Multivariate Meta-regression Analysis Research Articles

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis

Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. The Key Research and Development Program of China.

DOSE-RESPONSE EFFECT OF SODIUM REDUCTION ON BLOOD PRSSURE IN TREATED HYPERTENSIVES: A SYSTEMATIC REVIEW AND INSTRUMENTAL VARIABLE META-ANALYSIS

Objective: To evaluate the dose-response effects of a reduction in dietary sodium intake on blood pressure (BP) in hypertensive individuals who were on antihypertensive treatments. The impact of antihypertensive-drug class was also examined. Design and method: We searched Medline (via Ovid), Embase, Scopus, Cochrane Central Register of Controlled Trials, and reference lists of relevant articles up to 12 November 2023. We included randomised controlled trials (RCTs) comparing the effect on BP between different levels of dietary sodium intake in adults who were diagnosed as primary hypertension and treated with constant antihypertensive medications during the study period. We excluded RCTs with duration < 2 weeks. Dietary sodium intake was measured using 24-hour urinary sodium excretion. Instrumental variable meta-analyses were conducted to evaluate the dose-response effects of sodium reduction on BP. Subgroup analysis and multivariate meta-regression analysis were performed to examine the impact of antihypertensive-drug class. Results: 35 studies with 2885 participants were included. The pooled estimates of mean reduction in 24-hour urinary sodium excretion, systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were 68.74 (95% confidence interval: 62.30-75.19) mmol, 4.33 (3.37-5.29) mmHg, 2.60 mm Hg (2.04-3.17), and 3.19 (2.50-3.87), respectively. For every 100 mmol reduction in 24-hour urinary sodium excretion, SBP, DBP, and MAP decreased by 6.81 (4.96-8.66) mmHg, 3.85 (2.26-5.43) mmHg, and 4.83 (3.22-6.44) mmHg, respectively (Fig 1). The observed dose-response effects differed across class of antihypertensive medication (P-diff = 0.084 for SBP, and P-diff<0.05 for DBP and MAP). In Beta-blockers, Renin-Angiotensin-Aldosterone System (RAAS) inhibitors, and dual therapy groups, significant dose-response effects of sodium on SBP, DBP and MAP were observed. In Calcium Chanel Blockers (CCB) group, the dose-response relationship was only found for SBP. No dose-response effect on BP was observed in diuretics monotherapy group. Conclusions: Pooled evidence of RCTs suggests a dose-response relationship between sodium reduction and BP in treated hypertensives, which is impacted by class of antihypertensive medications.

Outcomes predictors in endoscopic ultrasound-guided choledochoduodenostomy with lumen-apposing metal stent: Systematic review and meta-analysis.

Background and study aims EUS-guided choledochoduodenostomy (EUS-CDS) is a minimally invasive procedure used to treat malignant biliary obstruction (MBO) by transduodenal placement of a lumen-apposing metal stent (LAMS) into the extrahepatic bile duct. To identify factors that contribute to safe and effective EUS-CDS using LAMS, we performed a systematic review of the literature and meta-analysis. Methods The methodology of our analysis was based on PRISMA recommendations. Electronic databases (Medline, Scopus, EMBASE) were searched up to November 2022. Full articles that included patients with distal malignant biliary obstruction who underwent EUS-CDS using LAMS after failed endoscopic retrograde cholangiopancreatography were eligible. Random-effect meta-analysis was performed reporting pooled rates of technical success, clinical success, and adverse events (AEs) by means of a random model. Multivariate meta-regression and subgroup analysis were performed to assess possible associations between the outcomes and selected variables to assess the correlation between outcomes and different variables. Results were also stratified according to stent size. Results Twelve studies with 845 patients were included in the meta-analysis. Pooled technical and clinical success rates were 96% (95% confidence interval [CI] 94%-98%; I 2 = 52.29%) and 96% (95%CI 95%-98%), respectively, with no significant association with baseline characteristics, such are sex, age, common bile duct diameter, or stent size. The pooled AE rate was 12% (95%CI: 8%-16%; I 2 = 71.62%). The AE rate was significantly lower when using an 8 × 8 mm stent as compared with a 6 × 8 mm LAMS (odds ratio 0.59, 0.35-0.99; P = 0.04), with no evidence of heterogeneity (I 2 = 0%). Conclusions EUS-CDS with LAMS is a safe and effective option for relief of MBO. Selecting an appropriate stent size is crucial for achieving optimal safety outcomes.

Effectiveness of lifestyle interventions to promote physical activity on glycated hemoglobin and physical activity in type 2 diabetes patients - Systematic review with meta-analysis

Introduction
 An increase in Type 2 diabetes (T2D) cases worldwide can be attributed to the prevalence of an unhealthy lifestyle. Engaging in regular exercise can significantly benefit individuals with T2D (Colberg et al., 2016). A multitude of studies have explored this impact through controlled exercise interventions (Hou et al., 2023). Nevertheless, our understanding of how lifestyle interventions can effectively promote physical activity (PA) and positively influence the progression of T2D in practical, real-world scenarios remains limited. The objective of this systematic review with meta-analysis is to investigate the impact of lifestyle interventions targeting the promotion of PA on glycated hemoglobin (HbA1c) levels and PA outcomes. Furthermore, the aim is to examine whether lifestyle interventions influence PA and therefore HbA1c.
 Methods
 We searched three databases (MEDLINE via PubMed, PsycINFO, and SPORTdiscus) using the expanded search strategy of “Type 2 diabetes” AND “lifestyle intervention” AND “randomized controlled trial” AND “physical activity” AND “HEMOGLOBIN A1C”. In order to provide a comprehensive overview, we examine the design of the studies and the structure of the lifestyle interventions. To address the aim of this study, we conducted a meta-analysis with the outcomes PA and HbA1c. Moreover, we performed a multivariate meta-regression analysis to explore the impact of the moderator variable, PA, on the study effect sizes of HbA1c.
 Results
 This review incorporated 12 studies (n = 2513 patients), exploring multiple lifestyle interventions with heterogeneity in design, components, and duration. Regarding PA outcomes, we found an increase in PA (g = 0.33, 95% CI = 0.21,0.45), with no disparity between objective and self-reported measurements of PA. For HbA1c, the effect size was g = -0.07 (95% CI -0.17,0.04). In multivariate meta-regression, the intercept was 0.004 (SE = 0.06, 95% CI -0.11,0.12), and the PA coefficient as a moderator was -0.05 (SE = 0.06, 95% CI -0.18,0.07). These findings suggest that physical activity does not act as a moderator for changes in HbA1c in the examined studies.
 Discussion/Conclusion
 The studies showed a small effect in increasing PA. Lifestyle interventions had no relevant impact on HbA1c compared to control conditions, and the role of PA as a moderator was inconclusive. Further research is required to determine if structured exercise programs, known for positively affecting HbA1c, could be a better alternative to lifestyle interventions for individuals with T2D. Additionally, there is a need to investigate ways to enhance the efficacy of lifestyle interventions in influencing PA and HbA1c levels.
 References
 Colberg, S. R., Sigal, R. J., Yardley, J. E., Riddell, M. C., Dunstan, D. W., Dempsey, P. C., Horton, E. S., Castorino, K., & Tate, D. F. (2016). Physical activity/exercise and diabetes: A position statement of the American Diabetes Association. Diabetes Care, 39(11), 2065-2079. https://doi.org/10.2337/dc16-1728
 Hou, L., Wang, Q., Pan, B., Li, R., Li, Y., He, J., Qin, T., Cao, L., Zhang, N., & Cao, C. (2023). Exercise modalities for type 2 diabetes: A systematic review and network meta‐analysis of randomized trials. Diabetes/Metabolism Research and Reviews, 39(1), Article e3591. https://doi.org/10.1002/dmrr.3591

Implications of Preoperative Depression for Lumbar Spine Surgery Outcomes

Comorbid depression is common among patients with degenerative lumbar spine disease. Although a well-researched topic, the evidence of the role of depression in spine surgery outcomes remains inconclusive. To investigate the association between preoperative depression and patient-reported outcome measures (PROMs) after lumbar spine surgery. A systematic search of PubMed, Cochrane Database of Systematic Reviews, Embase, Scopus, PsychInfo, Web of Science, and ClinicalTrials.gov was performed from database inception to September 14, 2023. Included studies involved adults undergoing lumbar spine surgery and compared PROMs in patients with vs those without depression. Studies evaluating the correlation between preoperative depression and disease severity were also included. All data were independently extracted by 2 authors and independently verified by a third author. Study quality was assessed using Newcastle-Ottawa Scale. Random-effects meta-analysis was used to synthesize data, and I2 was used to assess heterogeneity. Metaregression was performed to identify factors explaining the heterogeneity. The primary outcome was the standardized mean difference (SMD) of change from preoperative baseline to postoperative follow-up in PROMs of disability, pain, and physical function for patients with vs without depression. Secondary outcomes were preoperative and postoperative differences in absolute disease severity for these 2 patient populations. Of the 8459 articles identified, 44 were included in the analysis. These studies involved 21 452 patients with a mean (SD) age of 57 (8) years and included 11 747 females (55%). Among these studies, the median (range) follow-up duration was 12 (6-120) months. The pooled estimates of disability, pain, and physical function showed that patients with depression experienced a greater magnitude of improvement compared with patients without depression, but this difference was not significant (SMD, 0.04 [95% CI, -0.02 to 0.10]; I2 = 75%; P = .21). Nonetheless, patients with depression presented with worse preoperative disease severity in disability, pain, and physical function (SMD, -0.52 [95% CI, -0.62 to -0.41]; I2 = 89%; P < .001), which remained worse postoperatively (SMD, -0.52 [95% CI, -0.75 to -0.28]; I2 = 98%; P < .001). There was no significant correlation between depression severity and the primary outcome. A multivariable metaregression analysis suggested that age, sex (male to female ratio), percentage of comorbidities, and follow-up attrition were significant sources of variance. Results of this systematic review and meta-analysis suggested that, although patients with depression had worse disease severity both before and after surgery compared with patients without depression, they had significant potential for recovery in disability, pain, and physical function. Further investigations are needed to examine the association between spine-related disability and depression as well as the role of perioperative mental health treatments.

Outcomes in people with eating disorders: a transdiagnostic and disorder-specific systematic review, meta-analysis and multivariable meta-regression analysis.

Eating disorders (EDs) are known to be associated with high mortality and often chronic and severe course, but a recent comprehensive systematic review of their outcomes is currently missing. In the present systematic review and meta-analysis, we examined cohort studies and clinical trials published between 1980 and 2021 that reported, for DSM/ICD-defined EDs, overall ED outcomes (i.e., recovery, improvement and relapse, all-cause and ED-related hospitalization, and chronicity); the same outcomes related to purging, binge eating and body weight status; as well as mortality. We included 415 studies (N=88,372, mean age: 25.7±6.9 years, females: 72.4%, mean follow-up: 38.3±76.5 months), conducted in persons with anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), other specified feeding and eating disorders (OSFED), and/or mixed EDs, from all continents except Africa. In all EDs pooled together, overall recovery occurred in 46% of patients (95% CI: 44-49, n=283, mean follow-up: 44.9±62.8 months, no significant ED-group difference). The recovery rate was 42% at <2 years, 43% at 2 to <4 years, 54% at 4 to <6 years, 59% at 6 to <8 years, 64% at 8 to <10 years, and 67% at ≥10 years. Overall chronicity occurred in 25% of patients (95% CI: 23-29, n=170, mean follow-up: 59.3±71.2 months, no significant ED-group difference). The chronicity rate was 33% at <2 years, 40% at 2 to <4 years, 23% at 4 to <6 years, 25% at 6 to <8 years, 12% at 8 to <10 years, and 18% at ≥10 years. Mortality occurred in 0.4% of patients (95% CI: 0.2-0.7, n=214, mean follow-up: 72.2±117.7 months, no significant ED-group difference). Considering observational studies, the mortality rate was 5.2 deaths/1,000 person-years (95% CI: 4.4-6.1, n=167, mean follow-up: 88.7±120.5 months; significant difference among EDs: p<0.01, range: from 8.2 for mixed ED to 3.4 for BN). Hospitalization occurred in 26% of patients (95% CI: 18-36, n=18, mean follow-up: 43.2±41.6 months; significant difference among EDs: p<0.001, range: from 32% for AN to 4% for BN). Regarding diagnostic migration, 8% of patients with AN migrated to BN and 16% to OSFED; 2% of patients with BN migrated to AN, 5% to BED, and 19% to OSFED; 9% of patients with BED migrated to BN and 19% to OSFED; 7% of patients with OSFED migrated to AN and 10% to BN. Children/adolescents had more favorable outcomes across and within EDs than adults. Self-injurious behaviors were associated with lower recovery rates in pooled EDs. A higher socio-demographic index moderated lower recovery and higher chronicity in AN across countries. Specific treatments associated with higher recovery rates were family-based therapy, cognitive-behavioral therapy (CBT), psychodynamic therapy, and nutritional interventions for AN; self-help, CBT, dialectical behavioral therapy (DBT), psychodynamic therapy, nutritional and pharmacological treatments for BN; CBT, nutritional and pharmacological interventions, and DBT for BED; and CBT and psychodynamic therapy for OSFED. In AN, pharmacological treatment was associated with lower recovery, and waiting list with higher mortality. These results should inform future research, clinical practice and health service organization for persons with EDs.

Clinical and biochemical outcomes after adrenalectomy for primary aldosteronism in tertiary and quaternary referral centers: data from SOPRANO study.

Hypertension cure following adrenalectomy in unilateral primary aldosteronism (PA) remains uncertain. Previous meta-analyses have shown highly variable surgical outcomes. Our study aimed to determine the unknown proportion of complete clinical and biochemical success in tertiary and quaternary referral centers. We conducted a systematic review and meta-analysis of studies reporting surgical outcomes of unilateral PA patients within the Surgical Outcome of PRimary Aldosteronism progNostic mOdels (SOPRANO) study. From 27 publications we identified 32 eligible studies, of which 22 were judged to be at low risk of bias. Eighteen were single-center studies, while fourteen were multi-center studies, with patients recruited from 132 referral centers worldwide. Adrenalectomy was performed on 5887 patients, with 4861 (83%) included in the final analysis. The pooled estimates of complete clinical and biochemical success for all studies were 39% (95% CI: 34-44%) and 99% (95% CI: 96-99%), respectively, similar to that found for studies at low risk of bias. Multivariate meta-regression analyses for all studies and low-bias risk studies revealed that BMI (P < 0.01), recruitment time period (P < 0.01), and hypertension duration (P < 0.05) inversely correlated with complete clinical success, while BMI (P < 0.05) and the number of enrolled centers (P < 0.05) inversely correlated with complete biochemical success. In summary, our findings offer robust estimates of complete clinical and biochemical success rates following adrenalectomy for unilateral PA in tertiary and quaternary referral centers and identify new potential effect modifiers that can help clinicians to inform and counsel patients about post-surgery expectations, guaranteeing effective treatment and ultimately enhancing outcomes.

Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022

Background & AimsWe aimed to assess the secular trend of the global prevalence of H. pylori infection in adults and children/adolescence and to show its relation to that of gastric cancer incidence. MethodsWe performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. ResultsOf the 16,976 articles screened, a total of 1,748 articles from 111 countries were eligible for analysis. The crude global prevalence of H. pylori has reduced from 52.6% (95% CI 49.6-55.6) before 1990 to 43.9% (95% CI: 42.3-45.5) in adults during 2015-2022, but was as still as high as 35.1% (95% CI: 30.5 -40.1) in children and adolescents during 2015-2022. Secular trend and multivariate regression analyses showed that the global prevalence of H. pylori has declined by 15.9% (95% CI -20.5 to -11.3) over the last three decades in adults, but not in children and adolescence. Significant reduction of H. pylori prevalence was observed in adults in the Western-Pacific, South-East Asian, and African regions. However, there was no significant reduction of the H. pylori prevalence in children and adolescence in any WHO regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H. pylori infection has declined. ConclusionsThe global prevalence of H. pylori infection has declined during the last three decades in adults, but not in children and adolescence. The results raised the hypothesis that public health drive to reduce the prevalence of H. pylori as a strategy to reduce the incidence of gastric cancer in the population, which should be confirmed in large scale clinical trials.

Histological Chorioamnionitis and Funisitis as New Risk Factors for Retinopathy of Prematurity: A Meta-analysis.

The role of placental inflammation in neonatal morbidities is underestimated due to lack of placental examination. This meta-analysis aims to assess the association between histological chorioamnionitis (HCA) with and without funisitis (FUN) and risk of retinopathy of prematurity (ROP). Forty-five studies reporting (unadjusted) data on HCA without FUN and HCA with FUN in neonates with ROP were included. Primary outcomes were any stage ROP and severe ROP. Potential confounders explored were gestational age (GA) at birth, birthweight, maternal steroid use, necrotizing enterocolitis, sepsis (suspected/proven) and mechanical ventilation duration. Neonates with HCA had increased risk for any stage ROP (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.4) and severe ROP (OR 1.5; 95% CI 1.2-1.8) compared with neonates without HCA. The rates of any stage ROP (OR 1.8; 95% CI 1.4-2.2) and severe ROP (OR 1.4; 95% CI 1.1-1.6) were higher in neonates with FUN compared with neonates without FUN. Multivariate meta-regression analysis suggests that lower GA increases the effect size between FUN and severe ROP. This meta-analysis confirms that presence of HCA and FUN are risk factors for any stage ROP and severe ROP. Structured histological placental examination of HCA and FUN may be a tool to further refine the ROP risk profile. · This systematic review confirms that HCA is a risk factor for ROP.. · This meta-analysis reveals that FUN results in an even higher risk for developing ROP.. · Placental examination of HCA/FUN may be a tool to further refine the ROP risk profile..

Acceptance and Commitment Therapy Among Informal Caregivers of People With Chronic Health Conditions

Although there is substantial evidence to suggest the health benefits of acceptance and commitment therapy (ACT) among informal caregivers of people with chronic health conditions, the great variation in intervention designs among published studies limits its application. To identify intervention characteristics of ACT that are associated with improved psychological health and to assess the acceptability of ACT among informal caregivers. Seven English- and 3 Chinese-language databases without limits on publication dates, the reference lists of previous reviews, and gray literature were searched up to February 2023. Randomized clinical trials comparing the effect of ACT vs control groups on improving psychological health among informal caregivers. Two reviewers independently screened searched records and extracted data from eligible studies. Random-effects meta-analysis and mixed-effects metaregression were performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. Psychological health outcomes (eg, depressive symptoms) measured by valid measurements and the acceptability of ACT based on identified parameters. A total of 29 studies with 2010 participants, published between 2015 and 2023, were identified. ACT showed moderate to large effect sizes for improving psychological health at postintervention assessments (Hedges g range, -0.55 [95% CI, -0.98 to -0.12] to -1.14 [95% CI, -1.83 to -0.45]) and at 1-to-3-month and 4-to-6-month follow-ups (Hedges g range, -0.47 [95% CI, -0.69 to -0.25] to -1.29 [95% CI, -2.33 to -0.24]). Multivariable metaregression analysis regarding intervention characteristics found that ACT delivered in a mixed individual- and group-based format, face-to-face, or through more intervention sessions was associated with greater improvements for experiential avoidance (face-to-face: β = -1.170 [95% CI, -2.020 to -0.319]; number of sessions: β = -0.242 [95% CI, -0.353 to -0.130]), depressive symptoms (mixed delivery format: β = -2.583 [95% CI, -4.845 to -0.321]; face-to-face: β = -1.555 [95% CI, -3.002 to -0.108]), or anxiety symptoms (face-to-face: β = -1.241 [95% CI, -2.337 to -0.146]). In general, ACT had low attrition rates (11%), and participants' adherence (51%-80%) and satisfactory ratings (72%-95%) lend support to its acceptability. This systematic review and meta-analysis found that ACT was consistently associated with improvements in psychological health, supporting its application to improve informal care for chronic disease management. This review provides specific details on the design parameters of ACT for achieving greater efficacy.

Pharmacokinetics of Cannabidiol: A Systematic Review and Meta-Regression Analysis.

Background: In this review, we provide an updated assessment of available evidence on the pharmacokinetics (PK) of CBD and explore the impact of different factors on PK outcomes. Materials and Methods: This systematic review and meta-regression analysis was preregistered (PROSPERO: CRD42021269857). We systematically searched Medline, Embase, PsycInfo, and Web of Science Core Collection up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute's Quality Assessment Tool for Before-After Studies with no Control Group was used. Random-effects multivariable meta-regression analysis was conducted. Results: A total of 112 trial arms from 39 studies were included; 26 trial arms had a "Good" quality, 70 "Fair," and 16 "Poor." Eight arms used inhalation CBD, 29 oromucosal, 73 oral, and 2 intravenous. CBD formulations could be categorized to nanotech (n=14), oil-based (n=21), alcohol-based (n=10), water-based (n=12), Sativex (n=17), and Epidiolex® (n=22). For single-dose studies, CBD doses ranged between 2 and 100 mg in inhalation, 5-50 mg in oromucosal, and 0.42-6000 mg in oral administration. Sixty-six trial arms had only male participants or a higher number of male than female participants. The duration of the PK session was between 4 and 164 h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared with oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared with the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax. Conclusion: As expected, CBD dose, route of administration, and diet were major determinants of CBD PK with oral routes providing higher bioavailability and nanotechnology formulations a faster onset. Although CBD appeared to have a faster onset and longer duration in women, more studies are required to delineate the role of biological sex. Factors that influence CBD PK have implications for medication development and appropriate dosing in clinical practice.

Prevalence of suicide ideation, self-harm, and suicide among Chinese patients with schizophrenia: a systematic review and meta-analysis.

Suicide ideation, self-harm, and suicide are common in patients with schizophrenia, but the reported prevalence vary largely across studies. Improved prevalence estimates and identification of moderators of the above self-directed violence are needed to enhance recognition and care, and to guide future management and research. This systematic review aims to estimate the pooled prevalence and identify moderators of suicide ideation, self-harm, and suicide among patients diagnosed with schizophrenia in China. Relevant articles published until September 23, 2021, were searched using PubMed, EBSCO, Web of Science, Embase, Science Direct, CNKI, CBM, VIP, and Wanfang databases. Eligible studies published in English or Chinese which reported the prevalence of suicide ideation, self-harm, or suicide among Chinese patients with schizophrenia were collected. All studies passed a quality evaluation. This systematic review was registered with PROSPERO (registration number CRD42020222338). PRISMA guidelines were used in extracting and reporting data. Random-effects meta-analyses were generated using the meta package in R. A total of 40 studies were identified, 20 of which were evaluated as high-quality studies. Based on these studies, the prevalence of lifetime suicide ideation was 19.22% (95% CI: 7.57-34.50%), prevalence of suicide ideation at the time of investigation was 18.06% (95% CI: 6.49-33.67%), prevalence of lifetime self-harm was 15.77% (95% CI: 12.51-19.33%), and prevalence of suicide was 1.49% (95% CI: 0.00-7.95%). Multivariate meta-regression analysis revealed that age (β = - 0.1517, p = 0.0006) and dependency ratio (β = 0.0113, p < 0.0001) were associated with the lifetime prevalence of self-harm. Study assessment score (β = 0.2668, p < 0.0001) and dependency ratio (β = 0.0050, p = 0.0145) were associated with the lifetime prevalence of suicide ideation. Results of the spatial analysis showed that the prevalence of self-directed violence varied greatly across different provinces. This systematic review provides estimates of the prevalence of self-directed violence among Chinese patients with schizophrenia and explores its moderators and spatial patterns. Findings also have important implications for allocating prevention and intervention resources to targeted high-risk populations in high prevalence areas.

Exercise characteristics and blood pressure reduction after combined aerobic and resistance training: a systematic review with meta-analysis and meta-regression.

The purpose of this systematic review with meta-analysis was to determine the efficacy of combined aerobic and strength training in adults with hypertension and the influence of exercise training characteristics on blood pressure (BP) reduction. Randomized clinical trials of interventions involving combined aerobic and strength training versus nonexercise control groups (Control) in adults with hypertension were included. The literature search was conducted on PubMed, Cochrane Central, EMBASE, Scopus, and LILACS until December 2021. A random effects meta-analysis was performed using the mean difference in BP changes from baseline, comparing combined aerobic and strength training vs. Control as the effective measure. A multivariate meta-regression analysis was also performed to evaluate the relationship between exercise training characteristics and magnitudes of BP reductions. Thirty-seven studies with 41 exercise interventions (1942 participants) were analyzed. The pooled mean differences with a 95% confidence interval (95% CI) showed significant reductions in SBP (-6.4 mmHg; 95% CI, -9.1 to -3.6) and DBP (-3.7 mmHg; 95% CI, -4.9 to -2.4). Meta-regression analysis revealed that greater exercise intensity and a greater number of sets in resistance training were associated with greater reductions in SBP. Greater exercise intensity was also associated with greater decreases in DBP. Combined aerobic and resistance training is an effective intervention in reducing both SBP and DBP in adults with hypertension, with greater hypotensive effects expected with higher intensity and more volume.

Global Diabetes Prevalence in COVID-19 Patients and Contribution to COVID-19- Related Severity and Mortality: A Systematic Review and Meta-analysis.

COVID-19 and diabetes both contribute to large global disease burdens. To quantify the prevalence of diabetes in various COVID-19 disease stages and calculate the population attributable fraction (PAF) of diabetes to COVID-19-related severity and mortality. Systematic review identified 729 studies with 29,874,938 COVID-19 patients. Studies detailed the prevalence of diabetes in subjects with known COVID-19 diagnosis and severity. Study information, COVID-19 disease stages, and diabetes prevalence were extracted. The pooled prevalence of diabetes in stratified COVID-19 groups was 14.7% (95% CI 12.5-16.9) among confirmed cases, 10.4% (7.6-13.6) among nonhospitalized cases, 21.4% (20.4-22.5) among hospitalized cases, 11.9% (10.2-13.7) among nonsevere cases, 28.9% (27.0-30.8) among severe cases, and 34.6% (32.8-36.5) among deceased individuals, respectively. Multivariate metaregression analysis explained 53-83% heterogeneity of the pooled prevalence. Based on a modified version of the comparative risk assessment model, we estimated that the overall PAF of diabetes was 9.5% (7.3-11.7) for the presence of severe disease in COVID-19-infected individuals and 16.8% (14.8-18.8) for COVID-19-related deaths. Subgroup analyses demonstrated that countries with high income levels, high health care access and quality index, and low diabetes disease burden had lower PAF of diabetes contributing to COVID-19 severity and death. Most studies had a high risk of bias. The prevalence of diabetes increases with COVID-19 severity, and diabetes accounts for 9.5% of severe COVID-19 cases and 16.8% of deaths, with disparities according to country income, health care access and quality index, and diabetes disease burden.

Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies.

Many observational studies on the use of vedolizumab [VDZ] in patients with Crohn's disease [CD] and ulcerative colitis [UC] have been published in the past few years. We aimed to comprehensively summarise its effectiveness and safety by pooling data only from observational studies. PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalisation, loss of response, VDZ dose escalation, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes. In all, 88 studies comprising 25 678 patients [13 663 with CD and 12 015 with UC] met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC. Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.

Higher Risk of HEV Transmission and Exposure among Blood Donors in Europe and Asia in Comparison to North America: A Meta-Analysis.

The increasing number of diagnosed hepatitis E virus (HEV) infections in Europe has led to the implementation of the testing of blood products in various countries. Many nations have not yet implemented such screening. To assess the need for HEV screening in blood products worldwide, we conducted a systematic review and meta-analysis assessing HEV RNA positivity and anti-HEV seroprevalence in blood donors. Studies reporting anti-HEV IgG/IgM or HEV RNA positivity rates among blood donors worldwide were identified via predefined search terms in PubMed and Scopus. Estimates were calculated by pooling study data with multivariable linear mixed-effects metaregression analysis. A total of 157 (14%) of 1144 studies were included in the final analysis. The estimated HEV PCR positivity rate ranged from 0.01 to 0.14% worldwide, with strikingly higher rates in Asia (0.14%) and Europe (0.10%) in comparison to North America (0.01%). In line with this, anti-HEV IgG seroprevalence in North America (13%) was lower than that in Europe (19%). Our data demonstrate large regional differences regarding the risk of HEV exposure and blood-borne HEV transmission. Considering the cost-benefit ratio, this supports blood product screening in high endemic areas, such as Europe and Asia, in contrast to low endemic regions, such as the U.S.

P727 Effectiveness and Safety of Vedolizumab in Inflammatory Bowel Disease: A Comprehensive Meta-analysis of Observational Studies

Abstract Background Many observational studies on the use of vedolizumab (VDZ) in patients with Crohn’s disease (CD) and ulcerative colitis (UC) have been published in the last few years. We aimed to comprehensively summarize its effectiveness and safety by pooling data only from observational studies. Methods PubMed/Medline and Embase were systematically searched for observational studies on patients with CD and UC treated with VDZ through December 2021. The rates of clinical remission and overall adverse events were the primary outcomes. The rates of steroid-free clinical remission, clinical response, mucosal healing, C-reactive protein normalization, loss of response, colectomy, serious adverse events, infections, and malignancies were considered as secondary outcomes. Results Eighty-eight studies comprising 25,678 patients (13,663 with CD and 12,015 with UC) met the inclusion criteria. In patients with CD, the pooled estimate rates of clinical remission were 36% at induction and 39% at maintenance. In patients with UC, the pooled estimate rates of clinical remission were 40% at induction and 45% at maintenance. The pooled estimate of incidence rate of adverse events was 34.6 per 100 person-years. At multivariable meta-regression analysis, studies with increased male proportion were independently associated with higher rates of clinical remission and steroid-free clinical remission at both induction and maintenance, and clinical response at maintenance in patients with CD. Studies with increased disease duration were independently associated with higher mucosal healing rates at maintenance in patients with UC. Conclusion Observational studies demonstrated extensively the effectiveness of VDZ, with a reassuring safety profile.

Improving acupuncture research: progress, guidance, and future directions

This paper makes an interpretation of the collection Acupuncture: how to improve the evidence base published by BMJ & BMJ Open. Studies show that the quality of randomized controlled trial (RCT) of acupuncture is low, and multivariable Meta-regression analysis fails to confirm most factors commonly believed to influence the effect of acupuncture. The methodological challenges in design and conduct of RCT in acupuncture were analyzed, and a consensus on how to design high-quality acupuncture RCT was developed. The number of acupuncture systematic reviews was huge but the evidence was underused in clinical practice and health policy, and a large number of western clinical practice guidelines recommended acupuncture therapy, but the usefulness of recommendations needed to be improved. In view of the problems in clinical research on acupuncture mentioned in this collection, combined with the analysis of the purpose of clinical research on acupuncture, perspectives, study types, as well as the relationship between evidence and clinical decision-making, a five-stage study paradigm of clinical research on acupuncture is proposed.

Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

With the development and introduction of immune checkpoint inhibitors (ICIs) in cancer patients, immune-related side effects have increasingly attracted attention. However, the risks of immune-related renal toxicity are poorly characterized. In this study, we performed a network meta-analysis (NMA) of ICI-related randomized clinical trials (RCTs) to elucidate the comparative risk of acute kidney injury (AKI) in cancer patients receiving different ICIs. We also sought to identify other factors potentially affecting the risk of AKI. PubMed and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May 2021. Eligible studies were RCTs studying ICIs in cancer patients and reporting AKI data. We performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment groups. We also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct meta-analysis. Once significant heterogeneity was detected in a traditional direct meta-analysis, multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI. A total of 85 RCTs were included in this study. In the NMA for the risk of grade 1-5 and 3-5 AKI, ipilimumab showed a significantly higher risk than avelumab and durvalumab, whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab (N1I3) showed a significantly higher risk than other groups. In terms of treatment ranking, durvalumab ± low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI, whereas N1I3, ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 AKI. Compared with other cancers, renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of AKI. The incidence of AKI was significantly higher with ICI+chemotherapy than with ICI monotherapy. In this NMA involving large-scale up-to-date ICI trials, we demonstrated the comparative safety of existing ICI drugs for grade 1-5 and grade 3-5 AKI. Based on data from the ICI arms of these trials, we also revealed several potential risk factors for immune-related AKI, including tumor type and treatment paradigm.

Prevalence of Falls among Older Adults in Africa : A Meta-Analysis

The purpose of this study was to conduct a meta-analysis of studies that have examined the prevalence of falls among older adults living in Africa. Three investigators independently searched the databases of PubMed, EMBASE, Google Scholar, and Web of Science from their inception date until September 2019. Participants were 5,815 older adults aged 60 years and above. The prevalence of falls was determined using the random effects meta-analysis, whereas meta-regression was conducted to investigate the moderating factors. Eleven of the 921 potentially relevant studies met the inclusion criteria and were included in the meta-analysis. The meta-analysis revealed a pooled prevalence of fall rate of 24.2% (95% CI: 23.1%-25.3%, I2 = 95.2%). Multivariate meta-regression analysis found no moderating effects of study sub-region, study year, and sample size on fall prevalence (p values &gt; 0.05). Falls among older adults living in Africa are common and therefore need continuous research to examine the possible risk factors associated with falls among older adults and to establish effective policies and prevention approaches to reduce risk.