Search

Background and Hypothesis Based on a childhood intervention from ages 3 to 5 years that included additional fish consumption and which resulted in reduced schizotypal personality at age 23, we had previously hypothesized that omega-3 could reduce schizotypy. The current study tests the hypothesis that omega-3 supplementation reduces schizotypy in children. Study Design In this intention-to-treat, randomized, single-blind, stratified, factorial trial, a community sample of 290 children aged 11–12 years were randomized into Omega-3 Only, Cognitive Behavioral Therapy (CBT) Only, Omega-3 + CBT, and Control groups. Schizotypy was assessed using the SPQ-C (Schizotypal Personality Questionnaire for Children) at 0 months (baseline), 3 months (end of treatment), 6 months (3 months post-treatment), and 12 months (9 months post-treatment). Study Results A significant group × time interaction (P  = .013) indicated that, compared with Controls, total schizotypy scores were reduced in both Omega-3 Only and Omega-3 + CBT groups immediately post-treatment (d  = 0.56 and 0.47, respectively), and also 3 months after supplementation terminated (d  = 0.49, d  = 0.70). Stronger findings were observed for the interpersonal schizotypy factor, with both omega-3 groups showing reductions 9 months post-treatment compared with the CBT Only group. Schizotypy reductions were significantly stronger for those with higher dietary intake of omega-3 at intake. Sensitivity analyses confirmed findings. Conclusions Results are unique in the field and suggest that omega-3 can help reduce schizotypal personality in community-residing children. From an epidemiological standpoint, if replicated and extended, these findings could have implications for early prevention of more significant schizotypal features developing later in adolescence. Clinical Trial Registration "Healthy Brains & Behavior: Understanding and Treating Youth Aggression (HBB)." ClinicalTrials.gov Identifier: NCT00842439 , https://clinicaltrials.gov/ct2/show/NCT00842439. [ABSTRACT FROM AUTHOR]

Background and Aims In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. Methods The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. Results The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P -values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (P interaction =.03; adjusted P interaction =.33) and diabetics (P interaction =.01; adjusted P interaction =.06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. Conclusions This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients. [ABSTRACT FROM AUTHOR]

Aims Although metformin is widely used for treatment of type 2 diabetes (T2D), its glucose-lowering mechanism remains unclear. Using the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) antagonist exendin(9-39)NH2, we tested the hypothesis that postprandial GLP-1-mediated effects contribute to the glucose-lowering potential of metformin in T2D. Methods In a randomized, placebo-controlled, double-blind, crossover study, 15 individuals with T2D (median HbA1c 50 mmol/mol [6.7%], body mass index 30.1 kg/m2, age 71 years) underwent, in randomized order, 14 days of metformin and placebo treatment, respectively. Each treatment period was preceded by 14 days without any glucose-lowering medicine and concluded by two 4 h mixed meal tests performed in randomized order and separated by >24 h with either continuous intravenous exendin(9-39)NH2 or saline infusion. Results Compared to placebo, metformin treatment lowered fasting plasma glucose (mean of differences [MD] 1.4 mmol/L × min [95% CI 0.8-2.0]) as well as postprandial plasma glucose excursions during both saline infusion (MD 186 mmol/L × min [95% CI 64-307]) and exendin(9-39)NH2 infusion (MD 268 mmol/L × min [95% CI 108-427]). The metformin-induced improvement in postprandial glucose tolerance was unaffected by GLP-1R antagonization (MD 82 mmol/L × min [95% CI −6564-170]). Metformin treatment increased fasting plasma GLP-1 (MD 1.7 pmol/L × min [95% CI 0.39-2.9]) but did not affect postprandial GLP-1 responses (MD 820 pmol/L × min [95% CI −1750-111]). Conclusions Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin's beneficial effect on fasting plasma glucose in T2D. Trial registration: Clinicaltrials.gov NCT03246451 [ABSTRACT FROM AUTHOR]

Background: Vaginal laxity (VL) is a complaint of excessive vaginal looseness with a prevalence ranging from 24% to 38% across studies. Aim: The study sought to compare the effect of radiofrequency (RF) and pelvic floor muscle training (PFMT) on the treatment of women with VL. Methods: From February 2020 to December 2021, a prospective, parallel, noninferiority, randomized clinical trial was carried out in women ≥18 years of age and complaining of VL in a tertiary hospital. Two groups (RF and PFMT) were evaluated at the beginning of the study and 30 days and 6 months postintervention. A total of 42 participants per arm was sufficient to demonstrate a difference in sexual function on the Female Sexual Function Index at 90% power, 1-sided type 1 error of 0.025 with a noninferiority margin of 4 on the FSFI total score. Analysis was intention-to-treat and per-protocol based. Outcomes: The primary endpoint was the change of FSFI score after treatment, and the secondary outcomes were improvement in symptoms of VL and changes in questionnaire scores of sexual distress, vaginal symptoms, and urinary incontinence, in the quantification of pelvic organ prolapse, and pelvic floor muscle (PFM) contraction. Results: Of 167 participants recruited, 87 were included (RF: n = 42; PFMT: n = 45). All questionnaires improved (P < .05) their total scores and subscales in both groups and during the follow-ups. After 30 days of treatment, RF was noninferior to PFMT to improving FSFI total score (mean difference −0.08 [95% confidence interval, −2.58 to 2.42]) in the per-protocol analysis (mean difference −0.46 [95% confidence interval, −2.92 to 1.99]) and in the intention-to-treat analysis; however, this result was not maintained after 6 months of treatment. PFM contraction improved significantly in both groups (RF: P = .006, 30 days; P = .049, 6 months; PFMT: P < .001, 30 days and 6 months), with better results in the PFMT group. Clinical Implications: Sexual, vaginal, and urinary symptoms were improved after 30 days and 6 months of treatment with RF and PFMT; however, better results were observed in the PFMT group after 6 months. Strengths & Limitations: The present randomized clinical trial used several validated questionnaires evaluating quality of life, sexual function and urinary symptoms, in addition to assessing PFM contraction and classifying the quantification of pelvic organ prolapse aiming at anatomical changes in two follow-up periods. The limitations were the lack of a sham-controlled group (third arm) and the difficulty of blinding researchers to assess treatments due to the COVID-19 pandemic. Conclusion: After 30 days and 6 months of treatment, sexual, vaginal, and urinary symptoms improved with RF and PFMT; however, better results were observed in the PFMT group after 6 months. RF was noninferior to PFMT in improving FSFI total score after 30 days; however, this result was not maintained after 6 months of treatment. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does the Mind/Body Program for Infertility (MBPI) perform better, due to certain distinctive elements, than a partly matched support group in improving the wellbeing and medically assisted reproduction (MAR) outcomes of women with elevated distress levels in a clinical setting? SUMMARY ANSWER While robust enhancements occurred in the wellbeing overall, the cognitive behavioural and formalized stress management elements of the MBPI allowed a significantly stronger improvement in trait anxiety, but not in other mental health and MAR outcomes, compared with a support group. WHAT IS KNOWN ALREADY Mind-body psychological programmes adjacent to MAR have been found to improve women's mental states and possibly increase chances of pregnancy. However, not enough is known about the programme's effectiveness among patients with elevated distress levels in routine clinical settings, nor is it clear which of its particular ingredients are specifically effective. STUDY DESIGN, SIZE, DURATION A pre-post design, single-centre, randomized controlled trial was performed between December 2019 and October 2022 (start and end of recruitment, respectively). The sample size (n   =   168) was calculated to detect superiority of the MBPI in improving fertility-related quality of life. Randomization was computer-based, with random numbers concealing identities of patients until after allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS The trial was conducted at a large university teaching hospital. A total of 168 patients were randomly assigned to the mind-body (MBPI) group (n   =   84) and the fertility support (FS) control group (n   =   84). Patients received a 10-week, 135-min/week group intervention, with the FS group following the same format as the MBPI group, but with a less restricted and systematic content, and without the presumed effective factors. The number of patients analysed was n   =   74 (MBPI) and n   =   68 (FS) for post-intervention psychological outcomes, and n   =   54 (MBPI) and n   =   56 (FS) for pregnancy outcomes at a 30-month follow-up. MAIN RESULTS AND THE ROLE OF CHANCE Significant improvements occurred in both groups in all psychological domains (adjusted P  <   0.001), except for treatment-related quality of life. Linear mixed-model regression analysis did not reveal significantly greater pre-post improvements in the MBPI group than in the FS group in fertility-related quality of life (difference in differences (DD) = 4.11 [0.42, 7.80], d  =   0.32, adjusted P  =   0.124), treatment-related quality of life (DD = −3.08 [−7.72, 1.55], d  =   −0.20, adjusted P  =   0.582), infertility-specific stress (DD = −2.54 [−4.68, 0.41], d  =   −0.36, adjusted P  =   0.105), depression (DD = −1.16 [3.61, 1.29], d  =   −0.13, adjusted P  =   0.708), and general stress (DD = −0.62 [−1.91, 0.68], d  =   −0.13, adjusted P  =   0.708), but it did show a significantly larger improvement in trait anxiety (DD = −3.60 [−6.16, −1.04], d  =   −0.32, adjusted P  =   0.042). Logistic regression showed no group effect on MAR pregnancies, spontaneous pregnancies, or live births. LIMITATIONS, REASONS FOR CAUTION The follow-up only covered MAR-related medical outcomes and no psychological variables, and their rates were not equal in the two groups. Biological factors other than age, aetiology, and duration of infertility may have confounded the study results. Loss to follow-up was between 5% and 10%, which may have led to some bias. WIDER IMPLICATIONS OF THE FINDINGS The psychologically and medically heterogeneous sample, the normal clinical setting and the low attrition rate all raise the external validity and generalizability of our study. The MBPI works not only in controlled conditions, but also in routine MAR practice, where it can be introduced as a cost-effective, low-intensity psychological intervention, within the framework of stepped care. More studies are needed to further identify its active ingredients. STUDY FUNDING/COMPETING INTEREST(S) The authors received no financial support for the research, authorship, and/or publication of this article. The authors have no conflict of interest to disclose. TRIAL REGISTRATION NUMBER ClinicalTrials.gov NCT04151485. TRIAL REGISTRATION DATE 5 November 2019. DATE OF FIRST PATIENT'S ENROLMENT 15 December 2019. [ABSTRACT FROM AUTHOR]

Background The increasing incidence of chronic kidney disease (CKD) is straining the capacity of outpatient clinics. Remote healthcare delivery might improve CKD follow-up compared with conventional face-to-face follow-up. Patient-reported outcomes (PROs) are used to empower remote follow-up and patient engagement. The consequences of shifting from face-to-face follow-up to remote outpatient follow-up on kidney function, health resource utilisation and quality of life remain unknown. Methods We conducted a multicentre pragmatic non-inferiority trial at three outpatient clinics in the Central Denmark Region. A total of 152 incident outpatients with CKD were randomised (1:1:1) to either PRO-based, PRO-telephone follow-up or standard of care (SoC). The primary outcome was the annual change in kidney function measured by the slope of the estimated glomerular filtration rate (eGFR). The non-inferiority margin was an eGFR of 2.85 ml/min/1.73 m2/year. Mean differences were estimated using intention-to-treat (ITT), per protocol and random coefficient models. Results Mean eGFR slope differences between PRO-based and SoC were −0.97 ml/min/1.73 m2/year [95% confidence interval (CI) −3.00–1.07] and −1.06 ml/min/1.73 m2/year (95% CI −3.02–0.89) between PRO-telephone and SoC. Non-inferiority was only established in the per-protocol analysis due to CIs exceeding the margin in the ITT group. Both intervention groups had fewer outpatient visits: −4.95 (95% CI −5.82 to −4.08) for the PRO-based group and −5.21 (95% CI −5.95 to −4.46) for the PRO-telephone group. We found no significant differences in quality of life, illness perception or satisfaction. Conclusion Differences in the eGFR slope between groups were non-significant and results on non-inferiority were inconclusive. Thus, transitioning to remote PRO-based follow-up requires close monitoring of kidney function. Reducing patients' attendance in the outpatient clinic was possible without decreasing either quality of life or illness perception. ClinicalTrials.gov identifier: NCT03847766 [ABSTRACT FROM AUTHOR]

Background The popularity of temporary abstinence challenges (TACs) concerning alcohol consumption is increasing. Support is found to be essential for participants to help them get through a challenge. This study aimed to evaluate the additional effect of a self-help guide, based on health behaviour theories and behaviour change techniques, on (i) successful completion of a TAC and (ii) changes in drinking refusal self-efficacy (DRSE), behavioural automaticity, craving, and alcohol consumption. Methods A randomized controlled trial was performed (OSF registries: OSF.IO/B95VU). NoThanks participants received a questionnaire before the TAC (T0) and 8 months after the TAC (T1). Out of a subgroup of 1308 respondents who were interested in additional support, 652 were randomly assigned to receive the guide (experimental group), and 656 did not receive any additional support (control group). Logistic regressions and (generalized) linear mixed model analyses were used. Results After 8 months, all participants showed a significant decrease in behavioural automaticity, craving, and alcohol consumption, irrespective of group assignment. No significant changes were observed in the DRSE. This degree of change over time in behavioural automaticity, craving, and alcohol consumption did not differ between the experimental and control group. Sensitivity analyses with participants in the experimental group, who differed in exposure to the guide, did not show differences either. Conclusion The self-help guide, and how it was designed, added no value to the TAC. Future research should focus on more bottom-up, customized support and explore what (different subgroups of) participants think they need as extra support during a TAC. [ABSTRACT FROM AUTHOR]

Background Clinical trials of treatments for serious infections commonly use the primary endpoint of all-cause mortality. However, many trial participants survive their infection and this endpoint may not truly reflect important benefits and risks of therapy. The win ratio uses a hierarchical composite endpoint that can incorporate and prioritize outcome measures by relative clinical importance. Methods The win ratio methodology was applied post hoc to outcomes observed in the MERINO trial, which compared piperacillin-tazobactam with meropenem. We quantified the win ratio with a primary hierarchical composite endpoint, including all-cause mortality, microbiological relapse, and secondary infection. A win ratio of 1 would correspond to no difference between the 2 antibiotics, while a ratio <1 favors meropenem. Further analyses were performed to calculate the win odds and to introduce a continuous outcome variable in order to reduce ties. Results With the hierarchy of all-cause mortality, microbiological relapse, and secondary infection, the win ratio estimate was 0.40 (95% confidence interval [CI],.22–.71]; P =.002), favoring meropenem over piperacillin-tazobactam. However, 73.4% of the pairs were tied due to the small proportion of events. The win odds, a modification of the win ratio accounting for ties, was 0.79 (95% CI,.68–.92). The addition of length of stay to the primary composite greatly minimized the number of ties (4.6%) with a win ratio estimate of 0.77 (95% CI,.60–.99; P =.04). Conclusions The application of the win ratio methodology to the MERINO trial data illustrates its utility and feasibility for use in antimicrobial trials. [ABSTRACT FROM AUTHOR]

Objective To evaluate the efficacy and costs of a brief, group-delivered parenting intervention for families of children with eczema. Methods A randomized controlled trial design was used. Families attending the Queensland Children's Hospital and from the community (n  = 257) were assessed for eligibility (child 2–10 years, diagnosed with eczema, prescribed topical corticosteroids). Families who consented to participate (N  =   59) were assessed at baseline for clinician-rated eczema severity, parent-reported eczema symptom severity, and electronically-monitored topical corticosteroid adherence (primary outcomes); and parenting behavior, parents' self-efficacy and task performance when managing eczema, eczema-related child behavior problems, and child and parent quality of life (secondary outcomes). Families were randomized (1:1, unblinded) to intervention (n  =   31) or care-as-usual (n  =   28). The intervention comprised two, 2-hr Healthy Living Triple P group sessions (face-to-face/online) and 28 intervention families attended one/both sessions. All families were offered standardized eczema education. Families were reassessed at 4-weeks post-intervention and 6-month follow-up, with clinician-raters blinded to condition. Costs of intervention delivery were estimated. Results Multilevel modeling across assessment timepoints showed significant intervention effects for ineffective parenting (d  = .60), self-efficacy (d  = .74), task performance (d  = .81), and confidence with managing eczema-related child behavior (d  = .63), but not disease/symptom severity, treatment adherence or quality of life. Mean cost per participating family with parenting behavior (clinically) improved was $159. Conclusions Healthy Living Triple P is effective in reducing ineffective parenting practices and improving parents' self-efficacy and task performance when managing children's eczema and eczema-related behavior difficulties. There was no effect on disease/symptom severity, treatment adherence, or quality of life. Clinical Trial Registration ACTRN12618001332213 [ABSTRACT FROM AUTHOR]

Background Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. Methods The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. Results Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI},.86–1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI,.28–1.30]). Statistical power to assess effect modification in other subgroups was limited. Conclusions In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259. [ABSTRACT FROM AUTHOR]

This document highlights the challenges of diagnosing and treating unexplained infertility in heterosexual couples, emphasizing the need for advancements in diagnostic tests and individualized decision-making. The document also mentions a study that found intrauterine insemination with ovarian stimulation (IUI-OS) to be more effective in achieving live births compared to expectant management. It emphasizes the importance of accurately assessing coital frequency and timing, considering lifestyle factors, and developing better diagnostic tools. Further research is needed to improve treatment options and prognostic models for unexplained infertility. [Extracted from the article]

Background NULevel was a randomized control trial to evaluate a technology-assisted weight loss maintenance (WLM) program in the UK. The program included: (a) a face-to-face goal-setting session; (b) an internet platform, a pedometer, and wirelessly connected scales to monitor and report diet, physical activity, and weight, and; (c) regular automated feedback delivered by mobile phone, tailored to participants' progress. Components were designed to target psychological processes linked to weight-related behavior. Though intervention participants showed increased physical activity, there was no difference in WLM between the intervention and control groups after 12 months (Sniehotta FF, Evans EH, Sainsbury K, et al. Behavioural intervention for weight loss maintenance versus standard weight advice in adults with obesity: A randomized controlled trial in the UK (NULevel Trial). PLoS Med. 2019; 16(5):e1002793. doi:10.1371/journal.pmed.1002793). It is unclear whether the program failed to alter targeted psychological processes, or whether changes in these processes failed to influence WLM. Purpose We evaluate whether the program influenced 16 prespecified psychological processes (e.g. self-efficacy and automaticity toward diet and physical activity), and whether these processes (at 6 months) were associated with successful WLM (at 12 months). Methods 288 adults who had previously lost weight were randomized to the intervention or control groups. The control group received wireless scales and standard advice via newsletters. Assessments occurred in person at 0, 6, and 12 months. Results The intervention significantly altered 10 of the 16 psychological processes, compared with the control group. However, few processes were associated with WLM, leading to no significant indirect effects of the intervention via the processes on WLM. Conclusions Changes in targeted processes were insufficient to support WLM. Future efforts may more closely examine the sequence of effects between processes, behavior, and WLM. [ABSTRACT FROM AUTHOR]

Objective Knee osteoarthritis (KOA) is a common musculoskeletal problem worldwide and its key symptom is pain. Guidelines recommend incorporating comorbidity-specific therapies into patient-centered care. Patients diagnosed with KOA frequently have insomnia, which is associated with higher-pain severity. For this reason, this study protocol outlines the methodology of a randomized controlled trial (RCT) investigating the effectiveness of cognitive behavioral therapy for insomnia (CBTi) combined with best-practice KOA care (BPC) compared to best-practice KOA care and lifestyle education. Methods A 2-arm RCT in patients with KOA and insomnia is conducted, in which a total of 128 patients are randomly allocated to an intervention or control group. The experimental intervention consists of 12 sessions of physical therapist–led BPC with an additional 6 sessions of CBTi. The control intervention also receives BPC, which is supplemented with 6 general lifestyle information sessions. The primary outcome is the between-group difference in change in pain severity at 6 months after intervention. Secondary outcomes are pain-related outcomes, sleep-related outcomes, symptoms of anxiety and depression, level of physical activity and function, perceived global improvement, biomarkers of inflammation, and health-related quality of life. Assessments are conducted at baseline, immediately after intervention, and 3, 6, and 12 months after intervention. Furthermore, a cost-utility analysis for the proposed intervention will be performed alongside the RCT. Impact This is the first RCT investigating the clinical and cost-effectiveness of a physical therapist–led intervention integrating CBTi into BPC in patients with KOA and insomnia. The results of this trial will add to the growing body of evidence on the effectiveness of individualized and comorbidity-specific KOA care, which can inform clinical decision-making and assist policymakers and other relevant stakeholders in optimizing the care pathway for patients with KOA. [ABSTRACT FROM AUTHOR]

Background After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. Methods We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS–free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. Results Of 460 trial participants, 453 from Brazil, Côte d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29–43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38–239) cells/mm³, and median HIV RNA, 5.5 (IQR, 5.0–5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval.35–1.10). Factors associated with TB-IRIS were: CD4 ≤ 100 cells/μL, HIV RNA ≥500 000 copies/mL, and extrapulmonary/disseminated TB. Conclusions We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS. [ABSTRACT FROM AUTHOR]

Objectives To assess eligibility criteria that either explicitly or implicitly exclude older patients from randomized controlled trials (RCTs) in RA. Methods Our analysis included RCTs of pharmacological interventions registered with ClinicalTrials.gov and started between 2013 and 2022. Co-primary outcomes were proportions of trials with an upper age limit and the eligibility criteria indirectly increasing risk of the exclusion of older adults. Results A total of 143/290 (49%) trials had an upper age limit of 85 years or less. Multivariable analysis showed that the odds of an upper age limit were significantly lower in trials performed in the USA [adjusted odds ratio (aOR), 0.34; CI, 0.12–0.99; P  = 0.04] and intercontinental trials (aOR, 0.4; CI, 0.18–0.87; P  = 0.02). In total, 154/290 (53%) trials had at least one eligibility criterion implicitly excluding older adults. These included specific comorbidities (n  = 114; 39%), compliance concerns (n  = 67; 23%), and broad and vague exclusion criteria (n  = 57; 20%); however, we found no significant associations between these criteria and trial characteristics. Overall, 217 (75%) trials either explicitly or implicitly excluded older patients; we also noted a trend towards increasing proportion of these trials over time. Only one trial (0.3%) enrolled solely patients aged 65 and older. Conclusion Older adults are commonly excluded from RCTs in RA based on both age limits and other eligibility criteria. This seriously limits the evidence base for the treatment of older patients in clinical practice. Given the growing prevalence of RA in older adults, relevant RCTs should be more inclusive to them. [ABSTRACT FROM AUTHOR]

Background Emotional symptoms are recognized as a key feature in individuals with major depressive disorder. Previously, emotional blunting has been described both as a side effect of antidepressant treatment and as a symptom of depression. Little is known about the change of emotional blunting during antidepressant treatment. Methods The PREDDICT trial is a randomized, placebo-controlled, 6-week trial on the augmentation of vortioxetine with the anti-inflammatory agent celecoxib or placebo. Presently we report on exploratory secondary outcomes of changes in emotional blunting in depression assessed with the Oxford Depression Questionnaire (ODQ) total score and subscores from baseline to 8-week, 3-month, and 6-month follow-up assessments. Results In the whole group, there was a significant improvement in the ODQ total score and all subscores after 8 weeks. After stratification of participants into the treatment groups, the ODQ total score as well as subscores related to emotional blunting as a symptom of depression (reduction in positive emotions, not caring) improved between baseline and all follow-up time points in both treatment groups. Changes in subscores considered as a side effect of antidepressants (general reduction in emotions, emotional detachment) were inconclusive in both treatment groups. Overall, the placebo-augmented group showed slightly better results in changes of emotional blunting scores than the celecoxib group as did those with elevated inflammation at screening, regardless of treatment group. Conclusions This analysis suggests favorable effects of vortioxetine on emotional blunting in both short- and long-term course. The beneficial impact of vortioxetine on emotional blunting was weaker in celecoxib-augmented patients compared with placebo, possibly due to pharmacokinetic interactions. Clinical Trials Registration: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p. [ABSTRACT FROM AUTHOR]

Background Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. Methods We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile , and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. Results Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P =.195) and rCDI (3.3% vs 4.0%; P >.99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. Conclusions In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. Clinical Trials Registration www.clinicaltrials.gov (NCT02692651). [ABSTRACT FROM AUTHOR]

Background The BCG (Bacillus Calmette-Guérin) vaccine can induce nonspecific protection against unrelated infections. We aimed to test the effect of BCG on absenteeism and health of Danish health care workers (HCWs) during the coronavirus disease 2019 (COVID-19) pandemic. Methods A single-blinded randomized controlled trial included 1221 HCWs from 9 Danish hospitals. Participants were randomized 1:1 to standard dose BCG or placebo. Primary outcome was days of unplanned absenteeism. Main secondary outcomes were incidence of COVID-19, all-cause hospitalization, and infectious disease episodes. Results There was no significant effect of BCG on unplanned absenteeism. Mean number of days absent per 1000 workdays was 20 in the BCG group and 17 in the placebo group (risk ratio, 1.23; 95% credibility interval, 0.98–1.53). BCG had no effect on incidence of COVID-19 or all-cause hospitalization overall. In secondary analyses BCG revaccination was associated with higher COVID-19 incidence (hazard ratio [HR], 2.47; 95% confidence interval [CI], 1.07–5.71), but also reduced risk of hospitalization (HR, 0.28; 95% CI,.09–.86). The incidence of infectious disease episodes was similar between randomization groups (HR, 1.09; 95% CI,.96–1.24). Conclusions In this relatively healthy cohort of HCWs, there was no overall effect of BCG on any of the study outcomes. Clinical Trials Registration NCT0437329 and EU Clinical Trials Register (EudraCT number 2020-001888-90). [ABSTRACT FROM AUTHOR]

Background: Female sexual interest/arousal disorder (FSIAD) is the most common female sexual disorder with adverse effects on women's health and interpersonal relationships. Aim: This survey evaluated the effects of sexual counseling based on the "good enough sex" (GES) model on the sexual health variables of women with FSIAD. Methods: A randomized clinical trial with a 1:1 allocation ratio was conducted among 80 women with FSIAD in Iran in 2021. Eligible participants were randomly assigned to group A (women) and group B (couples). Women attended 4 weekly online group sexual counseling sessions based on the GES model, each lasting 120 minutes. In group B, husbands participated in sessions 2 and 3. Outcomes: Women's sexual health parameters—including sexual desire, sexual satisfaction, sexual function, sexual distress, sexual communication, frequency of sexual intercourse, and dysfunctional beliefs—were evaluated before and 3 months after counseling. The significance threshold considered P < .007 due to Bonferroni correction. Results: After the intervention, all sexual parameters except sexual dysfunctional beliefs showed significant improvement (P < .001) in both groups. During the follow-up period, the average scores for all sexual variables were slightly higher in group B vs group A. The between-group difference was significant only for frequency of sexual intercourse (P < .01). Clinical Implications: This study reaffirms the impact of the GES model as biopsychosocial therapy in managing female sexual problems. Considering men's reluctance to accompany their wives to sex clinics, counseling for women alone can play a significant role in solving sexual problems, especially in the case of FSIAD. Online sexual consultation offers cost and time savings, provides a secure space for discussing sensitive topics, and facilitates group program coordination. It ensures universal access to counseling, thereby addressing gender incompatibility issues. It is a powerful, interactive, and acceptable alternative to in-person visits, providing convenience and confidentiality for clients seeking sexual health support. Strengths and Limitations: The following were among the survey strengths: conducting a randomized controlled trial on women with FSIAD by applying an appropriate model and scales, involving spouses, and evaluating online group sexual counseling. However, the results of this study may not be generalizable to women without partners. Conclusion: The GES model, emphasizing intimacy and sexual dialogue, reduces unrealistic sexual expectations and improves women's sexual desire and overall health. Our results showed that instead of insisting on the physical presence of husbands in counseling sessions, clinicians should emphasize their emotional support and companionship during the treatment process. [ABSTRACT FROM AUTHOR]

Aims When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation. Methods and results ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation—force-sensing RF or cryoballoon (CB)—to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (−0.9%) than thermal ablation (−12%, posterior probability > 0.999)—primarily driven by the RF sub-cohort (−19.5%) vs. CB sub-cohort (−3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location. Conclusion In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing—thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue. [ABSTRACT FROM AUTHOR]

Background Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. Material and Methods In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. Results The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. Conclusion As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time. [ABSTRACT FROM AUTHOR]

Background Amphotericin B is the gold standard treatment for severe mycoses. A new orally delivered, less-toxic formulation of amphotericin has been developed. Methods In our randomized clinical trial, we tested oral lipid nanocrystal (LNC) amphotericin B (MAT2203, Matinas Biopharma) vs intravenous (IV) amphotericin for human immunodeficiency virus–associated cryptococcal meningitis in 4 sequential cohorts. Two pilot cohorts assessed safety and tolerability (n = 10 each), and 2 cohorts assessed efficacy with/without 2 IV loading doses (n = 40 each). The experimental arm received 1.8 g/d oral LNC amphotericin through 2 weeks with 100 mg/kg/d flucytosine, then 1.2 g/d LNC amphotericin through 6 weeks. The randomized control arm (n = 41) received 7 days of IV amphotericin with flucytosine, then 7 days of fluconazole 1200 mg/d. The primary end point was cerebrospinal fluid (CSF) early fungicidal activity (EFA). Results We randomized 80 participants to oral LNC amphotericin + flucytosine with (n = 40) and without (n = 40) 2 IV loading doses and 41 control participants to IV amphotericin + flucytosine. Mean EFA was 0.40 log10 colony-forming units (CFU)/mL/d for all-oral LNC amphotericin, 0.42 log10   Cryptococcus CFU/mL/d for oral LNC amphotericin with IV loading doses, and 0.46 log10 CFU/mL/d for IV amphotericin controls. LNC amphotericin groups achieved 2-week CSF sterility in 63% (44 of 70) vs 68% (23 of 34) of controls. The 18-week survival was 85% (34 of 40) with all-oral LNC amphotericin, 90% (36 of 40) with oral LNC amphotericin given IV loading doses, and 85% (35 of 41) with IV amphotericin. Grade 3–4 laboratory adverse events occurred less frequently in LNC amphotericin groups (41%) than the IV amphotericin group (61%, P =.05), particularly for anemia (21% vs 44%; P =.01) and potassium (5% vs 17%; P =.04). Conclusions This new oral amphotericin B LNC formulation appears promising for cryptococcal meningitis with antifungal activity, similar survival, and less toxicity than IV amphotericin. Clinical Trials Registration NCT04031833. [ABSTRACT FROM AUTHOR]

Aims Modern clinical management of patients with an implantable cardioverter defibrillator (ICD) largely consists of remote device monitoring, although a subset is at risk of mental health issues post-implantation. We compared a 12-month web-based intervention consisting of goal setting, monitoring of patients' mental health—with a psychological intervention if needed—psychoeducational support from a nurse, and an online patient forum, with usual care on participants' device acceptance 12 months after implantation. Methods and results This national, multi-site, two-arm, non-blinded, randomized, controlled, superiority trial enrolled 478 first-time ICD recipients from all 6 implantation centres in Denmark. The primary endpoint was patient device acceptance measured by the Florida Patient Acceptance Survey (FPAS; general score range = 0–100, with higher scores indicating higher device acceptance) 12 months after implantation. Secondary endpoints included symptoms of depression and anxiety. The primary endpoint of device acceptance was not different between groups at 12 months [ B = −2.67, 95% confidence interval (CI) (−5.62, 0.29), P = 0.08]. Furthermore, the secondary endpoint analyses showed no significant treatment effect on either depressive [ B = −0.49, 95% CI (−1.19; 0.21), P = 0.17] or anxiety symptoms [ B = −0.39, 95% CI (−0.96; 0.18), P = 0.18]. Conclusion The web-based intervention as supplement to usual care did not improve patient device acceptance nor symptoms of anxiety and depression compared with usual care. This specific web-based intervention thus cannot be recommended as a standardized intervention in ICD patients. [ABSTRACT FROM AUTHOR]

Background: This phase III, randomized, double-blind, placebo-controlled, parallel-group study assessed the efficacy and safety of tanezumab in subjects with cancer pain predominantly due to bone metastasis receiving background opioid therapy. Methods: Subjects were randomized (stratified by (1) tumor aggressiveness and (2) presence/absence of concomitant anticancer treatment) to placebo or tanezumab 20 mg. Treatment was administered by subcutaneous injection every 8 weeks for 24 weeks (3 doses) followed by a 24-week safety follow-up period. The primary outcome was change in daily average pain in the index bone metastasis cancer pain site (from 0 = no pain to 10 = worst possible pain) from baseline to week 8. Results: LS mean (SE) change in pain at week 8 was −1.25 (0.35) for placebo (n = 73) and –2.03 (0.35) for tanezumab 20 mg (n = 72). LS mean (SE) [95% CI] difference from placebo was –0.78 (0.37) [–1.52, –0.04]; P =.0381 with α = 0.0478. The number of subjects with a treatment-emergent adverse event during the treatment period was 50 (68.5%) for placebo and 53 (73.6%) for tanezumab 20 mg. The number of subjects with a prespecified joint safety event was 0 for placebo and 2 (2.8%) for tanezumab 20 mg (pathologic fracture; n = 2). Conclusion: Tanezumab 20 mg met the primary efficacy endpoint at week 8. Conclusions on longer-term efficacy are limited since the study was not designed to evaluate the durability of the effect beyond 8 weeks. Safety findings were consistent with adverse events expected in subjects with cancer pain due to bone metastasis and the known safety profile of tanezumab. Clinicaltrials.gov identifier: NCT02609828. Bone metastasis is a common cause of cancer-related pain. This article reports on the potential of anti-nerve growth factor therapies, such as tanezumab, to reduce pain caused by bone metastases. [ABSTRACT FROM AUTHOR]

Background and Objectives Outdoor falls can negatively affect the independence and well-being of community-dwelling older adults. Although there is some overlap, there are also differences in risk factors for indoor and outdoor falls. There are no existing community-based fall prevention programs that specifically target outdoor fall prevention. To fill this gap, the Stroll Safe program was developed. Research Design and Methods A cluster-randomized controlled trial design was used with randomization at the site level. Participants (N = 86) were aged 60 and older, with a history of an outdoor fall or who had a fear of falling outdoors. Eight naturally occurring retirement community program sites were randomly assigned to the treatment or wait list control group. Outcome measures included the Outdoor Falls Questionnaire, the Falls Behavioral Scale for the Older Person, and the Falls Efficacy Scale-International to examine knowledge of risks, safe strategy use, protective behaviors, and fear of falling. An Analysis of Covariance (ANCOVA) was used to compare change scores between groups with covariates included for any initial differences between groups. A linear mixed model was also conducted to account for any clustering effects. Results Significant differences (p s <.05) were found between groups for knowledge of outdoor fall risks and safe strategy use. Effect sizes were large (Cohen's d = 1.2–1.9). Results were retained at 6-week follow-up. Discussion and Implications Stroll Safe is effective in improving knowledge of outdoor fall risks and increasing safe strategy use for community mobility. Stroll Safe fills a gap in outdoor fall prevention programs. Clinical Trials Registration Number: NCT03624777 [ABSTRACT FROM AUTHOR]

Background and Aims Patients hospitalized for acute heart failure (AHF) continue to be discharged on an inadequate number of guideline-directed medical therapies (GDMT) despite evidence that inpatient initiation is beneficial. This study aimed to examine whether a tailored electronic health record (EHR) alert increased rates of GDMT prescription at discharge in eligible patients hospitalized for AHF. Methods Pragmatic trial of messaging to providers about treatment of acute heart failure (PROMPT-AHF) was a pragmatic, multicenter, EHR-based, and randomized clinical trial. Patients were automatically enrolled 48 h after admission if they met pre-specified criteria for an AHF hospitalization. Providers of patients in the intervention arm received an alert during order entry with relevant patient characteristics along with individualized GDMT recommendations with links to an order set. The primary outcome was an increase in the number of GDMT prescriptions at discharge. Results Thousand and twelve patients were enrolled between May 2021 and November 2022. The median age was 74 years; 26% were female, and 24% were Black. At the time of the alert, 85% of patients were on β-blockers, 55% on angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, 20% on mineralocorticoid receptor antagonist (MRA) and 17% on sodium-glucose cotransporter 2 inhibitor. The primary outcome occurred in 34% of both the alert and no alert groups [adjusted risk ratio (RR): 0.95 (0.81, 1.12), P =.99]. Patients randomized to the alert arm were more likely to have an increase in MRA [adjusted RR: 1.54 (1.10, 2.16), P =.01]. At the time of discharge, 11.2% of patients were on all four pillars of GDMT. Conclusions A real-time, targeted, and tailored EHR-based alert system for AHF did not lead to a higher number of overall GDMT prescriptions at discharge. Further refinement and improvement of such alerts and changes to clinician incentives are needed to overcome barriers to the implementation of GDMT during hospitalizations for AHF. GDMT remains suboptimal in this setting, with only one in nine patients being discharged on a comprehensive evidence-based regimen for heart failure. [ABSTRACT FROM AUTHOR]

Background Starting combination antiretroviral therapy (cART) during primary human immunodeficiency virus type 1 (HIV-1) infection results in a smaller HIV-1 latent reservoir, reduced immune activation, and less viral diversity compared to starting cART during chronic infection. We report results of a 4-year study designed to determine whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir (DTG) monotherapy. Methods EARLY-SIMPLIFIED is a randomized, open-label, noninferiority trial. People with HIV (PWH) who started cART <180 days after a documented primary HIV-1 infection with suppressed viral load were randomized (2:1) to DTG monotherapy with 50 mg daily or continuation of cART. The primary endpoints were the proportion of PWH with viral failure at 48, 96, 144, and 192 weeks; noninferiority margin was 10%. After 96 weeks, randomization was lifted and patients were permitted to switch treatment groups as desired. Results Of 101 PWH randomized, 68 were assigned to DTG monotherapy and 33 to cART. At week 96 in the per-protocol population, 64/64 (100%) showed virological response in the DTG monotherapy group versus 30/30 (100%) in the cART group (difference, 0.00%; upper bound of 95% confidence interval 6.22%). This demonstrated noninferiority of DTG monotherapy at the prespecified level. At week 192, the study end, no virological failure occurred in either group during 13 308 and 4897 person weeks of follow-up for the DTG monotherapy (n = 80) and cART groups, respectively. Conclusions This trial suggests that early cART initiation during primary HIV infection allows sustained virological suppression after switching to DTG monotherapy. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does assisted hatching increase the cumulative live birth rate in subfertile couples with repeated implantation failure? SUMMARY ANSWER This study showed no evidence of effect for assisted hatching as an add-on in subfertile couples with repeated implantation failure. WHAT IS KNOWN ALREADY The efficacy of assisted hatching, with regard to the live birth rate has not been convincingly demonstrated in randomized trials nor meta-analyses. It is suggested though that especially poor prognosis women, e.g. women with repeated implantation failure, might benefit most from assisted hatching. STUDY DESIGN, SIZE, DURATION The study was designed as a double-blinded, multicentre randomized controlled superiority trial. In order to demonstrate a statistically significant absolute increase in live birth rate of 10% after assisted hatching, 294 participants needed to be included per treatment arm, being a total of 588 subfertile couples. Participants were included and randomized from November 2012 until November 2017, 297 were allocated to the assisted hatching arm of the study and 295 to the control arm. Block randomization in blocks of 20 participants was applied and randomization was concealed from participants, treating physicians, and laboratory staff involved in the embryo transfer procedure. Ovarian hyperstimulation, oocyte retrieval, laboratory procedures, embryo selection for transfer and cryopreservation, the transfer itself, and luteal support were performed according to local protocols and were identical in both the intervention and control arm of the study with the exception of the assisted hatching procedure which was only performed in the intervention group. The laboratory staff performing the assisted hatching procedure was not involved in the embryo transfer itself. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were eligible for inclusion in the study after having had either at least two consecutive fresh IVF or ICSI embryo transfers, including the transfer of frozen and thawed embryos originating from those fresh cycles, and which did not result in a pregnancy or as having had at least one fresh IVF or ICSI transfer and at least two frozen embryo transfers with embryos originating from that fresh cycle which did not result in a pregnancy. The study was performed at the laboratory sites of three tertiary referral hospitals and two university medical centres in the Netherlands. MAIN RESULTS AND THE ROLE OF CHANCE The cumulative live birth rate per started cycle, including the transfer of fresh and subsequent frozen/thawed embryos if applicable, resulted in 77 live births in the assisted hatching group (n = 297, 25.9%) and 68 live births in the control group (n = 295, 23.1%). This proved to be statistically not significantly different (relative risk: 1.125, 95% CI: 0.847 to 1.494, P  = 0.416). LIMITATIONS, REASONS FOR CAUTION There was a small cohort of subfertile couples that after not achieving an ongoing pregnancy, still had cryopreserved embryos in storage at the endpoint of the trial, i.e. 1 year after the last randomization. It cannot be excluded that the future transfer of these frozen/thawed embryos increases the cumulative live birth rate in either or both study arms. Next, at the start of this study, there was no international consensus on the definition of repeated implantation failure. Therefore, it cannot be excluded that assisted hatching might be effective in higher order repeated implantation failures. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrated no evidence of a statistically significant effect for assisted hatching by increasing live birth rates in subfertile couples with repeated implantation failure, i.e. the couples which, based on meta-analyses, are suggested to benefit most from assisted hatching. It is therefore suggested that assisted hatching should only be offered if information on the absence of evidence of effect is provided, at no extra costs and preferably only in the setting of a clinical trial taking cost-effectiveness into account. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER Netherlands Trial Register (NTR 3387, NL 3235, https://www.clinicaltrialregister.nl/nl/trial/26138). TRIAL REGISTRATION DATE 6 April 2012 DATE OF FIRST PATIENT'S ENROLMENT 28 November 2012 [ABSTRACT FROM AUTHOR]

Background Older patients with multimorbidity are under-represented in experimental research. Objective To explore the barriers and facilitators to general practitioner (GP) and older patient recruitment and retention in a cluster randomized controlled trial (RCT). Method This descriptive study uses qualitative and quantitative data from a cluster RCT, designed to evaluate the effectiveness of a medicines optimization intervention. The SPPiRE cluster RCT enrolled 51 general practices and 404 patients aged ≥65 years and prescribed ≥15 medicines. Quantitative data were collected from all recruited practices and 32 additional practices who were enrolled, but unable to recruit sufficient participants. Qualitative data were collected from purposive samples of intervention GPs (18/26), patients (27/208), and researcher logs and analysed thematically using inductive coding. Results Enrolment rates for practices and patients were 37% and 25%, respectively. Barriers to GP recruitment were lack of resources and to patient recruitment were difficulty understanding trial material and concern about medicines being taken away. GPs' primary motivation was perceived importance of the research question, whereas patients' primary motivation was trust in their GP. All general practices were retained. Thirty-five patients (8.6%) were lost to follow-up for primary outcomes, mainly because they had died and 45% did not return patient-reported outcome measures (PROMs). Conclusion Patient retention for the primary outcome was high, as it was collected directly from patient records. Patient completion of PROM data was poor, reflecting difficulty in understanding trial material. Recruiting older patients with multimorbidity to clinical trials is possible but requires significant resource and planning. Trial registration ISRCTN Registry ISRCTN12752680. [ABSTRACT FROM AUTHOR]

STUDY QUESTION What is the effect of a blended preconception lifestyle programme on reproductive and lifestyle outcomes of couples going through their first 12 months of IVF as compared to an attention control condition? SUMMARY ANSWER This randomized controlled trial (RCT) was stopped prematurely because of the coronavirus disease 2019 (Covid-19) pandemic but the available data did not suggest that a blended preconception lifestyle programme could meaningfully affect time to ongoing pregnancy or other reproductive and lifestyle outcomes. WHAT IS KNOWN ALREADY Increasing evidence shows associations between a healthy lifestyle and IVF success rates. Lifestyle programmes provided through a mobile phone application have yet to be evaluated by RCTs in couples undergoing IVF. STUDY DESIGN, SIZE, DURATION A multicentre RCT (1:1) was carried out. The RCT started in January 2019 and was prematurely stopped because of the Covid-19 pandemic, leading to a reduced sample size (211 couples initiating IVF) and change in primary outcome (cumulative ongoing pregnancy to time to ongoing pregnancy). PARTICIPANTS/MATERIALS, SETTING, METHODS Heterosexual couples initiating IVF in five fertility clinics were randomized between an attention control arm and an intervention arm for 12 months. The attention control arm received treatment information by mobile phone in addition to standard care. The intervention arm received the blended preconception lifestyle (PreLiFe)-programme in addition to standard care. The PreLiFe-programme included a mobile application, offering tailored advice and skills training on diet, physical activity and mindfulness, in combination with motivational interviewing over the telephone. The primary outcome was 'time to ongoing pregnancy'. Secondary reproductive outcomes included the Core Outcome Measures for Infertility Trials and IVF discontinuation. Changes in the following secondary lifestyle outcomes over 3 and 6 months were studied in both partners: diet quality, fruit intake, vegetable intake, total moderate to vigorous physical activity, sedentary behaviour, emotional distress, quality of life, BMI, and waist circumference. Finally, in the intervention arm, acceptability of the programme was evaluated and actual use of the mobile application part of the programme was tracked. Analysis was according to intention to treat. MAIN RESULTS AND THE ROLE OF CHANCE A total of 211 couples were randomized (105 control arm, 106 intervention arm). The hazard ratio of the intervention for time to ongoing pregnancy was 0.94 (95% CI 0.63 to 1.4). Little to no effect on other reproductive or lifestyle outcomes was identified. Although acceptability of the programme was good (6/10), considerable proportions of men (38%) and 9% of women did not actively use all the modules of the mobile application (diet, physical activity, or mindfulness). LIMITATIONS, REASONS FOR CAUTION The findings of this RCT should be considered exploratory, as the Covid-19 pandemic limited its power and the actual use of the mobile application was low. WIDER IMPLICATIONS OF THE FINDINGS This is the first multicentre RCT evaluating the effect of a blended preconception lifestyle programme for women and their partners undergoing IVF on both reproductive and lifestyle outcomes. This exploratory RCT highlights the need for further studies into optimal intervention characteristics and actual use of preconception lifestyle programmes, as well as RCTs evaluating effectiveness. STUDY FUNDING/COMPETING INTEREST(S) Supported by the Research foundation Flanders (Belgium) (FWO-TBM; reference: T005417N). No competing interests to declare. TRIAL REGISTRATION NUMBER ClinicalTrials.gov Identifier: NCT03790449 TRIAL REGISTRATION DATE 31 December 2018 DATE OF FIRST PATIENT'S ENROLMENT 2 January 2019 [ABSTRACT FROM AUTHOR]

Background: Low-intensity shockwave therapy for erectile dysfunction is emerging as a promising treatment option. Aim: This randomized sham-controlled crossover trial assessed the efficacy of low-intensity shockwave therapy in the treatment of erectile dysfunction. Methods: Thirty-three participants with organic erectile dysfunction were enrolled and randomized to shockwave therapy (n = 17) or sham (n = 16). The sham group was allowed to cross over to receive shockwave therapy after 1 month. Outcomes: Primary outcomes were the changes in Sexual Health Inventory for Men (SHIM) score and Erection Hardness Score at 1 month following shockwave therapy vs sham, and secondary outcomes were erectile function measurements at 1, 3, and 6 months following shockwave therapy. Results: At 1 month, mean SHIM scores were significantly increased in the shockwave therapy arm as compared with the sham arm (+3.0 vs −0.7, P = .024). Participants at 6 months posttreatment (n = 33) showed a mean increase of 5.5 points vs baseline (P < .001), with 20 (54.6%) having an increase ≥5. Of the 25 men with an initial Erection Hardness Score <3, 68% improved to a score ≥3 at 6 months. When compared with baseline, the entire cohort demonstrated significant increases in erectile function outcomes at 1, 3, and 6 months after treatment. Clinical Implications: In this randomized sham-controlled crossover trial, we showed that 54.6% of participants with organic erectile dysfunction met the minimal clinically important difference in SHIM scores after treatment with low-intensity shockwave therapy. Strengths and Limitations: Strengths of this study include a sham-controlled group that crossed over to treatment. Limitations include a modest sample size at a single institution. Conclusions: Low-intensity shockwave therapy improves erectile function in men with erectile dysfunction as compared with sham treatment, which persists even 6 months after treatment. Clinical Trial Registration: ClinicalTrials.gov NCT04434352. [ABSTRACT FROM AUTHOR]

Although lung cancer screening (LCS) using low-dose CT is recommended for high-risk individuals, screening adherence remains low. We conducted a randomized trial to compare two methods of providing LCS education to Maryland Tobacco Quitline (MTQ) callers in order to assess whether this setting may serve as a teachable moment for LCS-eligible individuals. MTQ callers (50–80 years, 20+ pack-years, prior LCS ≥12 months) completed the baseline and were randomized to the Print- or Web-based version of ShouldIScreen.com. Participants completed 1- and 4-month follow-up assessments to evaluate intervention engagement and LCS-related outcomes. Participants (Print = 152, Web = 146) were 61.7 (SD = 6.3) years old and reported 63.5 pack-years (SD = 36.0). Most identified as Black (54.2%), female (66.1%), having internet access (78.9%), completing other recommended cancer screenings (86.3%), and that they would undergo LCS if recommended by their provider (91.3%). By 4 months, significantly more Print (75.0%) than Web (61.6%) participants had read the materials (P =.01). Most reported the interventions contained "the right amount" of information (92.6%) and prepared them to talk with their doctor (57.2%). Regarding screening-related outcomes, 42.8% (Print) and 43.8% (Web) had scheduled or completed a low-dose CT scan or a shared decision-making visit (P =.86). In a racially diverse sample of LCS-eligible quitline callers, offering LCS educational materials resulted in high intervention engagement and screening-related appointments. As >20% did not have internet access, providing participants' preferred modality (web/print) may improve intervention engagement and knowledge. Improving LCS awareness represents an important opportunity to increase screening among eligible but unscreened quitline callers. [ABSTRACT FROM AUTHOR]

Context β-Carotene, which is derived from most fruits and vegetables, is the most common type of carotenes. Existing studies have demonstrated that β-carotene is associated with some positive health outcomes. However, results about the effects of supplemental β-carotene on cancer are inconsistent. Objective To determine the association between supplemental β-carotene intake and the risk of cancers. Data sources Eight databases (PubMed, Web of Science, Embase, Cochrane, China National Knowledge Infrastructure, Wangfang, China Science and Technology Journal Database, and Chinese Biomedical Literature Database) were systematically searched until September 2022. Data extraction Only reports from randomized controlled trials in which an association between supplemental β-carotene intake and the risk of cancer was found were included in the meta-analysis. Data analysis A total of 18 eligible studies based on 8 different randomized controlled trials were included in the meta-analysis, with varying sample sizes from 391 to 39 876 participants. There was no significant association between supplemental β-carotene intake and overall cancer incidence rate after synthesizing all the results (risk ratio [RR]: 1.02; 95% confidence interval [CI], 0.99–1.05). Results from subgroup analysis indicated that intake of supplemental β-carotene significantly increased the risk of lung cancer (RR: 1.19; 95%CI: 1.08–1.32), whereas no significant associations were observed for other site-specific cancers. In addition, smokers and the subgroup of participants with only low-dose β-carotene intake had a risk increment of cancer if they took supplemental β-carotene (RR: 1.16; 95%CI: 1.05–1.29). Conclusion β-Carotene supplementation has no beneficial or harmful effect on cancer incidence; moreover, it might have potentially harmful effects on lung cancer, especially for people who smoke. On the basis of the evidence from this study, supplemental intake of β-carotene is not recommended for preventing cancer, and the establishment of a tolerable upper intake level of β-carotene should be considered. [ABSTRACT FROM AUTHOR]

Objectives Although the painful and disabling features of early diffuse cutaneous SSc (dcSSc) have an inflammatory basis and could respond to corticosteroids, corticosteroids are a risk factor for scleroderma renal crisis. Whether or not they should be prescribed is therefore highly contentious. Our aim was to examine safety and efficacy of moderate-dose prednisolone in early dcSSc. Methods PRedSS set out as a Phase II, multicentre, double-blind randomized controlled trial, converted to open-label during the Covid-19 pandemic. Patients were randomized to receive either prednisolone (∼0.3 mg/kg) or matching placebo (or no treatment during open-label) for 6 months. Co-primary endpoints were the HAQ Disability Index (HAQ-DI) and modified Rodnan skin score (mRSS) at 3 months. Over 20 secondary endpoints included patient reported outcome measures reflecting pain, itch, fatigue, anxiety and depression, and helplessness. Target recruitment was 72 patients. Results Thirty-five patients were randomized (17 prednisolone, 18 placebo/control). The adjusted mean difference between treatment groups at 3 months in HAQ-DI score was −0.10 (97.5% CI: −0.29, 0.10), P  = 0.254, and in mRSS −3.90 (97.5% CI: −8.83, 1.03), P  = 0.070, both favouring prednisolone but not significantly. Patients in the prednisolone group experienced significantly less pain (P  = 0.027), anxiety (P  = 0.018) and helplessness (P  = 0.040) than control patients at 3 months. There were no renal crises, but sample size was small. Conclusion PRedSS was terminated early primarily due to the Covid-19 pandemic, and so was underpowered. Therefore, interpretation must be cautious and results considered inconclusive, indicating the need for a further randomized trial. Trial registration ClinicalTrials.gov , https://clinicaltrials.gov , NCT03708718. [ABSTRACT FROM AUTHOR]

Baclofen may reduce the symptoms of alcohol withdrawal, as an alternative or as an adjuvant for benzodiazepines, but the available data are insufficient to support baclofen-assisted alcohol withdrawal. This study investigated the need for diazepam during acute alcohol withdrawal in patients receiving baclofen. In a single-blind, dose-dependent randomized controlled trial with three study arms, 63 patients with alcohol use disorder, starting in-patient benzodiazepine-assisted alcohol detoxification, were randomly assigned to receive placebo (n  = 18), baclofen 30 mg/day (N  = 20), or baclofen 60 mg/day (N  = 25) for 7 days. Diazepam was provided as needed based on the withdrawal symptoms stated by Clinical Institute Withdrawal Assessment for Alcohol-revised. The primary outcome measure was the number of patients in need of diazepam during alcohol detoxification. Secondary outcome measure included the between-group difference in the amount of diazepam needed during alcohol detoxification. Using baclofen 60 mg/day, 32% of patients needed additional diazepam compared to 35% on baclofen 30 mg/day and compared to 72% on placebo (P  = .013). The median total amount of diazepam needed was significantly lower in patients receiving baclofen 60 mg/day (0 ± 10 mg diazepam) and baclofen 30 mg/day (0 ± 10 mg diazepam) compared to placebo (10 ± 43 mg diazepam; P  = .017). Adverse events were comparable between patients on baclofen and placebo. Baclofen can reduce the withdrawal symptoms during alcohol detoxification. Baclofen was well tolerated and may be considered for the management of alcohol withdrawal syndrome, especially useful in situations where benzodiazepines should be withheld, such as patients with liver impairment. [ABSTRACT FROM AUTHOR]

Background Although learning health information is beneficial for physical well-being, many people opt to avoid learning this information due to its potentially threatening nature. Such avoidance can lead to delays in seeking treatment. Purpose This study tested the effectiveness of a self-regulation technique, mental contrasting (MC), specifically MC of a negative future with a positive current reality, in reducing health information avoidance regarding skin cancer (melanoma). We hypothesized that participants who engaged in MC would be more likely to choose to learn about their melanoma risk than those who completed a control, reflection activity. Methods We conducted a randomized controlled trial (N = 354). Participants were assigned to complete a MC or reflection (control) exercise prior to filling out a melanoma risk calculator. Participants were then asked whether they wanted to learn their melanoma risk, and how much information they would like to know. Results Chi-Square tests revealed that MC decreased melanoma risk information avoidance compared to the reflection activity (12% vs. 23.4%) but did not make participants more likely seek additional information. Conclusion MC is a brief, engaging, and effective strategy for reducing health information avoidance that could prove useful in medical settings. [ABSTRACT FROM AUTHOR]

Background Kidney transplant has become the preferred therapy for end-stage renal disease. However, kidney transplant recipients (KTRs) still face several challenges, such as physical inactivity. The purpose of this study was to explore the effects of a nurse-led physical exercise program in Chinese KTRs. Methods A total of 106 participants were enrolled from the Third Xiangya Hospital of Central South University between July 2021 and June 2022 and randomly assigned to the control or intervention groups. Participants in the control group were provided with routine nursing care and participants in the intervention group received a nurse-led rigorous physical exercise program that was divided into two stages: the pre-discharge stage and the post-discharge stage. The pre-discharge stage included the non-ambulatory and ambulatory stages. The Chinese traditional exercise Baduanjin was incorporated into the physical exercise during the ambulatory stage. The post-discharge stage continued the same exercise as the ambulatory stage at home. After 3 months of intervention, both groups received the same follow-up for 3 months. The primary and secondary outcomes of all participants were collected. The data were analysed with repeated measures analysis of variance to examine the effectiveness of the intervention. Results Compared with the control group, the intervention group had less fatigue and more motivation to be active in primary outcomes. Moreover, patients in the intervention group had a higher phase angle, a longer 6-minute walk distance, more 30-second chair stand times and decreased anxiety and depression levels in secondary outcomes. No adverse events were observed during the intervention. There were no significant differences in all dimensions of the quality-of-life questionnaire between the intervention and the control group. Conclusion Chinese KTRs could benefit from the nurse-led physical exercise program post-operatively. Trial registration ChiCTR2100048755 [ABSTRACT FROM AUTHOR]

COVID-19 misinformation has spread rapidly across social media. To counter misinformation, we designed a short, wordless and animated video (called the CoVideo) to deliver scientifically informed and emotionally compelling information about preventive COVID-19 behaviours. After 15 163 online participants were recruited from Germany, Mexico, Spain, the UK and the USA, we offered participants in the attention placebo control (APC) and do-nothing arms the option to watch the CoVideo (without additional compensation) as post-trial access to treatment. The objective of our study was to evaluate participant engagement by quantifying (i) the proportion of participants opting to watch the CoVideo and (ii) the duration of time spent watching the CoVideo. We quantified the CoVideo opt-in and view time by experimental arm, age, gender, educational status, country of residence and COVID-19 prevention knowledge. Overall engagement with the CoVideo was high: 72% of the participants [CI: 71.1%; 73.0%] opted to watch the CoVideo with an average view time of 138.9 out of 144.0 s [CI: 138.4; 139.4], with no statistically significant differences by arm. Older participants (35–59 years) and participants with higher COVID-19 prevention knowledge had higher view times than their counterparts. Spanish participants had the highest opt-in percentage whereas Germans exhibited the shortest view times of the five countries. Short, wordless and animated storytelling videos, optimized for 'viral spread' on social media, can enhance global engagement with COVID-19 prevention messages by transcending cultural, language and literary barriers. [ABSTRACT FROM AUTHOR]

Background and Aims Scepticism about the efficacy of thiopurines for ulcerative colitis [UC] is rising. This study aimed to evaluate mercaptopurine treatment for UC. Methods In this prospective, randomized, double-blind, placebo-controlled trial, patients with active UC, despite treatment with 5-aminosalicylates [5-ASA], were randomized for therapeutic drug monitoring [TDM]-guided mercaptopurine treatment or placebo for 52 weeks. Corticosteroids were given in the first 8 weeks and 5-ASA was continued. Proactive metabolite-based mercaptopurine and placebo dose adjustments were applied from week 6 onwards by unblinded clinicians. The primary endpoint was corticosteroid-free clinical remission and endoscopic improvement [total Mayo score ≤2 points and no item >1] at week 52 in an intention-to-treat analysis. Results Between December 2016 and April 2021, 70 patients were screened and 59 were randomized at six centres. In the mercaptopurine group, 16/29 [55.2%] patients completed the 52-week study, compared to 13/30 [43.3%] on placebo. The primary endpoint was achieved by 14/29 [48.3%] patients on mercaptopurine and 3/30 [10%] receiving placebo (Δ = 38.3%, 95% confidence interval [CI] 17.1–59.4, p = 0.002). Adverse events occurred more frequently with mercaptopurine [808.8 per 100 patient-years] compared to placebo [501.4 per 100 patient-years]. Five serious adverse events occurred, four on mercaptopurine and one on placebo. TDM-based dose adjustments were executed in 22/29 [75.9%] patients, leading to lower mercaptopurine doses at week 52 compared to baseline. Conclusions Optimized mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at 1 year following corticosteroid induction treatment in UC patients. More adverse events occurred in the mercaptopurine group. [ABSTRACT FROM AUTHOR]

Background Health care professionals seek information about effectiveness of treatments in patients who would be offered them in routine clinical practice. Electronic medical records (EMRs) and randomized controlled trials (RCTs) can both provide data on treatment effects; however, each data source has limitations when considered in isolation. Methods A novel modelling methodology which incorporates RCT estimates in the analysis of EMR data via informative prior distributions is proposed. A Bayesian mixed modelling approach is used to model outcome trajectories among patients in the EMR dataset receiving the treatment of interest. This model incorporates an estimate of treatment effect based on a meta-analysis of RCTs as an informative prior distribution. This provides a combined estimate of treatment effect based on both data sources. Results The superior performance of the novel combined estimator is demonstrated via a simulation study. The new approach is applied to estimate the effectiveness at 12 months after treatment initiation of acetylcholinesterase inhibitors in the management of the cognitive symptoms of dementia in terms of Mini-Mental State Examination scores. This demonstrated that estimates based on either trials data only (1.10, SE = 0.316) or cohort data only (1.56, SE = 0.240) overestimated this compared with the estimate using data from both sources (0.86, SE = 0.327). Conclusions It is possible to combine data from EMRs and RCTs in order to provide better estimates of treatment effectiveness. [ABSTRACT FROM AUTHOR]

To date, the VIT amin D and Omeg A -3 Tria L (VITAL) is the only large-scale randomized trial of marine omega-3 fatty acid (n −3 FA) supplementation for cardiovascular disease (CVD) prevention in a general population unselected for elevated cardiovascular risk. We review the findings of VITAL, as well as results from recent secondary prevention trials and updated meta-analyses of n −3 FA trials in the primary and secondary prevention of CVD. In VITAL, a nationwide sample of 25 871 US adults aged 50 and older, including 5106 African Americans, were randomized in a 2 × 2 factorial design to n −3 FAs (1 g/day; 1.2:1 ratio of eicosapentaenoic to docosahexaenoic acid) and vitamin D3 (2000 IU/day) for a median of 5.3 years. Compared with an olive oil placebo, the n −3 FA intervention did not significantly reduce the primary endpoint of major CVD events [composite of myocardial infarction (MI), stroke, and CVD mortality; hazard ratio (HR) = 0.92 (95% confidence interval 0.80–1.06)] but did significantly reduce total MI [HR = 0.72 (0.59–0.90)], percutaneous coronary intervention [HR = 0.78 (0.63–0.95)], fatal MI [HR = 0.50 (0.26–0.97)], and recurrent (but not first) hospitalization for heart failure [HR = 0.86 (0.74–0.998)]. The intervention neither decreased nor increased risk of atrial fibrillation. African Americans derived the greatest treatment benefit for MI and for recurrent hospitalization for heart failure (P interaction < 0.05 for both outcomes). Meta-analyses that include VITAL and high-risk or secondary prevention n −3 FA trials show coronary, but generally not stroke, risk reduction. More research is needed to determine which individuals may be most likely to derive net benefit. (VITAL clinicaltrials.gov identifier: NCT01169259). [ABSTRACT FROM AUTHOR]

Background Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. Methods Participants ages 4–21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. Results The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. Conclusions Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. Clinical Trials No NCT03982069 [ABSTRACT FROM AUTHOR]

Objective To develop a computable representation for medical evidence and to contribute a gold standard dataset of annotated randomized controlled trial (RCT) abstracts, along with a natural language processing (NLP) pipeline for transforming free-text RCT evidence in PubMed into the structured representation. Materials and methods Our representation, EvidenceMap , consists of 3 levels of abstraction: Medical Evidence Entity, Proposition and Map, to represent the hierarchical structure of medical evidence composition. Randomly selected RCT abstracts were annotated following EvidenceMap based on the consensus of 2 independent annotators to train an NLP pipeline. Via a user study, we measured how the EvidenceMap improved evidence comprehension and analyzed its representative capacity by comparing the evidence annotation with EvidenceMap representation and without following any specific guidelines. Results Two corpora including 229 disease-agnostic and 80 COVID-19 RCT abstracts were annotated, yielding 12 725 entities and 1602 propositions. EvidenceMap saves users 51.9% of the time compared to reading raw-text abstracts. Most evidence elements identified during the freeform annotation were successfully represented by EvidenceMap , and users gave the enrollment, study design, and study Results sections mean 5-scale Likert ratings of 4.85, 4.70, and 4.20, respectively. The end-to-end evaluations of the pipeline show that the evidence proposition formulation achieves F1 scores of 0.84 and 0.86 in the adjusted random index score. Conclusions EvidenceMap extends the participant, intervention, comparator, and outcome framework into 3 levels of abstraction for transforming free-text evidence from the clinical literature into a computable structure. It can be used as an interoperable format for better evidence retrieval and synthesis and an interpretable representation to efficiently comprehend RCT findings. [ABSTRACT FROM AUTHOR]

Context: The 2021 consensus report on the definition and interpretation of remission of type 2 diabetes (T2D) has been released. Although intermittent fasting diets (IF) are becoming very popular, no studies have investigated their benefit in diabetes remission. Objective: The present study examined the effectiveness of IF in diabetes remission and potential remission durability. Methods: Participants between ages 38 and 72 years with a duration of T2D of 1 to 11 years, a body mass index (BMI) of 19.1 to 30.4, 66.7% male, and antidiabetic agent use and/or insulin injection were randomly allocated at a ratio of 1:1 to the Chinese Medical Nutrition Therapy (CMNT) or control group. The primary outcome was diabetes remission, defined as a stable glycated hemoglobin A1c (HbA1c) level of less than 48 mmol/mol (< 6.5%) for at least 3 months after discontinuing all antidiabetic medications. The secondary outcomes included HbA1c level, fasting blood glucose level, blood pressure, weight, quality of life, and medication costs. We conducted a 12-month follow-up to assess the continuation of remission. Results: On completing the 3-month intervention plus 3-month follow-up, 47.2% (17/36) of participants achieved diabetes remission in the CMNT group, whereas only 2.8% (1/36) of individuals achieved remission in the control group (odds ratio 31.32; 95% CI, 2.39-121.07; P<0.0001). The mean body weight of participants in the CMNT group was reduced by 5.93 kg (SD 2.47) compared to 0.27 kg (1.43) in the control group. After the 12-month follow-up, 44.4% (16/36) of the participants achieved sustained remission, with an HbA1c level of 6.33% (SD 0.87). The medication costs of the CMNT group were 77.22% lower than those of the control group (60.4/month vs 265.1/month). Conclusion: This study demonstrated the clinical efficacy of CMNT in achieving diabetes remission for at least 1 year. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does a short interval (i.e. ≤90 min), compared to a long interval (i.e. ≥180 min), between semen collection and intrauterine insemination (IUI) increase the cumulative chance of an ongoing pregnancy after six IUI cycles? SUMMARY ANSWER A long interval between semen collection and IUI resulted in a borderline significant improvement in cumulative ongoing pregnancies and a statistically significant shorter time to pregnancy. WHAT IS KNOWN ALREADY Retrospective studies assessing the effect of the time interval between semen collection and IUI on pregnancy outcomes have shown inconclusive results. Some studies have indicated a beneficial effect of a short interval between semen collection and IUI on IUI outcomes, while others have not found any differences. To date, no prospective trials have been published on this subject. STUDY DESIGN, SIZE, DURATION The study was performed as a non-blinded, single-center RCT with 297 couples undergoing IUI treatment in a natural or stimulated cycle. The study was conducted between February 2012 and December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS Couples with unexplained or mild male subfertility and an indication for IUI were randomly assigned for up to six IUI cycles into either the control group (long interval, i.e. 180 min or more between semen collection and insemination) or the study group (short interval, i.e. insemination as soon as possible after semen processing and within 90 min of semen collection). The study was carried out in an academic hospital-based IVF center in the Netherlands. The primary endpoint of the study was ongoing pregnancy rate per couple, defined as a viable intrauterine pregnancy at 10 weeks after insemination. MAIN RESULTS AND THE ROLE OF CHANCE In the short interval group, 142 couples were analyzed versus 138 couples in the long interval group. In the intention-to-treat (ITT) analysis, the cumulative ongoing pregnancy rate was significantly higher in the long interval group (71/138; 51.4%) compared to that in the short interval group (56/142; 39.4%; relative risks 0.77; 95% CI 0.59–0.99; P  = 0.044). The time to pregnancy was significantly shorter in the long interval group (log-rank test, P  = 0.012). A Cox regression analysis showed similar results (adjusted hazard ratio 1.528, 95% CI 1.074–2.174, P  = 0.019). LIMITATIONS, REASONS FOR CAUTION Limitations of our study are the non-blinded design, the long inclusion and follow-up period of nearly seven years and the large number of protocol violations, especially because they predominantly occurred in the short interval group. The non-significant results in the per-protocol (PP) analyses and the weaknesses of the study should be taken into account in the assessment of the borderline significance of the results in the ITT analyses. WIDER IMPLICATIONS OF THE FINDINGS Because it is not necessary to perform the IUI immediately after semen processing, there can be more time available to choose the optimum work-flow and clinic occupancy. Clinics and laboratories should find their optimal timing of insemination, considering the time between human chorionic gonadotropin injection and insemination in relation to the sperm preparation techniques used as well as the storage time and conditions until insemination. STUDY FUNDING/COMPETING INTEREST(S) There were no external funding and no competing interests to declare. TRIAL REGISTRATION NUMBER Dutch trial registry, trial registration number NTR3144. TRIAL REGISTRATION DATE 14 November 2011. DATE OF FIRST PATIENT'S ENROLLMENT 5 February 2012. [ABSTRACT FROM AUTHOR]

Objective Alcohol withdrawal syndrome (AWS) is a frequent and potentially life-threatening condition experienced in alcohol use disorder. Since hypomagnesemia is involved in AWS's severity, we conducted a multicenter double-blind randomized placebo-controlled trial to examine the efficacy of oral magnesium supplementation as an adjuvant therapy of AWS. Material and Methods Inpatients were recruited in six different centers if they had a baseline score higher than eight on the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). The experimental treatment was magnesium lactate dehydrate, administrated three times per day providing a total of 426.6 mg per day and up to 15 days. The primary endpoint was the significant between-group difference of the CIWA-Ar total score change from baseline to 3 days later. The treatment group and baseline score were introduced as covariables in an analysis of covariance. Results A total of 98 inpatients were included {71.4% of men; mean age of 49.1 years [standard deviation (SD): 10.3]}. In the intention-to-treat population, the mean reduction of the CIWA-Ar score in the experimental group between baseline and 3 days later was 10.1 (SD: 5.2), whereas it was 9.2 (SD: 3.9) in the control group. The absolute difference of the adjusted mean in the experimental group compared with the control group was −0.69 (SD: 0.72), which did not correspond to a significant between-group difference (P  = 0.34). Per-protocol analysis and sensitivity analyses also supported this result. Supplementary analyses found no significant difference regarding benzodiazepine consumption, magnesium blood concentration, and satisfaction to care. Conclusions The present study does not support the rationale of systematic oral magnesium supplementation in patients with AWS. [ABSTRACT FROM AUTHOR]

BACKGROUND Disparities in hypertension outcomes persist among Black and Hispanic adults and persons living in poverty in the United States. The "LINKED-BP Program" is a multi-level intervention linking home blood pressure (BP) monitoring with a mobile health application, support from community health workers (CHWs), and BP measurement training at primary care practices to improve BP. This study is part of the American Heart Association RESTORE (Add RE ssing S ocial Determinants TO p R event hyp E rtension) Network. This study aims to examine the effect of the LINKED-BP Program on BP reduction and to evaluate the reach, adoption, sustainability, and cost-effectiveness of the intervention. METHODS Using a hybrid type I effectiveness-implementation design, 600 adults who have elevated BP or untreated stage 1 hypertension without diabetes, chronic kidney disease, history of cardiovascular disease (stroke or coronary heart disease) and age < 65 years will be recruited from 20 primary care practices including community health centers in the Maryland area. The practices are randomly assigned to the intervention or the enhanced usual care arms. Patients in the LINKED-BP Program receive training on home BP monitoring, BP telemonitoring through the Sphygmo app, and CHW telehealth visits for education and counseling on lifestyle modification over 12 months. The primary clinical outcome is change from baseline in systolic BP at 6 and 12 months. DISCUSSIONS The LINKED-BP Program tests a sustainable, scalable approach to prevent hypertension and advance health equity. The findings will inform implementation strategies that address social determinants of health and barriers to hypertension prevention in underserved populations. ClinicalTrials.gov IDENTIFIER NCT05180045. [ABSTRACT FROM AUTHOR]

Keywords: Randomized controlled trial; Clinical trial; Trial design; Registry; Heart failure; Reduced ejection fraction; Mildly reduced ejection fraction; Preserved ejection fraction; Outcomes; Mortality; Heart failure hospitalization EN Randomized controlled trial Clinical trial Trial design Registry Heart failure Reduced ejection fraction Mildly reduced ejection fraction Preserved ejection fraction Outcomes Mortality Heart failure hospitalization 1526 1529 4 05/03/23 20230501 NES 230501 Randomized controlled trials (RCTs) form the basis for guidelines, regulatory approval, and reimbursement.[1] They are commonly industry-funded and apply selective eligibility criteria,[2] potentially limiting generalizability. Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands: design and rationale of the chronic heart failure ESC guideline-based cardiology practice quality project (CHECK-HF) registry. [Extracted from the article]

Background We previously reported that modified-release nicotinamide (NAMR) was superior to placebo in reducing serum phosphate concentrations over 12 weeks in a large cohort of haemodialysis patients with hyperphosphataemia. Here we report outcomes after 52 weeks of treatment. Methods NOPHOS was a phase 3, international, randomized, controlled, double-blind trial with a parallel group design. NAMR (250–1500 mg/day) was investigated in comparison to placebo as an add-on therapy to an individual therapy with approved phosphate binders. Results In the intention-to-treat population (NAMR: n  = 539; placebo: n  = 183), serum phosphate was significantly lower in the NAMR group compared with the placebo group at week 24 (5.40 ± 1.55 versus 5.79 ± 1.37 mg/dl, P  < .001) with a mean difference of −0.39 mg/dl [95% confidence interval (CI) −0.66 to −0.13], but was comparable between the groups at week 52 [mean difference −0.08 (95% CI −0.36–0.20)]. In the completer population (n  = 358), statistical significance in favour of NAMR was reached at weeks 24 and 52. The treatment effect was reduced in patients with high baseline serum intact parathyroid hormone (iPTH) compared with patients with low baseline serum iPTH. Compliant patients in the NAMR group had a more pronounced and sustained reduction in serum phosphate than non-compliant patients. NAMR treatment was associated with a significantly increased risk of thrombocytopenia, pruritus, anaemia, and diarrhoea. Herpes zoster occurred exclusively in patients randomized to NAMR. Conclusions NAMR combined with phosphate binders significantly reduced serum phosphate over the first 24 weeks of treatment, but the treatment effect was not maintained up to week 52. Non-compliance may have contributed to reduced long-term efficacy. Several newly identified safety signals warrant further evaluation. [ABSTRACT FROM AUTHOR]

Background: Despite the frequent use of symptomatic therapies in cough, evidence of their benefits is lacking.Objective: We compared the effectiveness of 3 symptomatic therapies and usual care in acute bronchitis.Methods: Multicenter, pragmatic, multiarm parallel group, open randomized trial in primary care (ClinicalTrials.gov, Identifier: NCT03738917) was conducted in Catalonia. Patients ≥18 with uncomplicated acute bronchitis, with cough<3 weeks as the main symptom, scoring ≥4 in either daytime or nocturnal cough (7-point Likert scale), were randomized to usual care, dextromethorphan 15 mg t.i.d., ipratropium bromide inhaler 20 µg 2 puffs t.i.d, or 30 mg of honey t.i.d., all taken for up to 14 days. The main outcome measure was the number of days with moderate-to-severe cough. A symptom diary was given. A second visit was scheduled at days 2-3 for assessing evolution, with 2 more visits at days 15 and 29 for clinical assessment, evaluation of adverse effects, re-attendance, and complications.Results: We failed to achieve the sample size scheduled due to the COVID-19 pandemic. We finally recruited 194 patients. The median number of days with moderate-to-severe cough (score ≥ 3) in the usual care arm was 5 (interquartile range [IQR], 4, 8.75), 5 in the ipratropium bromide arm (IQR, 3, 8), 5 in the dextromethorphan arm (IQR, 4, 9.75), and 6 in the honey arm (IQR, 3.5, 7). The same results were obtained in the Kaplan-Meier survival analysis for the median survival time of each arm with the usual care as the reference group.Conclusion: The symptomatic treatment evaluated has shown to be ineffective against cough. [ABSTRACT FROM AUTHOR]