Efficacy of mesenchymal stem cell transplantation on major adverse cardiovascular events and cardiac function indices in patients with chronic heart failure: a meta-analysis of randomized controlled trials.

BACKGROUND: The effects of mesenchymal stem cells (MSCs) on heart failure (HF) have been controversial. This study was conducted to investigate whether the transplantation of MSCs after HF could help improve clinical outcomes and myocardial performance indices. METHODS: Using a systematic approach, electronic databases were searched for randomized controlled trials (RCTs), which evaluated the transplantation of MSCs after HF. The outcomes owf interest included clinical outcomes and myocardial function indices. We also assessed the role of age, cause of heart failure, cell origin, cell number, type of donor (autologous/allogeneic), and route of cell delivery on these outcomes. Using the random-effects method, a relative risk (RR) or mean difference (MD) and their corresponding 95% confidence intervals (CI) were pooled. RESULTS: Seventeen RCTs including 1684 patients (927 and 757 patients in the intervention and control arms, respectively) were enrolled. The RR (95% CI) of mortality was 0.78 (0.62; 0.99, p = 0.04) in the MSC group compared to the controls. HF rehospitalization decreased in the MSC group (RR = 0.85 (0.71-1.01), p = 0.06), but this was only significant in those who received autologous MSCs (RR = 0.67 (0.49; 0.90), p = 0.008). LVEF was significantly increased among those who received MSC (MD = 3.38 (1.89; 4.87), p < 0.001). LVESV (MD = -9.14 (-13.25; -5.03), p < 0.001), LVEDV (MD = -8.34 -13.41; -3.27), p < 0.001), and scar size (standardized MD = -0.32 (-0.60; -0.05), p = 0.02) were significantly decreased. NYHA class (MD = -0.19 (-0.34; -0.06), p = 0.006), BNP level (standardized MD = -0.28 (-0.50; -0.06), p = 0.01), and MLHFQ (MD = -11.55 (-16.77; -6.33), p = 0.005) significantly decreased and 6-min walk test significantly improved (MD = 36.86 (11.22; 62.50), p = 0.001) in the MSC group. Trials were not affected by the participants' etiology of heart failure, while trials with the autologous source of cells, MSC doses lower than 100 million cells, and intracoronary injection performed significantly better in some of the outcomes. CONCLUSION: Transplantation of MSCs for ischemic or dilated heart failure patients may reduce all-cause mortality and improve clinical condition. Moreover, this treatment would improve left ventricular function indices and reduce scar size.

The Impact of Hypertension on Cognitive Decline and Alzheimer's Disease and Its Management: A Systematic Review.

Hypertension, a major risk factor for cardiovascular diseases, has also been linked to cognitive decline and Alzheimer's disease (AD). This systematic review synthesizes the current evidence on how managing hypertension may influence cognitive health, particularly among elderly populations and those with cognitive impairments. By analyzing data from randomized controlled trials (RCTs), clinical trials, and cross-sectional studies, we evaluated the efficacy of various interventions, including pharmacological treatments, lifestyle modifications, and multidomain approaches that address blood pressure (BP) variability and intensive versus standard blood pressure control. Our findings reveal that effective blood pressure management can mitigate cognitive decline and potentially alter the course of Alzheimer's disease. However, the results also highlight complexities, such as the risk of adverse effects from intensive blood pressure control on cognitive processing and hippocampal volume. This review underscores the need for tailored hypertension management strategies that balance cardiovascular health with cognitive outcomes, suggesting that stabilizing blood pressure variability could play a crucial role. Future research should focus on longitudinal studies to refine these management strategies and enhance treatment guidelines, improving overall outcomes for patients at risk of cognitive decline.

The effect of virtual reality on perioperative pain management in patients undergoing gastrointestinal procedures and surgeries: a systematic review of clinical trials.

BACKGROUND: Virtual reality (VR) is an advanced technology that transports users into a virtual world. It has been proven to be effective in pain management via distraction and alteration of pain perception. However, the impact of VR on treating perioperative pain is inconclusive. This systematic review aimed to evaluate the effect of VR on perioperative pain after a gastrointestinal (GI) procedure or surgery. METHODS: A systematic review of randomized controlled trials was conducted from inception to January 31, 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The updated Cochrane risk of bias (RoB 2) assessment tool was used to evaluate the risk of bias. RESULTS: Of 724 articles screened, 8 studies with 678 participants were included in the systematic review. Four studies evaluated the effect of VR on perioperative pain during GI procedure (eg, colonoscopy) focused on its use after GI surgeries (eg, abdominal surgeries). Some studies reported a reduction in pain scores after the procedure; however, the findings of pain difference in before or during vs after the procedure in the VR vs control groups were mixed. CONCLUSION: VR is a promising tool to control perioperative pain after a GI procedure or surgery. Differences in study protocols, pain assessment scales, and pain therapy used were limitations in performing a comprehensive meta-analysis. Further studies are needed to better evaluate the effects of VR on perioperative pain compared with standard of care.

Effectiveness of platelet-rich plasma in treating female hair loss: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hair loss profoundly affects women's physical appearance and psychological health. Platelet-rich plasma (PRP) therapy has gained attention as a potential treatment for female hair loss. This systematic review and meta-analysis aim to evaluate the efficacy and safety of PRP in treating different forms of female hair loss. METHODS: A comprehensive search was conducted across PubMed, EMBASE, Scopus, Cochrane Library, Web of Science, and ClinicalTrials.gov from January 2000 to May 2024. The focus was on randomized controlled trials investigating PRP treatment for various types of hair loss in women. The research protocol is registered with International Prospective Register of Systematic Reviews (CRD42024556190). The quality of the studies was evaluated using the Cochrane risk of bias tool (RoB 2). RESULTS: A total of 21 studies comprising 628 participants were included in the analysis. PRP treatment was found to significantly enhance hair density and thickness. Additionally, there was a significant reduction in the number of hairs pulled in the PRP group. Adverse effects were generally mild and transient, with no notable difference in pain or discomfort between the PRP and control groups (risk ratio: 1.01; 95% CI: 0.87-1.18). CONCLUSION: PRP therapy effectively enhances hair density and thickness in women with hair loss, with a favorable safety profile. However, the effects of PRP on hair density and thickness vary with dosage, injection duration, and ethnicity, indicating the need for tailored treatment protocols.

Effect of astragalus injection on left ventricular remodeling in HFmrEF: a systematic review and meta-analysis.

Objectives: The aim of this meta-analysis is to evaluate the effect of astragalus injection (AI) on left ventricular remodeling (LVR) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: The randomized controlled trials (RCTs) of AI in treating HFmrEF were retrieved from 8 major English and Chinese electronic databases, up until November 30, 2023. To evaluate the methodological quality of the included studies, the Cochrane bias risk tool and the Modified Jadad Scale were employed. Stata 17.0 software was utilized for statistical analysis, sensitivity analysis, and assessment of publication bias. Results: Ten RCTs with 995 patients (562 males and 433 females) were identified. Meta-analysis indicated that compared to conventional treatment (CT), AI significantly improved LVR, specifically increasing left ventricular ejection fraction (LVEF, MD = 4.56, 95% CI: 3.68-5.44, p < 0.00001), decreasing left ventricular end-diastolic volume (LVEDV, MD = -7.89, 95% CI: -11.13 to -4.64, p < 0.00001), left ventricular end-diastolic diameter (LVEDD, MD = -4.18, 95% CI: -5.79 to -2.56, p < 0.00001), left ventricular end-systolic volume (LVESV, MD = -8.11, 95% CI: -11.79 to -4.43, p < 0.00001), and left ventricular end-systolic diameter (LVESD, MD = -3.42, 95% CI: -4.90 to -1.93, p < 0.00001). AI also improved clinical efficacy (RR = 4.62, 95% CI: 3.11-6.88, p < 0.00001), reduced N-terminal pro-brain natriuretic peptide (NT-pro BNP, MD = -27.94, 95% CI: -43.3 to -12.36) level, without increasing the incidence of adverse reactions (RR = 1.60, 95% CI: 0.59-4.29, p = 0.35). Sensitivity analysis confirmed the reliability of the merged results, and Begg's and Egger's tests showed no significant publication bias. Conclusion: The systematic review and meta-analysis revealed that combining AI with CT improves LVR without increasing adverse events in HFmrEF patients. However, caution is needed in interpreting the results due to limited evidence. Future high-quality RCTs are needed to support these conclusions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO [CRD42022347248].

Effectiveness and safety of Chinese herbal footbaths as an adjuvant therapy for dysmenorrhea: a systematic review and meta-analysis.

Objectives: To evaluate the effectiveness and safety of Chinese herbal footbaths (CHF) as an adjunctive therapy in managing dysmenorrhea. Methods: Ten electronic databases were searched to identify eligible randomized clinical trials (RCTs) from inception until June 2023. Outcome measurements encompassed the total effective rate, visual analog scale (VAS) score of pain intensity, Cox menstrual symptom scale (CMSS) score, symptom score, Traditional Chinese Medicine (TCM) syndrome scale, and any reported adverse events. The methodological quality of the included studies was assessed with the Cochrane collaboration tool. Review Manager 5.3 software was employed for quantitative synthesis, and funnel plots were utilized to evaluate potential reporting bias. Results: Eighteen RCTs with 1,484 dysmenorrhea patients were included. The aggregated results suggested that the adjunctive CHF could significantly ameliorate dysmenorrhea, as evident from the improved total effective rate [risk ratio (RR) 1.18, 95% confidence interval (CI): 1.12 to 1.23, P < 0.00001], VAS (MD 0.88, 95% CI: 0.68 to 1.09, P < 0.00001), CMSS (MD 3.61, 95% CI: 2.73 to 4.49, P < 0.00001), symptom score (SMD 1.09, 95% CI: 0.64 to 1.53, P < 0.00001), and TCM syndrome scale (MD 3.76, 95% CI: 2.53 to 4.99, P < 0.0001). In addition, CHF presented fewer adverse events with a better long-term effect (RR 1.34, 95% CI: 1.11 to 1.63, P < 0.01) and diminished recurrence rate (RR 0.19, 95% CI: 0.09 to 0.39, P < 0.0001). Conclusion: Current evidence implies that CHF may be an effective and safe adjunctive therapy for patients with dysmenorrhea. However, the methodological quality of the studies included was undesirable, necessitating further verification with more well-designed and high-quality multicenter RCTs. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=188256, identifier registration number.

Mental Health Interventions in Middle Schools: A 10-Year Review of Research.

Schools can play an important role in addressing growing concerns about adolescent mental health. Mental health of high school students has predominantly been the focus in literature with less emphasis on younger adolescents. This review identified articles published in the last decade that described evaluations of middle school-based mental health interventions and randomized participants to an intervention or control condition. Fourteen interventions met the inclusion criteria. About two-thirds of interventions were based on mindfulness or cognitive behavioral therapy. Many trials utilized racially diverse, low-income samples. All interventions were delivered to groups, and three contained a parent component. Five trials increased rigor by using an active control condition. Almost two-thirds of the interventions were effective (p < .10) in reducing at least one depression, anxiety, affect, or internalizing symptom outcome compared to a control group. This article provides information about intervention characteristics, efficacy, theoretical framework, and acceptability/feasibility.

Comparing the efficacy and safety of microneedling and its combination with other treatments in patients with acne scars: a network meta-analysis of randomized controlled trials.

This study aimed to analyze the efficacy and safety of microneedling (MN), both alone and in combination with other treatments, to refine the approach for treating acne scars using MN. We systematically searched Pubmed, Cochrane Library, Embase, and Web of Science for randomized controlled trials examining MN or its combinations in patients with acne scars. All statistical analyses were performed using Stata 18 software. A total of 24 studies involving 1546 participants were included. The analysis revealed that MN combined with chemical peels (CP) exhibited the best results in terms of degree of improvement, patient satisfaction, and treatment efficacy compared to other treatments examined, including MN alone, MN with hyaluronic acid (HA), MN with botulinum toxin­A (TA), MN with platelet-rich plasma (PRP), PRP alone, CP, and laser therapy. The results for MN combined with additional treatments were obviously better than for MN alone. Side effects such as erythema, pain, and post-inflammatory hyperpigmentation showed no significant differences across all treatments assessed.

A meta-analysis of therapeutic trials of topical ruxolitinib cream for the treatment of vitiligo: therapeutic efficacy, safety, and implications for therapeutic practice.

Vitiligo, an autoimmune condition characterized by depigmented skin patches due to the loss of functional melanocytes, has been linked to dysregulation in the JAK-STAT signaling pathway, particularly in IFN-g signaling. The use of JAK inhibitors, such as ruxolitinib cream, a JAK1 and JAK2 inhibitor, presents a promising approach for vitiligo treatment. This study aims to systematically assess the effectiveness and safety of ruxolitinib cream in patients with vitiligo. We conducted a systematic review and meta-analysis following PRISMA guidelines to evaluate the efficacy and safety of ruxolitinib cream for the treatment of vitiligo. A comprehensive search of PubMed, Google Scholar, and Cochrane Library databases for randomized controlled trials (RCTs). Data selection, screening, extraction, and risk of bias assessment were meticulously performed. Statistical analysis was conducted using Review Manager Software, version 5.4, with significant heterogeneity addressed through appropriate methods. Our meta-analysis included 3 studies with 830 vitiligo patients. Significant improvements were observed in F-VASI, T-VASI, F-BSA, and T-BSA scores, with greater efficacy at 24 weeks compared to 12 weeks [MD -24.17, 95% CI (-31.78 to -16.56), P < 0.00001], [MD -14.12, 95% CI (-20.54 to -7.70); P < 0.0000], [MD -16.25, 95% CI (-22.20 to -10.31), P < 0.00001], [MD -9.19, 95% CI (-13.47 to -4.92); P < 0.00001]. Ruxolitinib showed increased risk ratios for F-VASI75, F-VASI90, and F-VASI50, indicating better outcomes with longer treatment durations [MD 2.9, 95% CI 1.88-4.49; P < 0.00001], [MD 4.66, 95% CI 2.09-10.39; P = 0.0002], [MD 2.53, 95% CI 1.84-3.46; P < 0.00001]. No significant differences were found in mild and moderate adverse events, while severe cases favored ruxolitinib. Placebo had a significant advantage in any adverse events, with no significant difference in drug-related adverse events. Serious adverse events did not significantly differ between groups. The findings strongly support the efficacy of ruxolitinib therapy in improving various parameters over time for treating vitiligo. However, thorough consideration of its safety profile, particularly concerning adverse events and potential side effects, is warranted. Further studies with larger sample sizes are needed to confirm these conclusions.

Efficacy and safety of extracorporeal shock wave therapy for upper limb tendonitis: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study synthesized the highest level of evidence to analyse the effectiveness and safety of using extracorporeal shock wave therapy (ESWT) to treat upper limb tendonitis, which was unknown. Design: We conducted a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, Medline, and the Cochrane Library. Methods: Two researchers performed the screening, data extraction, literature quality assessment, and heterogeneity analysis of the searched RCTs. Results: The main types of morbidity included rotator cuff tendonitis, lateral epicondylitis, finger tendonitis, and long bicipital tendonitis. The results of the meta-analysis showed that ESWT was effective in relieving pain in all four types of tendonitis. In addition, ESWT was more effective in relieving pain in patients with upper limb tendonitis than placebo at the 3- and 6-month follow-ups, especially with radial ESWT (RESWT). Data analysis of the forest plot showed that the experimental group with ESWT as an intervention had a significant improvement in function in patients with rotator cuff tendonitis at the 3-month follow-up. However, subgroup analysis showed that low-energy ESWT was effective in improving function in patients with calcified and non-calcified rotator cuff tendonitis, whereas it was not effective in relieving pain. Conclusion: ESWT can effectively improve the functional activity in patients with rotator cuff tendonitis and may produce positive analgesic effects in patients with upper limb tendonitis. The incidence of adverse effects is low. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403594, identifier: PROSPERO, CRD42023403594.

Probiotics for the Prevention of Vaginal Infections: A Systematic Review.

Probiotics, particularly Lactobacillus strains, have been proposed as an alternative or adjunct therapy for bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC) due to their potential to restore a healthy vaginal microbiota. This systematic review evaluated 11 randomized controlled trials with a Jadad score greater than three, indicating high-quality studies based on criteria such as randomization, blinding, and dropout rates. The review demonstrated significant improvements in clinical outcomes and vaginal microbiota restoration. However, variability in results highlights the need for further research.

Improving the clinical meaning of surrogate endpoints: An empirical assessment of clinical progression in phase III oncology trials.

Disease progression in clinical trials is commonly defined by radiologic measures. However, clinical progression may be more meaningful to patients, may occur even when radiologic criteria for progression are not met, and often requires a change in therapy in clinical practice. The objective of this study was to determine the utilization of clinical progression criteria within progression-based trial endpoints among phase III trials testing systemic therapies for metastatic solid tumors. The primary manuscripts and protocols of phase III trials were reviewed for whether clinical events, such as refractory pain, tumor bleeding, or neurologic compromise, could constitute a progression event. Univariable logistic regression computed odds ratios (OR) and 95% CI for associations between trial-level covariates and clinical progression. A total of 216 trials enrolling 148,190 patients were included, with publication dates from 2006 through 2020. A major change in clinical status was included in the progression criteria of 13% of trials (n = 27), most commonly as a secondary endpoint (n = 22). Only 59% of trials (n = 16) reported distinct clinical progression outcomes that constituted the composite surrogate endpoint. Compared with other disease sites, genitourinary trials were more likely to include clinical progression definitions (16/33 [48%] vs. 11/183 [6%]; OR, 14.72; 95% CI, 5.99 to 37.84; p < .0001). While major tumor-related clinical events were seldom considered as disease progression events, increased attention to clinical progression may improve the meaningfulness and clinical applicability of surrogate endpoints for patients with metastatic solid tumors.

Nurse-led digital health program for home blood pressure monitoring in stroke patients: protocol for a pooled analysis of randomized controlled trials.

Background: Hypertension is a major risk factor for stroke recurrence in stroke patients. Home blood pressure monitoring, facilitated by digital health technologies and led by nurses, may improve blood pressure control in this high-risk population. However, the evidence is not yet conclusive. This study protocol outlines a pooled analysis of the current literatures to evaluate the effectiveness of nurse-led digital health programs for home blood pressure monitoring in stroke patients. Methods and analysis: We will conduct a comprehensive search of some major electronic databases (e.g., PubMed, EMBASE, Cochrane Library, and CINAHL) and trial registries for randomized controlled trials evaluating nurse-led digital health programs for home blood pressure monitoring in stroke patients. Two reviewers will independently screen titles and abstracts, review full-text articles, extract data, and assess risk of bias using the revised Cochrane risk-of-bias tool for randomized trials (RoB 2.0). The primary outcome measures will be changes in both systolic and diastolic blood pressure from baseline to the end of the intervention period. Secondary outcomes include adherence to the program, patient satisfaction, and stroke recurrence. Data will be pooled and analyzed using meta-analysis techniques, if appropriate. Discussion: This study will provide comprehensive evidence on the effectiveness of nurse-led digital health programs for home blood pressure monitoring in stroke patients. The findings could have substantial implications for clinical practice and health policy, potentially informing the development of guidelines and policies related to hypertension management and stroke prevention. Conclusion: By pooling the results of randomized controlled trials, this study will offer a robust evidence base to inform clinical practice and health policy in the context of stroke patients. Despite potential limitations such as heterogeneity among studies and risk of publication bias, the rigorous methodology and comprehensive approach to data synthesis will ensure the reliability and validity of the findings. The results will be disseminated through a peer-reviewed publication and potentially at relevant conferences. Registration DOI: https://doi.org/10.17605/OSF.IO/59XQA.

Influence of myo-inositol on metabolic status for gestational diabetes: a meta-analysis of randomized controlled trials.

INTRODUCTION: The efficacy of myo-inositol supplementation to treat gestational diabetes remains controversial, and this meta-analysis aims to study the efficacy of myo-inositol supplementation on metabolic status for gestational diabetes. METHODS: Several databases including PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systemically searched from inception to October 2021, and we included the randomized controlled trials (RCTs) assessing the effect of myo-inositol supplementation on the outcomes of women with gestational diabetes. Gestational diabetes was diagnosed if at least one threshold of glucose concentration was exceeded and the three thresholds included 92, 180, and 153 mg/dl for 0, 1 and 2 h, respectively, after a 75-g, 2-h glucose tolerance test. RESULTS: Four RCTs and 317 patients were included in this meta-analysis. Compared with routine treatment in pregnant women with gestational diabetes, myo-inositol supplementation could lead to remarkably decreased treatment requirement with insulin (odd ratio [OR] = 0.24; 95% confidence interval [CI] = 0.11-0.52; p = .0003) and homeostasis model assessment of insulin resistance (HOMA-IR, standard mean difference [SMD]= -1.18; 95% CI= -1.50 to -0.87; p < .00001), but demonstrated no obvious impact on birth weight (SMD= -0.11; 95% CI= -0.83 to 0.61 g; p = .76), cesarean section (OR = 0.82; 95% CI = 0.46-1.47; p = .51) or the need of NICU (OR = 0.88; 95% CI = 0.03-26.57; p = .94). CONCLUSIONS: Myo-inositol supplementation is effective to decrease the need of insulin treatment and HOMA-IR for gestational diabetes.

Blood pressure management after endovascular thrombectomy: Insights of recent randomized controlled trials.

BACKGROUND: The ideal blood pressure (BP) target in patients who undergo endovascular thrombectomy (EVT) with successful reperfusion is uncertain. Observational studies show that elevated BP during this period is associated with a higher risk of intracranial hemorrhage (ICH) and worse clinical outcomes. Several randomized controlled trials (RCTs) have explored whether intensive BP lowering improves clinical outcomes in these patients. AIMS: This review aims to summarize the recent RCTs that compare intensive and conventional BP management strategies following EVT and discuss the innovative directions to improve. RESULT: The recently published RCTs failed to demonstrate the benefit of intensive BP control on the functional outcome and decreasing the risk of ICH. The complex mechanism in cerebral blood flow regulation and the inappropriate BP range chosen in RCTs may be the reasons behind the inconsistent results between observational studies and RCTs. Individualized BP management, reducing BP variability, and multi-stage BP management should be paid more attention in future exploration. CONCLUSION: Intensive BP target did not improve clinical outcomes after successful EVT as compared with a conventional BP target. Further research is required to identify the optimal BP management strategy after reperfusion.

Clinical trials with mechanism evaluation of intervention(s): mind the power and sample size calculation.

BACKGROUND: Mediation analysis, often completed as secondary analysis to estimating the main treatment effect, investigates situations where an exposure may affect an outcome both directly and indirectly through intervening mediator variables. Although there has been much research on power in mediation analyses, most of this has focused on the power to detect indirect effects. Little consideration has been given to the extent to which the strength of the mediation pathways, i.e., the intervention-mediator path and the mediator-outcome path respectively, may affect the power to detect the total effect, which would correspond to the intention-to-treat effect in a randomized trial. METHODS: We conduct a simulation study to evaluate the relation between the mediation pathways and the power of testing the total treatment effect, i.e., the intention-to-treat effect. Consider a sample size that is computed based on the usual formula for testing the total effect in a two-arm trial. We generate data for a continuous mediator and a normal outcome using the conventional mediation models. We estimate the total effect using simple linear regression and evaluate the power of a two-sided test. We explore multiple data generating scenarios by varying the magnitude of the mediation paths whilst keeping the total effect constant. RESULTS: Simulations show the estimated total effect is unbiased across the considered scenarios as expected, but the mean of its standard error increases with the magnitude of the mediator-outcome path and the variability in the residual error of the mediator, respectively. Consequently, this affects the power of testing the total effect, which is always lower than planned when the mediator-outcome path is non-trivial and a naive sample size was employed. Analytical explanation confirms that the intervention-mediator path does not affect the power of testing the total effect but the mediator-outcome path. The usual effect size consideration can be adjusted to account for the magnitude of the mediator-outcome path and its residual error. CONCLUSIONS: The sample size calculation for studies with efficacy and mechanism evaluation should account for the mediator-outcome association or risk the power to detect the total effect/intention-to-treat effect being lower than planned.

Comparison of different doses of Tripterygium glycosides treating in IgA vasculitis nephritis: A Bayesian network meta-analysis.

Background: Tripterygium glycosides (TG) is extracted from the roots of Tripterygium wilfordii Hook F (Lei gong teng, a traditional Chinese medicine). It is widely used in China to treat immunoglobulin A vasculitis nephritis (IgAVN), which is a common secondary glomerular disease. As there are no guidelines for the rational application of TG, we performed this study to evaluate the efficacy and safety of different doses of TG and to determine the optimal treatment for IgAVN. Methods: Ten databases were searched from their inception to April 2023 for randomised controlled trials (RCTs) using TG, TG combined with glucocorticoids (GC), or TG combined with traditional Chinese medicine (TCM) to treat IgAVN. A network meta-analysis was performed following the protocol (CRD42023401645). Results: Forty-four eligible RCTs involving 3402 patients were included. For effective rate, TG 1.5 mg/kg/d (TG1.5) + TCM was ranked as the best intervention, followed by TG 1.0 mg/kg/d (TG1.0) + TCM, TG1.5, TG1.0+GC, TG1.0, TCM, GC, and routine treatment (RT). TG1.0+TCM ranked best in reducing recurrence, followed by TG1.0+GC, GC, TG1.5, and RT. Compared with TG1.0, TG1.0+TCM and TG1.5+TCM effectively reduced liver injury events. Compared with TG1.5, TG1.5+TCM and TG1.0+TCM effectively reduced leukopenia events. No significant differences in the reduction of gastrointestinal events were observed between the interventions. Subgroup analyses explored the effects of the participants' age. The intervention rankings of the outcomes generally remained consistent. Only a small difference was observed in gastrointestinal events. TCM was the best treatment for reducing gastrointestinal events in paediatric patients. Conclusions: The results showed a positive correlation between dose and efficacy, whereas no relationship was found between dose and adverse events. TCM can boost the efficacy and reduce adverse events when combined with TG. In conclusion, we consider TG1.5+TCM as the best treatment for IgAVN. However, further research is required to confirm these findings.

Representation of Low- and Middle-Income Countries in CKD Drug Trials: A Systematic Review.

RATIONALE & OBJECTIVE: Almost 80% of individuals with chronic kidney disease (CKD) reside in low- and middle-income countries (LMICs) and are potentially under-represented in randomized controlled clinical trials (RCTs). We assessed the global distribution of RCTs comparing pharmacological treatments for CKD over the past two decades, as well as the magnitude and evolution of participation by LMICs. STUDY DESIGN: Systematic review. SETTING & STUDY POPULATIONS: RCTs evaluating pharmacological interventions in adults with CKD. SELECTION CRITERIA FOR STUDIES: RCTs published between 2003-2023 and indexed in MEDLINE. DATA EXTRACTION: Each trial was reviewed and extracted independently by two investigators. Disagreements were settled by consensus or a third reviewer. ANALYTICAL APPROACH: RCT participation of World Bank-defined income groups and geographic regions were described and the representation indices (RI) according to RCT participants and estimated CKD prevalences were calculated. RCTs were also categorized as global, regional, or national in scope. RESULTS: Among 7,760 identified studies, we included 1,366 RCTs conducted in 84 countries with 301,158 participants. National, regional, and global RCTs represented 85.4%, 3.5%, and 11.1% of studies, respectively. LMICs were included in 34.7% of RCTs. No RCTs included participants from low-income countries, and lower-middle-income countries participated in 13.2%. Of participants from RCTs with available information, 25.4% (n=64,843/255,237) were from LMICs. According to the RI, six LMICs were over-represented (>1.25), seven adequately represented (0.75-1.25), and 26 under-represented (<0.75). Most (80.2%) global CKD RCTs included LMICs; however, LMIC participants constituted only 32.9% of the global trial population. We observed a positive trend in LMIC inclusion over time, rising from 22.9% (n=71/310) in 2003-2007 to 45.5% (n=140/308) in 2018-2023. LIMITATIONS: The use of an income-group dichotomy, exclusion of non-randomized studies of intervention, and studies identified in one database. CONCLUSIONS: Despite an increase in participation over the past two decades, individuals with CKD from LMICs remain significantly under-represented in RCTs. These findings suggest that increased efforts are warranted to increase LMIC representation in pharmacological CKD RCTs.