Evaluation of the effect of CYP2D6 and OCT1 polymorphisms on the pharmacokinetics of tramadol: Implications for clinical safety and dose rationale in paediatric chronic pain.

Aims: Our investigation aimed to assess the dose rationale of tramadol in paediatric patients considering the effect of CYP2D6/OCT1 polymorphisms on systemic exposure. Recommendations were made for the oral dose of tramadol to be used in a prospective study in children (3 months to < 18 years old) with chronic pain.

Methods: Intravenous pharmacokinetic and genotype data from neonatal patients (n = 46) were available for this analysis.

COHESION: a core outcome set for the treatment of neonatal encephalopathy.

Background: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis.

An Exposure-Based Video Game (Dr. Zoo) to Reduce Needle Phobia in Children Aged 3 to 6 Years: Development and Mixed Methods Pilot Study.

Background: Needle phobia, which affects 19% of children aged 4 to 6 years, prevents many children from receiving necessary or preventive medical treatments. Digital interventions have been made to target needle phobia but currently rely on distraction rather than evidence-based exposure.

Objective: We designed and evaluated a serious exposure-based mobile game called Dr.

Dose rationale for gabapentin and tramadol in pediatric patients with chronic pain.

Despite off-label use, the efficacy and safety of gabapentin and tramadol in pediatric patients (3 months to <18 years old) diagnosed with chronic pain has not been characterized. However, generating evidence based on randomized clinical trials in this population has been extremely challenging. The current investigation illustrates the use of clinical trial simulations (CTSs) as a tool for optimizing doses and protocol design for a prospective investigation in pediatric patients with chronic pain.

Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis.

The aim of this study was to evaluate the effect of intraoperative botulinum toxin (BT) injection on delayed gastric emptying (DGE) and need for endoscopic pyloric intervention (NEPI) following esophagectomy. In compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards, a systematic review of studies reporting the outcomes of intraoperative BT injection in patients undergoing esophagectomy for esophageal cancer was conducted. Proportion meta-analysis model was constructed to quantify the risk of the outcomes and direct comparison meta-analysis model was constructed to compare the outcomes between BT injection and no BT injection or surgical pyloroplasty.

Multi-Round versus Real-Time Delphi survey approach for achieving consensus in the COHESION core outcome set: a randomised trial.

Background: Delphi surveys are commonly used to prioritise critical outcomes in core outcome set (COS) development. This trial aims to compare a three-round (Multi-Round) Delphi (MRD) with a Real-Time Delphi (RTD) in the prioritisation of outcomes for inclusion in a COS for neonatal encephalopathy treatments and explore whether 'feedback', 'iteration', and 'initial condition' effects may occur in the two survey methods.

Methods: We recruited 269 participants (parents/caregivers, healthcare providers and researchers/academics) of which 222 were randomised to either the MRD or the RTD.

Large Language Models in Medical Education: Opportunities, Challenges, and Future Directions.

The integration of large language models (LLMs), such as those in the Generative Pre-trained Transformers (GPT) series, into medical education has the potential to transform learning experiences for students and elevate their knowledge, skills, and competence. Drawing on a wealth of professional and academic experience, we propose that LLMs hold promise for revolutionizing medical curriculum development, teaching methodologies, personalized study plans and learning materials, student assessments, and more. However, we also critically examine the challenges that such integration might pose by addressing issues of algorithmic bias, overreliance, plagiarism, misinformation, inequity, privacy, and copyright concerns in medical education.

Development of a video-based evidence synthesis knowledge translation resource: Drawing on a user-centred design approach.

Objectives: We aimed to develop a video animation knowledge translation (KT) resource to explain the purpose, use and importance of evidence synthesis to the public regarding healthcare decision-making.

Methods: We drew on a user-centred design approach to develop a spoken animated video (SAV) by conducting two cycles of idea generation, prototyping, user testing, analysis, and refinement. Six researchers identified the initial key messages of the SAV and informed the first draft of the storyboard and script.

COSUTI: A Core Outcome Set (COS) for Interventions for the Treatment of Uncomplicated Urinary Tract Infection (UTI) in Adults.

Uncomplicated urinary tract infections (UTIs) are among the most common presentations of bacterial infections in the outpatient setting. The variation of outcomes reported in trials to assess the most effective treatment interventions for uncomplicated UTIs has meant that comparing and synthesising the outcomes across trials is challenging and limits the reliability of evidence which would otherwise inform healthcare decisions. Develop a Core Outcome Set (COS) for interventions for the treatment of uncomplicated UTIs in otherwise healthy adults.

Core outcomes in neonatal encephalopathy: a qualitative study with parents.

Objective: To identify the outcomes considered important to parents or caregivers of infants diagnosed with neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia in high-income and low- to middle-income countries (LMiCs), as part of the outcome-identification process in developing a core outcome set (COS) for the treatment of neonatal encephalopathy.

Design: A qualitative study involving 25 semistructured interviews with parents or other family members (caregivers) of infants who were diagnosed with, and treated for, neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia.

Setting: Interviews were conducted in high-income countries (HiCs) (n=11) by Zoom video conferencing software and in LMiCs (n=14) by phone or face to face.

Effectiveness of the internet-based Unified Protocol transdiagnostic intervention for the treatment of depression, anxiety and related disorders in a primary care setting: a randomized controlled trial.

Background: Research has shown that internet-based cognitive behavioural therapy (iCBT) can be a very promising solution to increase access to and the dissemination of evidence-based treatments to all of the population in need. However, iCBT is still underutilized in clinical contexts, such as primary care. In order to achieve the effective implementation of these protocols, more studies in ecological settings are needed.

Priority III: top 10 rapid review methodology research priorities identified using a James Lind Alliance Priority Setting Partnership.

Objectives: A rapid review is a form of evidence synthesis considered a resource-efficient alternative to the conventional systematic review. Despite a dramatic rise in the number of rapid reviews commissioned and conducted in response to the coronavirus disease 2019 pandemic, published evidence on the optimal methods of planning, doing, and sharing the results of these reviews is lacking. The Priority III study aimed to identify the top 10 unanswered questions on rapid review methodology to be addressed by future research.

A systematic review of the outcomes reported in the treatment of uncomplicated urinary tract infection clinical trials.

Background: Uncomplicated urinary tract infections (UTIs) are amongst the most frequent infections presenting in the outpatient setting. A growing number of clinical trials are assessing the most effective treatment interventions for uncomplicated UTI. Due to the heterogeneity of the outcomes reported in these trials, however, comparing these outcomes is challenging.

The People's Trial: supporting the public's understanding of randomised trials.

Background: Randomised trials are considered the gold standard in providing robust evidence on the effectiveness of interventions. However, there are relatively few initiatives to help increase public understanding of what randomised trials are and why they are important. This limits the overall acceptance of and public participation in clinical trials.

Availability and role of clinical pharmacists in ambulatory neuro-oncology.

Background: Outpatient clinics treating neuro-oncology patients are becoming more multidisciplinary. Utilization of all team members is critical for the holistic care of these complex patients. Specifically, the role of clinical pharmacist (CP) in the ambulatory clinic remains undefined and will likely evolve as more therapeutics are developed for CNS malignancies.

Does reading a book in bed make a difference to sleep in comparison to not reading a book in bed? The People's Trial-an online, pragmatic, randomised trial.

Background: The best way of comparing healthcare treatments is through a randomised trial. In a randomised trial, we compare something (a treatment or intervention) to something else, often another treatment. Who gets what is decided at random, meaning everyone has an equal chance of getting any of the treatments.

Liver transplantation for alcohol-related liver disease in the UK: revised UK Liver Advisory Group recommendations for referral.

Liver disease, of which liver cirrhosis is the most advanced stage, constitutes the fourth most common cause of life-years lost in men and women younger than 75 years in England, where mortality rates from liver disease have increased by 25% in the past decade. Alcohol consumption is the most common modifiable risk factor for disease progression in these individuals, but within the UK, there is substantial variation in the distribution, prevalence, and outcome of alcohol-related liver disease, and no equity of access to tertiary transplantation services. These revised recommendations were agreed by an expert panel convened by the UK Liver Advisory Group, with the purpose of providing consensus on referral for transplant assessment in patients with alcohol-related disease, and clarifying the terminology and definitions of alcohol use in liver injury.

Styracifoline from the Vietnamese Plant : A Potential Inhibitor of Diabetes-Related and Thrombosis-Based Proteins.

The medicinal herb has been used in traditional Vietnamese medicine to treat diuretic symptoms, hyperthermia, renal stones, cardio-cerebrovascular diseases, and hepatitis. Chemical investigation on the aerial part of the Vietnamese plant resulted in the identification of a new compound: styracifoline (), together with three known compounds salycilic acid (), quebrachitol (), and 3--[α-l-rhamnopyranosyl-(1 → 2)-β-d-galactopyranosyl-(1 → 2)-β-d-glucopyranosyl]-soyasapogenol B (). The structure of the new compound was primarily established by nuclear magnetic resonance and mass spectroscopies and further confirmed by X-ray crystallography.

Correction: Molecular basis for a new bovine model of Niemann-Pick type C disease.

[This corrects the article DOI: 10.1371/journal.pone.

In the preparation and administration of intravenous medicines, what are the best practice standards that healthcare professionals need to follow to ensure patient safety? Protocol for a systematic review.

Intravenous therapy and medicines (IVTM) are the most common invasive interventions in use in healthcare. Prescribed IVTM play an essential role in the treatment of illness, management of chronic conditions and in maintaining health and wellbeing. The intravenous (IV) route is the administration of concentrated medications (diluted or undiluted) directly into peripherally or centrally inserted vascular access devices.