SGLT2i effect on atrial fibrillation: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Gliflozins are recommended as first-line treatment in patients with heart failure and/or cardiovascular comorbidities and are demonstrated to reduce atrial fibrillation (AF) occurrence. However, it is not well known which gliflozin yields the larger cardioprotection in terms of AF occurrence reduction. Hence, we aimed to compare data regarding AF recurrence associated with different gliflozins. METHODS: An accurate search of online scientific libraries (from inception to June 1, 2023) was performed. Fifty-nine studies were included in the meta-analysis involving 108 026 patients, of whom 60 097 received gliflozins and 47 929 received placebo. RESULTS: Gliflozins provided a statistically significant reduction of AF occurrence relative to standard of care therapy in the overall population (relative risks [RR]: 0.8880, 95% CI: [0.8059; 0.9784], p = .0164) and in patients with diabetes and cardiorenal diseases (RR: 0.8352, 95% CI: [0.7219; 0.9663], p = .0155). Dapagliflozin significantly decreased AF occurrence as compared to placebo (0.7259 [0.6337; 0.8316], p < .0001) in the overall population, in patients with diabetes (RR: 0.2482, 95% CI: [0.0682; 0.9033], p = .0345), with diabetes associated with cardiorenal diseases (RR: 0.7192, 95% CI: [0.5679; 0.9110], p = .0063) and in the subanalysis including studies with follow-up ≥1 year (RR: 0.7792, 95% CI: [0.6508; 0.9330], p = .0066). No significant differences in terms of AF protection were found among different gliflozins. CONCLUSIONS: Dapagliflozin use was associated with significant reduction in AF risk as compared to placebo in overall population and patients with diabetes, whereas the use of other gliflozins did not significantly reduce AF occurrence.

Estimating average treatment effects for clustered RCTs with recruitment bias.

In clustered randomized controlled trials (RCTs), sample recruitment is often conducted after cluster randomization. This timing can lead to recruitment bias if access to the intervention affects the composition of study-eligible cluster entrants and study consenters. This article develops a potential outcomes framework in such settings that yields a causal estimand that pertains to the always-recruited in either research condition. A consistent inverse probability weighting (IPW) estimator is developed using data on recruits only, and a generalized estimating equations approach is used to obtain robust clustered SE estimators that adjust for estimation error in the IPW weights. A simple data collection strategy is discussed to improve the predictive accuracy of the logit propensity score models. Simulations show that the IPW estimator achieves nominal confidence interval coverage under the assumed identification conditions. An empirical application demonstrates the methods using data from an RCT testing the effects of a behavioral health intervention in schools. An R program for estimation is available for download.

Outcome Heterogeneity in Prehabilitation Trials-Are We Comparing Apples and Oranges?

INTRODUCTION: Over the last decade, the number of prehabilitation randomised controlled trials (RCTs) has increased significantly. Therefore, this review aimed to describe the outcomes reported in prehabilitation RCTs in patients undergoing cancer surgery. METHODS: A search was conducted in Embase, Allied and Complementary Medicine Database, The Cochrane Library, PsycINFO, MEDLINE, and Cumulated Index to Nursing and Allied Health Literature from inception to July 2021. We included RCTs evaluating the effectiveness of preoperative exercise, nutrition, and psychological interventions on postoperative complications and length of hospital stay in adult oncology patients who underwent thoracic and gastrointestinal cancer surgery. The verbatim outcomes reported in each article were extracted, and each outcome was assessed to determine whether it was defined and measured using a validated tool. Verbatim outcomes were grouped into standardized outcomes and categorized into domains. The quality of outcome reporting in each identified article was assessed using the Harman tool (score range 0-6, where 0 indicated the poorest quality). RESULTS: A total of 74 RCTs were included, from which 601 verbatim outcomes were extracted. Only 110 (18.3%) of the verbatim outcomes were defined and 270 (44.9%) were labeled as either "primary" or "secondary" outcomes. Verbatim outcomes were categorized into 119 standardized outcomes and assigned into one of five domains (patient-reported outcomes, surgical outcomes, physical/functional outcomes, disease activity, and intervention delivery). Surgical outcomes were the most common outcomes reported (n = 71 trials, 95.9%). The overall quality of the reported outcomes was poor across trials (median score: 2.0 [IQR = 0.00-3.75]). CONCLUSIONS: Prehabilitation RCTs display considerable heterogeneity in outcome reporting, and low outcome reporting quality. The development of standardized core outcome sets may help improve article quality and enhance the clinical utility of prehabilitation following cancer surgery.

Fidelity, pragmatism and the "grey line" in between-exploring the delivery of a pragmatic physical activity randomised controlled trial-a secondary analysis.

BACKGROUND: Intervention fidelity in health services research has been poor with a reported lack of understanding about what constitutes pragmatic adaptation of interventions and what constitutes failure to maintain intervention fidelity. However, the challenges facing those delivering such interventions have not been thoroughly explored. The aims of this study were to critically explore the challenges in maintaining fidelity experienced by physiotherapy staff and support workers when delivering a complex intervention for older people living with frailty. METHODS: This study is a secondary analysis of data from a process evaluation of a large randomised controlled trial (RCT). The process evaluation employed qualitative methodologies with mixed methods including a variety of data collection methods, including participant observation, semi-structured interviews and documentary analysis. Thematic analysis was used to make sense of the data. RESULTS: Many therapy staff felt ongoing confusion about what was acceptable to adapt and what needed to follow the protocol exactly. We found that some therapy staff were able to embrace the challenges of pragmatically adapting interventions while maintaining intervention fidelity, others stuck rigidly to the protocol and failed to adapt interventions where it was necessary. CONCLUSION: It was clear that the understanding of fidelity and pragmatism was poor. While pragmatic trials are vital to replicate real world clinical practice, further guidance may need to be developed in order to guide the level of adaptation that is acceptable before fidelity is undermined.

Effective dosage and mode of exercise for enhancing cognitive function in Alzheimer's disease and dementia: a systematic review and Bayesian Model-Based Network Meta-analysis of RCTs.

OBJECTIVE: Research the dose-response relationship between overall and certain types of exercise and cognitive function in older adults with Alzheimer's disease and dementia. DESIGN: Systemic and Bayesian Model-Based Network Meta-Analysis. METHODS: In our study, we analyzed data from randomized controlled trials investigating the effects of different exercises on cognitive outcomes in older adults with AD. We searched the Web of Science, PubMed, Cochrane Central Register of Controlled Trials, and Embase up to November 2023. Using the Cochrane Risk of Bias tool (Rob2) for quality assessment and R software with the MBNMA package for data analysis, we determined standard mean differences (SMDs) and 95% confidence intervals (95%CrI) to evaluate exercise's impact on cognitive function in AD. RESULTS: Twenty-seven studies with 2,242 AD patients revealed a nonlinear relationship between exercise and cognitive improvement in AD patients. We observed significant cognitive enhancements at an effective exercise dose of up to 1000 METs-min/week (SMDs: 0.535, SD: 0.269, 95% CrI: 0.023 to 1.092). The optimal dose was found to be 650 METs-min/week (SMDs: 0.691, SD: 0.169, 95% CrI: 0.373 to 1.039), with AE (Aerobic exercise) being particularly effective. For AE, the optimal cognitive enhancement dose was determined to be 660 METs-min/week (SMDs: 0.909, SD: 0.219, 95% CrI: 0.495 to 1.362). CONCLUSION: Nonlinear dose-response relationship between exercise and cognitive improvement in Alzheimer's disease, with the optimal AE dose identified at 660 METs-min/week for enhancing cognitive function in AD.

Digital Self-Management Platform for Adult Asthma: Randomized Attention-Placebo Controlled Trial.

BACKGROUND: Asthma is one of the most common chronic conditions worldwide, with a substantial individual and health care burden. Digital apps hold promise as a highly accessible, low-cost method of enhancing self-management in asthma, which is critical to effective asthma control. OBJECTIVE: We conducted a fully remote randomized controlled trial (RCT) to assess the efficacy of juli, a commercially available smartphone self-management platform for asthma. METHODS: We conducted a pragmatic single-blind, RCT of juli for asthma management. Our study included participants aged 18 years and older who self-identified as having asthma and had an Asthma Control Test (ACT) score of 19 or lower (indicating uncontrolled asthma) at the beginning of the trial. Participants were randomized (1:1 ratio) to receive juli for 8 weeks or a limited attention-placebo control version of the app. The primary outcome measure was the difference in ACT scores after 8 weeks. Secondary outcomes included remission (ACT score greater than 19), minimal clinically important difference (an improvement of 3 or more points on the ACT), worsening of asthma, and health-related quality of life. The primary analysis included participants using the app for 8 weeks (per-protocol analysis), and the secondary analysis used a modified intention-to-treat (ITT) analysis. RESULTS: We randomized 411 participants between May 2021 and April 2023: a total of 152 (37%) participants engaged with the app for 8 weeks and were included in the per-protocol analysis, and 262 (63.7%) participants completed the week-2 outcome assessment and were included in the modified ITT analysis. Total attrition between baseline and week 8 was 259 (63%) individuals. In the per-protocol analysis, the intervention group had a higher mean ACT score (17.93, SD 4.72) than the control group (16.24, SD 5.78) by week 8 (baseline adjusted coefficient 1.91, 95% CI 0.31-3.51; P=.02). Participants using juli had greater odds of achieving or exceeding the minimal clinically important difference at 8 weeks (adjusted odds ratio 2.38, 95% CI 1.20-4.70; P=.01). There were no between group differences in the other secondary outcomes at 8 weeks. The results from the modified ITT analyses were similar. CONCLUSIONS: Users of juli had improved asthma symptom control over 8 weeks compared with users of a version of the app with limited functionality. These findings suggest that juli is an effective digital self-management platform that could augment existing care pathways for asthma. The retention of patients in RCTs and real-world use of digital health care apps is a major challenge. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) registry ISRCTN87679686; https://www.isrctn.com/ISRCTN87679686.

Effects of different natural products in patients with non-alcoholic fatty liver disease-A network meta-analysis of randomized controlled trials.

Due to a scarcity of appropriate therapeutic approaches capable of ameliorating or eliminating non-alcoholic fatty liver disease (NAFLD), many researchers have come to focus on natural products based on traditional medicine that can be utilized to successfully treat NAFLD. In this study, we aimed to evaluate the effects exerted by seven natural products (curcumin, silymarin, resveratrol, artichoke leaf extract, berberine, catechins, and naringenin) on patients with NAFLD. For this purpose, PubMed, Embase, Cochrane Library, and Web of Science, were searched for randomized controlled trials (RCTs) exclusively. The selected studies were evaluated for methodological quality via the Cochrane bias risk assessment tool, and data analysis software was used to analyze the data accordingly. The RCTs from the earliest available date until September 2022 were collected. This process resulted in 37 RCTs with a total sample size of 2509 patients being included. The results of the network meta-analysis showed that artichoke leaf extract confers a relative advantage in reducing the aspartate aminotransferase (AST) levels (SUCRA: 99.1%), alanine aminotransferase (ALT) levels (SUCRA: 88.2%) and low-density lipoprotein cholesterol (LDL-C) levels (SUCRA: 88.9%). Naringenin conferred an advantage in reducing triglyceride (TG) levels (SUCRA: 97.3%), total cholesterol (TC) levels (SUCRA: 73.9%), and improving high-density lipoprotein cholesterol (HDL-C) levels (SUCRA: 74.9%). High-density catechins significantly reduced body mass index (BMI) levels (SUCRA: 98.5%) compared with the placebo. The Ranking Plot of the Network indicated that artichoke leaf extract and naringenin performed better than the other natural products in facilitating patient recovery. Therefore, we propose that artichoke leaf extract and naringenin may exert a better therapeutic effect on NAFLD. This study may help guide clinicians and lead to further detailed studies.

Efficacy of Laser Acupuncture for Treatment of Chronic Low Back Pain: A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize and systematically analyze the efficacy of laser acupuncture (LA) interventions in reducing pain scores in patients suffering from chronic low back pain (LBP). METHODS: PubMed, EMBASE, and Scopus databases were searched for randomized controlled trials, published in peer-reviewed journals, and reporting LA interventions in patients with chronic LBP. All included studies had a comparison group of patients, receiving placebo treatment, sham intervention, conventional therapy, or no treatment. The outcome of interest was the pain intensity score. Pooled effect estimates were calculated using random-effects models and reported as weighted mean difference (WMD) with 95% confidence intervals (CI). RESULTS: A total of 20 studies were included. Compared to the control group, patients who underwent LA experienced a significant reduction in reported pain scores immediately after completing the treatment (WMD -1.14, 95% CI: -1.68 to -0.61). High dose of LA was associated with a more significant decrease in the pain scores (WMD -1.40, 95% CI: -1.94 to -0.85; N = 15, I2 = 81.0%). However, reported pain scores of patients who received LA were statistically similar to those of the control group at short-term (4-8 weeks after the treatment) and long-term (12 months) follow-ups. CONCLUSIONS: In patients with chronic LBP, LA may help in alleviating pain immediately after the treatment. However, this effect does not appear to be sustained on later follow-up assessments. Consequently, patients should be informed about the potential limitations of the treatment in providing lasting pain relief.

Is percutaneous tibial nerve stimulation (PTNS) effective for fecal incontinence (FI) in adults compared with sham electrical stimulation? A meta-analysis.

BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.

Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis.

CONTEXT: Chinese medicine injections (CMIs) are widely used as adjuvant therapy for cervical cancer in China. However, the effectiveness of different types of CMIs remains uncertain. OBJECTIVE: To assess the effectiveness and safety of CMIs when used in conjunction with radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in combination with cisplatin (DDP), docetaxel plus cisplatin (DP), and paclitaxel plus cisplatin (TP). MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in databases including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science from inception to September 2023. We calculated the risk ratio with a 95% confidence interval and the surface under the cumulative ranking area curve (SUCRA) for the clinical efficacy rate (CER), the efficacy rate by Karnofsky Performance Status (KPS), and the rates of leukopenia reduction (LRR) and gastrointestinal reactions (GRR). RESULTS: Forty-seven RCTs were included, including nine CMI types: Aidi, Fufangkushen, Huangqi, Kangai (KA), Kanglaite (KLT), Renshenduotang, Shenqifuzheng (SQFZ), Shenmai (SM), and Yadanzi. KLT and KA were likely optimal choices with radiotherapy for CER and KPS, respectively. KA and KLT were optimal choices with RT + DDP for CER and GRR, respectively. KLT was the likely optimal choice with RT + DP for CER and KA for both KPS and GRR. SM and SQFZ were the likely optimal choices with RT + TP for CER and LRR, respectively. CONCLUSIONS: The optimal recommendation depends on whether CMIs are used with radiotherapy or concurrent chemoradiotherapy. More high-quality RCTs are needed to confirm further and update the existing evidence.

Analysis of phase III clinical trials in metastatic NSCLC to assess the correlation between QoL results and survival outcomes.

BACKGROUND: In addition to improving survival outcomes, new oncology treatments should lead to amelioration of patients' quality of life (QoL). Herein, we examined whether QoL results correlated with PFS and OS outcomes in phase III randomized controlled trials (RCTs) investigating new systemic treatments in metastatic non-small cell lung cancer (NSCLC). METHODS: The systematic search of PubMed was conducted in October 2022. We identified 81 RCTs testing novel drugs in metastatic NSCLC and published in the English language in a PubMed-indexed journal between 2012 and 2021. Only trials reporting QoL results and at least one survival outcome between OS and PFS were selected. For each RCT, we assessed whether global QoL was "superior," "inferior," or with "non-statistically significant difference" in the experimental arm compared to the control arm. RESULTS: Experimental treatments led to superior QoL in 30 (37.0%) RCTs and inferior QoL in 3 (3.7%) RCTs. In the remaining 48 (59.3%) RCTs, a statistically significant difference between the experimental and control arms was not found. Of note, we found a statistically significant association between QoL and PFS improvements (X2 = 3.93, p = 0.0473). In more detail, this association was not significant in trials testing immunotherapy or chemotherapy. On the contrary, in RCTs testing target therapies, QoL results positively correlated with PFS outcomes (p = 0.0196). This association was even stronger in the 32 trials testing EGFR or ALK inhibitors (p = 0.0077). On the other hand, QoL results did not positively correlate with OS outcomes (X2 = 0.81, p = 0.368). Furthermore, we found that experimental treatments led to superior QoL in 27/57 (47.4%) trials with positive results and in 3/24 (12.5%) RCTs with negative results (p = 0.0028). Finally, we analyzed how QoL data were described in publications of RCTs in which QoL outcomes were not improved (n = 51). We found that a favorable description of QoL results was associated with sponsorship by industries (p = 0.0232). CONCLUSIONS: Our study reveals a positive association of QoL results with PFS outcomes in RCTs testing novel treatments in metastatic NSCLC. This association is particularly evident for target therapies. These findings further emphasize the relevance of an accurate assessment of QoL in RCTs in NSCLC.

Sex and Gender in Randomized Controlled Trials of Adults Receiving Maintenance Dialysis: A Meta-epidemiologic Study.

RATIONALE & OBJECTIVE: How sex and gender concepts are incorporated into randomized controlled trials (RCTs) in adults with kidney failure receiving maintenance dialysis is largely unknown. We describe these practices in published journal articles as well as investigate the proportion of women and female participants in these studies. STUDY DESIGN: Meta-epidemiologic study. SETTING & STUDY POPULATIONS: RCTs in maintenance dialysis. SELECTION CRITERIA FOR STUDIES: Trials published in high-impact journals in 2000-2020. DATA EXTRACTION: Implemented in duplicate with conflicts resolved by a third reviewer. ANALYTICAL APPROACH: Meta-regression was performed to identify trial characteristics independently associated with the proportion of women and female participants. RESULTS: Among 561 included RCTs, 69.7% were parallel and 28.0% were crossover in design; 80.6% were conducted in the hemodialysis population; and 25% of trials compared the treatment of interest with a placebo arm, 25% with a usual care treatment arm, and 50% with an active alternative therapy arm. Of the RCTS, 37.6% were masked. The median size was 60 (IQR, 26-151) participants, and the median follow-up period was 154 (IQR, 42-365) days. The mean proportion of women or female participants was 0.40±0.13 (SD): 39.0% of trials reported sex, and 26.6% reported the gender of the participants. Also, 56.2% referred to participants as females, 25.3% referred to participants as women, and 15.5% referred to both females and women. No trial characteristic other than region (ß of 0.062 [95% CI, 0.007-0.117] for Asia) was associated with the proportion of women or female participants. Considering trial design and conduct, 2.7% of trials used sex and/or gender as an inclusion criterion, 26.6% as an exclusion criterion, 4.5% for randomization, 4.8% for subgroup analyses, and 15.7% for covariate adjustment. LIMITATIONS: Only high-impact journal articles were studied; and the included studies lacked pediatric trials, those addressing chronic kidney disease or kidney transplantation, any trials from Africa and underrepresentation of other regions, and missing data. CONCLUSIONS: RCTs in dialysis are representative of the general dialysis population with regard to sex and gender but they uncommonly report both and often do not include either in their reporting or analysis.

Randomised controlled trials of antipsychotics for people with autism spectrum disorder: a systematic review and a meta-analysis.

BACKGROUND: Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common. METHODS: We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events. RESULTS: We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of -6.45 [95% confidence interval (CI) -8.13 to -4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects (p = 0.003) and also weight gain (p < 0.00001), sedation (p < 0.00001) and increased appetite (p = 0.001) in the antipsychotic group. CONCLUSIONS: There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.

Mesenchymal Stem Cell Therapy in the Treatment of Neurodegenerative Cerebellar Ataxias: a Systematic Review and Meta-analysis.

The objective of this study is to synthesise the findings of clinical studies in order to derive evidence for use of the mesenchymal stem cell (MSC) therapy in the treatment of neurodegenerative cerebellar ataxias. In order to find relevant studies for the systematic review, we searched through Medline (1985 to July 2020), PubMed and Clinical trial register. We included both single-arm and comparative studies in which MSCs were given as intervention in neurodegenerative ataxia patients at any time after the diagnosis. We used Joanna Briggs Institute (JBI) quality scale to evaluate the methodological qualities of the included studies. Our literature search obtained 81 publications. Three articles comprising a total of 47 patients were included in the meta-analysis. None of them were randomised controlled trials (RCTs). Pooled analysis noted that there was a decrease in the Berg Balance Scale (BBS)/Scale for the Assessment and Rating of Ataxia (SARA) score from pre to post assessment; however, the difference was statistically not significant (standardised mean difference (SMD) - 0.20; 95% CI - 0.78 to 0.38). No significant side effects were reported in any of the studies. We did not observe any statistically significant difference in the pooled mean difference in the International Cooperative Ataxia Rating Scale (ICARS) score between pre and post assessment in patients with ataxia after receiving the stem cells (SMD 0.36, 95% CI - 0.08 to 0.81). Our systematic review and meta-analysis concluded that MSC cell therapy appeared safe but provided insufficient evidence to support the use of MSCs to treat patients with neurodegenerative cerebellar ataxia at present. No l RCTs was available in the literature to test efficacy; therefore, well-designed RCTs are needed to ascertain the effectiveness of MSCs in patients with neurodegenerative cerebellar ataxias.

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

BACKGROUND AND OBJECTIVE: Integrated 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. METHODS: Through 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. RESULTS: A 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. CONCLUSION: Although 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.

Do Couple-Based Interventions Show Larger Effects in Promoting HIV Preventive Behaviors than Individualized Interventions in Couples? A Systematic Review and Meta-analysis of 11 Randomized Controlled Trials.

This systematic review and meta-analysis aims to compare the effects of couple-based prevention interventions against individual-level interventions on HIV prevention in randomized controlled trials (RCTs), identify potential moderators, and assess study quality. Eleven RCTs were included, comprising 3933 couples in the intervention group and 7125 individuals in the individual control group, predominantly in heterosexual couples from the USA and Africa. Couple-based interventions had a more significant effect in promoting condom use and HIV testing. Education levels of high school or above, residence in low- and middle-income countries, and intervention design incorporating HIV counseling and testing were associated with higher odds of condom use. The quality assessment analysis identified methodological and theoretical heterogeneity factors. Evidence of couple-based HIV prevention RCTs among men who have sex with men, injecting drug users, sex workers, and transgender women warrant further investigation. Recommendations are made to improve the quality and replicability of future intervention studies.

RESUMEN: Esta revista sistemática y metanálisis tiene por objeto comparar los efectos de las intervenciones de prevención basadas en pareja con las a nivel individual en la prevención del VIH en ensayos controlados aleatorios (ECA), identificar posibles moderadores y evaluar la calidad de los estudios. Se incluyeron once ECA, que comprendían 3.933 parejas en el grupo de intervención y 7.125 personas en el grupo de control individual, la mayoría de las cuales eran heterosexuales de EE.UU. y de África. Las intervenciones basadas en pareja son más eficaces para promover el uso de preservativos y pruebas del VIH. Los niveles de educación secundaria o superior, los países de ingresos bajos y medianos, y los diseños de intervención que incluyen pruebas y asesoramiento sobre el VIH se relacionan con más uso de preservativos. El análisis de evaluación de la calidad ha identificado factores de heterogeneidad metodológica y teórica. Las pruebas de ECA basadas en pareja para la prevención del VIH en hombres que tienen sexo con hombres, consumidores de drogas inyectables, trabajadoras sexuales y mujeres transgénero necesitan más investigación. Se hacen recomendaciones para mejorar la calidad y replicabilidad de futuros estudios de intervención.

Characteristics of baseline frequency data in spinal RCTs do not suggest widespread non-random allocation.

BACKGROUND: Recent signs of fraudulent behaviour in spine RCTs have queried the integrity of trials in the field. RCTs are particularly important due to the weight they are accorded in guiding treatment decisions, and thus, ensuring RCTs' reliability is crucial. This study investigates the presence of non-random baseline frequency data in purported RCTs published in spine journals. METHODS: A PubMed search was performed to obtain all RCTs published in four spine journals (Spine, The Spine Journal, the Journal of Neurosurgery Spine, and European Spine Journal) between Jan-2016 and Dec-2020. Baseline frequency data were extracted, and variable-wise p values were calculated using the Pearson Chi-squared test. These p values were combined for each study into study-wise p values using the Stouffer method. Studies with p values below 0.01 and 0.05 and those above 0.95 and 0.99 were reviewed. Results were compared to Carlisle's 2017 survey of anaesthesia and critical care medicine RCTs. RESULTS: One hundred sixty-seven of the 228 studies identified were included. Study-wise p values were largely consistent with expected genuine randomized experiments. Slightly more study-wise p values above 0.99 were observed than expected, but a number of these had good explanations to account for that excess. The distribution of observed study-wise p values was more closely matched to the expected distribution than those in a similar survey of the anaesthesia and critical care medicine literature. CONCLUSION: The data surveyed do not show evidence of systemic fraudulent behaviour. Spine RCTs in major spine journals were found to be consistent with genuine random allocation and experimentally derived data.

Effects of curcumin/turmeric supplementation on obesity indices and adipokines in adults: A grade-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

In the present study, we explored the effect of curcumin/turmeric supplementation on anthropometric indices of obesity, leptin, and adiponectin. We searched PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar up to August 2022. Randomized clinical trials (RCTs) investigating the impact of curcumin/turmeric on obesity indices and adipokines were included. We applied the Cochrane quality assessment tool to evaluate the risk of bias. The registration number is CRD42022350946. Sixty eligible RCTs, with a total sample size of 3691 individuals were included for quantitative analysis. We found that supplementation with curcumin/turmeric significantly reduced body weight (WMD: -0.82 kg, 95% CI: -1.30, -0.35; p = 0.001), body mass index (WMD: -0.30 kg/m2 , 95% CI: -0.53, -0.06, p = 0.013), waist circumference (WMD: -1.31 cm, 95% CI: -1.94, -0.69, p < 0.001), body fat percentage (WMD: -0.88%, 95% CI: -1.51, -0.25, p = 0.007), leptin (WMD = -4.46 ng/mL; 95% CI: -6.70, -2.21, p < 0.001), and increased adiponectin (WMD = 2.48 µg/mL; 95% CI: 1.34, 3.62, p < 0.001). Overall, our study shows that supplementation with curcumin/turmeric significantly improves anthropometric indices of obesity and adiposity-related adipokines (leptin and adiponectin). However, due to high between-studies heterogeneity, we should interpret the results with caution.

A meta-analytic framework to adjust for bias in external control studies.

While randomized controlled trials (RCTs) are the gold standard for estimating treatment effects in medical research, there is increasing use of and interest in using real-world data for drug development. One such use case is the construction of external control arms for evaluation of efficacy in single-arm trials, particularly in cases where randomization is either infeasible or unethical. However, it is well known that treated patients in non-randomized studies may not be comparable to control patients-on either measured or unmeasured variables-and that the underlying population differences between the two groups may result in biased treatment effect estimates as well as increased variability in estimation. To address these challenges for analyses of time-to-event outcomes, we developed a meta-analytic framework that uses historical reference studies to adjust a log hazard ratio estimate in a new external control study for its additional bias and variability. The set of historical studies is formed by constructing external control arms for historical RCTs, and a meta-analysis compares the trial controls to the external control arms. Importantly, a prospective external control study can be performed independently of the meta-analysis using standard causal inference techniques for observational data. We illustrate our approach with a simulation study and an empirical example based on reference studies for advanced non-small cell lung cancer. In our empirical analysis, external control patients had lower survival than trial controls (hazard ratio: 0.907), but our methodology is able to correct for this bias. An implementation of our approach is available in the R package ecmeta.

Critically Appraising Pragmatist Critiques of Evidence-Based Medicine: Is EBM Defensible on Pragmatist Grounds?

Significant contributions to debates in the philosophy of evidence-based medicine (EBM) have come from a variety of different philosophical quarters, yet mainstream discourse in the field has been largely devoid of contributions from scholars working in the pragmatist tradition. This is a particularly conspicuous omission, given pragmatism's commitment to the melioristic view that philosophy both can, and should, be about the business of concretely bettering the human estate. Two exceptions to this oversight come from Brian Walsh and Maya Goldenberg. Unfortunately, in both cases, the misapplication of pragmatist thinking leads to the mistaken view that EBM is committed to some form of pernicious objectivism. This article aims to revise these pragmatist critiques in order to bring them more consistently in line with pragmatist values and commitments. Doing so shows that EBM is defensible on pragmatist grounds against objectivist attacks.