Background: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive. Objectives: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients. Methods: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations. Results: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants. Conclusions: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake.

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.

BACKGROUND Several systematic reviews (SRs) have investigated the association between ultra -processed foods (UPFs) and the risk of hypertension in various populations. However, the quality of the evidence remains unclear. This umbrella review was thus conducted to fill this gap. METHODS We searched for SRs with and without meta -analyses comparing high UPF versus low UPF consumption on the risk of hypertension in the Cochrane Library, Embase, PubMed, and Web of Science from inception to August 2022. This study was registered in PROSPERO (No. CRD42022352934). The A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR -2) tool and the Preferred Reporting Item for Systematic Review and Meta -analysis 2009 (PRISMA 2009) statement were used to evaluate the methodological and reporting quality of the included SRs. Stata 15/SE was used to reanalyse the data using the random -effects model, and the risk of bias of observational studies from included SRs was reassessed using the Newcastle -Ottawa Scale (NOS) tool. The certainty of the evidence body was assessed using the GRADE recommendation. RESULTS Seven SRs were included in the umbrella review. Among them, nine observational studies (5 cross-sectional and 4 cohort studies), whose available data were resynthesised using meta -analysis. The methodological and reporting quality of the included SRs were relatively poor. The meta -analysis results revealed suggestive evidence of an association between high UPF consumption and the incidence of hypertension (odds ratio: 1.23, 95% con fidence interval: 1.11 to 1.37, p < 0.001, 95% prediction interval: 0.92 to 1.64, critically low certainty) compared to low UPF consumption. CONCLUSION High UPF consumption is associated with an increased risk of hypertension. However, well-conducted SRs, including high -quality prospective cohort studies, are needed to further verify these findings.

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.

The effect of various exercise modalities on people with sleep disorders remains unclear. This network meta analysis aims to explore the effects of various exercise modalities in improving sleep quality in people with sleep disorders. Four electronic databases were searched from inception to April 8, 2023. We conducted pairwise meta-analyses and frequentist network meta-analyses with random effects models. A total of 17 randomized controlled trials enrolled 1090 participants were included. Compared with passive control, with moderate-to-low certainty of evidence, mind-body exercise combined with treatment as usual [standard mean difference (SMD) =-2.26, 95% confidence interval (CI) (-3.29,-1,24)], moderate aerobic exercise combined with light strength exercise [SMD =-1.26, 95% CI (-2.22,-0.31)], mind-body exercise [SMD =-0.81, 95% CI (-1.37,-0.25)] and moderate aerobic exercise [SMD =-0.75, 95% CI (-1.38,-0.13)] were more effect in improving sleep disorders. Various exercise modalities have favorable effects on sleep quality for people with sleep disorders compared with passive control. However, due to the low quality of evidence, well-designed trials should be conducted to elucidate these promising findings in the future.

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.

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.

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.

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.