Meta-analysis Of Randomized Controlled Trials Research Articles

Are the Modern Diets for the Treatment of Obesity Better than the Classical Ones?

Conventional hypocaloric diets, providing continuous energy restriction, are considered to be the cornerstone of dietary management of obesity. Although energy-restricted diets are overall safe, healthy, and modestly effective, their long-term adherence is difficult to accomplish. Intermittent fasting and ketogenic diets have emerged as attractive alternative dietary options for weight loss and improvement in cardiometabolic risk. Intermittent fasting is a unique dietary pattern characterized by periods of eating alternated with periods of fasting. Ketogenic diets are very low in carbohydrate, modest in protein, and high in fat. Several systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported beneficial but short-lived effects of intermittent fasting and ketogenic diets on various obesity-related health outcomes. Although for both diets, the current evidence is promising and steadily evolving, whether they are better than traditional calorie-restricted diets, whether they can safely lead to sustained weight loss and overall health benefits, and their effects on body composition, weight loss maintenance, energy intake and expenditure, diet quality, and cardiometabolic risk factors are still not unequivocally proven. The aim of the present review is to summarize the current state of evidence regarding the effects of these two popular modern diets, namely intermittent fasting and ketogenic diets. We describe the rationale and characteristics of different dietary protocols, we analyze the major mechanisms explaining their weight loss and cardiometabolic effects, and we provide a concise update on their effects on body weight and cardiometabolic risk factors, focusing on meta-analyses of RCTs. We also discuss knowledge gaps in the field of these diets, and we indicate directions for future research.

Comparison of the efficacy and safety between different oral P2Y12 receptor inhibitors in patients with acute coronary syndrome: a systematic review and meta-analysis

Abstract Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor for at least 1 month is the mainstay of therapy after an acute coronary syndrome (ACS). Despite several randomized controlled trials (RCTs) having compared different DAPT regimens after an ACS, the choice of the optimal P2Y12 receptor inhibitor is still debated. Purpose We aimed to compare the efficacy and safety profiles of the new P2Y12 receptor inhibitors (prasugrel and ticagrelor) versus clopidogrel in patients with ACS through a meta-analysis of RCTs. Methods We performed an extensive literature search, from January 1970 to December 2021 using PubMed database. Studies were eligible if they were RCTs directly comparing different oral P2Y12 receptor inhibitors in patients with ACS. Data on study methods, patient characteristics, and outcomes of interest (all-cause and cardiovascular death, recurrent myocardial infarction, stroke, major and non-major bleeding) were extracted from the original publications. We performed a meta-analysis using a random-effects model with the Mantel–Haenszel method. The effect measures of each study included were calculated and reported as odds ratio (OR) with 95% confidence interval (CI), visually presented in forest plots. A two-sided p-value <0.05 was considered statistically significant. Heterogeneity was tested using the I2-statistic. Results A total of 117 studies were available for the analysis; after full reading 11 studies were eligible to be analyzed. The 11 studies reported data on 50,722 patients: 25,424 [50.1%] taking a new oral P2Y12 receptor inhibitor and 25,298 [49.9%] taking clopidogrel. Patients receiving ticagrelor or prasugrel showed a lower risk of all-cause mortality (OR 0.88, 95% confidence interval [CI] 0.80–0.97, I2=8%), cardiovascular mortality (OR 0.88, 95% CI 0.81–0.95, I2=0%), and recurrent myocardial infarction (OR 0.86, 95% CI 0.76–0.97, I2=43%) compared to those receiving clopidogrel. The two groups did not differ significantly concerning the risk of stroke (OR 0.98, 95% CI 0.82–1.17, I2=0%), major bleeding (OR 1.05, 95% CI 0.97–1.15, I2=0%), or non-major bleeding (OR 1.36, 95% CI 0.85–2.20, I2=67%). By restricting the analysis to the studies comparing ticagrelor versus clopidogrel, the ticagrelor group showed a lower risk of all-cause mortality (OR 0.79, 95% CI 0.70–0.90, I2=0%), but a higher risk of non-major bleeding (OR 1.67, 95% CI 1.05–2.66, I2=30%). There was no significant difference between ticagrelor and clopidogrel in terms of cardiovascular death (OR 0.87, 95% CI 0.73–1.05, I2=0%), stroke (OR 1.06, 95% CI 0.85–1.13, I2=0%), or major bleeding (OR 1.02, 95% CI 0.93–1.12, I2=0%). Conclusions In patients with an ACS, a DAPT strategy with aspirin plus either prasugrel or ticagrelor is associated with a reduced risk of all-cause and cardiovascular mortality as well as of recurrent myocardial infarction compared to aspirin plus clopidogrel, without an increased risk of bleeding. Funding Acknowledgement Type of funding sources: None.

Omega 3 fatty acid supplementation improves physical performance: a systematic review and meta-analysis of RCTs

Abstract Background Omega 3 polyunsaturated fatty acids (n-3, PUFA) show promise for improving muscle mass, strength and measures of physical performance that may ameliorate sarcopenia. Purpose To perform an updated meta-analysis of n-3 interventions with detailed subgroup analysis on physical performance/strength and muscle mass, with sub-group analysis on duration, age, BMI, sex, and location, amongst others. Methods We followed The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) –checklist for systematic reviews and meta-analysis. Literature was searched (ISI, Scopus and PubMed databases up to October 2021) with terms related to n-3 (alpha linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, fish oil etc.) muscle mass, strength and physical performance (using the 30 s Chair Stand Test [30CST] for muscle strength and endurance and the Timed Up an Go Test [TUG] for physical performance; both are useful and simple tools that can be used to assess sarcopenia). Human n-3 randomised controlled trials (RCTs) were included and assessed for methodological quality (Cochrane quality assessment tool). Weighted mean differences (WMDs) with 95% confidence intervals (CIs) and random-effect model analysis, and I-squared (I2) statistic were used to assess outcomes and heterogeneity respectively. Subgroup and sensitivity analysis were performed, and Begg's and Egger's tests evaluated publication bias. Statistical analysis used STATA 11 software and a p-value of <0.05 was considered statistically significant. Results The primary meta-analyses for functional performance (TUG, 7 RCTs, 8 interventions, n=259) and strength (30CST, 5 RCTs, 6 interventions, n=180), favoured n-3 PUFA (p<0.001). TUG (weighted mean change (WMD): −0.35 s; 95% CI: −0.53, −0.18; I2=0.0%) (Figure 1A) and 30CST (WMD: 2.23 repetitions; 95% CI: 1.34, 3.32; I2=67.6%) (Figure 1B). Subgroup analysis for TUG was significant for female sex (WMD: 2.92 reps; 95% CI: 2.37, 3.46; I2=33.1%), BMI ≥25 kg/m2 (WMD: −0.36 s; 95% CI: −0.58, −0.17; I2=16.9%), and for 30CST by duration ≥16 weeks (WMD: 2.60 reps; 95% CI: 1.37, 3.83; I2=0.0%) (all p<0.001). There were no significant effects on muscle mass and handgrip strength, and subgroup analysis showed negligible influence. Publication bias was minimal and sensitivity analysis did not influence findings. Conclusions We showed novel favourable effects of n-3 PUFA on specific measures of strength and physical performance in some populations but not on measures of muscle mass and other strength tests. The beneficial effects of n-3 on these measures may be due to various mechanisms that regulate muscle quality (rather than quantity). Further studies are needed to elucidate the dose, duration and other influential variables. Funding Acknowledgement Type of funding sources: None.

Efficacy of psychological interventions for mental health and pregnancy rates among individuals with infertility: a systematic review and meta-analysis.

Depression and anxiety are highly prevalent among individuals struggling with infertility. Thus, numerous psychological interventions have been adapted to infertility, with the aim of relieving distress as well as increasing pregnancy rates. This systematic review and meta-analysis aimed to identify all randomized controlled trials (RCTs) evaluating the effect of psychological interventions on infertility-related distress and pregnancy rates among individuals and/or couples with infertility and to analyse their overall effect. It also sought to examine potential treatment moderators, including intervention length, format and therapeutic approach. An electronic search of 11 databases, including MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials, was performed for studies published until January 2022. The inclusion criteria were RCTs conducted on humans and published in English. Psychological outcomes of interest included anxiety, depression, infertility-related distress, wellbeing and marital satisfaction. The Cochrane Risk of Bias tool was used to assess study quality, and the Grading of Recommendations Assessment, Development and Evaluation was used to assess the overall quality of the research evidence. There were 58 RCTs in total, including 54 which included psychological outcomes and 21 which assessed pregnancy rates. Studies originated from all regions of the world, but nearly half of the studies were from the Middle East. Although a beneficial effect on combined psychological outcomes was found (Hedge's g = 0.82, P < 0.0001), it was moderated by region (P < 0.00001) such that studies from the Middle East exhibited large effects (g = 1.40, P < 0.0001), while the effects were small among studies conducted elsewhere (g = 0.23, P < 0.0001). Statistically adjusting for study region in a meta-regression, neither intervention length, therapeutic approach, therapy format, nor participant gender (P > 0.05) moderated the effect of treatment. A beneficial treatment effect on pregnancy (RR (95% CI) = 1.25 (1.07-1.47), P = 0.005) was not moderated by region, treatment length, approach or format (P > 0.05). Largely due to the lack of high quality RCTs, the quality of the available evidence was rated as low to moderate. This is the first meta-analysis of RCTs testing the effect of psychological interventions on infertility-related distress and pregnancy rates. These findings suggest that in most regions of the world, psychological interventions are associated with small reductions in distress and modest effects on conception, suggesting the need for more effective interventions. These findings must be considered in light of the fact that the majority of the included RCTs were deemed to be at high risk of bias. Rigorously conducted trials are needed.

Safety and tolerability of solifenacin in children and adolescents with overactive bladder- a systematic review

Solifenacin is an anticholinergic that is used to treat overactive bladder syndrome (OAB) in children. It is important to ascertain the safety and tolerability of solifenacin in the paediatric population as solifenacin offers an alternative, is more bladder specific, and should have less anticholinergic side effects than other therapies. The aim of this study is to systematically evaluate the safety and tolerability of solifenacin in children and adolescents with OAB. We included studies that reported the safety and tolerability of solifenacin in children and adolescents. All study types were included. Electronic searches were conducted in Ovid MEDLINE, Ovid Embase, TRIP, CINAHL and ICTRP on the 18th of January 2022. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0 (ROB-2) for randomised controlled trials (RCTs) and the Newcastle-Ottowa scale for cohort studies. A total of twelve studies including two RCTs were included in this review. Results from the meta-analysis of RCTs showed the commonest side effects were constipation (RR 3.5, 95%CI 0.9-13.7) and dry mouth (RR 3.1 95%CI 0.2-53). In terms of tolerability, the effect estimate of ceasing solifenacin due to an adverse effect was 2.7 (95%CI 0.8-9.1). Within the cohort studies, out of the 779 patients 21.7% experienced side effects. The most common side effects were constipation (6.8%) and dry mouth/lips (6.0%) and 3.5% of patients ceased solifenacin due to adverse effects. Overall, the certainty of the evidence for side effects and tolerability were very low. The reported incidence of side effects is low, and less than reported with oxybutynin use. However, the very low certainty of the evidence means the findings should be interpreted with caution. There is limited reporting of a prolonged QTc interval on ECG. Studies that described this only had an increase of QTc from baseline and not a clinically significant prolonged QTc that resulted in arrhythmias. Solifenacin is an alternative anticholinergic for the treatment of OAB in children. However, given the paucity of good quality data on safety and tolerability it should be used cautiously in children with close monitoring for potential side effects.

Nutritional support after hospital discharge improves long-term mortality in malnourished adult medical patients: Systematic review and meta-analysis

In patients with malnutrition there is an increased long-term risk for mortality beyond the preciding hospital stay. We investigated the effects of postdischarge nutritional support in the outpatient setting on all-cause mortality in the populaton of malnourished medical patients in a systematic review of randomized controlled trials. We searched MEDLINE and EMBASE, from inception to December 21, 2022. Randomized-controlled trials investigating nutritional support in medical patients following hospital discharge vs. control group (usual care, placebo and no nutritional support) were included. Data were independently extracted by two authors and were pooled using random effects model. Our primary outcome was all cause-mortality up to 12-months (end of intervention) of hospital discharge. We included 14 randomized-controlled trials with a total of 2438 participants and mostly moderate trial quality. Compared to the control group, patients receiving outpatient nutritional support had lower mortality (13 trials, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.48 to 0.84, p=0.001, I2=1%). Nutritional support was also associated with a significant increase in the mean daily intake of energy (568kcal, 95% CI 24 to 1,113, p=0.04), proteins (24g, 95% CI 7 to 41), p=0.005) and body weight (1.1kg, 95% CI 0.6 to 1.7), p<0.001). No differences were found on hospital readmissions and handgrip strength. This meta-analysis of randomized-controlled trials with mostly moderate trial quality suggests that nutritional support in the outpatient setting significantly increases nutritional intake as well as body weight, and importantly improves survival. Further large-scale and high-quality intervention trials are needed to confirm these findings.

Mindfulness-Oriented Recovery Enhancement for Addictive Behavior, Psychiatric Distress, and Chronic Pain: A Multilevel Meta-Analysis of Randomized Controlled Trials.

ObjectivesMindfulness-Oriented Recovery Enhancement (MORE) is an integrative intervention designed to ameliorate addiction, chronic pain, and psychiatric symptoms. Although multiple randomized controlled trials (RCTs) have examined the clinical efficacy of MORE, no study has quantitatively synthesized this body of research. Thus, we conducted a meta-analysis of RCTs examining the effects of MORE on addictive behaviors, craving, opioid dose, pain, and psychiatric symptoms.MethodsRelevant manuscripts were identified through comprehensive searches of four bibliographic databases. Two- and three-level random-effects models were used to generate synthesized effect size estimates, and meta-regressions were performed to examine whether study and sample characteristics influenced the magnitude of aggregate effect sizes.ResultsOur search identified 16 manuscripts reporting data from eight RCTs (N = 816). Moderate to small effects in favor of MORE were observed for addictive behaviors (SMC = − .54, p = .007), craving (SMC = − .42, p = .010), opioid dose (MC = − 17.95, p < .001), chronic pain (SMC = − .60, p < .001), and psychiatric symptoms (SMC = − .34, p < .001). MORE’s effects on psychiatric symptoms and craving were not moderated by participant race, gender, age, or income.ConclusionsStudy findings provide empirical evidence of MORE’s efficacy for a wide diversity of individuals, and as such, MORE should now be disseminated broadly throughout the healthcare system.Meta-analysis Pre-registration: PROSPERO #CRD42022319006Supplementary InformationThe online version contains supplementary material available at 10.1007/s12671-022-01964-x.

A Network Meta-Analysis and GRADE Assessment of the Effect of Preoperative Oral Antibiotics with and Without Mechanical Bowel Preparation on Surgical Site Infection Rate in Colorectal Surgery.

To compare the effect of different methods of bowel preparation on the incidence of surgical site infections (SSI), anastomotic leakage (AL), and mortality in patients undergoing elective colorectal surgery. Recent guidelines advise mechanical bowel preparation with oral antibiotics (MBP-OA) for the prevention of SSI in colorectal surgery. Recent trials suggest oral antibiotics (OA) alone may be sufficient. PubMed, MEDLINE, and Embase were searched from inception until 10-08-2021. We included randomized controlled trials (RCTs) comparing multiple methods of bowel preparation (mechanical bowel preparation [MBP], OA, MBP-OA, or no preparation) with regards to clinical outcomes such as incidence of SSI, AL, and mortality rates. A frequentist random-effects network meta-analysis was conducted to estimate the network effects of the different treatment options. We included 48 studies with 13,611 patients. Compared to no preparation, combined direct and indirect network estimates showed a relative risk (RR) for SSI of 0.57 (95% confidence interval [CI], 0.45-0.72) for MBP-OA, 0.68 (95% CI, 0.49-0.95) for OA, and 1.05 (95% CI, 0.87-1.26) for MBP. The RR for MBP-OA compared to OA was 0.84 (95% CI, 0.60-1.19); in sensitivity analysis of mainly laparoscopic procedures this effect of MBP-OA was more profound (RR, 0.56; 95% CI, 0.31-0.99). This network meta-analysis of RCTs finds that both mechanical bowel preparation with oral antibiotics and oral antibiotics alone are comparably effective in the prevention of SSI. The evidence is uncertain about the relative benefit of MBP-OA compared to OA alone. Therefore, it seems justified to use either of the 2 for the prevention of SSI in colorectal surgery.

Comparing mid-term outcomes of Cox-Maze procedure and pulmonary vein isolation for atrial fibrillation after concomitant mitral valve surgery: A systematic review.

Although concomitant pulmonary vein isolation (PVI) is used more frequently than the Cox-Maze procedure, which is currently the gold standard treatment for atrial fibrillation (AF), data on the comparative effectiveness of the two procedures after concomitant mitral valve (MV) surgery are still limited. We conducted a systematic review to identify randomized controlled trials (RCTs) and observational studies comparing the mid-term mortality and recurrence of AF after concomitant Cox-Maze and PVI in patients with AF undergoing MV surgery based on 12-month follow-up. Medline, EMBASE databases, and the Cochrane Library were searched from 1987 up to March 2022 for studies comparing concomitant Cox-Maze and PVI. Additionally, a meta-analysis of RCTs was performed to compare the mid-term clinical outcomes between these two surgical ablation techniques. Three RCTs and three observational studies meeting the inclusion criteria were included in this systematic review with 790 patients in total (532 concomitant Cox-Maze and 258 PVI during MV surgery). Most studies reported that the concomitant Cox-Maze procedure was associated with higher freedom from AF at 12-month follow-up than PVI. Regarding AF recurrence, estimates pooled across the three RCTs indicated large heterogeneity and high uncertainty. In the largest and highest quality RCT, 12-month AF recurrence was higher in the PVI arm (risk ratio = 1.58, 95% CI: 0.91-2.73). In two out of three higher-quality observational studies, 12-month AF recurrence was higher in PVI than in the Cox-Maze arm (estimated adjusted probabilities 11% vs. 8% and 35% vs. 17%, respectively). RCTs demonstrated comparable 12-month mortality between concomitant Cox-Maze and PVI, while observational studies demonstrated the survival benefit of Cox-Maze. Concomitant Cox-Maze in AF patients undergoing MV surgery is associated with better mid-term freedom from AF when compared to PVI with comparable mid-term survival. Large observational studies suggest that there might be a mid-term survival benefit among patients after concomitant Cox-Maze. Further large RCTs with longer standardized follow-up are required to clarify the benefits of concomitant Cox-Maze in AF patients during MV surgery.

Efficacy and safety of permissive hypercapnia in preterm infants: A systematic review

In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, the findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial. To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation. MEDLINE, EMBASE, CENTRAL, and CINAHL STUDY SELECTION: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Two reviewers independently screened the title, abstract, and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment and Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model. Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR], 0.94; 95% confidence interval [CI], 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR, 1.05; 95% CI, 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR, 1.69; 95% CI, 0.98-2.91; very low CoE), but the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE). The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. Permissive hypercapnia did not have any significant benefit or harm in preterm infants.

Antioxidant-rich foods, antioxidant supplements, and sarcopenia in old-young adults ≥55 years old: A systematic review and meta-analysis of observational studies and randomized controlled trials

Sarcopenia is a disabling muscular multifactorial disease involving the oxidation process in old-young adults. We aimed to evaluate the relationship between antioxidant-rich foods (A-RF) and sarcopenia (muscle mass, strength, and function) based on observational studies (OS), and to assess the effectiveness of antioxidant interventions in ≥55-year-old adults via randomized controlled trials (RCTs). Moreover, to confirm if the OS results were in accordance with the RCTs results. We searched in the MEDLINE®/PubMed, Cochrane Library, and CINAHL databases from 2000 to 2020 about sarcopenia and specific nutrients/foods. The risk of bias was assessed and meta-analyses were performed using the Review Manager program. The systematic review included 28 studies (19 OS, 9 RCTs), whereas the meta-analysis included 4 RCTs. Results of the systematic review of OS revealed that higher A-RF consumption was associated with better sarcopenia outcomes. Results of the RCTs meta-analysis indicated that higher fruit/vegetable consumption, supplementation with magnesium, and vitamin E plus vitamin D and protein significantly reduced the time to complete 5 stands (mean difference; 95% CI;-1.11s; 1.70,-0.51; p<0.01). Additionally, including tea catechin supplementation significantly increased handgrip strength (1.02kg; 0.60, 1.44; p<0.01). In sum, A-RF or antioxidant supplementation could be effective tools for sarcopenia, especially improving muscle strength and function. The best interventions according to the meta-analysis of the RCTs were supplementation of vitamin E in combination with vitamin D and protein, magnesium, tea catechins, and increasing fruit and vegetable consumption. PROSPERO (CRD42020183045).

Efficacy and safety of intranasal ketamine compared with intranasal dexmedetomidine as a premedication before general anesthesia in pediatric patients: a systematic review and meta-analysis of randomized controlled trials.

To compare the efficacy and safety of intranasal ketamine with intranasal dexmedetomidine as a premedication in pediatric patients undergoing general anesthesia for elective surgery or other procedures. We conducted a systematic literature search in PubMed, PubMed Central, Scopus, LILACS, Google Scholar, the Cochrane Database of Systematic Reviews, and trial registries for randomized controlled trials (RCTs) comparing intranasal ketamine with intranasal dexmedetomidine as preanesthetic medication in elective surgery or other procedures in pediatric patients. We used Review Manager software version 5.4.1 for statistical analysis and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the methodological quality of the included studies with the RoB 2 risk of bias tool. All outcomes were pooled using the Mantle-Haenszel method and a random-effects model. The quality of evidence was assessed using the GRADE approach. Out of 2,445 full texts assessed, we included ten RCTs in the analysis. The efficacy outcomes did not fulfill the comparability criteria between intranasal ketamine and intranasal dexmedetomidine for sedation at parental separation (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.04; I2 = 89%; GRADE evidence, low), mask acceptance (RR, 0.86; 95% CI, 0.66 to 1.13; I2 = 50%; GRADE evidence, low), and iv canulation (RR, 1.16; 95% CI, 0.79 to 1.69; I2 = 69%; GRADE evidence, very low). Intranasal ketamine-treated patients showed a higher incidence of nausea and vomiting (RR, 2.47; 95% CI, 1.24 to 4.91; I2 = 0; GRADE evidence, moderate). Significantly more bradycardia was observed in the intranasal dexmedetomidine group (RR, 0.16; 95% CI, 0.04 to 0.70; I2 = 40%; GRADE evidence, moderate) than in the ketamine group. The low to very low-quality evidence in this systematic review and meta-analysis of RCTs neither confirmed nor refuted comparable premedication efficacy of intranasal ketamine and dexmedetomidine in terms of parental separation, mask acceptance, and iv cannulation in a pediatric population. Clinical decision-making is likely to be influenced by differences in gastrointestinal and cardiovascular safety profiles. PROSPERO (CRD42021262516); registered 22 July 2021.

Association Between Vitamin D Supplementation and Fall Prevention.

BackgroundFalls occur frequently among older individuals, leading to high morbidity and mortality. This study was to assess the efficacy of vitamin D in preventing older individuals from falling.MethodsWe searched the PubMed, Cochrane Library, and EMBASE databases systematically using the keywords “vitamin D” and “fall” for randomized controlled trials (RCTs) comparing the effects of vitamin D with or without calcium supplements with those of a placebo or no treatment on fall incidence in adults older than 50 years. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs) and 95% CIs with random-effects models.ResultsA total of 38 RCTs involving 61 350 participants fulfilled the inclusion criteria. Compared with placebo, high-dose vitamin D (≥ 700 IU) can prevent falls [RR, 0.87 (95% CI 0.79 to 0.96); ARD, -0.06 (95% CI, -0.10 to -0.02)]. Low-dose vitamin D (<700 IU) was not significantly associated with falls. Subgroup analysis showed that supplemental calcium, 25(OH) D concentration and frequency influenced the effect of vitamin D in preventing falls. Sensitivity analysis showed that vitamin D prevented falls, which was consistent with the primary analysis. In addition, the active form of vitamin D also prevented falls.ConclusionIn this meta-analysis of RCTs, doses of 700 IU to 2000 IU of supplemental vitamin D per day were associated with a lower risk of falling among ambulatory and institutionalized older adults. However, this conclusion should be cautiously interpreted, given the small differences in outcomes.Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42020179390.

A systematic review and meta-analysis of randomised controlled trials in the management of neovascular glaucoma: absence of consensus and variability in practice

PurposeNeovascular glaucoma (NVG) is characterised by neovascularisation of the angle and therefore elevated intraocular pressure (IOP). This results in progressive optic neuropathy and loss of visual acuity. Treatment aims to reduce IOP in order to prevent optic nerve damage. A systematic review was completed synthesising results from randomised control trials (RCTs) comparing interventions for the management of NVG and their efficacy and safety.MethodsData was sourced from Web of Science, Embase and Medline after 1st January 2000. The primary outcome measures were mean IOP at follow-up and success rate. The secondary outcomes included mean IOP lowering medications and total complications. A meta-analysis was completed on comparative studies using Revman (version 5.4).ResultsFor the two studies comparing Ahmed glaucoma valve (AGV) + pan-retinal photocoagulation (PRP) vs AGV + PRP + intra-vitreal bevacizumab (IVB), there was no difference in mean IOP or odds of success from the meta-analysis. From the 4 studies examining the utilisation of anti-vascular endothelial growth factor (anti-VEGF), one study showed lower mean IOP at 1 (p = 0.002) and 3 months (p = 0.033) for IVB vs sham injection. In the 2 studies studying transcleral diode laser (TDL), there were no significant findings. From the 4 studies looking at trabeculectomy (trab), lower mean IOP at 6 (p = 0.001), 9 (p = 0.01), 12 (p = 0.02) and 18 months (p = 0.004) was shown for intra-vitreal ranibizumab (IVR) + PRP + visco-trabeculectomy vs IVR + PRP + trab, and a significantly lower mean IOP was present in the Baerveldt group vs trab at 6 months (p = 0.03). In the 2 studies investigating the AGV, there was a lower mean IOP at 1 month (p = 0.01) in the AGV + triamcinolone (TCA) group. The risk of bias was low for 4 studies, high for 4 studies and 6 studies had some concerns.ConclusionThis is the first meta-analysis of RCTs in the management of neovascular glaucoma. The lack of high-quality evidence contributes to the lack of consensus in managing NVG. Our results highlight modern treatment strategies and the need for better powered RCTs with long-term follow-up in order to establish optimal treatment modalities and true patient outcomes.

Reporting conflicts of interest in randomised trials of patient blood management interventions in patients requiring major surgery: a systematic review and meta-analysis

ObjectiveThis study aimed to systematically review the effects of declared and undeclared conflicts of interest on randomised controlled trials (RCTs) of patient blood management (PBM) interventions.DesignWe performed a secondary analysis...

Clinical implication of recent randomized control trial in primary angle-closure disease management.

Blindness due to primary angle-closure glaucoma (PACG) can be reduced significantly if the ongoing angle-closure process is arrested at an early stage. Various treatments such as laser peripheral iridotomy (LPI), iridoplasty, and clear lens extraction (CLE) have been advocated as first-line therapy for primary angle-closure (PAC), PACG, and high-risk cases of primary angle-closure suspect (PACS). EAGLE study, propagated the effectiveness of CLE over LPI for the management of primary angle closure and have sparked controversy regarding the role of LPI as a first line procedure. Randomized controlled trials (RCT), systematic reviews, and meta-analyses of RCTs done on the same question provide us with a solid base for creating guidelines/modules for our day-to-day clinical practice. A systematic review was conducted, searching several databases, including PubMed, Cochrane Library, EMBASE, and ClinicalTrials.gov, for the last 16 years (January 2005-December 2021) for RCTs with data published related to primary angle-closure disease (PACD). The search strategy included the following terms: "Primary Angle Closure disease," "Primary Angle Closure Glaucoma," "Primary Angle Closure," "Primary Angle Closure Suspect," "clear lens extraction," "laser iridotomy," "laser peripheral iridotomy," "argon laser peripheral iridoplasty," "selective laser trabeculoplasty," "trabeculectomy," "randomized control trial," and "meta-analysis of randomized control trial." In this review, we will discuss recently published RCTs (within the last 16 years) for the management of PACD and their clinical implications in day-to-day practice.

Effects of core training on trunk function, balance, and gait in stroke patients: A systematic review and meta-analysis of randomised controlled trials

Objective The aim of this systematic review and meta-analysis of randomised controlled trials (RCTs) includes determining the effects of core training alone or combined with conventional therapy on trunk function, balance, and gait in stroke patients; analysing these effects considering the stroke stage and the core training type; establishing the methodological quality of the studies published to date; and knowing the best dosage and type of exercise these aspects. Data source Cochrane Library, Medline, Web of Science, Scopus, and Science Direct were searched from inception to January 2022. Review method A review and meta-analysis of RCTs about core intervention effects on trunk function, balance, and gait in stroke patients was carried out following the Preferred Items for Reporting in Systematic Review and Meta-Analyses guidelines. The Cochrane Collaboration tool was used to assess the risk of bias and internal validity of the included studies. Results Twenty-nine studies were included (1030 stroke patients). The mean age of the participants was 58.46 ± 9.89 years, and the average time since the stroke incident was 308.64 ± 175.52 days. The meta-analysis results showed significant improvements in core interventions for trunk function (P ≤ 0.008) and balance (P < 0.00001) but not for gait performance (P = 0.11 in chronic and P = 0.06 in pooled cases). In relation to the differential meta-analysis between training performed on stable and unstable surfaces, no significant differences were found in trunk function (P = 0.06) or balance measures (P = 0.05). Conclusion Core training improves trunk function and balance in acute and chronic patients, but no changes were found in gait performance.

O016 Antibiotics versus appendicectomy for uncomplicated acute appendicitis: an updated meta-analysis of randomised controlled trials

Abstract Introduction Previous meta-analyses of randomised controlled trials (RCTs) on patients with uncomplicated acute appendicitis have demonstrated reduced complication rates with primary antibiotic therapy when compared with appendicectomy. This aim of this systematic review and meta-analysis of RCTs was to provide an update of the efficacy of antibiotic therapy compared with appendicectomy in adult patients with uncomplicated acute appendicitis. Methods MEDLINE, EMBASE and CENTRAL databases were searched with no date or language restriction. Data on complications of treatment, treatment efficacy (defined in the antibiotic group as not undergoing appendicectomy at 1 year, versus surgery without complications or negative histology in the appendicectomy group), readmissions, and length of stay (LOS) were extracted. Results We included 8 RCTs involving 3203 participants (1613 antibiotics/1590 appendicectomy; 2041 males/1162 females). Antibiotics had a reduced treatment efficacy compared with primary appendicectomy (RR 0.75, 95% CI 0.63–0.89). There was no significant benefit of primary antibiotic treatment on complication rates (RR 0.66 95% CI 0.41–1.04). In total 1010/1613 (62.6%) patients had successful antibiotic treatment at 1 year. In the 5 studies which explicitly reported hospital re-admission as an outcome, primary antibiotic treatment had a six-fold increase in readmissions (RR 6.28 95% CI 2.87–13.74). There was no difference in index admission LOS [Mean Difference 0.15 days (95%CI -0.05–0.35)]. Conclusion Primary antibiotic treatment for acute appendicitis is associated with a reduced treatment efficacy and a significant readmission rate, without any benefit on complications or LOS. Approximately 40% of patients initially treated with antibiotics will require surgery within 1 year. Take-home message Contrary to previous meta-analyses, the current study suggests that although primary antibiotic therapy may be tried for uncomplicated acute appendicitis in adults, it is not definitive treatment in the long term.

Pain reduction and adverse effects of intravenous metoclopramide for acute migraine attack: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUNDMetoclopramide may be used to treat people suffering from acute migraine. However, no comprehensive investigation on this issue has been recorded. This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.AIMTo compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department (ED).METHODSWe included randomized controlled trials of participants older than 18 years with acute migraine headaches, which included at least one arm that received intravenous (IV) metoclopramide at the ED. A literature search of PubMed, Web of Science, Cochrane Collaboration, and Reference Citation Analysis on December 31, 2021 retrieved other drugs or placebo-controlled studies without language limitation. The risk of bias was assessed using the Cochrane risk of bias tool. The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment, as measured by the pain scale. Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.RESULTSFourteen trials with a total of 1661 individuals were eligible for review. The risk of bias ranged from low to intermediate. IV metoclopramide administration was not associated with higher pain reduction at 1 h (Standard mean difference [SMD] = -0.03, 95% confidence interval [CI]: -0.33-0.28, P = 0.87). However, metoclopramide was associated with better pain reduction than placebo (SMD = 1.04, 95%CI: 0.50-1.58, P = 0.0002). In addition, side effects were not significantly different between IV metoclopramide and other drugs or placebo (odds ratio [OR] = 0.76, 95%CI: 0.48-1.19, P = 0.09 and OR = 0.92, 95%CI: 0.31-2.74, P = 0.54, respectively).CONCLUSIONMetoclopramide is more effective than placebo in treating migraine in the ED. Despite the observed tendency of decreased side effects, its effectiveness compared to other regimens is poorly understood. More research on this area is needed to treat migraine in acute care settings effectively.

Effects of allopurinol on renal function in patients with diabetes: a systematic review and meta-analysis

Background/Objective Diabetes mellitus is a common “non-gout” disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus. Methods We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis. Results Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment (p = 0.0001) or placebo (p < 0.00001). Moreover, the levels of 24-hour urine protein were significantly lower in the allopurinol group (p < 0.00001). The subgroup analysis of Scr showed that the Scr of patients with an allopurinol treatment duration of fewer than six months was significantly lower than that of the control group (p = 0.03). No significant difference in adverse events (AEs) was identified between the treatment and control groups. Conclusions Our meta-analysis of RCTs showed that oral administration of allopurinol effectively reduced SUA levels in patients with diabetes, and patients’ renal function was protected. More RCTs with larger sample sizes and higher quality are needed to clarify the role of allopurinol use in decreasing blood pressure, maintaining blood glucose levels, and improving renal function in patients with diabetes.