Randomized Controlled Trials Research Articles

Long-term effects of non-pharmacological interventions in adolescents and young adults with type 1 diabetes: A systematic review and meta-analysis.

Consistent diabetes control is crucial for patients with type 1 diabetes (T1D) to prevent diabetic complications. Analyzing the long-term effects of non-pharmacological interventions can improve diabetes management. To examine the long-term effects of non-pharmacological interventions in adolescents and young adults with T1D through a systematic review and meta-analysis of randomized controlled trials (RCTs). The searches, without any year limitations, were conducted in seven databases. Two reviewers independently performed data extraction and risk of bias assessments. The meta-analysis was conducted using the RevMan 5.4 program and R Studio. The study was registered with PROSPERO (CRD42024503185). A total of 40 studies were included in the systematic review, of which 28 were included in the meta-analysis. Notably, non-pharmacological interventions were effective in improving glycated hemoglobin (HbA1c) at 6 months and self-care at >12 months of follow-up. Subgroup analyses revealed that combined interventions encompassing self-care behavior management, education, and psychological interventions could enhance self-care. Additionally, a combination of face-to-face and telephonic communication was effective in improving HbA1c. Non-pharmacological interventions are effective in improving HbA1c levels and self-care in adolescents and young adults undergoing long-term treatment. However, few studies have analyzed their effects on cardiovascular disease risk factors. Future studies should investigate the long-term effects of non-pharmacological interventions.

Efficacy of Photobiomodulation in Accelerating Orthodontic Tooth Movement: A Systematic Review of Literature

Aim and background: This systematic review aimed to investigate the efficacy of photobiomodulation (PBM) on the acceleration of orthodontic tooth movement (OTM). Review methods: An extensive electronic search for randomized control trials via Medline (via PubMed), The Cochrane Controlled Clinical Trials Register, and Science Direct up to October 15, 2023 was done. Hand searching was performed for relevant journals. Reference articles were retrieved and exported to Zotero software. The risk of bias was assessed using Version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). Results: A total of 14 articles were considered for systematic review. Most of the studies arrived at the consensus that photobiomodulation (PBM) indeed accelerates the pace of tooth movement and significantly diminishes the time required for achieving proper tooth alignment. Conclusion: The synthesis of available evidence in our analysis reveals a substantial body of research suggesting a positive effect of PBM on accelerating tooth movement. However, the existing variations in PBM parameters, and outcome measurements emphasize the necessity for more standardized approaches in future investigations.

Comparison of safety profile in patients with atopic dermatitis treated with dupilumab or conventional systemic treatment: real world data from the US network

Background Safety of dupilumab in atopic dermatitis (AD) was investigated in randomized controlled trials (RCT). However, head-to-head trials comparing with conventional systemic drugs are lacking and large real-world data on the long-term safety profile as compared are scarce. Objective To compare long-term safety profile of dupilumab with conventional systemic drugs used in the management of moderate to severe AD. Methods Data from electronic health records of AD patients treated with either dupilumab, azathioprine, Cyclosporine A, mycophenolate mofetil, methotrexate, or oral glucocorticoids were retrieved from the TriNetX US Collaborative Network. Risks of adverse events and new onset of type-2-inflammatory diseases within 5 years after treatment initiation was investigated. Results 5 propensity-matched cohorts, up to 18,708 individuals per cohort, were created. Dupilumab treatment displayed reduced risk for diseases of the circulatory, the upper respiratory, and the musculoskeletal system, infections, and type 2 diseases as compared to all other treatment options. In contrast risk for conjunctivitis was increased in dupilumab treated patients as compared to mycophenolate mofetil and methotrexate. Conclusion Here presented data indicates that treatment with dupilumab for AD has reduced risk for adverse effects of conventional systemic drugs and thus might be safer. Obtained data should be verified in prospective studies.

The Effects of Beta-Alanine Supplementation on Body Composition Indices: A Systematic Review and Meta-Analysis of Controlled Clinical Trials

Background: Beta-alanine is an important oral supplement for improving athletes’ performance, followed by probable effects on body composition. Current meta-analysis was performed to investigate the role of beta-alanine supplementation on body weight, fat mass, free fat mass, and body fat percentage in adults. Methods: Web of Science, PubMed, Scopus, Cochrane library databases, and EMBASE were searched between January 1990 and May 2021. Randomized controlled trials (RCTs) comparing beta-alanine supplementation with a placebo assessing anthropometric indices were included. Meta‐analysis was performed using the random‐effects model. Publication bias was evaluated using standard methods, and subgroup analysis and meta‐regression were carried out. Results: A total of 875 articles were identified through database searching, of which 12 RCTs with 15 datasets were included in the study. This study showed that beta-alanine supplementation did not have any significant effect on body weight [SMD, 0.08; 95% CI (−0.17, 0.33); P=0.517], fat percentage [SMD, 0.09; 95% CI (−0.18, 0.37); P=0.504], fat mass [SMD, 0.10; 95% CI (−0.29, 0.50); P=0.612], and fat free mass [SMD, 0.16; 95% CI (−0.18, 0.49); P=0.517]. Conclusions: Results showed that beta-alanine supplementation does not change body composition significantly.

Cognitive behavioral therapy combined with selective serotonin reuptake inhibitors for premature ejaculation: A systematic review and meta-analysis.

Premature ejaculation (PE) remains one of the most common male disorders. Many clinical trials have shown that cognitive behavioral therapy (CBT) has significant efficacy in the treatment of PE. The purpose of this article is to review the current evidence regarding the efficacy and safety of CBT combined with selective serotonin reuptake inhibitors (SSRIs) for treating PE. We selected eligible randomized controlled trials (RCTs) from databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang, VIP, China Biology Medicine (CBM), Pubmed, Embase, and Cochrane Library. All data in this paper were analyzed using STATA 17.1 software. Cochrane Evaluator's Manual 5.3 was used to assess the quality of the included literature. Data collection was conducted up until May 2024. Finally, 15 high-quality randomized controlled trials were included, with 1243 patients, 653 experimental groups and 590 control groups. The meta-analysis showed that, compared with SSRIs alone, behavioral therapy combined with SSRIs can significantly prolong the IELT of PE patients, and improve perceived control over ejaculation, Chinese Index of Premature ejaculation-5 (CIPE-5), sexual life satisfaction, and spouses' sexual life satisfaction. Furthermore, there were no significant differences in side effects between the two groups. In addition, the published bias test results showed no significant bias. CBT combined with SSRIs could be a viable alternative for the treatment of PE. Both cognitive and behavioral training or behavioral training alone as a supplement to SSRIs are effective, with no significant increase in adverse reactions.

Effect of exercise referral schemes and self-management strategies on healthcare service utilisation among community-dwelling older adults: secondary analyses of two randomised controlled trials.

The objective of this study is to explore whether offering an integrated self-management strategy and exercise referral scheme intervention (ERS+SMS) or a stand-alone ERS intervention is more effective in reducing healthcare service utilisation among community-dwelling older adults over time compared with a stand-alone SMS/control intervention. Secondary analyses of two randomised controlled trials (RCTs) with linkage to Danish national health registries. Three Danish municipalities: Esbjerg, Slagelse and Odense. Danish community-dwelling older adults, aged 65 years or older, were included in the study. Participants originated from two completed RCTs: the Welfare Innovation in Primary Prevention (WIPP, n=115) and the SITLESS project (SITLESS, n=333). Participants in the two trials were randomly assigned to one of three intervention groups: ERS in combination with SMS (ERS+SMS), ERS alone or an SMS/control intervention. Annual number of days with contact to general practice (GP) and days hospitalised for all causes. No statistically significant between-group difference was observed in the annual number of days with contact with GP between participants randomised to ERS+SMS (p=0.759) or ERS only (p=0.156) compared with those randomised to the SMS/control group. In addition, no statistically significant between-group differences in days hospitalised were observed when comparing the ERS+SMS (p=0.222) or ERS only (p=0.060) group to the SMS/control group. Neither the integrated intervention (ERS+SMS) nor the ERS alone intervention was more effective in reducing healthcare service utilisation during a 2-year follow-up period compared with a stand-alone SMS/control intervention. A potential stabilising effect of ERS and/or SMS interventions on the general age-related increase in healthcare service utilisation cannot be ruled out but needs further exploration in future studies along with the exploration of the effects of long-term interventions. NCT04531852 : and : NCT02629666 : .

Efficacy and Safety of Lumateperone for Bipolar Depression and Schizophrenia: A Systematic Review and Meta-Analysis.

This study aimed to evaluate the efficacy and safety of lumateperone in treating bipolar disorder and schizophrenia. A comprehensive literature search was conducted across multiple databases and websites from inception to July 16, 2024, to identify both published and unpublished randomized controlled trials (RCTs). Meta-analyses were performed using random-effects or fixed-effects models depending on statistical heterogeneity. Relative risks (RRs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to summarize the effects. Out of 931 records screened, seven RCTs (four focusing on bipolar depression and three on schizophrenia) were eligible for inclusion. Lumateperone was efficacious in reducing depressive symptoms in bipolar depression (SMDs = -0.36, 95% CI: -0.59 to -0.13). In treating schizophrenia, lumateperone exhibited a lower combined SMD of -0.14 (95% CI: -0.27 to 0, P = 0.051, I² = 49.6%), showing no significant difference from the placebo group, although the p-value approached significance. The lumateperone group showed significantly higher response rates compared to placebo in both bipolar depression (RRs = 1.27, 95% CI: 1.07 to 1.51) and schizophrenia (RRs = 1.44, 95% CI: 1.12 to 1.86). Common treatment-emergent adverse events included somnolence, dry mouth, dizziness, nausea, and headache (RRs = 1.30 to 3.29). Importantly, lumateperone did not significantly increase extrapyramidal symptoms (EPS, RRs = 1.46, 95% CI: 0.84 to 2.53). Lumateperone is effective in treating bipolar depression but does not significantly reduce symptom severity in schizophrenia. It has a favorable safety and tolerability profile. However, caution is warranted in interpreting these findings due to the limited number of studies included.

Effects of Licorice Functional Components Intakes on Blood Pressure: A Systematic Review with Meta-Analysis and NETWORK Toxicology.

To investigate the effects of licorice functional ingredient intake on blood pressure, explore its potential mechanisms of action, and provide safety information for personalized nutritional interventions in special populations and for the application of licorice-derived functional foods. PubMed, Cochrane Library, Medline, Embase, EBSCO, ScienceDirect, and Web of Science databases were searched from inception to 31 August 2024. Randomized controlled trials (RCTs) investigating the intake of licorice or its functional components were included. The range of continuous variables was assessed using the weighted mean difference (WMD) with 95% confidence intervals. Genes associated with hypertension were screened using an online database. Machine learning, receiver operating characteristic(ROC) curve analysis, molecular docking, and gene set enrichment analysis (GSEA) were employed to explore the potential mechanisms underlying licorice-induced blood pressure fluctuations. Eight RCTs (541 participants) were included in the meta-analysis, which indicated interventions containing glycyrrhizic acid (GA) as the main component increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) (SBP: WMD [95% CI] = 3.48 [2.74, 4.21], p < 0.001; DBP: WMD [95% CI] = 1.27 [0.76, 1.78], p < 0.001). However, interventions dominated by licorice flavonoids(LF) had no significant effect on SBP or DBP (SBP: WMD [95% CI] = 0.58 [-1.15, 2.31], p = 0.511; DBP: WMD [95% CI] = 0.17 [-1.53, 1.88], p = 0.843). Three machine learning algorithms identified five biomarkers associated with hypertension: calmodulin 3 (CALM3), cluster of differentiation 9 (CD9), growth factor independence 1B transcriptional repressor (GFI1B), myosin light chain kinase (MYLK), and Ras suppressor-1 (RSU1). After removing biomarkers with lower validity and reliability, GFI1B, MYLK, and RSU1 were selected for subsequent analysis. The network toxicology results suggested that GA and its metabolite glycyrrhetinic acid may act on GFI1B, MYLK, and RSU1, influencing blood pressure fluctuations by modulating nitrogen metabolism signaling pathways. There were distinct differences in the effects of licorice functional components on blood pressure. Functional constituents dominated by GA were shown to increase both SBP and DBP, whereas those dominated by LF did not exhibit significant effects on blood pressure. The hypertensive mechanism of GA may involve the modulation of GFI1B, MYLK, and RSU1 to regulate nitrogen metabolic pathways.

Romosozumab for the treatment of osteoporosis - a systematic review.

Romosozumab, a new treatment of osteoporosis, is a monoclonal antibody that targets sclerostin and thereby exhibits a dual mechanism of action by stimulating bone formation and inhibiting bone resorption. This systematic review aims to assess the clinical efficacy and safety of romosozumab for treatment of primary and secondary osteoporosis. A comprehensive literature search was conducted in October 2023 across multiple databases including Embase, PubMed and Cochrane Library. Randomized controlled trials (RCTs) and observational studies evaluating the impact of romosozumab on BMD, bone turnover markers (BTM), fracture outcomes, and its safety profile were included. Data extraction and quality assessment were performed independently by two reviewers in accordance with PRISMA guidelines. A total of 36 articles met the inclusion criteria. Romosozumab significantly increased BMD at the lumbar spine, total hip, and femoral neck compared to placebo and active comparators in patients with primary osteoporosis. Sequential therapy with romosozumab followed by antiresorptives maintained or further increased BMD and reduced fracture risk. Romosozumab was generally well tolerated, however, an imbalance in cardiovascular adverse event was observed in one large clinical trial. Observational studies supported these findings. Specific subgroups of patients with secondary osteoporosis were assessed, demonstrating overall positive outcomes with romosozumab treatment. Romosozumab effectively increases BMD and reduces fracture risk, particularly when used as initial therapy in high fracture-risk patients. Sequential therapy with subsequent antiresorptive treatment optimizes long-term benefits. While generally well-tolerated, its cardiovascular safety profile requires further long-term studies to ensure its safety in clinical practice. Additional studies are needed to confirm efficacy and safety in patients with secondary osteoporosis.

Newer glucose-lowering drugs reduce the risk of late-onset seizure and epilepsy: A meta-analysis.

Newer glucose-lowering drugs (GLDs) protect against cerebrovascular, neurodegenerative, and neuroinflammatory pathologies. Therefore, we performed a meta-analysis of randomized controlled trials (RCTs) comparing newer GLDs to placebo that assessed long-term cardiovascular and renal outcomes to analyze their potential to prevent late-onset seizures and epilepsy, separately and as a combined outcome. A comprehensive MEDLINE and CENTRAL databases search for DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitor RCTs, which reported adverse effects, including seizures and epilepsy on clinicaltrials.gov, yielded 413 studies. Of them, 27 studies with almost 200 000 patients (mean age 64.9 years, 65.6% males) were included. We calculated relative risk (RR) and odds ratio (OR) using the Mantel-Haenszel method and Peto's method. Patients taking newer GLDs had a 24% lower risk of late-onset seizures and epilepsy, combined, (RR: 0.76, 95% CI: 0.62-0.95) and 22% lower risk of late-onset seizures only (RR = 0.78; 95% CI = 0.60-1.00), compared to patients on placebo. This seizure and epilepsy prevention benefit was only noted among patients taking GLP-1 receptor agonists. Stroke incidence was comparable between newer GLDs and placebo group. GLP-1 receptor agonists like Semaglutide significantly reduce late-onset seizures and epilepsy, and their anti-epileptogenic potential in older adults needs further exploration. PLAIN LANGUAGE SUMMARY: Our analysis 27 clinical trials and nearly 200 000 patients evaluated the potential of newer glucose-lowering drugs (GLDs) to prevent late-onset seizures and epilepsy in older adults. The study found that newer GLDs, especially GLP-1 receptor agonists like Semaglutide, reduced the combined risk of seizures and epilepsy by 24% compared to placebo. These findings suggest that newer GLDs may offer prevention against the development of seizures and epilepsy in older adults. However, further research is needed to confirm their anti-epileptogenic effects.

Evaluating the effectiveness of recovery-oriented interventions for youth who vape nicotine: a systematic review protocol.

The increase in nicotine vaping among youth has emerged as a critical public health concern. Vaping among youth is linked to adverse health outcomes, including nicotine addiction, cardiovascular and pulmonary diseases and mental health challenges. Recently, there has been a growing demand for research to expand on treatments to enhance the recovery process from vaping nicotine in youth. To this date, no comprehensive review identifies all interventions available for vaping recovery and compares their effectiveness in youth. This proposed systematic review seeks to identify all recovery-oriented interventions for youth aged 10-24 that facilitate vaping recovery and evaluate the measured effectiveness. This review will serve to support healthcare practitioners, nurses and policymakers to further understand recovery interventions and aid in improving vaping recovery among youth. This protocol, registered with PROSPERO, adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) framework, and the final review will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to ensure quality and replicability. The review will comprise studies including youth aged 10-24 engaging in nicotine vaping. A comprehensive search will be conducted across MEDLINE, Embase, PsycINFO, Scopus and CINAHL, with no restrictions on the date range due to the recency of the topic. Two independent reviewers will screen the identified research for eligibility at the title and abstract levels, with any disagreements resolved by a third reviewer. The review will include randomised control trials and quasi-experimental studies. Full-text review and data extraction will be standardised and completed by the primary researcher. Additionally, studies will be assessed for quality and potential biases. Given that this is a review of existing literature, no ethics approval is required. The focus on youth necessitates careful consideration of ethical standards. This review is committed to contributing responsibly to public health knowledge regarding youth vaping recovery. The results from this review will be disseminated through publication in an open-access, peer-reviewed journal and likely through posters and presentations at scientific conferences. CRD42024543994.

Insomnia and its treatments—trend analysis and publication profile of randomized clinical trials

This study aimed to describe the publication profile of randomized controlled trials (RCTs) for insomnia. A systematic review of RCTs regarding interventions for non-comorbid insomnia in adults retrieved 132 RCTs: 58 related to pharmacological treatments, 71 to non-pharmacological treatments, and 3 to both interventions. The treatments with the biggest publication profile were digital CBT-I (dCBT-I) (n = 35), in-person CBT-I (n = 28) and zolpidem (n = 22). Regarding dCBT-I, the median publication year is 2019, with 1.13 ± 1.91 RCTs published per year. Regarding zolpidem, the median publication year is 2008, with 0.71 ± 0.97 RCTs per year. Regarding in-person CBT-I, the median publication year is 2018, with 0.90 ± 1.14 RCTs per year. The majority of the available RCTs are on non-pharmacological interventions, particularly CBT-I (mostly in the 2000s) and dCBT-I (mostly in the last decade), although presenting a reduced methodological quality in comparison to pharmacological interventions. These data suggest an increasing focus on non-pharmacological interventions for insomnia.

Treatment for essential tremor: a systematic review and Bayesian Model-based Network Meta-analysis of RCTs

Essential tremor (ET) significantly impacts patients' daily lives and quality of life, presenting a considerable challenge in clinical practice. In recent years, novel therapeutic regimens have been investigated in randomized controlled trials (RCTs). This study aims to investigate and evaluate the relative efficacy and safety of various therapeutic interventions for ET. We did a systematic review and Bayesian Model-based Network Meta-analysis (NMA) of RCTs. Following PRISMA-NMA guidelines, a comprehensive database search was conducted up to April 1, 2024 to identify RCTs focused on ET treatments. The Bayesian Markov Chain Monte Carlo (MCMC) method was utilized for the analysis, evaluating the relative efficacy and safety of treatments using standardized mean difference (SMD) and log odds ratios (log ORs), respectively. Additionally, the Surface Under the Cumulative Ranking Curve (SUCRA) was applied to assess the relative efficacy of the treatment modalities. PROSPERO registration: CRD42023415752. This study included 33 RCTs involving 1251 patients, covering 19 oral medication treatments and six non-oral medication treatments. NMA showed that deep brain stimulation (DBS) (SMD=-4.93; 95% CI: [-7.73,-2.13]), CX-8998 (SMD=-2.69; 95% CI: [-5.26,-0.14]), atenolol (SMD=-2.36; 95% CI: [-4.70,-0.10]), and propranolol (SMD=-1.59; 95% CI: [-2.25,-0.67]) showed relative efficacy compared to placebo, with DBS demonstrating relative efficacy compared to 15 other treatment methods. However, GRADE assessment indicated that the evidence level for these conclusions was "low" or "very low." According to SUCRA rankings, DBS (0.97) ranked first in relative efficacy, followed by CX-8998 (0.80), thalamotomy (0.79), atenolol (0.76), metoprolol (0.66), propranolol (0.64), magnetic resonance guided focus ultrasound (MR-FUS) (0.624), ICI-118551 (0.620), nimodipine (0.61) and phenobarbitone (0.59). In terms of safety, as a network graph could not be constructed, DBS and thalamotomy were excluded from the NMA, while other effective treatments showed no significant differences in safety compared to placebo. Our study results indicate that CX-8998, propranolol, and atenolol demonstrate relative efficacy and safety in treating ET. DBS is effective for medication-resistant ET and ranks first in relative efficacy, though our NMA lacks safety data for DBS. Given the low overall grade of evidence, these results should be applied cautiously in clinical practice. Further large-scale, head-to-head RCTs are needed. This work was supported by grants from the National Nature Science Foundation of China (Grant No. 82271459).

Use of commercially available wearable devices for physical rehabilitation in healthcare: a systematic review

ObjectivesTo evaluate whether commercially available ‘off-the-shelf’ wearable technology can improve patient rehabilitation outcomes, and to categorise all wearables currently being used to augment rehabilitation, including the disciplines and conditions under...

Selective outcome reporting among randomized controlled trials published in leading dental journals: A research-on-research study

ObjectivesTo study the prevalence and manifestation of selective outcome reporting (SOR) among randomized controlled trials (RCTs) published in leading dental journals, and to explore the association between SOR and potentially related factors. MethodsWe hand-searched RCTs published in the leading dental journals between 2018 and 2023. RCTs with registrations and defined primary outcomes were included, and their relevant characteristics were extracted for analysis. Discrepancies between publication and corresponding registration were compared regarding primary outcome and other study characteristics. The generalized estimating equation model was applied to identify factors associated with SOR. ResultsTwo hundred and seventy trials were included. SOR was identified in 51.5% (n = 139) of the included RCTs with the discrepancy in the assessment timing of the primary outcome as the most common manifestation (n = 86, 31.9%). Substantial discrepancies were observed regarding sample size (n = 148, 54.8%) and source of funding (n = 105, 38.9%). Sample size [odds ratio (OR) 0.61, 95% confidence interval (CI) 0.40 to 0.92], timing of registration (OR 2.10, 95% CI 1.03 to 4.31), and discrepancy in follow-up length (OR 32.01, 95% CI 11.80 to 86.83) were identified as statistically significant factors associated with SOR. ConclusionsSOR was prevalent among RCTs in leading dental journals. Researchers and other stakeholders should be aware of this reporting issue and make joint efforts to improve the outcome reporting quality. Clinical significanceThe findings of this research-on-research study indicate a substantial presence of SOR in the field of dentistry. Such bias can potentially mislead readers and distort the pooled effect estimates in evidence synthesis, ultimately influencing clinical decision-making.

Systematic Review and Meta-analysis: Placebo Response in Randomized Controlled Trials of Tourette's Disorder Medications.

To examine the magnitude of placebo response in randomized controlled trials (RCTs) of medications for Tourette's disorder. CENTRAL, Embase, PubMed, PsycInfo, Web of Science, WHO ICTRP, and ClinicalTrials.gov databases were searched to identify placebo-controlled RCTs assessing pharmacological interventions for Tourette's disorder. Standardized mean change and standardized mean difference were calculated for within-group (placebo, drug) and between-group (drug-placebo) change in tics. Data were pooled in random-effects meta-analysis. Meta-regressions were performed to identify study-level characteristics that could be differentially associated with placebo, drug, and drug-placebo response. Searchers identified 13,775 records, and 50 RCTs involving 1,566 participants were included in the placebo meta-analysis. Placebo response was medium to large (standardized mean change:-0.62; 95% CI:-0.75,-0.5; I2= 76%; τ2= 0.14). Several factors were associated with larger placebo responses (eg, non-US RCT, industry sponsorship, number of centers and participants). However, there was a moderate-to-high correlation between placebo and drug response (ρ= 0.66; 95% CI: 0.47, 0.79), and factors associated with larger placebo response were also generally associated with larger drug responses. There was not a significant correlation between placebo response and drug-placebo differences (ρ=-0.05; 95% CI:-0.32, 0.22), and factors associated with larger placebo response generally did not interfere in drug-placebo differences. The magnitude of placebo response in Tourette's disorder may be large, but similar to that in other child and adolescent psychiatric conditions. Clinical researchers may manipulate study-level factors to diminish placebo response (eg, carefully selecting study sites and keeping them at the minimum feasibility). However, drug-placebo differences may not increase as drug response will likely diminish as well. Comparative Efficacy, Tolerability, and Acceptability of Pharmacological Interventions for Chronic Tic Disorders Including Tourette's Syndrome in Children, Adolescents, and Adults: Protocol for a Systematic Review and Network Meta-analysis; https://www.crd.york.ac.uk; CRD42022296975. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

The efficacy of valproate in acute mania, bipolar depression and maintenance therapy for bipolar disorder: an overview of systematic reviews with meta-analyses.

This study aims to conduct an overview on the comparative efficacy of valproate in acute mania, bipolar depression and maintenance treatment of bipolar disorder (BD). We performed an overview of systematic reviews with meta-analyses of randomised controlled trials (RCTs), registered in PROSPERO (CRD42024497749). We searched Medline and Cochrane Database of Systematic Reviews. Summary measures comparing valproate with placebo or other active drugs were described. We included 26 systematic reviews. For acute mania (31 RCTs, n=4376), valproate showed a significantly better response than placebo in two high-quality systematic reviews (RR=1.42; 95% CI: 1.19 to 1.71) (OR=2.05; 95% CI: 1.32 to 3.20). No significant differences with lithium were found in most outcomes. Valproate had similar efficacy to quetiapine and lower efficacy compared with risperidone, with conflicting results when compared with olanzapine. In bipolar depression (7 RCTs, n=399), valproate was more effective than placebo in reducing depressive symptoms (OR=2.80; 95% CI: 1.26 to 6.18) and achieving remission (OR=2.4; 95% CI: 1.09 to 5.29) (OR=2.15; 95% CI: 0.82 to 5.6), considering the results of three high-quality systematic reviews. No significant difference was observed with lithium, lurasidone, quetiapine or olanzapine plus fluoxetine, but valproate showed superior efficacy to aripiprazole, ziprasidone and agomelatine. In maintenance treatment (11 RCTs, n=1063), valproate was superior to placebo in preventing relapse of any mood episode in two high-quality systematic reviews (RR=0.63; 95% CI: 0.48 to 0.83) (RR=0.63; 95% CI: 0.47 to 0.83). No significant difference was found with lithium, olanzapine or lamotrigine. This overview highlights favourable results for valproate compared with placebo in all phases of BD, as well as presenting specific results in comparison with other active drugs. However, these results must be interpreted considering the methodological limitations of our study.

Triggering oocyte maturation in IVF treatment in normal responders: a systematic review and network meta-analysis.

To compare efficacy and safety of hCG, GnRH agonist, dual, and double triggers in predicted normal responders undergoing ovarian stimulation and IVF DESIGN: A systematic review and network meta-analysis of randomized controlled trials (RCTs). RCTs indexed in PubMed, MEDLINE, EMBASE, clinical trial registries and Cochrane Database of Systematic Reviews up to December 2023. Twelve high-integrity RCTs comprising 1,931 women were included, which compared hCG trigger to GnRH agonist trigger, dual trigger, and double trigger. Statistical analysis was performed using STATA version 16. Key outcomes included clinical pregnancy rates (CPR), live birth rates (LBR), number of oocytes, number of mature oocytes, miscarriage rate and rates of ovarian hyperstimulation syndrome (OHSS). The network meta-analysis for CPR were relative risk (RR) 1.13 (95% Confidence Interval (CI):0.80-1.60) for hCG versus GnRH agonist trigger, RR 1.23 (95% CI:0.92-1.65) for hCG versus dual trigger, RR 0.38 (95% CI:0.21-0.69) for hCG versus double trigger, RR 1.09 (95% CI:0.70-1.70) for GnRH agonist versus dual trigger and 0.34 (95% CI:0.17-0.67) for GnRH agonist versus double trigger and RR 0.31 (95%CI:0.16-0.60) for double versus dual trigger. Dual trigger demonstrated the highest SUCRA (85.1%), indicating superior efficacy for clinical pregnancy rates. For LBR, while connectivity was limited, the RR was 1.31 (95% CI: 1.00-1.70) for dual versus hCG trigger, and RR 1.60 (95% CI: 1.05-2.43) for dual versus GnRH agonist trigger. OHSS rates were significantly lower with the GnRH agonist compared to hCG trigger (RR 0.56, 95% CI: 0.19-1.75). There were no randomized controlled trials reporting OHSS rates with the use of dual or double trigger. No significant differences were observed in the number of oocytes retrieved, mature oocytes, or miscarriage rates among the trigger protocols. The findings indicate that there is no evidence to suggest that using GnRH agonist, dual, or double protocols is superior to hCG trigger in improving clinical pregnancy rates. While live birth rates may benefit from dual trigger, results are limited by available RCTs. Larger, multicentre trials are needed for further evaluation of live birth rates and understanding of long-term outcomes.

Beef Consumption and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BackgroundResults from observational studies suggest associations of red meat intake with increased risk of cardiovascular disease (CVD); however, randomized controlled trials (RCT) have not clearly demonstrated a link between red meat consumption and CVD risk factors. Further, the specific effects of beef, the most consumed red meat in the US, have not been extensively investigated. ObjectiveTo perform a systematic review and meta-analysis of RCT data evaluating the effects of minimally or unprocessed beef intake on cardiovascular risk factors in adults. MethodsA search of the literature was conducted using PubMed and CENTRAL databases. RCTs in adults that provided diets with fresh or minimally processed beef were included. Data were extracted and pooled estimates from random effects models were expressed as standardized mean differences (SMD) between the beef intervention and comparator intervention with less or no beef. Sensitivity and subgroup analyses were also performed. ResultsTwenty relevant RCTs that met the criteria were included. Beef intake did not impact blood pressure or most lipoprotein-related variables, including total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), non-HDL-C, apolipoprotein (apo) A, apo B, and very low-density lipoprotein cholesterol (VLDL-C). Beef consumption had a small, but significant effect on low-density lipoprotein cholesterol (LDL-C) [0.11 (95% CI: 0.008, 0.20), p = 0.03] corresponding to ∼ 2.7 mg/dL higher LDL-C in diets containing more beef compared to low or no beef comparator diets. Sensitivity analyses show this effect was lost when one influential study was removed. ConclusionsDaily unprocessed beef intake did not significantly affect most blood lipids, apolipoproteins, or blood pressures, except for a small increase in LDL-C compared to diets with less or no beef. Thus, there may be other factors influencing the association of red meat and beef on CVD risk that deserve further investigation. Registry and registry number for systematic reviews or meta-analysesThis study was registered at INPLASY 202420013 (doi:10.37766/inplasy2024.2.0013).

Variability of quality-of-life measurements and reporting in randomised controlled trials of pancreatic cancer: a systematic review

ObjectivesThis systematic review aims to evaluate the methodology used in pancreatic cancer (PC) randomised controlled trials (RCTs) measuring quality of life (QOL) and focuses on the type, frequency, survey compliance and duration of these assessments.DesignSystematic review of PC RCTs measuring QOL.Data sourcesA search of PubMed.gov and ClinicalTrials.gov was conducted for PC RCTs measuring QOL from inception to 21 March 2023. Only phase III RCTs were included. Studies were excluded if QOL was not measured, the study was phase I/II, in the second-line setting or unavailable in English. Data were independently extracted by two reviewers in a standardised fashion.Primary and secondary outcome measuresPrimary outcomes included the type of QOL instrument used, the timing and frequency of assessments, methods of analysis and survey completion rates (SCRs) over time. Secondary outcomes included patient demographics, significant QOL improvements and the frequency of trials measuring QOL.ResultsOut of 269 studies screened, 54 RCTs were identified, and 24 measured QOL (involving 11 229 patients). Instruments used included the EORTC QLQ-C30 (n=15), FACT-HEP (n=3), Spitzer-QOL-Index (n=2), EQ-5D (n=2), LASA (n=1) and FACT-PA (n=1). Most trials assessed QOL until disease progression or death (10/24), with 4-week intervals being the most common (7/24). SCRs were reported in 15/24 trials, with disease stage influencing SCRs over time. In trials with metastatic, locally advanced/metastatic, and resectable disease, the median times to reach a 50% response rate—defined as the point where the number of surveys completed was half of the enrolled participants—were 12.41 weeks (n=2), 14.14 weeks (n=10), and 54.2 weeks (n=3), respectively.” Only 2/24 trials reported significant QOL improvements between treatment arms. Patient age was reported in all trials, while race/ethnicity was only reported in 4/24 trials.ConclusionsSignificant variability exists in the timing, methods and reporting of QOL assessments in PC trials. There is a need for further research to assess the implications of missing data and consider the temporality of QOL assessment in patients with advanced cancers and poor prognosis.