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).

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).

In most European countries, balneotherapy and spa therapy are widely prescribed by physicians and preferred by European citizens for the treatment of musculoskeletal problems including chronic low back pain (LBP). We aimed to review and evaluate the recent evidence on the effectiveness of balneotherapy and spa therapy for patients with LBP. We comprehensively searched data bases for randomized controlled trials (RCTs) published in English between July 2005 and December 2013. We identified all trials testing balneotherapy or spa therapy for LBP that reported that the sequence of allocation was randomized. We finally included total of eight RCTs: two on balneotherapy and six on spa therapy. All reviewed trials reported that balneotherapy was superior in long term to tap water therapy in relieving pain and improving function and that spa therapy combining balneotherapy with mud pack therapy and/or exercise therapy, physiotherapy, and/or education was effective in the management of low back pain and superior or equally effective to the control treatments in short and long terms. We used Jadad scale to grade the methodological quality. Only three out of total eight had a score of above 3 indicating the good quality. The data from the RCTs indicates that overall evidence on effectiveness of balneotherapy and spa therapy in LBP is encouraging and reflects the consistency of previous evidence. However, the overall quality of trials is generally low. Better quality RCTs (well designed, conducted, and reported) are needed testing short- and long-term effects for relieving chronic back pain and proving broader beneficial effects.

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.

Background Low anterior resection syndrome (LARS) is a frequent problem after rectal resection. Transanal irrigation (TAI) has been suggested as an effective treatment in patients who have developed LARS. This prospective RCT was undertaken to evaluate the effect of TAI as a prophylactic treatment to prevent symptoms of LARS. Methods Patients who had undergone ultralow rectal resection were randomized to start TAI on a daily basis, or to serve as a control with supportive therapy only after ileostomy closure. All patients were seen after 1 week, 1 month and 3 months, and the maximum number of defaecation episodes per day and night documented during follow‐up. Wexner score, LARS score and Short Form 36 questionnaire responses were evaluated in both groups. Results Thirty‐seven patients could be evaluated according to protocol (TAI 18, control 19). The maximum number of stool episodes per day and per night was significantly lower among patients who underwent TAI at 1 month (median 3 versus 7 episodes/day in TAI versus control group, P = 0·003; 0 versus 3 episodes/night, P = 0·001) and 3 months (3 versus 5 episodes per day, P = 0·006; 0 versus 1 episodes/night, P = 0·002). LARS scores were significantly better in the TAI group after 1 month (median 16 versus 32 in control group; P = 0·044) and 3 months (9 versus 31; P = 0·001). A significantly better result in terms of Wexner score was seen in the TAI group after 3 months (median 2 versus 6 in controls; P = 0·046). Conclusion Prophylactic TAI led to a significantly better functional outcome compared with supportive therapy for up to 3 months. Registration number: DRKS00011752 ( http://apps.who.int/trialsearch/). Low anterior resection syndrome is a frequently encountered disorder following rectal resection that strongly affects patients' quality of life. In this randomized multicentre trial, prophylactic application of transanal irrigation (after closure of the protective ileostomy) resulted in a significant improvement in functional outcome compared with that in a control group with supportive therapy only.

Background Minimally invasive surgery is the standard technique for many operations. Laparoscopic training has a long learning curve. Robotic solutions may shorten the training pathway. The aim of this study was to compare laparoscopic with robotic training in surgical trainees and medical students. Methods Surgical trainees (ST group) were randomized to receive 6 h of robotic or laparoscopic simulation training. They then performed three surgical tasks in cadaveric specimens. Medical students (MS group) had 2 h of robotic or laparoscopic simulation training followed by one surgical task. The Global Rating Scale (GRS) score (maximum 30), number of suture errors, and time to complete each procedure were recorded. Results The median GRS score for the ST group was better for each procedure after robotic training compared with laparoscopic training (total GRS score: 27·00 (i.q.r. 22·25–28·33) versus 18·00 (16·50–19·04) respectively, P < 0·001; 10 participants in each arm). The ST group made fewer errors in robotic than in laparoscopic tasks, for both continuous (7·00 (4·75–9·63) versus 22·25 (20·75–25·25); P < 0·001) and interrupted (8·25 (6·38–10·13) versus 29·50 (23·75–31·50); P < 0·001) sutures. For the MS group, the robotic group completed 8·67 interrupted sutures with 15·50 errors in 40 min, compared with only 3·50 sutures with 40·00 errors in the laparoscopic group (P < 0·001) (10 participants in each arm). Fatigue and physical comfort levels were better after robotic compared with laparoscopic operating for both groups (P < 0·001). Conclusion The acquisition of surgical skills in surgical trainees and the surgically naive takes less time with a robotic compared with a laparoscopic platform. Antecedentes La cirugía mínimamente invasiva (minimally invasive surgery, MIS) es la técnica considerada como el patrón oro para muchas intervenciones quirúrgicas. La formación en laparoscopia tiene una curva de aprendizaje larga. El empleo de la robótica puede acortar dicho periodo de entrenamiento. El objetivo de este estudio fue comparar el entrenamiento laparoscópico con el robótico en residentes de cirugía y estudiantes de medicina. Métodos Los integrantes del grupo de residentes de cirugía (surgical trainees, ST) fueron aleatorizados a recibir 6 horas de entrenamiento con simulación laparoscópica o robótica. Seguidamente, efectuaron tres procedimientos quirúrgicos en especímenes de cadáver. El grupo de estudiantes de medicina (medical students, MS) recibió 2 horas de entrenamiento de simulación laparoscópica o robótica, seguidas de un procedimiento quirúrgico. Se registró el resultado de la escala global de puntuación (global rating scale score, GRS, máxima puntuación = 30), el número de errores cometidos en las suturas y el tiempo para completar cada procedimiento. Resultados La mediana de GRS para el grupo ST fue mejor para cada procedimiento tras el entrenamiento robótico (GRS puntuación total 27,00 ± 6, n = 10) en comparación con el entrenamiento laparoscópico (18,00 ± 5, n = 10, P < 0,001). Se cometieron menos errores en las tareas robóticas en comparación con las laparoscópicas, tanto para las suturas continuas (7,00 ± 5 y 22,25 ± 5; P < 0,001) como discontinuas (8,25 ± 4 y 29,50 ± 8; P < 0,001). En el grupo de MS, el grupo de robótica completó 8,67 suturas discontinuas con 15,50 errores en 40 minutos, en comparación con solo 3,50 suturas con 40,00 errores en el grupo laparoscópico (P < 0,001). Los niveles de fatiga y de confort físico fueron mejores tras la cirugía robótica en comparación con la laparoscópica (P < 0,001) para ambos grupos. Conclusión En los residentes de cirugía y en personas sin contacto previo con la cirugía, las habilidades quirúrgicas se adquirieron en menos tiempo con una plataforma robótica que laparoscópica. Medical students and surgical trainees were randomized to robotic or laparoscopic simulator training followed by cadaveric surgical tasks. The robotic groups had a shorter learning curve with better task performance. Another advantage for robotic surgery

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..

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.

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.

The World Health Organization (WHO) urges global administration of at least one dose of the HPV vaccine, particularly for girls aged 9–14, to work towards the elimination of cervical cancer. However, data on the efficacy of a single dose of Cecolin®, a bivalent HPV vaccine, remain quite limited. Therefore, it is crucial to design studies investigating the protective effects of a single dose of Cecolin® in Chinese girls. The randomized clinical trial began on February 23, 2023 (NCT06345885). 198 Chinese girls aged 9–14 received a single dose of Cecolin® or Gardasil®. Seroconversion rates and geometric mean titers (GMTs) for HPV16 and HPV18 were assessed at one and two months post-vaccination. Non-inferiority was declared if the lower limit of the 95 % confidence interval (CI) exceeded −5 %. Safety of vaccine was evaluated in all vaccinated participants. At one month post-vaccination, both the Cecolin® and Gardasil® groups achieved 100 % seroconversion for HPV16 antibodies. The seroconversion rates for HPV18 were 97.9 % (95 % CI: 92.5 %, 99.7 %) in the Cecolin® group and 95.6 % (95 % CI: 89.1 %, 98.8 %) in the Gardasil® group. The GMTs in the Cecolin® group were significantly higher than those in the Gardasil® group for both HPV types, with GMT ratios of 1.5 (1.1, 2.1) for HPV16 and 2.84 (2.0, 4.1) for HPV18. The seroconversion rates and GMT ratios one month after a single dose of Cecolin® were non-inferior to those of Gardasil®, with results remaining consistent at two months. The incidence of adverse events was similar between the two groups throughout the study, with no statistically significant differences. The immunogenicity and safety of a single dose of Cecolin® in Chinese girls aged 9–14 years were comparable to those of Gardasil. These findings support the use of single-dose Cecolin® to enhance HPV vaccination coverage for cervical cancer prevention.