs. parenchymal-sparing), and tumor size on the outcomes. Ten eligible RCTs, reporting on 1216 patients in total, were identified. The combination of hepatectomy and adjuvant TACE was associated with superior OS (hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.52 to 0.85; p < 0.001) and RFS (HR: 0.70, 95% CI: 0.56 to 0.88; p < 0.001) compared to hepatectomy alone. There were significant concerns regarding the risk of bias in most of the included studies. Overall, adjuvant TACE may be associated with an oncologic benefit in select HCC patients. However, the applicability of these findings may be limited to Eastern Asian populations, due to the geographically restricted sample. High-quality multinational RCTs, as well as predictive tools to optimize patient selection, are necessary before adjuvant TACE can be routinely implemented into standard practice. PROSPERO Registration ID: CRD42021245758.

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Effect of Probiotic Consumption on Immune Response in Athletes: A Meta-analysis

International Journal of Sports Medicine ◽

10.1055/a-1463-3303 ◽

2021 ◽

Author(s):

Rahele Tavakoly ◽

Amir Hadi ◽

Nahid Rafie ◽

Behrouz Talaei ◽

Wolfgang Marx ◽

...

Keyword(s):

Randomized Controlled Trials ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Monocyte Count ◽

Randomized Controlled ◽

Immunological Markers ◽

Online Databases ◽

Immunological Effects

AbstractThe possible effect of probiotic interventions on immunological markers in athletes is inconclusive. Therefore, to synthesize and quantitatively analyze the existing evidence on this topic, systematic literature searches of online databases PubMed, Scopus, Cochrane Library, and ISI Web of Sciences was carried out up to February 2021 to find all randomized controlled trials (RCTs) concerning the immunological effects of probiotics in athletes. In the random-effects model, weighted mean difference (WMD) and 95% confidence interval (CI) explained the net effect. The authors assessed the likelihood of publication bias via Egger’s and Begg’s statistics. A total of 13 RCTs (836 participants) were retrieved. Probiotic consumption reduced lymphocyte T cytotoxic count significantly (WMD=−0.08 cells×109/L; 95% CI: −0.15 to −0.01; p=0.022) with evidence of moderate heterogeneity (I 2=59.1%, p=0.044) and monocyte count when intervention duration was ≤ 4 weeks (WMD=−0.08 cells×109/L; 95% CI: −0.16 to −0.001; I 2=0.0%). Furthermore, leukocyte count was significantly elevated (WMD=0.48 cells×109/L; 95% CI: 0.02 to 0.93; I 2=0.0%) when multi-strain probiotics were used. Probiotic supplements may improve immunological markers, including lymphocyte T cytotoxic, monocyte, and leukocyte in athletes. Further randomized controlled trials using diverse strains of probiotics and consistent outcome measures are necessary to allow for evidence-based recommendations.

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Early Versus Routine Stoma Closure in Patients With Colorectal Resection: A Meta-Analysis of 7 Randomized Controlled Trials

Surgical Innovation ◽

10.1177/1553350620907812 ◽

2020 ◽

Vol 27 (3) ◽

pp. 291-298

Author(s):

Yinyin Guo ◽

Yanxin Luo ◽

Hui Zhao ◽

Liangliang Bai ◽

Juan Li ◽

...

Keyword(s):

Colorectal Surgery ◽

Randomized Controlled Trials ◽

Bowel Obstruction ◽

Meta Analysis ◽

Cochrane Library ◽

Wound Complications ◽

Controlled Trials ◽

Stoma Closure ◽

Randomized Controlled ◽

Significant Difference

Background. A substantial proportion of patients undergoing colorectal surgery receive a temporary stoma, and the timing for stoma closure remains unclear. The aim of this study was to evaluate the safety and feasibility of early stoma closure (ESC) compared with routine stoma closure (RSC) after colorectal surgery. Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library for randomized controlled trials that compared ESC and RSC after colorectal surgery. Results. A total of 7 randomized controlled trials with 814 enrolled patients were identified for this meta-analysis. There were no significant differences between the ESC and RSC groups regarding the complications of stoma closure (26.8% and 16.6%, respectively; odds ratio [OR]: 1.30; 95% confidence interval [CI]: 0.89-1.90; P = .17). A subgroup analysis was conducted by Clavien-Dindo grade of complication, and no significant difference was observed in any subgroup ( P > .05). However, the ESC group had a significantly higher risk of wound complications than the RSC group (17.6% and 7.8%, respectively; OR: 2.61; 95% CI: 1.43-4.76; P = .002), and the RSC group had more cases of small bowel obstruction than the ESC group (3.1% and 8.4%, respectively; OR: 0.37; 95% CI: 0.15-0.87; P = .02). Conclusions. ESC is a safe and effective therapeutic approach in patients who have undergone colorectal surgery; it is associated with a reduced risk of bowel obstruction but a higher risk of wound complications.

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COVID-19 and Vitamin D (Co-VIVID Study): a systematic review and meta-analysis of randomized controlled trials

10.1101/2021.08.22.21262216 ◽

2021 ◽

Author(s):

Seshadri Reddy Varikasuvu ◽

Balachandar Thangappazham ◽

Hemanth Raj

Keyword(s):

Vitamin D ◽

Randomized Controlled Trials ◽

Literature Search ◽

Meta Analysis ◽

Statistical Significance ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled ◽

Individual Outcomes ◽

Vitamin D Levels

Background: Vitamin D levels have been reported to be associated with COVID-19 susceptibility, severity and mortality events.. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the use of vitamin D intervention on COVID-19 outcomes. Methods: Literature search was conducted using PubMed, Cochrane library, and ClinicalTrials.gov databases (latest search on August 5, 2021). We included RCTs reporting the use of vitamin D intervention to control/placebo group in COVID-19. Two independent researchers did literature search, abstracted data, and the risk of bias assessment. Results: A total of 6 RCTs with 551 COVID-19 patients were included. The overall collective evidence pooling all the outcomes across all RCTs indicated the beneficial use of vitamin D intervention in COVID-19 (relative risk, RR = 0.60, 95% CI 0.40 to 0.92, Z=2.33, p=0.02, I2 = 48%). However, no statistical significance was observed for individual outcomes of ICU care (RR = 0.11, 95% CI 0.15 to 1.30, Z=1.48, p=0.14, I2 = 66%) and mortality (RR = 0.78, 95% CI 0.25 to 2.40, Z=0.66, p=0.02, I2 = 33%), though decreased rates were noted. The rates of RT-CR positivity was significantly decreased in the intervention group as compared to the non-vitamin D groups (RR = 0.46, 95% CI 0.24 to 0.89, Z=2.31, p=0.02, I2 = 0%). Conclusion: COVID-19 patients supplemented with vitamin D are more likely to demonstrate fewer rates of ICU admission, mortality events and RT-PCR positivity. However, no statistical significance has been achieved for individual outcomes of ICU and deaths. More RCTs and completion of ongoing trials largely needed to precisely establish the association between vitamin D use and COVID-19.

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Poly(ADP-Ribose) Polymerase Inhibitors (PARPi) for Patients With Advanced Breast Cancer: a Meta-analysis of Randomized Controlled Trials

10.21203/rs.3.rs-48500/v1 ◽

2020 ◽

Author(s):

YongCheng Su ◽

XiaoGang Zheng

Keyword(s):

Breast Cancer ◽

Randomized Controlled Trials ◽

Fixed Effects ◽

Meta Analysis ◽

Parp Inhibitors ◽

Cochrane Library ◽

Controlled Trials ◽

Randomized Controlled ◽

Increased Risk ◽

Grade 3

Abstract BACKGROUND: Poly(ADP–ribose) polymerase (PARP) inhibitors are new class of drugs that are currently being studied in several malignancies. However, datas about the efficacy and safety of the PARP inhibitors are limited. Therefore, we conducted a meta-analysis of randomized controlled trials (RCT) in patients with breast cancer.METHODS: Pubmed/Medline, Embase, Cochrane Library, and abstracts presented at the annual meeting of the American Society of Clinical Oncology (ASCO) were searched for articles published from 2000 to June 2018.Summary incidences and the RR, HR with 95% confidence intervals, were calculated by using a random-effects or fixed-effects model.RESULTS: The summary HR indicated PARPi was not associated with OS (HR=0.83, 95%CI 0.66–1.06, Z=1.49, P=0.14), while it could significantly improve PFS ande time to deterioration (TTD) of global health status/quality of life(GHS/QoL) as compared with traditional standard therapy, the HR was 0.60(95%CI 0.50-0.72; Z=5.52, P＜0.00001) and 0.4 (95%CI 0.29–0.54,z=5.80 ,p=0.000),respectively.The RR of grade 3 or more anemia ,fatigue and headache was 3.02 (95% CI, 0.69–13.17;p = 0.14,,I2=90%),0.77 (95%CI, 0.34–1.73;p=0.52,I2=7%) and 1.13 (95% CI,0.30–4.18;p=0.86,I2=0%),respectively.CONCLUSION: The findings of this meta-analysis showed that PARPi has no significant effect on OS, while it could significantly improve in PFS and TTD of GHS/QoL for patients with advanced or metastatic breast cancer.Furthermore,our findings also demonstrated that the PARPi treatment is connected with an increased risk of grade 3 or more anemia adverse events.

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Impact of Ketamine on Pain Management in Cesarean Section: A Systematic Review and Meta-Analysis

January 2018 - Pain Physician ◽

10.36076/ppj.2020/23/135 ◽

2020 ◽

Vol 2;23 (4;2) ◽

pp. 135-148

Author(s):

Zifeng Xu

Keyword(s):

Cesarean Section ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Cochrane Library ◽

Control Group ◽

Controlled Trials ◽

Control Effect ◽

Randomized Controlled ◽

Time Required ◽

The Cochrane Library

Background: The pain control effect of ketamine versus control in women during cesarean operation is not well determined. Objectives: The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. Study Design: We used meta-analysis to address this concern. Setting: Meta-analysis-based study. Methods: The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. Results: A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], –1.10; 95% confidence interval [CI], –1.61, –0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, –6.11 mg; 95% CI, –9.93, –2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limitations: Limited patients were included with moderate strength. Conclusions: Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Key words: Ketamine, cesarean section, randomized controlled trials, meta-analysis

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The effect of non-benzodiazepine sedative hypnotics on CPAP adherence in patients with OSA: a systematic review and meta-analysis

SLEEP ◽

10.1093/sleep/zsab077 ◽

2021 ◽

Author(s):

Donghao Wang ◽

Yongkang Tang ◽

Yanghang Chen ◽

Sun Zhang ◽

Danjie Ma ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Cochrane Library ◽

Controlled Trials ◽

Cpap Adherence ◽

Randomized Controlled ◽

Obstructive Sleep ◽

Sedative Hypnotics

Abstract Study objectives This meta-analysis aimed to explore the effect of non-benzodiazepine sedative hypnotics (NBSH) on continuous positive airway pressure (CPAP) adherence in patients with obstructive sleep apnea (OSA). Methods We conducted a systematic search through PubMed, Medline, the Cochrane Library, EMBASE, Scopus and ClinicalTrials (all searched from inception to 15 August 2020). Publications were limited to articles, clinical conferences and letters, including randomized controlled trials and retrospective studies. We used a random-effects model to calculate the odds ratio (OR) and mean difference (MD) with corresponding confidence interval (CI). Subgroup analyses were conducted to analyze the sources of heterogeneity. Results Eight studies fulfilled the inclusion and exclusion criteria for patients newly diagnosed with obstructive sleep apnea. Overall, the use of NBSH was associated with increased use of CPAP per night (MD = 0.62 h; 95% CI = 0.26-0.98) and use for more nights (MD = 12.08%; 95% CI = 5.27-18.88). When a study seriously affecting heterogeneity was removed, more patients adhered well with CPAP use (pooled OR = 2.48; 95% CI = 1.75-3.52) with good adherence defined as CPAP use for＞4 h/night on＞70% of nights. Among prescribed NBSHs, eszopiclone showed the most significant effect on CPAP adherence. Conclusion CPAP adherence may increase in OSA patients treated with non-benzodiazepine sedative hypnotics especially eszopiclone. The effect of zolpidem and zaleplon on CPAP adherence requires further investigation by larger scale, randomized, controlled trials.

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Overall survival after perioperative chemotherapy in the management of pulmonary metastasis in osteosarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23508 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23508-e23508

Author(s):

Zeba Siddiqui ◽

Megan E Delisle ◽

Amirrtha Srikanthan ◽

Ying Wang

Keyword(s):

Overall Survival ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Pulmonary Metastasectomy ◽

Cochrane Library ◽

Controlled Trials ◽

Perioperative Chemotherapy ◽

Extrinsic Factors ◽

Term Survival ◽

Randomized Controlled

e23508 Background: Pulmonary metastasectomy is performed on a select cohort of patients with advanced osteosarcoma with the potential for long term survival. However, evidence on peri-operative chemotherapy at time of metastasectomy is not completely understood and difficult to summarize without a systematic examination of existing literature. The purpose of this project is to perform a meta-analysis of existing studies to determine overall survival (OS) and prognostic factors in adults and children with advanced and recurrent osteosarcoma receiving chemotherapy around time of metastasectomy. Methods: We reviewed survival studies conducted in children and adults with advanced and recurrent osteosarcoma who undergo pulmonary metastasectomy published in English with more than 5 patients. The primary outcome was overall survival. Literature searches were performed in multiple electronic databases including Ovid MEDLINE (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Two investigators independently screened all citations, abstracts, and full-text articles. Results: 24 out of 80 observational studies between 1977 to 2018 were included. 2146 patients were studied of which 987 underwent pulmonary metastasectomy for osteosarcoma. 822 patients received perioperative chemotherapy in this setting. No randomized controlled trials were identified. Studies included patients from Asia, Africa, Europe, and North America. The median OS ranged between 20 to 90 months. 5-year OS ranged between 15 to 63%. Factors associated with survival included: age, number of lesions, disease free interval, time of development of metastases, number of lesions and laterality of pulmonary disease. Conclusions: Overall survival in study has a significant range. Factors influencing survival included intrinsic factors such as patient age and disease characteristics, as well as extrinsic factors such as evolution of chemotherapy regimen over the past four decades. The main limitations are related to the inherently low-quality evidence as a result of lack of randomized controlled trials. More comprehensive data is needed to guide shared decision making in this area.

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The Long-Lasting Effects of “Placebo Injections” in Knee Osteoarthritis: A Meta-Analysis

Cartilage ◽

10.1177/1947603520906597 ◽

2020 ◽

pp. 194760352090659 ◽

Cited By ~ 7

Author(s):

Davide Previtali ◽

Giulia Merli ◽

Giorgio Di Laura Frattura ◽

Christian Candrian ◽

Stefano Zaffagnini ◽

...

Keyword(s):

Knee Osteoarthritis ◽

Randomized Controlled Trials ◽

Placebo Effect ◽

Meta Analysis ◽

Grey Literature ◽

Cochrane Library ◽

Controlled Trials ◽

Level Of Evidence ◽

Randomized Controlled ◽

The Impact

Objectives To quantify the placebo effect of intraarticular injections for knee osteoarthritis in terms of pain, function, and objective outcomes. Factors influencing placebo effect were investigated. Design Meta-analysis of randomized controlled trials; Level of evidence, 2. PubMed, Web of Science, Cochrane Library, and grey literature databases were searched on January 8, 2020, using the string: (knee) AND (osteoarthritis OR OA) AND (injections OR intra-articular) AND (saline OR placebo). The following inclusion criteria were used: double-blind, randomized controlled trials on knee osteoarthritis, including a placebo arm on saline injections. The primary outcome was pain variation. Risk of bias was assessed using the RoB 2.0 tool, and quality of evidence was graded following the GRADE (Grading of Recommendations Assessment, Development and Evaluation) guidelines. Results Out of 2,363 records, 50 articles on 4,076 patients were included. The meta-analysis showed significant improvements up to the 6-month follow-up: Visual Analogue Scale (VAS)-pain −13.4 mean difference (MD) (95% confidence interval [CI]: −21.7/−5.1; P < 0.001), Western Ontario and McMaster Osteoarthritis Index (WOMAC)-pain −3.3 MD (95% CI: −3.9/−2.7; P < 0.001). Other significant improvements were WOMAC-stiffness −1.1 MD (95% CI: −1.6/−0.6; P < 0.001), WOMAC-function −10.1 MD (95% CI: −12.2/−8.0; P < 0.001), and Evaluator Global Assessment −21.4 MD (95% CI: −29.2/−13.6; P < 0.001). The responder rate was 52% (95% CI: 40% to 63%). Improvements were greater than the “minimal clinically important difference” for all outcomes (except 6-month VAS-pain). The level of evidence was moderate for almost all outcomes. Conclusions The placebo effect of knee injections is significant, with functional improvements lasting even longer than those reported for pain perception. The high, long-lasting, and heterogeneous effects on the scales commonly used in clinical trials further highlight that the impact of placebo should not be overlooked in the research on and management of knee osteoarthritis.

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