Nursing students must be well-prepared and competent in medication administration (MA) and be able to apply pharmacology knowledge as registered nurses. MA is integral to ensuring patient safety, but nursing students find it challenging to acquire competency in MA. Little is known about assessing medication administration competency in various clinical practice settings.

To conduct a systematic review of how undergraduate nursing students' medication administration competency is assessed in clinical practice settings.

Original research studies were identified using PubMed, Web of Science, CINAHL, PsycINFO, Scopus, ScienceDirect, and ERIC. This systematic literature review included primary research studies using objective competency measures of MA assessment of undergraduate nursing students in a clinical practice setting, published in English between 1990 and 2023. Data was extracted and synthesised using the Preferred Reporting Items for Systematic Reviews.

32 original research papers were included in the review. Studies came from 12 countries. A quasi-experimental design was used by 75 % of studies to examine MA competency assessment. Medication assessments were conducted primarily in simulation labs. Simulation was found to have positive outcomes on MA competency on clinical placement. Studies were grouped into three categories: 'Using technology', 'Educational Strategies', and 'Focus on Safety skills'. Studies reported error rates associated with patient identification and hand hygiene, including those of senior nursing students. Quality appraisal was conducted using the Medical Education Research Study Quality Instrument (MERSQI). The MERSQI Mean score was 12.92/18. Several studies failed to report the sample size calculation and the validity of instruments.

A whole-curriculum approach with MA content and skills mapped and scaffolded across the undergraduate nursing program is required to enable students to achieve MA competency. Attention to the design of studies is required to ensure the reliability of results. Further research is required to understand the cognitive and affective behaviours contributing to the ongoing errors, focusing on assessing competency in clinical placement.

Aerobic exercise improves cognitive functions in older adults with mild cognitive impairment (MCI), while dance, combining music and synchronized movement, offers additional cognitive benefits. Despite music's potential role in enhancing cognitive outcomes, most research on aerobic exercise has not considered the impact of accompanying music. This review compared the effectiveness of aerobic exercise with music, aerobic exercise without music, and dance on cognitive function in adults with MCI. A total of 38 papers from 25 randomized controlled trials (N = 2048) were synthesized. The multilevel meta-analyses showed that compared to the control group, global cognition was improved by aerobic exercise with music (g = 1.2 [0.47, 1.94]), aerobic exercise without music (g = 0.48 [0.18, 0.79]), and dance (g = 0.55 [0.13, 0.96]). Dance also enhanced short-term memory (g = 0.41 [0.24, 0.59]), learning efficiency (g = 0.39 [0.14, 0.65]), and retrieval fluency (g = 0.7 [0.19, 1.22]). Bayesian network meta-analyses indicated that aerobic exercise with music had the highest probability of being the most effective for improving global cognition, executive function, and processing speed. Dance was likely to be the most beneficial for enhancing short-term memory, learning efficiency, and retrieval fluency. This study supports that incorporating music in exercise amplifies the cognitive benefits beyond exercise alone for individuals with MCI. The "Music Exercise Synergy Model" is proposed to explain the cognitive benefits of combining music with exercise. Dance strategically uses music for coordination, offering psychological, social, cognitive, and neurobiological benefits and contributing to the observed enhancements in memory functions.

ObjectiveThe current mixed-methods systematic review evaluated available literature to find out which attachment-based interventions have been implemented for people with intellectual disability and whether they are efficacious and acceptable.MethodsFive databases were searched (in July 2023 and April 2024), using terms related to intellectual disability and attachment-based interventions. The search yielded 793 papers; 15 papers (13 studies) met inclusion criteria. Relevant data was extracted from each study. Paper quality was appraised using the Mixed Methods Appraisal Tool. Findings were synthesised in an integrative review.ResultsOf the included studies, 7 had people with intellectual disability as participants and 6 had their caregivers. Interventions included education, psychotherapy, technology assisted therapy, video interaction guidance/feedback and circle of security. Research methods varied.ConclusionsEvidence for efficacy and acceptability of interventions was mixed but promising. Most studies had limited generalisability. Therefore, further research is required. Pre-registration with PROSPERO [351287].

Encoder-only transformer-based language models have shown promise in automating critical appraisal of clinical literature. However, a comprehensive evaluation of the models for classifying the methodological rigor of randomized controlled trials is necessary to identify the more robust ones. This study benchmarks several state-of-the-art transformer-based language models using a diverse set of performance metrics.

Seven transformer-based language models were fine-tuned on the title and abstract of 42,575 articles from 2003 to 2023 in McMaster University's Premium LiteratUre Service database under different configurations. The studies reported in the articles addressed questions related to treatment, prevention, or quality improvement for which randomized controlled trials are the gold standard with defined criteria for rigorous methods. Models were evaluated on the validation set using 12 schemes and metrics, including optimization for cross-entropy loss, Brier score, AUROC, average precision, sensitivity, specificity, and accuracy, among others. Threshold tuning was performed to optimize threshold-dependent metrics. Models that achieved the best performance in one or more schemes on the validation set were further tested in hold-out and external datasets.

A total of 210 models were fine-tuned. Six models achieved top performance in one or more evaluation schemes. Three BioLinkBERT models outperformed others on 8 of the 12 schemes. BioBERT, BiomedBERT, and SciBERT were best on 1, 1 and 2 schemes, respectively. While model performance remained robust on the hold-out test set, it declined in external datasets. Class weight adjustments improved performance in most instances.

BioLinkBERT generally outperformed the other models. Using comprehensive evaluation metrics and threshold tuning optimizes model selection for real-world applications. Future work should assess generalizability to other datasets, explore alternate imbalance strategies, and examine training on full-text articles.

The recent National Coverage Determination surrounding carotid stenting and shared decision-making has ushered in an era of patient-centric carotid care. However, historical carotid intervention endpoints have lacked patient-centered nuances to inform clinical decisions. Accordingly, we aimed to create a comprehensive novel, patient-centric textbook outcome (TO) to inform treatment paradigms.

We developed a novel composite TO for patients who underwent carotid revascularization reflecting a combination of patient-centric outcomes derived from previous patient interviews and the published literature. We defined a TO to include freedom from postprocedural neurologic events, myocardial infarction, cranial nerve injury, return to the operating room, reperfusion syndrome, or access site complications. The endpoint also included discharge on postprocedural day 1, home discharge, and 30-day survival. We measured the risk of a TO vs non-TO among asymptomatic patients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), or transfemoral carotid artery stenting (TF-CAS) in the Vascular Quality Initiative (VQI) from 2016 to 2023.

We studied 72,778 patients who underwent carotid revascularization, 70.3% CEA, 21.0% TCAR, and 8.7% TF-CAS. The mean age across all patients was 71.6 ± 8.4 years, 39.9% were female, and 91.7% were White. A TO was achieved in 76.9% of patients, and was 76.7% after CEA, 76.5% after TCAR, and 79.1% after TF-CAS (P < .001). Postprocedural length of stay was 2 days or more in 21.0% of patients, and was 21.1% after CEA, 21.6% after TCAR, and 18.4% after TF-CAS (P < .001). Postprocedural neurologic events occurred in 1.0% of patients after CEA, 1.3% after TCAR, and 1.4% after TF-CAS (P = .037). A sensitivity analysis of the TO that did not include postprocedural length of stay demonstrated a non-TO in 5.9% of patients after CEA, 5.5% after TCAR, and 6.3% after TF-CAS (P = .070). Patients who did not achieve a TO had inferior 5-year survival compared with patients who did have a TO across all three cohorts (log-rank P < .001).

This novel patient-centric endpoint demonstrated that a substantial percentage of patients fail to achieve a TO in current practice, and that failure to achieve a TO was associated with inferior 5-year survival. These findings are particularly important in light of the recent Medicare mandate for a shared decision-making approach to carotid care delivery and may help to best align patient preferences with procedure type.

Scientific publications are essential for uncovering insights, testing new drugs, and informing healthcare policies. Evaluating the quality of these publications often involves assessing their Risk of Bias (RoB), a task traditionally performed by human reviewers. The goal of this work is to create a dataset and develop models that allow automated RoB assessment in clinical trials.

We use data from the Cochrane Database of Systematic Reviews (CDSR) as ground truth to label open-access clinical trial publications from PubMed. This process enabled us to develop training and test datasets specifically for machine reading comprehension and RoB inference. Additionally, we created extractive (RoBInExt) and generative (RoBInGen) Transformer-based approaches to extract relevant evidence and classify the RoB effectively.

RoBIn was evaluated across various settings and benchmarked against state-of-the-art methods, including large language models (LLMs). In most cases, the best-performing RoBIn variant surpasses traditional machine learning and LLM-based approaches, achieving a AUROC of 0.83.

This work addresses RoB assessment in clinical trials by introducing RoBIn, two Transformer-based models for RoB inference and evidence retrieval, which outperform traditional models and LLMs, demonstrating its potential to improve efficiency and scalability in clinical research evaluation. We also introduce a public dataset that is automatically annotated and can be used to enable future research to enhance automated RoB assessment.

Primary biliary cholangitis is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with primary biliary cholangitis in whom ursodeoxycholic acid failed, based on a surrogate endpoint of reduction in ALP. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on clinical outcomes.

This trial emulation used data from the Komodo Healthcare Map claims database linked to US national laboratory, transplant, and death databases. Patients with compensated primary biliary cholangitis and intolerance/inadequate response to ursodeoxycholic acid who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to the first occurrence of death, liver transplant, or hospitalization for hepatic decompensation, analyzed using a propensity-score weighted Cox proportional hazards model. Baseline prognostic factors were balanced using standardized morbidity ratio weighting. For the primary analysis, 4174 patients contributed 11,246 control index dates, and 403 patients contributed OCA indexes. Weighted groups were well balanced. Median (95% CI) follow-up in the OCA and non-OCA arms was 9.3 (8.4-10.6) months and 17.5 (16.2-18.6) months (weighted population; censored at discontinuation). Eight events occurred in the OCA arm and 32 in the weighted control (HR = 0.37; 95% CI = 0.14-0.75; p < 0.001). Effects were consistent for each component of the composite endpoint.

We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.

HEROES; ClinicalTrials.gov NCT05292872.

Although information from real-world data can be used to identify factors that aid treatment choice, there are no guidelines for the use of such data. The aim of this Review is to summarise and evaluate definitions of treatment outcomes for antidepressants, antipsychotics, and mood stabilisers when using real-world data, and to suggest standards for the field. Given that no standards for the use of these data in estimating treatment outcomes exist, variability is high for treatment outcome definitions. We make recommendations for different scenarios of available data and highlight the importance of using other sources of information to validate proxy measures such as continued treatment, switching between medications, or polypharmacy of psychotropic medications. Well defined and validated treatment outcome measures that incorporate real-world data could facilitate the development of precision psychiatry approaches and support regulatory decision making regarding psychopharmacological agents.

Recent advancements in our understanding of the association between Epstein-Barr virus (EBV) and multiple sclerosis (MS), along with progress in EBV vaccine development, warrant serious considerations of future EBV vaccine-based MS-prevention studies. The clinical, financial, logistical, and technological considerations for designing and conducting retrospective and/or prospective prevention studies with the primary objective of evaluating the effectiveness of EBV vaccines in preventing MS and other EBV-associated sequelae are presented here. As implementation of these studies may require hundreds of thousands of participants, millions of dollars, and decades to observe if meaningful reductions in MS incidence occur, alternative approaches using pragmatic phase IV, post-licensure study designs focused on either the prevention of MS or infectious mononucleosis (IM), a common clinical manifestation of EBV infection that has been associated with increased risk of MS, are also explored. Current knowledge gaps in technology, funding, and research that must be addressed for a study protocol to be successfully designed and implemented are also discussed.

Peripheral Arterial Disease (PAD) is a chronic progressive vascular condition with high morbidity and mortality, often necessitating comprehensive management to mitigate cardiovascular risk.

This study assessed the feasibility of recruiting patients with PAD for a multidisciplinary team (MDT)-based care intervention, comparing its effectiveness to standard care within a clinical trial setting.

Conducted as a cross-sectional analysis nested within the ongoing TEAM-PAD trial, this study targeted the recruitment of 30 patients within 12 weeks and evaluated recruitment, consent, and retention rates to assess feasibility.

A total of 30 participants were consented within 11 weeks, with an overall recruitment rate of 36.4% and retention rate of 90%. Baseline characteristics were balanced between groups. Participants had a mean age of 68.9 years and a high prevalence of comorbidities. The mean 10-year cardiovascular risk (SMART-REACH) was 42.8%. In the intervention group, implementing MDT recommendations is projected to reduce this risk by 12.1%.

Recruitment of patients with PAD into an MDT intervention was feasible and timely, with strong retention and well-balanced baseline characteristics. While modelled estimates suggest a potential benefit from MDT recommendations, these findings are preliminary and based on a small interim cohort. Evaluation of clinical effectiveness within the larger ongoing randomised controlled trial is needed to evaluate the medium and long-term impacts of integrated vascular care.

Conducting multicenter randomized controlled trials (RCTs) in pediatric surgery for rare congenital anomalies presents unique challenges, including low patient recruitment, complex regulatory landscapes, and variability in care standards. This paper reflects on the experiences and lessons learned from the MUC-FIRE and STEPS-EA trials, supported by the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA), to provide guidance for future studies.A retrospective review was conducted on the design and execution of these trials, focusing on team composition, endpoint selection, patient recruitment strategies, regulatory compliance, and adaptive methodologies. Insights were derived from study protocols, monitoring reports, and the authors' experiences.Key factors contributing to trial success included multidisciplinary collaboration, leveraging existing research networks, and defining clear, measurable endpoints. Challenges such as recruitment delays, regulatory hurdles, and variations in care were mitigated through flexible protocols, proactive amendments, and stakeholder engagement. The COVID-19 pandemic amplified these difficulties, necessitating innovative strategies and extended timelines.The MUC-FIRE and STEPS-EA trials underscore the critical importance of international collaboration, adaptive strategies, and patient-centered approaches in overcoming the complexities of multicenter RCTs. Lessons from these experiences can inform the design and implementation of future trials, ultimately enhancing evidence generation and improving outcomes for children with rare congenital anomalies.

Recent years have seen a search for more effective forms of asthma therapy, with one possible option being vitamin D supplementation. The main objective of this study was to present the current state of knowledge on the effect of vitamin D supplementation on the course of asthma in children and adults; it also reviews the existing literature on prenatal vitamin D supplementation and asthma status. The search comprised articles, mostly randomized controlled trials (RCTs), included in the PubMed database and published after 2018. Most RCTs conducted on children indicate that vitamin supplementation did not affect the course of the disease, its control, or exacerbations; however, several trials in adults confirm it to have beneficial effects, with an important role being played by vitamin D deficiency. Unfortunately, the studies demonstrated considerable heterogeneity concerning the age and number of participants, dose, duration, and use of guidelines for pharmaceutical drugs, making it difficult to draw clear conclusions. Further, properly designed, large-scale studies with long-term follow-ups are needed.

Substance use among adolescents is a public health problem. We culturally adapted The Social Competence Promotion Program for Young Adolescents (SCPP-YA) program to the school context in Chile (henceforth "Mi Mejor Plan or MMP") and assessed the acceptability, feasibility, fidelity, and quality of the implementation among 6th graders. We also explored the efficacy of the program in improving individual protective factors and reducing risk factors and substance use.

Cluster randomized controlled trial conducted in Chile. The schools were randomly assigned to one of two conditions in a 1:1 ratio: 1) the "MMP" intervention group, and 2) the Control group. The program consisted of a 16-h class-based curriculum promoting social problem-solving skills delivered by a trained facilitator. Primary outcomes were acceptability, feasibility, fidelity, and quality of the implementation using detailed reports of facilitators and from observers of the performance of the facilitators in vivo. Additionally, we explored the efficacy of the intervention on secondary outcomes: 30-day prevalence of tobacco, alcohol, and cannabis use and individual risk and protective factors promoted by MMP. We performed an intention-to-treat analysis using mixed models, taking into account the hierarchical nature of the data.

Seven hundred sixty-five 6th graders from 11 schools were enrolled (one school dropped out after the randomization); 608 were analyzed at baseline, and 538 were analyzed post-intervention. 52.5% were male, and the average age was 11.3 in both groups. All 16 sessions were implemented, and students' attendance at each session ranged from 83.8% to 92.4%. The program was generally well-received, with up to 91.3% of students rating acceptability positively. Facilitators and observers reported high adherence to the contents of the program in most sessions. Protective factors, such as negative beliefs about tobacco and alcohol, increased significantly in the IG. Still, there were no significant changes in substance use, risk factors, emotion regulation, or school membership.

The MMP program was well accepted, and we achieved high levels of implementation and fidelity. The program improved some individual protective factors, such as negative beliefs about tobacco and alcohol, with no changes in substance use among adolescents.

ClinicalTrials.gov, number NCT04236947; registration date: 17/01/2020.

Statins have been appearing as a potential anti-cancer agent in numerous studies. The study aimed to unravel the impact of statins in pancreatic cancer in terms of reducing the occurrence (morbidity) and improving survival (mortality).

A comprehensive search of databases was carried out to collect the eligible studies up to July 2024. This meta-analysis evaluates two distinct questions: (1) whether statin use reduces the incidence of pancreatic ductal adenocarcinoma (PDAC) in the general population, and (2) whether statins improve survival among patients diagnosed with PDAC. In total, 39 studies were included in the meta-analysis, comprising 15 case-control studies, 20 cohort studies, three randomized controlled trials, and one non-randomized controlled trial. A generic inverse variance weighted random-effects model was applied to calculate the pooled risk ratio and 95% confidence intervals. Subgroup analyses were performed based on the availability of relevant information.

In the total meta-analysis, aggregated results demonstrated a substantial decrease in pancreatic cancer risk in all statin users (RR 0.94; 95% CIs, 0.90-0.97, and p-value = 0.0008). The pooled risk ratio estimate of lipophilic statins was 0.97 (95% CI, 0.87-1.07; P = 0.50; I2 = 0.0%). The estimated pooled risk ratios of long-term and short-term statin use were 0.80 (95% CI, 0.69-0.92; P = 0.002; I2 = 42%) and 0.86 (95% CI, 0.70-1.06; P = 0.15; I2 = 96%), respectively. For long-term and short-term follow-up, the risk ratios were 0.81 (95% CI, 0.70-0.94; P = 0.007; I2 = 55%) and 0.96 (95% CI, 0.90-1.02; P = 0.16; I2 = 26%), respectively. As for the studies collectively, heterogeneity was tested using the Cochrane chi square test (p-value = = 0.40, I2 = 4%). No publication bias was found.

The overall outcome of the study indicates that statins might lower the occurrence and increase the survival of PDAC patients.

Alcohol is an important risk factor for substance abuse and violence against women. Educating alcohol users has become important in preventing violence against women.

The aim of this study is investigate the impact of creative drama education on the attitudes of male patients with alcohol and substance dependence towards violence against women.

This study has a pre-test post-test parallel group randomized controlled design. This study as carried out at a treatment center for individuals with alcohol and substance addiction. The study was conducted with 35 male patients (Experimental group n = 18, Control group: n = 17) diagnosed with alcohol and substance addiction in a state hospital. Participants filled in the measurement tools before and after the training.

Post-intervention, the experimental group showed statistically significant improvements in total ISKEBE scores (Z = - 3.421, p = 0.001, Cohen's d = 1.44), as well as in the subdimensions of attitudes toward the body (Z = - 3.332, p = 0.001, d = 1.30) and identity (Z = - 3.075, p = 0.002, d = 1.18). No significant changes were observed in the control group (p > 0.05).

The findings suggest that creative drama education may have a beneficial effect on improving attitudes toward VAW among men with alcohol and substance use disorders. Further studies with larger and more diverse samples are recommended to confirm the generalizability and long-term impact of this approach.

NCT05595759-10/23/2022.

Some studies of obesity treatments use control groups identified from real-world registers, which may differ from people with obesity in the general population. We evaluated whether such control groups affect the results. The SOS study examines long-term mortality post-bariatric surgery. Among volunteers with obesity, 2,007 individuals underwent surgery, while a control group of 2,040 individuals was matched using 18 variables. Age was 37-60 years and BMI was ≥ 34/≥38 kg/m2 for men and women, respectively. We subdivided the control group into those with an obesity diagnosis (n = 177) and those without an obesity diagnosis (n = 1,863) in the Swedish National Patient Register prior to study inclusion. Mortality was determined over a median follow-up period of 26 years. The controls with a prior obesity diagnosis had a higher mortality rate than the controls without a prior obesity diagnosis, with 19.7 (95% CI, 15.5-25.1) and 14.4 (95% CI, 13.3-15.7) deaths per 1000 person-years, respectively. This corresponds to a hazard ratio of 1.45 (95% CI, 1.12-1.89; p = 0.005) and a 3.4-year shorter life expectancy. These results were confirmed in another cohort (n = 2,759, HR = 1.82 [95% CI, 1.47-2.25; p<0.001] and a 6.1-year shorter life expectancy). Controls with obesity identified from real-world datasets may be in poorer health than those who voluntarily participate in clinical studies. Consequently, selection bias could lead to an overestimation of the survival benefits of obesity treatments in research using controls identified by prior obesity diagnosis.

Indirect treatment comparisons can provide evidence of relative efficacy for novel therapies when implementation of a randomised controlled trial is infeasible. However, such comparisons are vulnerable to unmeasured confounding bias due to incomplete data collection and non-random treatment assignment. Quantitative bias analysis (QBA) is a framework used to assess the sensitivity of a study's conclusions to unmeasured confounding. As indirect comparisons between therapies with differing treatment modalities may result in violation of the proportional hazards (PH) assumption, QBA methods that are applicable in this context are required. However, few QBA methods are valid under PH violation.

We proposed a simulation-based QBA framework which quantifies the sensitivity of the difference in restricted mean survival time (dRMST) to unmeasured confounding, and is therefore valid under violation of the PH assumption. The proposed framework utilises Bayesian data augmentation for the multiple imputation of an unmeasured confounder with user-specified characteristics. Adjustment of dRMST is then implemented in a weighted analysis using the imputed values. The accuracy and precision of our proposed imputation-based adjustment method was assessed through a simulation study. Confounded data was simulated using a common non-PH data generating process, and imputation-based effect estimates were compared against estimates obtained following adjustment for all confounders. Implementation of the proposed QBA framework was also illustrated using a data from an external control arm study demonstrating clear PH violation.

Imputation-based adjustment using Bayesian data augmentation was observed to estimate the true adjusted dRMST with minimal bias. Moreover, the bias was comparable to that observed under adjustment when all confounders were measured. Application of the proposed QBA framework to an indirect treatment comparison study enabled identification of the characteristics of an unmeasured confounder that would be required to nullify the study's conclusions.

Imputation-based adjustment can accurately recover the true adjusted dRMST in the presence of unmeasured confounding with known exposure and outcome associations. Therefore, the proposed QBA framework can correctly determine the characteristics required by an unmeasured confounder to invalidate a study's conclusions. Consequently, this framework enables the construction of sensitivity analyses to investigate the robustness of relative efficacy evidence derived from indirect treatment comparisons which exhibit PH violation.

To perform a quantitative and qualitative analysis of spin bias in randomized clinical trials (RCTs) focusing on botulinum toxin (BTX-A) for managing bruxism.

This is a meta-epidemiologic study. The protocol was registered on the Open Science Framework.

We included RCTs that evaluated the effectiveness of BTX-A for managing bruxism, associated or not with signs and symptoms of temporomandibular disorders. The outcomes were changes in pain and bruxism events. Spin bias was investigated in abstract and main text. The frequency of spin bias was assessed, and a qualitative analysis was conducted. The study was classified as effective if the outcome analyzed was statistically significant (p-value 0.05) and reached the minimum important difference of 20% and ineffective if the reported outcome was statistically nonsignificant or the study did not report the p-value or the results did not reach the minimum important difference of 20%.

An overall frequency of 59.4% spin bias was identified in eight included RCTs. The conclusion in the main text (87.5%) was the section with the highest frequency of spin bias. In the qualitative analysis, the most common strategies identified were inadequate extrapolation to a large population (30.61%), inadequate implication for clinical practice (20.41%), and misleading reporting (12.25%).

There is a high frequency of spin bias in RCTs that evaluated BTX-A for bruxism management. Close to 90% of the selected RCTs presented spin bias in the main text's conclusion. The most common spin was the inadequate extrapolation of the results.

Applying BTX into the temporalis did not reduce muscle activity and the results for masseter injections remain controversial. It seems that BTX-A injections can reduce pain from two weeks to one year. It is not possible to have certainty about the efficacy and safety of using BTX-A to reduce pain and bruxism events.

Mendelian randomization (MR) is a widely used method for assessing causal relationships between risk factors and outcomes using genetic variants as instrumental variables (IVs). While traditional MR assumes uni-directional causality, bi-directional MR aims to identify the true causal direction. In uni-directional MR, invalid IVs due to pleiotropy can violate assumptions and introduce biases. In bi-directional MR, traditional MR can be performed separately for each direction, but the presence of invalid IVs poses even greater challenges. We introduce a new bi-directional MR method incorporating stepwise selection (Bidir-SW) designed to address these challenges. Our approach leverages public genome-wide association study (GWAS) datasets for two traits and uses model selection criteria to identify invalid IVs iteratively by stepwise selection. This method accounts for potential bi-directional causality in the presence of common invalid IVs for both directions, even if only GWAS summary statistics are provided. Through simulation studies, we demonstrate that our method outperforms traditional MR techniques, such as MR-Egger and inverse-variance weighted (IVW), with uncorrelated SNPs. We also provide simulations to compare our approach with existing transcriptome-wide association study (TWAS) to show its effectiveness. Finally, we apply the proposed method to genetic traits such as CRP levels and BMI to explore possible bi-directional relationships among these traits. We also used the proposed method to discover causal protein biomarkers. Our findings suggest that the Bidir-SW approach is a powerful tool for bi-directional MR or TWAS, which can provide a valuable framework for future genetic epidemiology studies.

This study investigates the causal association between genetic prediction of iron status and subarachnoid hemorrhage (SAH). A two-sample MR analysis was conducted using genome-wide association study (GWAS) summary data for four iron biomarkers: serum iron, serum ferritin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT). Genetic variants were selected as instrumental variables (IVs) to minimize confounding. Causal estimates were obtained using inverse variance weighting (IVW), MR-Egger, weighted median, and weighted mode methods. Sensitivity analyses, including Cochran's Q-test, MR-Egger regression, MR-PRESSO, and leave-one-out analysis, were performed to assess heterogeneity and pleiotropy. IVW analysis revealed a significant association between increased genetically predicted TIBC and higher SAH risk (OR = 1.71, 95% CI: 1.21-2.41, P = 0.002), while higher TSAT was associated with lower SAH risk (OR = 0.76, 95% CI: 0.62-0.93, P = 0.01). No causal association was found between serum iron, serum ferritin, and SAH. Sensitivity analyses confirmed the robustness of the results, with no evidence of horizontal pleiotropy. However, heterogeneity was detected in serum ferritin, suggesting potential variability in its effect. This MR study provides genetic evidence for the causal relationship between TIBC, TSAT, and SAH risk. These findings highlight the potential role of iron metabolism in SAH pathophysiology, warranting further investigation.

Previous studies have linked sleep quality to temporomandibular joint disorders (TMD), suggesting a role for snoring in this association. However, the directionality of this relationship remains a subject of debate. This investigation aimed to elucidate the connections between snoring and TMD.

This research employed a two-sample Mendelian randomization (MR) approach, leveraging publicly available large-scale genome-wide association study (GWAS) data on snoring and TMD. We utilised a suite of analytical methods, including the inverse variance weighted (IVW) method, maximum likelihood estimation, adjusted profile score, weighted median, MR-Egger regression, and a series of sensitivity analyses, to rigorously assess the existence of relationships.

Our findings indicate that a greater genetic predisposition to snoring is significantly associated with a reduced risk of TMD (IVW method; odds ratio [OR] = 0.156, 95% confidence interval [CI] = 0.028-0.843, p = 0.0309). Conversely, the analysis did not support a potential influence of TMD on snoring susceptibility (IVW method; 95% CI = 0.990 to 1.002, p = 0.1926). Additionally, our sensitivity analyses did not reveal any significant pleiotropy that could bias these findings.

This MR study provides limited but novel genetic evidence supporting a potential causal link between snoring and a decreased risk of developing TMD. On the other hand, it does not substantiate an effect of TMD on the likelihood of snoring.

Acellular dermal matrix (ADM) is pivotal in breast surgery, yet the statistical robustness of surgical outcomes remains underexplored. This study uses the fragility index (FI), reverse FI, and fragility quotient (FQ) to investigate the statistical fragility of ADM breast reconstruction outcomes.

Randomized controlled trials (2013 to present) with dichotomous outcomes were sourced from PubMed, Embase, SCOPUS, Medline, and Cochrane databases. FI and reverse FI (event reversals needed to alter outcome significance) and FQ (standardized fragility across trials) were computed and reported as median (interquartile range [IQR]). Subgroup analysis focused on intervention types.

Of 33 studies screened, 19 RCTs comprising 204 outcomes were included, with a median FI of 4 (IQR, 3 to 5) and FQ of 0.039 (IQR, 0.029 to 0.070). Twenty-six outcomes achieved statistical significance, with a median FI of 3.5 (IQR, 1 to 5) and FQ of 0.033 (IQR, 0.010 to 0.073). The remaining 178 outcomes were not significant, exhibiting a median FI of 4 (IQR, 3 to 5) and FQ of 0.040 (IQR, 0.030 to 0.070). Of the 204 outcomes, 18% had a number of patients lost to follow-up equal to or surpassing the FI. By intervention type, the median FIs were similar in value but remained low.

ADM-related breast reconstruction outcomes are statistically fragile; thus, reversal of a few outcomes or maintaining follow-up with patients may alter the significance of findings. Future researchers are thus recommended to report FI and FQ metrics with P values to accurately portray reconstructive surgery outcomes.

Sexual interest/arousal disorder (SIAD) is a common and distressing sexual dysfunction in women. Although efficacious psychological treatments for SIAD exist, they are generally underutilized and inaccessible. eSense is a feasible and useable online intervention containing Cognitive-Behavioral Therapy (CBT) and Mindfulness-Based Therapy (MBT) programs. Our goal was to test the efficacy of the CBT and MBT arms of eSense relative to a waitlist control condition.

Women with SIAD were randomized to eSense-CBT (n = 43), eSense-MBT (n = 43), or a waitlist (n = 43). Both interventions consisted of 8 modules with a recommended completion time of 8-12 weeks. Participants also met remotely with non-expert "navigators" for up to 12 weeks. Participants completed validated self-report measures of primary outcomes (sexual desire/arousal and distress) and secondary outcomes (sexual satisfaction, dissatisfaction, and overall sexual function) at baseline, mid-treatment, posttreatment, and 6-month posttreatment.

Compared to waitlist, both active treatment groups reported significant improvements in primary outcomes at post-treatment (desire/arousal d > .90; sexual distress d < -0.62) and these improvements were generally maintained at follow-up. The two active treatments did not differ in terms of primary outcomes. Effects on sexual satisfaction were also significant (d = 0.70-0.81) and MBT resulted in slightly greater improvements. There was no effect on sexual dissatisfaction. For overall sexual function, the effect was large (d = 1.20 to 1.23) with no between-arm differences. Future steps to improve engagement and increase access are discussed.

Dual antiplatelet therapy (DAPT) with oral P2Y12 inhibitors and aspirin is crucial for patients with acute coronary syndrome (ACS) and postpercutaneous coronary interventions (PCI). Concomitant proton pump inhibitor (PPI) therapy with DAPT can potentially reduce the risk of upper gastrointestinal bleeding (UGIB).

We conducted a meta-analysis of randomized controlled trials to evaluate the prevention of UGIB with concomitant use of PPI with DAPT.

We reviewed several databases to identify randomized controlled trials comparing the risk of UGIB in patients using DAPT + PPI vs . DAPT with no PPI or DAPT + Histamine 2 receptor antagonists. Our outcomes of interest were UGIB, major cardiovascular adverse events (MACE), myocardial infarction, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for all of the outcomes and analyzed data using random effect model. Heterogeneity was assessed using I 2 statistic.

Seven randomized controlled trials comprising 6708 patients were included. Rate of UGIB was significantly lower in the PPI + DAPT group, RR (95% CI): 0.39 (0.25-0.60). There was no significant difference in the rate of MACE between groups, RR (95% CI): 0.87 (0.69-1.10). Rate of MI was also not significantly different between groups, RR (95% CI): 0.93 (0.75-1.14). Rate of mortality was significantly lower in the PPI + DAPT group, RR (95% CI) 0.46 (0.27-0.80).

Our meta-analysis demonstrates that adding PPI therapy to DAPT significantly lowers the risk of UGIB and all-cause mortality, without adversely affecting major cardiovascular outcomes.

China has implemented accelerated drug marketing registration procedures (ADMRPs) since 2016, including priority review and approval (PRA), conditional approval (CA), and breakthrough therapy drugs (BTDs). This study analyzed the characteristics of drugs approved by ADMRPs from 2016 to 2024 and explored the implementation effectiveness of these procedures. Overall, 922 drugs were approved for marketing through five ADMRPs (or procedure combinations): PRA (759, 82.3%), CA (12, 1.3%), CA + PRA (108, 11.7%), BTD + PRA (23, 2.5%), and BTD + CA + PRA (20, 2.2%). Drugs approved through the different procedures differed widely in terms of drug attributes and clinical uses, clinical trial design, and drug registration and marketing. Implementing ADMRPs has demonstrated excellent results in accelerating the development and marketing of clinically value-driven drugs.

Men represent the majority of suicide deaths globally and men are more likely to die by suicide without contact with formal mental health services. In Australia, three-quarters of suicide deaths are men. If services were better able to meet their needs, men might be more likely to seek help. In this scoping review, we sought to describe the formal and informal service landscape for men at risk of suicide in Australia, and to determine the extent of research evidence for the effectiveness of these in lowering suicidality, and improving mental health or help-seeking behaviours. We limited our investigation to Australian services, in order to comprehensively identify all community and health system services.

Relevant services and initiatives in Australia were identified through multiple methods: (1) a hand search of key websites and directories; (2) a systematic search of PsycINFO, Cochrane Central, EmBASE, and PubMed; and (3) suggestions by researchers, consumers and clinicians. Evaluations were also identified using multiple methods, including the initial systematic search, targeted website searches, and via multiple search engines. Findings are presented using narrative synthesis.

Included services and initiatives (N = 88) were diverse in their characteristics (e.g., cost to the user, mode of delivery, location), however, there was considerable overlap in the types of components offered. Awareness and education were the most commonly offered (84.1% of services and initiatives). Only 22.7% of services and initiatives had been formally evaluated and existing evaluations varied in quality. Pre-post intervention designs were most often used, and only three evaluations assessed outcomes in a randomised controlled trial.

The service landscape for Australian men is broad. However, there appears to be substantial overlap in the components offered by services and initiatives. The prevalence of awareness and education-based offerings is disproportionate to evidence about men's preferences for support. There is a lack of high-quality evaluations. We conclude that the cohesiveness of men's suicide prevention approaches must improve through service development and policy.

Occupational workload can contribute to significant health problems such as chronic stress, fatigue and burnout. To investigate the underlying mechanisms, it is necessary to monitor brain activity in real work environments. Functional near-infrared spectroscopy (fNIRS) is a portable, non-invasive neuroimaging method that captures neural correlates of occupational workload under natural conditions. However, despite its increasing application, a comprehensive overview of fNIRS-based research in this field is lacking. Therefore, this systematic review examines how fNIRS can be utilized to investigate occupational workload.

Following PRISMA 2020 guidelines, we conducted our systematic review by searching Web of Science, PubMed, and Scopus between November 15, 2023 and March 20, 2025. We included all studies published in English or German at any date, as long as they examined healthy adult professionals performing occupational tasks with functional near-infrared spectroscopy (fNIRS). Extracted data included study characteristics, workload details, signal processing methods, main fNIRS findings, and study quality, assessed using the JBI Critical Appraisal Tool.

We included 41 studies. Of these, 23 reported a significant increase in oxygenated hemoglobin (HbO) concentration and functional connectivity in the prefrontal cortex (PFC) under higher occupational workload conditions. Only five studies examined typical office tasks. Nine studies analyzed differences in cortical activation between experts and novices, with experts showing increased HbO concentration in the PFC than novices. Regarding methodology, 26 studies used standardized optode placements, while only 17 applied systemic and extracerebral artifact correction. Small sample sizes and the absence of randomized controlled trials limited the reliability and reproducibility of the findings.

Functional near-infrared spectroscopy effectively detects neural correlates of occupational workload and provides objective insights into cognitive demands in real-world work settings. Standardizing optode placement, harmonizing signal-processing methods, and increasing sample sizes would enhance the validity and comparability of future research. Expanding investigations to typical office environments is also crucial for understanding daily workload and for developing interventions that promote employee well-being and productivity. Overall, fNIRS represents a promising tool for establishing evidence-based workplace health promotion strategies across diverse occupational settings.

Observational cohort studies are increasingly being used for comparative effectiveness research to assess the safety of therapeutics. Recently, various doubly robust methods have been proposed for average treatment effect estimation by combining the treatment model and the outcome model via different vehicles, such as matching, weighting, and regression. The key advantage of doubly robust estimators is that they require either the treatment model or the outcome model to be correctly specified to obtain a consistent estimator of average treatment effects, and therefore lead to a more accurate and often more precise inference. However, little work has been done to understand how doubly robust estimators differ due to their unique strategies of using the treatment and outcome models and how machine learning techniques can be combined to boost their performance, which we call double machine learning estimators. Here, we examine multiple popular doubly robust methods and compare their performance using different treatment and outcome modeling via extensive simulations and a real-world application. We found that incorporating machine learning with doubly robust estimators such as the targeted maximum likelihood estimator gives the best overall performance. Practical guidance on how to apply doubly robust estimators is provided.

Digital interventions have been increasingly applied in multidisciplinary care plans to improve medication adherence to oral systemic anticancer therapy (SACT), the crucial lifesaving treatments for many cancers. However, there is still a lack of consensus on the efficacy of those digital interventions.

This systematic review and meta-analysis aimed to investigate the efficacy of digital interventions in improving adherence to oral SACTs in patients with cancer.

This systematic review and meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guidelines. The protocol has been registered at PROSPERO (no. CRD42024550203). Fully published, randomized controlled trials (RCTs) in English on adults with cancer assessing digital interventions for improving adherence to oral SACTs were retrieved from MEDLINE, Embase, APA PsycINFO, and CINAHL Plus up to May 31, 2024. Adherence measures compared between digital intervention users and nonusers were extracted. The proportions of poor adherence were synthesized using a random-effects model. The pooled results were reported as the odds ratio and 95% CI. The heterogeneity was assessed with the I2 test (%). The mean difference and 95% CI were calculated from the mean adherence score and SD. A risk of bias assessment was conducted using version 2 of the Cochrane Risk of Bias Assessment Tool (RoB 2) for RCTs, which ensured that a quality assessment of all included studies was conducted as recommended by the Cochrane Collaboration.

This study included 13 RCTs on digital interventions for improving adherence to oral SACTs in patients with cancer. The 13 RCTs, published between 2016 and 2024, were conducted in the United States, South Korea, France, Egypt, Finland, Australia, Colombia, Singapore, and Turkey. The technologies used were mobile apps (n=4), reminder systems (n=4), telephone follow-ups (n=3), and interactive multimedia platforms (n=2). Adherence was measured by surveys (n=8), relative dose intensity (n=2), pill count (n=1), self-reported missed doses (n=1), a smart pill bottle (n=1), and urine aromatase inhibitor metabolite assays (n=1). Concerns regarding risk of bias primarily involved randomization, missing outcome data, and outcome measurement, including nonblinded randomization, subjective patient-reported data, and difficulties in distinguishing between missed appointments and actual medication nonadherence. Pooled results from 11 trials showed that digital technology users had significantly lower risk of poor adherence (odds ratio 0.60, 95% CI 0.47-0.77). Two studies reported positive mean differences in adherence scores comparing digital intervention users and nonusers. However, due to considerable heterogeneity (I²=73.1%), it is difficult to make a definitive conclusion from the pooled results about the effect of digital interventions upon adherence to oral anticancer therapy.

Digital intervention users exhibited significantly lower risk of poor oral SACTs adherence than nonusers. Acknowledging individual variation and tailoring digital technologies to prioritize patient needs is essential.

Respiratory Distress Syndrome (RDS) remains a leading cause of mortality among preterm infants weighing < 2000 g, particularly in resource-limited settings. While Kangaroo Mother Care (KMC) has shown promise in stable preterm infants, its effectiveness for those requiring respiratory support remains unclear. This study evaluated nurse-led implementation of KMC for preterm infants with RDS.

A prospective, multicenter, randomized controlled trial was conducted across four neonatal intensive care units in Tanta, Egypt (January 2023-June 2024). Two hundred forty preterm infants (<2000 g) with RDS were randomly assigned to either nurse-implemented KMC (n = 120) or standard care (n = 120). The KMC protocol, implemented for a minimum of 6 h per day until hospital discharge, integrated continuous skin-to-skin contact, exclusive breastfeeding promotion, and structured parental education. Outcomes included 28-day survival, respiratory status (Silverman-Anderson Scores), nosocomial infections, maternal-infant bonding, growth trajectories, and clinical course metrics.

The KMC intervention significantly improved 28-day survival (adjusted HR = 0.42, 95% CI 0.28-0.63, p < 0.001) and reduced nosocomial infections by 55% (RR = 0.45, 95% CI 0.27-0.75, p < 0.001). KMC recipients demonstrated faster respiratory improvement, shorter CPAP duration (-2.2 days, p < 0.001), and higher rates of exclusive breastfeeding at discharge (74.2% vs. 48.3%, p < 0.001). Maternal competency scores showed progressive improvement with enhanced bonding and responsiveness.

Nurse-implemented KMC is a safe, effective intervention for preterm infants with RDS, yielding significant improvements in survival, clinical outcomes, and family-centered care metrics.

These findings support the expansion of nursing roles in implementing KMC for high-risk infants in resource-limited settings.

ClinicalTrials.gov (NCT06707376).

To synthesise findings from randomised controlled trials (RCTs) on vascular access devices (VADs) in emergency departments (EDs).

VADs play a critical role in EDs, enabling rapid delivery of supportive therapies to address urgent medical needs. This scoping review will map current evidence and determine areas to focus future research priorities.

Following Arksey and O'Malley's scoping review framework, a comprehensive search was conducted (2012-2024) across four databases. RCTs that focused on peripheral intravenous catheters, central venous catheters, arterial catheters, or intraosseous catheters in an ED setting were included.

48 RCTs were included, a majority focused on peripheral intravenous catheters (n = 41, 85 %), followed by central venous catheters (n = 4, 8 %), arterial catheters (n = 2, 4 %), and intraosseous catheters (n = 1, 3 %). The findings were categorised by intervention type, including vessel visualisation technology, catheter design, dressing and securement design, distraction techniques, topical anaesthetics, inserter models, and other related techniques. The top three most frequently reported outcomes were insertion success (n = 21), time to successful insertion (n = 20), and catheter-related complications (n = 19).

This review provides ED clinicians with current evidence on VAD technologies and techniques, enabling them to select and implement the most effective options into daily practice reduce costs and improve patient satisfaction.

Current estimates suggest that nearly one in five youth in the United States have a clinically significant mental health problem. Many of these youth do not receive services, and if they do, they are often not evidence-based treatments. Parents are critical to the utilization of psychological services for youth; they are typically considered the gatekeepers to mental health services and frequently initiate help-seeking on behalf of their youth. Research has demonstrated that parents do not have sufficient knowledge and skills needed to handle youth mental health problems (i.e., mental health literacy), which likely contributes to the youth treatment disparity. To address this, the current systematic review explored global mental health literacy programs for parents to examine program effectiveness and parent satisfaction with programs. Nine programs were identified and described in terms of structure, content, and delivery method. Several programs demonstrated improvement in at least one component of parents' mental health literacy. Additionally, when assessed, parent satisfaction was generally positive, though areas for improvement were noted (e.g., program content lacked specificity, need for more practical parenting skills). Overall, findings have meaningful implications for future research and program development.

Randomisation controlled trial are the gold standard for causal inference, however the rapidly increasing development of new treatments and the movement towards personalised medicine mean there is a need to measure efficacy outside of the costly and time-consuming RCT.Here we propose a method of estimating treatment effects using parametric models to act as control against which to compare data from an experimental arm. This allows for treatment effects to be estimated where data are only available from an experimental arm and can be a tool useful in the analysis of observational cohorts or for the design and analysis of RCTs.We develop this approach using Bayesian estimation procedures and compare this approach against other casual inference tools. We then demonstrate how this may be used to estimate the efficacy between two treatment in different RCTs for the analysis of Pancreatic Cancer.It is proposed that with reasonable assumptions, this approach can produce a reliable estimate of efficacy and can have applications in both evaluating currently available data and in the efficient design of future trials.

In this study, we evaluate the long-term effects (±1.5 years postintervention) of 6-year exposure to the Lekker Fit! intervention on physical fitness and physical activity (PA).

The retrospective intervention evaluation is embedded within the Generation R Study in Rotterdam, the Netherlands, a population-based prospective birth cohort study.

Measurements took place in the research centre of the Generation R cohort study.

5489 adolescents from the Generation R Study were eligible for inclusion within this study. Successful linking to school career data was possible for 4129 adolescents who were then retrospectively subdivided into a Lekker Fit! group, mixed group and regular school group based on their primary school career.

The Lekker Fit! intervention is a multicomponent primary school-based intervention for the prevention of overweight. It focuses on a healthy diet and healthy lifestyle rather than focusing directly on the reduction of overweight. The intervention targets individual behaviour of children as well as their obesogenic environment and parental engagement in shaping their children's behaviour.

Aged 13/14 years old, physical fitness was measured with an incremental ergometer test. The actual highest achieved work rate was divided by the expected highest achieved work rate (age- and sex-related Dutch population-based reference data), and converted into z-scores. PA was determined by the number of days with at least 1 hour of PA, obtained by a self-reported questionnaire. Propensity score matching was performed to correct for non-random selection bias. Linear regression analyses were performed to estimate intervention effects.

Children from the Lekker Fit! group had significantly lower fitness z-scores (-0.18 (95% CI -0.29 to -0.06), n=1826) compared with children from the matched regular school group. No Lekker Fit! intervention effect was found on PA (-0.12 (95% CI -0.36 to 0.12), n=1258).

No evidence was found for long-term favourable effects of a school-based multicomponent intervention on physical fitness and PA. Recommendations for policy and future research are discussed.

Cottage cheese (CC) is a member of the "fresh cheese" family of cheeses and is widely consumed due to its culinary versatility and some perceived health benefits. However, the evidence of direct health effects of CC is not well established. This review describes the production and nutritional characteristics of CC, before exploring the evidence of health effects from human intervention, in vitro, and in vivo models. Despite widespread consumption and advocated health benefits, there is a dearth of evidence pertaining to the health effects of CC from high-quality human randomized controlled trials. To date, a limited number of human intervention models with CC have explored nutrient bioavailability, metabolic health, and appetite regulation, in small, niche study populations. Findings with in vitro and in vivo models suggest that CC may be an efficacious vehicle for bioactive compounds. In conclusion, CC is a cultured dairy product that could impose a myriad of benefits across health outcomes including cardiometabolic, gastrointestinal, body composition, appetite regulation, and nutrient status. However, there is a need for high-quality human randomized controlled trials to develop a substantiated evidence base relating to the full potential of CC in human health.

One of the most highly replicated neural correlates of Conduct Problems (CP) is amygdala hypoactivity to another person's fear. We recently reported that this correlate was only observed in boys with persistent CP (i.e. antisocial behaviour that persisted following a gold-standard psychological intervention), suggesting that amygdala hypoactivity to fear could be an important neural signature for treatment-resistant CP, and a putative target for future treatments. Potential treatment candidates include the oxytocin system, as this has been reported to modulate amygdala activity and social behaviour across species. Further, in adults with antisocial personality disorder, intranasal oxytocin improved facial emotion recognition for fearful and happy faces. However, to-date, no-one has studied whether intranasal oxytocin can normalise neural processing differences in children with CP. Twenty boys (mean age 9.85±1.26 years) with persistent CP underwent functional magnetic resonance imaging in a within-subject randomised control design to investigate whether, compared to placebo, a single-dose of intranasal oxytocin could 'shift' abnormal neural processing to fear. Oxytocin failed to reduce amygdala hypoactivity to fearful faces, but increased activation in the posterior cingulate cortex / precuneus to happy faces. These findings tentatively suggest that intranasal oxytocin may promote a more neurotypical profile in treatment-resistant CP children, therefore, supporting the merit of investigating oxytocin in further larger clinical studies in this population.

Cancer remains a leading cause of mortality and morbidity worldwide, imposing a significant public health burden. While cannabis and opioids are widely used in cancer pain management, their potential for abuse and addiction has raised concerns regarding their long-term health effects, including possible associations with cancer risk. However, the relationship between substance use disorders (SUDs) and cancer susceptibility remains controversial. This Mendelian randomization (MR) study aimed to investigate the potential causal effects of cannabis use disorder (CUD) and opioids use disorder (OUD) on cancer vulnerability.

We conducted a two-sample MR study using summary statistics from genome-wide association studies, including data from FinnGen and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW), complemented by a range of sensitivity analyses to assess the robustness of the findings.

IVW analysis identified a causal association between OUD and bladder cancer (OR = 1.040, 95% CI 1.004-1.078, P = 0.029, adj. P = 0.125), acute myeloid leukemia (OR = 0.931, 95% CI 0.885-0.978, P = 0.005, adj. P = 0.061) and ovarian cancer (OR = 0.937, 95% CI 0.891-0.984, P = 0.010, adj. P = 0.064). Sensitivity analysis yielded directionally consistent results. Reverse MR analysis provided no statistically significant evidence supporting a causal effect of these cancers on OUD (all P > 0.05). Additionally, no evidence of a significant causal relationship was observed between CUD and any cancer type (P > 0.05).

This study suggests a potential causal link between OUD and increased susceptibility to bladder cancer, acute myeloid leukemia, and ovarian cancer, warranting further investigation in larger, multi-ethnic population studies. These results contribute to the ongoing discourse on the long-term health impacts of substance use disorders and highlight the need for further research to elucidate their potential oncogenic effects.

Substantial healthcare barriers, especially to specialty and cancer care, exist for American Indian and Alaska Native (AI/AN) individuals and communities at all levels. The unique history of AI/AN Tribal Nations and resulting policies, treaties, and relationships with the US government and federal agencies have created specific barriers to healthcare and clinical trial access for AI/AN peoples. Commonly, AI/AN peoples harbor a long-standing mistrust of the healthcare system based on lived and historical experiences. The intersection of various barriers to care for AI/AN communities results in health inequities, lack of representation in clinical research, and other disparities faced by historically marginalized and underrepresented peoples. AI/AN patients face unique barriers in their healthcare journey due to a disproportionate burden of life-threatening and chronic diseases, including many cancers. Identifying barriers specific to AI/AN peoples and improving access to high-quality care, with a focus on building on the strengths and capacities in each AI/AN community are vital to improving health equity. In this review, we describe patient, provider, and institutional barriers to healthcare, particularly specialty care and clinical research, for AI/AN peoples, with a focus on the Northern Plains AI communities. Examples and best practices to improve AI/AN patient access to health services, including screening and specialty care, as well as to clinical research, are provided. We emphasize the importance of longitudinal community-based partnerships and strength- and trust-based approaches as essential components of promoting equitable access to high-quality specialty care and recruitment and participation of AI/AN individuals and communities in clinical research.

There are substantial financial incentives to develop orphan drugs for rare diseases, but concerns about the quality and volume of supporting evidence have emerged. We compare evidence used to evaluate orphan and nonorphan drugs approved by the Food and Drug Administration (FDA) between 2016 and 2023. This retrospective cross-sectional analysis utilizes FDA data on approvals and study information from ClinicalTrials.gov to compare characteristics of studies relevant to orphan and nonorphan drugs approved between 2016 and 2023. Of the 368 total drugs approved, 50% were orphan drugs. The FDA-approved drugs based on significantly fewer studies for orphan (1.5 studies/drug) compared to nonorphan (2.4 studies/drug). Additionally, a significantly lower proportion of studies were completed before FDA approval for orphan drugs (25% vs 41%). Orphan drugs were significantly less likely to be evaluated in randomized clinical trials (RCTs) (34% vs 63%). Of these RCTs, there were significantly fewer completed before approval (40% vs 54%) and that had results posted (35% vs 53%). There was a significant difference in the available evidence for orphan and nonorphan drugs. As new legislation like Cures 2.0 is developed, it is critical to examine the balance between an expedited approval timeline and the standard of clinical evidence.

To identify and compare interventions for upper extremity (UE) motor recovery poststroke in randomized controlled trials (RCTs) conducted in high-income countries (HICs) and low-to-middle-income countries (LMICs).

Systematic searches were conducted for RCTs published in English in 5 databases (CINAHL, Embase, PubMed, Scopus, and Web of Science) up to April 2021, in line with PRISMA guidelines.

RCTs, including crossover design, were included if they were in English and evaluated an intervention for poststroke UE motor rehabilitation, in an adult population (≥18y) diagnosed with stroke.

Data on country of origin and type of intervention in each RCT were extracted using a data extraction template in Covidence software. Study screenings and data extraction were performed by 2 independent reviewers.

A total of 1276 RCTs met the inclusion criteria, with 978 RCTs conducted in HICs and 298 in LMICs. A significantly larger proportion of RCTs evaluating robotics and task-specific training interventions were conducted in HICs, compared to LMICs (P<.009). In contrast, a higher proportion of RCTs conducted in LMICs examined acupuncture (P<.001) and repetitive transcranial magnetic stimulation (rTMS) (P=.001) when compared to HICs.

Poststroke rehabilitation in LMICs is conducted in a lower resource environment when compared to HICs. Some differences exist in the use of UE motor rehabilitation interventions between LMICs and HICs such as robotics, task-specific training, rTMS, and acupuncture; however, there was no significant difference between HICs and LMICs for most interventions.

People with intellectual disability (PwID) are 2% of the UK population. Constipation and bowel movement (BM) problems (diarrhoea/faecal incontinence etc.) affects over a third of PwID and is a serious cause of morbidity and mortality. Pw ID rely heavily on outside support (family/professional carers/healthcare professionals), many of whom are ignorant to bowel related harms. There is significant stigma to discuss BM particularly constipation. Serious Games (SG) are increasingly used for education of health needs. This review examines if game-based technology can assist improving knowledge and reducing stigma of BM problems particularly constipation.

To identify and gain evidence of SGs aimed at improving knowledge of BM management particularly constipation.

A systematic search of publications between 2010 and 2024 was conducted following the PRISMA ScR statement for scoping reviews. The search inclusion/exclusion criteria were designed and overseen by an information specialist. PUBMED, EMBASE and PsychINFO databases were searched. Extracted variables included SG title, co-production and expert involvement, target outcome, evaluation methodology, effectiveness, sustainability and game platform. Results were narratively synthesised.

Of 2966 papers retrieved, three were selected for inclusion, none RCTs. All three included SGs aimed to teach BM management or recognition to healthcare workers/ professionals. Two studies evaluated game efficacy. No SGs were assessed after initial trials, none were implemented in clinical practice. Only one game successfully improved participant knowledge. All game creators consulted experts during game design, but none consulted patients. None discussed reducing stigma amongst their audience.

Only one of three SGs identified improved BM knowledge in healthcare workers/professionals and was not specific to PwID. There is potential to co-produce with PwID and their carers a SG to support BM problems particularly constipation to reduce stigma, improve outcomes and be a templar for other similarly vulnerable groups like those with dementia.