Pooled Effect Estimates Research Articles

Cardiorespiratory Fitness and Physical Activity in Pediatric Diabetes

It is unclear whether cardiorespiratory fitness (CRF) and physical activity are lower among youths with type 1 diabetes (T1D) and type 2 diabetes (T2D) compared with youths without diabetes. To describe the magnitude, precision, and constancy of the differences in CRF and physical activity among youths with and without diabetes. MEDLINE, Embase, CINAHL, and SPORTDiscus were searched from January 1, 2000, to May 1, 2022, for eligible studies. Observational studies with measures of CRF and physical activity in children and adolescents aged 18 years or younger with T1D or T2D and a control group were included. Data extraction was completed by 2 independent reviewers. A random-effects meta-analysis model was used to estimate differences in main outcomes. The pooled effect estimate was measured as standardized mean differences (SMDs) with 95% CIs. The Preferred Reporting Items for Systematic Review and Meta-Analyses guideline was followed. The main outcomes were objectively measured CRF obtained from a graded maximal exercise test and subjective or objective measures of physical activity. Subgroup analyses were performed for weight status and measurement type for outcome measures. Of 7857 unique citations retrieved, 9 studies (755 participants) with measures of CRF and 9 studies (1233 participants) with measures of physical activity for youths with T2D were included; for youths with T1D, 23 studies with measures of CRF (2082 participants) and 36 studies with measures of PA (12 196 participants) were included. Random-effects models revealed that directly measured CRF was lower in youths with T2D (SMD, -1.06; 95% CI, -1.57 to -0.56; I2 = 84%; 9 studies; 755 participants) and in youths with T1D (SMD, -0.39; 95% CI, -0.70 to -0.09; I2 = 89%; 22 studies; 2082 participants) compared with controls. Random-effects models revealed that daily physical activity was marginally lower in youths with T1D (SMD, -0.29; 95% CI, -0.46 to -0.11; I2 = 89%; 31 studies; 12 196 participants) but not different among youths with T2D (SMD, -0.56; 95% CI, -1.28 to 0.16; I2 = 91%; 9 studies; 1233 participants) compared with controls. When analyses were restricted to studies with objective measures, physical activity was significantly lower in youths with T2D (SMD, -0.71; 95% CI, -1.36 to -0.05; I2 = 23%; 3 studies; 332 participants) and T1D (SMD, -0.67; 95% CI, -1.17 to -0.17; I2 = 93%; 12 studies; 1357 participants) compared with controls. These findings suggest that deficits in CRF may be larger and more consistent in youths with T2D compared with youths with T1D, suggesting an increased risk for cardiovascular disease-related morbidity in adolescents with diabetes, particularly among those with T2D. The findings reinforce calls for novel interventions to empower youths living with diabetes to engage in regular physical activity and increase their CRF.

A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of − 0.11 (95% CI − 0.15, − 0.07, Z = 5.45; P < 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.

Sustainable diets and risk of overweight and obesity: A systematic review and meta-analysis.

Sustainable diets are gaining interest as a possible approach to tackle climate change and the global extent of obesity. Yet, the association between sustainable diets and adiposity remains unclear. We performed a systematic review and meta-analysis, calculating summary relative risks and 95% confidence intervals (CI). We pooled maximally adjusted risk estimates, assessed heterogeneity and publication bias, calculated the E-value, and evaluated the risk of bias across the included studies. A total of eight studies were eligible for analysis. Comparing the highest versus the lowest levels of adherence to sustainable diets, the pooled effect estimate was 0.69 (95% CI =0.62-0.76) for overweight and 0.61 (95% CI =0.47-0.78) for obesity. These results suggest that sustainable diets may decrease the risk of overweight/obesity and therefore could serve as enablers for improving both public and planetary health. An agreed-upon clear definition of sustainable diets would enhance the comparability of future studies in this area.

Bayesian meta-analysis for evaluating treatment effectiveness in biomarker subgroups using trials of mixed patient populations.

During drug development, evidence can emerge to suggest a treatment is more effective in a specific patient subgroup. Whilst early trials may be conducted in biomarker-mixed populations, later trials are more likely to enroll biomarker-positive patients alone, thus leading to trials of the same treatment investigated in different populations. When conducting a meta-analysis, a conservative approach would be to combine only trials conducted in the biomarker-positive subgroup. However, this discards potentially useful information on treatment effects in the biomarker-positive subgroup concealed within observed treatment effects in biomarker-mixed populations. We extend standard random-effects meta-analysis to combine treatment effects obtained from trials with different populations to estimate pooled treatment effects in a biomarker subgroup of interest. The model assumes a systematic difference in treatment effects between biomarker-positive and biomarker-negative subgroups, which is estimated from trials which report either or both treatment effects. The systematic difference and proportion of biomarker-negative patients in biomarker-mixed studies are used to interpolate treatment effects in the biomarker-positive subgroup from observed treatment effects in the biomarker-mixed population. The developed methods are applied to an illustrative example in metastatic colorectal cancer and evaluated in a simulation study. In the example, the developed method improved precision of the pooled treatment effect estimate compared with standard random-effects meta-analysis of trials investigating only biomarker-positive patients. The simulation study confirmed that when the systematic difference in treatment effects between biomarker subgroups is not very large, the developed method can improve precision of estimation of pooled treatment effects while maintaining low bias.

The impact of ketogenic diet on drug-resistant epilepsy in children: A comprehensive review and meta-analysis.

The ketogenic diet (KD), characterized by high-fat and low-carbohydrate intake, is currently gaining widespread popularity as a treatment for drug-resistant epilepsy (DRE). In addition to the traditional ketogenic diet, several variants have been introduced to enhance compliance and flexibility, such as the modified Atkins diet (MAD) and the low glycemic index diet (LGID). These adaptations aim to provide patients with more manageable and sustainable options while harnessing the potential therapeutic benefits of DRE. The objective of this study is to evaluate the efficacy and safety of the KD in pediatric patients who exhibit DRE. In this study, we conducted a thorough review of existing literature by searching Cochrane, Embase, Medline, and PubMed. Our approach involved predefined criteria for data extraction and the assessment of study quality. Eleven RCTs with 788 participants were included in this study. The pooled effect estimates revealed a significant association between dietary interventions and seizure frequency reduction of > 50% (OR 6.68, 96% CI 3.52, 12.67) and > 90% (OR 4.37, 95% CI 2.04, 9.37). Dietary interventions also increased the odds of achieving seizure freedom (OR 4.13, 95% CI 1.61, 10.60). The common adverse effects included constipation (39.07%) and vomiting (10%). In conclusion, dietary interventions, notably the KD, hold promise for pediatric DRE, reducing seizures and achieving freedom. These non-pharmacological options improve the quality of life of non-responsive and non-surgical patients. The KD has emerged as a potential therapeutic approach. Further research is needed to address the limitations and investigate their long-term effects.

Effects of robot-assisted gait training on motor performance of lower limb in poststroke survivors: a systematic review with meta-analysis.

This study aimed to investigate the effects of robot-assisted gait training (RAGT) on improving walking ability, and to determine the optimal dosage of task-specific training based on RAGT for stroke patients. Two investigators independently searched electronic databases, including PubMed, Embase, Cochrane Library, and Physiotherapy Evidence Database (PEDro) from inception to 31 January 2020. The study design was a systematic review with meta-analysis of randomized controlled trials (RCTs), comparing the intervention of RAGT plus conventional therapy to conventional therapy alone. RCTs mainly focus on lower limb motor function as the primary outcomes, while the secondary outcomes involve gait speed, walking distance, cadence, balance, and activities of daily living (ADL). Pooled effect estimates were calculated by comparing the change from baseline to the end of the study in each group. Twenty-eight RCTs were included. The pooled analysis showed that RAGT had a significantly short-term effect on improving lower limb function [standardized mean difference (SMD) 0.32, 95% CI 0.10 to 0.55]. Additionally, there were significant improvements in gait speed (MD 0.10, 95% CI 0.06 to 0.14) and ADL (SMD 0.17, 95% CI 0.02 to 0.32). Subgroup analyses indicated that RAGT lasting for 30-60 minutes per day over 4 weeks yielded a moderate effect size (SMD 0.53, 95% CI 0.16 to 0.90). Additionally, RAGT significantly promoted lower limb function recovery in the early stage after a stroke (SMD 0.33, 95% CI 0.07 to 0.58) or in non-ambulatory patients (SMD 0.35, 95% CI 0.10 to 0.59). RAGT demonstrated significant positive effects on lower limb function post-stroke. Our results provide additional evidence to support that RAGT is a potentially appropriate intervention to promote lower limb recovery in individuals who have had a stroke.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: A systematic review and meta-analysis.

Background and study aims Gastroesophageal reflux disease (GERD) is a widespread chronic gastrointestinal condition with an increasing worldwide prevalence. This research was a systematic review and meta-analysis evaluating the efficacy, safety, and long-term outcomes of endoscopic full-thickness plication (EFTP) for the treatment of GERD. Methods A comprehensive search of databases was conducted for studies published up to April 2023. We included randomized controlled trials (RCTs) and prospective observational studies that examined the use of EFTP in treating GERD among adult patients. We calculated pooled effect estimates using a random-effects model. Results EFTP significantly improved GERD Health-Related Quality of Life (GERD-HRQL) scores at 3-, 6-, and 12-month follow-up intervals. A considerable proportion of patients discontinued proton pump inhibitors, with cessation rates of 59% (95% confidence interval [CI]: 0.47-0.71), 68% (95% CI: 0.58-0.78), and 67% (95% CI: 0.46-0.89,) at 3, 6, and 12 months, respectively. At 3 and 6 months, 61% (95% CI: 0.54-0.68) and 66% (95% CI: 0.56-0.76) of patients experienced ≥50% improvement in GERD-HRQL scores. EFTP demonstrated a favorable safety profile, with a low rate of severe adverse events. We observed a 6.76% reduction (95% CI: -14.53-1.02) in the percentage of time with esophageal pH <4, a decrease in DeMeester scores, and fewer total reflux episodes. The average procedure time was 22.75 minutes (95% CI: 22.03-23.48). Subgroup analyses suggest that both the GERDx system and the NDO Plicator are effective and safe in treating GERD. Conclusions The findings from our study reveal that EFTP is a safe and effective treatment for GERD patients who have not responded adequately to conventional therapies. Given its minimally invasive nature, effectiveness, and limited adverse effects, EFTP emerges as a compelling alternative to conventional surgical procedures.

Correlation of AMH with Cardiometabolic Markers in Polycystic Ovarian Syndrome: Systematic Review and Meta-Analysis

ABSTRACT Objective: The purpose of this systematic review and meta-analysis was to determine whether there is a connection between polycystic ovarian syndrome (PCOS)-affected women’s levels of the anti-Mullerian hormone (AMH) and certain cardiometabolic indicators. Materials and Methods: To find pertinent recent research published between 2017 and 2023, a thorough search was done in PubMed. Studies were included if they looked into the relationship between PCOS-related women’s AMH levels and cardiometabolic markers. To determine pooled effect estimates, data from the included studies were examined using random-effects models. Results: Five papers were included in the meta-analysis since they satisfied the inclusion requirements. The meta-analysis found substantial positive relationships between AMH levels and markers of insulin resistance, fasting blood sugar levels, and dyslipidemia measures such as total cholesterol (SMD: 0.68, 95% confidence interval: 0.34–1.00, P &lt; 0.001). Conclusion: This systematic review and meta-analysis show that AMH levels in PCOS-affected women significantly positively correlate with markers of insulin resistance, fasting glucose levels, and dyslipidemia parameters. These findings imply that the pathogenesis of the cardiometabolic abnormalities seen in PCOS may include AMH. AMH may be used as a biomarker to estimate the cardiometabolic risk in PCOS-affected women, but more studies are required to determine its clinical applicability.

Modification of heat-related effects on mortality by air pollution concentration, at small-area level, in the Attica prefecture, Greece

BackgroundThe independent effects of short-term exposure to increased air temperature and air pollution on mortality are well-documented. There is some evidence indicating that elevated concentrations of air pollutants may lead to increased heat-related mortality, but this evidence is not consistent. Most of these effects have been documented through time-series studies using city-wide data, rather than at a finer spatial level. In our study, we examined the possible modification of the heat effects on total and cause-specific mortality by air pollution at municipality level in the Attica region, Greece, during the warm period of the years 2000 to 2016.MethodsA municipality-specific over-dispersed Poisson regression model during the warm season (May–September) was used to investigate the heat effects on mortality and their modification by air pollution. We used the two-day average of the daily mean temperature and daily mean PM10, NO2 and 8 hour-max ozone (O3), derived from models, in each municipality as exposures. A bivariate tensor smoother was applied for temperature and each pollutant alternatively, by municipality. Α random-effects meta-analysis was used to obtain pooled estimates of the heat effects at different pollution levels. Heterogeneity of the between-levels differences of the heat effects was evaluated with a Q-test.ResultsA rise in mean temperature from the 75th to the 99th percentile of the municipality-specific temperature distribution resulted in an increase in total mortality of 12.4% (95% Confidence Interval (CI):7.76–17.24) on low PM10 days, and 21.25% (95% CI: 17.83–24.76) on high PM10 days. The increase on mortality was 10.09% (95% CI: − 5.62- 28.41) on low ozone days, and 14.95% (95% CI: 10.79–19.27) on high ozone days. For cause-specific mortality an increasing trend of the heat effects with increasing PM10 and ozone levels was also observed. An inconsistent pattern was observed for the modification of the heat effects by NO2, with higher heat effects estimated in the lower level of the pollutant.ConclusionsOur results support the evidence of elevated heat effects on mortality at higher levels of PM10 and 8 h max O3. Under climate change, any policy targeted at lowering air pollution levels will yield significant public health benefits.

Circulating levels of advanced glycation end products in females with polycystic ovary syndrome: a meta-analysis

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by a hormonal imbalance that affects females of reproductive age. The association between advanced glycation end products (AGEs) and PCOS has attracted considerable attention in recent years, highlighting the potential of AGEs as biomarkers for this disorder. In the present systematic review and meta-analysis, we aimed to examine the association between AGEs and PCOS, evaluate their potential as biomarkers, and improve our understanding of the pathophysiology of PCOS and its associated metabolic complications. A literature search was performed using various databases from January 2000 to March 2023 to identify relevant studies investigating the association between AGEs and PCOS. Pooled effect estimates were calculated using standardized mean differences (SMD) with 95% confidence intervals (CIs). Sub-group and meta-regression analyses were performed to examine potential sources of heterogeneity. The meta-analysis included six studies with a total of 623 participants. Our results revealed a significant increase in circulating AGE levels in females with PCOS compared to healthy females (SMD = 2.35; 95% CI: 1.10–3.60; P &lt;0.001). Significant heterogeneity was observed between the studies (I 2 = 96.37%; P &lt;0.001), indicating the presence of several factors influencing the association. Sub-group analyses based on body mass index, age, and homeostatic model assessment for insulin resistance indicated differential effects of AGEs on specific sub-groups. This systematic review and meta-analysis support the association between elevated AGE levels and PCOS, thereby suggesting the potential role of AGEs as biomarkers in PCOS.

Opportunistic salpingectomy at the time of vaginal hysterectomy: A systematic review and meta-analysis.

Despite the rising rates of opportunistic salpingectomy at the time of surgery for non-malignant conditions, salpingectomy is not widely adopted during vaginal hysterectomy (VH) and has not been extensively investigated. The aim of the primary study was to determine the feasibility of bilateral opportunistic salpingectomy at the time of VH. Secondary aims included surgical outcomes, factors associated with patient selection, and the prevalence of incidental tubal malignancies. In this systematic review and meta-analysis we searched Pubmed, Embase and ClinicalTrials.gov databases from inception to September 1, 2023, using relevant keywords. Original articles with no language restriction reporting outcomes of women undergoing planned VH with opportunistic salpingectomy, were considered eligible. Studies including patients undergoing VH with and without opportunistic salpingectomy were also included. The Newcastle-Ottawa scale was used to assess quality of observational studies. DerSimonian-Laird random effects meta-analysis was performed and pooled effect estimates and proportions with corresponding 95% confidence intervals were computed. Heterogeneity was assessed using the I2 statistic. Seven observational cohort studies including 4808 women undergoing opportunistic salpingectomy at the time of VH and 10 295 patients undergoing VH alone were selected. The pooled proportion of success was 81.83 per 100 observations (95% CI: 75.35-87.54). Opportunistic salpingectomy at the time of VH, when feasible, was associated with a significant reduction in intraoperative complications (OR 0.06, 95% CI: 0.01, -0.37, P = 0.03) and total operative time (95% CI: -17.80, -1.07, P = 0.03) compared to those where it failed. Successful salpingectomy was significantly hindered by nulliparity (OR 0.12, 95% CI: -17.69, -1.21, P < 0.001) and favored by pelvic organ prolapse (OR 3.20, 95% CI: 1.35, 7.55, P = 0.008). Immunohistochemical tubal abnormalities were found in 13/579 (2.1%) patients. The overall quality of the evidence, according to the GRADE assessment, was low. Opportunistic salpingectomy is safe, effective, and feasible at the time of VH. Nulliparity and pelvic organ prolapse are factors potentially influencing surgical outcomes.

Efficacy and safety of traditional plant-based medicines for preventing chronic oxaliplatin-induced peripheral neurotoxicity in patients with colorectal cancer: A systematic review and meta-analysis with core herb contribution

Ethnopharmacological relevanceTraditional plant-based medicines (TMs) have been widely used to prevent chronic oxaliplatin-induced peripheral neurotoxicity (OIPN). However, the prevention and safety of TMs for chronic OIPN remain ambiguous. Furthermore, diverse TM prescriptions and complicated components limit in-depth research on the mechanisms of TMs. Aim of this studyTo determine core TMs and potential pharmacological pathways on the basis of a thorough investigation into the preventive benefits and safety of oral TMs for chronic OIPN in colorectal cancer (CRC). MethodsA search of the PubMed, Cochrane, Embase, CNKI, VIP, and Wanfang databases for RCTs reporting on TMs for chronic OIPN was conducted through December 1, 2022. Subgroup analysis, sensitivity analysis and meta-regression were applied to assess the impacts of influencing variables. The assessment of Risk of Bias was relied on Cochrane Risk of Bias tool. The funnel plot, Egger's test, and the Trim and Fill method were applied to identify potential publication bias. Trial sequential analyses (TSA) were carried out by the TSA tool to increase the robustness. The assessment of the quality of evidence was according to the GRADE system. System pharmacology analysis was employed to screen core herbal combinations to elucidate possible mechanisms for preventing chronic OIPN in CRC. ResultsThe pooled effect estimate with robustness increased by TSA analysis demonstrated that oral TMs appeared to significantly decrease the incidence of chronic OIPN (RR = 0.66, 95% CI (0.56, 0.78); P＜0.00001), leukocytopenia (RR = 0.65, 95% CI (0.54,0.79); P＜0.00001), and nausea and vomiting (RR = 0.72, 95% CI (0.61,0.84); P＜0.0001) as well as improve the Objective Response Rate (ORR) (RR = 1.31, 95% CI (1.09,1.56); P = 0.003). The incidence of severe chronic OIPN was revealed a significant reduction, particularly when chemotherapy was administered for periods of time shorter than six months (RR = 0.33, 95% CI (0.15,0.71); P = 0.005; actuation duration＜3 months; RR = 0.33, 95% CI (0.17,0.62); P = 0.0007; actuation duration≥3 months, ＜6 months). The considerable heterogeneity among studies may be attributable to the severity of dysfunction categorized by grade and accumulated dosage. Using core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf. To regulate nuclear factor-kappa B against inflammation caused by activation of microglia might be an approach to preventing chronic OIPN. ConclusionsTMs appear to be effective and safe in the prevention of chronic OIPN, especially severe chronic OIPN. Additionally, core TMs consisting of Astragalus membranaceus (Fisch.) Bunge, Atractylodes Macrocephala Koidz., Poria cocos (Schw.) Wolf, and Codonopsis pilosula (Franch.) Nannf were presumably responsible for reducing the incidence of chronic OIPN, and the mechanism may be related to relieving inflammation. However, quality-assured trials with long-term follow-up for exploring inflammatory factors and preliminary research on core TMs and pharmacological pathways are needed.

Effects of acupuncture treatment for myasthenia gravis: A systematic review and meta-analysis.

Randomized controlled trials (RCTs) of acupuncture for myasthenia gravis (MG) were searched and the efficacy of acupuncture in the treatment of MG was evaluated by meta-analysis. We searched for RCTs in six main electronic databases, and collected RCTs of acupuncture treatment for MG from database creation to 28 February 2023. The main outcome was the effective rate and the secondary outcome was the Traditional Chinese Medicine (TCM) relative clinical score, absolute clinical score (ACS) of MG, Quantitive myasthenia gravis score (QMG), quality of life, and adverse events. Odds ratios (ORs) and weighted mean differences (WMD) and 95% confidence intervals (CI) were used to assess pooled effect estimates using Review Manager software. A total of 14 RCTs were included. Meta-analysis showed that the effective rate in the acupuncture group was significantly improved compared with conventional Western medicine alone [OR = 4.28, 95% CI (2.95, 6, 22), P<0.005]. The pooled WMDs revealed that TCM relative clinical score [WMD = -2.22, 95% CI = (-2.53, -1.90), P<0.005], ACS of MG [WMD = -3.14, 95% CI = (-3.67, -2.62), P<0.005], and QMG [WMD = -0.88, 95% CI = (-1.46, -0.29), P<0.005] in the acupuncture group was lower than the control group. Adverse reactions related to acupuncture and quality of life were less mentioned among included RCTs. This meta-analysis demonstrated that acupuncture as an auxiliary may play a positive role in treating MG. It can improve the effective rate of treatment, and reduce TCM relative clinical score, ACS of MG, and QMG. However, the quality of included studies was generally low and caution should be exercised when considering this treatment option. In the future, more rigorous study designs and high-quality RCTs are needed to verify the efficacy of acupuncture in the treatment of MG, because the results of high-quality RCTs are more reliable and accurate.

Comparative efficacy of intratympanic gentamicin and intratympanic corticosteroid in the treatment of Meniere's disease: a systematic review and meta-analysis.

We aimed to evaluate the efficacy of gentamicin compared to corticosteroids for the treatment of Meniere's disease. An extensive search was conducted in PubMed, Embase, and Web of Science until May 2024. For continuous outcomes, pooled effect estimates were determined by calculating the weighted mean difference (WMD), while for binary outcomes, the risk ratio (RR) was used, each accompanied by their respective 95% confidence intervals (CIs). Heterogeneity among the studies was assessed using Cochran's I 2 and Q statistics. A total of 12 studies were selected, involving 694 patients. Our analysis found that the gentamicin group demonstrates superior vertigo control rates compared to the corticosteroid group (RR: 1.36, 95% CI: 1.13 to 1.65, p < 0.001). In subgroup analysis, the gentamicin group showed a higher vertigo control rates at 6 months compared to the corticosteroid group (RR: 1.69, 95% CI: 1.28 to 2.24, p < 0.001); however, there was no statistically significant difference between the two groups at 12 months (RR: 1.48, 95% CI: 0.88 to 2.49, p = 0.14). Regarding changes in pure tone average, the corticosteroid group was superior to the gentamicin group (WMD: 4.41, 95% CI: 3.31 to 5.52, p < 0.001). Our study suggests that the intratympanic gentamicin group achieves higher vertigo control rates, whereas the corticosteroid group demonstrates better improvement in pure tone averages. However, the high heterogeneity in vertigo control rates warrants caution. Larger sample-sized randomized controlled trials are needed to further validate these findings.

Exploring the relationship between ambient sulfur dioxide and semen quality parameters: A systematic review and meta-analysis

Objective: To investigate the relationship between ambient sulfur dioxide (SO2) exposure and semen quality parameters. Methods: A systematic literature search was conducted to identify relevant studies investigating the association between SO2 exposure and semen quality parameters. This search encompassed the timeframe from January 2000 to May 2023 and included electronic databases such as Web of Science, Google Scholar, PubMed, Cochrane, and Scopus. Pooled effect estimates with 95% confidence intervals (CI) were calculated using percent changes (PC). The meta-analysis included seven studies with 6 711 participants and 15 087 semen samples. Results: The results revealed a significant negative association between ambient SO2 exposure and certain semen quality parameters. In particular, SO2 exposure was associated with a significant decrease in progressive motility (PC=0.032; 95% CI: -0.063 to -0.001; P=0.044) and sperm concentration (PC = -0.020; 95% CI: -0.036 to -0.005; P=0.012). However, no statistically significant associations were observed for total sperm count (PC = -0.038; 95% CI: -0.079 to 0.003; P=0.070), seminal fluid volume (PC = -0.009; 95% CI: -0.048 to -0.030; P=0.662) and sperm motility (PC = -0.17; 95% CI: -0.363 to 0.022; P=0.830). In addition, the results of the subgroup analysis revealed specific variables that were associated with the decrease in relevant sperm parameters. Conclusions: This systematic review and meta-analysis provides compelling evidence supporting a consistent negative association between exposure to ambient SO2 and semen quality parameters.

A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

Meta-analysis of randomized controlled trials of the effectiveness of Prospekta in the treatment of vascular cognitive impairment of varying severity

To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of Prospekta in the treatment of SCI of varying severity. The meta-analysis included the results of RCTs of the efficacy of Prospekta in the treatment of VCI, the severity of which was assessed using the Montreal Cognitive Scale (MoCA). The pooled effect estimate included all publications of double-blind, placebo-controlled RCTs that provided sufficient MoCA efficacy data to support further statistical analysis. The main result of the meta-analysis was obtained for the final values of the efficacy indicator in the groups of patients receiving the drug Prospekta, in comparison with the placebo group. A meta-analysis of the effectiveness of Prospekta in the treatment of SCI of varying severity was carried out based on data from 3 RCTs and 2 CTs involving 12.701 patients aged 18 years and older. When using the mixed models method, the effect size for the endpoint «change in total MoCA score from baseline to follow-up visit» was 3.4 points for Prospekta (2.7 points for placebo, p<0.0001); for the end point «∆ between changes in the total score on the MoCA scale while taking Prospekta and placebo» - 0.6736 points (p<0.0001). A statistically significant improvement in cognitive function according to the MoCA scale was demonstrated in patients with VCI using the drug Prospekta.

Long-term ozone exposure and all-cause mortality: Cohort evidence in China and global heterogeneity by region

BackgroundCohort evidence linking long-term ozone (O3) exposure to mortality remained largely mixed worldwide and was extensively deficient in densely-populated Asia. This study aimed to assess the long-term effects of O3 exposure on all-cause mortality among Chinese adults, as well as to examine potential regional heterogeneity across the globe. MethodsA national dynamic cohort of 42153 adults aged 16+ years were recruited from 25 provinces across Chinese mainland and followed up during 2010–2018. Annual warm-season (April–September) O3 and year-round co-pollutants (i.e., nitrogen dioxide [NO2] and fine particulate matter [PM2.5]) were simulated through validated spatial-temporal prediction models and were assigned to each enrollee in each calendar year. Cox proportional hazards models with time-varying exposures were employed to assess the O3-mortality association. Concentration-response (C-R) curves were fitted by natural cubic spline function to investigate the potential nonlinear association. Both single-pollutant model and co-pollutant models additionally adjusting for PM2.5 and/or NO2 were employed to examine the robustness of the estimated association. The random-effect meta-analysis was adopted to pool effect estimates from the current and prior population-based cohorts (n = 29), and pooled C-R curves were fitted through the meta-smoothing approach by regions. ResultsThe study population comprised of 42153 participants who contributed 258921.5 person-years at risk (median 6.4 years), of whom 2382 death events occurred during study period. Participants were exposed to an annual average of 51.4 ppb (range: 22.7−74.4 ppb) of warm-season O3 concentration. In the single-pollutant model, a significantly increased hazard ratio (HR) of 1.098 (95% confidence interval [CI]: 1.023−1.179) was associated with a 10-ppb rise in O3 exposure. Associations remained robust to additional adjustments of co-pollutants, with HRs of 1.099 (95% CI: 1.023−1.180) in bi-pollutant model (+PM2.5) and 1.093 (95% CI: 1.018−1.174) in tri-pollutant model (+PM2.5+NO2), respectively. A J-shaped C-R relationship was identified among Chinese general population, suggesting significant excess mortality risk at high ozone exposure only. The combined C-R curves from Asia (n = 4) and North America (n = 17) demonstrated an overall increased risk of all-cause mortality with O3 exposure, with pooled HRs of 1.124 (95% CI: 0.966−1.307) and 1.023 (95% CI: 1.007−1.039) per 10-ppb rise, respectively. Conversely, an opposite association was observed in Europe (n = 8, HR: 0.914 [95% CI: 0.860−0.972]), suggesting significant heterogeneity across regions (P < 0.01). ConclusionsThis study provided national evidence that high O3 exposure may curtail long-term survival of Chinese general population. Great between-region heterogeneity of pooled O3-mortality was identified across North America, Europe, and Asia.

Topical and oral steroids for otitis media with effusion (OME) in children.

Topical and oral steroids for otitis media with effusion (OME) in children.

Post-discharge malaria chemoprevention in children admitted with severe anaemia in malaria-endemic settings in Africa: a systematic review and individual patient data meta-analysis of randomised controlled trials

Severe anaemia is associated with high in-hospital mortality among young children. In malaria-endemic areas, surviving children also have an increased risk of mortality or readmission after hospital discharge. We conducted a systematic review and individual patient data meta-analysis to determine the efficacy of monthly post-discharge malaria chemoprevention in children recovering from severe anaemia. This analysis was conducted according to PRISMA-IPD guidelines. We searched multiple databases on Aug 28, 2023, without date or language restrictions, for randomised controlled trials comparing monthly post-discharge malaria chemoprevention with placebo or standard of care among children (aged <15 years) admitted with severe anaemia in malaria-endemic Africa. Trials using daily or weekly malaria prophylaxis were not eligible. The investigators from all eligible trials shared pseudonymised datasets, which were standardised and merged for analysis. The primary outcome was all-cause mortality during the intervention period. Analyses were performed in the modified intention-to-treat population, including all randomly assigned participants who contributed to the endpoint. Fixed-effects two-stage meta-analysis of risk ratios (RRs) was used to generate pooled effect estimates for mortality. Recurrent time-to-event data (readmissions or clinic visits) were analysed using one-stage mixed-effects Prentice-Williams-Peterson total-time models to obtain hazard ratios (HRs). This study is registered with PROSPERO, CRD42022308791. Our search identified 91 articles, of which 78 were excluded by title and abstract, and a further ten did not meet eligibility criteria. Three double-blind, placebo-controlled trials, including 3663 children with severe anaemia, were included in the systematic review and meta-analysis; 3507 (95·7%) contributed to the modified intention-to-treat analysis. Participants received monthly sulfadoxine-pyrimethamine until the end of the malaria transmission season (mean 3·1 courses per child [range 1-6]; n=1085; The Gambia), monthly artemether-lumefantrine given at the end of weeks 4 and 8 post discharge (n=1373; Malawi), or monthly dihydroartemisinin-piperaquine given at the end of weeks 2, 6, and 10 post discharge (n=1049; Uganda and Kenya). During the intervention period, post-discharge malaria chemoprevention was associated with a 77% reduction in mortality (RR 0·23 [95% CI 0·08-0·70], p=0·0094, I2=0%) and a 55% reduction in all-cause readmissions (HR 0·45 [95% CI 0·36-0·56], p<0·0001) compared with placebo. The protective effect was restricted to the intervention period and was not sustained after the direct pharmacodynamic effect of the drugs had waned. The small number of trials limited our ability to assess heterogeneity, its sources, and publication bias. In malaria-endemic Africa, post-discharge malaria chemoprevention reduces mortality and readmissions in recently discharged children recovering from severe anaemia. Post-discharge malaria chemoprevention could be a valuable strategy for the management of this group at high risk. Future research should focus on methods of delivery, options to prolong the protection duration, other hospitalised groups at high risk, and interventions targeting non-malarial causes of post-discharge morbidity. The Research-Council of Norway and the Bill-&-Melinda-Gates-Foundation through the Worldwide-Antimalarial-Research-Network.