ObjectivesTo compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer’s disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits.MethodsElectronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre–post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined.ResultsWe included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%–11.1%). HFrTMS (1.08, 9, 0.35–1.80) and atDCS (0.56, 0.03–1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (−0.79, –2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77–2.54) and ctDCS (2.57, 0.20–4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated.ConclusionsHFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

Background People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia.Methods For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786.Findings Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5•90, 95% CI 3•53 to 9•86), and the HR for all-cause mortality was highest for Lewy body dementia (17•88, 5•87 to 54•46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5•8 years (SD 2•0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1•33, 1•21 to 1•46), a shorter survival time from diagnosis (MD -1•12 years, 95% CI -1•52 to -0•72), and a younger age at death (-1•76 years, -2•66 to -0•85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD -1•27 years, -1•90 to -0•65) and dementia with Lewy bodies (MD -1•06 years, -1•68 to -0•44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I²>75%) was observed for most of the study outcomes. Interpretation Alzhei...

Background: Previous studies have suggested that biologic therapy for psoriasis might relate to body weight gain.Objective: To assess the changes in body weight and body mass index (BMI) in psoriasis patients after receiving various biologics.Methods: We conducted a systematic review and network meta-analysis to evaluate the changes in body weight and BMI in psoriasis patients receiving biologics. On March 1, 2019, we searched Medline, Embase, and Cochrane Central Register of Controlled Trials for relevant studies. The Newcastle-Ottawa scale was used to assess the risk of bias.Results: We included 6 studies with 862 psoriasis patients. Compared with conventional systemic treatments, treatment with tumor necrosis factor a inhibitors was associated with a significant increase in body weight (mean difference 1.40 kg, 95% confidence interval 0.88-1.93 kg) and BMI (0.39 kg/m 2 , 95% confidence interval 0.24-0.54 kg/m 2 ). In contrast, no significant increase in body weight or BMI was found among patients receiving anti-interleukin (IL)-12/23 or anti-IL-17 biologics.Limitations: Only 1 study reported body weight and BMI for patients receiving the anti-IL-17 biologic. Conclusion:Tumor necrosis factor a inhibitor treatment appears to be associated with an increase in body weight and BMI, and treatment with anti-IL-12/23 and anti-IL-17 biologics do not. This association should be considered before initiating biologics for overweight and obese patients.

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Smoking cessation is a public health priority to reduce smoking-related morbidity and mortality. However, weight gain is a known primary reason for not trying to quit smoking.The aim of the current study was to investigate differences in weight gain associated with different pharmacological smoking cessation interventions. Randomized controlled trials (RCTs) that reported weight gain related to pharmacologic treatments for smoking Abbreviations: AUC, area under the curve; BW, body weight; CI, confidence interval; DSM, Diagnostic and Statistical Manual of Mental Disorders; ES, effect size; FDA, Food and Drug Administration; ICD, International Classification of Diseases; MD, mean difference; NMA, network meta-analysis; NRT, nicotine replacement therapy; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses; RCT, randomized control trial; SUCRA, surface under the cumulative ranking curve Meng-Tsang Hsieh and Ping-Tao Tseng contributed equally as first authors.

Objective To systematically examine the effectiveness and tolerability of psilocybin for treating end-of-life anxiety symptoms.Methods The Medline, Embase, CENTRAL, and PsycINFO databases were searched up to November 25, 2020. We enrolled clinical trials investigating psilocybin for treating end-of-life anxiety symptoms. Meta-analysis was conducted using random-effects model.Results Overall, five studies were included, revealing that psilocybin was superior to the placebo in treating state anxiety at 1 day (Hedges’ g, -0.70; 95% confidence interval, -1.01 to -0.39) and 2 weeks (-1.03; -1.47 to -0.60) after treatment. Psilocybin was more effective than placebo in treating trait anxiety at 1 day (-0.71; -1.15 to -0.26), 2 weeks (-1.08; -1.80 to -0.36), and 6 months (-0.84; -1.37 to -0.30) after treatment. Psilocybin was associated with transient elevation in systolic (19.00; 13.58–24.41 mm Hg) and diastolic (8.66; 5.18–12.15 mm Hg) blood pressure compared with placebo. The differences between psilocybin and placebo groups with regard to allcause discontinuation, serious adverse events, and heart rates were nonsignificant.Conclusion Psilocybin-assisted therapy could ameliorate end-of-life anxiety symptoms without serious adverse events. Because of the small sample sizes of the included studies and high heterogeneity on long-term outcomes, future randomized controlled trials with large sample sizes are needed.

We examined the cardiovascular safety, acceptability, and trajectory of the antidepressant effects of psilocybin after single- or two-dose administration. Four major electronic databases were systematically searched. Data were pooled using a multivariate random-effects meta-analysis. Primary outcomes were changes in depressive symptoms. Secondary outcomes were cardiovascular safety and acceptability. Ten studies were included. The estimated effect sizes (standardized mean difference (SMD) with 95% confidence intervals) for psilocybin were −0.75 (−1.15 to −0.35) on day 1, −1.74 (−2.15 to −1.32) at 1 week, −1.35 (−1.77 to −0.93) at 1 month, −0.91 (−1.31 to −0.51) at 3 months, and −1.12 (−1.56 to −0.68) at 6 months. Higher doses and two sessions of psilocybin treatment were significantly associated with superior antidepressant effects. The all-cause discontinuation and heart rate after psilocybin administration were comparable to placebo; meanwhile, psilocybin increased systolic and diastolic blood pressure by 19.00 mmHg and 8.66 mmHg, respectively. There were no significant differences between SMD derived from placebo-controlled trials compared to those from pre–post changes and SMD in randomized controlled trials (RCTs) compared to those in non-RCTs. The present study demonstrates that single- or two-dose psilocybin administration has rapid and sustained antidepressant effects for up to 6 months, with favorable cardiovascular safety and acceptability.

Background and Objectives: To compare the efficacy and safety of biologic treatments for moderate-to-severe pediatric psoriasis approved by the US Food and Drug Administration and European Medicines Agency.Patients and Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs) were searched for the identification of eligible RCTs until May 7, 2021. Fixed-effect frequentist network meta-analysis (NMA) was performed with the surface under the cumulative ranking curve (SUCRA) calculated for ranking. Our primary outcomes included ≥ 90 % improvement of Psoriasis Area and Severity Index score (PASI 90) at 12-16 weeks and discontinuation owing to adverse events (DAE) through the first 12-16 weeks.Results: Five RCTs involving 798 pediatric psoriasis patients were included. Compared to placebo, all biologic regimens exhibited a significantly higher PASI 90 response but did not differ in the risk for DAE. Based on the SUCRA, secukinumab-low dose (SEC-L) ranked first in the achieved PASI 90 response (84.7 %), followed by ixekizumab (70.8 %).Conclusions: Among all biologic treatments, SEC-L showed the best PASI 90 response without increasing the risk for DAE. More long-term studies are warranted.