Absence Of Heterogeneity Research Articles

Copula-Based Model for Incorporating Single-Agent Historical Data into Dual-Agent Phase I Cancer Trials

Phase I clinical trials for testing the combination of anticancer drugs (combination trials) generally start after the tolerability of each drug is evaluated in phase I clinical trials for monotherapy (single-agent trials). In either trial, one of the crucial objectives is to identify the maximum tolerated dose (or dose combination). Several methods to incorporate data from single-agent trials (SA historical data) into subsequent combination trials have been proposed. However, the effect of using SA historical data under the presence of heterogeneity in data between single-agent and combination trials has not been discussed sufficiently. In this study, we examined the relationships among the presence and absence of heterogeneity, the amount of SA historical data incorporated, and the performance of dose-finding designs (e.g., the percentages of correct selection of maximum tolerated dose combination) by conducting an extensive simulation study with 100,000 random toxicity scenarios. In this evaluation, we used a dose-finding design based on a copula-based model that could easily leverage SA historical data. Although our simulations showed that incorporating SA historical data under homogeneity between SA historical and the current data is beneficial, we found advantages in incorporating heterogeneous data, provided heterogeneity is not extremely large.

Is robotic assistance an added value in minimally invasive mitral valve surgery? A meta-analysis from propensity score-matched series.

There is still ongoing debate about the benefits of robotic assistance (R-MVS) in comparison with video assistance (V-MVS) in minimally invasive mitral valve surgery. This study aims to update the current evidence. Three propensity score-matched studies published from 2011 to 2021 were included with a total of 1193 patients operated on from 2005 (R-MVS: 536, V-MVS: 657). Data regarding early mortality, postoperative event, and time-related outcomes were extracted and submitted to a meta-analysis using weighted random-effects modeling. The incidence of early mortality, stroke, renal failure, conversion, atrial fibrillation, and prolonged ventilation were similar, all in the absence of heterogeneity. Reoperation for bleeding (odds ratio [OR]: 0.36, 95% confidence interval [CI] 0.16-0.81, p = 0.01) and the need for blood transfusion (OR: 0.30, 95% CI, 0.20-0.56, p = 0.001) were significantly lower in V-MVS group. Regarding time-related outcomes, there was evidence for important heterogeneity of treatment effect among the studies. Operative times were longer in R-MVS: differences in means were 20.7 min for cross-clamp time (95% CI, 9.07-32.3, p = 0.001), 20.7 min for cardiopulmonary bypass time (95% CI, 2.5-38.9, p = 0.03) and 40.2 min for total operative time (95% CI, 24.5-55.8, p < 0.001). Intensive care unit stay and hospital stay were reported in one study, and longer after R-MVS compared to V-MVS; the differences in means were 0.17 days (p = 0.005) and 0.6 days (p = 0.017), respectively. Total cost of both procedures was reported in an additional dedicated propensity score-matched series including 448 patients; it was 21% higher for R-MVS than for V-MVS. This meta-analysis showed excellent outcomes of both video and robotic techniques with low incidence of morbidity and mortality. However, there is no evidence for an added value of robotic assistance in comparison with video assistance; the drawbacks of mini access are reported higher regardless the induced over cost.

On predicting heterogeneity in nanoparticle dosage

Nanoparticles are increasingly employed as a vehicle for the targeted delivery of therapeutics to specific cell types. However, much remains to be discovered about the fundamental biology that dictates the interactions between nanoparticles and cells. Accordingly, few nanoparticle-based targeted therapeutics have succeeded in clinical trials. One element that hinders our understanding of nanoparticle–cell interactions is the presence of heterogeneity in nanoparticle dosage data obtained from standard experiments. It is difficult to distinguish between heterogeneity that arises from stochasticity in nanoparticle-cell interactions, and that which arises from heterogeneity in the cell population. Mathematical investigations have revealed that both sources of heterogeneity contribute meaningfully to the heterogeneity in nanoparticle dosage. However, these investigations have relied on simplified models of nanoparticle internalisation. Here we present a stochastic mathematical model of nanoparticle internalisation that incorporates a suite of relevant biological phenomena such as multistage internalisation, cell division, asymmetric nanoparticle inheritance and nanoparticle saturation. Critically, our model provides information about nanoparticle dosage at an individual cell level. We perform model simulations to examine the influence of specific biological phenomena on the heterogeneity in nanoparticle dosage in the absence of heterogeneity in the cell population. Under certain modelling assumptions, we derive analytic approximations of the nanoparticle dosage distribution. We demonstrate that the analytic approximations are accurate, and show that nanoparticle dosage can be described by a Poisson mixture distribution with rate parameters that are a function of Beta-distributed random variables. We discuss the implications of the analytic results with respect to parameter estimation and model identifiability from standard experimental data. Finally, we highlight extensions and directions for future research.

Impact of diabetes mellitus on rifampicin's plasma concentration and bioavailability in patients with tuberculosis: A systematic review and meta-analysis study

To assess the impact of diabetes mellitus on plasma concentration and bioavailability of rifampicin. Web of Science, Cochrane Library, PubMed and Scopus databases were screened until September 2020 on studies reported rifampicin's plasma concentration, bioavailability among diabetic tuberculosis patients and non-diabetic tuberculosis patients. According to the presence or absence of heterogeneity, the pooled estimate was operated by a random or fixed effect model. Sensitivity analysis or subgroup analysis were conducted. Attributed risk fraction of diabetes mellitus in the incidence of low rifampicin's plasma concentration 2-h after administration was calculated. Seventeen studies including 3478 tuberculosis patients were included in this study. Diabetic tuberculosis patients had 1.59 folds incidence of low rifampicin's plasma concentration 2-h after administrations (risk ratio 1.59, 95% confidence interval (1.16, 2.19), p = 0.004) and lower rifampicin's plasma concentration 2-h after administrations (mean difference -1.4, 95% confidence interval (-2.65,-0.15), p = 0.03) compared with non-diabetic tuberculosis patients. The attributed risk fraction of diabetes mellitus in the incidence of low rifampicin's plasma concentration 2-h after administration was 37%. There were no significant difference in rifampicin's maximum plasma concentration, event of low maximum plasma concentration, bioavailability and half-life between both groups. Diabetes mellitus attributed with 37% of low rifampicin's plasma concentration 2-h after administration but not influenced rifampicin's maximum plasma concentration, bioavailability and half-life. The negative effect of diabetes on plasma concentration 2hours after administration was influenced by diabetes management, income level, type of tuberculosis and its recurrence.

Restaurant sector efficiency frontiers: a meta-analysis

ABSTRACT In recent years, there has been a growing interest in assessing the level of performance and efficiency of the foodservice industry. As a result, an increasing number of studies applied efficiency frontiers methods to quantify firm (in)efficiency. Starting from the benchmarking studies on restaurant efficiency, this paper aims to develop a meta-analysis based on 77 observations from 25 studies published in scientific journals from 1998 to 2020. The estimated effect size in our meta-analysis is equal to 0.842 and is statistically different from zero, while the Cochran’s Q test for the heterogeneity in our sample hints at the absence of heterogeneity in the previous studies on restaurant efficiency. A meta-regression analysis partially supports this result but also highlights the importance of assuming an appropriate return to scale, given the peculiarity of the sector.

The impact of diabetes mellitus on the pharmacokinetics of rifampicin among tuberculosis patients: A systematic review and meta-analysis study

Background and aimsDiabetes mellitus has a negative impact on the treatment outcome of tuberculosis, increasing the incidence of treatment failure and relapse. There is a scarcity of knowledge concerning the impact of diabetes mellitus on the pharmacokinetics of rifampicin. This study was conducted to evaluate the impact of diabetes mellitus on the pharmacokinetics of rifampicin among patients with tuberculosis. MethodsWe explored the Web of Science, Cochrane Library, PubMed, and Scopus databases for articles that reported the pharmacokinetic parameters of rifampicin in diabetic and nondiabetic patients with tuberculosis published until September 2020. Based on the presence or absence of heterogeneity, pooled estimates were calculated using a random or fixed effect model. ResultsSeven studies were relevant and included in this study. The Tmax of rifampicin increased in diabetic patients with tuberculosis compared with nondiabetic patients with tuberculosis (MD 0.84, 95% CI (0.32, 1.35), p = 0.002). No significant differences were detected in rifampicin Cmax (MD 0.18, 95% CI (−0.52, 0.88), p = 0.61), AUC0–24 (SMD -0.02, 95% CI (−0.34, 0.30), p = 0.90), Vd (MD -3.89, 95% CI (−11.17, 3.38), p = 0.29), CL (MD -0.13, 95%CI (−0.88, 0.61), p = 0.72), and MRT (MD 1.89, 95% CI (−0.03, 3.81), p = 0.05) between diabetic and nondiabetic patients with tuberculosis. ConclusionDiabetes mellitus increased the Tmax of rifampicin without further impact on other rifampicin pharmacokinetic parameters such as Cmax, AUC0–24, Vd, CL and MRT. Early therapeutic drug monitoring of rifampicin is necessary for diabetic tuberculosis patients.

Orthodontic bracket bonding techniques and adhesion failures: A systematic review and meta-analysis.

BackgroundThis systematic review compared the bonding failures of orthodontic brackets bonded by indirect or direct techniques. Data sources: The searched databases were Cochrane Library, LILACS, BBO, PubMed, Scopus, Web of Science. Material and MethodsA search for randomized clinical trials comparing the two techniques was carried out to answer the research question: When considering orthodontic bracket bonding on permanent teeth, does the indirect technique reduce the number of bonding failures compared to the direct one over time? The quality of the included papers was assessed with Cochrane risk of bias tool and the quality of evidence with GRADE. ResultsFrom 3096 articles identified, seven were included in the systematic review (five at unclear; two at low risk of bias). Meta-analysis was carried out according to the follow-up periods (0-6 months and 12-15 months). ResultsIn the first period, bonding techniques were similar with regard to adhesion failures (RR = 0.59; 95% CI 0.10-3.62; p = 0.00001; I2 = 92%); in the 12-to-15-month period, the direct bonding technique proved to be superior (RR = 1.44; 95% CI 1.05 - 1.99; p = 0.41; I2 = 0%). The quality of evidence was classified as low for the 0-6 months follow-up and high for the 12 months. ConclusionsBased on the absence of heterogeneity and the high quality of evidence, it is concluded that the direct bracket bonding technique has a lower failure rate than the indirect technique in the long term (12-15 months). Key words:Orthodontic brackets, fixed orthodontics, systematic review.

Effect of homophily and correlation of beliefs on COVID-19 and general infectious disease outbreaks.

Contact between people with similar opinions and characteristics occurs at a higher rate than among other people, a phenomenon known as homophily. The presence of clusters of unvaccinated people has been associated with increased incidence of infectious disease outbreaks despite high population-wide vaccination rates. The epidemiological consequences of homophily regarding other beliefs as well as correlations among beliefs or circumstances are poorly understood, however. Here, we use a simple compartmental disease model as well as a more complex COVID-19 model to study how homophily and correlation of beliefs and circumstances in a social interaction network affect the probability of disease outbreak and COVID-19-related mortality. We find that the current social context, characterized by the presence of homophily and correlations between who vaccinates, who engages in risk reduction, and individual risk status, corresponds to a situation with substantially worse disease burden than in the absence of heterogeneities. In the presence of an effective vaccine, the effects of homophily and correlation of beliefs and circumstances become stronger. Further, the optimal vaccination strategy depends on the degree of homophily regarding vaccination status as well as the relative level of risk mitigation high- and low-risk individuals practice. The developed methods are broadly applicable to any investigation in which node attributes in a graph might reasonably be expected to cluster or exhibit correlations.

Considering the Contradictions of Religion and Orthodox Christianity as concomitantly endorsing strife and accord – a Social Capital Perspective

This paper contributes to the existing literature by providing an discussion and a critique of the discourse of social capital as it relates to Christianity and in particular to an Orthodox stance. Religion is acknowledged as responsible for promoting factions in the world, as well as for the strife amongst the various religious groups. The New Testament is studied with the constituents of social capital – networks (groups), norms and trust – as a foundation for evaluating the ministries and teaching of Christianity with regards to the role thereof in promoting strife and unity and ultimately harmony amongst people. The ministry of Jesus Christ was distinctly opposed to the prevailing social capital in the then Jewish territories, as is the case in the epistles when speaking to the non-Jewish parishes. The prevailing normative principles were frequently censured, and the confrontational manner in which the established social groups were related to, aggravated by the entirely inclusive but absolutely exclusive standpoint, is deemed inexcusable and resulted in the execution of Christ and a number of his apostles and other followers. The threat to the trust amongst the Jewish citizens and also between the general population groups and religious leaders proved to be a major driving force in ongoing persecutions. Unity amongst the early Christians proved elusive and the absence of heterogeneity as a requirement for socially cohesive networks and groups served to explain this challenge. Diversity of ethnicity, language and culture impeded the spontaneous social associations. The epistles provide us with a rich account of the significance of diversity and the constant efforts towards unity and societal harmony. This is in concord with the Orthodox faith which is strongly in favour of acceptance of diversity and love for others. Social capital is an stimulating idea that has since biblical days become a focus for community advancement initiatives. The social capital perspective of the New Testament easily transcends into our reality of today and supports the relevance of Christian principles two thousand years later.

Comparison of complications of early and delayed open reduction and internal fixation for treating pilon fracture: A protocol of systematic review and meta-analysis.

BackgroundTibial Pilon fractures are severe fractures accompanied by soft tissue injury. Although open reduction and internal fixation (ORIF) are effective in treating Pilon fractures, there is a controversy over time to surgery due to reported postoperative complications. However, there is no systematic review evaluating the difference of postoperative complications between early and delayed ORIF for treating pilon fractures.MethodsRelevant literature written in English will be searched through PubMed, Cochrane Library, Embase, MEDLINE, and Web of Science. The study aims to compare the effects and complications of early and delayed ORIF for treating fresh pilon fractures in adult patients. The primary outcome will be infection rate, fracture union time, nonunion and malunion rate. And the secondary outcome will be metalwork removal, amputation, and ankle function grade. Two reviewers will independently assess the eligibility of the studies according to the pre-defined inclusion and exclusion criteria. A meta-analysis for the available data will be conducted using Revman 5.3. To measure effect size, odds ratios (ORs) and mean difference will be used for dichotomous and continuous data, respectively. Statistical heterogeneity will be explored. And a random-effects model or a fixed-effects will be used in pooled data on the basis of the existence or absence of heterogeneity. Subgroup analysis will be conducted to identify sources of heterogeneity and sensitivity analysis to test the results’ robustness. We will assess the risk of bias by four different quality assessment tools according to the study design. Publication bias will be evaluated by funnel plot. The study data will be stored in the Open Science Framework website.PROSPERO registration number CRD42020207465

Association between SARS-CoV-2 infection and disease severity among prostate cancer patients on androgen deprivation therapy: a systematic review and meta-analysis

PurposeAndrogen-regulated enzymes such as the angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are involved in the SARS-CoV-2 infection process. The expression of TMPRSS2 and its fusion gene, which are increased in the epithelium of the human prostate gland during prostate carcinogenesis, are regulated by androgens. Our goal was to assess the risk of the SARS-CoV-2 infection and the severity of the disease in PCa patients treated with androgen deprivation therapy (ADT).MethodsWe conducted a systematic review and meta-analysis according to PRISMA guidelines. We queried PubMed and Web of Science databases on 1 July 2021. We used random- and/or fixed-effects meta-analytic models in the presence or absence of heterogeneity according to Cochrane’s Q test and I2 statistic, respectively.ResultsSix retrospective studies (n = 50,220 patients) were selected after considering inclusion and exclusion criteria for qualitative evidence synthesis. Four retrospective studies were included to assess the SARS-CoV-2 infection risk in PCa patients under ADT vs. no ADT and the summarized risk ratio (RR) was 0.8 (95% confidence intervals (CI) 0.44–1.47). Five retrospective studies were included to assess the severity of coronavirus disease 2019 (COVID-19) in PCa patients under ADT versus no ADT and the summarized RR was 1.23 (95% CI 0.9–1.68).ConclusionWe found a non-significant association between the risk of SARS-CoV-2 infection and COVID-19 severity in PCa patients treated with ADT. However, our results suggest that during the COVID-19 pandemic PCa patients can safely undergo ADT as a cancer therapy without worsening COVID-19 risk and trajectory.

Intraoperative Neural Monitoring for Early Vocal Cord Function Assessment After Thyroid Surgery: A Systematic Review and Meta-Analysis.

Objective This study evaluated the diagnostic accuracies of various forms of intraoperative neural monitoring (IONM) in terms of predicting vocal cord palsy after thyroidectomy. Methods Two authors independently reviewed the six databases (PubMed, the Cochrane database, Embase, the Web of Science, SCOPUS, and Google Scholar) from their dates of inception to March 2021. Intraoperative electromyographic neuromonitoring (IONM) was compared with laryngoscopic detection (the reference method). True-positive, true-negative, false-positive, and false-negative data were extracted from each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies ver. 2 tool. Results Twenty-seven prospective or retrospective studies were included. The diagnostic odds ratio for IONM was 152.9623 ([95% confidence interval [75.4249; 310.2085]. The area under the summary receiver operating characteristic curve was 0.966. The sensitivity, specificity, negative predictive value, and positive predictive value were 0.8219 ([0.6862; 0.9069]), 0.9783 ([0.9659; 0.9863]), 0.9943 ([0.9880; 0.9973]), and 0.5523 ([0.4458; 0.6542]), respectively. The correlation between sensitivity and false-positive rate was 0.200, indicating the absence of heterogeneity. Subgroup analysis showed that the diagnostic accuracies of the continuous IONM was higher than those of intermittent IONM, and recent publications (> 2011) was higher than early publication (< 2010). Conclusions As the technology and knowledge of IONM have been accumulated and progressed over the past decades, the predictive value of IONM in postoperative vocal cord palsy has also improved. Moreover, the advances of continuous IONM technology could make a breakthrough in vocal cord evaluation after thyroid surgery.

Applications of simple and accessible methods for meta-analysis involving rare events: A simulation study.

Meta-analysis of clinical trials targeting rare events face particular challenges when the data lack adequate number of events and are susceptible to high levels of heterogeneity. The standard meta-analysis methods (DerSimonian Laird (DL) and Mantel–Haenszel (MH)) often lead to serious distortions because of such data sparsity. Applications of the methods suited to specific incidence and heterogeneity characteristics are lacking, thus we compared nine available methods in a simulation study. We generated 360 meta-analysis scenarios where each considered different incidences, sample sizes, between-study variance (heterogeneity) and treatment allocation. We include globally recommended methods such as inverse-variance fixed/random-effect (IV-FE/RE), classical-MH, MH-FE, MH-DL, Peto, Peto-DL and the two extensions for MH bootstrapped-DL (bDL) and Peto-bDL. Performance was assessed on mean bias, mean error, coverage and power. In the absence of heterogeneity, the coverage and power when combined revealed small differences in meta-analysis involving rare and very rare events. The Peto-bDL method performed best, but only in smaller sample sizes involving rare events. For medium-to-larger sample sizes, MH-bDL was preferred. For meta-analysis involving very rare events, Peto-bDL was the best performing method which was sustained across all sample sizes. However, in meta-analysis with 20% or more heterogeneity, the coverage and power were insufficient. Performance based on mean bias and mean error was almost identical across methods. To conclude, in meta-analysis of rare binary outcomes, our results suggest that Peto-bDL is better in both rare and very rare event settings in meta-analysis with limited sample sizes. However, when heterogeneity is large, the coverage and power to detect rare events are insufficient. Whilst this study shows that some of the less studied methods appear to have good properties under sparse data scenarios, further work is needed to assess them against the more complex distributional-based methods to understand their overall performances.

Association Between SHMT1 rs1979277 Polymorphism and Risk of Acute Lymphoblastic Leukemia: A Systematic Review and Meta-analysis.

The aim of this study was to explore the potential association the cytosolic serine hydroxy methyltransferase (SHMT1) rs1979277 polymorphism and the risk of acute lymphoblastic leukemia (ALL). Comprehensive search of Web of Science, PubMed, Ovid, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature Database electronic database, was performed to identify relevant studies published throughout April 30, 2019. The heterogeneity in the study was judged by the I2 and P-values, and then the random ratio or fixed effect was used to calculate the pooled odds ratios (OR) based on the presence or absence of heterogeneity. Sensitivity analysis is used to estimate the impact of individual studies on aggregate estimates. The publication bias of the study was tested using a funnel plot and an Egger regression. Nine studies with a total of 6492 participants (2971 patients; 3521 controls) were included in this meta-analysis. We found that SHMT1 rs1979277 polymorphism was not significantly associated with the risk of ALL in the dominant model: CC versus CT+TT (OR=0.84, 95% confidence interval [CI]: 0.46-1.54, P=0.57), recessive model: CC+CT versus TT (OR=0.81, 95% CI: 0.44-1.49, P=0.50) and allele model: C versus T (OR=0.84, 95% CI: 0.52-1.35, P=0.48). In subgroup analysis by ethnicity, no significant association were found in dominant, recessive and allele models in both Caucasian and Asian populations. Our study indicated that the SHMT1 rs1979277 polymorphism was not associated with the risk of susceptibility to ALL.

Extension of SKAT to multi-category phenotypes through a geometrical interpretation.

Rare genetic variants are expected to play an important role in disease and several statistical methods have been developed to test for disease association with rare variants, including variance-component tests. These tests however deal only with binary or continuous phenotypes and it is not possible to take advantage of a suspected heterogeneity between subgroups of patients. To address this issue, we extended the popular rare-variant association test SKAT to compare more than two groups of individuals. Simulations under different scenarios were performed that showed gain in power in presence of genetic heterogeneity and minor lack of power in absence of heterogeneity. An application on whole-exome sequencing data from patients with early- or late-onset moyamoya disease also illustrated the advantage of our SKAT extension. Genetic simulations and SKAT extension are implemented in the R package Ravages available on GitHub ( https://github.com/genostats/Ravages ).

Association of statins use and mortality outcomes in prostate cancer patients who received androgen deprivation therapy: a systematic review and meta-analysis.

IntroductionWhile several recent studies investigated the influence of statins on survival outcomes in prostate cancer (PCa) patients on androgen deprivation therapy (ADT), definitive conclusions are still missing. The present systematic review and meta-analysis aimed to develop an overarching framework for the association of statins use and survival outcomes in PCa patients who receive ADT.Material and methodsWe conducted a systematic review and meta-analysis of the literature assessing the survival outcomes for statin compared to non-statin users in PCa patients who received ADT. We searched PubMed and Web of Science for studies published before March 1, 2021. We used the random effect model in the presence of heterogeneity and the fixed-effects model in the absence of heterogeneity per the I 2 statistic. We did two meta-analyses; the primary meta-analysis was accomplished for articles reporting cancer-specific survival (CSS) as an outcome. A secondary meta-analysis was completed for articles reporting overall survival (OS) as an outcome.ResultsTen studies were eligible for inclusion. Nine studies included in the first meta-analysis comprising 136,285 patients showed no statistically significant difference in CSS (HR 0.77; 95% CI 0.49–1.21) between statin users and non-users in PCa patients who received ADT. In four studies included in the second meta-analysis comprising 95,032 patients, statin users had a significantly better OS compared to non-users (HR 0.67; 95% CI 0.62–0.73).ConclusionsAlthough the combination of statins and ADT in PCa patients significantly improves OS, it seems not to be through an effect on cancer-specific factors.

Efficacy of toluidine blue in the diagnosis and screening of oral cancer and pre-cancer: A systematic review and meta-analysis.

The accuracy of toluidine blue (TB) and chemiluminescence for diagnosing oral cancer and pre-cancer was evaluated. Two authors (working independently) comprehensively reviewed six databases (PubMed, Cochrane database, Embase, Web of Science, SCOPUS and Google Scholar) from their dates of inception until March 2020. Oral mucosal disorder, as detected by TB, was compared with that detected by chemiluminescence. True-positive, true-negative, false-positive and false-negative data were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2). The extent of interrater agreement was also assessed. Twenty-nine prospective and retrospective studies were included. The diagnostic odds ratio (DOR) of TB was 7.017 (95% confidence interval [CI], 4.544; 10.836). The area under the summary receiver operating characteristic curve was 0.766. The correlation between the sensitivity and the false-positive rate was 0.196, indicating the absence of heterogeneity. TB exhibited moderate interrater reliability (0.6777; 95% CI, 0.43; 0.7455). Compared with chemiluminescence, as used in nine studies, TB had a lower sensitivity (0.659 vs 0.841), but a higher specificity (0.809 vs 0.345), negative predictive value (0.766 vs 0.690) and DOR (10.565 vs 5.203). Compared with clinical examination, as used in four studies, TB method had a higher sensitivity (0.891 vs 0.891), specificity (0.739 vs 0.634), negative predictive value (0.920 vs 0.714) and DOR (28.491 vs 8.526). Subgroup analysis showed that screening for severe dysplasia or more severe disease was significantly more sensitive, but less specific, than screening for all dysplasias. Although the diagnostic accuracy of TB in the diagnostic work-up of oral cancer and pre-cancer was higher than that of clinical examination, it was not high enough for TB to reliably be used alone. Instead, it should be combined with chemiluminescence or other diagnostic tools.

Effect of Continuous Positive Airway Pressure on Weight and Local Adiposity in Adults with Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis of the Randomized Controlled Trials

Background: Evidence suggests that continuous positive airway pressure (CPAP) treatment promotes weight gain in obstructive sleep apnea (OSA) patients. However, it is unclear whether weight gain is influenced by CPAP adherence or comorbid disorders. Methods: In this systematic review and meta-analysis, we searched PubMed/Medline, Embase and Cochrane through to December 2019. Randomized controlled trials (RCTs) of CPAP versus controls with at least 4 weeks treatment were included. The random or fixed effects model was conducted in presence or absence of heterogeneity respectively. This study is registered with PROSPERO (CRD 42018105839). Findings: A total of 39 RCTs with 3510 subjects in the CPAP group and 3444 subjects in the control group were included. In intention-to-treat analysis, BMI increased significantly after CPAP treatment compared to controls (WMD=0·148 kg/m2, 95%CI=0·04-0·26, P=0·010). In studies demonstrating an increase in BMI, waist and neck circumferences were also significantly increased. Subgroup-analyses revealed that increased BMI was attributable to CPAP use of ≤5 hours/night (WMD=0·231), but not in those with CPAP use of >5 hours/night (WMD=0·001, between-group P-value=0·049). Furthermore, BMI increased significantly in patients without cardiovascular disease (CVD, WMD=0·200), whereas decreased significantly in those with CVD at baseline (WMD=-0·188, between-group P-value<0·001). Moreover, BMI increased significantly in patients with dysglycemia (WMD=0·499), but not in those without dysglycemia at baseline (WMD=0·100, between-group P-value=0·032). Meta-regression showed that CPAP use of ≤5 hours/night, absence of CVD and presence of dysglycemia at baseline predict post-CPAP BMI increase. Interpretation: BMI increased significantly in OSA patients after CPAP treatment, especially in those with CPAP use of ≤5 hours/night, without CVD and/or with dysglycemia at baseline. Decreased BMI in CVD patients might be related to favorable effects of CPAP treatment on excess fluid. CPAP use of at least 5 hours/night seems to be necessary in mitigating the risk for weight gain in OSA patients. Funding Statement: This study was supported by National Natural Science Foundation of China (No.81970087), Grant for Key Disciplinary Project of Clinical Medicine under the Guangdong High-level University Development Program and Department of Educational of Guangdong Province (2017KTSCX065) and 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant (2020LKSFG05B). Declaration of Interests: Dr. Drager received equipment from Philips Respironics for developing investigator initiated research projects. He is also a member of the MedXCloud team work (ResMed) for performing bid data analysis on positive airway pressure (PAP) telemonitoring. The other authors report no biomedical financial interests or potential conflicts of interest.

Genetic association of vascular endothelial growth factor (VEGF) gene variants with the risk for diabetic retinopathy: a meta-analysis

The vascular endothelial growth factor (VEGF) significantly contributes to the manifestation of neovascularization in the retina which progressively develops retinopathy in diabetic patients. The aim of this study was to assess the role of VEGF polymorphisms in the pathogenesis of diabetic retinopathy (DR). This meta-analysis comprised a total of six case-control and cohort studies published in the last 6 years. The selection of studies was done by sorting in reliable database searches: NCBI, Ensemble, GenBank, Embase, UCSC Genome Browser. After the extraction of data, the Q test of heterogeneity was performed. The Stata Software version 13.1 was used as the statistical package. Fixed and random effect models were applied for forest plot depiction while funnel plot and Egger’s test were carried out for the evaluation of publication bias. A significant relationship was found between the risk allele of VEGF polymorphism rs3025039 with predisposition of DR (OR = 1.45, 95%CI = 1.04–1.86) in the absence of heterogeneity by three studies. Furthermore, significant association was also observed for four polymorphisms of VEGF (rs833061, s13207351, rs1570360, and rs2010963) with higher susceptibility of DR among the population of Pakistan (OR = 1.46, 95%CI = 1.21–1.71). The meta-analysis suggested the substantial role of VEGF polymorphism rs3025039 as a possible biomarker for the assessment of DR risk. However, genome-wide association study (GWAS) is required in future to elucidate the multi-SNP effect of these polymorphisms in VEGF gene.

Smoking Status Affects the Association Between Hematoma Heterogeneity and Hematoma Expansion

ObjectiveThe purpose of this study was to verify the relationship between hematoma heterogeneity and hematoma expansion and explore any effect modifiers through subgroup analyses.MethodsClinical records of 357 patients with spontaneous cerebral hemorrhage at Shenzhen Second People’s Hospital from March 2016 to October 2018 were included in the study. Hematoma heterogeneity was measured on the first noncontrast computed tomography image according to the Barras scale. Hematoma expansion was defined as an absolute hematoma volume increase of 6 mL, or a 33% increase. We performed univariate and multivariate logistic regression analyses, as well as subgroup analyses, to assess the relationship between the presence of heterogeneity on noncontrast computed tomography and hematoma expansion.ResultsHematoma expansion occurred in 79 (22.13%) of the 357 patients with intracerebral hemorrhage (ICH). Among the patients with ICH, there were 83 smokers, accounting for 23.24%. The average patient age was 56.21 ± 13.75 years, and 74.51% were male. Compared with the absence of heterogeneity, the risk of hematoma expansion increased by 1.06 times (odds ratio, 2.06; 95% confidence interval, 1.10–3.86). Based on the subgroup analysis, smoking status was found to modify the association between heterogeneity and hematoma expansion; the association was stronger in smokers than in nonsmokers (odds ratio, 10.23; 95% confidence interval, 2.15–48.65).ConclusionsHeterogeneity independently predicts hematoma expansion, especially in smoking patients.