High Between-study Heterogeneity Research Articles

The Debated Issue on Tissue Copper Levels in Colorectal Cancer Patients: A Meta-analysis and Replication Study.

Colorectal cancer (CRC) is a growing public health problem. Several clinical studies have shown a potentially oncogenic role of copper in CRC progression, but the reports are inconsistent. To examine published evidence on the association between tissue copper status and CRC, we carried out a systematic review and meta-analysis, searching Cochrane Library, EBSCOhost, Embase, ProQuest, PubMed/Medline, Scopus, and Web of Science for studies reporting colon tumor and matched non-cancerous tissue copper concentrations in CRC patients for articles published till June 2023. Based on a random effects model, standardized mean differences (SMD) were assessed. We also completed a replication study on 17 CRC patients that analyzed copper levels in both cancer tissue specimens and healthy mucosa dissected from the same patient. Thirteen studies investigating copper levels (including the replication study) in colorectal specimens from a pooled total of 312 CRC and 298 healthy mucosa were selected. Our meta-analysis estimated a high between-study heterogeneity (I2 = 96%) and lower levels of copper in CRC tissue cancer specimens than in matched healthy mucosa: the decrease was equal to - 0.74 (95% CI, - 2.18; 0.71) but was not significant. The replication study showed a significant decrease in tissue cancer specimens. Sensitivity analyses of the meta-analysis revealed that pre-analytical methodology for tissue preparation significantly reduced the between-study heterogeneity strongly influencing copper levels (p < 0.01), indicating a copper decrease in the cytoplasmic copper pool of the tumor tissue suggesting a rapid turnover of the metal in cancer cells.

The Effect of Adding Protein to a Carbohydrate Meal on Postprandial Glucose and Insulin Responses: A Systematic Review and Meta-Analysis of Acute Controlled Feeding Trials

BackgroundProtein influences acute postprandial glucose and insulin responses, but the effects of dose, protein type, and health status are unknown. ObjectivesWe aimed to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers. MethodsWe searched MEDLINE, EMBASE, and Cochrane databases through 30 July, 2023 for acute, crossover trials comparing acute postprandial responses elicited by carbohydrate-containing test meals with and without added protein in adults without diabetes or with type 2 (T2DM) or type 1 (T1DM) diabetes mellitus. Group data were pooled separately using generic inverse variance with random-effects models and expressed as the ratio of means with 95% confidence interval. Risk of bias and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation) were assessed. ResultsIn 154 trial comparisons of animal, dairy, and plant proteins (without diabetes, n = 22, 67, 32, respectively; T2DM, n = 14, 16, 3, respectively), each gram protein per gram available carbohydrate (g/g) reduced the glucose area under the curve (AUC) less in adults with T2DM than in those without diabetes (−10% compared with −50%, P < 0.05) but increased the insulin AUC similarly (+76% compared with +56%). In subjects without diabetes, each g/g of dairy and plant protein reduced glucose AUC by 52% and 55%, respectively, and increased the insulin AUC by 64% and 45%, respectively (all P < 0.05). Animal proteins significantly reduced the glucose AUC by 31% and increased the insulin AUC by 37% (pooled effects) but without a significant dose-response. In adults with T2DM, animal protein reduced the glucose AUC by 13% and increased the insulin AUC by 105%, with no significant dose-response. Dairy protein reduced the glucose AUC by 18% (no dose-response), but each g/g increased the insulin AUC by 34% (P < 0.05). In adults with T1DM, protein increased the glucose AUC by 40% (P < 0.05, n = 5). Data source (reported AUC compared with calculated AUC) and study methodology quality significantly modified some outcomes and contributed to high between-study heterogeneity. ConclusionsIn people without diabetes, adding dairy or plant protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose AUC and increases insulin AUC. Animal protein may slightly reduce the glucose AUC and may increase the insulin AUC. In people with T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein source.This study was registered at PROSPERO as CRD42022322090.

Diagnostic performance of the O-RADS MRI system for magnetic resonance imaging in discriminating benign and malignant adnexal lesions: a systematic review, meta-analysis, and meta-regression.

After the introduction of the Ovarian-Adnexal Reporting and Data System (O-RADS) for magnetic resonance imaging (MRI), several studies with diverse characteristics have been published to assess its diagnostic performance. This systematic review and meta-analysis aimed to assess the diagnostic performance of O-RADS MRI scoring for adnexal masses, accounting for the risk of selection bias. The PubMed, Scopus, Web of Science, and Cochrane databases were searched for eligible studies. Borderline or malignant lesions were considered malignant. All O-RADS MRI scores ≥4 were considered positive. The quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity, specificity, and likelihood ratio (LR) values were calculated, considering the risk of selection bias. Fifteen eligible studies were found, and five of them had a high risk of selection bias. Between-study heterogeneity was low-to-moderate for sensitivity but substantial for specificity (I2 values were 35.5% and 64.7%, respectively). The pooled sensitivity was significantly lower in the studies with a low risk of bias compared with those with a high risk of bias (93.0% and 97.5%, respectively; P = 0.043), whereas the pooled specificity was not different (90.4% for the overall population). The negative and positive LRs were 0.08 [95% confidence interval (CI) 0.05–0.11] and 10.0 (95% CI 7.7–12.9), respectively, for the studies with low risk of bias and 0.03 (95% CI 0.01–0.10) and 10.3 (95% CI 3.8–28.3), respectively, for those with high risk of bias. The overall diagnostic performance of the O-RADS system is very high, particularly for ruling out borderline/malignant lesions, but with a moderate ruling-in potential. Studies with a high risk of selection bias lead to an overestimation of sensitivity. The O-RADS system demonstrates considerable diagnostic performance, particularly in ruling out borderline or malignant lesions, and should routinely be used in practice. The high between-study heterogeneity observed for specificity suggests the need for improvement in the consistent characterization of the benign lesions to reduce false positive rates.

Green spaces and respiratory, cardiometabolic, and neurodevelopmental outcomes: An individual-participant data meta-analysis of >35.000 European children

Studies evaluating the benefits and risks of green spaces on children’s health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV1 (β = 0.06; 95 %CI: 0.03, 0.09 I2 = 4.03 %, p < 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I2 = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = −0.04; 95 %CI: −0.07, −0.02, I2 = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Turmeric as a Gut-Microbiota Modulator for Cardio-Metabolic Risk Factors: An Updated Comprehensive Review

Turmeric is a medicinal herb with antioxidant and anti-inflammatory components that can affect metabolic parameters via various pathways, including the gut-brain axis. Although positive effects of turmeric on health have been reported, findings are conflicting. Accordingly, the current review aimed to provide an overview of the biochemical and biological characteristics of turmeric and examine the impacts of turmeric on cardio-metabolic risk factors with a special focus on its abilities to modulate gut microbiota. In the present comprehensive review, findings of systematic reviews/narrative reviews, clinical trials, animal, and in vitro studies on turmeric in the English language published between 2010 and March 2023 were summarized. Findings revealed that turmeric is a safe medicinal herb with mild gastrointestinal side effects in some cases. It can help improve the glycemic status, lipid profile, and blood pressure. However, food processing and fermentation can affect the bioavailability of its effective components, including curcumin. Several mechanisms, including those affecting intestinal microbiota diversity, intestinal permeability, inflammatory and oxidative pathways, are proposed for their positive effects on metabolic factors. However, due to high between-study heterogeneity, limited high-quality clinical trials, differences in the duration of the intervention, and the form of turmeric supplement, more studies on each metabolic parameter are needed to determine effective dosages and confirm its efficacy as a complementary therapy to modulate microbiota and cardio-metabolic parameters.

Varroa destructor control strategies in Apis mellifera colonies: a meta-analysis and systematic revision on natural compounds efficacy

The parasitic mite Varroa destructor is a sanitary threat to beekeeping and causes significant losses in honey bee colonies. Thus, different acaricides have been applied as a strategy to control this disease. In the context of Integrated Pest Management, acaricides based on natural compounds, such as organic acids and essentials oils, are chosen by beekeepers to minimize negative effects on colonies and hive products. Considering the variety of natural active ingredients reported to have varroacidal activity and their different application systems, the aim of this work was to synthesize and quantify scientific knowledge on the acaricide performance of natural compounds to control V. destructor populations in Apis mellifera colonies. A systematic revision and a meta-analysis on the percentage of efficacy published for these formulations were conducted by selecting articles published between 2002 and 2022. According to our results, most publications investigated the efficacy of natural compounds in temperate climates and in European honey bee colonies since Varroa control is practically compulsory under these conditions. Thymol (THY) showed higher estimated efficacy compared to oxalic and formic acids (FA) and other essential oils (EOs). Variable efficacies were found in colonies treated with the natural compounds considered in this study according to different doses and application methods. The high between-study heterogeneity found in this revision might be explained by several factors, including the number of colonies and intra-apiary variation. As such, standardized protocols for field assays are key to improving efficacy evaluation. In addition, methodological implications are discussed.

Cancer screening in sexual and gender minority populations: A systematic review and meta-analysis.

10540 Background: The sexual and gender minority (SGM) populations experience a greater cancer burden than their heterosexual or cisgender counterparts. Screening rates for cancer within this cohort are frequently suboptimal, highlighting notable deficiencies in screening recommendations. Inadequate culturally competent care and screening guidelines may contribute to delays in cancer diagnosis and treatment, ultimately impacting survival and quality of life. We sought to investigate the existing disparities in cancer screening among SGM populations. Methods: We conducted a systematic review and meta-analysis to assess the cancer screening rates in SGM. The SGM population included in this study were gays, lesbians, bisexuals, transgender men, and transgender women. Two reviewers conducted a systematic search of numerous databases, including PubMed, PsycINFO, and CINAHL, and then extracted relevant information from eligible studies. For this study, we conducted a meta-analysis using a random-effects model. Pooled estimates of the odds ratio were calculated for any combination of outcomes and population when at least two studies had relevant data. Study heterogeneity was assessed using I² statistics. Meta-regression, accounting for the study weight, year, and latitude, was performed on variables potentially associated with heterogeneity. Newcastle-Ottawa Scale was used to assess the quality of selected studies. Results: We analyzed data from a total of 60 eligible studies with 65,315 patients. Pooled analysis showed that sexual minority groups were at lower risk for cancer screening such as breast cancer screening (OR: 0.79, 95% CI, 0.75-0.82; Chi2=835.23; p&lt;0.001; I2=97%), cervical cancer screening (OR: 0.62, 95% CI, 0.56-0.72; Chi2=926.23; p&lt;0.001; I2=96%), colorectal cancer screening (OR: 0.51, 95% CI, 0.45-0.61; Chi2=3272.21; p&lt;0.001; I2=98%), and prostate cancer screening (OR: 0.71, 95% CI, 0.63-0.82; Chi2=1282.92; p&lt;0.001; I2=99%). The prevalence of lung cancer (p&lt;0.001) and anal cancer screening (p&lt;0.001) were also lower in sexual minority groups. The analysis also showed no small study effects (Egger test: 1.33; 95% CI: −5.42, −0.63; p=0.182). All the subgroups (geographical location, screening procedure, screening period) had high between-study heterogeneity. Conclusions: Our findings indicate that cancer screening rates for breast, cervical, colorectal, prostate, lung, and anal cell cancer are significantly lower in SGM populations and emphasize the urgent need for targeted interventions, culturally competent care, and inclusive screening guidelines to address these disparities. Understanding and addressing these issues are crucial for reducing delays in cancer diagnosis and improving survival and quality of life for SGM population. Further research and comprehensive strategies are warranted to bridge these gaps in cancer screening accessibility and uptake.

A systematic review with meta-analysis of heritability estimates for temperament-related traits in beef and dairy cattle populations.

Temperament (docility) is a key breeding goal in the cattle industry due to its direct relationship with animal welfare, cattle handler's safety and animal productivity. Over the past six decades, numerous studies have reported heritability estimates for temperament-related traits in cattle populations ranging from low to high values. Therefore, the primary objective of this study was to perform a comprehensive systematic review with meta-analysis to obtain weighted estimates of heritability for temperament-related traits in worldwide cattle populations. After data editing and quality control, 106 studies were included in the systematic review, of which 29.2% and 70.8% reported estimates of heritability for temperament-related traits in dairy and beef cattle populations, respectively. Meta-analyses were performed for 95 heritability estimates using a random model approach. The weighted heritability estimates were as follow: (a) flight score at weaning = 0.23 (95% CI: 0.15-0.32); (b) flight speed at weaning = 0.30 (95% CI: 0.26-0.33); (c) joint analysis of flight speed and flight score at weaning = 0.27 (95% CI: 0.22-0.31); (d) flight speed at yearling = 0.26 (95% CI: 0.21-0.30); (e) joint analysis of flight speed at weaning and yearling = 0.27 (95% CI: 0.24-0.30); (f) movement score = 0.12 (95% CI: 0.08-0.15); (g) crush score at weaning = 0.21 (95% CI: 0.17-0.25); (h) pen score at weaning = 0.27 (95% CI: 0.19-0.34); (i) pen score at yearling = 0.20 (95% CI: 0.17-0.23); (j) joint analysis of pen score at weaning and yearling = 0.22 (95% CI: 0.18-0.26); (k) cow's aggressiveness at calving = 0.10 (95% CI: 0.01-0.19); (l) general temperament = 0.13 (95% CI: 0.06-0.19); (m) milking temperament = 0.16 (95% CI: 0.11-0.21); and (n) joint analysis of general and milking temperament = 0.14 (95% CI: 0.11-0.18). The heterogeneity index ranged from 0% to 77%, and the Q-test was significant (p < 0.05) for four single-trait meta-analyses. In conclusion, temperament is moderately heritable in beef cattle populations, and flight speed at weaning had the highest weighted heritability estimate. Moreover, between-study heterogeneity was low or moderate in beef cattle traits, suggesting reasonable standardization across studies. On the other hand, low-weighted heritability and high between-study heterogeneity were estimated for temperament-related traits in dairy cattle, suggesting that more studies are needed to better understand the genetic inheritance of temperament in dairy cattle populations.

Impact of Multidisciplinary Prehabilitation Interventions on Postoperative Hospital Length of Stay and Functional Capacity in Patients Undergoing Resection of Colorectal Cancer: A Systematic Review and Meta-analysis.

Although surgery is commonly regarded as the primary curative treatment for colorectal cancer, it could potentially be associated with postoperative morbidity and mortality. To determine the pooled effect of exercise and multidisciplinary prehabilitation interventions on postoperative hospital length of stay and functional capacity in patients undergoing resection of colorectal cancer. A systematic search was conducted in MEDLINE (via PubMed) and Web of Science databases from inception to November 2022. The original systematic search retrieved 2005 studies. After the removal of duplicates and screening by title and abstract, 77 eligible full-text documents were evaluated for final inclusion in the meta-analysis. A total of 12 randomized controlled trials, 5 nonrandomized controlled trials, and 3 uncontrolled before-and-after studies were selected. Postoperative hospital length of stay (in days) and functional capacity (assessed with the peak of oxygen consumption [VO2 peak] and 6-minute walking test) were the outcome measures. The meta-analysis was conducted on 20 studies (3805 participants). Randomized controlled trials and nonrandomized controlled trials showed significant reductions in postoperative hospital length of stay (d = -0.10, nearly 2 days) and significant incremental improvements in VO2 peak (d = 0.27) and 6-minute walking test (d = 0.31). Regarding the before-and-after studies, the pooled effect of multidisciplinary prehabilitation interventions was positively significant for VO2 peak (d = 0.29) and 6-minute walking test (d = 0.29). There was no risk of publication bias (Egger test: p > 0.05), with a score of 0.71 (0-1) on average. There was a high between-studies heterogeneity, and several outcomes did not have the required number of studies for a desirable statistical power. These findings suggest that multidisciplinary prehabilitation interventions might be effective at decreasing postoperative hospital length of stay (nearly 2 days) and improving functional capacity. PROSPERO registration number CRD42022373982.

Performance of Diffusion-weighted Imaging-based Noncontrast MRI Protocols for Diagnosis of Breast Cancer: A Systematic Review and Meta-Analysis.

Background Diffusion-weighted imaging (DWI) is increasingly recognized as a powerful diagnostic tool and tested alternative to contrast-enhanced (CE) breast MRI. Purpose To perform a systematic review and meta-analysis that assesses the diagnostic performance of DWI-based noncontrast MRI protocols (ncDWI) for the diagnosis of breast cancer. Materials and Methods A systematic literature search in PubMed for articles published from January 1985 to September 2023 was performed. Studies were excluded if they investigated malignant lesions or selected patients and/or lesions only, used DWI as an adjunct technique to CE MRI, or were technical studies. Statistical analysis included pooling of diagnostic accuracy and investigating between-study heterogeneity. Additional subgroup comparisons of ncDWI to CE MRI and standard mammography were performed. Results A total of 28 studies were included, with 4406 lesions (1676 malignant, 2730 benign) in 3787 patients. The pooled sensitivity and specificity of ncDWI were 86.5% (95% CI: 81.4, 90.4) and 83.5% (95% CI: 76.9, 88.6), and both measures presented with high between-study heterogeneity (I 2 = 81.6% and 91.6%, respectively; P < .001). CE MRI (18 studies) had higher sensitivity than ncDWI (95.1% [95% CI: 92.9, 96.7] vs 88.9% [95% CI: 82.4, 93.1], P = .004) at similar specificity (82.2% [95% CI: 75.0, 87.7] vs 82.0% [95% CI: 74.8, 87.5], P = .97). Compared with ncDWI, mammography (five studies) showed no evidence of a statistical difference for sensitivity (80.3% [95% CI: 56.3, 93.3] vs 56.7%; [95% CI: 41.9, 70.4], respectively; P = .09) or specificity (89.9% [95% CI: 85.5, 93.1] vs 90% [95% CI: 61.3, 98.1], respectively; P = .62), but ncDWI had a higher area under the summary receiver operating characteristic curve (0.93 [95% CI: 0.91, 0.95] vs 0.78 [95% CI: 0.74, 0.81], P < .001). Conclusion A direct comparison with CE MRI showed a modestly lower sensitivity at similar specificity for ncDWI, and higher diagnostic performance indexes for ncDWI than standard mammography. Heterogeneity was high, thus these results must be interpreted with caution. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Kataoka and Iima in this issue.

Systematic Review and Meta-analysis: Rates of Violence During First-Episode Psychosis (FEP).

Most people with psychotic disorders will never commit an act of violence. However, the risk of violence committed by people with schizophrenia is higher than the general population. Violence risk is also known to be highest during the first episode of psychosis compared to later stages of illness. Despite this, there have been no comprehensive reviews conducted in the past 10 years examining rates of violence during FEP. We aimed to provide an updated review of the rate of violence in people with FEP. Meta-analytical techniques were used to identify pooled proportions of violence according to severity (less serious, serious, severe) and timing of violence (before presentation, at first presentation, after presentation to services). Twenty-two studies were included. The pooled prevalence was 13.4% (95% CI [9.0%-19.5%]) for any violence, 16.3% (95% CI [9.1%-27.4%]) for less serious violence, 9.7% (95% CI [5.4%-17.0%]) for serious violence and 2.7% for severe violence, regardless of time point. The pooled prevalence of any violence was 11.6% (95% CI [6.8%-18.9%]) before presentation, 20.8% (95% CI [9.8%-38.7%]) at first presentation and 13.3% (95% CI [7.3%-23.0%]) after presentation to services. Overall, rates of violence appear to be lower in more recent years. However, due to the high between-study heterogeneity related to study design, the findings must be interpreted with consideration of sample characteristics and other contextual factors. The prevalence of violence remained high at all-time points, suggesting that more targeted, holistic, and early interventions are needed for clinical FEP groups.

The effects of low-dose aspirin on preterm birth: a systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that evaluated the efficacy of low-dose aspirin (LDA, ≤ 160mg/day) on preventing preterm birth (PB). Five databases were screened from inception until June 25, 2023. The RCTs were assessed for quality according to Cochrane's risk of bias tool. The endpoints were summarized as risk ratio (RR) with 95% confidence interval (CI). Overall, 40 RCTs were analyzed. LDA significantly decreased the risk of PB < 37weeks (RR: 0.91, 95% CI 0.87, 0.96, p < 0.001, moderate certainty of evidence) with low between-study heterogeneity (I2 = 23.2%, p = 0.11), and PB < 34weeks (RR: 0.78, 95% CI 0.61, 0.99, p = 0.04, low certainty of evidence) with high between-study heterogeneity (I2 = 58.3%, p = 0.01). There were no significant differences between both groups regarding the risk of spontaneous (RR: 0.94, 95% CI 0.83, 1.07, p = 0.37) and medically indicated (RR: 1.28, 95% CI 0.87, 1.88, p = 0.21) BP < 37weeks. Sensitivity analysis revealed robustness for all outcomes, except for the risk of PB < 34weeks. For PB < 37weeks and PB < 34weeks, publication bias was detected based on visual inspection of funnel plots for asymmetry and statistical significance for Egger's test (p = 0.009 and p = 0.0012, respectively). LDA can significantly reduce the risk of PB < 37 and < 34weeks. Nevertheless, further high-quality RCTs conducted in diverse populations, while accounting for potential confounding factors, are imperative to elucidate the optimal aspirin dosage, timing of initiation, and treatment duration for preventing preterm birth and to arrive at definitive conclusions.

Abstract 141: Physician Transfer versus Patient Transfer for Mechanical Thrombectomy in Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Background: Physician transfer has been explored as an alternate option to patient transfer for the expedient performance of mechanical thrombectomy in acute ischemic stroke patients. Methods: We conducted a systematic review to identify studies that evaluate the effect of physician transfer in patients with acute ischemic stroke who undergo mechanical thrombectomy. Data were extracted from relevant studies found through a search of PubMed, Scopus, and Web of Science until March 2023. A statistical pooling with random-effects meta-analysis was performed to examine the odds of reduced time interval between stroke onset and recanalization, functional independence, mortality, and time from stroke onset to recanalization with physician transfer against no patient transfer. Results: A total of 12 studies (11 nonrandomized observational studies, and 1 non-randomized controlled trial) were included. Physician transfer significantly reduced the time interval between stroke onset and recanalization with a pooled standardized mean difference estimate of -0.60 (95% CI [-1.17, -0.04], p = 0.035, 8 studies involving 1419 patients, and with high between-study heterogeneity in the estimates (I 2 =91.7%). The odds for functional independence at 90 days were significantly higher (OR 1.29, 95% CI 1.00-1.66, p = 0.046, 7 studies involving 1222 patients) with physician transfer with low between-study heterogeneity (I 2 =0%). Physician transfer was associated with higher odds of near complete or complete angiographic recanalization (OR 1.18, 95%CI 0.89-1.57, p = 0.25, I 2 =2.8%, 11 studies, 1856 subjects). Conclusions: We found a significant reduction in the mean time interval between symptom onset and recanalization associated with physician transfer with increased odds for functional independence at 90 days among patients undergoing mechanical thrombectomy.

Neuropsychological Function in Migraine Headaches: An Expanded Comprehensive Multidomain Meta-Analysis

A sizable literature has studied neuropsychologic function in persons with migraine (PwM), but despite this, few quantitative syntheses exist. These focused on circumscribed areas of the literature. In this study, we conducted an expanded comprehensive meta-analysis comparing performance on clinical measures of neuropsychological function both within and across domains, between samples of PwM and healthy controls (HCs). For this Meta-analyses Of Observational Studies in Epidemiology-compliant meta-analysis, a unified search strategy was applied to OneSearch (a comprehensive collection of electronic databases) to identify peer-reviewed original research published across all years up until August 1, 2023. Using random-effects modeling, we examined aggregated effect sizes (Hedges' g), between-study heterogeneity (Cochran Q and I2), moderating variables (meta-regression and subgroup analyses), and publication bias (Egger regression intercept and Duval and Tweedie Trim-and-Fill procedure). Study bias was also coded using the NIH Study Quality Assessment Tools. Omnibus meta-analysis from the 58 studies included (PwM n = 5,452, HC n = 16,647; 612 effect sizes extracted) indicated lower overall cognitive performance in PwM vs HCs (g = -0.37; 95% CI -0.47 to -0.28; p < 0.001), and high between-study heterogeneity (Q = 311.25, I2 = 81.69). Significant domain-specific negative effects were observed in global cognition (g = -0.46, p < 0.001), executive function (g = -0.45, p < 0.001), processing speed (g = -0.42, p < 0.001), visuospatial/construction (g = -0.39, p = 0.006), simple/complex attention (g = -0.38, p < 0.001), learning/memory (g = -0.25, p < 0.001), and language (g = -0.24, p < 0.001). Orientation (p = 0.146), motor (p = 0.102), and intelligence (p = 0.899) were not significant. Moderator analyses indicated that age (particularly younger HCs), samples drawn from health care facility settings (e.g., tertiary headache centers) vs community-based populations, and higher attack duration were associated with larger (negative) effects and accounted for a significant proportion of between-study heterogeneity in effects. Notably, PwM without aura yielded stronger (negative) effects (omnibus g = -0.37) vs those with aura (omnibus g = -0.10), though aura status did not account for heterogeneity observed between studies. Relative to HCs, PwM demonstrate worse neurocognition, as detected by neuropsychological tests, especially on cognitive screeners and tests within executive functioning and processing speed domains. Effects were generally small to moderate in magnitude and evident only in clinic (vs community) samples. Aura was not meaningfully associated with neurocognitive impairment.

Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis.

Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy. There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. CRD42023398476 (PROSPERO).

Does repetitive transcranial magnetic stimulation improve cognitive function in age-related neurodegenerative diseases? A systematic review and meta-analysis.

High-frequency, repetitive transcranial magnetic stimulation (rTMS) targeted over the dorsolateral prefrontal cortex (DLPFC) is widely used in research to promote neuroplasticity and cognitive enhancement. RTMS is a promising intervention to tackle cognitive decline in people with age-related neurodegenerative diseases. However, there is currently no systematic evidence examining the effects of DLPFC-targeted, high-frequency rTMS on cognitive function in this population. The aim of this systematic review was to evaluate the efficacy and moderators of this treatment intervention. A comprehensive literature search of five electronic databases was performed to identify articles published before October, 2022. Following PRISMA guidelines, the identified articles were screened, data was extracted, and the methodological quality was assessed using the Cochrane tool, Risk of Bias 2. Meta-analyses were performed using R Studio (v.4.1.2). Sixteen studies involving 474 participants met the inclusion criteria, of which 8 studies measured global cognitive function. The results from the random-effects meta-analysis showed rTMS significantly improved global cognitive function relative to control groups shown by a large, significant effect size (g=1.39, 95% CI, 0.34-2.43; p=0.017). No significant effects were found between subgroups or for individual cognitive domains. High-frequency rTMS, targeted over the DLPFC, appears to improve global cognitive function in people with age-related neurodegenerative diseases. However, these results should be interpreted with caution due to the small number of studies included, and high between-study heterogeneity.

Health Effects of Cyclones: A Systematic Review and Meta-Analysis of Epidemiological Studies.

More intense cyclones are expected in the future as a result of climate change. A comprehensive review is urgently needed to summarize and update the evidence on the health effects of cyclones. We aimed to provide a systematic review with meta-analysis of current evidence on the risks of all reported health outcomes related to cyclones and to identify research gaps and make recommendations for further research. We systematically searched five electronic databases (MEDLINE, Embase, PubMed, Scopus, and Web of Science) for relevant studies in English published before 21 December 2022. Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, we developed inclusion criteria, screened the literature, and included epidemiological studies with a quantitative risk assessment of any mortality or morbidity-related outcomes associated with cyclone exposures. We extracted key data and assessed study quality for these studies and applied meta-analyses to quantify the overall effect estimate and the heterogeneity of comparable studies. In total, 71 studies from eight countries (the United States, China, India, Japan, the Philippines, South Korea, Australia, Brazil), mostly the United States, were included in the review. These studies investigated the all-cause and cause-specific mortality, as well as morbidity related to injury, cardiovascular diseases (CVDs), respiratory diseases, infectious diseases, mental disorders, adverse birth outcomes, cancer, diabetes, and other outcomes (e.g., suicide rates, gender-based violence). Studies mostly included only one high-amplitude cyclone (cyclones with a Saffir-Simpson category of 4 or 5, i.e., Hurricanes Katrina or Sandy) and focused on mental disorders morbidity and all-cause mortality and hospitalizations. Consistently elevated risks of overall mental health morbidity, post-traumatic stress disorder (PTSD), as well as all-cause mortality or hospitalizations, were found to be associated with cyclones. However, the results for other outcomes were generally mixed or limited. A statistically significant overall relative risk of 1.09 [95% confidence interval (CI): 1.04, 1.13], 1.18 (95% CI: 1.12, 1.25), 1.15 (95% CI: 1.13, 1.18), 1.26 (95% CI: 1.05, 1.50) was observed for all-cause mortality, all-cause hospitalizations, respiratory disease, and chronic obstructive pulmonary disease hospitalizations, respectively, after cyclone exposures, whereas no statistically significant risks were identified for diabetes mortality, heart disease mortality, and preterm birth. High between-study heterogeneity was observed. There is generally consistent evidence supporting the notion that high-amplitude cyclones could significantly increase risks of mental disorders, especially for PTSD, as well as mortality and hospitalizations, but the evidence for other health outcomes, such as chronic diseases (e.g., CVDs, cancer, diabetes), and adverse birth outcomes remains limited or inconsistent. More studies with rigorous exposure assessment, of larger spatial and temporal scales, and using advanced modeling strategy are warranted in the future, especially for those small cyclone-prone countries or regions with low and middle incomes. https://doi.org/10.1289/EHP12158.

Hidradenitis Suppurativa and Risk of Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Patients with hidradenitis suppurativa (HS) may have a higher risk of coronary artery disease (CAD) due to the excessive inflammatory burden. However, data on this association is still relatively limited. To investigate the association between HS and risk of prevalent and incident CAD by combining result from all available studies using systematic review and meta-analysis technique. Potentially eligible studies were identified from Medline and EMBASE databases from inception to November 2021 using search strategy that comprised of terms for 'hidradenitis suppurativa' (HS) and 'coronary artery disease' (CAD). Eligible study must be cohort study that consisted of one cohort of patients with HS and another cohort of individuals without HS. The study must report incidence or prevalence of CAD in both groups. The retrieved point estimates with standard errors from each study were summarized into pooled result using random-effect model and generic inverse variance method. Meta-analyses of the prevalent and incident CAD were conducted separately. A total of 876 articles were identified. After two rounds of independent review by three investigators, seven cohort studies (four incident studies and three prevalent studies) met the eligibility criteria and were analysed in the meta-analyses. The meta-analysis found a significantly elevated risk of both incident and prevalent CAD in patients with HS compared to individuals without psoriasis with the pooled risk ratio of 1.38 (95% CI, 1.21-1.58; I2 83%) and 1.70 (95% CI, 1.13-2.57; I2 89%), respectively. Limited accuracy of diagnosis of HS and CSD as most included studies relied on diagnostic codes and high between-study statistical heterogeneity. The current systematic review and meta-analysis found a significantly increased risk of both prevalent and incident CAD among patients with HS.

Sex-disaggregated effectiveness data reporting in COVID-19 vaccine research: a systematic review

BackgroundSex and gender are believed to influence vaccine response. Yet, the relationship between sex and gender and COVID-19 vaccine efficacy is poorly understood and remains under-investigated.MethodsWe conducted a systematic review to determine whether and to what extent post-approval COVID-19 vaccine effectiveness (VE) studies report sex-disaggregated VE data.We searched four publication and pre-publication databases and additional grey literature sources for relevant published/preprint studies released between 1 January 2020 and 1 October 2021 (i.e., pre-Omicron era). We included observational studies providing VE estimates for one or more licensed/approved COVID-19 vaccines and including both males and females. Two reviewers independently assessed study eligibility, extracted data, and assessed risk-of-bias through a modified version of Cochrane’s ROBINS-I tool. A qualitative data synthesis was performed.ResultsHere we show that, among 240 eligible publications, 68 (28.3%) do not report the sex distribution among participants. Only 21/240 (8.8%) studies provide sex-disaggregated VE estimates, and high between-study heterogeneity regarding design, target population, outcomes, and vaccine type/timing prevent the assessment of sex in determining COVID-19 VE across studies.ConclusionsOur findings indicate that few COVID-19 vaccine research publications account for sex. Improved adherence to recommended reporting guidelines will ensure that the evidence generated can be used to better understand the relationship between sex and gender and VE.

A Systematic Review and Meta-Analysis of Basal and Post-Stress Circulating Cortisol Concentration in an Important Marine Aquaculture Fish Species, European Sea Bass, Dicentrarchus labrax.

European sea bass is a species characterized by high and dispersed cortisol levels. The aim of the present study was to analyze all published data on basal and post-acute stress cortisol levels in this species. For this systematic review and meta-analysis the Web of Science and Scopus databases were searched for papers reporting plasma or serum cortisol levels in E. sea bass, without language or date restrictions. Data were extracted directly for the reported results and were analyzed separately for basal and post-acute stress levels, as well their standardized mean differences (SMD) using random-effects meta-analyses. Of 407 unique records identified, 69 were eligible. Basal cortisol levels had a pooled effect of 88.7 ng mL-1 (n = 57), while post-acute stress levels were 385.9 ng mL-1 (n = 34). The average SMD between basal and post-stress was calculated to be 3.02 (n = 22). All analyses had a high between-study heterogeneity. Results for basal and post-stress levels were affected by the assay type and anesthesia prior to blood sampling. Cortisol levels in E. sea bass are higher than most studied fish species and display large heterogeneity. Application of stress led to elevated cortisol levels in all studies examined. In all cases, sources of between-studies heterogeneity were identified.