Inverse Variance Heterogeneity Research Articles

Exploring causal correlations between inflammatory cytokines and knee osteoarthritis: a two-sample Mendelian randomization.

Knee osteoarthritis (KOA) and certain inflammatory cytokines (such as interleukin 1 [IL-1] and tumor necrosis factor alpha [TNF-a]) are related; however, the causal relationship remains unclear. Here, we aimed to assess the causal relationship between 41 inflammatory cytokines and KOA using Mendelian randomization (MR). Two-sample bidirectional MR was performed using genetic variation data for 41 inflammatory cytokines that were obtained from European Genome-Wide Association Study (GWAS) data (n=8293). KOA-related genetic association data were also obtained from European GWAS data (n=40,3124). Inverse variance weighting (IVW), MR, heterogeneity, sensitivity, and multiple validation analyses were performed. Granulocyte colony-stimulating factor (G-CSF) or colony-stimulating factor 3 (CSF-3) levels were negatively associated with the risk of developing KOA (OR: 0.93, 95%CI:0.89-0.99, P=0.015). Additionally, macrophage inflammatory protein-1 alpha (MIP-1A/CCL3) was a consequence of KOA (OR: 0.72, 95%CI:0.54-0.97, P=0.032). No causal relationship was evident between other inflammatory cytokines and KOA development. This study suggests that certain inflammatory cytokines may be associated with KOA etiology. G-CSF exerts an upstream influence on KOA development, whereas MIP-1A (CCL-3) acts as a downstream factor.

The association between restricted activity and patient outcomes in older adults: systematic literature review and meta-analysis

BackgroundRestricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health.MethodsA search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis.ResultsThe search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51–16.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60–11.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25–9.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes.ConclusionsLimited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.

Transanal irrigation in children with functional constipation: A systematic review and meta-analysis.

Refractory functional constipation is a challenging condition to manage in children. The use of transanal irrigation (TAI) is well reported in children with neurological disorders as well as anorectal malformations but less so in children with functional disorders of defecation. The objective of our study was to evaluate the effectiveness, safety and outcomes of TAI in children with functional constipation. PubMed, Scopus and Google Scholar were searched for publications related to the use of TAI in functional constipation. Data regarding the study design, sample size, patient characteristics, investigator-reported response to TAI and adverse effects were extracted from studies that met the selection criteria. The inverse variance heterogeneity model was used for ascertaining the summary effect in this meta-analysis. The search strategy yielded 279 articles of which five studies were included in the final review. The studies were from the United Kingdom (n = 2), Netherlands (n = 2) and Denmark (n = 1). These studies included 192 children with a median age ranging from 7 to 12.2 years old. The TAI systems used in these studies were: Peristeen (n = 2), Peristeen or Qufora (n = 1), Alterna (n = 1) and Navina (n = 1). The follow-up duration ranged from 5.5 months to 3 years. Eleven (5.7%) children did not tolerate TAI and withdrew from treatment soon after initiation. The pooled investigator-reported success of TAI was 62% (95% CI: 52%-71%). The most common adverse event was pain which was experienced by 21.7% of children. A total of 27 (14%) were successfully weaned off TAI at the last follow-up. TAI is reported to be successful in 62% of children with refractory functional constipation. There is a need for well-designed prospective trials to evaluate this treatment option in children with refractory functional constipation.

Estimates of the prevalence of male circumcision in sub-Saharan Africa from 2010-2023-A systematic review and meta-analysis.

Male circumcision (MC) is a key part of the package of interventions to prevent HIV, the biggest health challenge in sub-Saharan Africa. To estimate the male circumcision prevalence and to evaluate the progress towards meeting WHO targets in sub-Saharan Africa during the period 2010-2023. We carried out a systematic review and meta-analysis of studies published during the period 2010-2023. We searched PubMed, Scopus, Cochrane CENTRAL, Google Scholar, WHO and the Demographic and Health Survey for reports on MC prevalence in sub-Saharan Africa. MC prevalence was synthesized using inverse-variance heterogeneity models, heterogeneity using I2 statistics and publication bias using funnel plots. A total of 53 studies were included. The overall prevalence during the study period was 45.9% (95% CI 32.3-59.8), with a higher MC prevalence in Eastern (69.9%, 95%CI 49.9-86.8) compared to Southern African (33.3%, 95%CI 21.7-46.2). The overall prevalence was higher in urban (45.3%, 95%CI 27.7-63.4) compared to rural settings (42.6%, 95% 26.5-59.5). Male circumcision prevalence increased from 40.2% (95% CI 25.0-56.3) during 2010-2015 to 56.2% (95% CI 31.5-79.5) during 2016-2023. Three countries exceeded 80% MC coverage, namely, Ethiopia, Kenya and Tanzania. Overall, the current MC prevalence is below 50%, with higher prevalence in Eastern African countries and substantially lower prevalence in Southern Africa. Most of the priority countries need to do more to scale up medical male circumcision programs.

Comparison of bias adjustment in meta-analysis using data-based and opinion-based methods.

Several methods exist for bias adjustment of meta-analysis results, but there has been no comprehensive comparison with unadjusted methods. We compare 6 bias-adjustment methods with 2 unadjusted methods to examine how these different methods perform. We re-analyzed a meta-analysis that included 10 randomized controlled trials. Two data-based methods (Welton's data-based approach and Doi's quality effects model) and 4 opinion-informed methods (opinion-based approach, opinion-based distributions combined statistically with data-based distributions, numerical opinions informed by data-based distributions, and opinions obtained by selecting areas from data-based distributions) were used to incorporate methodological quality information into the meta-analytical estimates. The results of these 6 methods were compared with 2 unadjusted models: the DerSimonian-Laird random effects model and Doi's inverse variance heterogeneity model. The 4 opinion-based methods returned the random effects model estimates with wider uncertainty. The data-based and quality effects methods returned different results and aligned with the inverse variance heterogeneity method with some minor downward bias adjustment. Opinion-based methods seem to only add uncertainty rather than bias adjust.

Global Prevalence of Adolescent Use of Nonprescription Weight-Loss Products

Use of nonprescribed weight-loss products in adolescents is a public health concern that is associated with negative physical and psychological consequences. However, the prevalence of nonprescribed weight-loss product use in adolescents is unknown. To determine the global prevalence of nonprescription weight-loss product use in children and adolescents. Four databases, including MEDLINE, PsycINFO, CINAHL (Cumulative Index of Nursing and Allied Health), and EMBASE, were searched for quantitative studies that reported prevalence data on use of nonprescription weight-loss products with no restrictions on publication date. The search was performed December 1, 2020, and updated March 6, 2023. Studies were included in the meta-analysis if they reported the prevalence of weight-loss product use, were published in English, and included individuals 18 years or younger. Data extraction was completed by 2 independent reviewers. Data analysis determined the overall pooled proportion of weight-loss product use in total and during the past week, past 30 days, past year, or lifetime. Inverse variance heterogeneity effect models were used. The main outcome measure was the prevalence of nonprescription weight-loss product use in adolescents for all included studies and over the past week, past month, past year, or lifetime. Subgroup analysis included separation of groups by sex, specific weight-loss product types, geographical location, and study publication time. A total of 90 articles (604 552 unique participants) were included in the meta-analysis. Of these, 50 studies (56%) were from North America. The reported prevalence of weight-loss product use in adolescents was 5.5% (96% CI, 5.5%-5.6%) overall. When identifying use of weight-loss products in the general population, prevalence was 2.0% (95% CI, 1.9%-2.1%) in the past week, 4.4% (95% CI, 4.3%-4.5%) in the past month, 6.2% (95% CI, 6.1%-6.3%) in the past year, and 8.9% (95% CI, 8.6%-9.2%) in their lifetime. Use of weight-loss products was higher among girls than boys. This meta-analysis found that use of weight-loss products occurs at high levels in adolescents, especially girls. These findings suggest that, given the ineffectiveness of these products for weight loss coupled with their harmful long-term health consequences, interventions are required to reduce use of weight-loss products in this group.

Resistance training and inter-interindividual response differences on cardiorespiratory fitness in older adults: An ancillary meta-analysis of randomized controlled trials.

Examine true inter-individual response differences (IIRD) as a result of resistance training on cardiorespiratory fitness in older adults. Data from a recent meta-analysis of 22 randomized controlled trials representing 552 men and women (292 resistance training, 260 control) ≥ 60 years of age were included. The primary outcome was cardiorespiratory fitness (VO2max) in ml.kg-1.min-1. Using the inverse variance heterogeneity (IVhet) model, statistically significant treatment effect (resistance training minus control) increases in VO2max in ml.kg-1.min-1 were found (mean, 1.8, 95% CI, 0.4 to 3.3 ml.kg-1.min-1, p = 0.01; Q = 82.8, p < 0.001; I2 = 74.6%, 95% CI, 61.6 to 83.3%; =1.1). The 95% prediction interval (PI) was -0.8 to 4.5 ml.kg-1.min-1. However, no statistically significant IIRD was observed (mean, 0.6, 95% CI, -1.1 to 1.4 ml.kg-1.min-1; =1.5). The 95% PI was -1.8 to 2.0 ml.kg-1.min-1. In conclusion, while progressive resistance training may increase VO2max in ml.kg-1.min-1, a lack of true resistance-training-associated IIRD exist.

Interindividual response variation to exercise-based cardiac rehabilitation on changes in cardiorespiratory fitness in heart transplant patients: A secondary meta-analysis of randomized controlled trials

PurposeDetermine whether true inter-individual exercise response differences (IIRD) occur in cardiorespiratory fitness (CRF) as a result of exercise-based cardiac rehabilitation in heart transplant patients. MethodsUsing data from a recent (2023) meta-analysis of nine RCTs representing 296 patients (163 exercise, 133 control), an aggregate data meta-analysis of treatment effects (change outcome differences between exercise and control groups) was conducted as well as an IIRD meta-analysis using the inverse variance heterogeneity (IVhet) model. The primary outcome was cardiorespiratory fitness (VO2max) in mL.kg-1.min-1. ResultsStatistically significant and clinically important increases equivalent to 14.5% were observed for VO2max in mL.kg-1.min-1 (X̅, 3.0, 95% CI, 2.4 to 3.7 mL.kg-1.min-1, p <0.001; Q=11.8, p=0.16; I2=32.0%, 95% CI, 0% to 68.8%; τ2=0.4). The 95% prediction interval (PI) was 1.2 to 4.7 mL.kg-1.min-1. However, no statistically significant IIRD were observed (X̅, 0.6, 95% CI, -1.1 to 1.4 mL.kg-1.min-1; τ2=2.9). The 95% PI was -2.7 to 2.8 mL.kg-1.min-1. ConclusionsWhile exercise-based cardiac rehabilitation increases VO2max in mL.kg-1.min-1 in heart transplant patients, a lack of true exercise-associated IIRD exist. A need exists for additional well-designed randomized controlled trials of longer duration to determine the long-term effects of exercise-based cardiac rehabilitation on VO2max in mL.kg-1.min-1 among heart transplant patients.

How effective is extracorporeal life support for patients with out-of-hospital cardiac arrest initiated at the emergency department? A systematic review and meta-analysis.

Extracorporeal cardiopulmonary resuscitation (ECPR) is commonly initiated for adults experiencing cardiac arrest within the cardiac catheterization lab or the intensive care unit. However, the potential benefit of ECPR for these patients in the emergency department (ED) remains undocumented. This study aims to assess the benefit of ECPR initiated in the ED for patients with out-of-hospital cardiac arrest (OHCA). We conducted a systematic review and meta-analysis of studies comparing ECPR initiated in the ED versus conventional CPR. Relevant articles were identified by searching several databases including PubMed, EMBASE, Web of Science, and Cochrane collaborations up to July 31, 2022. Pooled estimates were calculated using the inverse variance heterogeneity method, while heterogeneity was evaluated using Q and I2 statistics. The risk of bias in included studies was evaluated using validated bias assessment tools. The primary outcome was a favorable neurological outcome at hospital discharge, and the secondary outcome was survival to hospital discharge or 30-day survival. Sensitivity analyses were performed to explore the benefits of ED-initiated ECPR in studies utilizing propensity score (PPS) analysis. Publication bias was assessed using Doi plots and the Luis Furuya-Kanamori (LFK) index. The meta-analysis included a total of eight studies comprising 51,173 patients. ED-initiated ECPR may not be associated with a significant increase in favorable neurological outcomes (odds ratio [OR] 1.43, 95% confidence interval [CI] 0.30-6.70, I2 = 96%). However, this intervention may be linked to improved survival to hospital discharge (OR 3.34, 95% CI 2.23-5.01, I2 = 17%). Notably, when analyzing only PPS data, ED-initiated ECPR demonstrated efficacy for both favorable neurological outcomes (OR 1.89, 95% CI 1.26-2.83, I2 = 21%) and survival to hospital discharge (OR 3.37, 95% CI 1.52-7.49, I2 = 57%). Publication bias was detected for primary (LFK index 2.50) and secondary (LFK index 2.14) outcomes. The results of this study indicate that ED-initiated ECPR may not offer significant benefits in terms of favorable neurological outcomes for OHCA patients. However, it may be associated with increased survival to hospital discharge. Future studies should prioritize randomized trials with larger sample sizes and strive for homogeneity in patient populations to obtain more robust evidence in this area.

Prevalence and trends of advanced HIV disease among antiretroviral therapy-naïve and antiretroviral therapy-experienced patients in South Africa between 2010-2021: a systematic review and meta-analysis

BackgroundDespite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022.MethodsWe searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I2 statistic and publication bias using the Egger and Begg’s test.ResultsWe identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1–46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution.ConclusionDespite HIV’s evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART.

The effect of chronic high-intensity interval training programs on glycaemic control, aerobic resistance, and body composition in type 2 diabetic patients: a meta-analysis.

Type 2 diabetes is an increasing health problem worldwide. HIIT has been proposed as an exercise alternative to be part of integral type 2 diabetes treatment. The aim of this meta-analysis was to determine the effect of different types of chronic HIIT on glycaemic control, aerobic resistance, and body composition in individuals above 18years with T2D. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered with PROSPERO on November 21st, 2021. A systematic literature search of the following databases: EbscoHost (Academic Search Ultimate, Fuente Académica Plus, MEDline and SportDiscus), Web of Science, PubMed, and EMBASE between April of 2021 and April of 2023 was conducted. Eligibility criteria included (1) participants aged ≥ 18years with a diagnosis of type 2 diabetes, (2) an HIIT protocol with detailed description, (3) control group and/or continuous aerobic training comparison group, (4) report of pre-test and post-test values for at least one of the studied variables (from glycaemic control, aerobic resistance, and/or body composition), and (5) experimental or quasi-experimental intervention design. Meta-analysis was made by a pre-post-test between-group analysis following the inverse variance heterogeneity model for each variable, and then, a subgroup analysis by type of HIIT was conducted. Of the 2817 records obtained, 180 records were included for meta-analysis. Significant improvements were found in the most part of the variables when HIIT was compared to control group, while fat-free mass kept without changes. HIIT vs. continuous aerobic training results showed and advantage in favor of HIIT for fasting blood glycemia. Subgroup analysis refers a possible advantage of SI-HIIT and SIT-HIIT in the improvement of fasting glycemia and SIT-HIIT advantage in HOMA 1-IR decrease. HIIT improves glycaemic control, aerobic resistance, and % fat and waist circumference, and kept fat-free mass unchanged in individuals with T2D. SI-HIIT and SIT-HIIT could be better than the other types of HIIT. HIIT benefit is similar to continuous aerobic training except for fasting blood glycemia.

The impact of inpatient bloodstream infections caused by antibiotic-resistant bacteria in low- and middle-income countries: A systematic review and meta-analysis.

Bloodstream infections (BSIs) produced by antibiotic-resistant bacteria (ARB) cause a substantial disease burden worldwide. However, most estimates come from high-income settings and thus are not globally representative. This study quantifies the excess mortality, length of hospital stay (LOS), intensive care unit (ICU) admission, and economic costs associated with ARB BSIs, compared to antibiotic-sensitive bacteria (ASB), among adult inpatients in low- and middle-income countries (LMICs). We conducted a systematic review by searching 4 medical databases (PubMed, SCIELO, Scopus, and WHO's Global Index Medicus; initial search n = 13,012 from their inception to August 1, 2022). We only included quantitative studies. Our final sample consisted of n = 109 articles, excluding studies from high-income countries, without our outcomes of interest, or without a clear source of bloodstream infection. Crude mortality, ICU admission, and LOS were meta-analysed using the inverse variance heterogeneity model for the general and subgroup analyses including bacterial Gram type, family, and resistance type. For economic costs, direct medical costs per bed-day were sourced from WHO-CHOICE. Mortality costs were estimated based on productivity loss from years of potential life lost due to premature mortality. All costs were in 2020 USD. We assessed studies' quality and risk of publication bias using the MASTER framework. Multivariable meta-regressions were employed for the mortality and ICU admission outcomes only. Most included studies showed a significant increase in crude mortality (odds ratio (OR) 1.58, 95% CI [1.35 to 1.80], p < 0.001), total LOS (standardised mean difference "SMD" 0.49, 95% CI [0.20 to 0.78], p < 0.001), and ICU admission (OR 1.96, 95% CI [1.56 to 2.47], p < 0.001) for ARB versus ASB BSIs. Studies analysing Enterobacteriaceae, Acinetobacter baumanii, and Staphylococcus aureus in upper-middle-income countries from the African and Western Pacific regions showed the highest excess mortality, LOS, and ICU admission for ARB versus ASB BSIs per patient. Multivariable meta-regressions indicated that patients with resistant Acinetobacter baumanii BSIs had higher mortality odds when comparing ARB versus ASB BSI patients (OR 1.67, 95% CI [1.18 to 2.36], p 0.004). Excess direct medical costs were estimated at $12,442 (95% CI [$6,693 to $18,191]) for ARB versus ASB BSI per patient, with an average cost of $41,103 (95% CI [$30,931 to $51,274]) due to premature mortality. Limitations included the poor quality of some of the reviewed studies regarding the high risk of selective sampling or failure to adequately account for relevant confounders. We provide an overview of the impact ARB BSIs in limited resource settings derived from the existing literature. Drug resistance was associated with a substantial disease and economic burden in LMICs. Although, our results show wide heterogeneity between WHO regions, income groups, and pathogen-drug combinations. Overall, there is a paucity of BSI data from LMICs, which hinders implementation of country-specific policies and tracking of health progress.

Potential noninvasive biomarkers for the malignant transformation of oral leukoplakia: A systematic review and meta-analysis.

The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.

A commentary on 'A comparison of regional anesthesia techniques in patients undergoing video-assisted thoracic surgery: A network meta-analysis'.

Dear Editor: We read with great interest the article titled ‘A comparison of regional anesthesia techniques in patients undergoing video-assisted thoracic surgery: A network meta-analysis’ published in the recent issue of the International Journal of Surgery1. This study quantified the relative efficacy and safety of video-assisted thoracic surgery (VATS) patients receiving 18 different regional analgesic interventions and attempted to find an optimal approach that could be used as a reference for clinical medicine. The authors concluded that thoracic paravertebral block showed superior analgesia, ranking highest in reducing pain scores and lowering opioid consumption in the early postoperative period. This study provides available clinical evidence on the choice of the best regional analgesia technique for patients undergoing VATS. We would like to revisit this article from the following three perspectives to further refine this important study. The authors searched the target articles in the following four databases: Embase, Cochrane Library, PubMed, and Web of Science citation index. Nevertheless, the search for English databases should be expanded appropriately, and other commonly used databases, including PsycINFO, Google Scholar, Scopus, and ClinicalTrial.gov, should also be considered. In addition, the authors emphasized that the search process had no language limitation. Therefore, some commonly used Chinese databases, such as Wanfang and China Knowledge Network, should also be searched comprehensively. Secondly, we believe that the authors did not fully follow the inclusion criteria they set in the identification of studies. The authors clearly emphasized the inclusion of only randomized controlled trials in the text, so why include a nonrandomized prospective study2 and a retrospective study3 in the analysis? In addition, we found that the authors did not accurately assess the risk of bias in the included studies. For example, in the study of Dikici et al.4, the method of randomization was not described in detail in the text thus, the risk of randomization should be unknown; Dikici et al. simply stated in the text that the anesthesiologist was blinding, but this does not mean that the patients were also blinded, so the risk of performance bias was high. For another example, Fiorelli et al.5 emphasized that blindness was limited to anesthesiologists, but the authors considered performance bias to be a low risk. Therefore, we believe that the authors should reassess the risk of bias in all studies. Another worrying drawback is the high heterogeneity of the pooled outcomes in pairwise analyses, which may affect the accuracy of the conclusions. The heterogeneity of outcomes is mainly caused by a combination of various confounding factors, including different designs among studies, different patient characteristics, diversity in drug doses, differences in surgical and anesthetic techniques, and inconsistent follow-up time points, which are inevitable to some extent. However, we suggest that the authors use inverse variance heterogeneity (IV-het) models to validate the true effect sizes of the outcomes. The IV-het model can solve the known problems of underestimating statistical error and false overconfidence estimation using the random effect model. In addition, although the authors included 38 randomized controlled studies, the number of studies and sample size on which most of the pooled outcomes were based was limited. Therefore, it was difficult for the authors to reveal the sources of heterogeneity in the results through subgroup analysis and meta-regression analysis. More high-quality randomized controlled trials are needed in the future to elucidate further the optimal regional analgesia technique in patients with VATS. Ethical approval Not applicable. Sources of funding None. Author contribution The author read and approved the final version of the letter to the Editor. Conflicts of interest disclosure None. Research registration unique identifying number (UIN) Not applicable. Guarantor Li Guo. Provenance and peer review Commentary, internally reviewed.

Effectiveness of early rhythm control in improving clinical outcomes in patients with atrial fibrillation: a systematic review and meta-analysis

BackgroundCurrent guidelines recommend rhythm control for improving symptoms and quality of life in symptomatic patients with atrial fibrillation (AF). However, the long-term prognostic outcomes of rhythm control compared with rate control are still inconclusive. In this meta-analysis, we aimed to assess the effects of early rhythm control compared with rate control on clinical outcomes in newly diagnosed AF patients.MethodsWe systematically searched the PubMed and Embase databases up to August 2022 for randomized and observational studies reporting the associations of early rhythm control (defined as within 12 months of AF diagnosis) with effectiveness outcomes. The primary outcome was a composite of death, stroke, admission to hospital for heart failure (HF), or acute coronary syndrome (ACS). Hazard ratios (HRs) and 95% confidence intervals (CIs) from each study were pooled using a random-effects model, complemented with an inverse variance heterogeneity or quality effects model.ResultsA total of 8 studies involving 447,202 AF patients were included, and 23.5% of participants underwent an early rhythm-control therapy. In the pooled analysis using the random-effects model, compared with rate control, the early rhythm-control strategy was significantly associated with reductions in the primary composite outcome (HR = 0.88, 95% CI: 0.86–0.89) and secondary outcomes, including stroke or systemic embolism (HR = 0.78, 95% CI: 0.71–0.85), ischemic stroke (HR = 0.81, 95% CI: 0.69–0.94), cardiovascular death (HR = 0.83, 95% CI: 0.70–0.99), HF hospitalization (HR = 0.90, 95% CI: 0.88–0.92), and ACS (HR = 0.86, 95% CI: 0.76–0.98). Reanalyses using the inverse variance heterogeneity or quality effects model yielded similar results.ConclusionsOur current meta-analysis suggested that early initiation of rhythm control treatment was associated with improved adverse effectiveness outcomes in patients who had been diagnosed with AF within 1 year.RegistrationThe study protocol was registered to PROSPERO (CRD42021295405).

Should studies with no events in both arms be excluded in evidence synthesis?

ObjectivesIn safety assessment, studies with no events are a frequent occurrence when conducting meta-analyses. The current approach in meta-analysis is to exclude double-zero studies from the synthesis. In this study, we compared the performance of excluding and including double-zero studies. MethodsA simulation with 5000 iterations was conducted based on the real-world dataset from Cochrane reviews. The true distribution of the rare events rather than normal distribution for the effects were used in the data generating mechanism to simulate aggregate meta-analysis data. We used Doi's inverse variance heterogeneity (IVhet) model for the meta-analyses with continuity correction (of 0.5) to include double-zero studies and used the odds ratio effect size. The performance of including versus excluding double-zero studies were then compared. ResultsGenerally, there was much larger mean squared error when double zero studies were excluded than when double-zero studies were included. The coverage when studies were excluded rapidly deteriorates as heterogeneity increased, while remained at or above the nominal level when double-zero studies were included. When there were very few double-zero studies, the performances was almost the same when including or excluding these studies. Subgroup analysis showed that, even for meta-analyses with unbalanced sample size across the two arms, including double-zero studies improved performance compared to when they were excluded. ConclusionsIncluding double-zero studies in meta-analysis improved performance substantively when compared to excluding them, especially when the proportion of double-zero studies was large. Continuity correction with use of the IVhet model is therefore a good solution to deal with double-zero studies and should be considered in future meta-analyses.

Representation of adults with rheumatoid arthritis in US-based randomized controlled exercise trials: a systematic review with meta-analysis.

The purpose of this study was to conduct a systematic review with meta-analysis to determine the representation of adults with rheumatoid arthritis (RA) according to sex, race, and ethnicity in exercise randomized controlled trials (RCTs) conducted in the USA. Exercise RCTs ≥ 4weeks conducted in the USA in adults ≥ 18years with RA were eligible. Studies were retrieved by searching six electronic databases, cross-referencing and searching a clinical trials registry. Dual, independent, study selection and data abstraction were conducted. The primary outcomes were the proportion of participants in each study according to sex as well as race/ethnicity. Results were pooled meta-analytically using the inverse-variance heterogeneity (IVhet) model after applying the double-arcsine transformation. Of the 1030 unique articles screened, five RCTs representing 353 participants with RA were included. The pooled participant prevalence was 83% (95% CI = 73 to 92%) for women and 17% (95% CI = 8 to 27%) for men, suggesting an over-representation of women and an under-representation of men by approximately 7.4% based on current prevalence US estimates for each. Qualitative examination for race and ethnicity demonstrated an under-representation of racial/ethnic minority groups. There is a lack of representation of men with RA in US-based randomized controlled exercise intervention studies. Additional US-based randomized controlled exercise trials, including greater inclusion and reporting of the racial/ethnic composition of participants, are also needed. Key Points • This systematic review with meta-analysis of US studies found an under-representation of men in randomized controlled trials examining the effects of exercise in those with rheumatoid arthritis (RA). • Qualitative examination according to race/ethnicity found both a lack of reporting as well as under-representation of selected racial/ethnic minorities in US-based randomized controlled exercise studies among adults with RA. • This study highlights the need for additional US-based randomized controlled trials of exercise in adults with RA that better represent the RA population in the USA.

Inter-individual Differences In Anxiety As A Result Of Aerobic Exercise In Adults With Fibromyalgia: Meta-analysis

It is unknown whether true inter-individual response differences (IIRD) exist with respect to changes in anxiety as a result of aerobic exercise training in adults with fibromyalgia (FM). PURPOSE: Determine whether true IIRD exist with respect to changes in anxiety as a result of aerobic exercise training in adults with FM. METHODS: Data from a previous as well as updated meta-analytic database of randomized controlled trials of exercise in adults with arthritis and other rheumatic diseases were sourced. Randomized controlled trials limited to aerobic exercise training on anxiety in adults >18 years of age with FM were included. Change outcome standard deviations treated as point estimates for anxiety were used to calculate true IIRD from each study. In addition, treatment effect data were extracted. The inverse variance heterogeneity (IVhet) model was used to pool all results. RESULTS: For the five studies and 321 participants in which results were pooled, statistically significant treatment effect reductions in anxiety were observed (Mean, -0.77 points, 95% CI, -1.25 to -0.77). However, no significant IIRD were found (Mean, 0.6 points, 95% confidence interval, -1.2 to 1.5). The 95% prediction interval for true IIRD in a future study was -1.7 to 0.8. The percent chance, i.e., probability, of a clinically meaningful difference in variability, i.e., IIRD, was 61.5% (only possibly clinically important). CONCLUSION: While aerobic exercise is associated with reductions in anxiety among adults with fibromyalgia, there is currently a lack of convincing evidence to support the notion that true IIRD exist. Therefore, a search for potential mediators and moderators associated with aerobic exercise and changes in anxiety among adults with FM may not be warranted. However, additional research is needed before any true level of certainty can be established. This includes (1) the assessment of IIRD in future randomized controlled trials, (2) randomized controlled trials of longer duration, and (3) an increase in the proportion of men included in randomized controlled trials.

The Analgesic Efficacy of Ultrasound-guided Quadratus Lumborum Block Transmuscular or Posterior Approach After Hip Surgery: A Systematic Review and Meta-analysis with Trial Sequential Analysis.

No review or meta-analysis exists to elucidate the efficacy and safety of quadratus lumborum block (QLB) on the pain intensity, opioid requirement, and mobilization in patients undergoing hip surgery. This systematic review and meta-analysis of randomized controlled trials were designed to compare QLB with no block or placebo (without other nerve/plexus blocks) for patients undergoing hip surgery. Two individual researchers conducted the platform searches on the PubMed, Cochrane Library, and Embase databases from inception to June 12, 2021. Only English publications were included. The pain at rest score at 12 postoperative hours was designated as the primary outcome. Secondary outcomes included rest pain at rest scores at 6 and 24 postoperative hours, dynamic pain score at 6, 12, and 24 postoperative hours, total opioid consumption, postoperative nausea and vomiting, and patient satisfaction. Seven trials including 514 patients were included. When compared with controls, the QLB technique significantly reduced pain at rest scores at 12 hours after surgery (mean difference -1.15, -1.52 to -0.77, P <0.0001). The secondary outcomes were limited by heterogeneity: secondary pain outcomes and opioid consumption were consistently improved with QLB ( P <0.05); patient satisfaction and postoperative nausea and vomiting were similar between the groups based on the Inverse Variance Heterogeneity model ( P >0.05). The overall quality of evidence was moderate. There is moderate evidence that QLB employment in hip surgery produces significant reduction in pain scores and opioid consumption within 24 hours. QLB appears to be an appropriate option for postoperative analgesia after hip surgery.

Precision-based exercise in people with anxiety and stress related disorders: Are there interindividual differences in anxiolytic effects? An ancillary meta-analysis of randomized controlled trials

Interest in the individualized responses to exercise has been growing within mental health care and psychiatry. This meta-analysis examined if true interindividual differences (IIDs) in anxiolytic effects of exercise exist among adults with anxiety- and stress-related disorders. Data were extracted from a previous meta-analysis of randomized controlled trials (RCTs) and searches in CINAHL, Embase and Medline were updated (8 arms from 7 original studies, n participants=322). Change outcome standard deviations treated as point estimates for anxiety were extracted to calculate true IIDs. Inverse variance heterogeneity and restricted maximum likelihood models were used. Aerobic exercise and resistance training showed significant anxiolytic effects. No significant pooled IIDs were found for aerobic exercise nor resistance training demonstrating that there is currently a lack of convincing evidence to support the notion that true IIDs exist for the anxiolytic effects of exercise among adults with anxiety- and stress-related disorders. Consequently, clinical practice can focus on general population physical activity guidelines for patients with anxiety- and stress-related disorders rather than aiming for highly specific, individualized recommendations. Future research could prioritize investigating how to motivate patients with anxiety- and stress-related disorders to meet general population physical activity guidelines.