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Background: Younger age is an independent risk factor for breast cancer (BC) prognosis, and BC in young women is often considered more aggressive. BC patients with different age and molecular subtypes have different metastasis patterns and survival. Herein, we aim to explore the metastasis patterns, characteristics and treatment methods of young patients with BC, and to compare them with older patients. Methods: Data of young patients (aged ≤40 years old) and older patients (aged >40 years old) with BC were extracted from the Surveillance, Epidemiology, and End Results (SEER) registration database in 2010–2019 in this retrospective cohort study. Univariate and multivariate competing risk models and proportional hazard models were used to explore the association between different metastasis patterns and treatments and BC prognoses in young and older patients. Kaplan-Meier (KM) curves were drawn to reflect the survival probability of patients with BC who have different metastasis patterns. Also, we performed subgroup analysis of different metastasis patterns to explore the association between different treatments and overall survival (OS)/cancer specific survival (CSS) in patients with BC. The evaluation index was hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Totally, 5,984 patients died, and 92.56% of them died from BC. There were respectively 1,089 young patients and 9,105 older patients, and we found some differences of characteristics and metastasis patterns between them. After adjusting for covariates, young patients who had brain metastasis and multiple sites metastasis seemed to have high risk of both lower OS and CSS. Among older patients with BC, brain metastasis, liver metastasis, and multiple sites metastasis were all positively associated with both lower OS and CSS. In young and older patients, those who not receive radiotherapy or surgery, or received non-surgery combined with radiotherapy seemed to have high risk of both lower OS and CSS. Breast-conserving surgery (BCS) and surgery combined with radiotherapy were associated with higher OS and CSS in young patients, while only older patients received surgery combined with radiotherapy had higher OS and CSS. Results of subgroup analysis indicated that for patients with different metastasis patterns, developing a personalized treatment plan is necessary. Conclusions: Characteristics of BC between young patients and older patients were different. Clinicians should focus on different metastasis sites and choose appropriate treatments in patients with different ages, which may improve the prognoses. [ABSTRACT FROM AUTHOR]

Background and Objectives: Vericiguat is a soluble guanylate cyclase stimulator indicated to reduce the risk of cardiovascular death and hospitalization due to heart failure. A dedicated QTc study in patients with chronic coronary syndromes demonstrated no clinically relevant QTc effect of vericiguat for exposures across the therapeutic dose range (2.5–10 mg). Interval prolongation concentration-QTc (C-QTc) modeling was performed to complement the statistical evaluations of QTc in the dedicated QTc study. Methods: Individual time-matched, baseline- and placebo-corrected Fridericia-corrected QT interval values (ΔΔQTcF) were derived. Two approaches for ΔΔQTcF calculation were investigated: (1) ΔΔQTcF correction with data from a single baseline (as in the primary statistical analysis); and (2) ΔΔQTcF correction with a modeled baseline (considering all available individual non-treatment baselines). The ΔΔQTcF values were related to observed vericiguat concentrations with linear mixed-effects modeling. Results: For both modeling approaches, a positive relationship was found between ΔΔQTcF and vericiguat concentration; however, the slope for the single-baseline approach was not statistically significant, whereas the slope from the modeled-baseline approach was statistically significant. The upper bound of the two-sided 90% confidence interval for model-derived QTc was < 10 ms at the highest observed exposure (745 μg/L; investigated dose range 2.5–10 mg). Conclusion: By applying a single-baseline approach and a modeled-baseline approach that integrated all available QTc data across doses to characterize the QTc prolongation potential, this study showed that vericiguat 2.5–10 mg is not associated with clinically relevant QTc effects, in line with the conclusion from the primary statistical analysis. Clinical Trials Registration Number: ClinicalTrials.gov NCT03504982. [ABSTRACT FROM AUTHOR]

Background: Anxiety and depression are common among older adults and can intensify during perioperative periods, but few mental health interventions are designed for older surgical patients' unique needs. As part of the feasibility trial, we developed and adapted a perioperative mental health (PMH) bundle for older patients comprised of behavioral activation (BA) and medication optimization (MO) to ameliorate anxiety and depressive symptoms before, during, and after cardiac, orthopedic, and oncologic surgery. Methods: We used mixed-methods including workshop studios with patients, caregivers, clinicians, researchers, and interventionists; intervention refinement and reflection meetings; patient case review meetings; intervention session audio-recordings and documentation forms; and patient and caregiver semi-structured interviews. We used the results to refine our PMH bundle. We used multiple analytical approaches to report the nature of adaptations, including hybrid thematic analysis and content analysis informed by the Framework for Reporting Adaptations and Modifications – Expanded. Results: Adaptations were categorized by content (intervention components), context (how the intervention is delivered, based on the study, target population, intervention format, intervention delivery mode, study setting, study personnel), training, and evaluation. Of 51 adaptations, 43.1% involved content, 41.2% involved context, and 15.7% involved training and evaluation. Several key adaptations were noted: (1) Intervention content was tailored to patient preferences and needs (e.g., rewording elements to prevent stigmatization of mental health needs; adjusting BA techniques and documentation forms to improve patient buy-in and motivation). (2) Cohort-specific adaptations were recommended based on differing patient needs. (3) Compassion was identified by patients as the most important element. Conclusions: We identified evidence-based mental health intervention components from other settings and adapted them to the perioperative setting for older adults. Informed by mixed-methods, we created an innovative and pragmatic patient-centered intervention bundle that is acceptable, feasible, and responsive to the needs of older surgical populations. This approach allowed us to identify implementation strategies to improve the reach, scalability, and sustainability of our bundle, and can guide future patient-centered intervention adaptations. Clinical trials Registration: NCT05110690 (11/08/2021). [ABSTRACT FROM AUTHOR]

With increasing numbers of older prisoners, effective strategies for preventing and treating age-associated diseases, such as cognitive disorders, are needed. As pharmacological therapies are limited, non-pharmacological interventions are increasingly recognized as potential treatment strategies. One approach is cognitive training (CT). However, no study has investigated CT in the prison setting. Thus, this one-arm feasibility trial aims to analyze the feasibility of (i) the study protocol and (ii) the implementation of multimodal CT for older prisoners. Eighteen older male prisoners from two specific divisions for older prisoner participated in 12 weekly CT sessions using the NEUROvitalis program. The feasibility analysis included recruitment, dropout, and CT participation rates, and motivation for and satisfaction with CT (using 6-point Likert-scales). The study protocol demonstrated sufficient feasibility with high recruitment rates between 46 and 50%. Therefore, the CT implementation was successful: Only one prisoner ceased participation; all others completed the CT sessions (i.e., attended > 75% of the sessions). Prisoners reported high CT motivation and satisfaction, and would recommend CT. This is the first study to demonstrate CT feasibility in older prisoners. Although more research is needed, these results are a starting point for expanding services to include cognitively enhancing activities for older prisoners. This one-arm feasibility study was pre-registered in the German Clinical Trials Register (DRKS; ID: DRKS00020227).), Registered 11 Mai 2021 https://drks.de/search/de/trial/DRKS00020227. [ABSTRACT FROM AUTHOR]

Background: High-quality evidence is still required to affirm the efficacy of mindfulness-based interventions (MBIs) in craving reduction. MBIs may be particularly appropriate for this purpose given the neurobiological mechanisms of addiction with automatic behavior in response to the negative affect. In this systematic review and meta-analysis, we aimed to study the efficacy of MBIs in craving reduction and to synthetize the newly published data. Methods: We searched four databases and three clinical trial registries for randomized controlled trials (RCTs) up to August 2023, including studies with MBIs in all types of substance use disorders or behavioral addictions. We chose as our outcome of interest the change from the baseline of craving measures at posttreatment. Standardized mean difference was used as an effect size estimator. Results: We included 17 RCTs with 1228 participants. The overall effect size was estimated at -0.70 (95% CI -1.15, -0.26) in favor of MBIs. Conclusion: Due to the high inconsistency (I2 = 92%), we were unable to conclude that there is a medium to large effect size. Overall risk of bias was high for most studies, and the GRADE approach detected a low quality of evidence. Previous clinical and fundamental research suggest that MBIs have a promising potential in addiction medicine. However, further investigation of whether MBIs effectively reduce craving is needed, and innovative solutions for resolving methodological limitations in MBI research are warranted. Trial registration: PROSPERO registration ID CRD42020221141. [ABSTRACT FROM AUTHOR]

Background: Worldwide, many guidelines recommend the use of expressed breast milk (EBM) and maternal expression of breast milk for the prevention and treatment of neonatal hypoglycemia. However, the impact of both practices on neonatal hypoglycemia is unclear. This study aims to determine the effectiveness of EBM and maternal expression of breast milk in preventing and treating neonatal hypoglycemia. Methods: We registered our review in PROSPERO (CRD42022328072). We systematically reviewed five databases and four clinical trial registries to identify randomized controlled trials (RCT), non-randomized studies of intervention (NRSI), and cohort studies that compared infants who received EBM to infants who did not, and similar study designs that compared infants whose mothers expressed breast milk to infants whose mothers did not. Two independent reviewers carried out screening, data extraction, and quality assessment. The quality of included RCT, NRSI, and cohort studies were respectively assessed with the Cochrane Risk of Bias 2, Risk Of Bias In Non-randomised Studies—of Interventions, and the Newcastle–Ottawa Scale tools. Results from studies on EBM were synthesized separately from those on maternal expression of breast milk. Meta-analysis was undertaken using Revman 5.4. and fixed-effect models. Results: None of the ten included studies was specifically designed to determine the effect of EBM or maternal expression of breast milk on neonatal hypoglycemia. The effect of EBM on neonatal hypoglycemia was not estimable. There was no difference in the risk of hypoglycaemia among neonates whose mothers expressed breast milk compared to those whose mothers did not [RR (95%CI); one RCT: 0.92 (0.77, 1.10), high-certainty evidence; one cohort: 1.10 (0.74, 1.39), poor quality study]. Conclusions: There is insufficient evidence to determine the effectiveness of EBM for preventing or treating neonatal hypoglycemia. Limited data suggests maternal breast milk expression may not alter the risk of neonatal hypoglycemia. High-quality randomized controlled trials are needed to determine the effectiveness of EBM and maternal expression of breast milk for the prevention and treatment of neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aims to: assess the effectiveness and safety of orally administered Chinese herbal medicines (CHMs) as adjuncts to the post-surgical management of chronic rhinosinusitis (CRS); inform clinicians of the current evidence; identify the best available evidence; and suggest directions for further research. Randomised controlled trials (RCTs) were identified from searches of nine databases plus clinical trial registries. Participants were adults and/or children diagnosed with sinusitis or rhinosinusitis, with or without nasal polyps, who had received surgery. Interventions were CHMs used orally following surgery for CRS as additions to conventional post-surgical management. Controls received conventional post-surgical management without CHMs. Studies reported results for Sino-Nasal Outcome Test (SNOT), visual analogue scales (VAS), Lund-Mackay computed tomography score (LM), Lund-Kennedy endoscopic score (LK), mucociliary transport time (MTT), mucociliary transport rate (MTR), mucociliary clearance (MC) or quality of life (QoL). Twenty-one RCTs were included. All used oral CHMs following functional endoscopic sinus surgery (FESS). The pooled results showed no significant difference between groups for SNOT-20 at the end of treatment (EoT) but there was a significant difference at follow up (FU) in favour of additional CHMs. The VAS for total nasal symptoms (VAS-TNS) showed greater improvements in the CHM groups at EoT and FU. Only FU data were reported for LM which showed greater improvement in the CHM groups. LK showed greater improvements at EoT and FU. The measures of mucociliary transport (MTT, MTR, and MC) each showed significantly greater improvement at EoT in the group that received additional CHMs. No study reported QoL. Adverse events were not serious, but reporting was incomplete. The meta-analyses suggested the addition of oral CHMs to conventional management following FESS may improve recovery. However, most studies were not blinded, and substantial heterogeneity was evident in some meta-analyses. Blinded studies are required to further investigate the roles of oral CHMs in post-surgical recovery. Systematic review registration number: The protocol was registered in PROSPERO (CRD42019119586). [ABSTRACT FROM AUTHOR]

Background: Burnout and psychosocial distress are serious and growing issues for healthcare workers (HCWs) and healthcare systems across the globe. Exacerbated by changes in healthcare delivery during and following the Covid-19 pandemic, these issues negatively affect HCW wellbeing, clinical outcomes and patient safety. Art Therapy has demonstrated promise as a suitable but under researched intervention, warranting further investigation. This systematic review aims to ascertain what art therapy-based interventions used to address burnout and / or psychosocial distress in HCWs have been reported in the health and social care literature and how these have been evaluated. Methods: Six databases (PubMed, PsycINFO, MEDLINE, EMBASE, CINAHL, ProQuest Central), Google Scholar and three clinical trial registries (CENTRAL, ICTRP and ClinicalTrials.gov) were searched for studies using art therapy-based methods to engage with burnout risk or psychosocial distress in HCWs. Following screening for eligibility study characteristics and outcomes were extracted by two reviewers independently. Studies were evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Tools. Outcomes were grouped for analysis. Quantitative and qualitative results were synthesised and integrated using narrative synthesis. Results: Twenty-seven studies, drawn from thirteen countries, spanning five continents were selected for inclusion. Fifty percent were published in the last five years, indicating growing global research in the field. Fourteen studies used quantitative research methods and thirteen used qualitative methods. A total of 1580 participants took part in the studies, with nurses most broadly represented (59%). Interventions were mostly delivered in groups (95%) and by an art therapist (70%). Heterogeneity and insufficient randomised controlled trials precluded the possibility of meta-analysis. However, a review of available data showed evidence of medium to large effects for emotional exhaustion (burnout), work-related stress and common mental health issues. A content analysis of qualitative data of perceived effect complemented quantitative findings. Conclusion: Global research into the use of art therapy-based methods to address burnout and psychosocial distress in HCWs is growing. Whilst further high-quality evidence such as randomised controlled trials would be beneficial, findings suggest that art therapy-based methods should be strongly considered as an acceptable and effective treatment for symptoms of emotional exhaustion (burnout) and psychosocial distress in HCWs. [ABSTRACT FROM AUTHOR]

Introduction: Clinical trials are the gold standard for testing new therapies. Databases like ClinicalTrials.gov provide access to trial information, mainly covering the US and Europe. In 2006, WHO introduced the global ICTRP, aggregating data from ClinicalTrials.gov and 17 other national registers, making it the largest clinical trial platform by June 2019. This study conducts a comprehensive global analysis of the ICTRP database and provides framework for large-scale data analysis, data preparation, curation, and filtering. Materials and methods: The trends in 689,793 records from the ICTRP database (covering trials registered from 1990 to 2020) were analyzed. Records were adjusted for duplicates and mapping of agents to drug classes was performed. Several databases, including DrugBank, MESH, and the NIH Drug Information Portal were used to investigate trends in agent classes. Results: Our novel approach unveiled that 0.5% of the trials we identified were hidden duplicates, primarily originating from the EUCTR database, which accounted for 82.9% of these duplicates. However, the overall number of hidden duplicates within the ICTRP seems to be decreasing. In total, 689 793 trials (478 345 interventional) were registered in the ICTRP between 1990 and 2020, surpassing the count of trials in ClinicalTrials.gov (362 500 trials by the end of 2020). We identified 4 865 unique agents in trials with DrugBank, whereas 2 633 agents were identified with NIH Drug Information Portal data. After the ClinicalTrials.gov, EUCTR had the most trials in the ICTRP, followed by CTRI, IRCT, CHiCTR, and ISRCTN. CHiCTR displayed a significant surge in trial registration around 2015, while CTRI experienced rapid growth starting in 2016. Conclusion: This study highlights both the strengths and weaknesses of using the ICTRP as a data source for analyzing trends in clinical trials, and emphasizes the value of utilizing multiple registries for a comprehensive analysis. [ABSTRACT FROM AUTHOR]

Introduction: In 2019, the Central Drugs Standard Control Organization (CDSCO) introduced the New Drugs and Clinical Trials Rules 2019 (NDCTR), which separated the research guidelines for "Clinical Trials" and "Biomedical and Health Research." As a result, guidelines issued by Indian Council of Medical Research were stated to apply to academic clinical trials (ACTs). This change is important because academic studies are crucial for scientific advancement and repurposing of approved drugs in health-care industry. However, conducting an ACT can pose challenges. We assessed the level of awareness, knowledge, and challenges faced by investigators. Our aim is to overcome some of these challenges and encourage more academic studies for the betterment of healthcare and scientific knowledge in India. Methodology: The study was conducted in two phases after obtaining approval from the Institutional Ethics Committee (EC) of three tertiary care hospitals in Mumbai. In the first phase, the number of ACTs was assessed from the clinical trial registry India website, while the number of registered and re-registered ECs were assessed from the CDSCO website. The second phase involved assessing investigator awareness and knowledge about ACTs using a prevalidated questionnaire with a content validity index score of 0.93. Results: In 2020, the highest numbers of studies were registered, with the highest numbers of registered and re-registered ECs from Maharashtra. All participants completed the questionnaire and were aware of the need to follow guidelines for clinical trials. Sixty-seven percent of participants knew that the guidelines for ACTs differed from those of sponsored clinical trials, but only 58% were aware of the exact definition of an ACT as per NDCTR, 2019. Eighty-five percent of participants knew who could initiate an ACT, but only 27% knew about the applicability of results of an ACT and 33% had in-depth knowledge about the required approvals, while only 10% knew the archival period. Although 71% of participants had knowledge about serious adverse event reporting, few answered in-depth questions correctly. Only 31 participants reported facing varied challenges. Conclusion: To conduct ACTs effectively and contribute to healthcare and scientific advancement, it is crucial to enhance investigators' existing knowledge about ACTs. [ABSTRACT FROM AUTHOR]

Transcranial alternating current stimulation (tACS) may modulate neuronal oscillations by applying sinusoidal alternating current, thereby alleviating associated symptoms in schizophrenia. Considering its possible utility in schizophrenia, we reviewed the literature for tACS protocols administered in schizophrenia and their findings. A scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline in databases and clinical trial registers. The search resulted in 59 publications. After excluding review articles unrelated to tACS, trials without published results or not involving patients with schizophrenia, 14 studies were included. Among the included studies/case reports only 5 were randomized controlled therapeutic trials. The studies investigated the utility of tACS for clinical and neurobiological outcomes. All studies reported good tolerability with only transient mild side effects. It was administered mostly during the working memory task (such as computerized n-back task, dual back task, and computerized digit symbol substitution task) for schizophrenia patients with cognitive deficits and during resting state while targeting positive symptoms. A possible reduction in hallucinations and delusions using alpha tACS, and improvement in negative and cognitive deficits with theta and gamma tACS were reported. Nevertheless, one of the randomized controlled trials targeting hallucinations was negative and rigorous large-sample studies are lacking for other domains. The current evidence for tACS in schizophrenia is preliminary though promising. In future, more sham controlled randomized trials assessing the effect of tACS on various domains are needed to substantiate these early findings. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are widely used drugs that reduce gastric acid secretion. In recent years, there has been a gradual increase in their use. The safety of prolonged PPI therapy and the potential for cumulative side effects of these drugs raise legitimate concerns. An association between PPI administration and the risk of Clostridioides difficile infection has been suggested. The findings regarding this phenomenon require further unequivocal verification. Material and methods: A review of publications obtained from the PubMed database and published between 2016-2023. Based on the keywords "proton pump inhibitor", "PPI" and "Clostridium", 132 articles were selected. Finally, 6 meta-analyses were included in the analysis. Results: Studies conducted in recent years have shown a statistically significant increase in the risk of C. difficile infection in patients taking PPIs compared to those who avoid this therapy. The aforementioned relationship was observed in both adults and pediatric patients. One study proved that the risk remained high even up to 1 year after the end of treatment. The described relationship is still a matter of debate due to the fact that patients using antacids are usually elderly, have several comorbidities and a higher risk of developing C. difficile infection regardless of PPI use. Conclusions: The relationship between the use of PPIs and the risk of developing C. difficile infection is still controversial, which justifies the need for continued clinical trials to objectively resolve this issue. PPIs exert high efficacy in the treatment of acid-dependent diseases, but due to the many ambiguities surrounding possible side effects, caution in their administration seems warranted, especially for long-term therapy in elderly patients with polypharmacy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the treatment efficacy of fluoride toothpaste alone and those of adjunctive use of resin infiltration, sodium fluoride varnish, and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on white spot lesions (WSLs). Materials and methods: Seventy-nine patients (356 teeth) with WSLs after orthodontic treatment were randomly allocated into four groups. The WSLs of the participants received resin infiltration only at baseline, and the other groups received fluoride varnish, CPP-ACP mousse, and placebo treatment every 6 months, respectively. A toothpaste containing 1400 ppm fluoride and toothbrushes were distributed to all participants, and oral hygiene instructions were provided. Photos of the teeth with WSL were taken to compare the change between groups which was measured by ImageJ software. Results: Twelve months later, different degrees of reduction in the area of WSLs were observed in all groups. The percentage of lesion area reduction in WSLs in the resin infiltration group was 46.6%, which was significantly higher than that in fluoride varnish group (26.6%), CPP-ACP group (28.6%), and control group (29.8%), and the differences were statistically significant (p < 0.001). Conclusions: This study shows that after 1-year follow-up, the use of fluoride toothpaste, with or without the use of fluoride varnish or CPP-ACP, can reduce the area of WSLs. While resin infiltration can immediately improve dental aesthetics and continuously improved in 12 months, resin infiltration group showed much better results than other groups. Trial registration: Clinical Trials Registration Number: ChiCTR2000032516. Clinical significance: The use of fluoride toothpaste, with or without adjunctive use of fluoride varnish and CPP-ACP, can reduce the area of WSLs, while resin infiltration treatment has additional effect and can immediately improve dental aesthetics. [ABSTRACT FROM AUTHOR]

Background: Ischemia/reperfusion injury contributes to periprocedural myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). PMI can be estimated by the elevation of troponin (Tn) and creatine kinase-MB (CKMB) plasma levels, and it is associated with increased risk of cardiovascular events and mortality. Vitamin C might have a beneficial effect on PMI by improving endothelial function, improving myocardial perfusion, and by reducing oxidative stress generated during/after reperfusion. In several small animal models of cardiac stress, vitamin C reduced the increase in Tn and CKMB levels. The aim of this meta-analysis was to investigate whether vitamin C administration may have an effect on Tn and CKMB levels in patients undergoing PCI or CABG. Methods: We searched PubMed, Cochrane, Embase and Scopus databases for controlled clinical trials reporting on Tn and CKMB levels in adult patients who underwent PCI or CABG and received vitamin C. As secondary outcomes we collected data on biomarkers of oxidative stress in the included trials. In our meta-analysis, we used the relative scale and estimated the effect as the ratio of means. Results: We found seven controlled trials which included 872 patients. All included trials administered vitamin C intravenously, with a range from 1 to 16 g/day, and all initiated vitamin administration prior to the procedure. Vitamin C decreased peak Tn plasma levels in four trials on average by 43% (95% CI: 13 to 63%, p = 0.01) and peak CKMB plasma levels in five trials by 14% (95% CI: 8 to 21%, p < 0.001). Vitamin C also significantly decreased the biomarkers of oxidative stress. Conclusions: Vitamin C may decrease cardiac enzyme levels in patients undergoing elective PCI or CABG. This may be explained partially by its antioxidant effects. Our findings encourage further research on vitamin C administration during cardiac procedures and in other clinical contexts that increase the level of cardiac enzymes. Future studies should search for an optimal dosing regimen, taking baseline and follow-up plasma vitamin C levels into account. [ABSTRACT FROM AUTHOR]

Justifying sample size for a pilot trial is a reporting requirement, but few pilot trials report a clear rationale for their chosen sample size. Unlike full-scale trials, pilot trials should not be designed to test effectiveness, and so, conventional sample size justification approaches do not apply. Rather, pilot trials typically specify a range of primary and secondary feasibility objectives. Often, these objectives relate to estimation of parameters that inform the sample size justification for the full-scale trial, many of which are binary. These binary outcomes are referred to as "feasibility outcomes" and include expected prevalence of the primary trial outcome, primary outcome availability, or recruitment or retention proportions. For pilot cluster trials, sample size calculations depend on the number of clusters, the cluster sizes, the anticipated intra-cluster correlation coefficient for the feasibility outcome and the anticipated proportion for that outcome. Of key importance is the intra-cluster correlation coefficient for the feasibility outcome. It has been suggested that correlations for feasibility outcomes are larger than for clinical outcomes measuring effectiveness. Yet, there is a dearth of information on realised values for these correlations. In this tutorial, we demonstrate how to justify sample size in external pilot cluster trials where the objective is to estimate a binary feasibility outcome. We provide sample size calculation formulae for a variety of scenarios, make available an R Shiny app for implementation, and compile a report of intra-cluster correlations for feasibility outcomes from a convenience sample. We demonstrate that unless correlations are very low, external pilot cluster trials can be made more efficient by including more clusters and fewer observations per cluster. [ABSTRACT FROM AUTHOR]

Introduction: The sequelae post-COVID can affect different systems. In this sense, considering the multi-factorial etiology of COVID-19, multi-professional interventions could be a relevant strategy for recovery health indicators. Objective: This study aimed to investigate the effects of multi-professional intervention on body composition, physical fitness, and biomarkers in overweight COVID-19 survivors with different symptomatology. Methodology: A non-randomized parallel group intervention included 69 volunteers (BMI ≥25 kg/m2 ), divided into three groups according to SARS CoV-2 symptomatology, but only 35 finished the longitudinal protocol [control group (n = 11); moderate group (n = 17) and severe group (n = 7)]. The groups were submitted to a multi-professional program (nutritional intervention, psychoeducation, and physical exercise intervention) for 8 weeks, and the volunteers underwent body composition assessments (primary outcome) and physical and biochemical tests (secondary outcome) in pre- and post-intervention. This study was registered on the Clinical Trials Registration Platform number: RBR-4mxg57b and with the local research ethics committee protocol under number: 4,546,726/2021. Results: After the 8-week multi-professional intervention, the following results were observed for the moderate COVID-19 group: improved dynamic strength of lower- and (p = 0.003), upper-limbs (p = 0.008), maximal isometric lumbar)traction strength (p = 0.04), flexibility (p = 0.0006), and albumin (p = 0.0005), as well as a reduction in the C reactive protein (CRP) (p = 0.003) and fasting glucose (p = 0.001); for the severe COVID-19 group: an improvement in dynamic lower-body strength (p = 0.001), higher values of albumin (p = 0.005) and HDL-c (p = 0.002), and lower values of CRP (p = 0.05), and for the control group: an improvement in sit-up repetitions (p = 0.008), and a reduction of CRP (p = 0.01), fasting glucose (p = 0.001) and total cholesterol (p = 0.04) were identified. All experimental groups reduced triglycerides after intervention (p < 0.05). Conclusion: Finally, 8 weeks of multiprofessional intervention can be an efficient tool for reversing the inflammatory process and promoting improvements in daily activities and quality of life, although it is believed that the severe COVID-19 group needs longer interventions to improve different health indicators. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this review was to evaluate the survival rates of restorations utilizing titanium base abutments (TBA) for restoring single‐unit implant prostheses. Materials and Methods: This review was conducted following the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. The focus question was: In patients who require the restoration of a single dental implant utilizing a titanium base abutment, what are the determining factors and outcomes relating to implant prosthesis prognosis and survival? A comprehensive search of databases (PubMed, EMBASE, and Cochrane Library) was conducted on 16 April 2023 and updated on 5 May 2023. Randomized clinical trials (RCT), retrospective studies and prospective studies, reporting on the use of TBA for single implant prostheses, were reviewed. A Cochrane collaboration risk of bias assessment analysis was performed for randomized clinical studies, and the Newcastle–Ottawa Scale tool was applied for non‐randomized studies. A meta‐analysis was performed on clinical trials reporting on survival rates of both TBA and other abutments. Other clinical studies, reporting on TBA only, were included for descriptive statistics. Results: The search provided 1159 titles after duplicates were removed. Six RCTs were included to perform a meta‐analysis and compare the survival of the TBA to other abutments [OR 0.74; 95% CI: 0.21–2.63, heterogeneity; I2 0%; p =.99]. Twenty‐three prospective and retrospective studies fulfilled the criteria and were included in the meta‐analysis after 12 months of function. A total of 857 single implant‐supported prostheses fabricated with a TBA were included. TBA abutments have an estimate 98.6% survival rate after 1 year in function (95% CI: 97.9%–99.4%). The mean follow‐up period was 31.2 ± 16.9 months. Conclusions: Single implant prosthesis restored with titanium base abutments showed favourable short‐term survival rates. [ABSTRACT FROM AUTHOR]

The Brazilian Federal Senate created a Parliamentary Inquiry Commission (CPI) to investigate the Bolsonaro government's irregularities in the management of the COVID‐19 pandemic. One of the cases that drew attention was the research conducted by Prevent Senior, a private health insurance company, on the early treatment of COVID‐19. The article analyzes the scientific validity of the research and the ethical problems related to its implementation. It is based on analysis of Prevent Senior's report of the clinical study, the Brazilian and USA clinical trial registries, the Senate's CPI report, and on the information reported by the media. This case of scientific fraud and political‐ideological bias exemplifies how Prevent Senior, using a questionable protocol to enhance its reputation and gain government support, was instrumental in building the "early treatment" narrative for COVID‐19, and shows how it served as a basis for a government public policy that promoted the use of ineffective drugs. [ABSTRACT FROM AUTHOR]

Schizophrenia is a serious mental illness that imposes huge burden of illness on the society. We aimed to conduct a meta-analytic and systematic review of literature on the effectiveness of community-based rehabilitation interventions on symptoms and functioning for people with schizophrenia. The PubMed, Embase, the Cochrane Library, Web of Science, and CINAHL databases were searched through April 16 and 17, 2021, including clinical trial registries and previous Cochrane reviews. We included 24 randomized controlled trials in this review. The content of interventions varied from single-faceted rehabilitation intervention or cognitive retraining, to multi-component rehabilitation interventions or case management. Among 20 studies that reported effects of community-based rehabilitation interventions on symptoms, the pooled SMDs across all interventions was 0.94 (95% CI = 0.11, 1.76; P < 0.001; I2 = 99.1%; n = 3694), representing a strong effect. 21 included studies showed that community-based rehabilitation interventions also had beneficial impacts on functioning (SMD = 1.65; 95% CI = 0.88, 2.43; P < 0.001; I2 = 98.9%; n = 3734). Overall quality of evidence was moderate with a high level of heterogeneity. Community-based rehabilitation interventions have positive effectiveness in improving patients' symptoms and functioning. Community-based rehabilitation interventions should therefore be provided as an adjuvant service in addition to facility-based care for people with schizophrenia. [ABSTRACT FROM AUTHOR]

Clinical research in academic medical centers can be difficult to conduct and meet enrollment goals. Students under‐represented in medicine (URiM) are also under‐represented in academic leadership positions and as physician‐scientists but are critical to help solve health disparities. Barriers in pursuing medicine as a career may be high for URiM students, therefore it is important to create pre‐medicine opportunities accessible to all students interested in healthcare careers. We describe an undergraduate clinical research platform, the Academic Associate (AcA) program, embedded in the medical system that supports clinical research for academic physician scientists and provides students equitable access to experiences and mentoring opportunities. Students have the opportunity of completing a Pediatric Clinical Research Minor (PCRM) degree. This program satisfies many pre‐medicine opportunities for undergraduate students, including those URiM, and allows access to physician mentors and unique educational experiences for graduate school or employment. Since 2009, 820 students participated in the AcA program (17.5% URiM) and 235 students (18% URiM) completed the PCRM. Of the 820 students, 126 (10% URiM) students matriculated to medical school, 128 (11%URiM) to graduate school, and 85 (16.5% URiM) gained employment in biomedical research fields. Students in our program supported 57 publications and were top‐enrollers for several multicentered studies. The AcA program is cost‐effective and achieves a high level of success enrolling patients into clinical research. Additionally, the AcA program provides equitable access for students URiM to physician mentorship, pre‐medical experiences, and an avenue to early immersion in academic medicine. [ABSTRACT FROM AUTHOR]

Publication bias is a major concern in conducting systematic reviews and meta‐analyses. Various sensitivity analysis or bias‐correction methods have been developed based on selection models, and they have some advantages over the widely used trim‐and‐fill bias‐correction method. However, likelihood methods based on selection models may have difficulty in obtaining precise estimates and reasonable confidence intervals, or require a rather complicated sensitivity analysis process. Herein, we develop a simple publication bias adjustment method by utilizing the information on conducted but still unpublished trials from clinical trial registries. We introduce an estimating equation for parameter estimation in the selection function by regarding the publication bias issue as a missing data problem under the missing not at random assumption. With the estimated selection function, we introduce the inverse probability weighting (IPW) method to estimate the overall mean across studies. Furthermore, the IPW versions of heterogeneity measures such as the between‐study variance and the I2 measure are proposed. We propose methods to construct confidence intervals based on asymptotic normal approximation as well as on parametric bootstrap. Through numerical experiments, we observed that the estimators successfully eliminated bias, and the confidence intervals had empirical coverage probabilities close to the nominal level. On the other hand, the confidence interval based on asymptotic normal approximation is much wider in some scenarios than the bootstrap confidence interval. Therefore, the latter is recommended for practical use. [ABSTRACT FROM AUTHOR]

Background Time to symptom resolution measures were used in outpatient coronavirus disease 2019 (COVID-19) treatment trials without prior validation. Methods ACTIV-2/A5401 trial participants completed a COVID-19 diary assessing 13 targeted symptoms and global experience (overall COVID-19 symptoms, return to pre–COVID-19 health) daily for 29 days. We evaluated concordance of time to sustained (2 days) resolution of all targeted symptoms (TSR) with resolution of overall symptoms and return to health in participants receiving placebo. Results The analysis included 77 high-risk and 81 standard-risk participants with overall median 6 days of symptoms at entry and median age 47 years, 50% female, 82% white, and 31% Hispanic/Latino. Correlation between TSR and resolution of overall symptoms was 0.80 and 0.68, and TSR and return to health, 0.66 and 0.57 for high- and standard-risk groups, respectively. Of the high- and standard-risk participants, 61% and 79%, respectively, achieved targeted symptom resolution, of which 47% and 43%, respectively, reported symptom recurrence. Requiring >2 days to define sustained resolution reduced the frequency of recurrences. Conclusions There was good internal consistency between TSR and COVID-19–specific global outcomes, supporting TSR as a trial end point. Requiring >2 days of symptom resolution better addresses natural symptom fluctuations but must be balanced against the potential influence of non-COVID-19 symptoms. Clinical Trials Registration NCT04518410. [ABSTRACT FROM AUTHOR]

Clinical Trials Registration ClinicalTrials.gov Identifier: NCT04518410. [ABSTRACT FROM AUTHOR]

Study aims were to (I) transfer the measurement of the approach bias (Apb) related to alcoholic stimuli via the Approach Avoidance Task (AAT) into Virtual Reality (VR), (II) check whether measuring Apb in VR leads to similar or different results compared to the classical PC-based version, (III) check the validity of VR versus PC-based bias scores in terms of relatedness to clinical variables. Different 'grasping-conditions' were tested and contrasted in VR concerning (Ia) feasibility (performance): (1) never grasp, (2) always grasp, (3) grasp when PULLing stimuli towards oneself. (Ib) Differences in the bias scores between patients with alcohol use disorder (AUD) and healthy controls (HC) were examined for each grasping-condition. (II) PC-based bias scores were computed and contrasted for AUD versus HC. (III) Correlations of the different VR- versus PC-based bias scores with AUD symptom severity and impulsivity were checked to evaluate validity. (Ia) Grasping-condition 1, followed by 3, showed acceptable (> 50%) and good (> 80%) rates of correct performances allowing for robust median estimation. (Ib) Significant differences in the resulting bias scores emerged between AUD and HC only for grasping-condition 1 (p = 0.034) and 3 at trend-level (p = 0.093). For grasping-condition 1 the Apb Median for AUD was different from zero at a non-significant trend-level (p = 0.064). (II) The PC-based bias scores did not discriminate between AUD versus HC groups. (III) Grasping-condition 1 and 3 VR-based bias scores correlated significantly with impulsivity. In sum, transferring the AAT into VR is feasible, valid, and best implemented without an additional grasping-component when using the VR-controller. This way of Apb assessment represents a viable, perhaps even superior, alternative to PC-based assessments. Trial registration The trial was pre-registered at AsPredicted #76854: 'Transferring the approach avoidance task into virtual reality', 10/13/2021; prior to any analyses being undertaken. [ABSTRACT FROM AUTHOR]

Background: Robust synthesis of evidence to support treatment recommendations for preschoolers with attention‐deficit/hyperactivity disorder (ADHD) is lacking. The aim of this systematic review and meta‐analysis was to review currently available evidence to evaluate the efficacy and acceptability of stimulants for preschool children with ADHD. Methods: We searched electronic databases (CENTRAL, Embase, PubMed) from the database inception to March, 2022; and clinical trial registries through WHO ICTRP from the database inception to July, 2022, and selected double‐blinded randomized controlled trials (RCTs) that compared stimulants against placebo for the treatment of preschoolers (age ≤ 7 years) with ADHD. Change in ADHD symptom severity was the primary outcome (efficacy) and all‐cause dropout rates (acceptability) was the secondary outcome. Data were pooled with random‐effects models weighted by the inverse of the variance. Risk of bias of individual studies were assessed with the Cochrane Risk of Bias tool version 2. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the quality of evidence. This study is registered with PROSPERO (CRD42022348597). Results: Five RCTs (three methylphenidate immediate‐release, one methylphenidate extended‐release, and one lisdexamfetamine) were included. The analysis of efficacy was based on 489 participants. Meta‐analysis of change in ADHD symptom severity demonstrated a significant effect in favor of stimulants over placebo (standardized mean difference = −0.59; 95% CI −0.77, −0.41; p < 0.0001). There was no evidence of heterogeneity but some concerns about publication bias. Regardless, the confidence of evidence was considered moderate. For acceptability, stimulants did not lead to an increased rate of all‐cause discontinuation rates in comparison to placebo (OR = 0.59; 95% CI 0.15, 2.37; p = 0.45) but the confidence of estimate was very low. Conclusions: Our findings demonstrated that stimulants are efficacious in reducing ADHD symptoms among preschool children. Clinicians should consider the use of stimulants when making treatment recommendations for preschoolers with ADHD. [ABSTRACT FROM AUTHOR]

(1) Background: This systematic review and meta-analysis aims to evaluate the impact of a low glycemic index (LGI) and low glycemic load (LGL) diet on children with overweight and obesity, analyzing any changes in anthropometric, cardiometabolic, and glucometabolic parameters. (2) Methods: Three electronic databases (PubMed, Scopus, CENTRAL), as well as clinical trial registries and reference lists of the included studies, were searched for eligible randomized control trials (RCTs). Two independent reviewers performed the screening of the studies, data extraction, and risk of bias assessment. Mean difference (MD) and 95% confidence intervals (CI) using a random effects model were calculated for each outcome. (3) Results: Eleven RCTs (n = 634) examining the effect of LGI diet versus control were identified. The synthesized data provided from the RCTs indicate no difference between intervention and control groups regarding primary outcomes (body weight (MD: −0.14; 95% CI −1.93 to 1.64, 5 trials), body mass index (BMI) (MD: −0.31; 95% CI −0.85 to 0.23, 6 trials), BMI z-score (MD: −0.03; 95% CI −0.09 to 0.02, 5 trials), and waist circumference (MD: −0.52; 95% CI −2.35 to 1.31, 5 trials)) and other measures of cardiometabolic and glucometabolic parameters. The majority of trials were classified as "some concerns". (4) Conclusions: LGI and LGL diets do not seem to be associated with changes in adiposity, cardiometabolic or glucometabolic markers in children with overweight or obesity. Further research comparing the LGI diet to a high glycemic index diet, with proper methodological standards, is required to clarify the benefits of a LGI diet in this population. [ABSTRACT FROM AUTHOR]

Introduction: Menopause is a condition for metabolic disorders. This study aimed to evaluate the effect of Nigella sativa (NS), curcumin nanomicelle (CN), lipid profile, glycemic status and 17-β estradiol (ES) levels in postmenopausal women. Methods: Triple-blind randomized clinical trial was conducted on 120 postmenopausal women. Participants were randomly assigned to four groups: 1) NS capsule 1000 mg and CN placebo, 2) 80 mg CN capsule and NS placebo, 3) both NS and CN capsules and 4) NS and CN placebo. Participants received a single dose daily for 6 months. The serum lipid profile, glycemic control biomarkers, and ES were measured pre-and post-intervention using biochemical methods. Results: Total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, fasting blood sugar (FBS), fasting insulin (FI), insulin resistance (IR), and ES showed significant improvement in NS group. CN significantly reduced TC, FI, and IR, and significantly increased ES. The combination of NS-CN significantly decreased TC, LDL, FI, and IR, and increased HDL and ES. The comparison of the studied with the placebo groups showed that these changes were significant in glycemic indices and NS significantly increased estrogen. Conclusion: NS, CN and NS-CN improved lipid profiles, blood sugar, and hormone levels. However, this improvement was significant in glycemic indices and estrogen levels compared to the placebo group. No superiority of combined NS-CN over NS or CN was found in this trial. [ABSTRACT FROM AUTHOR]

Background: The current standard operation for proximal gastric and gastroesophageal junction (P/GEJ) cancers with limited esophageal extension is total gastrectomy (TG). TG is associated with impaired appetite and weight loss due to the loss of gastric functions such as production of ghrelin and with anemia due to intrinsic factor loss and vitamin B12 malabsorption. Theoretically, proximal gastrectomy (PG) can mitigate these problems by preserving gastric function. However, PG with direct esophagogastric reconstruction is associated with severe postoperative reflux, delayed gastric emptying, and poor quality of life (QoL). Minimally invasive PG (MIPG) with antireflux techniques has been increasingly performed by experts but is technically demanding owing to its complexity. Moreover, the actual advantages of MIPG over minimally invasive TG (MITG) with regards to postoperative QoL are unknown. Our overall objective of this study is to determine the short-term QoL benefits of MIPG. Our central hypotheses are that MIPG is safe and that patients have improved appetite after MIPG with effective antireflux techniques, which leads to an overall QoL improvement when compared with MITG. Methods: Enrollment of a total of 60 patients in this prospective survey-collection study is expected. Procedures (MITG versus MIPG, antireflux techniques for MIPG [double-tract reconstruction versus the double-flap technique]) will be chosen based on surgeon and/or patient preference. Randomization is not considered feasible because patients often have strong preferences regarding MITG and MIPG. The primary outcome is appetite level (reported on a 0-10 scale) at 3 months after surgery. With an expected 30 patients per cohort (MITG versus MIPG), this study will have 80% power to detect a one-point difference in appetite level. Patient-reported outcomes will be longitudinally collected (including questions about appetite and reflux), and specific QoL items, body weight, body mass index and ghrelin, albumin, and hemoglobin levels will be compared. Discussion: Surgeons from the US, Japan, and South Korea formed this collaboration with the agreement that the surgical approach to P/GEJ cancers is an internationally important but controversial topic that requires immediate action. At the completion of the proposed research, our expected outcome is the establishment of the benefit and safety of MIPG. Trial registration: This trial was registered with Clinical Trials Reporting Program Registration under the registration number NCI-2022–00267 on January 11, 2022, as well as with ClinicalTrials.gov under the registration number NCT05205343 on January 11, 2022. [ABSTRACT FROM AUTHOR]

Key Points: Question: Can an individualized treatment rule identify patients who benefit as much or more from self-guided internet-delivered cognitive behavioral therapy (i-CBT) as from guided i-CBT? Findings: In this secondary analysis of a randomized clinical trial of 1319 university students with anxiety and/or depression, guided i-CBT optimized the probability of (1) joint remission of anxiety and depression for 91.7% of participants, (2) remission of anxiety for 100% of participants, and (3) remission of depression for 71.5% of participants. Self-guided i-CBT, in comparison, optimized the probability of remission of depression for the remaining 28.5% of participants. Meaning: Self-guided i-CBT is sometimes equally or more effective than guided i-CBT for depression but not anxiety. Importance: Guided internet-delivered cognitive behavioral therapy (i-CBT) is a low-cost way to address high unmet need for anxiety and depression treatment. Scalability could be increased if some patients were helped as much by self-guided i-CBT as guided i-CBT. Objective: To develop an individualized treatment rule using machine learning methods for guided i-CBT vs self-guided i-CBT based on a rich set of baseline predictors. Design, Setting, and Participants: This prespecified secondary analysis of an assessor-blinded, multisite randomized clinical trial of guided i-CBT, self-guided i-CBT, and treatment as usual included students in Colombia and Mexico who were seeking treatment for anxiety (defined as a 7-item Generalized Anxiety Disorder [GAD-7] score of ≥10) and/or depression (defined as a 9-item Patient Health Questionnaire [PHQ-9] score of ≥10). Study recruitment was from March 1 to October 26, 2021. Initial data analysis was conducted from May 23 to October 26, 2022. Interventions: Participants were randomized to a culturally adapted transdiagnostic i-CBT that was guided (n = 445), self-guided (n = 439), or treatment as usual (n = 435). Main Outcomes and Measures: Remission of anxiety (GAD-7 scores of ≤4) and depression (PHQ-9 scores of ≤4) 3 months after baseline. Results: The study included 1319 participants (mean [SD] age, 21.4 [3.2] years; 1038 women [78.7%]; 725 participants [55.0%] came from Mexico). A total of 1210 participants (91.7%) had significantly higher mean (SE) probabilities of joint remission of anxiety and depression with guided i-CBT (51.8% [3.0%]) than with self-guided i-CBT (37.8% [3.0%]; P =.003) or treatment as usual (40.0% [2.7%]; P =.001). The remaining 109 participants (8.3%) had low mean (SE) probabilities of joint remission of anxiety and depression across all groups (guided i-CBT: 24.5% [9.1%]; P =.007; self-guided i-CBT: 25.4% [8.8%]; P =.004; treatment as usual: 31.0% [9.4%]; P =.001). All participants with baseline anxiety had nonsignificantly higher mean (SE) probabilities of anxiety remission with guided i-CBT (62.7% [5.9%]) than the other 2 groups (self-guided i-CBT: 50.2% [6.2%]; P =.14; treatment as usual: 53.0% [6.0%]; P =.25). A total of 841 of 1177 participants (71.5%) with baseline depression had significantly higher mean (SE) probabilities of depression remission with guided i-CBT (61.5% [3.6%]) than the other 2 groups (self-guided i-CBT: 44.3% [3.7%]; P =.001; treatment as usual: 41.8% [3.2%]; P <.001). The other 336 participants (28.5%) with baseline depression had nonsignificantly higher mean (SE) probabilities of depression remission with self-guided i-CBT (54.4% [6.0%]) than guided i-CBT (39.8% [5.4%]; P =.07). Conclusions and Relevance: Guided i-CBT yielded the highest probabilities of remission of anxiety and depression for most participants; however, these differences were nonsignificant for anxiety. Some participants had the highest probabilities of remission of depression with self-guided i-CBT. Information about this variation could be used to optimize allocation of guided and self-guided i-CBT in resource-constrained settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04780542 This prespecified secondary analysis of a randomized clinical trial discusses the development of an individualized treatment rule using machine learning methods for guided vs self-guided internet-delivered cognitive behavioral therapy based on a rich set of baseline predictors. [ABSTRACT FROM AUTHOR]

Purpose: Wii Fit exergames have been less commonly used for the rehabilitation of athletes after Anterior Cruciate Ligament Reconstruction (ACLR). This study aims to investigate the effects of an expert system using Wii Fit exergames compared to conventional rehabilitation following ACLR. A forward-chaining rule-based expert system was developed which proposed a rehabilitation program that included the number and type of exercise in terms of difficulty and ease and the duration of each exercise in a progressive manner according to the patient's physical condition. Materials and methods: Twenty eligible athletes aged 20–30 who underwent ACLR were enrolled in this study and randomly assigned to two groups; and received 12 sessions of either Wii Fit exergames as Wii group (n = 10) or conventional rehabilitation as CL group (n = 10). Results: The main outcomes consisted of pain (Visual Analogue Scale (VAS)), knee effusion, knee flexion range (KFR), thigh girth (TG), single-leg hop for distance (SLHD), and for time (SLHT), static and dynamic balance tests. Both groups had considerable improvement in all outcomes, also there were significantly differences between Wii and CL groups as follows; VAS (P < 0.001), knee effusion (P < 0.001), TG (P = 0.001), KFR (P = 0.012), static balance in stable position (P < 0.001) and in unstable position (P = 0.001), dynamic balance in the anterior (P < 0.001), posteromedial (P < 0.001), posterolateral (P = 0.004) directions, symmetry index of SLHD (P < 0.001) and symmetry index of SLHT (P = 0.013). Conclusions: The findings showed that using Wii Fit exergames in post-ACLR patients reduced pain and effusion while also improving function and balance significantly. Iranian Registry of Clinical Trials registration number is IRCT20191013045090N1, and the registration date is 03-03-2020. [ABSTRACT FROM AUTHOR]

Background: Fussy eating is most often a developmentally typical behaviour, generally presenting during toddlerhood. However, up to half of parents of young children are concerned about fussy eating, and this concern may mediate the use of nonresponsive feeding practises, such as coercive or unstructured feeding and using food to reward eating. Despite the high prevalence of parental concern for fussy eating and the negative impacts nonresponsive feeding practises have on children's health and diets, no previous digital intervention to improve the feeding practises of parents of toddlers concerned about fussy eating has been evaluated. Aim: This article describes the protocol of a randomised controlled feasibility pilot aiming to evaluate Fussy Eating Rescue, a purely web app based intervention for parents of toddlers. The primary aim is to investigate feasibility and acceptability; secondary aims are to explore indications of intervention effect on parents' feeding practises or children's eating behaviours. Methods: Fussy Eating Rescue features include: (1) a Tracker, that allows parents to track repeated offers of food, (2) Topics, providing information on fussy eating, effective feeding strategies, and general nutrition, (3) Rescues, containing quick references to material supporting Topics contents, (4) Recipes, and (5) SMS notifications. Parents of toddlers (12–36 months old, n = 50) who have concerns about fussy eating will be recruited via Facebook. Parents will be randomised to an intervention group, which receives access to the app for 6 weeks, or to wait-listed control. Outcomes will be assessed at baseline and 6 weeks after app use, using online questionnaires and app usage statistics. Primary outcomes include participant retention rate, intervention engagement, app usability, perceived ease in using the app, perceived usefulness of the app, and user satisfaction. Secondary outcome measures include parents' feeding practises and children's eating behaviours. Discussion: Results will inform whether Fussy Eating Rescue is a feasible way to engage parents concerned for their toddler's fussy eating behaviours. If feasible and acceptable to users, a larger trial will further examine the efficacy of the Fussy Eating app in improving parents' feeding practises and children's eating behaviours. Trial registration: Prospectively registered with the Australian New Zealand Clinical Trials Registry on 15 July, 2021 (ACTRN12621000925842). [ABSTRACT FROM AUTHOR]

Background: The United Kingdom nutrition database monitors the changing landscape of adult home parenteral nutrition support (HPS) to inform clinicians and policy makers of the need for this life‐saving treatment. Methods: The UK database is administered by the British Association for Parenteral and Enteral Nutrition. Data for home parenteral nutrition (HPN) has been collected since 2005 and home intravenous fluids (HIVFs) since 2011. During this study the reporting of data to the database by healthcare workers has been voluntary. Data were analyzed using linear regression. Results: A threefold increase of new registrations for patients receiving HPS was noted on this 10‐year period, with a notable increase in the number of patients with advanced malignancy supported with HPS. Crohn's disease and short bowel syndrome were the leading causes for both HPN and HIVF use in the UK. A statistically significant increase in older (P < 0.001) and less independent patients using HPS was noted. Conclusion: The prevalence of HPS is steadily increasing in size with the broadening of its acceptable performance status. The launch of the Intestinal Failure Registry and mandatory registration will increase accuracy in data reporting. [ABSTRACT FROM AUTHOR]

Objective: The Core Clinical Journals (CCJ) list, produced by the U.S. National Library of Medicine (NLM), has been used by clinicians and librarians for half a century for two main purposes: narrowing a literature search to clinically useful journals and identifying high priority titles for library collections. After documentation of low usage of the existing CCJ, a review was undertaken to assess current validity, followed by an update to current clinical needs. Methods: As the subject coverage of the 50-year-old list had never been evaluated, the CCJ committee began its innovative step-wise approach by analyzing the existing subject scope. To determine whether clinical subjects had changed over the last half-century, the committee collected data on journal usage in hospitals and medical facilities, adding journal usage from Morning Report blogs recording the journal article citations used by physicians and residents in response to clinical questions. Patient-driven high-frequency diagnoses and subjects added contextual data by depicting the clinical environment. Results: The analysis identified a total of 80 subjects and selected 241 journals for the updated Clinical Journals filter, based on actual clinical utility of each journal. Discussion: These data-driven methods created a different framework for evaluating the structure and content of this filter. It is the real-world evidence needed to highlight CCJ clinical impact and push clinically useful journals to first page results. Since the new process resulted in a new product, the name warrants a change from Core Clinical Journals (CCJ) to Clinically Useful Journals (CUJ). Therefore, the redesigned NLM Core Clinical Journals/AIM set from this point forward will be referred to as Clinically Useful Journals (CUJ). The evidence-based process used to reframe evaluation of the clinical impact and utility of biomedical journals is documented in this article. [ABSTRACT FROM AUTHOR]

Background: Improving depression is critical to the success of HIV treatment. Concerns about the adverse effects of pharmacotherapy have led to non-pharmacological treatments for depression in people living with HIV (PLWH) becoming increasingly popular. However, the most effective and acceptable non-pharmacological treatments for depression in PLWH have not yet been determined. This protocol for a systematic review and network meta-analysis aims to compare and rank all available non-pharmacological treatments for depression in PLWH in the global network of countries as well as in the network of low-income and middle-income countries (LMICs) only. Methods: We will include all randomized controlled trials of any non-pharmacological treatments for depression in PLWH. The primary outcomes will consider efficacy (the overall mean change scores in depression) and acceptability (all-cause discontinuation). Published and unpublished studies will be systematically searched through the relevant databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PsycINFO, CINAHL, ProQuest, and OpenGrey), international trial registers, and websites. There is no restriction by language and publication year. All study selection, quality evaluation, and data extraction will be independently conducted by at least two investigators. We will perform a random-effects network meta-analysis to synthesize all available evidence for each outcome and obtain a comprehensive ranking of all treatments for the global network of countries as well as for the network of LMICs only. We will employ validated global and local approaches to evaluate inconsistency. We will use OpenBUGS (version 3.2.3) software to fit our model within a Bayesian framework. We will evaluate the strength of evidence using the Confidence in Network Meta-Analysis (CINeMA) tool, a web application based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Ethics and dissemination: This study will use secondary data and therefore does not require ethical approval. The results of this study will be disseminated through peer-reviewed publication. Trial registration: PROSPERO registration number: CRD42021244230. [ABSTRACT FROM AUTHOR]

Background: As a practice-oriented discipline, strict adherence to reporting guidelines is particularly important in randomized controlled trial (RCT) abstracts of the nursing area. However, whether abstract reports after 2010 have complied with the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) guideline is unclear. This study aimed to evaluate whether the publication of CONSORT-A has improved abstract reporting in nursing and explores the factors associated with better adherence to the guidelines. Methods: We searched the Web of Science for 200 RCTs randomly selected from ten nursing journals. We used a data extraction form based on CONSORT-A, including 16 items, to analyze the reporting adherence to the guidelines, and the reporting rate of each item and the total score for each abstract were used to indicate adherence and overall quality score (OQS, range 0–16). A comparison of the total mean score between the two periods was made, and affecting factors were analyzed. Results: In the studies we included, 48 abstracts were published pre-CONSORT-A whereas 152 post-CONSORT-A. The overall mean score for reporting adherence to 16 items was 7.41 ± 2.78 and 9.16 ± 2.76 for pre- and post-CONSORT-A, respectively (total score: 16). The most poorly reported items are "harms (0%)," "outcomes in method (8.5%)," "randomization (25%)," and "blinding (6.5%)." Items including the year of publication, impact factor, multiple center trial, word count, and structured abstract are significantly associated with higher adherence. Conclusions: The adherence to abstract reporting in nursing literature has improved since the CONSORT-A era, but the overall completeness of RCT abstracts remained low. A joint effort by authors, editors, and journals is necessary to improve reporting quality of RCT abstracts. [ABSTRACT FROM AUTHOR]

Background: The optimal dose of tenecteplase vs. alteplase for acute ischemic stroke (AIS) has yet to be established. Therefore, we included the latest randomized controlled trials (RCT) to assess the efficacy and safety of different doses of tenecteplase vs. alteplase for AIS within 4.5 hours of symptom onset. Methods: Literature was searched in PubMed, Cochrane Library, Embase, Web of Science, and clinical trial registries until February 12, 2023. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using Bayesian network meta-analysis (NMA). Treatments were ranked based on efficacy and safety using the surface under the cumulative ranking curve (SUCRA). Results: Eleven RCTs with 5,475 patients were included. Tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg had signicantly higher rates of excellent functional outcome (tenecteplase: OR, 1.85; 95% CrI, 1.44--2.37; alteplase: OR, 1.60; 95% CrI, 1.29--1.97) and good functional outcome (tenecteplase: OR, 1.54; 95% CrI, 1.19-- 1.98; alteplase: OR, 1.40; 95% CrI, 1.14--1.74) than placebo, despite an increased risk of symptomatic intracranial hemorrhage. Furthermore, the NMA (OR, 1.16; 95% CrI, 1.01--1.33) and the pairwise meta-analysis (OR, 1.16; 95% CI, 1.02--1.33; P = 0.03) indicated that tenecteplase 0.25 mg/kg was superior to alteplase 0.9 mg/kg in excellent functional outcome. Alteplase 0.9 mg/kg (OR, 2.54; 95% CrI, 1.45-- 8.08) signicantly increased the risk of any intracranial hemorrhage compared with placebo. SUCRA results demonstrated that tenecteplase 0.25 mg/kg ranked rst and tenecteplase 0.4 mg/kg ranked last in efficacy outcomes. Conclusions: The NMA indicated that tenecteplase 0.25 mg/kg and alteplase 0.9 mg/kg are safe and signicantly improve clinical outcomes in patients with AIS within 4.5 h of symptom onset. Furthermore, tenecteplase 0.25 mg/kg provides more benet and has the potential to replace alteplase 0.9 mg/kg in AIS treatment. [ABSTRACT FROM AUTHOR]

Background: Gender-based violence (GBV) is a major public health concern and a human rights issue disproportionately affecting disabled women. Disabled women are twice as likely to experience GBV than nondisabled women, yet there has been a lack of attention to this issue. This review aims to gain a greater understanding of the experiences of GBV of disabled women through a systematic and qualitative meta-synthesis. The qualitative meta-synthesis will be conducted by a research team of academic and community members and students with varying lived and service provider experiences with disabilities and GBV. The study findings aim to promote best practices by offering solutions to increase accessible and inclusive resources and services responsive to disabled women. Methods: A systematic review of qualitative studies will be performed based on searches of 12 academic databases, including MEDLINE (Ovid), APA PsycINFO (EBSCO), Sociological Abstracts (ProQuest), Social Services Abstracts (ProQuest), and SocINDEX (EBSCO). A search of the gray literature will be performed by searching the Google search engine, Google Scholar, the Community Health Online Digital Archive and Research Resource (CHODARR), and the Global Database on Violence Against Women. In addition to the database and gray literature searching, we will complete backward and forward citation tracing. Two research team members will be involved in all screening, review, data extraction, and quality assessment of studies. A third reviewer will resolve any disagreements and consult with the research team. Thematic synthesis steps will include becoming familiar with the data, developing a thematic framework, indexing the data to identify themes and codes, charting the data, and mapping and interpreting the data. The Critical Appraisal Skills Programme checklist will be used to appraise the quality of included studies. Confidence in the meta-synthesis findings will be assessed by applying the GRADECERQual approach. Review Registration: This protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO): CRD42023400410. [ABSTRACT FROM AUTHOR]

This study aims to examine functional idiosyncrasies of seemingly synonymous constructions and explain their frequency distributions in different spoken registers. To this end, lexical and discoursal approaches in the corpus-based research of constructions are combined to investigate how significant collocates of three suggesting constructions – namely, let's , what/how about and why don't you/we – are contextually situated in British English. Constructional analyses of the spoken part of the British National Corpus show that the three suggesting constructions primarily perform different metadiscourse and directive functions. Based on these functional variations, the present study explains the distribution and usage of the three suggesting constructions across the five spoken registers. [ABSTRACT FROM AUTHOR]

Background: The anti‐inflammatory effect of vitamin D in patients with chronic kidney disease (CKD) remains controversial. This study aimed to conduct a meta‐analysis of randomized controlled trials to assess the anti‐inflammatory effects of vitamin D in patients with CKD. Methods: We searched Embase, Science Citation Index, Medline, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials that comparing vitamin D with control groups for inflammatory markers in patients with CKD. Subgroup analysis was performed based on treatment duration (short‐term treatment, long‐term treatment), type of patients (predialysis CKD, dialysis, kidney transplant), 25(OH)D levels (25(OH)D deficiency or normal 25(OH)D), and methods of C‐reactive protein (CRP) test (standard CRP test or high‐sensitivity CRP [hs‐CRP] test). Results: Eighteen trials with 1834 patients were included in the present study. There were no significant differences between the vitamin D group and control group for CRP (WMD, −0.3 mg/L; 95% CI, −0.81 to 0.22, p = 0.26, I2 = 62%), interleukin‐6 (IL‐6) (WMD, −1.07 pg/ml; 95% CI, −2.44 to 0.30, p = 0.12, I2 = 52%), and tumor necrosis factor‐α (TNF‐α) (WMD, −0.00 pg/ml; 95% CI, −0.36 to 0.35, p = 0.99, I2 = 0%) in patients with CKD. Subgroup analysis showed vitamin D can improve hs‐CRP, but not CRP. The rest of subgroups showed that no significant differences were observed between the vitamin D group and control group based on 25(OH)D levels, treatment duration, and predialysis CKD or dialysis patients. Conclusion: This meta‐analysis demonstrates that vitamin D supplementation does not have anti‐inflammatory effects in CKD patients. Well‐designed randomized controlled trials with large samples are required to confirm this conclusion. It is still needed to find an effective treatment for inflammatory state in CKD. [ABSTRACT FROM AUTHOR]

Background: Multi-professional cooperation between healthcare providers is a key quality criterion of hospice and palliative care. While hospice and palliative care networks can support cooperation on a local level, opportunities for wider cooperation through the establishment and development of regional hospice and palliative care networks in Germany have not yet been explored systematically. Aims: The HOPAN study aims at: (1) identifying regional hospice and palliative care networks in Germany, (2) analysing these networks using an adapted quality assessment tool, and (3) proposing setting-sensitive recommendations for network development and exploring the benefits of these recommendations. Methods: HOPAN is a prospective, observational, mixed-methods study comprising three work packages (WPs). In WP1, the stock of regional hospice and palliative care networks in Germany will be identified via database, literature, and internet research. In WP2a, focus groups will be conducted to adapt an existing maturity model for healthcare networks to regional hospice and palliative care networks. In WP2b, a questionnaire will be sent to each identified regional hospice and palliative care network to gain insight into their structure and status of development. In WP2c, group discussions will be conducted to develop setting-sensitive recommendations for these networks. Finally, in WP3, these recommendations will be sent to all participating hospice and palliative care networks, and the benefits of the recommendations will be evaluated via a questionnaire. Discussion: Empirically developed setting-sensitive recommendations should enable the systematic establishment and management of regional hospice and palliative care networks in Germany, considering the specific needs and potential of each network. The study findings are expected to improve the overall development of hospice and palliative care services. Trial registration: The study was prospectively registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien) (Registration N° DRKS00030629; date of registration: 02 November 2022). The study is searchable under the International Clinical Trials Registry Platform Search Portal of the World Health Organization, under the German Clinical Trials Register number. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does exogenous estrogen use affect COVID-19-related mortality in women? SUMMARY ANSWER Menopausal hormone therapy (MHT) was associated with a lower likelihood of all-cause fatality related to COVID-19 in postmenopausal women (odds ratio (OR) 0.28, 95% CI 0.18, 0.44; 4 studies, 21 517 women) but the combined oral contraceptive pill in premenopausal women did not have a significant effect (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). WHAT IS KNOWN ALREADY Men are much more likely to die from COVID-19 than women. STUDY DESIGN, SIZE, DURATION In this systematic meta-analysis, a literature search was conducted using the following search terms related toCOVID-19 and estrogen, sex hormones, hormonal replacement, menopause, or contraception. The PubMed, Scopus, Cochrane Library, and EMBASE databases were searched to identify relevant studies published between December 2019 and December 2021. We also searched MedRxiv as a preprint database and reviewed the reference lists of all included studies and clinical trial registries for ongoing clinical studies until December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS All comparative studies that compared the rates mortality and morbidity (hospitalization, intensive care unit (ICU) admission, and ventilation support) due to COVID-19 in women using exogenous estrogen to a control group of women (nonusers) were included. A review of the studies for inclusion, extraction of data, and assessment of the risk of bias was performed independently by two reviewers. The ROBINS-I tool and the RoB 2 tool were used for bias assessment of the included studies. Pooled odds ratios (ORs) with 95% CIs were calculated using Review Manager V5.4.1. The I 2 statistic was used to quantify heterogeneity. The quality of the evidence was assessed using GRADE criteria. MAIN RESULTS AND THE ROLE OF CHANCE After searching the databases, we identified a total of 5310 studies. After removing duplicate records, ineligible studies, and ongoing studies, a total of four cohort studies and one randomized controlled trial comprising 177 809 participants were included in this review. There was a moderate certainty of evidence that MHT was associated with a lower likelihood of all-cause fatality related to COVID-19 (OR 0.28, 95% CI 0.18, 0.44; I 2 = 0%; 4 studies, 21 517 women). The review indicated a low certainty of evidence for other outcomes. The mortality rate of premenopausal women in the combined oral contraceptive pill group did not differ significantly from the control group (OR 1.00, 95% CI 0.42–2.41; 2 studies, 5099 women). MHT marginally increased the rate of hospitalization and ICU admission (OR 1.37, 95% CI 1.18–1.61; 3 studies, 151 485 women), but there was no significant difference in the need for respiratory support between MHT users and nonusers (OR 0.91, 95% CI 0.52–1.59; 3 studies, 151 485 women). Overall, the tendency and magnitude of the effects of MHT in postmenopausal women with COVID-19 were consistent across the included studies. LIMITATIONS, REASONS FOR CAUTION The certainty of the evidence for other outcomes of this review may be limited, as all included studies were cohort studies. In addition, the dosages and durations of exogenous estrogen used by postmenopausal women varied from study to study, and combined progestogen administration may have had some effect on the outcomes. WIDER IMPLICATIONS OF THE FINDINGS The findings of this study can aid in counseling postmenopausal women taking MHT when they are diagnosed with COVID, as they have a lower chance of death than those not taking MHT. STUDY FUNDING/COMPETING INTEREST(s) Khon Kaen University provided financial support for this review and had no involvement at any stage of the study. The authors have no conflicts of interest to declare. REGISTRATION NUMBER PROSPERO, CRD42021271882. [ABSTRACT FROM AUTHOR]

As word formation can be conceptualized as an act of creativity with considerable space for differences among speakers, we present pilot research aimed at the examination of the role of Big-Five personality domains in the formation of new complex words. The sample consisted of 197 participants who underwent a word formation test and a personality assessment via The Next Big-Five Inventory. The results indicate that when ordinal regression is conducted with an aim of accounting for age and gender, open-mindedness is shown as a potentially important predictor – it positively predicted economy of expression and negatively predicted semantic transparency. Furthermore, a more nuanced approach differentiating three facets of open-mindedness shows that creative imagination predicted semantic transparency positively while esthetic sensitivity predicts semantic transparency negatively (the reverse is true for the economy of expression). These findings provide a promising starting point for future research. [ABSTRACT FROM AUTHOR]

Agitation is common in the early recovery period following traumatic brain injury (TBI), known as post-traumatic amnesia (PTA). Non-pharmacological interventions are frequently used to manage agitation, yet their efficacy is largely unknown. This systematic review aims to synthesize current evidence on the effectiveness of non-pharmacological interventions for agitation during PTA in adults with TBI. Key databases searched included MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO and CENTRAL, with additional online reviewing of key journals and clinical trial registries to identify published or unpublished studies up to May 2020. Eligible studies included participants aged 16 years and older, showing agitated behaviours during PTA. Any non-pharmacological interventions for reducing agitation were considered, with any comparator accepted. Eligible studies were critically appraised for methodological quality using Joanna Briggs Institute Critical Appraisal Instruments and findings were reported in narrative form. Twelve studies were included in the review: two randomized cross-over trials, three quasi-experimental studies, four cases series and three case reports. Non-pharmacological interventions were music therapy, behavioural strategies and environmental modifications, physical restraints and electroconvulsive therapy. Key methodological concerns included absence of a control group, a lack of formalised agitation measurement and inconsistent concomitant use of pharmacology. Interventions involving music therapy had the highest level of evidence, although study quality was generally low to moderate. Further research is needed to evaluate non-pharmacological interventions for reducing agitation during PTA after TBI. Systematic review registration number: PROSPERO (CRD42020186802), registered May 2020. [ABSTRACT FROM AUTHOR]

Background: Hip resurfacing arthroplasty (HRA) is associated with excellent functional outcomes and return to pre-disease level of activity. The time for return to sport (RTS) following HRA remains unknown. The aim of this meta-analysis was to establish the time for RTS following HRA. Methods: A search was performed on PUBMED, MEDLINE, EMBASE, and the Cochrane Library for trials on HRA and RTS, in the English language, published from the inception of the database to October 2020. In addition, a manual search was performed of relevant sports medicine and orthopaedic journals, and the bibliographies reviewed for eligible trials. All clinical trials reporting on time to RTS following HRA were included. Data relating to patient demographics, methodological quality, operation type, RTS, clinical outcomes, and complications were recorded by two independent reviewers. The PRISMA guidelines for reporting meta-analyses was used to undertake this study. Results: The initial literature search identified 1559 studies and nine further studies were found. Of these, 11 studies with a total of 659 patients matched the inclusion criteria. Two studies involving a total of 94 patients demonstrated an overall pooled proportion of 91.8% (95% CI 71.8–100) of patients RTS by three months post-operatively. Four studies including a total of 265 patients determined a pooled proportion of 96.8% (95% CI 91.0–99.7) of patients able to RTS by the 6-month post-operative stage. Pooled proportion analysis from all 11 studies comprising 659 patients showed 90.9% (95% CI 82.2–96.9) of patients were able to RTS by final follow up of 3 years. Conclusion: Pooled proportion analysis showed an increasing number of patients were able to RTS after HRA over the first one year after surgery. There remains marked inter and intra-study variations in time for RTS but the pooled analysis shows that over 80% of patients were able to RTS at 6 to 12 months after HRA. The findings of this meta-analysis will enable more informed discussions between patients and healthcare professionals about time for RTS following HRA. [ABSTRACT FROM AUTHOR]

Purpose: In Australia and elsewhere, suicide rates among construction workers remain high. Construction workplaces are thus an important setting for targeted suicide prevention programs. This study aimed to compare suicide prevention literacy and help-seeking intentions among participants receiving face-to-face suicide prevention training, with those receiving face-to-face training augmented by a smartphone application. Methods: A two-arm randomised controlled trial of a smartphone suicide prevention intervention was conducted among construction workers in four Australian states (trial registration number: ACTRN12619000625178). All participants received face-to-face training and were randomised to the control condition (face-to-face only, n = 575), or MATESmobile condition (face-to-face + smartphone application,n = 509). Surveys administered at baseline and 3-month follow-up measured suicide prevention literacy and help-seeking intentions for personal/emotional problems and suicidal thoughts. A mixed-model repeated measures (MMRM) analysis included all 1084 randomised participants. Results: Outcomes did not differ significantly for suicide prevention literacy, nor help-seeking intentions from formal sources, informal sources outside the workplace, or no one (did not intend to seek help from anyone). However, relative to those in the control condition, those in the MATESmobile group showed greater increase in help-seeking intentions for emotional problems from a MATES worker/Connector (mean difference 0.54, 95% CI 0.22–0.87) and help-seeking intentions for suicidal thoughts from a workmate (mean difference 0.47, 95% CI 0.10–0.83) or MATES worker/Connector (mean difference 0.47, 95% CI 0.09–0.85). Conclusion: Results indicate that the MATESmobile application, together with face-to-face training, is beneficial in enhancing help-seeking intentions from MATES workers/Connectors and workmates to a greater extent than face-to-face training only. While this research provides some evidence that smartphone applications may support suicide prevention training, further research is needed. [ABSTRACT FROM AUTHOR]

Ordinal endpoints are common in clinical studies. For example, many clinical trials for evaluating COVID-19 infection therapies have adopted an ordinal scale as recommended by the World Health Organization. Despite their importance in clinical studies, design methods for ordinal endpoints are limited; in practice, a dichotomized approach is often used for simplicity. Here, we introduce a Bayesian group sequential scheme to assess ordinal endpoints, which considers a proportional-odds (PO) model, a nonproportional-odds (NPO) model, and a PO/NPO-switch model to handle various scenarios. Extensive simulations are conducted to demonstrate desirable performance, and the R package BayesOrdDesign has been made publicly available. [ABSTRACT FROM AUTHOR]

Background: Paediatric trials must contend with many challenges that adult trials face but often bring additional obstacles. Decentralised trials, where some or all trial methods occur away from a centralised location, are a promising strategy to help meet these challenges. This scoping review aims to (a) identify what methods and tools have been used to create and conduct entirely online-decentralised trials with children and (b) determine the gaps in the knowledge in this field. This review will describe the methods used in these trials to identify their facilitators and the gaps in the knowledge. Methods: The methods were informed by guidance from the Joanna Briggs Institute and the PRISMA extension for scoping reviews. We systematically searched MEDLINE, CENTRAL, CINAHL, and Embase databases, trial registries, pre-print servers, and the internet. We included randomised and quasi-randomised trials conducted entirely online with participants under 18 published in English. A risk of bias assessment was completed for all included studies. Results: Twenty-one trials met our inclusion criteria. The average age of participants was 14.6 years. Social media was the most common method of online recruitment. Most trials employed an external host website to store and protect their data. Duration of trials ranged from single-session interventions up to ten weeks. Fourteen trials compensated participants. Eight trials involved children in their trial design process; none reported compensation for this. Most trials had a low risk of bias in "random sequence generation", "selective reporting", and "other". Most trials had a high risk of bias in "blinding participants and personnel", "blinding of outcome assessment", and "incomplete outcome data". "Allocation concealment" was unclear in most studies. Conclusions: There was a lack of transparent reporting of the recruitment, randomisation, and retention methods used in many of the trials included in this review. Patient and public involvement (PPI) was not common, and the compensation of PPI partners was not reported in any study. Consent methods and protection against fraudulent entries to trials were creative and thoroughly discussed by some trials and not addressed by others. More work and thorough reporting of how these trials are conducted is needed to increase their reproducibility and quality. Ethics and dissemination: Ethical approval was not necessary since all data sources used are publicly available. [ABSTRACT FROM AUTHOR]

Objectives: Traumatic brain injury (TBI) is one of the top causes of morbidity and mortality worldwide. The review aimed to discuss and summarize the current evidence on the effectiveness of adjuvant neuroprotective treatments in terms of their effect on brain injury biomarkers in TBI patients. Methods: To identify relevant studies, four scholarly databases, including PubMed, Cochrane, Scopus, and Google Scholar, were systematically searched using predefined search terms. English-language randomized controlled clinical trials reporting changes in brain injury biomarkers, namely, neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1) and/or S100 beta (S100 ß), were included. The methodological quality of the included studies was assessed using the Cochrane risk-of-bias tool. Results: A total of eleven studies with eight different therapeutic options were investigated; of them, tetracyclines, metformin, and memantine were discovered to be promising choices that could improve neurological outcomes in TBI patients. The most utilized serum biomarkers were NSE and S100 ß followed by GFAP, while none of the included studies quantified UCHL1. The heterogeneity in injury severity categories and measurement timing may affect the overall evaluation of the clinical efficacy of potential therapies. Therefore, unified measurement protocols are highly warranted to inform clinical decisions. Conclusion: Few therapeutic options showed promising results as an adjuvant to standard care in patients with TBI. Several considerations for future work must be directed towards standardizing monitoring biomarkers. Investigating the pharmacotherapy effectiveness using a multimodal biomarker panel is needed. Finally, employing stratified randomization in future clinical trials concerning potential confounders, including age, trauma severity levels, and type, is crucial to inform clinical decisions. [ABSTRACT FROM AUTHOR]