Individual Randomized Controlled Trials Research Articles

Impact of selective reporting bias on stroke trials: potential compromise in evidence synthesis - A cross-sectional study

BackgroundAccurate reporting of outcomes is crucial for interpreting the results of randomized controlled trials (RCTs). However, selectively reporting outcomes in publications to achieve researchers’ anticipated results still occurs frequently. This study aims to investigate the prevalence of selective reporting of outcomes in RCTs on treating acute ischemic stroke (AIS), identify factors contributing to this issue, and assess its potential impact on the degree and direction of intervention effect.MethodsA search was conducted in MEDLINE, Embase, and the Cochrane Library to collect interventional RCTs on AIS published from 2020 to 2022. Full texts of RCTs were reviewed, and only those reporting International Clinical Trials Registry Platform primary registry numbers were included. Registration information of the RCTs was extracted from the registry platforms and compared with the publications’ details to assess the selective reporting of outcomes. Bayesian multilevel logistic regression was used to analyze the reasons behind selective reporting.ResultsAmong the total of 159 AIS RCTs identified, 82 (51.6%) were ultimately included, as they reported registration numbers, which encompassed 819 outcomes. Among them, 72 RCTs (87.8%) and 497 outcomes (60.7%) exhibited selective reporting. Omission-type selective reporting (downgrading, omitting, or ambiguously reporting) accounted for 36.4%, while addition-type selective reporting (upgrading, adding, or altering the measurement scope of outcomes) comprised 63.6%. Omission-type selective reporting correlated with negative results (OR: 7.39; 95% CI: 4.08—13.44), whereas addition-type selective reporting correlated with positive results (OR: 2.07; 95% CI: 1.34—3.26) and publication in journals that are not in the top quartile of the Journal Citation Reports (OR: 2.48; 95% CI: 1.15—5.38).ConclusionsRegistered interventional AIS RCTs still face significant issues regarding selective reporting of outcomes. Therefore, it is necessary to further evaluate the influence of selective reporting bias on the positive results obtained from individual AIS RCTs and the systematic reviews based on these RCTs.

Efficacy and safety of cangfu daotan decoction as an adjuvant treatment of Diane-35 for polycystic ovary syndrome: A systematic review and meta-analysis

ObjectiveCangfu Daotan decoction is a classic traditional Chinese medicine formula that has been found to be beneficial for treating polycystic ovarian syndrome (PCOS) in animal models. This systematic review aimed to assess the efficacy and safety of Cangfu Daotan decoction as an adjuvant treatment to Diane-35 for PCOS in humans. MethodsSeven electronic databases were searched up to June 22, 2024, to identify randomized controlled trials (RCTs) that evaluated Cangfu Daotan decoction combined with Diane-35 versus Diane-35 alone for the treatment of PCOS. The effects of individual RCTs were combined via meta-analysis and were measured as relative risks (RRs) or weighted mean differences (WMDs). ResultsTwenty-five RCTs with a moderate to high risk of bias were included, involving 1845 patients with PCOS. Meta-analyses indicated that compared with Diane-35 alone, the combination of Diane-35 and Cangfu Daotan decoction significantly improved the response rate (RR 1.19, 95 % confidence interval [CI] 1.14 to 1.24), pregnancy rate (RR 1.57, 95 % CI 1.18 to 2.09), ovulation rate (RR 1.22, 95 % CI 1.11 to 1.35), and ovarian volume (WMD -1.43 cm3, 95 % CI -2.46 to −0.39). Cangfu Daotan decoction also significantly reduced the luteinizing hormone (LH) level, LH:FSH ratio, testosterone level, prolactin level, body mass index (BMI) and hirsutism and acne scores but had no significant effect on the follicle-stimulating hormone (FSH) level. All adverse events were mild and not related to Cangfu Daotan decoction treatment. ConclusionsThe findings suggest that Cangfu Daotan decoction, as an adjuvant therapy to Diane-35 for the treatment of PCOS, can reduce multiple sex hormone levels and BMI, relieve hyperandrogenism signs, and ultimately improve pregnancy outcomes, with good safety. The effect of Cangfu Daotan decoction on FSH remains uncertain. Due to limitations of risk of bias and heterogeneity, the quality of evidence was rated as moderate to very low.

How to distinguish promotion, prevention and treatment trials in public mental health? Study protocol for the development of the VErona-LUgano Tool (VELUT)

IntroductionPromoting mental health, preventing and treating mental disorders are critically important in public health, and many randomised controlled trials (RCTs) evaluate intervention strategies for these objectives. However, distinguishing promotion from...

Poster 295: Evidence Suggesting Beneficial Effects of Platelet-Rich Plasma Over Alternative Injections for Knee Osteoarthritis Is Fairly Robust: A Systematic Review and Statistical Fragility Index-Based Meta-Analysis of Randomized Controlled Trials

Objectives: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. The purpose of this study is to evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. Methods: All RCTs comparing PRP to alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse fragility index (RFI) were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from one or more trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. Results: In total, this analysis included outcomes from 1993 patients with a mean (± standard deviation) age of 58.0 ± 3.8 years. The mean number of events required to reverse significance (FI) was 4.57 ± 5.85. This corresponded to a fragility quotient of 0.060 ± 0.075, meaning the significance of the results was contingent on 6 events per 100 participants. For non-significant outcome events, the mean number of events required to reverse statistical nonsignificance (RFI) was 4.41 ± 2.22. This corresponded to a reverse fragility quotient of 0.065 ± 0.056, meaning the non-significance of the results was contingent on 6.5 events per 100 participants (Figure 1). Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared to hyaluronic acid (p = 0.002, odds ratio 95% CI = 2.19 [1.33-3.62]) (Figure 2) as well as higher rates of patient-reported symptom relief (p = 0.019, odds ratio [95% CI] = 1.55 [1.07-2.24]) (Figure 3), not requiring a reintervention after the initial injection treatment (p = 0.002, odds ratio [95% CI] = 2.17 [1.33-3.53]) (Figure 4), and achieving the minimal clinically important difference (MCID) for pain improvement (p = 0.007, odds ratio [95% CI] = 6.19[1.63-23.42]) when compared to all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. Conclusions: Individual RCTs evaluating PRP for knee OA possess slight robustness. Upon meta-analysis, PRP demonstrated a significant advantage over HA as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared to alternative, nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and healthcare. Future RCTs and meta-analyses should consider reporting fragility indices and quotients to facilitate interpretation of results in their proper context. In addition, the robustness of these findings suggests that reconsideration of the American Academy of Orthopaedic Surgeons clinical practice guidelines around the use of PRP for knee OA may be warranted.

Fast-track recovery after surgery for perforated peptic ulcer safely shortens hospital stay: A systematic review and meta-analysis of six randomized controlled trials and 356 patients.

Postoperative management after surgery for perforated peptic ulcer is still burdened by old traditions. All available data for fast-track recovery in this setting are either very unspecific or underpowered. The aim of this study was to evaluate fast-track recovery in this diagnosis-specific context in a larger sample. Electronic data sources were searched. Eligible studies were randomized controlled trials (RCTs) comparing fast-track recovery and traditional management after surgery for perforated peptic ulcer in adults. A systematic review and meta-analysis was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines regulated the process. Quality and risk of bias assessments of individual RCTs were performed by means of the Let Evidence Guide Every New Decision criteria and the Cochrane risk-of-bias tool. Primary endpoints were length of hospital stay and risk of complications. Random or fixed effects modeling were applied as indicated. Outcomes were measured by mean difference and risk difference. Six RCTs with a total cohort of 356 patients were included. Results of our meta-analysis showed significantly shortened length of hospital stay (mean difference -3.50days [95% CI -4.51 to -2.49], p≤0.00001), significantly less superficial and deep surgical-site infections (risk differences -0.12 [95% CI -0.20, -0.05], p=0.002 and -0.03 [95% CI -0.09, 0.03], and p=0.032, respectively), and significantly fewer pulmonary complications (risk difference -0.10 [95% CI -0.17, -0.03], p=0.004) in the fast-track group. This systematic review and meta-analysis shows that fast-track recovery after surgery for perforated peptic ulcer significantly shortened hospital stay in the studied cohort without increasing the risk of postoperative complications.

Social Skills Interventions for Adolescents with Level 1 Autism Spectrum Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials.

Evidence on the efficacy of social skills training for adolescents with Level 1 Autism Spectrum Disorder (ASD) is unclear. We searched Pubmed, Scopus, and Web of Science until July 27th, 2023, for randomized controlled trials (RCTs) of social skills training for pre-adolescents and adolescents (aged 9-18) with Level 1 ASD. We then pooled data on efficacy from individual RCTs by conducting multivariate mixed-effects meta-analyses in R. We estimated possible bias in the retained RCTs using the RoB2 tool. We retained 36 RCTs (encompassing 2796 participants), including 18 RCTs comparing an experimental treatment to a waiting list, and 18 RCTs comparing it to standard care/control treatment. Meta-analyses showed that experimental treatments were significantly more efficacious than waiting list or standard care/ control treatments in improving social skills (SMD = 0.3745; 95%CI = [0.2396; 0.5093]), as well as reducing behavioral symptoms (0.3154;0.1783, 0.4525) and anxious/depressive symptoms (0.2780; 0.0432, 0.5128). However, for some outcomes there was significant heterogeneity across studies and evidence of publication bias. Subgroup analyses and meta-regressions did not identify any specific clinical or demographic factors as significant predictors of outcome. The most common risk of bias across studies was related to deviations from intended interventions and measurement of the outcomes. At the group level, social skills training for adolescents with Level 1 ASD is efficacious, with small-to-moderate effect size. Future research should focus on personalized medicine approaches, aimed at tailoring interventions to specific characteristics of adolescents with Level 1 ASD.

Effectiveness of Problem-Solving Therapy in Improving Patient Mental Health, Function, Quality of Life, and Mortality Post-Stroke: A Systematic Review.

Problem-solving therapy (PST) is a potential psychological intervention aimed at preventing and treating psychological issues in stroke patients, although its efficacy is not clearly established. This systematic review assessed the effectiveness of PST in improving mental health, functioning, quality of life, and mortality in this population. Six databases were searched for literature indexed through March 2024, including the Cochrane Library, PubMed, Scopus, CINAHL, NeuroBITE, and OTseeker. This review (CRD42023483757) followed the PRISMA guidelines and the Cochrane Library Handbook, utilizing the RoB 2 tool and GRADE system to assess the quality of the evidence. It included eight randomized controlled trials (RCTs) involving 1249 patients with stroke. Among them, five RCTs showed that PST might improve depression. Additionally, individual RCTs demonstrated the efficacy of PST in addressing patient anxiety, apathy, and coping. With respect to mental health, PST might affect patient quality of life and mortality. However, the results of four RCTs demonstrated no effect of PST on patient functioning. The quality of evidence for the outcomes ranged from very low to high. PST may improve mental health, quality of life, and mortality in patients with stroke.

Reporting quality of heart failure randomized controlled trials 2000-2020: Temporal trends in adherence to CONSORT criteria.

Heart failure (HF) is a major cause of morbidity and mortality in older adults. Randomized controlled trials (RCTs) inform HF policy and practice, but the accurate interpretation of results is contingent on clear and transparent reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement serves as a guide to RCT reporting. We evaluated the quality of reporting in HF RCTs in high-impact journals by assessing their adherence to CONSORT. We searched MEDLINE, EMBASE and CINAHL for HF RCTs published in high-impact journals 2000-2020. We assessed the proportion of CONSORT criteria that individual HF RCTs adhered to, and used the Jonckheere-Terpstra test to examine temporal trends in adherence. Multivariable linear regression explored the association between trial characteristics and adherence to CONSORT. Primary analysis assessed adherence to CONSORT 2010 update. A sensitivity analysis assessed adherence to the original (1996) CONSORT criteria. Among 221 RCTs analysed, the mean (standard deviation [SD]) adherence was suboptimal overall (mean [SD] adherence 69.7 [11.5]%) (5513/7913 criteria), with a temporal increase in adherence over the 20-year period (p < 0.001). Factors associated with adherence included publication after versus during/before 2010 (β = 10.17, 95% confidence interval [CI] 7.64-12.70; p < 0.001); two-group parallel individual-level randomization versus other (including multi-group or cluster randomization) (β = 5.81, 95% CI 2.88-8.73; p < 0.001); and multicentre versus single-centre trials (β = 7.26, 95% CI 3.25-11.27; p < 0.001). There was no difference in trial adherence to the updated CONSORT (2010) versus the original (1996) CONSORT criteria, and temporal trends in adherence to both sets of criteria were similar, likely due to overlap between the two sets of criteria. Trials with greater adherence to CONSORT were published in higher impact factor journals, with a positive correlation (r = 0.312; p < 0.001). The quality of reporting in HF RCTs, as measured by CONSORT adherence, has improved over time but remains suboptimal.

Clinical evaluation of marketed and non-marketed orthodontic products: are researchers now ahead of the times? A meta-epidemiological study

BackgroundThe advertisement and adoption of untested orthodontic products is common. This study aimed to provide an update regarding the prevalence of clinical trials in orthodontics evaluating commercially marketed products. Associations between marketed/non-marketed products and study characteristics such as direction of effect, declaration of conflict of interest and industry sponsorship were evaluated. In addition, within the marketed products associations between direction of effect and study characteristics were explored.Material and methodsElectronic searching of a single database (Medline via PubMed) was undertaken to identify Randomized controlled trials (RCTs) published over a 5-year period (1st January 2017 to 31st December 2021). Descriptive statistics and associations between trial characteristics were explored.Results196 RCTs were analysed. RCTs were frequently published in Angle Orthodontist (18.4%), American Journal of Orthodontics and Dentofacial Orthopedics (14.8%) and European Journal of Orthodontics (13.3%). 65.3% (128/196) of trials assessed marketed products after their introduction. The majority of trials assessed interventions to improve treatment efficiency (33.7%). Growth modification appliances were typically analysed in non-marketed compared to marketed products. An association between the type of product (marketed vs non-marketed) and both the declaration of conflict of interest and industry sponsorship was detected. For individual RCTs assessing marketed products either a positive effect (45.3%) or equivalence between interventions or between intervention and untreated control (47.7%) was evident. In 27% of these trials either no conflict of interest or industry funding was not clearly declared. Within the marketed products, no association between the direction of the effect and conflict of interest or funding was detected.ConclusionsThe analysis of marketed orthodontic products after their introduction is still common practice. To reduce research waste, collaboration prior to the licensing and marketing of orthodontic products between researchers, industry and manufacturers is recommended.

Fascial Defect Closure During Ventral Hernia Repair: A Systematic Review of Randomized Controlled Trials.

During minimally invasive ventral hernia repair (VHR) it is unknown if a fascial defect closure, as opposed to a bridged repair (current care), is beneficial for patients. We sought to systematically review the published literature on the role of fascial defect closure during minimally invasive VHR. PubMed, Embase, Scopus, Cochrane, and Clinicaltrials.gov were reviewed for randomized controlled trials (RCTs) that compared fascial defect closure with bridged repair. The primary outcome was major complications defined as deep/organ-space surgical site infections (SSIs), reoperations, hernia recurrences, or deaths. Secondary outcomes included SSI, seroma, eventration, hernia recurrence, post-operative pain, and quality of life (QOL). Pooled risk ratios with 95% confidence intervals were obtained through random effect meta-analyses. Of 579 screened articles, 6 publications of 5 RCTs were included. No significant difference in major complications (10.6% vs 10.4%, RR=1.05, 95% CI=0.51-2.14, P=.90) or recurrences (9.0% vs 10.6%, RR=0.92, 95% CI=0.32-2.61, P=.87) were found between groups. Fascial defect closure decreased the risk of seromas (22.9% vs 34.2%, RR=0.60, 95% CI=0.37-0.97, P=.04) and may decrease the risk of eventrations (6.7% vs 9.0%, RR=0.74, 95% CI=0.37-1.50, P=.41) at the expense of potentially increasing the risk of SSI (3.2% vs 1.4%, RR=1.89, 95% CI=0.60-5.93; P=.28). Reporting of pain and QOL scores was inconsistent. While most individual RCTs demonstrated benefit with fascial defect closure during minimally invasive VHR, our meta-analysis of fascial defect closure demonstrated only a statistically significant difference in seromas compared to bridged repair. Large, multi-center RCTs are needed.

Efficacy and safety of moxibustion on cancer-related fatigue: a systematic review and meta-analysis of randomized controlled trials.

The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = - 1.66, 95% CI = - 2.05, - 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality.

Effects of turmeric (Curcuma longa) supplementation on glucose metabolism in diabetes mellitus and metabolic syndrome: An umbrella review and updated meta-analysis.

This study aims to comprehensively review the existing evidence and conduct analysis of updated randomized controlled trials (RCTs) of turmeric (Curcuma longa, CL) and its related bioactive compounds on glycemic and metabolic parameters in patients with type 2 diabetes (T2DM), prediabetes, and metabolic syndrome (MetS) together with a sub-group analysis of different CL preparation forms. An umbrella review (UR) and updated systematic reviews and meta-analyses (SRMAs) were conducted to evaluate the effects of CL compared with a placebo/standard treatment in adult T2DM, prediabetes, and MetS. The MEDLINE, Embase, The Cochrane Central Register of Control Trials, and Scopus databases were searched from inception to September 2022. The primary efficacy outcomes were hemoglobin A1C (HbA1C) and fasting blood glucose (FBG). The corrected covered area (CCA) was used to assess overlap. Mean differences were pooled across individual RCTs using a random-effects model. Subgroup and sensitivity analyses were performed for various CL preparation forms. Fourteen SRMAs of 61 individual RCTs were included in the UR. The updated SRMA included 28 studies. The CCA was 11.54%, indicating high overlap across SRMAs. The updated SRMA revealed significant reduction in FBG and HbA1C with CL supplementation, obtaining a mean difference (95% confidence interval [CI]) of -8.129 (-12.175, -4.084) mg/dL and -0.134 (-0.304, -0.037) %, respectively. FBG and HbA1C levels decreased with all CL preparation forms as did other metabolic parameters levels. The results of the sensitivity and subgroup analyses were consistent with those of the main analysis. CL supplementation can significantly reduce FBG and HbA1C levels and other metabolic parameters in T2DM and mitigate related conditions, including prediabetes and MetS. PROSPERO (CRD42016042131).

Efficacy and Safety of Clonidine in the Treatment of Acute Mania in Bipolar Disorder: A Systematic Review.

Clonidine, an alpha-2 adrenergic agonist, has been proposed as an antimanic agent that acts by reducing noradrenergic transmission. We conducted a systematic review to examine the efficacy and safety of clonidine for acute mania/hypomania. A comprehensive literature search was performed to identify randomized controlled trials (RCT) and non-randomized studies investigating the efficacy and safety of monotherapy/adjuvant treatment with clonidine for acute mania/hypomania in patients with bipolar disorder (BD). Nine studies (n = 222) met our inclusion criteria, including five RCTs (n = 159) and four non-randomized studies (n = 63). Non-randomized studies showed clonidine to help reduce symptoms of mania. However, data from placebo controlled RCTs were inconsistent. One RCT showed adjuvant clonidine as superior to placebo, whereas another RCT reported that clonidine was not better than placebo. In individual RCTs, lithium and valproate offered better antimanic effects compared to clonidine. Studies reported hypotension, depression, and somnolence as common adverse effects. Significant differences in study design and sample size contributed to high heterogeneity. This systematic review suggests low-grade evidence for clonidine as an adjuvant treatment for acute mania with mood stabilizers and inconclusive efficacy as monotherapy, warranting further well-designed RCTs.

The effect of curcumin supplementation on weight loss and anthropometric indices: an umbrella review and updated meta-analyses of randomized controlled trials

BackgroundCurcumin supplementation may promote weight loss and ameliorate obesity-related complications through its antioxidative and anti-inflammatory properties. ObjectiveAn umbrella review and updated meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effect of curcumin supplementation on anthropometric indices. MethodsSystematic reviews and meta-analyses (SRMAs) of RCTs were identified from electronic databases (Medline, Scopus, Cochrane, and Google Scholar) up to 31 March, 2022, without language restriction. SRMAs were included if they assessed curcumin supplementation on any of the following: BMI, body weight (BW), or waist circumference (WC). Subgroup analyses were performed, stratifying by patient types, severity of obesity, and curcumin formula. The study protocol was a priori registered. ResultsFrom an umbrella review, 14 SRMAs with 39 individual RCTs were included with a high degree of overlap. In addition, searching was updated from the last search of included SRMAs in April 2021 up to 31 March, 2022, and we found 11 additional RCTs, bringing the total up to 50 RCTs included in the updated meta-analyses. Of these, 21 RCTs were deemed of high risk of bias. Curcumin supplementation significantly reduced BMI, BW, and WC with mean differences (MDs) of −0.24 kg/m2 (95% CI: −0.32, −0.16 kg/m2), −0.59 kg (95% CI: −0.81, −0.36 kg), and −1.32 cm (95% CI: −1.95, −0.69 cm), respectively. The bioavailability-enhanced form reduced BMI, BWs, and WC more, with MDs of −0.26 kg/m2 (95% CI: −0.38, −0.13 kg/m2), −0.80 kg (95% CI: −1.38, −0.23 kg) and −1.41 cm (95% CI: −2.24, −0.58 cm), respectively. Significant effects were also seen in subgroups of patients, especially in adults with obesity and diabetes. ConclusionsCurcumin supplementation significantly reduces anthropometric indices, and bioavailability-enhanced formulas are preferred. Augmenting curcumin supplement with lifestyle modification should be an option for weight reduction.This trial was registered at PROSPERO as CRD42022321112 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022321112).

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Therapeutic Neovascularization for Refractory Angina-Are We Any Closer?

Some considerations on target estimands for health technology assessment.

Some considerations on target estimands for health technology assessment.

Reconsideration of the Benefits of Pharmacological Interventions for the Attenuation of the Cognitive Adverse Effects of Electroconvulsive Therapy.

The cognitive adverse effects (AEs) of electroconvulsive therapy (ECT) limit the wider use of the treatment. These AEs can be attenuated by changing the way ECT is administered; however, such changes may reduce the response rate, the speed of response, or both. A recent systematic review and meta-analysis identified more than a dozen pharmacologic interventions in 26 randomized controlled trials (RCTs) that sought to reduce ECT-induced cognitive AEs. Because of large differences across RCTs, only a few outcomes for a few interventions could be pooled in meta-analysis, and most pooled analyses included only 2-3 RCTs. Important findings were that acetylcholinesterase inhibitors, ketamine, memantine, and liothyronine were associated with improved global cognitive functioning at 1-14 days post-ECT. Anti-inflammatory treatments and opioid receptor antagonists were not associated with improvement in general cognitive outcome at 1-14 days post-ECT. Meta-analysis was not possible for the remaining interventions, including piracetam, melatonin, pemoline, nortriptyline, herbal agents, drugs acting on the cortisol pathway, opioid receptor antagonists, l-tryptophan, vasopressin analogs, calcium channel blockers, and others; in individual RCTs, some of these interventions attenuated some cognitive measures as some time points after ECT. Regrettably, none of the RCTs examined clinically meaningful outcomes such as subjective cognitive impairment, impairments in daily life, and persistent autobiographical memory deficits. Future research should study such clinically meaningful outcomes (rather than laboratory tests), using pharmacologic interventions, perhaps in combination, for ECT procedures that are associated with higher cognitive AE burden. A risk is that whatever attenuates ECT-induced cognitive AEs may also attenuate ECT-related therapeutic benefits.

Risk of Candida Infection and Serious Infections in Patients with Moderate-to-Severe Psoriasis Receiving Biologics: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background Biological agents used to treat moderate-to-severe plaque psoriasis have been associated with Candida infection and other serious infections. It is, however, necessary to verify whether biologic agents increase the risk of Candida infection and serious infections and whether these risks vary among biologics. Methods PubMed, EMBASE, and Cochrane Library were searched for eligible randomized controlled trials (RCTs) from their inception to December 2021. Results from individual RCT were pooled using Peto's method with a fixed-effects model, and I2 was calculated to assess the heterogeneity. A Cochrane collaboration tool was used to examine bias risk, and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) were used to assess the quality of evidence. Results This study included 48 published articles with data from 52 RCTs involving 27297 participants. The anti-interleukin (IL)-17 agents (95% confidence interval (CI) = 1.54–3.45, P < 0.0001) and anti-IL-12/23 agents (95% CI = 1.69–3.83, P < 0.0001) were associated with an increased risk of Candida infection compared with placebos, but there was no difference in Candida infection risk between anti-IL-17 agents and tumor necrosis factor inhibitors (TNFi) (95% CI = 0.92–3.07, P=0.09). There was no evidence that the biological agents increased the risk of serious infections in adult psoriasis (95% CI = 0.93–2.06, P=0.11) or that the biologics differed in the risk of serious infections. Conclusions Our results indicated that anti-IL-17 agents, especially secukinumab, were associated with the increased risk of Candida infection. The clinically used biological agents did not increase the risk of serious infections.

Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis.

BackgroundDietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD.MethodsThe literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis.ResultsThe RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from Cornus mas L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients.ConclusionBased on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.

Probiotics for preventing acute upper respiratory tract infections.

Probiotics for preventing acute upper respiratory tract infections.