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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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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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The relationship of publication language, study population, risk of bias, and treatment effects in acupuncture related systematic reviews: a meta-epidemiologic study
Background There are debates in acupuncture related systematic reviews and meta-analyses on whether searching Chinese databases to get more Chinese-language studies may increase the risk of bias and overestimate the effect size, and whether the treatment effects of acupuncture differ between Chinese and non-Chinese populations.Methods In this meta-epidemiological study, we searched the Cochrane library from its inception until December 2021, and identified systematic reviews and meta-analyses with acupuncture as one of the interventions. Paired reviewers independently screened the reviews and extracted the information. We repeated the meta-analysis of the selected outcomes to separately pool the results of Chinese- and non-Chinese-language acupuncture studies and presented the pooled estimates as odds ratios (OR) with 95% confidence interval (CI). We calculated the Ratio of ORs (ROR) by dividing the OR of the Chinese-language trials by the OR of the non-Chinese-language trials, and the ROR by dividing the OR of trials addressing Chinese population by the OR of trials addressing non-Chinese population. We explored whether the impact of a high risk of bias on the effect size differed between studies published in Chinese- and in non-Chinese-language, and whether the treatment effects of acupuncture differed between Chinese and non-Chinese population.Results We identified 84 Cochrane acupuncture reviews involving 33 Cochrane groups, of which 31 reviews (37%) searched Chinese databases. Searching versus not searching Chinese databases significantly increased the contribution of Chinese-language literature both to the total number of included trials (54% vs. 15%) and the sample size (40% vs. 15%). When compared with non-Chinese-language trials, Chinese-language trials were associated with a larger effect size (pooled ROR 0.51, 95% CI 0.29 to 0.91). We also observed a higher risk of bias in Chinese-language trials in blinding of participants and personnel (97% vs. 51%) and blinding of outcome assessment (93% vs. 47%). The higher risk of bias was associated with a larger effect estimate in both Chinese-language (allocation concealment: high/unclear risk vs. low risk, ROR 0.43, 95% CI 0.21 to 0.87) and non-Chinese-language studies (blinding of participants and personnel: high/unclear risk vs. low risk, ROR 0.41, 95% CI 0.23 to 0.74). However, we found no evidence that the higher risk of bias would increase the effect size of acupuncture in Chinese-language studies more often than in non-Chinese-language studies (the confidence intervals of all ROR in the high-risk group included 1, Table 3). We further found acupuncture appeared to be more effective in Chinese than in non-Chinese population (Table 4).Conclusions The findings of this study suggest the higher risk of bias may lead to an overestimation of the treatment effects of acupuncture but would not increase the treatment effects in Chinese-language studies more often than in other language studies. The difference in treatment effects of acupuncture was probably associated with differences in population characteristics.
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Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of pulmonary embolism
Background Pulmonary embolism (PE) is a potentially life-threatening condition in which a clot can migrate from the deep veins, most commonly in the leg, to the lungs. Conventional treatment of PE used unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and vitamin K antagonists (VKAs). Recently, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors. DOACs have characteristics that may be favourable to conventional treatment, including oral administration, a predictable effect, no need for frequent monitoring or re-dosing, and few known drug interactions. This review reports the efficacy and safety of these drugs in the long-term treatment of PE (minimum duration of three months). This is an update of a Cochrane Review first published in 2015. Objectives To assess the efficacy and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of PE. Search methods The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases, the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials registers to 2 March 2022. We checked the reference lists of relevant articles for additional studies. Selection criteria We included randomised controlled trials (RCTs) in which people with a PE confirmed by standard imaging techniques were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with a conventional anticoagulant or compared with each other for the long-term treatment of PE (minimum duration three months). Data collection and analysis We used standard Cochrane methods. Our primary outcomes were recurrent PE, recurrent venous thromboembolism (VTE), and deep vein thrombosis (DVT). Secondary outcomes were all-cause mortality, major bleeding, and health-related quality of life. We used GRADE to assess the certainty of evidence for each outcome. Main results We identified five additional RCTs with 1484 participants for this update. Together with the previously included trials, we have included ten RCTs with a total of 13,073 participants. Two studies investigated an oral DTI (dabigatran) and eight studies investigated oral factor Xa inhibitors (three rivaroxaban, three apixaban, and two edoxaban). The studies were of good methodological quality overall. Meta-analysis showed no clear difference in the efficacy and safety of oral DTI compared with conventional anticoagulation in preventing recurrent PE (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.50 to 2.04; 2 studies, 1602 participants; moderate-certainty evidence), recurrent VTE (OR 0.93, 95% CI 0.52 to 1.66; 2 studies, 1602 participants; moderate-certainty evidence), DVT (OR 0.79, 95% CI 0.29 to 2.13; 2 studies, 1602 participants; moderate-certainty evidence), and major bleeding (OR 0.50, 95% CI 0.15 to 1.68; 2 studies, 1527 participants; moderate-certainty evidence). We downgraded the certainty of evidence by one level for imprecision due to the low number of events. There was also no clear difference between the oral factor Xa inhibitors and conventional anticoagulation in the prevention of recurrent PE (OR 0.92, 95% CI 0.66 to 1.29; 3 studies, 8186 participants; moderate-certainty evidence), recurrent VTE (OR 0.83, 95% CI 0.66 to 1.03; 8 studies, 11,416 participants; moderate-certainty evidence), DVT (OR 0.77, 95% CI 0.48 to 1.25; 2 studies, 8151 participants; moderate-certainty evidence), all-cause mortality (OR 1.16, 95% CI 0.79 to 1.70; 1 study, 4817 participants; moderate-certainty evidence) and major bleeding (OR 0.71, 95% CI 0.36 to 1.41; 8 studies, 11,447 participants; low-certainty evidence); the heterogeneity for major bleeding was significant (I-2 = 79%). We downgraded the certainty of the evidence to moderate and low because of imprecision due to the low number of events and inconsistency due to clinical heterogeneity. None of the included studies measured health-related quality of life. Authors' conclusions Available evidence shows there is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent PE, recurrent VTE, DVT, all-cause mortality, and major bleeding. The certainty of evidence was moderate or low. Future large clinical trials are required to identify if individual drugs differ in effectiveness and bleeding risk, and to explore effect differences in subgroups, including people with cancer and obesity.
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Long-term exposure to particulate matter on cardiovascular and respiratory diseases in low- and middle-income countries: A systematic review and meta-analysis
BackgroundLong-term exposure to particulate matter (PM) has essential and profound effects on human health, but most current studies focus on high-income countries. Evidence of the correlations between PM and health effects in low- and middle-income countries (LMICs), especially the risk factor PM1 (particles < 1 mu m in size), remains unclear. ObjectiveTo explore the effects of long-term exposure to particulate matter on the morbidity and mortality of cardiovascular and respiratory diseases in LMICs. MethodsA systematic search was conducted in the PubMed, Web of Science, and Embase databases from inception to May 1, 2022. Cohort studies and case-control studies that examine the effects of PM1, PM2.5, and PM10 on the morbidity and mortality of cardiovascular and respiratory diseases in LMICs were included. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Outcomes were analyzed via a random effects model and are reported as the relative risk (RR) with 95% CI. ResultsOf the 1,978 studies that were identified, 38 met all the eligibility criteria. The studies indicated that long-term exposure to PM2.5, PM10, and PM1 was associated with cardiovascular and respiratory diseases: (1) Long-term exposure to PM2.5 was associated with an increased risk of cardiovascular morbidity (RR per 1.11 mu g/m(3), 95% CI: 1.05, 1.17) and mortality (RR per 1.10 mu g/m(3), 95% CI: 1.06, 1.14) and was significantly associated with respiratory mortality (RR 1.31, 95% CI: 1.25, 1.38) and morbidity (RR 1.08, 95% CI: 1.02, 1.04); (2) An increased risk of respiratory mortality was observed in the elderly (65+ years) (RR 1.21, 95% CI: 1.00, 1.47) with long-term exposure to PM2.5; (3) Long-term exposure to PM10 was associated with cardiovascular morbidity (RR 1.07, 95% CI 1.01, 1.13), respiratory morbidity (RR 1.43, 95% CI: 1.21, 1.69) and respiratory mortality (RR 1.28, 95% CI 1.10, 1.49); (4) A significant association between long-term exposure to PM1 and cardiovascular disease was also observed. ConclusionsLong-term exposure to PM2.5, PM10 and PM1 was all related to cardiovascular and respiratory disease events. PM2.5 had a greater effect than PM10, especially on respiratory diseases, and the risk of respiratory mortality was significantly higher for LMICs than high-income countries. More studies are needed to confirm the effect of PM1 on cardiovascular and respiratory diseases.
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Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review
The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12-24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12-24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. (c) 2022 American Society for Bone and Mineral Research (ASBMR).
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Parathyroid Hormone Therapy for Managing Chronic Hypoparathyroidism: A Systematic Review and Meta-Analysis
The efficacy and safety of parathyroid hormone (PTH) therapy for managing long-term hypoparathyroidism is being evaluated in ongoing clinical trials. We undertook a systematic review and meta-analysis of currently available randomized controlled trials to investigate the benefits and harms of PTH therapy and conventional therapy in the management of patients with chronic hypoparathyroidism. To identify eligible studies, published in English, we searched Embase, PubMed, and Cochrane CENTRAL from inception to May 2022. Two reviewers independently extracted data and assessed the risk of bias. We defined patients' important outcomes and used grading of recommendations, assessment, development, and evaluation (GRADE) to provide the structure for quantifying absolute effects and rating the quality of evidence. Seven randomized trials of 12 publications that enrolled a total of 386 patients proved eligible. The follow-up duration ranged from 1 to 36 months. Compared with conventional therapy, PTH therapy probably achieves a small improvement in physical health-related quality of life (mean difference [MD] 3.4, 95% confidence interval [CI] 1.5-5.3, minimally important difference 3.0, moderate certainty). PTH therapy results in more patients reaching 50% or greater reduction in the dose of active vitamin D and calcium (relative risk [RR] = 6.5, 95% CI 2.5-16.4, 385 more per 1000 patients, high certainty). PTH therapy may increase hypercalcemia (RR =2.4, 95% CI 1.2-5.04, low certainty). The findings may support the use of PTH therapy in patients with chronic hypoparathyroidism. Because of limitations of short duration and small sample size, evidence from randomized trials is limited regarding important benefits of PTH therapy compared with conventional therapy. Establishing such benefits will require further studies. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Electronic cigarettes versus nicotine-replacement therapy for smoking cessation: A systematic review and meta-analysis of randomized controlled trials
INTRODUCTION Nicotine-replacement therapy (NRT) and electronic cigarettes (e-cigarettes) have been frequently used for smoking cessation. The aim of this review is to investigate the effectiveness and safety of e-cigarettes versus NRT for smoking cessation. METHODS We searched PubMed, EMBASE, the Cochrane Library from inception to 10 October 2021. We included randomized controlled trials (RCTs) comparing e-cigarettes versus NRT for smoking cessation. Two authors independently screened titles, abstracts and full texts for eligibility. Paired authors extracted data, assessed risk of bias, and used GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) to rate the certainty of evidence. RESULTS The study included five RCTs with 1748 participants. The meta-analysis suggested the e-cigarettes versus NRT increased the >= 6 months continuous abstinence rate (RR=1.67; 95% CI: 1.21-2.28; 55 more per 1000 participants, low certainty), and 7-day point abstinence rate at >= 6 months follow-up (RR=1.43; 95% CI: 1.19-1.72; 84 more per 1000, low certainty). However, we found no evidence that e-cigarettes versus NRT increased 3-6 months continuous abstinence rate (RR=1.07; 95% CI: 0.73-1.57; 10 more per 1000, very low certainty) and = 6 months continuous abstinence rate and 7-day point abstinence rate. At short-term duration, we found no evidence that e-cigarettes compared to NRT increased the <6 months continuous abstinence rate and 7-day point abstinence rate.
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PROTOCOL: The association between marital transitions and physical and mental health in late life: A systematic review
This is the protocol for a Campbell systematic review. The objectives are as follows: What is the association between marital transitions and physical health among people older than 60? What is the association between marital transitions and mental health among people older than 60? What is the role of gender, age, and education on the association between marital transitions and health among people older than 60? What is the influence of geographical region, housing, neighborhood, and social support on the association between marital transitions and health status among people older than 60?
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