Meta-analysis Of Clinical Trials Research Articles

The effects of ketogenic diet on metabolic and hormonal parameters in patients with polycystic ovary syndrome: a systematic review and meta-analysis of clinical trials

The effects of ketogenic diet on metabolic and hormonal parameters in patients with polycystic ovary syndrome: a systematic review and meta-analysis of clinical trials

Efficacy and safety of venetoclax-based combination therapy for previously untreated acute myeloid leukemia: a meta-analysis

ABSTRACT Purpose: To explore the efficacy and safety of venetoclax-based combination therapy for older patients with newly diagnosed acute myeloid leukemia (AML). Methods: We performed a systematic review and meta-analysis of clinical trials comparing venetoclax plus hypomethylating agents (HMAs) or low-dose cytarabine (LDAC) with mono-HMAs or LDAC. The random or fixed effects model was applied to the studies based on heterogeneity. Dichotomous data were summarized using the risk ratio (RR) and 95% confidence interval (CI). Continuous variable data were reported as weighted mean differences (WMDs). Results: Nine studies, including a total of 1232 patients, were included in this meta-analysis. Thec complete remission (CR)/complete remission with incomplete hematological recovery (CRi) rate of the venetoclax (Ven) + azacytidine (Aza) group was significantly greater than that of the Aza monotherapy group (RR: 2.42; 95% CI: 1.85–3.15; P < 0.001). Similarly, the CR/CRi rate of the Ven + LDAC group was also significantly greater than that of the LDAC monotherapy group (RR: 2.57; 95% CI: 1.58–4.17; P = 0.00). The same results were observed for OS among these groups. However, the incidence of febrile neutropenia was greater in the Ven + Aza group than in the Ven + Decitabine (Dec) or monotherapy Aza group (RR: 0.69; 95% CI: 0.53–0.90; P = 0.006 and RR: 2.19; 95% CI: 1.58–3.03; P < 0.001, respectively). In addition, the Ven + LDAC group had significantly greater rates of constipation, diarrhea, nausea, and vomiting than the LDAC monotherapy group, with RRs and CIs of 0.61 (95% CI 0.44–0.83, P = 0.002), 1.81 (95% CI 1.22–2.67, P = 0.003), 1.39 (95% CI 1.06–1.82, P = 0.016), and 1.80 (95% CI 1.19–2.72, P = 0.005), respectively. Conclusion: Venetoclax combined with azacitidine, decitabine, or LDAC significantly improved the CR/CRi and OS of patients with previously untreated AML. However, venetoclax plus azacitidine or LDAC was more likely to lead to increased febrile neutropenia and gastrointestinal toxicity.

P060 Multi-targeted therapy better in achieving a complete response in Lupus Nephritis: A systematic review and meta-analysis

Abstract Background/Aims Overall management of SLE and Lupus Nephritis (LN) has significantly improved over the last four decades. Recently great therapeutic strides have been made in management of LN using newer agents alone or combination of older therapies. With the availability of increased number of options choosing the optimal treatment regimen for LN has become challenging. Identifying the treatment regimen most effective in achieving complete response while minimizing adverse events is crucial for improving patient outcomes. We performed a systematic review and meta-analysis of clinical trials to explore optimal treatment regimen for LN. Methods The systematic review and meta-analysis were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was conducted using public databases, such as the Cochrane Library, Web of Science and PubMed. Only randomized controlled clinical trials with either active comparator or placebo arms were included. Studies were excluded if they were retrospective, with no comparative drug arm, or less than 20 subjects per treatment response arm. Due to lack of agreed upon outcome measures, complete response (CR) and partial response (PR) criteria were determined as per the definition used by individual studies. Severe adverse reaction (SAE) frequencies were determined for each study for safety evaluation. Publication bias was detected by using funnel plots. Forest plots were used to summarize data, generate frequencies, odds ratio (OR), relative risks (RR) and corresponding 95% confidence intervals (CI) for each subgroup. Heterogeneity was evaluated using the I2 statistic, and labelled as low (25%), moderate (50%) and high (75%). All analyses were performed using R Statistical Software meta package (v4.2.1; R Core Team 2022). Results 31 eligible studies comprising 5495 SLE patients were included in analyses, the study characteristic features are shown in Table 1. Overall significant OR for achieving CR was reported by 10 studies (Figure 1). The highest effect was reported from study by Bao et.al using a combination of tacrolimus(TAC) and mycophenolate mofetil (MMF) compared to cyclophosphamide (CYC) (OR = 10.5, 95% CI 2.27; 48.76), another study using TAC+MMF combo reported OR = 2.49, 95% CI 1.59;3.88. The study by Ginzler et.al reported OR = 5.06 (95% CI 1.6:16.02) in favor of using MMF. Studies using CYC, voclosporin + MMF, and belimumab also reported significant OR for achieving CR. Data for the frequency of SAE were available in 22 studies. The frequency of SAE was not significantly different between treatments arms (OR: 1.07, 95%CI: 0.93-1.23, p &amp;gt; 0.05) Conclusion Our meta-analysis suggests multi-target treatment strategies, by adding calcineurin inhibitors to MMF may be better for achieving complete response in LN. Furthermore, using this combination treatment did not seem to increase the risk of side effects. Heterogenous treatment response criteria and variable comparator arms were major limiting factors of this study. Disclosure O. Pamuk: None. B. Shaikh: None. S. Khan: None. S. Abi Doumeth: None. S. Hasni: None.

Associations Between Surrogate Markers and Clinical Outcomes for Nononcologic Chronic Disease Treatments

Surrogate markers are increasingly used as primary end points in clinical trials supporting drug approvals. To systematically summarize the evidence from meta-analyses, systematic reviews and meta-analyses, and pooled analyses (hereafter, meta-analyses) of clinical trials examining the strength of association between treatment effects measured using surrogate markers and clinical outcomes in nononcologic chronic diseases. The Food and Drug Administration (FDA) Adult Surrogate Endpoint Table and MEDLINE from inception to March 19, 2023. Three reviewers selected meta-analyses of clinical trials; meta-analyses of observational studies were excluded. Two reviewers extracted correlation coefficients, coefficients of determination, slopes, effect estimates, or results from meta-regression analyses between surrogate markers and clinical outcomes. Correlation coefficient or coefficient of determination, when reported, was classified as high strength (r ≥ 0.85 or R2 ≥ 0.72); primary findings were otherwise summarized. Thirty-seven surrogate markers listed in FDA's table and used as primary end points in clinical trials across 32 unique nononcologic chronic diseases were included. For 22 (59%) surrogate markers (21 chronic diseases), no eligible meta-analysis was identified. For 15 (41%) surrogate markers (14 chronic diseases), at least 1 meta-analysis was identified, 54 in total (median per surrogate marker, 2.5; IQR, 1.3-6.0); among these, median number of trials and patients meta-analyzed was 18.5 (IQR, 12.0-43.0) and 90 056 (IQR, 20 109-170 014), respectively. The 54 meta-analyses reported 109 unique surrogate marker-clinical outcome pairs: 59 (54%) reported at least 1 r or R2, 10 (17%) of which reported at least 1 classified as high strength, whereas 50 (46%) reported slopes, effect estimates, or results of meta-regression analyses only, 26 (52%) of which reported at least 1 statistically significant result. Most surrogate markers used as primary end points in clinical trials to support FDA approval of drugs treating nononcologic chronic diseases lacked high-strength evidence of associations with clinical outcomes from published meta-analyses.

Effect of metformin on anti-mullerian hormone levels in women with polycystic ovarian syndrome: a systematic review and meta-regression analysis of randomized controlled trials with

BackgroundSeveral interventional studies have evaluated the potential anti-Mullerian hormone (AMH)-reduction effect of metformin. However, the results are still contradictory. In order to obtain a better viewpoint from them, this study aimed to comprehensively investigate the effects of metformin on AMH in the women with with polycystic ovarian syndrome (PCOS).MethodsScopus, PubMed/Medline, Web of Science, Cochrane, and Embase databases were searched using standard keywords to identify all controlled trials investigating the AMH levels following metformin administration. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model analysis for the best estimation of outcomes.ResultsSixteen studies with 484 participants’ were included in this article. The pooled findings showed that AMH levels in the single arm clinical trials were significantly reduced (pooled WMD of -3.06 ng/ml; 95% confidence interval [CI] -4.03 to -2.10; P < 0.001) after use of metformin. Furthermore, compared to the control group, in randomized clinical trials, a reduced significant effect on AMH levels was observed following use of metformin (pooled WMD of -3.47 ng/ml; 95% CI -7.14 to -0.19; P = 0.047). Furthermore, higher reduction in the AMH levels with a metformin dosage ≤ 1500 mg/day and duration of treatment ≤ 12 weeks when compared to higher dosages and duration of intervention, observed in this meta-analysis.ConclusionsIn conclusion, results this meta-analysis of clinical trials confirms the beneficial effect of the treatment with metformin in the reduction of the AMH levels in women.

Accuracy of implant placement with computer-aided static, dynamic, and robot-assisted surgery: a systematic review and meta-analysis of clinical trials

This systematic review explores the accuracy of computerized guided implant placement including computer-aided static, dynamic, and robot-assisted surgery. An electronic search up to February 28, 2023, was conducted using the PubMed, Embase, and Scopus databases using the search terms “surgery”, “computer-assisted”, “dynamic computer-assisted”, “robotic surgical procedures”, and “dental implants”. The outcome variables were discrepancies including the implant’s 3D-coronal, -apical and -angular deviations. Articles were selectively retrieved according to the inclusion and exclusion criteria, and the data were quantitatively meta-analysed to verify the study outcomes. Sixty-seven articles were finally identified and included for analysis. The accuracy comparison revealed an overall mean deviation at the entry point of 1.11 mm (95% CI: 1.02–1.19), and 1.40 mm (95% CI: 1.31–1.49) at the apex, and the angulation was 3.51˚ (95% CI: 3.27–3.75). Amongst computerized guided implant placements, the robotic system tended to show the lowest deviation (0.81 mm in coronal deviation, 0.77 mm in apical deviation, and 1.71˚ in angular deviation). No significant differences were found between the arch type and flap operation in cases of dynamic navigation. The fully-guided protocol demonstrated a significantly higher level of accuracy compared to the pilot-guided protocol, but did not show any significant difference when compared to the partially guided protocol. The use of computerized technology clinically affirms that operators can accurately place implants in three directions. Several studies agree that a fully guided protocol is the gold standard in clinical practice.

Response to Nguyen et al.'s letter regarding "Anteriolateral versus anterior-posterior electrodes in external cardioversion of atrial fibrillation: A systematic review and meta-analysis of clinical trials".

Response to Nguyen et al.'s letter regarding "Anteriolateral versus anterior-posterior electrodes in external cardioversion of atrial fibrillation: A systematic review and meta-analysis of clinical trials".

Safety and efficacy of acetylcholinesterase inhibitors for Alzheimer's disease: A systematic review and meta-analysis.

Alzheimer's disease (AD) affects millions of people worldwide. The most commonly used drugs are acetylcholinesterase inhibitors, i.e., donepezil, galantamine and rivastigmine, which increase levels of acetylcholine. However, the exact efficacy and safety of acetylcholinesterase inhibitors in the treatment of AD is still unclear. The main objective of the current study was to determine the exact safety and efficacy profile of acetylcholinesterase inhibitors in the treatment of AD by conducting a systematic review and meta-analysis of clinical trials according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We conducted a web-based literature search of PubMed and clinical trial websites using relevant keywords. Data were extracted from eligible records and pooled as mean difference (MD) or risk ratio (RR) values with their 95% confidence interval (95% CI) using Review Manager software (v. 5.3 for Windows). Heterogeneity was calculated using χ2 and I2 tests. The standard mean difference (SMD) was -0.33 [-0.52, -0.13] for donepezil, -0.48 [-0.58, -0.38] for galantamine and -0.65 [-1.06, -0.23] for rivastigmine, indicating a significant effect of these drugs on cognitive outcomes. Here we show the significant effects of all available acetylcholinesterase inhibitors on cognitive function in patients with AD. However, further studies are needed to draw valid conclusions about the effects of acetylcholinesterase inhibitors on functional outcomes and adverse events.

Efficacy and safety of probiotics in irritable bowel syndrome: A systematic review and meta-analysis

BackgroundIrritable bowel syndrome (IBS) is a common gastrointestinal disease characterized by abdominal pain, distension, and altered bowel habits. Probiotics may alleviate IBS symptoms, but clinical trials remain conflicting. AimsTo conduct a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety of probiotics for IBS patients. MethodsWe searched relevant trials in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar from 2000 to June 2023. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated for continuous outcomes. A risk ratio (RR) and a 95% CI were calculated for dichotomous outcomes. ResultsA total of 20 studies involving 3011 patients were obtained. The results demonstrated that probiotics are more effective than placebo in reducing global IBS symptoms improvement rate (RR = 1.401, 95% CI 1.182 - 1.662, P < 0.001) and quality of life scores (SMD = 0.286, 95% CI = 0.154 - 0.418, P < 0.001). Subgroup analyses showed that a shorter treatment time (less than eight weeks) could reduce distension scores (SMD = 0.197, 95% CI = 0.038 - 0.356, P = 0.015). High doses (daily dose of probiotics ≥ 10ˆ10) or multiple strains of probiotics exhibit beneficial effects on abdominal pain (SMD = 0.412, 95% CI = 0.112 - 0.711, P = 0.007; SMD = 0.590, 95% CI = 0.050 - 1.129, P = 0.032; respectively). However, there was no significant benefit on global symptom scores (SMD = 0.387, 95% CI 0.122 to 0.653, P = 0.004) with statistically high inter-study heterogeneity (I2 = 91.9%, P < 0.001). Furthermore, there was no significant inter-group difference in terms of adverse events frequency (RR = 0.997, 95% CI 0.845 - 1.177, P = 0.973). ConclusionProbiotics are effective and safe for IBS patients. High doses or multiple probiotic strains seem preferable, but definite conclusions are challenging due to the high heterogeneity. Large-scale, well-designed, and rigorous trials are needed to confirm their effectiveness.

Effect of hospital elder life program on the incidence of delirium: A systematic review and meta-analysis of clinical trials

Objective: This meta-analysis aims to investigate the effect of the Hospital Elder Life Program (HELP) on the incidence of delirium, delirium scores, length of hospital stay, and incidence of falls.Methods: Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched from inception until January 18, 2024. The search specifically targeted randomized controlled trials (RCTs). Two independent researchers conducted literature screening, quality assessment, and data extraction. The meta-analysis was performed using Review Manager 5.4.1 and Stata 15.1 software.Results: The final analysis included a total of 9 RCTs with 2583 patients. The findings from the meta-analysis indicated that HELP was found to considerably reduce the incidence of delirium and the length of hospital stay when compared to the control group. Nevertheless, no statistically significant differences were observed between the two groups in terms of delirium scores and fall rates.Conclusion: In this meta-analysis, HELP can effectively reduce the incidence of delirium and lead to a shorter hospital stay.

Continuous Positive Airway Pressure vs. Nasal Intermittent Positive Pressure Ventilation in Preterm Neonates: What if Mean Airway Pressures were Equivalent?

Respiratory support for preterm neonates in modern neonatal intensive care unit is predominantly with the use of non-invasive interfaces. Continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) are the prototypical and most commonly utilized forms of non-invasive respiratory support, and each has unique gas flow characteristics. In meta-analyses of clinical trials till date, NIPPV has been shown to likely reduce respiratory failure and need for intubation compared to CPAP. However, a significant limitation of the included studies has been the higher mean airway pressures used during NIPPV. Thus, it is unclear to what extent any benefits seen with NIPPV are due to the cyclic pressure application vs. the higher mean airway pressures. In this review, we elaborate on these limitations and summarize the available evidence comparing NIPPV and CPAP at equivalent mean airway pressures. Finally, we call for further studies comparing non-invasive respiratory support modes at equal mean airway pressures.

Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

Does Quinoa (Chenopodium quinoa) Consumption Improve Blood Glucose, Body Weight and Body Mass Index? A Systematic Review and Dose-Response Meta-Analysis of Clinical Trials.

Quinoa (Chenopodium quinoa) has a structure similar to whole grains and contains phytochemicals and dietary fiber. Hence, it is considered a food substance with a high nutritional value. The purpose of the present study was to assess the efficacy of quinoa in reducing fasting blood glucose (FBG), body weight (BW), and body mass index (BMI) in a meta-analysis of randomized clinical trials. A comprehensive search in ISI Web of Science, Scopus, and PubMed databases as well as Google Scholar, was conducted up to November 2022 to identify reports of randomized clinical trials that investigated the effect of quinoa on FBG, BW, and BMI. Seven trials comprising 258 adults with mean ages of 31 to 64 years were included in this review. Studies used 15 to 50 grams of quinoa/per day as an intervention, and the intervention was between 28 to 180 days. In a dose-response analysis of FBG, there was significant evidence of a nonlinear association between intervention and FBG based on the quadratic model (P-value for nonlinearity = 0.027); hence, the slope of the curve increased when quinoa intake was nearly 25 g/- day. In comparison between quinoa seed supplementation and placebo, our findings showed that quinoa seed supplementation did not have a significant effect on BMI (MD: -0.25; 95% CI: -0.98, 0.47; I2=0%, P = 0.998) and BW (MD: -0.54; 95% CI: -3.05, 1.97; I2=0%, P = 0.99), when compared with placebo. Evidence of publication bias was not found among the included studies. The present analysis revealed the beneficial effects of quinoa on the blood glucose level. Further studies on quinoa are needed to confirm these results.

Efficacy of autologous platelet concentrate products for alveolar preservation: A meta-analysis.

The purpose of the study was to systematically evaluate the efficacy of autologous platelet concentrate products in the preservation of the alveolar ridge after tooth extraction through meta-analysis and provide a theoretical basis for the clinical application of autologous platelet concentrates to reduce alveolar bone resorption. This study conducted a meta-analysis of clinical trials between 2013 and 2023, focusing on autologous platelet concentrate products (e.g., PRP, PRF, CGF, and PRCF) used for alveolar ridge preservation after tooth extraction. The analysis included 122 articles and 371 extraction sockets. All statistical analyses were performed using Review Manager version 5.4. Results indicate that these platelet concentrates effectively reduced changes in horizontal width 1 mm below the alveolar crest and vertical socket height. They also promoted a higher percentage of new bone formation in extraction sockets compared with control groups. However, they did not significantly prevent horizontal bone resorption at 3 and 5 mm below the alveolar crest. In conclusion, autologous platelet concentrates are useful for alveolar ridge preservation, but larger clinical studies are needed to confirm these findings due to the relatively small sample size in this study.

Can the Evidence-Based Use of Probiotics (Notably Saccharomyces boulardii CNCM I-745 and Lactobacillus rhamnosus GG) Mitigate the Clinical Effects of Antibiotic-Associated Dysbiosis?

Dysbiosis corresponds to the disruption of a formerly stable, functionally complete microbiota. In the gut, this imbalance can lead to adverse health outcomes in both the short and long terms, with a potential increase in the lifetime risks of various noncommunicable diseases and disorders such as atopy (like asthma), inflammatory bowel disease, neurological disorders, and even behavioural and psychological disorders. Although antibiotics are highly effective in reducing morbidity and mortality in infectious diseases, antibiotic-associated diarrhoea is a common, non-negligible clinical sign of gut dysbiosis (and the only visible one). Re-establishment of a normal (functional) gut microbiota is promoted by completion of the clinically indicated course of antibiotics, the removal of any other perturbing external factors, the passage of time (i.e. recovery through the microbiota's natural resilience), appropriate nutritional support, and-in selected cases-the addition of probiotics. Systematic reviews and meta-analyses of clinical trials have confirmed the strain-specific efficacy of some probiotics (notably the yeast Saccharomyces boulardii CNCM I-745 and the bacterium Lactobacillus rhamnosus GG) in the treatment and/or prevention of antibiotic-associated diarrhoea in children and in adults. Unusually for a probiotic, S.boulardii is a eukaryote and is not therefore directly affected by antibiotics-making it suitable for administration in cases of antibiotic-associated diarrhoea. A robust body of evidence from clinical trials and meta-analyses shows that the timely administration of an adequately dosed probiotic (upon initiation of antibiotic treatment or within 48h) can help to prevent or resolve the consequences of antibiotic-associated dysbiosis (such as diarrhoea) and promote the resilience of the gut microbiota and a return to the pre-antibiotic state. A focus on the prescription of evidence-based, adequately dosed probiotics should help to limit unjustified and potentially ineffective self-medication.

Effect of Fibrate Treatment on Circulating Adipokine Levels: A Systematic Review and Meta-analysis of Randomized Clinical Trials

Fibrates are widely used in the treatment of dyslipidemia and associated metabolic abnormalities; however, their effects on adipokines are unclear. This meta-analysis of clinical trials aimed to evaluate the effect of fibrates on circulating adipokine levels. Only randomized controlled trials investigating the impact/effect of fibrate treatment on circulating adipokine levels were included from searches in PubMed-Medline, SCOPUS, ClinicalTrials.gov, Web of Science, and Google Scholar databases. A random effects model and the generic inverse variance method were used for the meta-analysis. Sensitivity analysis was conducted using the leave-one-out method. This meta-analysis of 22 clinical trials showed a significant reduction on/in leptin (WMD: -1.58 ng/mL, 95% CI: -2.96, -0.20, p = 0.02, I2 = 0%), plasminogen activator inhibitor-1 (PAI-1) (WMD: -13.86 ng/mL, 95% CI: -26.70, -1.03, p = 0.03, I2 = 99%), and visfatin (WMD: -1.52 ng/mL, 95% CI: -2.49, -0.56, p = 0.002, I2 = 0%) after fibrate therapy; no significant effect was observed on adiponectin (WMD: -0.69 µg/ml, 95% CI: -1.40, 0.02, p = 0.06, I2 = 83%) and resistin (WMD: -2.27 ng/mL, 95% CI: -7.11, 2.57, p = 0.36, I2 = 0%). The sensitivity analysis was robust only for visfatin, while the effect size was sensitive to one arm for leptin, four for adiponectin, and two for PAI-1. This meta-analysis showed that fibrate treatment significantly improves adipokine levels with a decrease in leptin, PAI-1, and visfatin, suggesting potential additional clinical therapeutic benefits through/of fibrate treatment on adipose tissue.

Pathologic complete response among patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A meta-analysis.

305 Background: Although neoadjuvant therapy improves overall survival in esophageal cancers, the benefit is largely confined to those with the greatest pathologic response. Current estimates of pathologic complete response (pCR) rates come from individual studies and lack precision. With this study, we sought to estimate summary pCR rates in patients with non-metastatic esophageal cancer who received either neoadjuvant chemotherapy or chemoradiation by conducting a systematic review and meta-analysis of clinical trials. Methods: Studies were identified from the Medline, EMBASE, and CENTRAL database searches. Eligible studies were published in English from 1992-2022 and consisted of clinical trials that focused on incident non-metastatic esophageal cancer or cancer of the gastroesophageal junction. Trials were required to contain at least one arm of patients receiving neoadjuvant chemotherapy (including perioperative) or neoadjuvant chemoradiation (including treatment with induction chemotherapy). Eligible studies had to report pCR in at least 20 patients who underwent neoadjuvant therapy and surgery. Pooled pCR prevalence was determined using the Freeman-Tukey double arcsine transformation and a random effects model. Results: Among 6,575 records first identified, we included 75 studies with 5,988 patients in the meta-analysis. Of the included studies, 38 (51%) were single arm trials, 35 (47%) were randomized trials, and 2 (3%) were non-randomized trials of multiple treatments. Geographically, 28 (37%), 24 (32%), 21 (28%), and 2 (3%) of the included trials were performed in Asia, Europe, North America, and Australia, respectively. Across 91 trial arms that delivered either neoadjuvant chemotherapy or chemoradiation, platinum and fluorouracil-based regimens were the most common (48.4%), followed by platinum and taxane-based regimens (26.4%), regimens that contained platinum-based agents, fluorouracil, and a taxane (13.2%), and other regimens (12.1%). The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6% – 14%) across 16 studies, ranging from 0%-32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26% – 39%) across 21 studies, ranging from 8% to 66%. For adenocarcinomas, the pooled prevalence of pCR was 2% (95% CI: 0% – 7%) after neoadjuvant chemotherapy, across 3 studies, and 22% (17% - 27%) after neoadjuvant chemoradiation across 11 studies. Conclusions: In this meta-analysis, we found that under one-third of patients with non-metastatic esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. As pCR represents an increasingly utilized as an endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

PD-L1 as a predictor of chemo-immunotherapy response in biliary tract cancers: A systematic review and meta-analysis.

541 Background: Advanced biliary tract cancers (BTCs) are rare and aggressive malignancies with limited treatment options. Recently, immune checkpoint inhibitors in combination with chemotherapy (ICI-C) gained approval as first-line therapy for unresectable or metastatic BTCs. Two large phase III clinical trials of ICI-C in BTCs did not show a significant correlation between PD-L1 expression and therapeutic response. However, in a phase II study of single-agent nivolumab, there was an association. In light of these conflicting findings, we conducted a comprehensive systematic review and meta-analysis of clinical trials investigating ICI-C in BTCs to assess whether PD-L1 expression could predict treatment response. Methods: We searched PubMed, Web of Science, EMBASE, and Cochrane databases to identify relevant studies. Patient characteristics, method of PD-L1 assessment, and measures of treatment response including hazard ratio (HR), objective response rate (ORR), progression-free-survival (PFS), and overall survival (OS) were extracted. Pooled ORR and HR were calculated using random effect model and assessed for study heterogeneity. Results: Among the 4,882 studies screened, seven clinical trials evaluating the efficacy of ICI-C in BTCs were identified. Of these trials, two randomized phase III trials report HR between PD-L1 positive and negative patients, while five phase II clinical trials reported ORR based on PD-L1 expression. Out of the 1,069 patients included in these trials, 954 underwent assessment for PD-L1 expression. 66.4% (n=634) exhibited PD-L1 expression level ≥ 1% as determined by either tumor proportion score (TPS) or combined positive score (CPS), while 33.5% (n=320) were classified as PD-L1 negative. Notably, 115 patients were not tested for PD-L1 expression, a variety of PD-L1 assays were used across the studies, and only some studies reported multiple PD-L1 cutoffs. Pooled analysis of two-phase III trials demonstrated that PD-L1 expression ≥ 1% was associated with improved OS (pooled HR 0.83, 95% CI 0.72-0.95) compared to PD-L1 &lt; 1% (pooled HR 0.85, 95% CI 0.67-1.07). Additionally, pooled ORR from five phase II studies showed a trend towards an improved response in patients with PD-L1 expression ≥ 1% (pooled ORR 64%, 95% CI 52-74%) compared to PD-L1 &lt;1% (pooled ORR 46%, 95% CI 31-62%) with a subgroup difference p-value of 0.08. Conclusions: This meta-analysis suggests that BTCs patients with PD-L1 expression ≥ 1% may exhibit a more favorable response to chemo-immunotherapy, and that a majority of BTCs have this level of expression. These findings support further investigation of the use of PD-L1 as a biomarker, and in particular investigation of different PD-L1 levels, which may inform treatment for patients with relative contraindications to immunotherapy use.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

Effects of whole-body vibration exercise on physical function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundThe current state of knowledge regarding the efficacy of whole-body vibration (WBV) training for individuals with chronic kidney disease (CKD) is limited. To address this gap, the present study seeks to undertake a comprehensive systematic review and meta-analysis of clinical trials to evaluate the impact of WBV on physical function and quality of life outcomes in CKD patients.MethodsA systematic search was performed on the PubMed, Embase, Web of Science, and Scopus databases from inception to March 2023 and updated in June 2023. The inclusion criteria comprised randomized controlled studies, quasi-experimental studies, and single-arm trials that evaluated the impact of WBV on physical function, encompassing cardiopulmonary fitness, muscle strength, mobility, and balance, in CKD patients. Adverse events that were included in the study reports were recorded. The pooled evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.ResultsNine studies were identified, of which seven were included in the meta-analysis. The results of the meta-analysis indicated a statistically significant improvement in upper (mean difference: 3.45 kg; 95% confidence interval 1.61 to 5.29) and lower (standardized mean difference: 0.34, 95% confidence interval 0.08 to 0.59) extremity muscle strength in patients with CKD who underwent WBV training compared to baseline (low-level evidence). Furthermore, WBV training favored improved cardiorespiratory fitness, mobility, and balance function, but no statistical difference was observed. The impact of WBV training on quality of life in patients with CKD requires further validation. Notably, only one adverse event (nausea) was reported in the included studies.ConclusionsWBV has demonstrated efficacy and feasibility in enhancing muscle strength among patients with CKD. However, further investigation is warranted to determine its potential for improving cardiorespiratory adaptations, mobility, balance function, and quality of life. Additionally, future research should prioritize comprehensive reporting of WBV protocols to establish an optimal training regimen for the CKD population.