Explore the vast range of titles available.

Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients’ health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40–50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients’ mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).

Background Patient outcomes can depend on the treating centre, or health professional, delivering the intervention. A health professional’s skill in delivery improves with experience, meaning that outcomes may be associated with learning. Considering differences in intervention delivery at trial design will ensure that any appropriate adjustments can be made during analysis. This work aimed to establish practice for the allowance of clustering and learning effects in the design and analysis of randomised multicentre trials. Methods A survey that drew upon quotes from existing guidelines, references to relevant publications and example trial scenarios was delivered. Registered UK Clinical Research Collaboration Registered Clinical Trials Units were invited to participate. Results Forty-four Units participated ( N  = 50). Clustering was managed through design by stratification, more commonly by centre than by treatment provider. Managing learning by design through defining a minimum expertise level for treatment provider was common (89%). One-third reported experience in expertise-based designs. The majority of Units had adjusted for clustering during analysis, although approaches varied. Analysis of learning was rarely performed for the main analysis ( n  = 1), although it was explored by other means. The insight behind the approaches used within and reasons for, or against, alternative approaches were provided. Conclusions Widespread awareness of challenges in designing and analysing multicentre trials is identified. Approaches used, and opinions on these, vary both across and within Units, indicating that approaches are dependent on the type of trial. Agreeing principles to guide trial design and analysis across a range of realistic clinical scenarios should be considered.

The continuing evolution of influenza viruses poses a challenge to vaccine prevention, highlighting the need for a universal influenza vaccine. We evaluated the safety and immunogenicity of one such candidate, Multimeric-001 (M-001), when used as a priming vaccine prior to administration of quadrivalent inactivated influenza vaccine (IIV4). Healthy adults 18 to 49 years of age were enrolled in a phase 2 randomized, double-blind placebo-controlled trial. Participants received two doses of either 1.0-mg M-001 or saline placebo (60 per study arm) on Days 1 and 22 followed by a single dose of IIV4 on about Day 172. Safety, reactogenicity, cellular immune responses and influenza hemagglutination inhibition (HAI) and microneutralization (MN) were assessed. The M-001 vaccine was safe and had an acceptable reactogenicity profile. Injection site tenderness (39% post-dose 1, 29% post-dose 2) was the most common reaction after M-001 administration. Polyfunctional CD4+ T cell responses (perforin-negative, CD107α-negative, TNF-α+, IFN-γ+, with or without IL-2) to the pool of M-001 peptides increased significantly from baseline to two weeks after the second dose of M-001, and this increase persisted through Day 172. However, there was no enhancement of HAI or MN antibody responses among M-001 recipients following IIV4 administration. M-001 administration induced a subset of polyfunctional CD4+ T cells that persisted through 6 months of follow-up, but it did not improve HAI or MN antibody responses to IIV4. (clinicaltrials.gov NCT03058692).

This randomised clinical trial aimed to evaluate the effect of a pro-breast-feeding (BF) and healthy complementary feeding intervention performed during infants’ first months of life on ultraprocessed food (UPF) consumption at 4–7 years. We enrolled 323 teenage mothers and their infants from South Brazil, 163 allocated to the intervention group and 160 to the control group. Intervention consisted of sessions on BF and healthy complementary feeding promotion and was carried out in the maternity ward and at home after delivery. Food consumption was assessed using three 24-h food recalls at child’s age of 4–7 years. Foods were classified according to NOVA classification. Dietary contribution of UPF was adjusted for intra-individual variability by the SPADE method and categorised into tertiles. We used Poisson regression models with robust variance, adjusted for confounders, to estimate the effect of the intervention and duration of BF on the risk of high consumption of UPF. Our final analysis included 194 children, with mean age of 6·1 (sd 0·5) years. Mean dietary contribution of UPF was 38 % in the intervention group and 42·7 % in the control group, from total daily intakes. Results adjusted for BF duration, propensity score, income and total energy content demonstrated that the intervention reduced the risk of high consumption of UPF by 35 % (relative risk 0·65, 95 % CI 0·43, 0·98). BF duration was not associated with UPF consumption. The intervention was effective in reducing the risk of high UPF consumption at the age of 4–7 years.

Studies in rodents and humans have indicated that omega-3 polyunsaturated fatty acids (n-3 PUFA) may reduce weight. The aim of this meta-analysis was to evaluate evidence for the efficacy of n-3 PUFA in managing overweight and obesity. We performed a systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials until May 2015. Two reviewers independently determined the eligibility of studies and assessed the reporting quality of included randomized controlled trials (RCTs). A total of 11 RCTs involving 617 participants were included in this meta-analysis. Based on the meta-analysis of nine studies, a statistically nonsignificant difference was revealed in weight loss between n-3 PUFA and placebo (p=0.99; weighted mean difference [WMD]: 0.00; 95% confidence interval [CI] −0.42 to 0.43), whereas n-3 PUFA was superior to placebo in reducing serum triglyceride levels (p=0.0007; standard median difference [Std MD]: −0.59; 95% CI −0.93 to −0.25). Based on meta-analysis of seven studies, the analysis of aggregated data showed a significant reduction in waist circumference (p=0.005; WMD: −0.53; 95% CI −0.90 to −0.16). There were no significant differences in body mass index, total serum levels of cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and fasting glucose levels. The evidence from RCTs showed that n-3 PUFA might effectively reduce waist circumference and triglyceride levels in overweight and obese adults, but n-3 PUFA may not effectively reduce body weight. Given the small number and poor quality of RCTs included in the meta-analysis, these results are inconclusive. A large-scale, well-designed RCT is needed to further address this issue..

The effect of a combination of magnesium, vitamins B6, B9, B12, rhodiola and green tea/L-theanine (Mg-Teadiola) on stress was evaluated in chronically stressed, otherwise healthy individuals. Effects on stress-related quality-of-life parameters (sleep and perception of pain) were also explored. Adults with stress for ≥1 month, scoring ≥14 points on the Depression Anxiety Stress Scale (DASS)-42 questionnaire, were randomized (1:1) to receive oral Mg-Teadiola (n = 49) or a placebo (n = 51), for 28 days, with a follow-up assessment on Day 56 (NCT04391452). The primary endpoint was the change in the DASS-42 stress score from baseline to Day 28 with Mg-Teadiola versus placebo. The DASS-42 stress scores significantly decreased from baseline to Day 28 with Mg-Teadiola versus placebo (effect size, 0.29; 95% CI [0.01, 0.57]; p = 0.04). Similar reductions were observed on Day 14 (p = 0.006) and Day 56 (p = 0.02). A significant reduction in sensitivity to cold pain (p = 0.01) and a trend for lower sensitivity to warm pain was observed (p = 0.06) on Day 28. Improvements in daytime dysfunction due to sleepiness (Pittsburgh Sleep Quality Index-7 component score) were reported on Day 28, and were significant on Day 56 (p < 0.001). Mg-Teadiola is effective in managing stress in otherwise healthy individuals. Its beneficial effects on sleep and pain perception need further investigation.

Heart failure (HF) is associated with a reduction of skeletal muscle mass. Whey protein isolate (WPI) has been beneficial in increasing muscle mass and strength, in addition to improving body composition. The goal of this research was to evaluate the effect of WPI on the body composition, muscle mass, and strength of chronic HF patients. For this purpose, twenty-five patients of both genders with predominantly NYHA I functional class and a median age of 65.5 (60.5–71.0) years were used to conduct a randomized, single-blind, placebo-controlled clinical trial and received 30 g per day of WPI for 12 weeks. Anthropometric measurements, body composition analysis, and biochemical exams were performed at the beginning and end of the study. An increase in skeletal muscle mass was observed in the intervention group after 12 weeks. A reduction in waist circumference, body fat percentage, and an increase in skeletal muscle index was observed when compared to the placebo group. No significant effect on muscle strength was observed after 12 weeks of intervention. These data demonstrate that WPI consumption contributed to the increase of skeletal muscle mass, strength, and reduction of body fat in HF patients.

Abstract Real world data (RWD) refers to healthcare information that is routinely collected in electronic healthcare records (EHR), hospital and pharmacy records, patient and disease registries, and health insurance databases. The collection and analysis of this vast amount of data is an important complement to that obtained from conventional randomised controlled trials (RCT). Real world data has been used for healthcare quality improvements, to conduct clinical trials, to support drug and device development, and to inform medical guidelines. The utility of RWD may be facilitated by common data models, which standardise format and content, and allow data from different health systems to be analysed together. The European Society of Cardiology (ESC) supports the use of RWD in collaboration with national cardiac societies, regulatory authorities, and industry to encourage continuous quality of care improvements at the hospital and country level, to conduct registry-based randomised clinical trials (R-RCT) and to facilitate safety surveillance of novel drugs and devices. The European Medicines Agency (EMA) is developing systems and processes to enable the use of RWD that can help in trial planning, defining clinical contexts, and enhancing outcome assessments. RWD can also contribute to the measurement of the impact of regulatory actions, such as contraindications or restriction of indications by looking at medicines use patterns over time across European Member States. A number of other initiatives from the European Commission and the EMA are underway to strengthen the EU's health security framework, and foster the collection and utilisation of RWD. Graphical Abstract Graphical Abstract Examples of types of data that can be collected as part of routine care.

Purpose This study aimed to investigate the effects of vitamin K 2 supplementation in the form of menaquinone-7 (MK-7) on glucose, insulin, and lipid metabolism in patients with type 2 diabetes mellitus (T2DM). Methods In this double-blinded, placebo-controlled, randomized trial, 68 insulin-independent people with diabetes received either 180 µg MK-7 twice a day or placebo for 12 weeks. We assessed fasting plasma glucose (FPG) and insulin concentrations (primary outcomes), glycated hemoglobin (HbA1c), insulin sensitivity indices, and lipid profiles (secondary outcomes) at baseline and end of the trial. Results At the end of the trial, FPG (effect size (ES) = − 0.68; p -adjusted = 0.031) and HbA1c (ES = − 0.36; p -adjusted = 0.004) were significantly lower in the vitamin K 2 group compared with the placebo at the end of the trial. The number of participants achieved the target levels of glycemic control based on FPG, and HbA1c concentrations were significantly higher in the vitamin K 2 group compared to the placebo group. Insulin concentrations (ES = − 0.29; p  = 0.019) and homeostatic model assessment for insulin resistance (HOMA-IR) significantly decreased in the vitamin K 2 group (ES = − 0.29; p  = 0.019) compared to baseline, but their values were not significantly different compared to the placebo group at the end of the trial. No significant variation was observed in lipid profiles. Conclusion Daily intake of 360 µg Vitamin K 2 in the form of MK-7 for 12-weeks reduces FPG and HbA1c in patients with T2DM but does not have a lipid-lowering effect.

PurposeFatalities due to heart and cerebrovascular diseases caused by uncontrolled hyperlipidaemia increase every year; on the other hand, lipid-lowering drugs are known to cause side effects. The gut microbiota has been thoroughly investigated by researchers and consumers, because they have unique functional properties and littler side effects. However, the effects of the gut microbiota remain controversial. We conducted a meta-analysis to assess the effects of products designed to modulate the gut microbiota on various hyperlipidaemias.MethodsWe systematically searched PubMed, Embase, Cochrane Library (Central), and Web of Science for randomized controlled trials (published before June 2017, and those only in English) to compare treatment (products designed to modulate the gut microbiota) versus placebo. Our main endpoints were total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in serum. We assessed pooled data using a fixed effects model.ResultsOf 1337 identified studies, 21 were eligible and included in our analysis (n = 1436 participants). The combined estimate of effect size for the impact of products designed to modulate the gut microbiota on serum TC (WMD − 11.07 mg/dL, 95% CI − 13.72 to − 8.43, p < 0.001), LDL-C (WMD − 10.96 mg/dL, 95% CI − 13.37 to − 8.56, p < 0.001), and HDL-C (WMD 0.72 mg/dL, 95% CI 0.06–1.38, p = 0.032) were statistically significant, while no significant effect was found on TG concentrations (WMD − 0.56 mg/dL, 95% CI − 5.59 to 4.47, p = 0.828). Subgroup analysis showed parallel trials, probiotics, and long-term intervention had better effects on lowering blood lipid levels.ConclusionProducts designed to modulate the gut microbiota results in changes of the plasma lipid concentrations and these changes may protect against cardiovascular disease.