Meta-analysis Of Randomized Controlled Trials Research Articles

#1526 Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic review and meta-analysis of randomized controlled trials

Abstract Background and Aims To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). Method We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN. Literature searching was performed via PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and hand searching of the reference lists. Systematic reviews and meta-analyses of RCTs that evaluated the effects of any dietary intervention on clinical outcomes of DN were included. Two reviewers evaluated the methodological quality of the included articles through AMSTAR score. In addition, according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as “high”, “moderate”, “low” or “very low” quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories (class I to IV and non-significant (NS)). Results We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles (Fig. 1). Moderate quality evidence suggested that probiotics supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in DN patients. Low quality evidence indicated that probiotics supplementation significantly improved serum creatinine, urinary albumin creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low quality evidence suggested that a salt restriction diet could significantly improve creatinine clearance rate (CrCl) in patients with DN. Low quality evidence suggested that vitamin D supplementation could significantly improve UACR in patients with DN. Besides, low quality evidence indicated that soy isoflavone supplementation could significantly improve BUN, FBG, TC, triglycerides (TG) and LDL-C in patients with DN. Furthermore, low quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low quality evidence suggested supplementation of antioxidant vitamins could significantly improve serum creatinine, systolic blood pressure, and HbA1c in patients with DN. The remaining outcomes were rated as very low quality due to significant risk of bias, significant heterogeneity, imprecision, and publication bias. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence (Fig. 2). Conclusion Moderate to low evidence suggests that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, and salt-restricted diets may significantly improve clinical outcomes in patients with DN.

Role of pravastatin in the prevention of preeclampsia: A systematic review and meta-analysis of randomized-controlled trials

Context: Preeclampsia prevention is important for reducing maternal mortality and morbidity worldwide. Recent studies have explored the use of to prevent preeclampsia and improve maternal, perinatal, or neonatal outcomes. However, the results are still debatable. Aims: To evaluate the role of pravastatin in the prevention of preeclampsia in pregnant women. Methods: This study is a systematic review and meta-analysis of randomized controlled trials (RCTs) involving studies with healthy pregnant women receiving pravastatin vs. control to observe the risk of preeclampsia. Literature searching was conducted in PubMed, Science Direct, EBSCO/CINAHL, PROQUEST, and SCOPUS. Statistical analyses were performed using the Review Manager 5.4.1 software. Results: Five studies were initially identified for meeting the inclusion criteria; 2 studies were treatment studies and had to be excluded, and one small study only used pravastatin for a few weeks, leaving only two studies for statistical analysis. Administration of pravastatin was associated with a reduced risk of preeclampsia (OR: 0.51; 95% CI: 0.29-0.90; p= 0.02) and preterm delivery (OR: 0.31; 95% CI: 0.16-0.58; p<0.01). The risk of preeclampsia with severe features and small for gestational ages was not different. Only one study (INOVASIA) reported on preterm preeclampsia, prophylactic pravastatin was associated with a marked and significant reduction of preterm preeclampsia rates (OR: 0.034; 95% CI: 0.202-0.905). Pregnant women receiving pravastatin had better perinatal outcomes in terms of birthweight, Apgar scores, NICU admission, length of stay, and respiratory distress syndrome. Conclusions: Pravastatin has the potential to prevent the occurrence of preeclampsia, premature birth, and perinatal morbidity in pregnant women. However, it is necessary to conduct more RCTs with a larger sample size and appropriate follow-up of the offspring to further examine the efficacy of pravastatin in preeclampsia prevention.

Catheter ablation for atrial fibrillation in heart failure with reduced ejection fraction patients: A meta-analysis

BackgroundThe optimal treatment of atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF) remains unsettled. ObjectiveThe purpose of this study was to assess the efficacy of catheter ablation (CA) and medical therapy compared to medical therapy alone in patients with AF and HFrEF. MethodsWe performed a systematic review of randomized controlled trials (RCTs) comparing CA with guideline-directed medical therapy for AF in patients with HFrEF (left ventricular ejection fraction [LVEF] ≤ 40%). We systematically searched PubMed, Embase, and Cochrane for eligible trials. A random effects model was used to calculate the risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CIs). ResultsSix RCTs comprising 1055 patients were included, of whom 530 (50.2%) were randomized to CA. Compared with medical therapy, CA was associated with a significant reduction in heart failure (HF) hospitalization (RR 0.57; 95% CI 0.45–0.72; P < .01), cardiovascular mortality (RR 0.46; 95% CI 0.31–0.70; P < .01), all-cause mortality (RR 0.53; 95% CI 0.36–0.78; P < .01), and AF burden (MD –29.8%; 95% CI –43.73% to –15.90%; P < .01). Also, there was a significant improvement in LVEF (MD 3.8%; 95% CI 1.6%–6.0%; P < .01) and quality of life (Minnesota Living with Heart Failure Questionnaire; MD –4.92 points; 95% CI –8.61 to –1.22 points; P < .01) in the ablation group. ConclusionIn this meta-analysis of RCTs of patients with AF and HFrEF, CA was associated with a reduction in HF hospitalization, cardiovascular mortality, and all-cause mortality as well as a significant improvement in LVEF and quality of life.

Folic acid supplementation for stroke prevention: a systematic review and meta-analysis of 21 randomized clinical trials worldwide

Background & aimsThe AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. MethodsPubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. ResultsResults from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR=0.83, 95% CI 0.75 to 0.93; RR=1.04 in areas with grain fortification, P-interaction=0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR=0.77, 95% CI 0.68 to 0.86; RR=0.94 for participants with a history of stroke or myocardial infarction, P-interaction=0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. ConclusionsThis is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.

Once-weekly insulin icodec versus once-daily long-acting insulins for type 2 diabetes mellitus: Systematic review and meta-analysis

BackgroundInsulin icodec is a novel, long-acting, once-weekly basal insulin analog. Its comparative efficacy and safety with basal once-daily insulins in type 2 diabetes mellittus is uncertain. ObjectiveEvaluate potential efficacy, benefits and risks associated with icodec compared to once-daily basal insulin analogs (degludec or glargine). MethodsWe systematically searched PubMed, Cochrane, and Embase for randomized controlled trials (RCTs) published until June 2023 comparing icodec versus long-acting insulin analogs (degludec and glargine) in type 2 diabetes mellitus (T2DM) with at least 12 weeks of follow-up. Binary endpoints were assessed with risk ratios (RRs) and continuous endpoints were compared using mean differences (MDs), with 95% confidence intervals (CIs). The protocol was registered in PROSPERO (CRD42023452468). ResultsA total of seven RCTs and 3286 patients with T2DM were included, of whom 1509 (60.6%) received icodec treatment. The follow-up period ranged from 16 to 78 weeks. Compared with once-daily basal insulin analogs, icodec led to a greater improvement in HbA1c (MD -0.15%; 95% CI -0.21, −0.10; p < 0.0001; I2 = 0%) and time in range (TIR) (MD 2.83%; 95%CI 0.94; 4.71; p = 0.003; I2 = 22%). Body weight was increased with icodec treatment (MD 0.78 Kg; 95%CI 0.42, 1.15; p < 0.01; I2 = 86%). There was also a higher rate of injection site reactions (RR 1.89; 95%CI 1.12, 3.18; p = 0.016; I2 = 0%) and nasopharyngitis (RR 1.94; 95%CI 1.11, 3.38; p = 0.020; I2 = 0%) in the icodec group, compared with once-daily regimens. There was no significant difference between groups in fasting plasma glucose. ConclusionsIn this meta-analysis of RCTs, insulin icodec led to better control of HbA1c and TIR as compared with once-daily insulin regimens, albeit with increased weight gain and a higher rate of injection site reaction in the Icodec group.

Endovascular Thrombectomy for Large Ischemic Strokes with ASPECTS 0-2: aMeta-analysis of Randomized Controlled Trials.

Randomized controlled trials (RCTs) demonstrated atreatment effect of endovascular thrombectomy in acute ischemic stroke with large infarct, commonly defined as an Alberta Stroke Program Early CT Score (ASPECTS) of 3-5. However, data on endovascular thrombectomy in patients with very low ASPECTS of 0-2 remain scarce. We conducted asystematic review and meta-analysis of RCTs comparing endovascular thrombectomy versus medical treatment alone in acute ischemic anterior circulation stroke with very large infarct, defined as ASPECTS of 0-2. The primary outcome was the shift toward better functional outcomes on the 90-day modified Rankin Scale (mRS). Random effects meta-analysis was performed using the generic inverse variance method. Literature research identified four RCTs which evaluated the treatment effect of endovascular thrombectomy for large infarcts and provided asubgroup analysis of the mRS shift in patients with ASPECTS of 0-2. The pooled analysis showed asignificant shift toward better 90-day mRS scores in favor of endovascular thrombectomy (pooled odds ratio, 1.62, 95% confidence interval, 1.29-2.04, P < 0.001). This meta-analysis suggests atreatment effect of endovascular thrombectomy in specific patients with very low ASPECTS of 0-2, challenging the use of ASPECTS for treatment selection in acute ischemic stroke due to large vessel occlusion. An individual patient meta-analysis of RCTs would strengthen evidence in the treatment of patients with ASPECTS of 0-2.

Effects of dietary intervention on diabetic nephropathy: an umbrella review of systematic reviews and meta-analyses of randomized controlled trials.

To evaluate the quality of evidence, potential biases, and validity of all available studies on dietary intervention and diabetic nephropathy (DN). We conducted an umbrella review of existing meta-analyses of randomized controlled trials (RCTs) that focused on the effects of dietary intervention on DN incidence. The literature was searched via PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. According to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE), evidence of each outcome was evaluated and graded as "high", "moderate", "low" or "very low" quality to draw conclusions. Additionally, we classified evidence of outcomes into 4 categories. We identified 36 meta-analyses of RCTs and 55 clinical outcomes of DN from 395 unique articles. Moderate-quality evidence suggested that probiotic supplementation could significantly improve blood urea nitrogen (BUN), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels in DN patients. Low-quality evidence indicated that probiotic supplementation significantly improved the serum creatinine concentration, urinary albumin-creatinine ratio (UACR), fasting blood glucose (FBG), HbA1c and high-density lipoprotein cholesterol (HDL-C) in DN patients. In addition, low-quality evidence suggested that a salt restriction diet could significantly improve the creatinine clearance rate (CrCl) in patients with DN. Low-quality evidence suggested that vitamin D supplementation could significantly improve the UACR in patients with DN. In addition, low-quality evidence has indicated that soy isoflavone supplementation could significantly improve BUN, FBG, total cholesterol (TC), triglyceride (TG) and LDL-C levels in patients with DN. Furthermore, low-quality evidence suggested that coenzyme Q10 supplementation could significantly improve HbA1c, TC and HDL-C in patients with DN, and dietary polyphenols also significantly improved HbA1c in patients with DN. Finally, low-quality evidence suggested that supplementation with antioxidant vitamins could significantly improve the serum creatinine concentration, systolic blood pressure, and HbA1c level in patients with DN. Given the small sample size, all significantly associated outcomes were evaluated as class IV evidence. Moderate to low amounts of evidence suggest that supplementation with probiotics, vitamin D, soy isoflavones, coenzyme Q10, dietary polyphenols, antioxidant vitamins, or salt-restricted diets may significantly improve clinical outcomes in patients with DN. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024512670.

Risk factors for inadequate bowel preparation before colonoscopy: A meta-analysis.

This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP). We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals. A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate. We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

Evaluating the efficacy and safety of platelet-rich plasma injection for erectile dysfunction: a systematic review and meta-analysis of randomized controlled trials.

Platelet-rich plasma (PRP) is rich in factors that play a role in stem cell recruitment, inflammation modulation, and angiogenesis. With numerous preclinical and clinical studies exploring PRP as a potential treatment for erectile dysfunction (ED), this study focused on assessing the effectiveness of intracorporeal PRP injection for ED patients based on randomized controlled trials (RCTs). The study sought to evaluate the efficacy and safety of intracorporeal injection of PRP in treating ED through a systematic review and meta-analysis of RCTs. This study adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was conducted on online databases (PubMed, Scopus, and ScienceDirect) to identify RCTs comparing PRP with a placebo for ED treatment. The primary outcomes assessed were the proportion of patients achieving the minimal clinically important difference in the International Index of Erectile Function (IIEF) domain and the change in the IIEF domain from baseline. The results were combined as a standardized mean difference between the PRP and placebo groups. Three RCTs comprising 230 patients were included. The overall effect favored PRP over placebo: total patients attaining minimal clinically important difference in the IIEF domain (odds ratio [OR], 5.64; 95% confidence interval [CI], 2.05 to 15.55; P = .0008), IIEF change from baseline (mean difference [MD], 2.99; 95% CI, 1.74 to 4.24; P = .00001), PSV (MD, 9.34; 95% CI, 0.84 to 17.84; P = .03), end-diastolic volume (standardized MD, 0.50; 95% CI, 0.17 to 0.83; P = .003), Sexual Encounter Profile question 3 (standardized MD, 0.78; 95% CI, 0.45 to 1.12; P = .00001), and visual analog scale score (MD, -0.30; 95% CI, -0.53 to -0.08; P = .008). PRP appears to be a safe and effective treatment for mild-to-moderate ED. However, further support from high-quality RCTs is needed to strengthen these findings.

Abstract P484: Systematic Review and Meta-Analysis of Cardiometabolic Effects of Trans Fatty Acids From Dairy Foods

As global initiatives to eliminate industrially-produced trans fatty acids (TFA) are implemented, dairy/ruminant-derived foods will become the major dietary TFA source. Such changes warrant better understanding of health effects from ruminant food-TFA consumption. This systematic review and meta-analysis aimed to assess cardiometabolic impacts of TFA from dairy foods, by evaluating findings from randomized controlled trials (RCTs) and prospective cohort studies (PCs). Separate searches for RCTs and PCs were conducted in PubMed and EMBASE databases using PRISMA guidelines. RCTs with at least a three-week intervention among adults compared the impact on blood lipids of regular dairy foods with TFA-enhanced dairy fat/foods produced by altering the cow’s diet. Selected PCs with at least four years of observation analyzed relationships between blood levels of specific TFA, such as vaccenic acid or trans palmitoleic acid (TPA) and risk of cardiovascular diseases (CVD) or type 2 diabetes among adults. A pooled meta-analysis of RCTs using the random effects model was performed for TC, LDL-C, HDL-C, TC/HDL-C, LDL-C/HDL-C, TG, ApoA1, ApoB as continuous variables with a statistical significance of p &lt; 0.05, 95% confidence interval (CI). For PCs, risk estimates and 95% CI using maximally adjusted models for contrasting exposures of circulating TFA levels were tabulated. Among 13 experimental groups from ten RCTs, there were no statistically significant differences in mean difference (MD) and 95% CI for any lipid biomarkers except a slight decrease in HDL-C (MD: -0.05mmol/L; CI: -0.10, 0.00 mmol/L) for TFA-enriched vs regular dairy foods. Among PCs, four found no association of circulating TPA with risk of CVD mortality or incidence and one found no association of circulating vaccenic acid with risk of CVD mortality. Additionally, three of five PCs found no significant association while two found a significant inverse association of TPA and type 2 diabetes. Our findings indicate that consumption of TFA (0.8 - 12.2 g/d) from different types of dairy foods does not confer adverse effects on cardiometabolic health.

The Use of Mobile Technologies to Promote Physical Activity and Reduce Sedentary Behaviors in the Middle East and North Africa Region: Systematic Review and Meta-Analysis.

The Middle East and North Africa (MENA) region faces unique challenges in promoting physical activity and reducing sedentary behaviors, as the prevalence of insufficient physical activity is higher than the global average. Mobile technologies present a promising approach to delivering behavioral interventions; however, little is known about the effectiveness and user perspectives on these technologies in the MENA region. This study aims to evaluate the effectiveness of mobile interventions targeting physical activity and sedentary behaviors in the MENA region and explore users' perspectives on these interventions as well as any other outcomes that might influence users' adoption and use of mobile technologies (eg, appropriateness and cultural fit). A systematic search of 5 databases (MEDLINE, Embase, CINAHL, Scopus, and Global Index Medicus) was performed. Any primary studies (participants of all ages regardless of medical condition) conducted in the MENA region that investigated the use of mobile technologies and reported any measures of physical activity, sedentary behaviors, or user perceptions were included. We conducted a narrative synthesis of all studies and a meta-analysis of randomized controlled trials (RCTs). The Cochrane risk-of-bias tool was used to assess the quality of the included RCTs; quality assessment of the rest of the included studies was completed using the relevant Joanna Briggs Institute critical appraisal tools. In total, 27 articles describing 22 interventions (n=10, 37% RCTs) and 4 (15%) nonexperimental studies were included (n=6141, 46% women). Half (11/22, 50%) of the interventions included mobile apps, whereas the other half examined SMS. The main app functions were goal setting and self-monitoring of activity, whereas SMS interventions were primarily used to deliver educational content. Users in experimental studies described several benefits of the interventions (eg, gaining knowledge and receiving reminders to be active). Engagement with the interventions was poorly reported; few studies (8/27, 30%) examined users' perspectives on the appropriateness or cultural fit of the interventions. Nonexperimental studies examined users' perspectives on mobile apps and fitness trackers, reporting several barriers to their use, such as perceived lack of usefulness, loss of interest, and technical issues. The meta-analysis of RCTs showed a positive effect of mobile interventions on physical activity outcomes (standardized mean difference=0.45, 95% CI 0.17-0.73); several sensitivity analyses showed similar results. The trim-and-fill method showed possible publication bias. Only 20% (2/10) of the RCTs measured sedentary behaviors; both reported positive changes. The use of mobile interventions for physical activity and sedentary behaviors in the MENA region is in its early stages, with preliminary evidence of effectiveness. Policy makers and researchers should invest in high-quality studies to evaluate long-term effectiveness, intervention engagement, and implementation outcomes, which can inform the design of culturally and socially appropriate interventions for countries in the MENA region. PROSPERO CRD42023392699; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=392699.

Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials

Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n=155), lipid profiles (n=83), glycemic profiles (n=57), circulatory system index (n=41), appetite (n=9), and others (n=6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p<0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD=-1.02cm; 95% CI:-1.99 to-0.06; p=0.038), fat mass (MD=-0.72kg; 95% CI:-1.32 to-0.12; p=0.019), fasting insulin (SMD=-0.21; 95% CI:-0.40 to-0.02; p=0.030), low-density lipoprotein cholesterol (LDL-C) (SMD=-0.20; 95% CI:-0.38 to-0.02; p=0.027), total cholesterol (TC) (SMD=-0.29; 95% CI:-0.48 to-0.10; p=0.003), and triacylglycerols (TG) (SMD=-0.23; 95% CI:-0.39 to-0.06; p=0.007), but increased fat free mass (FFM) (MD=0.98kg; 95% CI: 0.18-1.78; p=0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD=-0.70kg; 95% CI:-1.38 to-0.02; p=0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD=0.03mmol/L; 95% CI: 0.01-0.05; p=0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD=0.21; 95% CI: 0.05-0.36; p=0.008). Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

Metabolic Effects of Brown Adipose Tissue Activity Due to Cold Exposure in Humans: A Systematic Review and Meta-Analysis of RCTs and Non-RCTs.

Brown adipose tissue (BAT), specialized in thermoregulation in mammals, has been linked to improved glucose and lipid homeostasis when activated by cold exposure (CE). This systematic review and meta-analysis assessed the metabolic effects of CE-induced BAT activation in healthy humans, examining changes in glucose and lipid metabolism compared to thermoneutrality (TN). A literature search was conducted, identifying relevant human studies, including randomized controlled trials (RCTs) and non-RCTs, based on predefined inclusion criteria. Seven studies (a total of 85 participants) fully met the criteria. Data on plasma glucose, insulin, triglycerides (TGs), and free fatty acids (FFAs) were extracted for meta-analysis. When comparing TN and CE under fasting conditions, there were no significant changes in glucose, insulin, or TG concentrations (all p > 0.36). In contrast, CE significantly increased FFA concentrations (p = 0.002; n = 38). Bias was absent for all parameters, but heterogeneity was observed for insulin (I2 = 74.8%). CE primarily affects FFA concentration, likely reflecting cold-induced BAT activity. This suggests that circulating FFAs, serving as the primary fuel for thermogenesis, could indicate BAT activation. However, understanding the effects of BAT activation on overall metabolism requires a broader approach beyond fasting glucose and lipid concentration measurements.

Effects of internet-based exercise intervention on depression and anxiety: A systematic review and meta-analysis.

While exercise is acknowledged for its positive effects on depression and anxiety symptoms, the benefits of internet-based exercise on mental health have not been extensively examined. This study seeks to systematically review and quantify the outcomes of high-quality randomized controlled trials (RCTs) that investigate the impact of internet-based exercise on depression and anxiety symptoms. Following the PRISMA 2020 guidelines, we conducted a comprehensive meta-analysis of RCTs. Databases, including Web of Science Core Collection, PubMed, PsycINFO, Medline, BIOSIS Previews, SPORTDiscus, and Education Source, were scoured through in September 2023. After quality assessment and data extraction, the analysis was performed using R. Using random effects models, effect sizes were determined and subsequently represented as standardized mean differences (SMD). Our analysis incorporated data from 11 RCTs, involving a cohort of 1009 participants. We observed a modest yet significant reduction in depression and anxiety symptoms, with an SMD of -0.44 [95% confidence interval (CI) (-0.63, -0.26), I^2 = 79.3%, P < .01]. Interestingly, the effects were more pronounced in individuals diagnosed with depression, as indicated by an SMD of -0.96 [95% CI (-1.55, -0.37), I^2 = 82%, P < .01]. Furthermore, participants utilizing smartphone applications as part of their intervention reported a meaningful reduction in their symptoms, evidenced by an SMD of -0.52 [95% CI (-0.90, -0.14), I^2 = 87%, P < .01]. Additionally, short-term interventions, specifically those lasting <12 weeks, indicated a notable alleviation in depression symptoms, with an SMD of -0.76 [95% CI (-1.38, -0.14), I^2 = 86%, P < .01]. Internet-based exercise interventions yield significant amelioration in depression and anxiety symptoms, with heightened efficacy observed among individuals with depression. Notably, short-term interventions, specifically those under 12 weeks, demonstrate enhanced benefits for depression relief.

Short Versus Regular Periods of Cast Immobilization for Distal Radial Fractures: A Systematic Review and Meta-Analysis.

The current research on the recommended durations for cast immobilization in adults with distal radial fractures (DRFs) lacks a clear consensus or definitive conclusion. The standard practice involves casting immobilization for five to six weeks. The debate revolves around the potential benefits of shorter periods (three to four weeks) without compromising patient outcomes. While previous research has delved into this subject through systematic reviews, our study stands out by conducting a meta-analysis, aiming for a more precise understanding of whether short or regular cast immobilization duration proves more effective for treating DRFs. A systematic search was conducted across PubMed, Embase, and the Cochrane Library databases to identify relevant studies. The focus was on comparing the outcomes of DRFs between short (three to four weeks) and regular (five to six weeks) periods of cast immobilization. The evaluated parameters include the shortened disabilities of the arm, shoulder, and hand questionnaire (quick (q) DASH); patient-rated wrist evaluation (PRWE); visual analog scale (VAS) score after cast removal; total complications; and the occurrence of complex regional pain syndrome (CRPS). Data synthesis employed the random-effects models, presenting the results as mean difference (MD) and weighted odds ratio (OR) with corresponding 95% confidence intervals (CI). We included three randomized controlled trials (RCTs) with 252 patients, of whom 125 (49.6%) were immobilized in a cast for three to four weeks. The average age of participants was 61.20 years, and the follow-up duration was one year. The QDASH scores were significantly lower at 12 weeks (MD -6.72; 95% CI -10.76 to -2.69; p = 0.001), six months (MD -4.46; 95% CI -7.42 to -1.50; p = 0.003), and one year (MD -4.89; 95% CI -7.45 to -2.33; p = 0.0002) in patients treated with short periods compared to those with regular periods. The PRWE scores at six months (MD -2.33; 95% CI -8.10 to 3.43; p=0.43) did not significantly differ between groups. Also, the PRWE scores were significantly lower at one year (MD -4.93; 95% CI -9.03 to -0.82; p = 0.02) in the shorter cast-immobilization-period group. There were no significant differences in VAS score after cast removal, total complications, or CRPS. The meta-analysis of RCTs on DRFs reveals that shorter periods of cast immobilization lead to better patient-reported functional outcomes (qDASH and PRWE). This suggests a potential benefit of reducing the immobilization duration for DRF patients, offering clinicians valuable insights for improved patient care and informed decision-making in clinical practice.

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials

BackgroundThe benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated.MethodsWe searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs).ResultsThree studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49–0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62–0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87–1.53; p = 0.34).ConclusionsIn this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.

Treatment of pulmonary arterial hypertension in patients with connective tissue diseases: a systematic review and meta-analysis

The evidence for the treatment of connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) mostly depends on subgroup or post hoc analysis of randomized controlled trials (RCTs). Thus, we performed a meta-analysis of RCTs that reported outcomes for CTD-PAH. PubMed and EMBASE were searched for CTD-PAH treatment. The selected outcomes were functional class (FC) change, survival rates, 6-min walk distance (6-MWD), clinical worsening (CW), N-terminal prohormone BNP (NT-proBNP), pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), right atrial pressure (RAP), and cardiac index (CI). The meta-analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42020153560). Twelve RCTs conducted with 1837 patients were included. The diagnoses were systemic sclerosis in 59%, SLE in 20%, and other CTDs in 21%. The pharmacological interventions were epoprostenol, treprostinil, sildenafil, tadalafil, bosentan, macitentan, ambrisentan, riociguat, and selexipag. There was a significant difference between interventions and placebo in FC, 6MWD, CW, PVR, RAP, and CI that favored intervention. Our analysis showed a 39% reduction in the CW risk with PAH treatment. The short-term survival rates and mean serum NT-proBNP changes were similar between the study and control groups. Treatment for CTD-PAH had favorable effects on clinical and hemodynamic outcomes but not on survival and NT-proBNP levels. Different from the previous meta-analyses that focused on 6-MWD, time to clinical worsening, and CW as outcomes, this meta-analysis additionally reports the pooled analysis of change in FC, hemodynamic measurements (RAP, PVR, CI), and NT-proBNP, some of which have prognostic value for PAH.

Aspirin for the Primary Prevention of Cardiovascular Diseases in Patients with Chronic Kidney Disease: An Updated Meta-analysis.

Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin administered for primary prevention of CVD in patients with chronic kidney disease. PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 22 June 2023. Randomized controlled trials (RCTs) and cohort studies evaluating aspirin as primary prevention of CVD in chronic kidney disease were included. Meta-analysis was conducted using random-effects models. Overall, 11 studies (6 RCTs and 5 cohort studies) with 24,352 patients were included. The meta-analysis of RCTs indicated that aspirin was associated with lower risk of major adverse cardiovascular events [hazard ratio (HR): 0.79; 95% confidence intervals (CI): 0.64-0.97] and higher risk of major bleeding [risk ratio (RR): 1.35; 95% CI 1.15-1.58]. Incorporating observational evidence led to statistically non-significant findings in terms of risk of both cardiovascular events (pooled HR: 0.97; 95% CI 0.75-1.25; low certainty) and major bleeding (pooled RR: 1.21; 95% CI 0.99-1.48; moderate certainty). No statistically significant differences between aspirin and placebo were observed in the outcomes of mortality, coronary heart disease, stroke and renal events. RCT evidence points to a possible benefit in cardiovascular event reduction from aspirin administration, at the cost of increased major bleeding risk. This finding was not confirmed when the existing observational evidence was incorporated. Further research should determine the most appropriate subpopulation of chronic kidney disease patients that would benefit the most from prophylactic aspirin therapy. The study protocol has been prospectively registered and is publicly available from: https://doi.org/10.17504/protocols.io.261ged63jv47/v1 .

Efficacy of antithrombin administration for patients with sepsis: A systematic review, meta-analysis, and meta-regression.

There have been inconsistent reports regarding the effect of antithrombin on sepsis; furthermore, there are limited reports on how dosage affects therapeutic efficacy. Thus, we aimed to perform a systematic review and meta-analysis of the use of antithrombin for sepsis and a meta-regression analysis of antithrombin dosage. We included randomized controlled trials (RCTs) and observational studies of adult patients with sepsis who received antithrombin. Outcomes included all-cause mortality and serious bleeding complications. Statistical analyses and data synthesis were performed using a random-effects model; further, meta-regression and funnel plots were used to explore heterogeneity and biases. Seven RCTs and six observational studies were included. Most patients in the RCTs and observational studies had severe sepsis and septic-disseminated intravascular coagulation (DIC), respectively. A meta-analysis using RCTs showed no significant differences in mortality between the antithrombin and control groups. However, the meta-analysis of observational studies indicated a trend of decreasing mortality rates with antithrombin administration (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.68-0.92; p = 0.002). Bleeding complications were significantly higher in the antithrombin group than in the control group in both study types (OR, 1.90; 95% CI, 1.52-2.37; p < 0.01). The meta-regression analysis showed no correlation between antithrombin dosage and mortality. A meta-analysis of RCTs confirmed no survival benefit of antithrombin, whereas that of observational studies, which mostly focused on septic DIC, showed a significant beneficial effect on improving outcomes. Indications of antithrombin should be considered based on its beneficial and harmful effects.

Effectiveness of Faster Aspart versus Insulin Aspart in Children with Type 1 Diabetes: A Meta-Analysis.

Intensive insulin regimens are recommended to achieve glycemic goals in children and adolescents with type 1 diabetes. Fast-acting insulin aspart (faster aspart) is a new formulation of insulin aspart (IAsp) in which L-arginine and niacinamide are added to assure formulation stability, early absorption, and ultra-fast action. This meta-analysis compares faster aspart with IAsp for blood sugar control in children with type 1 diabetes. This study suggested treating diabetes with insulin, especially in children with type 1 diabetes. PubMed, MEDLINE, Embase, Cochrane Library, Web of Science, and Google Scholar were searched from 2000 to 2023 without language restrictions. Blood glucose monitoring, HbA1c, care model, insulin aspart, IAsp, faster aspart, type 1 diabetes, and pediatrics are Mesh keywords. Cochrane Q statistics and index tested heterogeneity. To account for heterogeneity, Q=145.99 (P-value < 0.001) and =97.26%, and the random-effect model was used to aggregate primary study results. The meta-analysis of randomized-controlled trials was conducted in accordance with PRISMA standards. The overall estimate measure i.e. mean difference was found to be 5.44 [0.45, 10.44] and 7.71 [7.16, 8.26] which indicate significant reduction in the HbA1C level in the fast acting insulin aspart group as compared to the IAsp in T1D. However, the mean difference with respect to BMI was found to be -0.06 [-0.60, 0.48] which indicate non-significant reduction. Faster aspart had faster onset and more early exposure than IAsp in children and adolescents with greater and more variable anti-insulin antibody levels than adults did. Hence fast-acting insulin aspart may provide better glucose control than IAsp in T1D.