Pooled Effect Estimates Research Articles

Climate change and epidemiological trends of malaria and Lassa fever transmission in Nigeria (2015-2022): A systematic review and meta-analysis

Background: Climate change exacerbates infectious disease transmission in Nigeria, a country with a high burden of infectious diseases. Objective: To conduct a systematic review and meta-analysis examining the relationship between climate variability and infectious disease transmission in Nigeria. Methods: We systematically searched major databases, identifying 25 studies, with 11 studies meeting the inclusion criteria for meta-analysis using R version 4.4.1. Results: The meta-analysis revealed significant associations between temperature increases and malaria (pooled effect estimate = 1.034, 95% CI: 1.016-1.052) and Lassa fever (pooled effect estimate = 1.029, 95% CI: 1.015-1.043) transmission. Egger's funnel plot showed no significant publication bias, and sensitivity analysis confirmed the robustness of the findings. Conclusion: This study provides evidence for the association between climate variability and infectious disease transmission in Nigeria. This underscores the urgent need for targeted interventions to protect vulnerable populations, including children under 5, pregnant women, the elderly, people with comorbidity, and low-income communities.

The effect of Glucagon-like peptide-1 receptor agonists on cardiovascular outcomes in type 2 diabetes mellitus patients with coronary artery disease

Abstract Background Cardiovascular disease is the primary cause of mortality in patients with type 2 diabetes mellitus (T2DM). Randomized controlled trials (RCT) have shown that Glucagon-like peptide-1 receptor agonists (GLP-1RA) improve cardiovascular outcomes in T2DM patients, with greater therapeutic benefits observed in patients with established atherosclerotic cardiovascular disease. However, the effect of GLP1-RA therapy on cardiovascular outcomes has been inconsistent and the RCT have not been sufficiently powered to examine the effect of GLP1-RA on mortality or their therapeutic effect in different subgroups of T2DM patients. Purpose This study aimed to examine the effect of GLP1-RA therapy on cardiovascular outcomes and mortality in a real-world cohort of T2DM patients with coronary artery disease (CAD). Methods This study included T2DM patients with CAD who were treated with metformin at a daily dose of ≥ 1g for a period of ≥ 180 days. CAD was defined as ≥ 50% luminal stenosis in any coronary artery segment according to a nationwide angiography and angioplasty registry. We performed sequential emulated target trials at monthly intervals between January 1, 2013 and December 31, 2020 to examine the effect of GLP1-RA therapy on major adverse cardiovascular outcomes (MACE), a composite of myocardial infarction, ischemic stroke and all-cause mortality. Secondary outcomes included the individual components of MACE. Marginal structural models were used to compute pooled effect estimates. This was an intention-to-treat analysis with 5 years of follow-up for each emulated target trial. Inverse probability of treatment weighting was used to adjust for confounding due to differences in patient demographics at baseline. Results This study consisted of 26,746 individuals who were treated with GLP1-RA and 74,638 controls. The 5-year cumulative risk of MACE was 27.7 % in the GLP1-RA group and 32.7 % in the control group (risk ratio 0.85 [95% confidence interval 0.82 – 0.88]). GLP1-RA therapy was associated with a lower risk of all-cause mortality (risk ratio 0.76 [95% confidence interval 0.72 – 0.79]) and myocardial infarction (risk ratio 0.95 [95% confidence interval 0.89 – 1.00]). We found little or no effect of GLP1-RA therapy on the risk of ischemic stroke (risk ratio 1.13 [95% confidence interval 0.97 – 1.27]). Conclusions In this large real-world cohort of T2DM patients with established CAD, we observed that GLP1-RA therapy was associated with a lower risk of MACE, myocardial infarction and all-cause mortality.

Waist circumference as a parameter in school-based interventions to prevent overweight and obesity - a systematic review and meta-analysis

BackgroundPreventing childhood obesity remains an important public health issue worldwide. Since visceral fat in particular is understood as an important risk factor for many chronic diseases, waist circumference is recommended as a measurement parameter for global obesity surveillance. This systematic review and meta-analysis focused on waist circumference as an outcome parameter for studies of school-based interventions to prevent overweight and obesity.MethodsA systematic literature search was conducted at the end of 2019 in nine data bases, including Medline and Embase, in order to identify relevant studies evaluating interventions in schools aimed at preventing obesity. Eligibility criteria admitted randomised and non-randomised controlled trials. After screening titles, abstracts and full texts, the data of the identified studies were systematically extracted. Risk of bias was assessed according to study type with the appropriate Cochrane Risk of Bias Tool. The review gives a qualitative overview over all included studies structured by extracted data. Separate meta-analyses were done for the outcome mean difference in change in waist circumference, measured in cm or reported as z-score value, using an inverse variance random-effects model due to study design.ResultsA total of 2421 publications were screened based on titles, abstracts and full texts. Complemented by results of a former systematic literature search 44 studies were identified for inclusion, comprising a total of 39.837 participants (age range: 6 to 18 years). Nearly half of the studies were conducted in Europe, two-thirds combined diet and exercise-based interventions. Likewise two thirds of the studies were conducted as cluster-randomised trials. Most of the reported effects favoured the experimental groups, indicating the basic effectiveness of school-based measures. Based on reported data, only one third of the studies could be included in the meta-analyses. For the difference in mean change of the outcome parameter waist circumference measured in cm (95% CI), we found a pooled effect estimate of -0.95 (-1.87; -0.46). For the difference in mean change of the outcome parameter waist circumference reported as z-score value (95% CI), the pooled effect estimate was -0.10 (-0.15; -0.05). Both effect estimates were in favour of the experimental group. The overall effect sizes were small with a p-value < 0.05.ConclusionsPooled effect estimates were small but in favour of the experimental groups. The same applies to the majority of the effects reported in the included studies. The included cluster of randomised controlled trials demonstrated an especially sound methodological standard. The possibility of achieving larger effects in studies of preventive interventions and health promotion is limited. Schools can only realise their full potential in preventing overweight and obesity in children and adolescents if they are accompanied by measures in other areas of the obesogenic environment.

Efficacy of Thiocolchicoside for Musculoskeletal Pain Management: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Despite the fact that thiocolchicoside has been widely used in the treatment of musculoskeletal pain, its efficacy has never been systematically evaluated. We carried out a systematic review and meta-analysis of randomized clinical trials (RCTs) to appraise the existing evidence on the efficacy of thiocolchicoside for musculoskeletal pain management. Methods: The literature search was performed on multiple databases, extracting reports of RCTs evaluating the efficacy of thiocolchicoside compared to placebo or no exposure. The reduction in pain intensity was evaluated through between-groups mean differences (MDs) in Visual Analogue Scale (VAS) scores after the intervention. The pooled effect estimates were compared to a minimally important difference (MID) of 1 point on a scale from 0 to 10. Results: We retrieved eight RCTs, including a total of 1397 patients. All the included studies were determined as being at high risk of bias. Seven trials evaluated patients with acute low back pain. After 2-3 days of treatment, the pooled MD in VAS score was -0.49 (95%CI = -0.90; -0.09) compared to controls. After 5-7 days of treatment, the summary MD was -0.82 (95%CI = -1.46; -0.18). Conclusions: Although thiocolchicoside was found to significantly reduce patient-reported low back pain, the clinical impact was very small, as the pooled effect estimates were below the MID, and the overall certainty of evidence was very low. In light of the safety concerns raised by the European Medicine Agency, an in-depth analysis on the risk-benefit balance of thiocolchicoside is required.

The associations of post-stroke delirium with outcomes: a systematic review and meta-analysis

BackgroundPublished data on whether post-stroke delirium (PSD) is an independent predictor of outcomes in patients with acute stroke are inconsistent and have not yet been synthesized and quantified via meta-analyses.MethodsThis systematic review and meta-analysis followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The study protocol involved a search of the PubMed, Embase, PsycINFO, and Medline databases from 1946 to November 1, 2023, of which prospective observational and case–control studies were included. The quality of the included studies was rated using the Newcastle Ottawa Scale. Pooled effect estimates calculated using a random-effects model were expressed as the odds ratios (ORs), hazard ratios (HRs), and standardized mean differences (SMDs) with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023472551).ResultsThe search yielded 39 eligible articles comprising 3295 and 9643 patients with and without PSD, respectively. Thirty studies were high quality, while 9 had moderate quality. The primary analyses, adequately adjusting for predefined confounders, showed that PSD was significantly associated with mortality risk (average follow-up of 19.50 months; OR, 3.47; 95% CI, 2.35–5.12; I2, 26.0%) and poor neurological function (average follow-up of 21.75 months; OR, 3.62; 95% CI, 2.15–6.09; I2, 0). Secondary analyses, with or without inadequate adjustment, showed that PSD was significantly associated with prolonged hospital length of stay, increased risk of institutionalization, poor cognitive outcomes, and quality of life after discharge.ConclusionsThis systematic review and meta-analysis provides evidence that PSD was independently associated with mortality and poor neurological function after controlling for pre-specified confounders. The prevention of PSD remains a high clinical and research priority.

Relationship between radiofrequency-electromagnetic radiation from cellular phones and brain tumor: meta-analyses using various proxies for RF-EMR exposure-outcome assessment

IntroductionThe authors conducted meta-analyses regarding the association between cellular and mobile phone use and brain tumor development by applying various radiofrequency-electromagnetic radiation (RF-EMR) exposure subcategories. With changing patterns of mobile phone use and rapidly developing Wireless Personal Area Network (WPAN) technology (such as Bluetooth), this study will provide insight into the importance of more precise exposure subcategories for RF-EMR.MethodsThe medical librarian searched MEDLINE (PubMed), EMBASE, and the Cochrane Library until 16 December 2020.ResultsIn these meta-analyses, 19 case-control studies and five cohort studies were included. Ipsilateral users reported a pooled odds ratio (OR) of 1.40 (95% CI 1.21–1.62) compared to non-regular users. Users with years of use over 10 years reported a pooled OR of 1.27 (95% CI 1.08–1.48). When stratified by each type of brain tumor, only meningioma (OR 1.20 (95% CI 1.04–1.39)), glioma (OR 1.45 (95% CI 1.16–1.82)), and malignant brain tumors (OR 1.93 (95% CI 1.55–2.39)) showed an increased OR with statistical significance for ipsilateral users. For users with years of use over 10 years, only glioma (OR 1.32 (95% CI 1.01–1.71)) showed an increased OR with statistical significance. When 11 studies with an OR with cumulative hours of use over 896 h were synthesized, the pooled OR was 1.59 (95% CI 1.25–2.02). When stratified by each type of brain tumor, glioma, meningioma, and acoustic neuroma reported the pooled OR of 1.66 (95% CI 1.13–2.44), 1.29 (95% CI 1.08–1.54), and 1.84 (95% CI 0.78–4.37), respectively. For each individual study that considered cumulative hours of use, the highest OR for glioma, meningioma, and acoustic neuroma was 2.89 (1.41–5.93) (both side use, > 896 h), 2.57 (1.02–6.44) (both side use, > 896 h), and 3.53 (1.59–7.82) (ipsilateral use, > 1640 h), respectively. For five cohort studies, the pooled risk ratios (RRs) for all CNS tumors, glioma, meningioma, and acoustic neuroma, were statistically equivocal, respectively. However, the point estimates for acoustic neuroma showed a rather increased pooled RR for ever-use (1.26) and over 10 years of use (1.61) compared to never-use, respectively.DiscussionIn this meta-analysis, as the exposure subcategory used became more concrete, the pooled ORs demonstrated higher values with statistical significance. Although the meta-analysis of cohort studies yielded statistically inconclusive pooled effect estimates, (i) as the number of studies included grows and (ii) as the applied exposure subcategories become more concrete, the pooled RRs could show a different aspect in future research. Additionally, future studies should thoroughly account for changing patterns in mobile phone use and the growing use of earphones or headphones with WPAN technology.

Effect of pharmacist interventions in chronic kidney disease: a meta-analysis.

Pharmacists are uniquely placed with their therapeutic knowledge to manage people with chronic kidney disease (CKD). Data is limited regarding the impact of pharmacist interventions on economic, clinical, and humanistic outcomes (ECHO). A systematic review and meta-analysis of randomized controlled trials (RCTs) of interventions with pharmacist input was conducted, which included adults with a diagnosis of CKD, including those with and without kidney replacement therapy. Data was extracted on ECHO: economic (e.g. healthcare-associated costs), clinical (e.g. mortality), and humanistic (e.g. patient satisfaction) outcomes. Where appropriate, a random-effects model meta-analysis generated a pooled estimate of effect. A direction of effect plot was used to summarize the overall effects for clinical outcome domains. 32 RCTs reported a total of 10 economic, 211 clinical, and 18 humanistic outcomes. Pharmacist interventions resulted in statistically significant improvements in systolic blood pressure and hemoglobin levels, but not in diastolic blood pressure, estimated glomerular filtration rate, creatinine, and low-density lipoprotein cholesterol levels. Mixed findings were reported for clinical and economic outcomes, whilst pharmacist interventions resulted in an improvement in humanistic outcomes such as patient satisfaction and patient knowledge. Findings showed pharmacist interventions had mixed results for various outcomes. Future studies should be more robustly designed and take into consideration the role of the pharmacist in prescribing and deprescribing, the findings of which will help inform research and clinical practice.

Inflated effect estimates for vitamin D supplementation are driven by common meta-analytical errors.

Han et al. (J Int Soc Sports Nutr 16:55, 2019) sought to quantify the effects of vitamin D supplementation on strength outcomes among athletes in a meta-analysis. The authors reported a pooled effect size (standardized mean difference; SMD) of -0.75 (95% CI: -1.82 to 0.32, p = 0.17) in favor of supplementation, but the analytical approach was not appropriate for a pooled analysis of randomized controlled trials and the effect sizes were calculated incorrectly. This letter discusses how these issues impact the results and interpretation of the paper, then provides an update on the estimated average effect of vitamin D on strength outcomes in athletes. Identified errors included the use of within-group rather than between-group effect size metrics, the use of standard error values in place of standard deviations, and failure to account for correlated observations within the model. The data were reanalyzed after correcting for these common meta-analytic errors. The results of this reanalysis reflect a dramatically smaller and statistically nonsignificant pooled effect estimate of SMD = 0.16 (-0.24 to 0.56, p = 0.43) in favor of supplementation. Further, the model from this reanalysis has more favorable statistical characteristics than the original analysis, as evidenced by a fairly symmetrical funnel plot and a nonsignificant result for Cochrane's Q test (Q = 5.02, p = 0.41). In order to disseminate robust information to sports nutrition practitioners and researchers, it is critically important for meta-analyses to produce valid effect estimates that are appropriate for the underlying study designs and calculated without error. This letter highlights common errors to inform the calculation and interpretation of future meta-analyses in sports nutrition.

Transportation noise and cardiovascular health: an Umbrella+ review

A significant number of studies have shown an association between transportation noise and cardiovascular diseases. With this Umbrella+ review, we aimed to provide a comprehensive overview of the literature on the relation between transportation noise and various cardiovascular health outcomes such as ischaemic heart disease, stroke, heart failure, blood pressure and hypertension, as well as cardiovascular mortality. Following the Umbrella+ approach, we first identified the newest review of high quality and then original high-quality studies published thereafter. Further, by including the latest studies we performed a meta-analysis to derive up-to-date exposure-response functions for each noise source (road traffic, railway and aircraft) separately. We found that compared to road traffic noise, less research was available for railway and aircraft noise. Regarding road traffic noise, we identified a significantly increased risk for multiple cardiovascular health outcomes. For example, the pooled effect estimate for cardiovascular mortality was 1.05 (95% CI: 1.02-1.07) per 10dB(A) increase in noise, for the incidence of ischaemic heart disease it was 1.04 (95% CI: 1.02-1.06) and for stroke incidence 1.05 (95% CI: 1.01-1.08) per 10dB(A) increase in noise. This work will be used to quantify the burden of disease from transportation noise for the general population in Europe.

Social determinants of injection drug use-associated bacterial infections and treatment outcomes: systematic review and meta-analysis.

Individual injecting practices (e.g., intramuscular injecting, lack of skin cleaning) are known risk factors for injection drug use-associated bacterial and fungal infections; however, social contexts shape individual behaviours and health outcomes. We sought to synthesize studies assessing potential social determinants of injecting-related infections and treatment outcomes. We searched five databases for studies published between 1 January 2000 and 18 February 18 2021 (PROSPERO CRD42021231411). We included studies of association (aetiology), assessing social determinants, substance use, and health services exposures influencing development of injecting-related infections and treatment outcomes. We pooled effect estimates via random effects meta-analyses. We screened 4,841 abstracts and included 107 studies. Several factors were associated with incident or prevalent injecting-related infections: woman/female gender/sex (adjusted odds ratio [aOR] 1.57, 95% confidence interval [CI] 1.36-1.83; n=20 studies), homelessness (aOR 1.29, 95%CI 1.16-1.45; n=13 studies), cocaine use (aOR 1.31, 95%CI 1.02-1.69; n=10 studies), amphetamine use (aOR 1.74, 95%CI 1.39-2.23; n=2 studies), public injecting (aOR 1.40, 95%CI 1.05-1.88; n=2 studies), requiring injecting assistance (aOR 1.78, 95%CI 1.40-2.27; n=8 studies), and use of opioid agonist treatment (aOR 0.92, 95%CI 0.89-0.95; n=9 studies). Studies assessing outcomes during treatment (e.g., premature hospital discharge) or afterward (e.g., rehospitalization; all-cause mortality) typically had smaller sample sizes and imprecise effect estimates. Injecting-related infections and treatment outcomes may be shaped by multiple social contextual factors. Approaches to prevention and treatment should look beyond individual injecting practices towards addressing the social and material conditions within which people live, acquire and consume drugs, and access health care.

Assessment of the Effects of Subclinical Hypothyroidism on Male Reproductive Parameters: A Meta-Analysis Approach

Subclinical hypothyroidism (SCH) is a common endocrine disorder that potentially affects reproductive health. Despite its prevalence, the precise relationship between SCH and sperm quality remains unclear. A comprehensive search was conducted across electronic databases to identify relevant studies exploring the association between SCH and sperm quality parameters, covering literature published from January 2000 to January 2024. The standard mean difference (SMD) was used to compute pooled effect estimates with 95% confidence intervals (CIs). Additionally, meta-regression and subgroup analyses were performed to investigate the potential sources of heterogeneity. The meta-analysis included a thorough examination of ten studies comprising 2239 participants. According to the findings of this meta-analysis, SCH significantly affects sperm quality. Specifically, the study suggests a decrease in the volume of seminal fluids (SMD = -0.186; 95% CI: -0.385 to 0.013; P = 0.067), total sperm count (SMD = -0.604; 95% CI: -1.178 to -0.030; P = 0.039), sperm morphology (SMD = -0.784; 95% CI: -1.405 to -0.162; P = 0.013), and progressive motility (SMD = -1.437; 95% CI: -2.147 to -0.727; P &lt; 0.001). However, SCH was also associated with an increase in sperm concentration (SMD = 0.112; 95% CI: -0.058 to 0.281; P = 0.017). Our meta-analysis provides compelling evidence of the adverse effects of SCH on sperm quality parameters. These findings underscore the importance of considering the thyroid function in the assessment and management of male infertility.

Chronic disease associated with bullous pemphigoid risk: A systematic review and meta-analysis

BackgroundBullous pemphigoid (BP) is a chronic autoimmune blistering disease prevalent in elderly, often accompanied by renal comorbidities. Immune dysregulation can lead to secondary BP and increased mortality rates in those already diagnosed. MethodsA literature review identified studies on the association between kidney disease and other comorbidities with BP. Pooled effect estimates were analyzed utilizing a random-effects model. ObjectiveTo assess comorbidity risks with BP and determine mortality risk among BP patients with comorbidities. ResultsAnalysis included 45,323 BP patients from 49 studies. Kidney diseases were significantly linked to higher BP incidence (SDHR 1.51, 95% CI: 1.10-2.07) and increased mortality (HR 1.62, 95% CI: 1.13-2.32). Cerebrovascular diseases, dementia, and diabetes also showed significant associations with both increased BP incidence and mortality (p < 0.05). However, cardiovascular diseases and malignancy were only associated with increased mortality among BP patients (p < 0.001), without affecting BP incidence (p = 0.785 and p = 0.792, respectively). LimitationThe study comprises mostly case-control, prospective, and retrospective observational studies, alongside data heterogeneity. ConclusionThis study reveals the association of several chronic conditions including kidney diseases with BP, contributing to elevated mortality rates. The findings emphasize the importance of management targeting both BP and associated comorbidities to improve patient outcomes.

The role of prophylactic transfusion on the maternal and fetal outcomes in pregnant women with sickle cell disease: A systematic review and meta-analysis.

In the present review, we aimed to synthesize evidence from studies on the safety and effectiveness of prophylactic blood transfusion in pregnant women with sickle cell disease. To gather relevant information, we conducted systematic electronic searches of databases such as SCOPUS, Medline via PubMed, Web of Science, and Cochrane Central Register of Controlled Trials. We included both retrospective and prospective studies that examined the impact of prophylactic blood transfusions during pregnancy. The collected data were analyzed using Review Manager, version 5.3. The review included 15 cohort studies. The overall findings indicated a preference for the prophylactic blood transfusion group over the control group across several key parameters. Specifically, the prophylactic group demonstrated lower rates of maternal mortality (odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.10-1.13; P = .08), reduced incidence of vaso-occlusive painful events (OR = 0.31; 95% CI = 0.14-0.73; P = .007), fewer pulmonary complications (OR = 0.21; 95% CI = 0.08-0.53; P = .001), decreased perinatal mortality (OR = 0.35; 95% CI = 0.17-0.75; P = .03), and lower likelihood of preterm birth (OR = 0.67; 95% CI = 0.47-0.96; P = .02). Notably, statistically significant heterogeneities were observed in the pooled effect estimates. The present meta-analysis indicated that prophylactic blood transfusion in pregnant women with sickle cell disease may improve maternal and fetal outcomes. However, substantial variations in the methodology and transfusion protocols among the included studies limited the credibility of the current evidence supporting the routine clinical use of prophylactic transfusion for SCD during pregnancy.

Comparison of Extracorporeal and Intracorporeal Urinary Diversion after Robot-Assisted Radical Cystectomy for Bladder Cancer: A Meta-Analysis.

To explore the therapeutic efficacy of intracorporeal urinary diversion (ICUD) and extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy for bladder cancer through systematic review. This study systematically retrieved electronic databases of PubMed, Web of Science, Cochrane Library, CNKI, and Wanfang to include peer-reviewed studies comparing ICUD and ECUD after robot-assisted radical cystectomy for bladder cancer. Relative risk (RR) and mean difference (MD) were used to represent the pooled effect size and estimate its 95% confidence interval (CI). This study included 15 studies with good quality, involving 5,370 patients undergoing robot-assisted radical cystectomy for bladder cancer. Meta-analysis showed that ICUD reduced intraoperative bleeding volume by 64.12 ml (95% confidence interval [CI]: [-100.95, -27.29]), significantly decreased the risk of blood transfusion (RR: 0.40; 95% CI: [0.24, 0.68]) and gastrointestinal complications (odds ratio [OR]: 0.61; 95% CI: [0.47, 0.80]), with shorter postoperative time of exhaust (MD: -9.27; 95% CI: [-18.47, -0.08]) and oral intake (MD: -0.92; 95% CI: [-1.30, -0.54]). However, ICUD had a relatively longer surgical duration (MD: 30.84 min, 95% CI: [5.03, 56.66]). In addition, there was no statistically significant difference concerning the impact of ICUD and ECUD on the length of stay in the hospital (MD: -0.68d; 95% CI: [-1.79, 0.42]), overall complications (30-day: RR: 1.16; 95% CI: [0.93, 1.46]; and 90-day, RR: 0.85; 95% CI: [0.69, 1.04]) and readmission rate (30-day: RR: 0.96; 95% CI: [0.72, 1.27]; and 90-day: RR: 1.15; 95% CI: [0.80, 1.64]). ICUD after robot-assisted laparoscopic radical cystectomy for bladder cancer exhibits obvious positive effects, especially in reducing the risk of blood transfusion and gastrointestinal complications, and shortening postoperative time of exhaust and oral intake. The findings in this meta-analysis should be confirmed by multiple high-quality studies in the future.

Estimating Additive Interaction in Two-Stage Individual Participant Data Meta-Analysis.

Individual participant data (IPD) meta-analysis provides important opportunities to study interaction and effect modification for which individual studies often lack power. While previous meta-analyses have commonly focused on multiplicative interaction, additive interaction holds greater relevance for public health and may in certain contexts better reflect biological interaction. Methodological literature on interaction in IPD meta-analysis does not cover additive interaction for models including binary or time-to-event outcomes. We aimed to describe how the Relative Excess Risk due to Interaction (RERI) and other measures of additive interaction or effect modification can be validly estimated within two-stage IPD meta-analysis. First, we explain why direct pooling of study-level RERI estimates may lead to invalid results. Next, we propose a three-step procedure to estimate additive interaction: 1) estimate effects of both exposures and their product term on the outcome within each individual study; 2) pool study-specific estimates using multivariate meta-analysis; 3) estimate an overall RERI and 95% confidence interval based on the pooled effect estimates. We illustrate this procedure by investigating interaction between depression and smoking and risk of smoking-related cancers using data from the PSYchosocial factors and Cancer (PSY-CA) consortium. We discuss implications of this procedure, including the application in meta-analysis based on published data.

The Impact of the Middle Ear Microbiota on Otitis Media Outcomes: A Meta-Analysis of Longitudinal Studies

Introduction: Otitis media (OM), a prevalent middle ear inflammation, often involves microbial colonization. The composition of the middle ear microbiota may influence OM outcomes, including recurrence, persistence, and treatment response. This meta-analysis investigated the relationship between the middle ear microbiota and OM outcomes. Methods: Longitudinal studies published from 2018 to 2024 that explored the middle ear microbiota and OM outcomes were systematically searched in PubMed, Embase, and Web of Science. Data on study design, participant characteristics, microbiota analysis, and OM outcomes were extracted. The risk of bias was assessed using the Newcastle-Ottawa Scale. A random-effects model was used to pool effect estimates. Results: A total of 15 studies (n = 2,540 participants) met the inclusion criteria. The middle ear microbiota diversity was significantly lower in children with recurrent OM compared to those without (standardized mean difference [SMD] = -0.45, 95% confidence interval [CI] -0.62 to -0.28, p &lt; 0.001). The presence of specific pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, was associated with an increased risk of OM recurrence (odds ratio [OR] 1.75, 95% CI 1.32 to 2.31, p &lt; 0.001). Additionally, microbial dysbiosis was associated with delayed resolution of OM and increased antibiotic treatment failure. Conclusion: The middle ear microbiota composition significantly impacts OM outcomes. Reduced diversity and specific pathogens are associated with increased OM recurrence. These findings highlight the potential for microbiota-targeted interventions in OM management.

Brain and Heart Interactions Delineating Cardiac Dysfunction in Four Common Neurological Disorders: A Systematic Review and Meta-analysis.

Neurological and cardiovascular disorders are the leading causes of morbidity and mortality worldwide. While the effects of cardiovascular disease (CD) on the nervous system are well understood, understanding of the reciprocal relationship has only recently become clearer. Based on disability-adjusted life years, this systematic review and meta-analysis present the pooled incidence and association of CD in 4 selected common, noncommunicable neurological disorders: (1) migraine, (2) Alzheimer disease and other dementias, (3) epilepsy, and (4) head injury. Sixty-five studies, including over 4 and a half million patients, were identified for inclusion in this review. Among the 4 neurological disorders, the majority of patients (89.4%) had epilepsy, 9.6% had migraine, and 0.97% had head injury. Alzheimer disease and other dementias were reported in only 0.02% of patients. The pooled effect estimates (incidence and association) of CD in the 4 neurological disorders was 10% (95% CI: 5.8%-16.9%; I2 = 99.94%). When stratified by the neurological disorder, head injury was associated with the highest incidence of CD (28%). The 4 neurological disorders were associated with a 2-fold increased odds for developing CD in comparison to patients without neurological disorders. Epilepsy was associated with the greatest increased odds of developing CD (odds ratio: 2.25; 95% CI: 1.82-2.79; P = 0.04). In studies that reported this variable, the pooled hazard ratio was 1.64 (95% CI: 1.38-1.94), with head injury having the highest hazard ratio (2.17; 95% CI: 1.30-3.61). Large prospective database studies are required to understand the long-term consequences of CD in patients with neurological disorders.

Utility and Outcomes of Ovarian Tissue Cryopreservation and Transplantation for Gynecologic Cancers: A Systematic Review and Meta-analysis.

To evaluate the utility, success, and safety of ovarian tissue cryopreservation and autologous cryopreserved ovarian tissue transplantation for fertility preservation in patients with gynecologic cancers. A comprehensive search was performed of the MEDLINE, EMBASE, ClinicalTrials.gov, and Cochrane Library databases to identify relevant studies on the utility and outcomes of ovarian tissue cryopreservation and autologous cryopreserved ovarian tissue transplantation for gynecologic cancers from inception until January 23, 2024. Two reviewers independently performed the study selection, data extraction, and risk-of-bias assessment, and the results were then reviewed together. Twenty-three studies were included in the current systematic review. The resultant data were meta-analyzed to produce a pooled-effect estimate of the utility of ovarian tissue cryopreservation and autologous transplantation in gynecologic cancers as a proportion of all indications. We found that 7.5% and 9.6% of women undergoing ovarian tissue cryopreservation and autologous transplantation, respectively, had gynecologic cancers. In comparison, hematologic malignancies and breast cancer accounted for approximately 66.0% of all indications for these procedures. The return rate for autologous cryopreserved ovarian tissue transplantation in gynecologic cancers (6.0%) was not statistically different from those for other indications. Among women with gynecologic cancer who underwent ovarian stimulation, 27.3% had at least one child, and the ovarian endocrine function was restored in 78.1% of the women after autologous transplantation. The median graft longevity was 32 months, and no graft-site recurrence was reported after autologous transplantation in women with gynecologic cancer. Our results suggest that ovarian tissue cryopreservation and autologous transplantation are feasible options for preserving ovarian function in women with gynecologic cancers, although ovarian tissue cryopreservation is underutilized, and further studies are needed to determine the longer-term outcomes of autologous transplantation. PROSPERO, CRD42024498522.

The impact of probiotics on core autism symptoms - A systematic review and meta-analysis of randomized clinical trials

Background & AimsStudies have shown evidence of gut dysbiosis in individuals with autism spectrum disorder (ASD). Various microbiome-modifying treatments, including probiotics, have been proposed. This review systematically assessed the evidence on the effects of probiotics on core autism symptoms in children with ASD. MethodsWe performed a comprehensive literature search in Medline, Embase, CENTRAL, PsycInfo, and clinical trial registries, up to March 2023, and updated on January 10, 2024. Randomized controlled trials (RCTs) of parallel-group and cross-over designs were eligible. The population included individuals below 20 years of age diagnosed with ASD. Trials evaluating the effects of probiotics (any strain or dose) compared to placebo, no treatment, or another intervention were included. The outcomes of interest included the core autism symptoms: deficits in social skills, communication skills, and restricted, repetitive behaviors. No language restrictions were applied. Studies were excluded if an additional active compound was administered. The risk of bias was assessed using the Revised Cochrane Risk of Bias tool (RoB 2). This review was registered in PROSPERO (CRD42023393000). ResultsIn total, 12 RCTs assessing 630 participants were included. A borderline significant beneficial effect of probiotics on core ASD symptoms was found (8 RCTs, mean difference -0.21; 95% CI –0.39 to -0.03). Subgroup analysis according to study type showed a significant positive effect in parallel group trials (6 RCTs, mean difference -0.26; 95% CI –0.48 to -0.05). The pooled effect estimates for the other outcomes didn’t reveal significant differences between the groups. Importantly, the risk of bias was high in nine studies. ConclusionsAvailable data do not provide high-quality evidence supporting the use of probiotics for ASD symptoms in children.

The impact of targeted local outreach clinics to improve COVID-19 vaccine uptake: controlled interrupted time series in South West England

BackgroundOutreach clinics were part of efforts to maximise uptake in COVID-19 vaccination.MethodsWe used controlled interrupted time series, matching on age, sex, deprivation and vaccination eligibility date, to determine the effect of outreach clinics on time to first COVID-19 vaccine, using a population-based electronic health record database of 914,478 people, from December 2020 to December 2021; people living within 1 mile of each outreach clinics were exposed.Results50% of 288,473 exposed citizens were white British, and 71% were aged 0–49 years. There was no evidence for an overall statistically significant increase in cumulative percentage vaccinated due to the outreach clinic at 6 weeks, with an overall pooled effect estimate of -0.07% (95% CI: -1.15%, 1.02%). The pooled estimate for increased cumulative vaccine uptake varied slightly depending on how the analysis was stratified; by ethnic group it was − 0.12% (95% CI: -0.90%, 0.66%); by age group it was − 0.06% (95% CI: -0.41%, 0.28%); and by deprivation it was 0.03% (95% CI: -0.74%, 0.79%).ConclusionsLiving within a mile of an outreach clinic was not associated with higher vaccine uptake. Evaluation of future outreach clinics should consider the relative importance of travel amongst other barriers to accessing vaccines.