Eligible Randomized Controlled Trials Research Articles

Direct Oral Anticoagulation Versus Warfarin in Left Ventricular Thrombus: Pooled Analysis of Randomized Controlled Trials.

Patients with impaired left ventricular (LV) function can develop LV thrombus, a potentially life-threatening condition due to risk of stroke and embolization. Conventional treatment with vitamin K antagonists (VKAs; e.g., warfarin) puts patients at risk of bleeding, and the use of direct oral anticoagulants (DOACs) appears promising, although data are scant. We searched the published English language literature for randomized controlled trials (RCTs) comparing DOACs with VKAs in LV thrombus. End points were failure to resolve, thromboembolic events (stroke, embolism), bleeding, or any adverse event (composite of thromboembolism or bleeding), or all-cause death. Data were pooled and analyzed in hierarchical Bayesian models. In three eligible RCTs, 141 patients were studied during an average of 4.6months (53.8 patient-years; n=71 assigned to DOAC, n=70 assigned to VKA). A similar number of patients in each treatment arm demonstrated failure to resolve (DOAC: 14/71 vs. VKA: 15/70) and death events (3/71 vs. 4/70). However, patients on DOACs suffered fewer strokes/thromboembolic events (1/71 vs. 7/70; log odds ratio [OR], -2.02 [95% credible interval (CI95 ), -4.53 to -0.31]) and fewer bleeding events (2/71 vs. 9/70; log OR, -1.62 [CI95 , -3.43 to -0.26]), leading to fewer patients on DOACs with any adverse event versus VKAs (3/71 vs. 16/70; log OR, -1.93 [CI95 , -3.33 to -0.75]). In conclusion, pooled analysis of RCT data favors DOACs over VKAs in patients with LV thrombus in terms of both efficacy and safety.

Reporting quality of randomized controlled trials of angina pectoris with integrated traditional Chinese and western medicine interventions: a cross-sectional study

Background and objectiveIntegrated traditional Chinese and western medicine (ITCWM), as a representative type of complex intervention, is commonly used for the treatment of angina pectoris (AP) in clinical practice. However, it is unclear whether the details of ITCWM interventions, such as rationale for selection and design, implementation and potential interactions for different therapies, were adequately reported. Therefore, this study aimed to describe the reporting characteristics and quality in randomized controlled trials (RCTs) of AP with ITCWM interventions.MethodsThrough a search of 7 electronic databases, we identified RCTs of AP with ITCWM interventions published in both English and Chinese from 1st Jan 2017 to 6th Aug 2022. The general characteristics of included studies were summarized, further, the quality of reporting was assessed based on three Checklists, including the CONSORT with 36 items (except for one item 1b about abstract), the CONSORT for abstracts (17 items), and a self-designed ITCWM-related checklist (21 items covering rationale and details of interventions, outcome assessment and analysis). The quality of RCTs published in English and Chinese, as well as journals and dissertations were also compared.ResultsA total of 451 eligible RCTs were included. For the reporting compliance, the mean score (95% Confidence Interval) of the CONSORT (72 scores in total), CONSORT for abstract (34 scores in total), and ITCWM-related (42 scores in total) checklists was 27.82 (27.44–28.19), 14.17 (13.98–14.37) and 21.06 (20.69–21.43), respectively. More than half items were evaluated as poor quality (reporting rate < 50%) among each Checklist. Moreover, the reporting quality of publications in English journals was higher than that in Chinese journals in terms of the CONSORT items. The reporting of published dissertations was better than that in journal publications regarding both the CONSORT and ITCWM-specific items.ConclusionAlthough the CONSORT appears to have enhanced the reporting of RCTs in AP, the quality of ITCWM specifics is variable and in need of improvement. Reporting guideline of the ITCWM recommendations should be developed thus to improve their quality.

P15 EFFICACY AND SAFETY OF LEFT ATRIAL APPENDAGE CLOSURE COMPARED WITH ORAL ANTICOAGULATION IN ATRIAL FIBRILLATION: A META–ANALYSIS OF RANDOMIZED CONTROLLED TRIALS AND PROPENSITY–MATCHED STUDIES

Abstract Backgrounds In the recent years, two randomized controlled trials (RCTs), the PROTECT–AF trial and the PREVAIL trial demonstrated that in atrial fibrillation (AF) patients, left atrial appendage closure (LAAC) compared with oral anticoagulants (OAC), showed a non–inferiority in the prevention of stroke and even a reduction in mortality. Nevertheless, this net clinical benefit was not confirmed in the most recent RCT comparing LAAC vs OAC, the PRAGUE–17 trial. The aim of the present meta–analysis was to evaluate the efficacy and safety of LAAC compared to OAC among available high–quality studies. Methods A systematic search of electronic databases (Medline, Scopus, Embase and the Cochrane Library) was performed to identify eligible RCTs and observational studies with propensity score matching (PSM) analysis. PRISMA guidelines were used for abstracting data and assessing data quality and validity. Outcomes of interest were the occurrence of cardiovascular death (CVD), all cause death, all–type stroke, and major bleedings. Results A total of 3 RCTs and 6 PMS studies involving 6924 patients were identified. After a median follow–up of 2.7 years (IQR 2–4.5), patients who received LAAC had a lower risk of CVD (OR=0.58; 95%CI 0.48–0.71, I2=0%), all cause death (0.59; 95% CI 0.45–0.76, I2 67%) and major bleedings (OR=0.58; 95%CI 0.43–78 I2=52%) compared with patients on OAC. No difference was found between the two groups regarding strokes incidence (OR=0.94; 95% CI 0.76–1.16, I2=0%). Conclusions According to this meta–analysis, LAAC presents a comparable efficacy in the prevention of stroke compared to OAC with a reduced risk of major bleedings, all cause death and CVD that may stand out with longer follow–up.

Ticagrelor vs. clopidogrel for coronary microvascular dysfunction in patients with STEMI: a meta-analysis of randomized controlled trials.

Approximately half of ST-segment elevation myocardial infarction (STEMI) patients who undergo revascularization present with coronary microvascular dysfunction. Dual antiplatelet therapy, consisting of aspirin and a P2Y12 inhibitor (e.g., clopidogrel or ticagrelor), is recommended to reduce rates of cardiovascular events after STEMI. The present study performed a pooled analysis of randomized controlled trials (RCTs) to compare effects of ticagrelor and clopidogrel on coronary microcirculation dysfunction in STEMI patients who underwent the primary percutaneous coronary intervention. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible RCTs up to September 2022, with no language restriction. Coronary microcirculation indicators included the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), myocardial blush grade (MBG), TIMI myocardial perfusion grade (TMPG), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). Seven RCTs that included a total of 957 patients (476 who were treated with ticagrelor and 481 who were treated with clopidogrel) were included. Compared with clopidogrel, ticagrelor better accelerated microcirculation blood flow [cTFC = -2.40, 95% confidence interval (CI): -3.38 to -1.41, p < 0.001] and improved myocardial perfusion [MBG = 3, odds ratio (OR) = 1.99, 95% CI: 1.35 to 2.93, p < 0.001; MBG ≥ 2, OR = 2.57, 95% CI: 1.61 to 4.12, p < 0.001]. Ticagrelor has more benefits for coronary microcirculation than clopidogrel in STEMI patients who undergo the primary percutaneous coronary intervention. However, recommendations for which P2Y12 receptor inhibitor should be used in STEMI patients should be provided according to results of studies that investigate clinical outcomes.

Black representation in critical care randomized controlled trials: a meta-epidemiological study.

The under-representation of Black people within critical care research limits the generalizability of randomized controlled trials (RCTs). This meta-epidemiologic study investigated the proportionate representation of Black people enrolled at USA and Canadian study sites from high impact critical care RCTs. We searched for critical care RCTs published in general medicine and intensive care unit (ICU) journals between 1 January 2016 and 31 December 2020. We included RCTs that enrolled critically ill adults at USA or Canadian sites and provided race-based demographic data by study site. We compared study-based racial demographics with site-level city-based demographics and pooled representation of Black people across studies, cities, and centres using a random effects model. We used meta-regression to explore the impact of the following variables on Black representation in critical care RCTs: country, drug intervention, consent model, number of centres, funding, study site city, and year of publication. We included 21 eligible RCTs. Of these, 17 enrolled at only USA sites, two at only Canadian sites, and two at both USA and Canadian sites. Black people were under-represented in critical care RCTs by 6% compared with population-based city demographics (95% confidence interval, 1 to 11). Using meta-regression, after controlling for pertinent variables, the country of the study site was the only significant source of heterogeneity (P = 0.02). Black people are under-represented in critical care RCTs compared with site-level city-based demographics. Interventions are required to ensure adequate Black representation in critical care RCTs at both USA and Canadian study sites. Further research is needed to investigate the factors contributing to Black under-representation in critical care RCTs.

Clinical efficacy and safety of prolonged versus intermittent administration of antipseudomonal beta-lactam antibiotics in adults with severe acute infections: A meta-analysis of randomized controlled trials

IntroductionIn order to compare the clinical efficacy and safety of prolonged versus intermittent antipseudomonal beta-lactam antibiotic infusion for the treatment of severe acute infections in adult patients, a meta-analysis of randomized controlled trials (RCTs) was performed. MethodsWe systematically searched MEDLINE and Cochrane Library databases until December 2022. The outcomes were all-cause mortality, clinical success, microbiological eradication and adverse events. The pooled risk ratios (RR) were estimated by the fixed or random effect methods according to heterogeneity statistics. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the certainty of evidence for each outcome. ResultsTwenty eligible RCTs with 2081 participants were included in the meta-analysis. The risk of all-cause mortality was significantly lower in the prolonged infusion group than in the intermittent infusion group (RR 0.77, 95% confidence interval [CI] 0.63–0.95, p = 0.01, I2 = 0%; moderate certainty). Treatment with prolonged infusion showed significant benefit in clinical success (RR 1.09, 95% CI 1.02–1.17, p = 0.008, I2 = 19%; moderate certainty). There were no significant differences in microbiological eradication (RR 1.12, 95% CI 0.99–1.28, p = 0.07, I2 = 49%; low certainty), any adverse events (RR 0.96, 95% CI 0.86–1.08, p = 0.50, I2 = 27%; moderate certainty) and serious adverse events (RR 0.99, 95%CI 0.70–1.39 p = 0.95, I2 = 0%; low certainty). ConclusionsProlonged antipseudomonal beta-lactam infusion probably decreases all-cause mortality. Additionally, it probably increases clinical success in adults with severe acute infections. This infusion strategy may result in little to no difference in microbiological eradication and is probably not associated with a rise in any adverse events.The evidence suggests that prolonged infusion may not increase serious adverse events.

The effect of whole grape products on blood pressure and vascular function: A systematic review and meta-analysis of randomized controlled trials

Background and aimsGrape consumption-associated improvements in cardiovascular health have received significant attention over the last few years; however, major gaps have remained in the meta-evidence related to this topic. This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to explore the effect of whole grapes and its products on blood pressure, endothelial function, heart rate, and pulse rate. Methods and resultsFour database (PubMed, Scopus, Web of Sciences, and the Cochrane Library) were searched until the 14th of January 2022. The pooled effect size of interested outcomes was calculated using the random-effects model. Thirty eligible RCTs were identified. Pooled results indicated that compared to the control group, consumption of grape products significantly decreased systolic blood pressure (SBP) (WMD = −3.17 mmHg; 95% CI: −5.36, −0.99 mmHg; P = 0.004; I2 = 64%; P-heterogeneity<0.001); while, vascular cell adhesion molecule-1 (VCAM-1) increased (WMD = 34.11 ng/ml; 95% CI: 0.98, 67.25 ng/ml; P = 0.04; I2 = 2%; P-heterogeneity = 0.4). Although, the certainty of evidence was low and very low, respectively. No significant effect was observed on diastolic blood pressure, endothelial function, heart rate, pulse rate, and soluble intercellular adhesion molecule-1 (sICAM-1). In a subgroup analysis, consumption of whole grape products (raisin and grape powder) induced a significant decrease in SBP (WMD = −2.69 mmHg; 95% CI: −4.81, −0.57; P = 0.01; I2 = 18.1%; P-heterogeneity < 0.001), while grape juice did not. ConclusionThe low certainty of evidence from RCTs revealed that consumption of grape products, especially in whole forms, resulted in a small reduction of SBP but did not influence other markers of cardiovascular health. Prospero registration codeCRD42022379231.

Effects of green tea on lipid profile in overweight and obese women.

The effect of green tea administration on serum lipids' concentrations remains unclear as various investigations, which have explored this topic, have produced conflicting results. Gender might be one of the factors influencing the impact of green tea on the lipid profile. Hence, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of green tea intake on the lipid profile in overweight and obese women. We searched five databases (Web of Science, SCOPUS, Embase, PubMed/Medline, and Google Scholar) using a combination of MeSH and non-MeSH terms. Results were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) and synthesized with a random-effects model. In total, 15 eligible RCTs with 16 arms (1818 participants) were included in the meta-analysis. The combined effect size revealed a significant reduction in total cholesterol (TC) (WMD: -4.45 mg/dl, 95% CI: -6.63, -2.27, P<0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: -4.49 mg/dl, 95% CI: -7.50 to -1.47, P=0.003) concentrations following green tea supplementation in overweight and/or obese women. In addition, a more pronounced reduction of triglyceride (TG) levels occurred when the baseline TG value was ≥150 mg/dL (WMD: -24.45 mg/dL, 95% CI: -40.63 to -8.26, P=0.003). Moreover, a significant decrease in TG concentrations occurred in RCTs conducted on overweight subjects (BMI: 25-29.99 kg/m2) (WMD: -5.88 mg/dl, 95% CI: -10.76 to -0.99, P=0.01). In the subgroup analyses based on the study population, a notable increase in high-density lipoprotein cholesterol (HDL-C) values was observed in obese individuals (>30 kg/m2) (WMD: 2.63 mg/dl, 95% CI: 0.10 to 5.16, P=0.041). Consumption of green tea causes a reduction in LDL-C and TC concentrations in overweight and obese women. The decline in TG levels was notable particularly in overweight patients with hypertriglyceridemia at baseline. In addition, a significant increase in HDL-C was detected in obese subjects following intake of green tea.

Effectiveness of telerehabilitation and home-based falls prevention programs for community-dwelling older adults: a systematic review and meta-analysis protocol

IntroductionFalls among older adults are associated with adverse sequelae including fractures, chronic pain and disability, which can lead to loss of independence and increased risks of nursing home admissions. The...

Postoperative Analgesic Effects of Serratus Anterior Plane Block for Thoracic and Breast Surgery: A Meta-analysis of Randomized Controlled Trials

BACKGROUND: Postoperative pain is a concern after thoracic and breast surgeries. Recent studies have demonstrated that ultrasound-guided serratus anterior plane block (SAPB) could provide postoperative analgesia. OBJECTIVE: The objective of this systematic review and meta-analysis was to examine the effects of SAPB on postoperative analgesia in thoracic and breast surgery. STUDY DESIGN: A systematic review and meta-analysis of randomized control trials (RCTs). METHODS: We systematically queried the PubMed, Embase, Web of Science, and Cochrane Library online databases from their establishment through Mar 31, 2022. Eligible RCTs were selected for the purpose of conducting the meta-analysis. The risk of bias of the included trials was assessed by Cochrane Review Manager. The level of certainty was examined utilizing the GRADE (Grade of Recommendations Assessment, Development, and Evaluation) scale to determine whether the evidence was of high quality or not. RESULTS: During the process of the meta-analysis, a total of 27 pieces of literature was included in the present research. SAPB significantly reduced the intraoperative opioid consumption (mean difference [MD] = -9.52 mg of morphine equivalent, 95% CI, -15.50 to -3.54; P &lt; 0.01, I2 = 98%) and postoperative pain opioid consumption (MD = -23.12 mg of morphine equivalent, 95% CI, -30.59 to -15.65; P &lt; 0.01, I2 = 100%. Also, patients in the SAPB group had lower pain scores during the first postoperative 24 hours. Furthermore, SAPB attenuated the occurrence of postsurgical nausea and vomiting, as well as chronic postsurgical pain. LIMITATIONS: Double-blinding was not performed in some trials, also some assessors were not blinded; the included sample sizes of eligible trials which reported the incidence of chronic postsurgical pain were relatively small; the comparisons between SAPB and other types of blocks were not performed in our meta-analysis. CONCLUSION: Our findings suggest that SAPB not only relieves acute pain after thoracic and breast surgery, but also reduces the incidence of chronic postsurgical pain. KEY WORDS: Thoracic and breast surgery, serratus anterior plane block, meta-analysis

Laparoscopic Nissen Versus Toupet Fundoplication for Short- and Long-Term Treatment of Gastroesophageal Reflux Disease: A Meta-Analysis and Systematic Review.

Laparoscopic Nissen fundoplication (LNF) is the most common standard technique worldwidely for Gastroesophageal reflux disease (GERD). Another type of fundoplication, laparoscopic Toupet fundoplication (LTF), intends to reduce incidence of postoperative complications. A systematic review and meta-analysis are required on short- and long-term outcomes based on randomized controlled trials (RCTs) between LNF and LTF. We searched databases including PubMed, Cochrane, Embase, and Web of Knowledge for RCTs comparing LNF and LTF. Outcomes included postoperative reflux recurrence, postoperative heartburn, dysphagia and postoperative chest pain, inability to belch, gas bloating, satisfaction with intervention, postoperative esophagitis, postoperative DeMeester scores, operating time (min), in-hospital complications, postoperative use of proton pump inhibitors, reoperation rate, postoperative lower oesophageal sphincter (LOS) pressure (mmHg). We assessed data using risk ratios and weighted mean differences in meta-analyses. Eight eligible RCTs comparing LNF (n = 605) and LTF (n = 607) were identified. There were no significant differences between the LNF and LTF in terms of postoperative reflux recurrence, postoperative heartburn, postoperative chest pain, satisfaction with intervention, reoperation rate in short and long term, in-hospital complications, esophagitis in short term, and gas bloating, postoperative DeMeester scores, postoperative use of proton pump inhibitors, reoperation rate in long term. LTF had lower LOS pressure (mmHg), fewer postoperative dysphagia and inability to belch in short and long term and gas bloating in short term compared to LNF. LTF were equally effective at controlling reflux symptoms and improving the quality of life, but with lower rate of complications compared to LNF. We concluded that LTF surgical treatment was superior for over 16 years old patients with typical symptoms of GERD and without upper abdominal surgical history upon high-level evidence of evidence-based medicine.

Trends and quality of randomized controlled trials on acupuncture conducted in Japan by decade from the 1960s to the 2010s: a systematic review

BackgroundMore new randomized controlled trials (RCTs) on acupuncture have been published in Japan since our last updated systematic review (2010). This systematic review aimed to evaluate the quality of RCTs on acupuncture conducted in Japan and understand the decade-wise changes in the methodological characteristics of the relevant RCTs.MethodsThe literature search was performed using Ichushi Web, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed and our team’s compilation of relevant papers. We included full-length papers reporting RCTs that examined the clinical effects of acupuncture on patients in Japan published in or before 2019. We assessed the risk of bias (RoB), sample size, control setting, negative trial reporting, informed consent, ethics approval, trial registration, and adverse event reporting.ResultsA total of 99 articles reporting 108 eligible RCTs were identified. The number of RCTs published in each decade was 1, 6, 9, 5, 40, and 47 in the 1960s, 1970s, 1980s, 1990s, 2000s, and 2010s, respectively. Quality assessment using the Cochrane RoB tool revealed that “sequence generation” improved in and after 1990 (73%–80% of RCTs were rated as “low”) and “blinding of outcome assessors” slightly improved in and after the 2000s (40%–50% judged as “low”). However, “high” or “unclear” remained the dominant grades in other domains. Clinical trial registration and adverse events were reported only in 9% and 28% of the included RCTs even in the 2010s, respectively. A different acupuncture method or different point selection (e.g., deep vs. shallow insertion) was the most dominant control setting before 1990, while sham (or “placebo”) needling and/or sham acupoints became the most dominant in the 2000s. The proportion of RCTs with positive results was 80% in the 2000s and 69% in the 2010s.ConclusionsThe quality of RCTs on acupuncture conducted in Japan did not appear to have improved over the decades except for “sequence generation.” While the culture of submitting negative trial reports was prevalent in the Japanese acupuncture research milieu as late as the 1990s, the overall quality of the relevant trials needs to be further improved.

Effectiveness and safety of traditional Chinese medicine decoction for diabetic gastroparesis: A network meta-analysis.

Diabetic gastroparesis (DGP) is a prevalent complication of diabetes that impairs people's quality of life and places a significant financial burden on them. The gastrointestinal symptoms of DGP patients can be improved by several Traditional Chinese Medicine (TCM) decoctions that have been shown to be effective in treating the disease. There are still many unanswered questions regarding the identification of appropriate therapeutic agents for the treatment of DGP in clinical practice. To analyze the efficacy of several TCM decoctions in the treatment of DGP using Bayesian network meta-analysis for reference. PubMed, EMBASE, Cochrane Library, Web of Science, China National Kno-wledge Infrastructure, The China Biology Medicine DVD, Wanfang, and CQVIP were searched from inception to September 17, 2022, to collect randomized controlled trials (RCTs) about TCM decoctions for DGP. Clinical effects and symptom scores were the primary outcomes. Additionally, we assessed motilin (MOT), somatostatin (SS), gastrin (GAS), gastric emptying rate, gastric emptying time, and adverse drug events as secondary outcomes. A total of 67 eligible RCTs involving 4790 DGP patients and 7 TCM decoctions were included. The results of network meta-analysis (NMA) and surface under the cumulative ranking curve showed that with western medicine (WM) as a common control, the Banxia Xiexin Decoction (BXXD) + WM was most effective in clinical effects and enhancing early satiety scores; the Simo decoction (SMD) + WM was most effective in improving nausea and vomiting scores and anorexia scores, bloating scores; the Chaishao Liujunzi Decoction (CSLJD) was most effective in MOT, the Zhishi Xiaopi Decoction (ZSXPD) was most effective in SS and upgrading emptying rate; the Jianpi Xiaozhi Decoction was most effective in GAS; the CSLJD + WM was most effective in improving gastric emptying time. These NMA results suggest that the BXXD + WM and SMD + WM may be one of the potential optimal treatments. Due to various limitations, further large-sample, double-blind, multi-center randomized RCTs are needed.

Comparison of complications and bowel function among different reconstruction techniques after low anterior resection for rectal cancer: a systematic review and network meta-analysis

BackgroundAnastomosis for gastrointestinal reconstruction has been contentious after low anterior resection of rectal cancer for the past 30 years. Despite the abundance of randomized controlled trials (RCTs) on colon J-pouch (CJP), straight colorectal anastomosis (SCA), transverse coloplast (TCP), and side-to-end anastomosis (SEA), most studies are small and lack reliable clinical evidence. We conducted a systematic review and network meta-analysis to evaluate the effects of the four anastomoses on postoperative complications, bowel function, and quality of life in rectal cancer.MethodsWe assessed the safety and efficacy of CJP, SCA, TCP, and SEA in adult patients with rectal cancer after surgery by searching the Cochrane Library, Embase, and PubMed databases to collect RCTs from the date of establishment to May 20, 2022. Anastomotic leakage and defecation frequency were the main outcome indicators. We pooled data through a random effects model in a Bayesian framework and assessed model inconsistency using the deviance information criterion (DIC) and node-splitting method and inter-study heterogeneity using the I-squared statistics (I2). The interventions were ranked according to the surface under the cumulative ranking curve (SUCRA) to compare each outcome indicator.ResultsOf the 474 studies initially evaluated, 29 were eligible RCTs comprising 2631 patients. Among the four anastomoses, the SEA group had the lowest incidence of anastomotic leakage, ranking first (SUCRASEA = 0.982), followed by the CJP group (SUCRACJP = 0.628). The defecation frequency in the SEA group was comparable to those in the CJP and TCP groups at 3, 6, 12, and 24 months postoperatively. In comparison, the defecation frequency in the SCA group 12 months after surgery all ranked fourth. No statistically significant differences were found among the four anastomoses in terms of anastomotic stricture, reoperation, postoperative mortality within 30 days, fecal urgency, incomplete defecation, use of antidiarrheal medication, or quality of life.ConclusionsThis study demonstrated that SEA had the lowest risk of complications, comparable bowel function, and quality of life compared to the CJP and TCP, but further research is required to determine its long-term consequences. Furthermore, we should be aware that SCA is associated with a high defecation frequency.

Determining minimal important differences for patient-reported outcome measures in shoulder, lateral elbow, patellar and Achilles tendinopathies using distribution-based methods

BackgroundMinimal important difference (MID) is a concept used inconsistently and arbitrarily in tendinopathy research. Our aim was to determine the MIDs for the most commonly used tendinopathy outcome measures using data-driven approaches.MethodsRecently published systematic reviews of randomised controlled trials (RCTs) on tendinopathy management were identified and used for extraction of eligible studies through a literature search. Each eligible RCT was used to obtain information on MID where this was used and it also contributed data for the calculation of the baseline pooled standard deviation (SD) for each tendinopathy (shoulder, lateral elbow, patellar and Achilles). The rule of “half SD” was used for the computation of MIDs for patient-reported pain (visual analogue scale, VAS 0–10, single-item questionnaire) and function (multi-item questionnaires) and the rule of “one standard error of measurement (SEM)” was additionally used for the multi-item functional outcome measures.ResultsA total of 119 RCTs were included for the 4 tendinopathies. MID was defined and used by 58 studies (49%) and there were significant inconsistencies amongst studies where the same outcome measure was used as MID. From our data-driven methods the following suggested MIDs were obtained: a) Shoulder tendinopathy, pain VAS (combined) 1.3 points, Constant-Murley score 6.9 (half SD) and 7.0 (one SEM) points; b) lateral elbow tendinopathy, pain VAS (combined) 1.0 point, Disabilities of Arm, Shoulder and Hand questionnaire 8.9 (half SD) and 4.1 (one SEM) points; c) Patellar tendinopathy, pain VAS (combined) 1.2 points, Victorian Institute of Sport Assessment – Patella (VISA-P) 7.3 (half SD) and 6.6 points (one SEM); d) Achilles tendinopathy, pain VAS (combined) 1.1 points, VISA-Achilles (VISA-A) 8.2 (half SD) and 7.8 points (one SEM). The rules of half SD and one SEM produced very similar MIDs except for DASH due to its very high internal consistency. MIDs were also calculated for different pain settings for each tendinopathy.ConclusionsOur computed MIDs can be used in tendinopathy research to increase consistency. Clearly defined MIDs should be used with consistency in tendinopathy management studies in the future.

Clinician- versus caregiver-rated scales as outcome measures of repetitive-restricted behaviors in clinical trials of autism: A systematic review and meta-analysis

The agreement between treatment effects measured by clinician- and caregiver-ratings of repetitive-restricted behaviors (RRBs) is important for clinical practice and research but is still unclear.Therefore, we conducted a post-hoc meta-analysis of placebo-controlled randomized-controlled trials (RCTs) investigating pharmacological and dietary-supplement treatments for autism that reported both clinician- and caregiver-ratings of RRBs. Treatment effects between medications and placebo were quantified with standardized mean differences (SMDs). The agreement between clinician- and caregiver-rated SMDs was investigated with an intraclass correlation coefficient (ICC) and random-effects meta-analysis of their difference (Δg). A meta-regression investigated the association between clinician (dependent) and caregiver-rated SMDs (independent variable). Certainty in the evidence was evaluated using the GRADE approach.We identified 15 eligible placebo-controlled RCTs with 1567 participants, from which 13 included children/adolescents and 9 reported data for the pair of the clinician-rated Yale-Brown Obsessive Compulsive Scale (YBOCS) and the caregiver-rated Aberrant Behavior Checklist-Stereotypic Behavior (ABC-S). There was on average a good agreement between clinician- and caregiver-rated SMDs (ICC=0.84, 95% confidence intervals [0.55, 0.95]), no clear difference between them (Δg=0.08, 95%CI[-0.06, 0.21], 95% prediction intervals [-0.16, 0.31]), and the beta of the meta-regression was 0.62, 95%CI[0.27, 0.97]. The certainty of the evidence was low due to concerns in imprecision and inconsistency.Our analysis showed on average a good agreement between clinician- and caregiver-rated treatment effects in RRBs, yet discordance could be expected in future RCTs, given the wide prediction intervals. It is also not certain that these results could be generalizable to other rating scales and intervention modalities.Ethics committee approval: Not applicable as a meta-analysis of previously published studies..

Abstract P2-02-06: Adjuvant Denosumab treatment in early breast cancer: a systematic review and meta-analysis of randomized controlled clinical trials

Abstract Background. Adjuvant denosumab treatment improved bone-health related outcomes in early breast cancer (BC) patients with discordant survival results. We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess efficacy and safety of adjuvant denosumab in addition to standard anticancer therapy. Methods. PubMed, CENTRAL, Scopus, Embase, clinicaltrials.gov and key oncological meetings websites were screened to identify potentially eligible RCTs based on the PICOs model: P) Participant: pre and postmenopausal early BC patients; I) Intervention: adjuvant denosumab; C) Comparator: placebo; O) Outcomes: Disease-free survival (DFS), Bone Metastasis-free survival (BMFS), Overall Survival (OS), fracture incidence and time to first fracture were adopted as survival endpoints, and Adverse Events, Serious Adverse Events, Osteonecrosis of the Jaw (ONJ) and Atypical Femur Fractures (AFF) as safety endpoints; S) Study design: phase III RCTs. Risk of bias was assessed with Cochrane Collaboration Risk of Bias Tool. Pooled hazard ratios (HR), risk ratios (RR), risk differences (RD) and respective confidence intervals (CI) were computed using both a fixed and a random effect model. Subgroup analyses based on menopausal status, hormone receptor and HER2 status and immunophenotype were performed. Results. Two phase III RCTs were included (ABCSG-18, D-CARE), for an overall population of 7929 early BC patients receiving denosumab or placebo. Denosumab addition to standard of care anticancer treatment showed no difference in DFS (HR 0.93; 95% CI 0.75-1.16, p=0.53), BMFS (HR 0.90; 95% CI 0.75-1.07, p=0.23) and OS (HR 0.92; 95% CI 0.72-1.17, p=0.49). In hormone receptor-positive/HER2 negative patients, denosumab significantly prolonged both DFS (HR 0.88; 95% CI 0.78-0.99, p=0.04) and BMFS (HR 0.83; 95% CI 0.71-0.97, p=0.02). No interaction was found between denosumab addition and menopausal status. Fracture incidence (RR 0.79; 95% CI 0.70-0.89, p&amp;lt; 0.01) and time to first fracture (HR 0.76; 95% CI 0.66-0.87, p&amp;lt; 0.01) were also improved with denosumab. No association between denosumab addition and overall toxicity was seen and no difference was observed in terms of ONJ and AFF between the 60mg every 6 months schedule and placebo (RD 0.001, 95% CI from -0.001 to 0.002, p=0.48) Conclusions. Findings from this meta-analysis validate the role of denosumab as a highly effective anti-resorptive agent. We provide robust evidence that its addition to standard anticancer treatment significantly improves survival outcomes in hormone receptor-positive/HER2 negative early BC patients, suggesting that the implementation of denosumab use in combination with endocrine therapy in this patient population should be reconsidered. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022332787. Citation Format: Luca Mastrantoni, Giovanna Garufi, Elena Di Monte, Noemi Maliziola, Mariangela Pasqualoni, Letizia Pontolillo, Sergio Pannunzio, Maria Chiara Cannizzaro, Armando Di Bello, Alessandra Fabi, Antonella Palazzo, Emilio Bria, Giampaolo Tortora, Armando Orlandi. Adjuvant Denosumab treatment in early breast cancer: a systematic review and meta-analysis of randomized controlled clinical trials. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-06.

Efficacy of psychological interventions for post-traumatic stress disorder in children and adolescents exposed to single versus multiple traumas: meta-analysis of randomised controlled trials.

Previous meta-analyses of psychotherapies for children and adolescents with post-traumatic stress disorder (PTSD) did not investigate whether treatment efficacy is diminished when patients report multiple (versus single) traumas. To examine whether efficacy of psychological interventions for paediatric PTSD is diminished when patients report multiple (versus single) traumas. We systematically searched PsycInfo, MEDLINE, Web of Science and PTSDpubs on 21 April 2022 and included randomised controlled trials (RCTs) meeting the following criteria: (a) random allocation; (b) all participants presented with partial or full PTSD; (c) PTSD is the primary treatment focus; (d) sample mean age <19 years; (e) sample size n ≥ 20. Trauma frequency was analysed as a dichotomous (single versus ≥2 traumas) and continuous (mean number of exposures) potential moderator of efficacy. Of the 57 eligible RCTs (n = 4295), 51 RCTs were included in quantitative analyses. Relative to passive control conditions, interventions were found effective for single-trauma-related PTSD (Hedges' g = 1.09; 95% CI 0.70-1.48; k = 8 trials) and multiple-trauma-related PTSD (g = 1.11; 95% CI 0.74-1.47; k = 12). Psychotherapies were also more effective than active control conditions in reducing multiple-trauma-related PTSD. Comparison with active control conditions regarding single-event PTSD was not possible owing to scarcity (k = 1) of available trials. Efficacy did not differ with trauma exposure frequency irrespective of its operationalisation and subgroup analyses (e.g. trauma-focused cognitive-behavioural therapy only). The current evidence base suggests that psychological interventions for paediatric PTSD can effectively treat PTSD in populations reporting single and multiple traumas. Future trials for PTSD following single-event trauma need to involve active control conditions.

A Systematic Review and Meta-Analysis Protocol to Establish How Common Clinical Acupoint Stimulation-Related Therapies Should Be Used for Managing Insomnia.

Many studies have now investigated the effects of common clinical acupoint stimulation-related therapies (ASRTs) following the meridian theory of traditional Chinese medicine for the management of insomnia. However, ASRT choice is currently based on personal clinical experience or patient preference. This study will review the common ASRTs reported in clinical trials and analyze their efficacy and safety for managing insomnia with or without co-morbidities. English and Chinese databases will be thoroughly searched, and other potentially eligible trials will be obtained by reviewing reference lists of identified studies and previous reviews. Only randomized controlled trials (RCTs) of common clinical ASRTs to manage insomnia published in peer-reviewed journals will be considered. Sleep quality questionnaires or indices will be considered as the main outcome, while the secondary outcomes will include sleep parameters, daytime dysfunction, quality of life, and adverse effects. Two reviewers will independently investigate eligible RCTs, extract information, analyze their methodological quality, and employ Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria to evaluate the strength of the evidence. The treatment impact of various ASRTs will be calculated using meta-analysis techniques, and the degree of study heterogeneity will be assessed using Cochrane's Q and I-squared statistics. Subgroup and sensitivity analyses will be used to evaluate the reliability of the results. Our systematic review and meta-analysis will present up-to-date evidenceon: 1) which common clinical ASRTs are beneficial for the management of insomnia; and 2) whether the effects of common clinical ASRTs on insomnia vary depending on clinical, participant, and treatment characteristics. The results of our review should help decision-makers make educated choices regarding evidence-based non-pharmacological management options for insomnia. The International Platform of Registered Systematic Review and Meta-analysis (INPLASY), record INPLASY2021120137.

Abstract P606: Effectiveness of Randomized Dietary Interventions for the Primary Prevention of Incident Cardiovascular Disease and Type 2 Diabetes

Objective: Randomized controlled trials (RCTs) provide opportunities to estimate the causal effects of interventions on disease risk; however, large-scale, long-term RCTs of diet for the prevention of major chronic disease endpoints are sparse. We sought to summarize RCTs comparing the effectiveness of dietary interventions for the primary prevention of clinical cardiovascular disease (CVD) events and type 2 diabetes (T2D) in adults. Methods: We conducted a systematic review and meta-analysis (PROSPERO #CRD42021283728) of RCTs exclusively with dietary interventions with outcomes of incident primary CVD events and/or T2D among adults. We searched MEDLINE and other databases and references. Eligible interventions included those providing instruction, education, and/or provisions to modify intakes of nutrients, foods, or overall dietary patterns. We excluded meal replacement products, dietary supplements, interventions with concomitant comprehensive lifestyle programs, exercise regimens, etc., trials in secondary prevention populations, and trials assessing risk factor or biomarker changes only, rather than clinical events. Two investigators performed screening and data extraction in parallel. We conducted a random effects meta-analysis to estimate the pooled effectiveness of dietary interventions compared with usual diet or low-fat control groups for CVD and T2D outcomes, separately. Results: Among the 5365 citations generated in our searches, we identified 4 eligible RCTs, representing 56,721 participants with mean ages ranging from 44.7 to 67.9 years. Mean intervention duration was 2.3 to 8.1 years, resulting in 3,151 CVD events and 3,603 T2D cases. Compared with the control diets, the various healthy dietary patterns were related to a combined 7% (relative risk [RR] = 0.93, confidence interval [CI] = 0.87-1.00) lower CVD risk and 8% (RR = 0.92, CI = 0.86-0.98) lower T2D risk. Conclusion: Despite major morbidity and mortality from CVD and T2D, there have been few large, population-based, long-term RCTs assessing the exclusive effectiveness of dietary modification for the primary prevention of clinical CVD events or T2D. Results, however, indicate that various healthy diets may be modestly effective for primary prevention.