Efficacy and safety of metformin for melasma treatment: a systematic review and meta-analysis

Objective: Metformin has recently been demonstrated to have an anti-melanogenic activity. Nevertheless, clinical evidence of the effectiveness of metformin in melasma is lacking. The objective of this study was to assess the efficacy and safety of metformin in the treatment of melasma.Methods: MEDLINE, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, CINAHL, and grey literature databases were searched to 4 October 2022 and updated on 26 February 2023. Randomized controlled trials (RCTs), quasi-RCTs, observational studies, case series, and case reports investigating the efficacy and safety of metformin for melasma were included. The Melasma Area Severity Index (MASI) scores that changed from baseline were pooled using fixed-effects model and expressed as standardized mean differences (SMDs) and 95% confidence intervals (CIs).Results: Three RCTs including 140 patients with melasma were included. The results demonstrated that after 8 weeks, 15% topical metformin significantly reduced the Melasma Area Severity Index (MASI) score compared to placebo (1 trial; n = 60; MD, −0.56; 95% CI, −1.07 to −0.04; p = 0.034). Furthermore, when compared to triple combination cream (TCC), 30% topical metformin demonstrated similar efficacy in reducing the MASI score after 8 weeks (2 trials; n = 80; MD, 0.19, 95% CI, −0.25 to 0.63; p = 0.390). Patients using 30% topical metformin had fewer adverse events compared to TCC users, although no statistical difference was found.Conclusion: Topical metformin was as effective as triple combination cream (TCC) in decreasing changes in the MASI score in patients with melasma, with minimum adverse events. Further studies with larger sample sizes, longer follow-up times, and well-designed trials are required.Systematic Review Registration: Identifier PROSPERO (CRD42022351966)

Clinical Outcomes, Patient-Reported Outcomes, and Economic Burden for Thai People Living with Chronic Urticaria (CORE-CU) in routine practice: A study protocol for a monocentric prospective longitudinal study.

BackgroundFew prospective longitudinal studies have been conducted in Thailand to account for the long-term response to chronic urticaria (CU) treatment, clinical outcomes, and patient-reported outcomes (PROs) among people living with CU based on routine practice. As such, a prospective longitudinal study will be conducted to better understand the long-term responses to treatment options and the burden of disease in Thai CU patients.Methods and designThis study is a routine clinical practice registry-based, monocentric, prospective, observational longitudinal study in the northern region of Thailand. Adult patients in an outpatient clinic diagnosed with CU, including both chronic spontaneous urticaria and chronic inducible urticaria will be recruited for this study. The cohort will be collected and registered using the joint routine clinical practice data based on multiple datasets including claims outpatient and inpatient data, routine laboratory results, medication utilization, health care costs, clinical characteristics, long-term urticaria care and monitoring, and PRO measures. The point prevalence of adverse health outcomes will be estimated and reported corresponding to 95% confidence intervals (95% CIs). The overall trend analysis will be analyzed to explore the effect of over time across the cohort time frame.ConclusionThis prospective longitudinal study will report the clinical outcomes, PROs, and economic burden among Thai people living with CU based on routine clinical practice. Findings will provide comprehensive evidence and could facilitate best practices for CU care management for health care professionals, researchers, policymakers, and public society.Trial registrationThai Clinical Trials Registry (TCTR, thaiclinicaltrials.org) registration TCTR20210706005. Registered on July 6, 2021

Evidence Gaps in Clinical Trials of Pharmacologic Treatment for H1-Antihistamine-Refractory Chronic Spontaneous Urticaria: A Systematic Review and Future Perspectives

No data addressing issues concerning disparities in participant and trial characteristics and trial outcome reporting have been established in clinical trials for H1-antihistamine-refractory chronic spontaneous urticaria (CSU). To better harmonize and compare the different treatment interventions, we systematically evaluated the overall landscape of pharmacological treatments for H1-antihistamine-refractory CSU clinical trials published between 2000 and 2021. This systematic review included 23 randomized clinical trials involving 2480 participants from 22 countries. We found significant increases in the number of globally published and newly tested drugs, especially biologic drugs. Regarding relatively small trials, we found that people living with H1-antihistamine-refractory CSU who were identified as members of minority groups (non-white population), populations of regions other than North America/Europe, and populations of low- to lower/upper-middle-income countries are underrepresented. Most trials were designed to evaluate treatment efficacy and safety profiles; however, less than half of the included trials reported the patient’s perspective in terms of patient-reported outcomes. Disparities in outcome reporting, including clinimetric tools for assessing treatment response and outcome sets, were observed. To close the evidence gap in H1-antihistamine-refractory CSU trials, strategies for improving trial and participant enrollment and standardizing core outcome sets for trial reporting are needed

Comparative effectiveness of glucagon-like peptide-1 receptor agonists on body composition and anthropometric indices: A protocol for a systematic review and network meta-analysis of randomized controlled trials.

BackgroundTo date, no studies have addressed the comparative efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) therapy on body composition and anthropometric indices among adult overweight or obese patients with or without type 2 diabetes. To provide evidence-based recommendations, we will conduct a traditional pairwise and network meta-analysis of all available randomized clinical trials that evaluated the effects of GLP1-RAs interventions for adult overweight or obese patients with or without type 2 diabetes.Methods and designElectronic databases, including Medline, Embase, PubMed, Cochrane Library (CENTRAL), Scopus, and CINAHL, will be searched from inception without language restriction. Grey literature will be searched, including Google Scholar, ongoing clinical trial registries, and preprint reports. Reference lists of included trials, relevant major endocrinology scientific meetings, and manual hand searches from key general medicine and obesity and endocrinology journals will also be browsed. Two authors will screen, select, extract, appraise the risk of bias, and rate the evidence findings. Any disagreement will be resolved through team discussion. Based on a random-effects model, we will employ a two-step approach of traditional pairwise meta-analysis and network meta-analysis for quantitative synthesis. The pooled effect estimates using a frequentist approach with 95% confidence intervals for continuous endpoints will be expressed as the standardized mean difference, whereas odds ratios will be used for categorical endpoints. The quality of included trials will be evaluated using the Cochrane risk-of-bias version 2 assessment tool. Certainty of evidence for each outcome will be assessed using the modified confidence in network meta-analysis approach and the Grading of Recommended Assessment, Development, and Evaluation approach. The magnitude of the effect size, prediction intervals, surface under the cumulative ranking curve values, and certainty of evidence will be incorporated to draw evidence-based conclusions.ConclusionThis systematic review and network meta-analysis will summarize the comparative efficacy of GLP1-RAs therapy on body composition and anthropometric indices. Evidence identified from this review will promote the rational use of interventions for adult overweight or obese patients with or without type 2 diabetes and will serve as an important step for evidence-based practice within this area.Trial registrationPROSPERO registration number: CRD42023458228

Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy–Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients

Fear of COVID-19 and Perceived Stress: The Mediating Roles of Neuroticism and Perceived Social Support

Background: Fear of COVID-19 leads to stress and may result in various kinds of mental health problems. Many factors are associated with an individual’s perception of stress, including neuroticism and perceived social support. This study aimed to examine the role of neuroticism and perceived social support as mediators of fear of COVID-19 on perceived stress. Methods: Data from 3299 participants aged ≥18 years from the HOME-COVID-19 survey in 2020 were used for analysis. Measurements used included the Fear of COVID-19 and Impact on Quality of Life Scale, the Perceived Stress Scale-10, the Neuroticism inventory and the Multidimensional Scale of Perceived Social Support-12. A parallel mediation model within a structural equation modeling framework with 5000 bootstrapping sampling was used to test the mediating effect. Results: Fear of COVID-19 had a direct effect on perceived stress (B  =  0.100, 95% CI = 0.080–0.121, p < 0.001), whereas neuroticism, but not perceived social support, partially mediated the relationship between fear of COVID-19 and perceived stress (B = 0.018, 95% CI = 0.000–0.036). Among all types of social support, only perceived support from friends was a significant mediator (B = 0.016, 95% CI = 0.006–0.025). Conclusions: Neuroticism and perceived support from friends are critical factors in the relationship between fear of COVID-19 and perceived stress

Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy&ndash;Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients

Benefits and Harms of Treatment and Preventive Interventions for Hereditary Angioedema: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Background: Hereditary angioedema (HAE) is a rare genetic disease that can lead to potentially life-threatening airway attacks. Although novel therapies for HAE treatment have become available over the past decades, a comparison of all available treatments has not yet been conducted. As such, we will perform a systematic review and network meta-analysis to identify the best evidence-based treatments for the management of acute attacks and prophylaxis of HAE. Methods: This study will include both parallel and crossover randomized controlled trials that have investigated prevention or treatment strategies for HAE attacks. We will search electronic databases, including Medline, Embase, PubMed, Cochrane Library, Scopus, and CINAHL, from inception with no language restrictions. Potential trials will be supplemented through a gray literature search. The process of study screening, selection, data extraction, risk-of-bias assessment, certainty assessment and classification of treatments will be performed independently by a pair of reviewers. Any discrepancy will be addressed through team discussion. A two-step approach of pairwise and network meta-analysis will be performed. The summarized effect estimates of direct and indirect treatment comparisons will be pooled using DerSimonion–Laird random-effects models. The incoherence assumption, in terms of the consistency of direct and indirect effects, will be assessed. An evidence-based synthesis will be performed, based on the magnitudes of effect size, evidence certainty, and ranking of treatment effects, with respect to treatment benefits and harms. Discussion: This systematic review and network meta-analysis will summarize evidence-based conclusions with respect to the ratio of benefits and harms arising from interventions for the treatment of acute attacks and prophylaxis of HAE. Evidence from this network estimate could promote the rational use of interventions among people living with HAE in clinical practice settings. PROSPERO registration number: CRD42021251367