Differences In Effect Estimates Research Articles

A252 DRUG DISCONTINUATION AND PERSISTENT SYMPTOMS AMONG THE USERS OF BIOSIMILAR AND LEGACY ANTI-TNF DRUGS IN A REAL-WORLD CANADIAN IBD COHORT

Abstract Background Biosimilars and their reference originator drugs are increasingly used for inducing and maintaining remission in Inflammatory Bowel Diseases (IBD). Persistent symptoms, such as fatigue and joint pain, have been reported among individuals with IBD in remission. However, there is limited data on the persistence of symptoms among long-term users of biological therapy. Aims We report on drug discontinuation and persistent symptoms among a multicentre cohort of IBD patients 12 months after initiating anti-TNF originators or biosimilars. Methods We enrolled and followed individuals with IBD (ampersand:003E18 years) who initiated therapy with infliximab or adalimumab, bio-originators/biosimilars, between January 2019 and March 2023. We determined the rate of discontinuation of therapy, persistent symptoms, and quality of life (QoL) after 12 months. Difference in effect estimates (proportions and means) between the two groups (originators versus biosimilars) was determined. Results 181 individuals with IBD (CD = 58%, female = 46%, Caucasian = 85%) were enrolled. 62% were biologic-naïve at initiation. Of the 119 participants who completed a 12-month follow-up visit, about 19% (n = 34) discontinued drug use (all were infliximab users). Insufficient disease control was the most common reason for drug discontinuation (18.2%, n = 33). There was a significant reduction in the number of corticosteroid users at follow-up in both originator (rate ratio: 0.33, 95% confidence interval (CI): 0.16-0.49) and biosimilar users (rate ratio: 0.22, 95% CI: 0.14-0.30). With our limited power, we were unable to detect significant reductions in ER visits and hospitalizations in the first year after initiation of anti-TNF agents compared to that in the preceding year. The severity of pain/discomfort anywhere and the frequency of fatigue and anxiety/depression was not significantly reduced at 12 months in either of the groups. The percentage of those reporting moderate/severe abdominal pain was reduced among biosimilar users (46% to 20%; rate ratio of 0.26, 95% CI: 0.15-0.38), and originator users (28% to 13%, rate ratio 0.16, 95% CI: -0.02, 0.33). The proportion of those reporting rectal urgency at least some of the time was also reduced among both originators (30% at baseline to 9% at follow-up) and biosimilar users (33% to 17%). There was a significant improvement in QoL scores among both originator users (mean difference (MD) 13.0, 95% CI: 6.00-22.0) and biosimilar users (MD 10.0, 95% CI: 6.00-14.0) on the SIBDQ. This improvement was replicated on the EQ-5D only among biosimilar users. Conclusions Our study results suggest that even though the use of anti-TNF drugs leads to improvement in QoL, there may be no reduction in some symptoms, such as fatigue, anxiety, depression. Funding Agencies CIHR

Exploring the impact of personalized and adaptive learning technologies on reading literacy: A global meta-analysis

Fostering proficient reading literacy among students has long been a central educational pursuit, considering that it is one of the most cognitively demanding skills to acquire. Technology that tailors learning experiences to fit students’ strengths and needs (i.e., personalized and adaptive learning; PAL) can be more effective than the traditional curricular approaches. However, the literature on PAL effectiveness presents an inconclusive assessment of its impact on student reading achievement, and a global synthesis has not been conducted. This meta-analysis sought to assess the degree for differences in effect estimates, and to explore reasons for the differences across a wider range of populations and interventions. Twenty-seven studies were reviewed and an effect size of g = 0.29 was found. Implications for future policy and practice are presented.

Dietary patterns in relation to incidence rate of pancreatic cancer - the Norwegian women and cancer cohort study.

Despite development in cancer treatment and prevention options during the past few years, cancer of the pancreas remains a diagnosis associated with poor prognosis and limited options for prevention. Diet has proven to be an important risk factor for development of many types of cancer, particularly for cancers of the digestive system. Still, evidence regarding its relation to pancreatic cancer remains ambiguous. To investigate the relationship between diet and pancreatic cancer, an analysis of dietary patterns in participants from the Norwegian Women and Cancer Study (n = 89,156; 305 pancreatic cancer cases) was performed. Cox regression analysis was used for studying possible associations between dietary patterns, derived from principal component analysis, and pancreatic cancer incidence. The four most prominent dietary patterns were identified and described: European pattern, animal food consumers' dietary pattern, traditional Norwegian pattern, and alcohol-abstaining dietary pattern. In analysis without adjustment for confounders, being in the highest tertile of the abstaining dietary pattern was associated with lower risk of pancreatic cancer in comparison to the lowest tertile (hazard ratios [HR]: 0.66, 95% confidence interval [CI]: 0.49-0.89). After additional adjustment for height and smoking status, no dietary pattern was associated with increased pancreatic cancer risk, nor was there any difference in effect estimates between strata of smokers and non-smokers. The results of our current analysis do not support the role of major dietary patterns in the development of pancreatic cancer.

Ambient climatic factors and term birthweight: A study of critical windows of exposure in the Republic of Cyprus

BackgroundReduced birthweight is associated with adverse perinatal and long-term outcomes. A few studies examined the association between climatic factors and birthweight with inconsistent results probably due to differences in exposure assessment, statistical models, climatic parameters, and study populations. MethodsWe obtained data from the Republic of Cyprus birth registry from 2007 to 2020, and matched climatic exposures (i.e., temperature, relative humidity, temperature variability, humidity variability) by the hospital district at birth. We used distributed lag models to examine the association between term birthweight, temperature, humidity, and their variability to identify critical windows. Our models were adjusted for coarse particulate matter level (≤10 μm [PM10), and individual-level covariates. Subgroup analysis was conducted to examine effect modification by maternal age and education. ResultsWe identified two critical windows of exposure to ambient temperature at early and late pregnancy. The cumulative change of birthweight per 5 °C increases in mean weekly temperature was −57.27 (2%) (95% Confidence Interval [CI]: 99.62 (3.1%), −14.92 (0.5%)) and −79.2 (2.5%) (95%CI: 117.03 (3.5%), −41.52 (1.3%)) grams during weeks 1–8 and weeks 28–37, respectively. There was no significant effect of humidity, temperature variability, or humidity variability on birthweight. Based on subgroup analysis, mothers with post-secondary education were more sensitive to temperature, but the marginal significance of differences in effect estimates may be linked with differences in sample size. ConclusionOur study suggests that higher ambient temperature exposure during early and late pregnancy is associated with lower birthweight in main and subgroup analysis. The findings demonstrate in a country highly impacted by climate change like Cyprus that rising temperatures may be associated with perinatal outcomes in susceptible populations during sensitive windows of exposure.

Long-term exposure to air pollution and natural mortality: variations related to the use of different exposure indicators in the cohorts of BIGEPI project

appropriate assessment of exposure to air pollution is crucial for the estimation of adverse effects on human health, both in the short and long term. Within the BIGEPI project, different indicators of long-term exposure to air pollution, in association with mortality by cause, were tested within the Italian longitudinal metropolitan studies (LMS). This allowed an evaluation of differences in effect estimates using the different exposure indicators. closed cohort. subjects aged >=30, who took part in the 2011 census, residents in 5 cities (Turin, Bologna, Rome, Brindisi and Taranto). at the time of enrolment, residential exposure levels to particulate matter <=10 μm (PM10), PM <=2.5 μm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) for the period April-September (O3 warm season) were obtained from models at different spatial resolutions, from 1x1km to 200x200m (from the BEEP project) to 100x100m (ELAPSE project). In addition, locally developed models were used in each area (FARM photochemical model at 1x1-km for the cities of Rome, Taranto and Brindisi, Land-Use Regression (LUR) model for the city of Turin, PESCO model for Bologna). Cox proportional hazards models were applied to assess the association between exposure to air pollution (assessed using different exposure indicators) and natural mortality, adjusting for both individual and area covariates. the exposure levels derived by the different models varied between pollutants, with differences between the averages ranging from 3 to 20% for PM10, from 1 to 23% for PM2.5, and from 3 to 28% for NO2; the results for O3 were more heterogeneous. A total of 267,350 deaths from natural causes were observed. There is low heterogeneity in the effect estimates calculated from different environmental models, while there is greater variability in average exposure values, with different behaviour depending on the model and the characteristics of the area investigated. Differences are more pronounced where local risk factors are relevant, e.g., in industrial cities, thus suggesting the need of considering industrial exposure separately from other sources. the numerous heterogeneities in the data used make it difficult to draw conclusions about the comparisons studied. Nevertheless, this study suggests that different approaches to the assessment of environmental exposure should be evaluated depending on the national or local level of interest, also according to the specifities of the investigated areas.

Impact of exposure measurement error in multi-pollutant models: a simulation study in the time-series framework

BACKGROUND AND AIM Exposure measurement error in air pollutants can lead to biased health effect estimates and effect transfer from more poorly to better measured exposures. While some studies have estimated the impact of error in single-exposure models we aimed to quantify the effect of measurement error in multi-pollutant models, specifically in time-series analysis of PM₂.₅, NO₂, and mortality using simulations, under various plausible scenarios for exposure errors. METHODS Measurement error was defined as the difference between ambient concentrations and personal exposure from outdoor sources. Error-free exposures with their consequent health outcome and error-prone exposures of various error types (classical/Berkson/mixture) were generated using information from the literature. Bias was quantified as the relative difference in effect estimates of the error-free and error-prone exposures. RESULTS NO₂ was assumed to be more prone to error than PM₂.₂, based on separate work, and, thus, its mortality effect estimates were more affected by measurement error bias. The observed bias was up to 37% towards the null, when low ratios of the true exposure variance over the error variance were assumed. Higher ratios resulted in smaller, but still substantial health effect underestimation, up to 19% for both pollutants. Significant effect transfer was observed from NO₂ to PM₂.₅ as the general underestimation due to measurement error was worsened for the former and lessened for the latter compared to single-pollutant model estimates. CONCLUSIONS Our results indicated an underestimation of true independent health effects of multiple exposures due to measurement error. Effect transfer showed that less precise measurements for one pollutant yield more bias, while the co-pollutant associations were found closer to the true. Using error parameter information in future epidemiological studies should provide more accurate concentration-response functions for health impact assessment. KEYWORDS Air pollution, Measurement error, Mixture error, Effect transfer, Simulations

Bridging differences across cohorts in the relationship between prenatal secondhand smoke exposure and birth weight: Transportability of effect estimates in the ECHO consortium

Background and Aim: Transportability of effect estimates in epidemiology can potentially help investigators explain the differences in effect estimates for the same exposure-outcome relationships observed across different cohorts. In this study we aim to explain potential differences in the relationship between prenatal secondhand smoke exposure (SHS) and birth weight across different cohorts of the Environmental influences on Child Health Outcomes (ECHO) consortium that may be due to population differences in sociodemographic characteristics. Methods: We assessed transportability of effect estimates across 5 different cohorts in the ECHO consortium consisting of 6582 mother-offspring dyads. We first estimated individual cohort effects using Targeted Maximum Likelihood Estimation adjusting for several sociodemographic covariates. We then proceeded to estimate transported effects from one cohort to each of the remaining cohorts using a robust non-parametric estimation approach. We compared the transported effect estimates to the original effect estimates for these cohorts with any decrease in differences between cohort-specific estimates potentially attributable to different sociodemographic variable distributions. Results: Individual cohort effects associated with SHS exposure varied across the 5 cohorts with a range of strongly suggestive results for harmful effects of exposure (149.0 gram decrease in birthweight (95% confidence interval (CI): -254.4, -43.5), to results on the protective side of the null albeit with very wide confidence intervals. Transported effect estimates partially explained differences in 3 out of the 4 cohort pairs, explaining 7% to 97% of the differences in the effect point estimates. Conclusion: Differences in sociodemographic characteristics across different populations may partially explain differences observed in the relationship between prenatal SHS exposure and birth weight across cohorts in the ECHO consortium. This framework could have broader implications in in multi-cohort consortiums by aiding in the comparability of cross-cohort results. Keywords: transportability, causal inference, machine learning, secondhand smoke, birth outcomes

The association between tropical cyclones and dengue fever in the Pearl River Delta, China during 2013-2018: A time-stratified case-crossover study.

Studies have shown that tropical cyclones are associated with several infectious diseases, while very few evidence has demonstrated the relationship between tropical cyclones and dengue fever. This study aimed to examine the potential impact of tropical cyclones on dengue fever incidence in the Pearl River Delta, China. Data on daily dengue fever incidence, occurrence of tropical cyclones and meteorological factors were collected between June and October, 2013-2018 from nine cities in the Pearl River Delta. Multicollinearity of meteorological variables was examined via Spearman correlation, variables with strong correlation (r>0.7) were not included in the model simultaneously. A time-stratified case-crossover design combined with conditional Poisson regression model was performed to evaluate the association between tropical cyclones and dengue fever incidence. Stratified analyses were performed by intensity grades of tropical cyclones (tropical storm and typhoon), sex (male and female) and age-groups (<18, 18-59, ≥60 years). During the study period, 20 tropical cyclones occurred and 47,784 dengue fever cases were reported. Tropical cyclones were associated with an increased risk of dengue fever in the Pearl River Delta region, with the largest relative risk of 1.62 with the 95% confidence interval (1.45-1.80) occurring on the lag 5 day. The strength of association was greater and lasted longer for typhoon than for tropical storm. There was no difference in effect estimates between males and females. However, individuals aged over 60 years were more vulnerable than others. Tropical cyclones are associated with increased risk of local dengue fever incidence in south China, with the elderly more vulnerable than other population subgroups. Health protective strategies should be developed to reduce the potential risk of dengue epidemic after tropical cyclones.

Quadriceps Tendon Autograft Versus Bone–Patellar Tendon–Bone and Hamstring Tendon Autografts for Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

Background: The best type of autograft for anterior cruciate ligament (ACL) reconstruction remains debatable. Hypothesis: Compared with bone–patellar tendon–bone (BPTB) and hamstring tendon (HT) autografts, the quadriceps tendon (QT) autograft has comparable graft survival as well as clinical function and pain outcomes. Study Design: Meta-analysis; Level of evidence, 4. Methods: A systematic literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library to July 2020. Randomized controlled trials (RCTs) and observational studies reporting comparisons of QT versus BPTB or HT autografts for ACL reconstruction were included. All analyses were stratified according to study design: RCTs or observational studies. Results: A total of 24 studies were included: 7 RCTs and 17 observational studies. The 7 RCTs included 388 patients, and the 17 observational studies included 19,196 patients. No significant differences in graft failure (P = .36), the International Knee Documentation Committee (IKDC) subjective score (P = .39), or the side-to-side difference in stability (P = .60) were noted between QT and BPTB autografts. However, a significant reduction in donor site morbidity was noted in the QT group compared with the BPTB group (risk ratio [RR], 0.17 [95% CI, 0.09-0.33]; P < .001). No significant differences in graft failure (P = .57), the IKDC subjective score (P = .25), or the side-to-side stability difference (P = .98) were noted between QT and HT autografts. However, the QT autograft was associated with a significantly lower rate of donor site morbidity than the HT autograft (RR, 0.60 [95% CI, 0.39-0.93]; P = .02). A similar graft failure rate between the QT and control groups was observed after both early and late full weightbearing, after early and late full range of motion, and after using the QT autograft with a bone plug and all soft tissue QT grafts. However, a significantly lower rate of donor site morbidity was observed in the QT group compared with the control group after both early and late full weightbearing, after early and late full range of motion, and after using the QT autograft with a bone plug and all soft tissue QT grafts. No difference in effect estimates was seen between RCTs and observational studies. Conclusion: The QT autograft had comparable graft survival, functional outcomes, and stability outcomes compared with BPTB and HT autografts. However, donor site morbidity was significantly lower with the QT autograft than with BPTB and HT autografts.

Quantifying the short-term effects of air pollution on health in the presence of exposure measurement error: a simulation study of multi-pollutant model results

BackgroundMost epidemiological studies estimate associations without considering exposure measurement error. While some studies have estimated the impact of error in single-exposure models we aimed to quantify the effect of measurement error in multi-exposure models, specifically in time-series analysis of PM2.5, NO2, and mortality using simulations, under various plausible scenarios for exposure errors. Measurement error in multi-exposure models can lead to effect transfer where the effect estimate is overestimated for the pollutant estimated with more error to the one estimated with less error. This complicates interpretation of the independent effects of different pollutants and thus the relative importance of reducing their concentrations in air pollution policy.MethodsMeasurement error was defined as the difference between ambient concentrations and personal exposure from outdoor sources. Simulation inputs for error magnitude and variability were informed by the literature. Error-free exposures with their consequent health outcome and error-prone exposures of various error types (classical/Berkson) were generated. Bias was quantified as the relative difference in effect estimates of the error-free and error-prone exposures.ResultsMortality effect estimates were generally underestimated with greater bias observed when low ratios of the true exposure variance over the error variance were assumed (27.4% underestimation for NO2). Higher ratios resulted in smaller, but still substantial bias (up to 19% for both pollutants). Effect transfer was observed indicating that less precise measurements for one pollutant (NO2) yield more bias, while the co-pollutant (PM2.5) associations were found closer to the true. Interestingly, the sum of single-pollutant model effect estimates was found closer to the summed true associations than those from multi-pollutant models, due to cancelling out of confounding and measurement error bias.ConclusionsOur simulation study indicated an underestimation of true independent health effects of multiple exposures due to measurement error. Using error parameter information in future epidemiological studies should provide more accurate concentration-response functions.

Intake of artificial sweeteners among adults is associated with reduced odds of gastrointestinal luminal cancers: a meta-analysis of cohort and case-control studies

The association between artificial sweetener (AS) consumption and the risk of organ-specific cancers has been debated for decades. We hypothesized that AS consumption is associated with reduced risk of gastrointestinal (GI) cancers. We aimed to test this hypothesis by conducting a systematic review and meta-analysis of the association between AS and GI cancers. We searched 4 databases for comparative studies of AS consumption (exposed) versus no consumption (nonexposed) and the odds or risk of GI luminal or non–luminal cancer (primary outcome). Estimates were pooled using a random-effects model. Studies were evaluated for quality, bias, and heterogeneity. We analyzed 8 (4 prospective, 4 case-control) studies comprising data on 1,043,496 individuals, among whom 3271 pancreatic, 395 gastric, 304 esophageal, 3008 colorectal, and 598 oropharyngeal cancers occurred. While there was no significant association between AS consumption and odds of GI cancer overall, AS consumption was associated with 19% reduced likelihood of luminal GI cancer (OR 0.81, 95% CI:0.68-0.97). There was no association between AS consumption and non–luminal GI cancer. Meta-regression demonstrated no difference in effect estimates based on study type. Based on this first meta-analysis of AS and GI cancer, we demonstrated that AS consumption is associated with a significantly lower likelihood of luminal, but not non–luminal, GI cancer.

Early Optimistic Effect in Periodontology and Implant Dentistry Trials

Differences in effect estimates between early primary trials included in a meta-analysis and the pooled estimate of meta-analysis might indicate potential novelty bias. The objective of this study was to assess the presence of novelty bias in a sample of studies published in periodontology and implant dentistry. On August 7, 2020, we searched the PubMed database for meta-analyses of clinical studies published between August 2015 and August 2020. Meta-analyses with at least 4 primary studies were selected for assessment. We fitted logistic regression models using trial characteristics as predictors to assess the association between these characteristics and 1) the odds of the first trial’s estimate to be included in the meta-analysis confidence interval (CI) and 2) the odds of overlap between the first trial’s CI and the meta-analysis prediction interval (PI). Ninety-two meta-analyses provided data for assessment. In absolute values, 70% of the meta-analyses have a pooled estimate smaller than the corresponding estimate of the first trial, although there was overlap of the CI of estimates from the first trial and the meta-analysis in 87% of the cases. This is probably due to the small number of trials in most meta-analyses and the subsequently large uncertainty associated with the pooled effect estimate. As the number of trials in the meta-analysis increased, the odds of the treatment effect estimate of the first trial to be included in the meta-analysis CI decreased by 15% for every additional trial (odds ratio, 0.85; 95% CI, 0.73 to 0.96). Meta-analytic effect estimates appear to be more conservative than those from the first trial in the meta-analysis. Our findings show evidence of novelty bias in periodontology and implant dentistry; therefore, clinicians should be aware of the risk of making decisions based on the information reported in new trials because of the risk of exaggerated estimates in these trials.

Systematic differences in effect estimates between observational studies and randomized control trials in meta-analyses in nephrology

The limited availability of randomized controlled trials (RCTs) in nephrology undermines causal inferences in meta-analyses. Systematic reviews of observational studies have grown more common under such circumstances. We conducted systematic reviews of all comparative observational studies in nephrology from 2006 to 2016 to assess the trends in the past decade. We then focused on the meta-analyses combining observational studies and RCTs to evaluate the systematic differences in effect estimates between study designs using two statistical methods: by estimating the ratio of odds ratios (ROR) of the pooled OR obtained from observational studies versus those from RCTs and by examining the discrepancies in their statistical significance. The number of systematic reviews of observational studies in nephrology had grown by 11.7-fold in the past decade. Among 56 records combining observational studies and RCTs, ROR suggested that the estimates between study designs agreed well (ROR 1.05, 95% confidence interval 0.90–1.23). However, almost half of the reviews led to discrepant interpretations in terms of statistical significance. In conclusion, the findings based on ROR might encourage researchers to justify the inclusion of observational studies in meta-analyses. However, caution is needed, as the interpretations based on statistical significance were less concordant than those based on ROR.

Combining Effect Estimates Across Cohorts and Sufficient Adjustment Sets for Collaborative Research: A Simulation Study.

Collaborative research often combines findings across multiple, independent studies via meta-analysis. Ideally, all study estimates that contribute to the meta-analysis will be equally unbiased. Many meta-analyses require all studies to measure the same covariates. We explored whether differing minimally sufficient sets of confounders identified by a directed acyclic graph (DAG) ensures comparability of individual study estimates. Our analysis applied four statistical estimators to multiple minimally sufficient adjustment sets identified in a single DAG. We compared estimates obtained via linear, log-binomial, and logistic regression and inverse probability weighting, and data were simulated based on a previously published DAG. Our results show that linear, log-binomial, and inverse probability weighting estimators generally provide the same estimate of effect for different estimands that are equally sufficient to adjust confounding bias, with modest differences in random error. In contrast, logistic regression often performed poorly, with notable differences in effect estimates obtained from unique minimally sufficient adjustment sets, and larger standard errors than other estimators. Our findings do not support the reliance of collaborative research on logistic regression results for meta-analyses. Use of DAGs to identify potentially differing minimally sufficient adjustment sets can allow meta-analyses without requiring the exact same covariates.

Emulating Randomized Clinical Trials With Nonrandomized Real-World Evidence Studies: First Results From the RCT DUPLICATE Initiative.

Regulators are evaluating the use of noninterventional real-world evidence (RWE) studies to assess the effectiveness of medical products. The RCT DUPLICATE initiative (Randomized, Controlled Trials Duplicated Using Prospective Longitudinal Insurance Claims: Applying Techniques of Epidemiology) uses a structured process to design RWE studies emulating randomized, controlled trials (RCTs) and compare results. We report findings of the first 10 trial emulations, evaluating cardiovascular outcomes of antidiabetic or antiplatelet medications. We selected 3 active-controlled and 7 placebo-controlled RCTs for replication. Using patient-level claims data from US commercial and Medicare payers, we implemented inclusion and exclusion criteria, selected primary end points, and comparator populations to emulate those of each corresponding RCT. Within the trial-mimicking populations, we conducted propensity score matching to control for >120 preexposure confounders. All study measures were prospectively defined and protocols registered before hazard ratios and 95% CIs were computed. Success criteria for the primary analysis were prespecified for each replication. Despite attempts to emulate RCT design as closely as possible, differences between the RCT and corresponding RWE study populations remained. The regulatory conclusions were equivalent in 6 of 10. The RWE emulations achieved a hazard ratio estimate that was within the 95% CI from the corresponding RCT in 8 of 10 studies. In 9 of 10, either the regulatory or estimate agreement success criteria were fulfilled. The largest differences in effect estimates were found for RCTs where second-generation sulfonylureas were used as a proxy for placebo regarding cardiovascular effects. Nine of 10 replications had a standardized difference between effect estimates of <2, which suggests differences within expected random variation. Agreement between RCT and RWE findings varies depending on which agreement metric is used. Interim findings indicate that selection of active comparator therapies with similar indications and use patterns enhances the validity of RWE. Even in the context of active comparators, concordance between RCT and RWE findings is not guaranteed, partially because trials are not emulated exactly. More trial emulations are needed to understand how often and in what contexts RWE findings match RCTs. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03936049, NCT04215523, NCT04215536, NCT03936010, NCT03936036, NCT03936062, NCT03936023, NCT03648424, NCT04237935, NCT04237922.

Vaginal microbiota diversity and paucity of Lactobacillus species are associated with persistent hrHPV infection in HIV negative but not in HIV positive women

The vaginal microbiota is thought to play a role in modulating risk of high-risk human papillomavirus (hrHPV) infection. We examined the relationship between the vaginal microbiota and persistent hrHPV infection in HIV-negative and HIV-positive women. We used 16S-rRNA sequencing to characterize the vaginal microbiota of two serial samples taken six months apart from 211 Nigerian women (67%, 142/211 HIV-positive and 33%, 69/211 HIV-negative) and evaluated the association between the vaginal microbiota and persistent hrHPV infection using generalized estimating equation logistic regression models and linear discriminant analysis effect size (LEfSe) algorithm to identify phylotypic biomarkers of persistent hrHPV infection. The high diversity microbiota, Community State Type IV-B, was the most prevalent in both HIV-negative (38% at baseline, 30% at the follow-up visit) and HIV-positive (27% at baseline, 35% at the follow-up visit) women. The relationship between the vaginal microbiota and persistent hrHPV was modified by HIV status. In HIV-negative women, women with Lactobacillus dominant microbiota had lower odds (OR: 0.35, 95% CI 0.14–0.89, p = 0.03) of persistent hrHPV compared to women with Lactobacillus deficient microbiota. While among HIV-positive women, the odds of being persistently infected with hrHPV was higher in women with Lactobacillus dominant microbiota (OR: 1.25, 95% CI 0.73–2.14 p = 0.41). This difference in effect estimates by HIV was statistically significant (p = 0.02). A high diversity vaginal microbial community with paucity of Lactobacillus species was associated with persistent hrHPV infection in HIV-negative women but not in HIV-positive women.

Environmental and behavioural interventions for reducing physical activity limitation and preventing falls in older people with visual impairment.

Environmental and behavioural interventions for reducing physical activity limitation and preventing falls in older people with visual impairment.

Transcatheter aortic valve replacement and percutaneous coronary intervention versus surgical aortic valve replacement and coronary artery bypass grafting in patients with severe aortic stenosis and concomitant coronary artery disease: A systematic review and meta‐analysis

We performed a systematic review and meta-analysis to evaluate the early and midterm outcomes of patients who underwent surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) against patients who had transcatheter aortic valve replacement (TAVR) and percutaneous coronary intervention (PCI). Contemporary guidelines suggest that surgical or percutaneous revascularization of significant coronary artery disease (CAD) in patients with severe aortic stenosis (AS) is a reasonable strategy. We conducted a comprehensive search of Medline and Embase to identify studies comparing a percutaneous transcatheter versus a surgical approach. Random effects meta-analyses using the Mantel-Haenszel method were performed to estimate the effect of percutaneous compared surgical strategies using aggregate data. Six studies reporting on 1770 participants were included in the meta-analysis. There were no significant differences in effect estimates for early and midterm mortality (OR: 0.78; 95% CI, 0.50-1.20 and OR: 1.09; 95% CI, 0.80-1.49, respectively) or myocardial infarction (OR: 0.52; 95% CI, 0.20-1.33 and OR: 1.34; 95% CI, 0.67-2.65, respectively). No significant difference was shown for peri-procedural stroke (OR: 0.80; 95% CI, 0.35-1.87). A transcatheter approach had a higher rate of major vascular complications (OR: 14.44; 95% CI, 4.42-47.16), but a lower rate of acute kidney injury (OR: 0.41; 95% CI, 0.19-0.91). Our analysis suggests that a percutaneous transcatheter approach confers similar outcomes compared to a surgical approach in patients with severe AS and CAD. However, our findings are based on low quality studies and should serve as hypothesis generating. In the absence of adequately powered studies yielding high level evidence, individualized decision making should be based on surgical risk assessment.

Psychological therapies for people with borderline personality disorder.

Psychological therapies for people with borderline personality disorder.

Sex-specific association between type 1 diabetes and the risk of end-stage renal disease: a systematic review and meta-analysis.

This meta-analysis was conducted given the inconsistent findings of studies regarding the sex discrepancy in the relationship between type 1 diabetes (T1D) and the risk of end-stage renal disease (ESRD). Articles published on PubMed between January 1, 1966 and March 31, 2019 were systematically retrieved without language restrictions. The included articles all presented sex-specific data of the incidence rate ratio, standardized incidence or mortality ratio, hazard ratio, relative risk, or odds ratio, or provided data to estimate the association between T1D and ESRD or kidney disease-related mortality. The gender-specific effect estimates and pooled ratio (female-to-male) for ESRD and for deaths from T1D-related renal disease were acquired via a random-effects meta-analysis with inverse variance weighting, regardless of heterogeneity evaluated based on the I2 statistic. Nineteen studies, including 122,842 individuals, were finally selected for this meta-analysis. Sex differences in effect estimates were found in ESRD (pooled ratio = 0.81 (95% confidence interval 0.69-0.94)) with considerable heterogeneity (I2 = 66.9%), but not in mortality with T1D-associated renal disease. Women with T1D have a lower risk of ESRD compared with that in men, but this finding may be biased by potential confounding factors and must be verified by other well-planned prospective studies.