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Background Published analyses of prostate cancer nested case–control and survival data in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort suggested that men with higher baseline vitamin D [25(OH)D] concentrations have both (i) increased prostate cancer risk and (ii) decreased prostate cancer-specific fatality. Methods To investigate possible factors responsible for a spurious association with prostate cancer fatality, we reanalysed baseline serum vitamin D associations with prostate cancer risk and prostate cancer-specific fatality in case–control data nested within the ATBC Study (1000 controls and 1000 incident prostate cancer cases). Conditional logistic regression and Cox proportion hazard models were used, respectively, to estimate odds ratios for risk and hazard ratios for prostate cancer-specific fatality, overall and by disease aggressiveness. We replicated these case–control analyses using baseline serum measurements of alpha-tocopherol (vitamin E), beta-carotene and retinol (vitamin A), and used the entire ATBC Study cohort (⁠ n  = 29 085) to estimate marginal associations between these baseline vitamins and prostate cancer incidence and fatality following blood collection. Results Vitamin D analyses agreed closely with those originally published, with opposite risk and fatality associations. By contrast, the analyses of alpha-tocopherol, beta-carotene and retinol yielded concordant associations for prostate cancer incidence and prostate cancer-specific fatality. Conclusions We found evidence of neither artefacts in the nested prostate cancer case–control data set nor detection or collider biases in the fatality analyses. The present findings therefore support a valid inverse (i.e. beneficial) association between vitamin D and prostate cancer-specific survival that warrants further evaluation, including possibly in controlled trials. [ABSTRACT FROM AUTHOR]

Dementia negatively affects the wellbeing of both caregivers and care recipients. Community-based therapeutic choir singing offers opportunities for music participation and social engagement that are accessible and mutually enjoyable for people with dementia and their family caregivers and promotes shared and meaningful musical interactions, which may support relationship quality. This study aimed to investigate the impact of the Remini-Sing therapeutic choir intervention on relationship quality, quality of life, depression, and social connectedness for dyads, as well as caregiver burden and care recipient anxiety. A randomized-controlled trial design was used with a target sample of 180 dyads. Due to recruitment difficulties, 34 participant dyads were recruited and randomly assigned to a 20-week group singing condition (n  = 16) or a waitlisted control group (n  = 18). Participant dyads consisted of people with dementia and their family caregivers who resided at home in the community. The Remini-Sing therapeutic choirs were held in community settings. Assessments were conducted by masked assessors at baseline, 11 weeks, and 21 weeks. Twenty-one dyads completed assessments at the primary timepoint (Week 11). Issues with recruitment and retention resulted in an unpowered study with no statistically significant findings. Mean decreases in anxiety and depression for choir participants with dementia were supported by medium to large effect sizes, indicating a potential intervention effect to be explored in future powered studies. Key learnings related to study design are discussed regarding recruitment, retention, participant burden, and sustainability, with recommendations made for future dementia research. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Aerobic exercise interventions in people with schizophrenia have been demonstrated to improve clinical outcomes, but findings regarding the underlying neural mechanisms are limited and mainly focus on the hippocampal formation. Therefore, we conducted a global exploratory analysis of structural and functional neural adaptations after exercise and explored their clinical implications. Study Design In this randomized controlled trial, structural and functional MRI data were available for 91 patients with schizophrenia who performed either aerobic exercise on a bicycle ergometer or underwent a flexibility, strengthening, and balance training as control group. We analyzed clinical and neuroimaging data before and after 6 months of regular exercise. Bayesian linear mixed models and Bayesian logistic regressions were calculated to evaluate effects of exercise on multiple neural outcomes and their potential clinical relevance. Study Results Our results indicated that aerobic exercise in people with schizophrenia led to structural and functional adaptations mainly within the default-mode network, the cortico-striato-pallido-thalamo-cortical loop, and the cerebello-thalamo-cortical pathway. We further observed that volume increases in the right posterior cingulate gyrus as a central node of the default-mode network were linked to improvements in disorder severity. Conclusions These exploratory findings suggest a positive impact of aerobic exercise on 3 cerebral networks that are involved in the pathophysiology of schizophrenia. Clinical Trials Registration The underlying study of this manuscript was registered in the International Clinical Trials Database, ClinicalTrials.gov (NCT number: NCT03466112, https://clinicaltrials.gov/ct2/show/NCT03466112?term=NCT03466112&draw=2&rank=1) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804). [ABSTRACT FROM AUTHOR]

N-acetyl cysteine (NAC) is a potent antioxidant that modulates glutamatergic signalling which is thought to play a role in alcohol use disorder (AUD). There have been no clinical trials investigating NAC for AUD. We aimed to conduct a 28 day double-blind, placebo-controlled (PL) randomized trial of NAC in the treatment of AUD (NCT03879759). A total of 42 participants with AUD (56% alcohol-related liver disease) were randomized to receive placebo or NAC 2400 mg/day. Feasibility outcomes included treatment retention and adverse events. Primary clinical outcomes included alcohol consumption (heavy drinking days, standard drinks per drinking day). Secondary clinical outcome measures included craving, liver tests, and psychological outcomes. There were no significant differences in overall retention between treatment groups (χ2(1) = 0.14, P  = 0.71: 86% vs 76% for placebo and NAC, respectively). The most commonly reported adverse event in NAC-treated individuals included headache (14%). For standard drinks per drinking day, there was a significant overall effect of time (F  = 9.18, P  < 0.001), no significant effect of treatment (F  = 0.75, P  = 0.79), and a significant time x treatment (NAC vs PL) effect (F  = 2.73, P  < 0.05). For number of heavy drinks per day, there was a significant overall effect of time (F  = 3.16, P  < 0.05) but no significant effect of treatment or time x treatment (P  = 0.17). There were no significant NAC vs PL effects on secondary clinical outcome measures. In the first trial of NAC for the management of AUD, NAC appears to be feasible and safe. Although there was a significant effect of NAC vs placebo on some alcohol measures such as drinks per drinking day, there does appear to be a variable pattern of effect across time suggesting that a larger trial incorporating a longer treatment duration is now required to determine efficacy. [ABSTRACT FROM AUTHOR]

Objective: This study examined the impact of a humanoid robot (MEDi®) programmed to teach deep breathing as a coping strategy, on children's pain and fear as primary and secondary outcomes, respectively, during intravenous (IV) line placement. The completion of IV induction was also examined as an exploratory outcome.Methods: In this randomized controlled, two-armed trial, 137 children (4-12 years) were recruited in Short Stay Surgery at a tertiary pediatric hospital. Patients were randomly assigned to standard care (SC) with Ametop© only (N = 60) or SC and robot-facilitated intervention (N = 59) before induction. Pain and fear before, during, and after IV insertion were rated by patients and observers.Results: No significant differences were found between groups and there were no changes over time for pain or fear (ps > .05). Exploratory analyses show that patients in the MEDi® group were 5.04 times more likely to complete IV induction, compared to SC, Fisher's exact test: X2 (1) = 4.85, p = .04, φc = 0.22, odds ratio = 5.04, 95% CI [1.06, 24.00].Conclusion: This study was the first to examine children's IV induction experience when provided MEDi® support. Reasons for nonsignificance, limitations, and research suggestions were made. [ABSTRACT FROM AUTHOR]

Background: It has been proposed that maternal folic-acid supplement use may alter the DNA-methylation patterns of the offspring during the in-utero period, which could influence development and later-life health outcomes. Evidence from human studies suggests a role for prenatal folate levels in influencing DNA methylation in early life, but this has not been extended to consider persistent effects into adulthood.Methods: To better elucidate the long-term impact of maternal folic acid in pregnancy on DNA methylation in offspring, we carried out an epigenome-wide association study (EWAS) nested within the Aberdeen Folic Acid Supplementation Trial (AFAST-a trial of two different doses: 0.2 and 5 mg, folic acid vs placebo). Offspring of the AFAST participants were recruited at a mean age of 47 years and saliva samples were profiled on the Illumina Infinium Human Methylation450 array. Both single-site and differentially methylated region analyses were performed.Results: We found an association at cg09112514 (p = 4.03×10-9), a CpG located in the 5' untranslated region of PDGFRA, in the main analysis comparing the intervention arms [low- (0.2 mg) and high-dose (5 mg) folic acid combined (N = 43)] vs placebo (N = 43). Furthermore, a dose-response reduction in methylation at this site was identified in relation to the intervention. In the regional approach, we identified 46 regions of the genome that were differentially methylated in response to the intervention (Sidak p-value <0.05), including HLA-DPB2, HLA-DPB1, PAX8 and VTRNA2-1. Whereas cg09112514 did not replicate in an independent EWAS of maternal plasma folate, there was suggested replication of differential methylation in PAX8.Conclusions: The results of this study suggest that maternal folic-acid supplement use is associated with changes in the DNA methylation of the offspring that persist for many years after exposure in utero. These methylation changes are located in genes implicated in embryonic development, immune response and cellular proliferation. Further work to investigate whether these epigenetic changes translate into detectable phenotypic differences is required. [ABSTRACT FROM AUTHOR]

Background: Physical activity confers numerous health benefits, yet few adults meet recommended physical activity guidelines.Purpose: The impact of brief messages providing descriptive and injunctive social norm feedback on physical activity was tested in this conceptual pilot study.Methods: Young adults (N = 111) were randomly assigned to one of three conditions: descriptive norm feedback, descriptive-plus-injunctive norm feedback, or no social feedback (control condition). Participants used pedometers for eight weekdays and recorded their step counts each evening. The descriptive norm group received feedback about the average number of steps taken by group members the previous day. The descriptive-plus-injunctive norm group received feedback about the group average, as well as a sad face if the participant was below the average or a happy face if the participant was above the average. The control group received no feedback throughout the study.Results: By days 7 and 8, the descriptive-plus-injunctive norm group reported significantly more steps relative to the control group, whereas the descriptive norm group showed a trend toward higher step counts relative to the control group. These effects did not differ for participants above versus below the group average at baseline.Conclusion: The combined use of descriptive and injunctive social norms increased physical activity over a short period. This simple feedback strategy has potential for achieving wide reach and dissemination on its own or combined with more comprehensive interventions. This initial evidence can guide larger trials of longer duration.Trial Registration Number: The trial was registered with the ClinicalTrials.gov database (NCT02710201). [ABSTRACT FROM AUTHOR]

Optimal albuminuria reduction is considered essential to halting chronic kidney disease (CKD) progression. Both vitamin D receptor activator (VDRA) treatment and dietary sodium The ViRTUE study is an investigator-initiated, prospective, multi-centre, randomized, double-blind (paricalcitol versus placebo), placebo-controlled trial targeting stage 1-3 CKD patients with residual albuminuria of >300 mg/day due to nondiabetic glomerular disease, despite angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. During run-in, all subjects switched to standardized RAAS blockade (ramipril 10 mg/day) and blood pressure titrated to <140/90 mmHg according to a standardized protocol. Eligible patients are subsequently enrolled and undergo four consecutive study periods in random order of 8 weeks each: (i) paricalcitol (2 µg/day) combined with a liberal sodium diet (~200 mmol Na+/day, i.e. mean sodium intake in the general population), (ii) paricalcitol (2 µg/day) combined with dietary sodium restriction (target: 50 mmol Na+/day), (iii) placebo combined with a liberal sodium diet and (iv) placebo combined with dietary sodium restriction. Data are collected at the end of each study period. The primary outcome is 24-h urinary albumin excretion. Secondary study outcomes are blood pressure, renal function (estimated glomerular filtration rate), plasma renin activity and, in a sub-population (N = 9), renal haemodynamics (measured glomerular filtration rate and effective renal plasma flow). A sample size of 50 patients provides 90% power to detect a 23% reduction in albuminuria, assuming a 25% dropout rate. Further reduction of residual albuminuria by combination of VDRA treatment and sodium restriction during single-agent RAAS-blockade will justify long-term studies on cardiorenal outcomes and safety. [ABSTRACT FROM AUTHOR]

Acupuncture is often used for primary dysmenorrhea. To assess the efficacy of a single point of acupuncture in the management of primary dysmenorrhea compared with sham acupuncture and no acupuncture. Patients with primary dysmenorrhea were randomly assigned to acupoint group ( n = 50), unrelated acupoint group ( n = 50), nonacupoint group ( n = 46), or no acupuncture group ( n = 48). Acupuncture and sham acupuncture were administered once-daily for 3 days with electro-acupuncture at Sanyinjiao (SP6) that was specifically designed to treat primary dysmenorrhea, or an unrelated acupoint (Xuanzhong, GB39), or nonacupoint location. The primary outcome was pain intensity as measured by a 100-mm visual analog scale (VAS) at baseline; 5, 10, 30, and 60 minutes following the start of the first intervention. Cox retrospective symptom scale (RSS), verbal rating scale (VRS), pain total time, and proportion of participants using analgesics were also recorded during three menstrual cycles. The primary comparison of VAS scores demonstrated that patients receiving acupuncture (−15.56 mm, 95% CI −22.16 to −8.95, P < 0.001), unrelated acupoint (−18.14 mm, 95% CI −24.81 to −11.47, P < 0.001), and nonacupoint (−10.96 mm, 95% CI −17.62 to −4.30, P = 0.001) treatment presented significant improvements compared with no acupuncture group. There were no significant differences among the four groups with respect to secondary outcomes. Acupuncture was better than no acupuncture for relieving the pain of dysmenorrhea following a single point of acupuncture, but no differences were detected between acupoint acupuncture and unrelated acupoint acupuncture, acupoint acupuncture and nonacupoint acupuncture. [ABSTRACT FROM AUTHOR]