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Network meta-analysis of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults
ObjectiveTo compare the outcomes associated with the use of probiotics, prebiotics, and synbiotics for the treatment of chronic constipation in adults.MethodsWe searched eight electronic databases from database inception to July 11, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the treatment of chronic constipation. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of the evidence was assessed using the Confidence in Network Meta-Analysis framework. The analysis was conducted using R version 4.3.0.ResultsOut of the 37 RCTs, a total of 21 different types of interventions were reported, involving 3,903 patients. This NMA demonstrated that both prebiotics and synbiotics resulted in an increase in frequency of stool movements per week. Compared to placebo, lactulose (Mean difference [MD] = 3.39, 95% Confdence interval [CI] [1.13, 5.65], moderate certainty), mix2 (consisting of Lactulose and Bacillus coagulans) (MD = 3.63, 95% CI [1.37, 5.89], moderate certainty), mix6 (consisting of Lactulose and Bifidobacterium coagulans) (MD = 4.30, 95% CI [1.04, 7.54], low certainty), and mix7 (consisting of Lactulose, Bifidobacterium subtilis, and Enterococcus faecium) (MD = 4.58, 95% CI [1.35, 7.78], moderate certainty) exhibited a significant effect. Notably, mix7 demonstrated the highest probability of being the most effective intervention (94.8%). Furthermore, when compared to L. plantarum, four probiotics and two synbiotics showed significant advantages in the Patient Assessment of Constipation Symptoms (PAC-SYM) score. L. reuteri (MD = -13.74, 95% CI [-22.20, -4.66], very low certainty) exhibited a significant effect in improving the Patient Assessment of Constipation Quality of Life (PAC-QoL) score. In terms of safety, there were no statistically significant differences between the intervention and control groups in all adverse event analyses.ConclusionsModerate to very low evidence supports the use of lactulose and synbiotics to increase the number of weekly stool movements in patients, particularly highlighting the significant impact of synbiotics in increasing the number of weekly stool movements in patients with constipation. The use of L. paracasei showed improvements in PAC-SYM scores, while L. reuteri demonstrated enhancements in PAC-QoL scores.
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Comparison of effectiveness and safety of lasmiditan and CGRP-antagonists for the acute treatment of migraine in adults: systematic review and network meta-analysis of randomised trials
ObjectiveTo compare the outcomes associated with the use of lasmiditan, rimegepant, ubrogepant, and zavegepant for the acute management of migraine headaches.MethodsWe searched four electronic databases from database inception to August 31, 2023, to identify randomized controlled trials (RCTs) that report efficacy and safety for the acute treatment of migraine. The risk of bias in the included RCTs was evaluated according to the Cochrane tool, and the certainty of evidence using the CINeMA approach. We conducted frequentist network meta-analyses (NMA) to summarise the evidence. Data were analyzed using R-4.3.1.ResultsA total of 18 eligible studies including 10 different types of interventions with 22,429 migraine patients were included. NMA results showed that compared to ubrogepant (25 mg and 50 mg) and zavegepant, lasmiditan (100 mg and 200 mg) exhibits an elevated probability of achieving pain relief within a 2-hour interval. Similarly, relative to zavegepant, rimegepant (75 mg) and ubrogepant (50 mg and 100 mg) demonstrate an enhanced likelihood of sustaining pain relief over a 24-hour period. Furthermore, in contrast to ubrogepant (25 mg) and lasmiditan (50 mg), rimegepant (75 mg) presents a heightened probability of achieving freedom from photophobia within 2 h. Regarding safety, lasmiditan carries the highest risk of adverse events, which are associated with an increased incidence of adverse effects, including dizziness, somnolence, asthenia, paresthesia, and fatigue.ConclusionsIn this NMA, a spectrum of evidence ranging from very low to high levels underscores the favorable efficacy and tolerability of rimegepant 75 mg and ubrogepant 100 mg, positioning them as potential candidates for the acute management of migraine. Concurrently, lasmiditan (100 mg and 200 mg) exhibits notable efficacy, albeit accompanied by an increased susceptibility to adverse events. These findings should still be approached with caution, primarily due to the intrinsic limitations associated with indirect comparisons.
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Efficacy and safety of pharmacological intervention for smoking cessation in smokers with diseases: A systematic review and network meta-analysis
ObjectiveTo investigate the most effective and best-tolerated drugs for treating diseased smokers.MethodsEight databases were searched for randomized controlled trials (RCTs) involving different pharmacological interventions for smoking cessation in disease patients (January 2023). Network meta-analysis was performed using STATA 15.1 software. The Cochrane Risk of Bias Tool assessed the risk of bias, and confidence in evidence was assessed using CINeMA.ResultsA total of 60 RCTs involving 13,009 patients of 12 disease categories were included. All trials reported 13 interventions, resulting in 78 comparisons. Network meta-analysis showed that varenicline (OR = 2.30, 95% CI (1.77, 3.00)) and bupropion (OR = 1.65, 95% CI (1.29, 2.11)) showed favorable abstinence effects compared to placebo in the cardiovascular disease population. Nicotine replacement therapy (NRT) had better withdrawal advantages than placebo (OR = 11.18, 95% CI (2.25, 55.54)) in the chronic obstructive pulmonary disease (COPD) population. Some combination treatments showed better results than monotherapy, such as bupropion + NRT was superior to bupropion (OR = 8.45, 95% CI (1.84, 38.89)) and NRT (OR = 4.98, 95% CI (1.25, 19.78)) in mental illness population. The final surface under the cumulative ranking curve indicated that bupropion + NRT achieved the best smoking cessation effect. Overall confidence in the evidence was low. In a comparison of drugs, the results showed that bupropion + NRT had the best safety.ConclusionsMost interventions show the benefit of quitting smoking compared with placebo, including monotherapy and combination therapy. Moreover, varenicline or bupropion combined with NRT is superior to some monotherapies.
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Non-pharmacological interventions for smoking cessation: analysis of systematic reviews and meta-analyses
Background: Although non-pharmacological smoking cessation measures have been widely used among smokers, current research evidence on the effects of smoking cessation is inconsistent and of mixed quality. Moreover, there is a lack of comprehensive evidence synthesis. This study seeks to systematically identify, describe, and evaluate the available evidence for non-pharmacological interventions in smoking populations through evidence mapping (EM), and to search for best-practice smoking cessation programs. Methods: A comprehensive search for relevant studies published from the establishment of the library to January 8, 2023, was conducted in PubMed, Web of Science, Embase, the Cochrane Library, CNKI, CBM, Wan Fang, and VIP. Two authors independently assessed eligibility and extracted data. The PRISMA statement and AMSTAR 2 tool were used to evaluate the report quality and methodology quality of systematic reviews/meta-analyses (SRs/MAs), respectively. Bubble plots were utilized to display information, such as the study population, intervention type, evidence quality, and original study sample size. Results: A total of 145 SRs/MAs regarding non-pharmacological interventions for smoking cessation were investigated, with 20 types of interventions identified. The most commonly used interventions were cognitive behaviour education (n = 32, 22.07%), professional counselling (n = 20, 13.79%), and non-nicotine electronic cigarettes (e-cigarettes) (n = 13, 8.97%). Among them, counselling and behavioural support can improve smoking cessation rates, but the effect varies depending on the characteristics of the support provided. These findings are consistent with previous SRs/MAs. The general population (n = 108, 74.48%) was the main cohort included in the SRs/MAs. The total score of PRISMA for the quality of the reports ranged from 8 to 27, and 13 studies (8.97%) were rated as high confidence, and nine studies (6.21%) as moderate confidence, in the AMSTAR 2 confidence rating. Conclusions: The abstinence effect of cognitive behaviour education and money incentive intervention has advantages, and non-nicotine e-cigarettes appear to help some smokers transition to less harmful replacement tools. However, the methodological shortcomings of SRs/MAs should be considered. Therefore, to better guide future practice in the field of non-pharmacological smoking cessation, it is essential to improve the methodological quality of SRs and carry out high-quality randomized controlled trials (RCTs).
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The Effects of Selenium Supplementation in the Treatment of Autoimmune Thyroiditis: An Overview of Systematic Reviews
Objective: The available evidence on selenium supplementation in the treatment of autoimmune thyroiditis (AIT) was inconclusive. This research serves to assess the effects of selenium supplementation in the treatment of AIT. Methods: Online databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 10 June 2022. The AMSTAR-2 tool was used to assess the methodological quality of included studies. The information on the randomized controlled trials of the included studies was extracted and synthesized. The GRADE system was used to assess the certainty of evidence. Results: A total of 6 systematic reviews with 75 RCTs were included. Only one study was rated as high quality. The meta-analysis showed that in the levothyroxine (LT4)-treated population, thyroid peroxidase antibody (TPO-Ab) levels decreased significantly in the selenium group at 3 months (SMD = -0.53, 95% CI: [-0.89, -0.17], p < 0.05, very low certainty) and 6 months (SMD = -1.95, 95% CI: [-3.17, -0.74], p < 0.05, very low certainty) and that thyroglobulin antibody (Tg-Ab) levels were not decreased. In the non-LT4-treated population, TPO-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. Tg-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. The adverse effects reported in the selenium group were not significantly different from those in the control group, and the certainty of evidence was low. Conclusion: Although selenium supplementation might reduce TPO-Ab levels at 3 and 6 months and Tg-Ab levels at 3 and 6 months in the non-LT4-treated population, this was based on a low certainty of evidence.
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Efficacy and safety of antidepressants for smoking cessation: A systematic review and network meta-analysis
To evaluate the effectiveness, safety and tolerability of antidepressants in helping smokers quit tobacco dependence, five databases were searched for randomized controlled trials (RCTS ) on different antidepressant interventions involving smoking cessation in populations (September 2022). The STATA 15.1 software was used to perform network meta-analysis. The Cochrane bias risk tool was used to assess the risk of bias, and CINeMA was used to evaluate the evidence credibility for the effect of different interventions on smoking cessation. In all, 107 RCTs involving 42 744 patients were included. Seven studies were rated as having a low risk of bias. All trials reported 18 interventions and 153 pairwise comparisons were generated. The network meta-analysis showed that compared with placebo, varenicline + bupropion (OR = 3.53, 95% CI [2.34, 5.34]), selegiline + nicotine replacement therapy (NRT) (OR = 3.78, 95% CI [1.20, 11.92]), nortriptyline + NRT (OR = 2.33, 95% CI [1.21, 4.47), nortriptyline (OR = 1.58, 95% CI [1.11,2.26]), naltrexone + bupropion (OR = 3.84, 95% CI [1.39, 10.61]), bupropion + NRT (OR = 2.29, 95% CI [1.87, 2.81]) and bupropion (OR = 1.70, 95% CI [1.53, 1.89]) showed benefits with respect to smoking cessation. In addition, bupropion + NRT showed better effects than bupropion (OR = 1.35, 95% CI [1.12, 1.64]) and NRT (OR = 1.38, 95% CI [1.13, 1.69]) alone. The final cumulative ranking curve showed that varenicline + bupropion was the most likely to be the best intervention. There was moderate- to very-low-certainty evidence that most interventions showed benefits for smoking cessation compared with placebo, including monotherapy and combination therapies. Varenicline + bupropion had a higher probability of being the best intervention for smoking cessation.
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Effectiveness of Multicomponent Interventions in Office-Based Workers to Mitigate Occupational Sedentary Behavior: Systematic Review and Meta-Analysis
Background: Sedentary time in workplaces has been linked to increased risks of chronic occupational diseases, obesity, and overall mortality. Currently, there is a burgeoning research interest in the implementation of multicomponent interventions aimed at decreasing sedentary time among office workers, which encompass a comprehensive amalgamation of individual, organizational, and environmental strategies. Objective: This meta-analysis aims at evaluating the effectiveness of multicomponent interventions to mitigate occupational sedentary behavior at work compared with no intervention. Methods: PubMed, Web of Science, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from database inception until March 2023 to obtain randomized controlled trials (RCTs) assessing the efficacy of multicomponent interventions on occupational sedentary behavior among office-based workers. Two reviewers independently extracted the data and assessed the risk of bias by using the Cochrane Collaboration's risk of bias tool. The average intervention effect on sedentary time was calculated using Stata 15.1. Mean differences (MDs) with 95% CIs were used to calculate the continuous variables. Subgroup analyses were performed to determine whether sit-stand workstation, feedback, and prompt elements played an important role in multicomponent interventions. Further, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the certainty of evidence. Results: A total of 11 RCTs involving 1894 patients were included in the analysis. Five studies were rated as low risk of bias, 2 as unclear risk of bias, and 4 as high risk. The meta-analysis results showed that compared with no intervention, multicomponent interventions significantly reduced occupational sitting time (MD=-52.25 min/8-h workday, 95% CI -73.06 to -31.44; P<.001) and occupational prolonged sitting time (MD=-32.63 min/8-h workday, 95% CI -51.93 to -13.33; P=.001) and increased occupational standing time (MD=44.30 min/8-h workday, 95% CI 23.11-65.48; P<.001), whereas no significant differences were found in occupational stepping time (P=.06). The results of subgroup analysis showed that compared with multicomponent interventions without installment of sit-stand workstations, multicomponent interventions with sit-stand workstation installment showed better effects for reducing occupational sitting time (MD=-71.95 min/8-h workday, 95% CI -92.94 to -51.15), increasing occupational standing time (MD=66.56 min/8-h workday, 95% CI 43.45-89.67), and reducing occupational prolonged sitting time (MD=-47.05 min/8-h workday, 95% CI -73.66 to -20.43). The GRADE evidence summary showed that all 4 outcomes were rated as moderate certainty. Conclusions: Multicomponent interventions, particularly those incorporating sit-stand workstations for all participants, are effective at reducing workplace sedentary time. However, given their cost, further research is needed to understand the effectiveness of low-cost/no-cost multicomponent interventions.
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Preferences for training needs of village doctors in China: a systematic review
Background Village doctors, as gatekeepers of the health system for rural residents in China, are often confronted with adversity in providing the basic public healthcare services. Objective We sought to summarize the training contents, training method, training location, and training costs most preferred by village doctors in China and hope to provide evidence and support for the government to deliver better training in the future. Methods Eight databases were searched to include studies that reported on the training needs of village doctors in China. We undertook a systematic review and a narrative synthesis of data. Results A total of 38 cross-sectional studies including 35,545 participants were included. In China, village doctors have extensive training needs. “Clinical knowledge and skill” and “diagnosis and treatment of common disease” were the most preferred training content; “continuing medical education” was the most preferred delivery method; above county- and county-level hospitals were the most desirable training locations, and the training costs were expected to be low or even free. Conclusion Village doctors in various regions of China have similar preferences for training. Thus, future training should focus more on the training needs and preferences of village doctors.
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Adverse effects associated with acupuncture therapies: An evidence mapping from 535 systematic reviews
Background and ObjectiveConsidering that physicians and patients widely use acupuncture, it is necessary to explore its adverse effects during treatment. Herein, an evidence map was generated based on published studies to identify acupuncture-induced adverse effects and assess their severity, with the overarching goal of providing references for safe and effective implementation.MethodsA comprehensive literature search was performed in four public databases (PubMed, Embase, Web of science, and the Cochrane Library) to identify relevant studies published up to 15(th) June 2022. In addition, relevant studies were explored in the Epistemonikos database and reference lists were retrieved as a supplement. A MeaSurement Tool to Assess systematic Reviews, Version 2 (AMSTAR-2) quality assessment tool was applied to determine the methodological quality of included systematic reviews (SRs) and/or meta-analysis (MAs), whereas Microsoft Excel 2019 tool was used for data extraction and coding. Heatmaps were generated to display disease type, countries of origin for the first authors, and the sample sizes of original studies. Moreover, bubble charts comprehensively presented intervention categories, adverse reaction types, and evidence levels.ResultsA total of 535 SRs involving 33 adverse reactions were included. Among them, 22 studies were rated as high quality, 28 as moderate, 106 as low, and the rest were of critically-low quality. Numerous adverse effects were described in the studies, including syncope (86 SRs), organ or tissue injury (233 SRs), systemic reactions (113 SRs), infection (19 SRs), and other adverse events (373 SRs). Importantly, these adverse reactions were mainly associated with 19 acupuncture techniques, including electroacupuncture (n = 67), manual acupuncture (n = 47) and acupoint catgut embedding (n = 41). Furthermore, the 535 SRs described 23 diseases, among which symptoms, signs or clinical findings (83 SRs), mental, behavioral or neurodevelopmental disorders (67 SRs), and diseases of the nervous system (66 SRs) had the highest incidence.ConclusionThis evidence mapping explores the adverse effects of acupuncture, showing that there are multiple types of adverse reactions to acupuncture, with milder symptoms. The methodological assessment revealed that most of the included studies were of low- or critically low-quality. Therefore, there is a need for future randomized controlled trials and SRs to comprehensively analyze acupuncture-related adverse events in order to provide reliable and credible evidence.
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