Search Results for: Short Acting Opioid

Introduction
Type 1 diabetes (T1D) is associated with changes in brain structure, cognition, mental health, and functional outcomes. While these changes have been linked to dysregulated glycaemic control, findings are inconsistent, and their long-term impact remains unclear. Most evidence comes from cross-sectional or short-term longitudinal studies, limiting insights into causal associations. To address this, we aim to study individuals with T1D approximately 30 years after onset to assess how early dysglycaemic insults during neurodevelopment influence cognitive and functional outcomes in mid-adulthood.

Methods and analysis
This protocol paper outlines an observational, case/control, cross-sectional/longitudinal and descriptive study that follows up the original Royal Children’s Hospital (RCH) Diabetes Cohort Study. The initial study recruited children in Australia diagnosed with T1D between 1990 and 1992, conducting five waves of data collection. We now introduce the Cognition and Longitudinal Assessments of Risk Factors over 30 Years (CLARiFY) Diabetes Complications Study to assess brain, cognition and functional outcomes in mid-adulthood, approximately 30 years post-T1D onset. Both T1D participants from the original cohort and healthy controls will participate in semistructured interviews, neuroimaging and cognitive testing. T1D participants will also undergo complications screening. Data from this study and previous waves will be used to (Aim 1) explore cross-sectional and longitudinal impacts of T1D on brain health over 30 years. Linear regression will analyse cross-sectional outcomes, and multivariate analysis will assess cognitive variables jointly. Longitudinal outcomes will be examined using linear mixed-effects regression for IQ patterns, with secondary outcomes analysed via generalised linear models. Additionally, linear mixed-effects regression (Aim 2) will identify T1D-related metabolic factors affecting brain outcomes, with covariate selection informed by the construction of directed acyclic graphs (DAGs).

Ethics and dissemination
The study was approved by the Royal Children’s Hospital Human Research Ethics Committee (HREC 35 240F and 2019.065). The research findings will be disseminated through peer-reviewed publications, conference presentations, and print and social media. Participants will receive a summary of the study findings on its completion.

Objective
For every 100 women having a vaginal birth, approximately four will experience a severe (third-degree or fourth-degree) perineal tear. Severe perineal tears are associated with significant short-term and long-term consequences if not recognised and repaired. There are global efforts to reduce incidence of severe perineal tears including initiatives to strengthen education and training of clinicians in perineal anatomy and perineal tear assessment and classification. This systematic review aimed to describe and evaluate the effectiveness of these initiatives.

Design
Systematic review, reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Data sources
Medline (Ovid), CINAHL Complete (EBSCO), MIDIRS and EMBASE (Ovid) were searched through 15 February 2024.

Eligibility criteria
Studies reporting simple or complex interventions aimed at improving the skills and knowledge of clinicians in perineal anatomy and/or the clinical assessment and classification of perineal tears were eligible.

Data extraction and synthesis
Two reviewers independently screened studies for eligibility and appraised the quality of individual studies using the Cochrane Risk of Bias (RoB) 2.0 tool or Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool.

Results
In total, 7645 citations were screened and 39 studies included. We identified nine unique interventions including training programmes, short workshops and senior obstetrician supervision. Many studies were from high-income countries, in primary care settings and at high risk of bias.

Conclusions
Effective education included practical components, such as hands-on skills and training in perineal anatomy, assessment and classification, rather than senior supervision alone. Ongoing review of practice appears to be crucial for maintaining knowledge and skills. Future research should focus on interventions tailored to limited-resource settings, and the optimal length and intensity of training programmes to assess and classify perineal tears.

PROSPERO registration number
CRD42020185431.

Introduction
Caesarean birth (CB) under neuraxial anaesthesia (NA) is the most performed inpatient operation in the UK. The incidence of intraoperative pain during caesarean delivery performed under neuraxial anaesthesia is unclear, with limited data that used patient-reported measures to investigate intraoperative pain. The short- and medium-term impacts on patients of this adverse event are unknown.

Methods and analysis
We will undertake a multicentre, prospective observational cohort study to evaluate the incidence and impact of pain experienced by patients during CB performed under neuraxial anaesthesia. Routine audit data will be collected for all patients undergoing caesarean delivery for any indication during a 1 week window at participating hospitals within the UK and Queensland, Australia. The dataset will include patient, anaesthetic, obstetric and neonatal risk factors for intraoperative pain. Local investigators will then seek informed consent from patients either before or within 24 hours of delivery to record patient experience and patient-reported outcomes at 24 hours and 6 weeks postdelivery. Local investigators at participating hospitals will also complete a survey evaluating compliance with evidence-based structural standards at their sites. The patient characteristics, structures, processes and outcomes will be described. Inferential techniques will be used to evaluate the relationship between risk factors and postoperative outcomes.

Ethics and dissemination
This study received ethical approval from the Leicester Health Research Authority and Care Research Wales, REC reference 24/EM/0084) on 24 May 24. The study received ethical approval from the Human Research Ethics Committee of Metro North Health in Australia on 25 March 2024 (REC Ref HREC/2024/MNHA/103767). The results of the study will be reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement. The results will be disseminated via conference presentations, peer-reviewed academic journals and reports prepared for patients, the public and policy makers.

Trial registration number
ISRCTN15269213.

Approximately 13 million newborns were preterm (born before 37 weeks of gestation) across all member states of the World Health Organization in 2020. In 2023, the US preterm birth rate was 10.4%. Nearly all preterm infants require specialized in-hospital care to support their immature respiratory, cardiovascular, central nervous, digestive, and immune function. The length of the initial hospital stay depends on the duration of gestation, the medical condition at birth, and the development of complications such as infections or chronic lung disease. The main determinant of discharge readiness is the infant’s physiological maturity, defined as adequate control of breathing, respiratory stability, full oral feeding with appropriate weight gain, and good temperature control in a crib. In addition, the preparedness of the family and the suitability of the home environment should be confirmed. Most very preterm infants (those born between 28 and

Introduction
Postoperative nausea and vomiting (PONV) is a common complication following various surgical procedures, significantly contributing to patient discomfort and increasing healthcare costs. Despite the widespread use of multiple drug combinations, PONV remains a persistent challenge, particularly in high-risk populations. Existing evidence suggests a potential interaction between 5-HT3 receptors and μ-opioid receptors, indicating that they may function as co-receptors with a competitive relationship. Based on this hypothesis, we designed experiments to investigate this correlation.

Methods and analysis
This randomised, parallel, positive-controlled, double-blind (both intervener and participant) trial will take place at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. Based on relevant literature and our pre-test, the incidence of PONV in the intervention group is estimated to be approximately 30%. With an expected 10% loss-to-follow-up rate and a desired statistical power of 0.9 (1-β), the required sample size for each group is 65 participants, totalling 130 subjects to be enrolled from 30 March 2025 to 30 April 2025. Eligible patients will be randomly allocated to either the intervention or control group. Ondansetron will be administered 15 min before anaesthesia induction in the intervention group (n=65) and at the end of surgery in the control group (n=65). The primary outcome is the incidence of PONV within the 0–24-hour postoperative period. The sample size will be calculated using PASS 15, statistical analysis will be conducted using SPSS 25 and missing data will be addressed using the Last Observation Carried Forward method. Two-tailed tests will be employed, with significance set at α=0.05. Results will be considered significant if p

Background
There is increasing awareness of the impact of living with multiple long-term conditions (referred to as multimorbidity) on patients and health systems. Managing multimorbidity remains a challenge for primary care providers; necessitating tailored interventions that are both clinically and cost effective. In the Irish health system, two pilot trials have demonstrated promising results for patients living with multimorbidity. The first, MultimorbiditY COllaborative Medication Review And DEcision making (MyComrade), involved pharmacists supporting the management of polypharmacy, and the second, Link MultiMorbidity (LinkMM), involved link workers delivering social prescribing. This definitive trial aims to evaluate the clinical and cost effectiveness of both these interventions, as well as conduct a process evaluation.

Methods
This is a pragmatic, multi-arm, definitive, cluster randomised controlled trial in Irish general practices. The trial will include three arms: (1) MyComrade; (2) LinkMM and (3) usual care, acting as an efficient shared control arm for both interventions. For this trial, 672 patients will be recruited from 48 general practices. The eligibility criteria for the patients will be: (1) over 18 years of age; (2) has two or more chronic conditions; (3) taking 10 or more regular medicines and (4) attending their general practice team for chronic disease management. Outcome data will be collected for all participants, across all trial arms at baseline and 6 months. Primary outcomes include the number of medicines (reflecting the MyComrade intervention) and patient capability (reflecting the LinkMM intervention). Secondary outcomes include proportions and types of potentially inappropriate medications, patient experience of care, patient activation, self-rated health, health-related quality of life, mortality and healthcare utilisation. Quantitative and qualitative data will be collected to inform the process evaluation. Additionally, an economic evaluation will be conducted to evaluate the cost-effectiveness of both interventions compared with the control arm.

Ethics and dissemination
The trial protocol was approved by the Irish College of General Practice (ICGP) Ethical Review Board (ref: ICGP_Rec_2023_016). A formal knowledge dissemination plan has been developed for the trial, which includes peer-reviewed publications, conference presentations and reports to healthcare professionals, commissioners and policymakers.

Trial registration number
ISRCTN11585238.

Introduction
Peripheral artery disease (PAD) is a chronic condition causing arterial narrowing or blockage, leading to significant morbidity and mortality. Hybrid revascularisation combines open surgical and endovascular techniques to manage multilevel disease by addressing inflow and outflow obstructions. Despite increasing adoption, evidence on the long-term outcomes of these procedures remains limited.

Objective
To evaluate the long-term outcomes of hybrid revascularisation procedures in PAD, including patency rates, limb salvage, survival, reintervention rates and complications, and to provide evidence-based insights for clinical practice and research.

Methods and analysis
This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. It will include randomised controlled trials, cohort studies, case-control studies and large case series (≥10 patients, with at least 1 year of follow-up) assessing adult patients undergoing hybrid revascularisation for PAD. Primary outcomes are patency rates, limb salvage and survival; secondary outcomes include complication rates, functional improvements and quality of life. Searches will be conducted in PubMed, Embase, Cochrane Library, CINAHL and ClinicalTrials.gov. Study selection, data extraction and quality assessment will be performed independently in duplicate by two reviewers. Meta-analyses with random-effects models will summarise findings where feasible, while narrative synthesis will address instances of insufficient data. Subgroup analyses will explore outcomes by demographics, lesion characteristics and procedural details. Risk of bias will be assessed using Cochrane and Newcastle-Ottawa tools.

Ethics and dissemination
Ethical approval is not required. Findings will be published in peer-reviewed journals and presented at conferences.

PROSPERO registration number
CRD42024615809.

Introduction
The EQ-5D-Y (the youth version of EQ-5D) is widely used to assess children’s health-related quality of life (HRQoL), yet its psychometric properties across administration modes remain insufficiently explored, particularly in paediatric oncology and rare diseases. Additionally, the broader impact of childhood illness on family caregivers (spillover effects) is underexamined. This study aims to evaluate the validity, reliability and responsiveness of the three-level version of EQ-5D-Y (EQ-5D-Y-3L) and the five-level version of EQ-5D-Y (EQ-5D-Y-5L) across different modes while also assessing the EQ-5D five-level version (EQ-5D-5L) and the new EQ Health and Well-being Short Version (EQ-HWB-9) in capturing spillover effects. Originally designed for social care interventions, the EQ-HWB-9 is expected to be applicable to caregivers.

Methods and analysis
This prospective observational study will recruit children aged 5–16 years with pneumonia, central nervous system (CNS) solid tumours or immune thrombocytopenic purpura (ITP) from three hospitals in China, along with their caregivers. A total of 360 dyads (patients and their caregivers) are planned for recruitment. Children will complete EQ-5D-Y-3L, EQ-5D-Y-5L and Paediatric Quality of Life Inventory (PedsQL) in self-complete (SC), interviewer-administered (IA) and proxy-reported modes by caregivers. Caregivers will complete EQ-5D-5L and EQ-HWB-9 to assess spillover effects. Data will be collected at baseline and follow-up (2–3 weeks). Primary outcomes include psychometric assessments (construct validity, reliability and responsiveness) of all the instruments. Secondary outcomes include HRQoL scores, ceiling effects and the correlation between EQ-5D-Y and PedsQL. A qualitative substudy will explore children’s response interpretation and factors contributing to ceiling effects. Statistical analyses will include intraclass correlation coefficients for test–retest reliability, analysis of variance for known-groups validity, effect sizes for responsiveness, regression for spillover effects and thematic analysis for qualitative data.

Ethics and dissemination
Ethical approval has been obtained from three ethics committees: the Guizhou Medical University (IRB:2024159), the Children’s Hospital, Zhejiang University School of Medicine (IRB:2024-IRB-0158-P-01) and Guizhou Provincial People’s Hospital (IRB:2024073). Written informed consent will be secured from caregivers, and assent will be obtained from children aged 8 years and older. Study findings will be disseminated through national/international conferences and peer-reviewed journals.

Trial registration number
ClinicalTrials.gov, NCT06873672.

Introduction
The treatment of paediatric AIS is particularly challenging due to its rarity, limited clinical awareness and absence of targeted treatment protocols and evidence-based data. This study aims to address these gaps by investigating the epidemiology, risk factors, aetiology and treatment of stroke in children in China and to observe the short-term and long-term functional outcomes of paediatric stroke and explore the factors that influence outcomes.

Method and analysis
The Chinese Paediatric Ischaemic Stroke Registry (CPISR) is a multicentre, prospective observational study that plans to consecutively recruit patients at 85 centres across 20 provinces in China. To streamline data collection, a WeChat-based programme has been developed to allow participating institutions to input standardised questionnaire data directly and upload electronic medical records. Comprehensive demographic, clinical, neuroimaging and laboratory data are collected and tracked for registered patients. All patients undergo detailed assessment at the time of admission and during scheduled follow-up visits.

Ethics and dissemination
Ethical approval has been obtained from the Ethics Committee of the First Affiliated Hospital of University of Science and Technology of China (2022KY071). The findings of this study will be disseminated through peer-reviewed journals, national and international conference presentations and reports to participating institutions and relevant stakeholders.

Trial registration number
ChiCTR2200059915.

Objectives
To compare the effectiveness of buprenorphine-naloxone (bup/nal) and methadone maintenance therapy (MMT) in the treatment of patients with opioid use disorder (OUD) during the fentanyl era.

Design
Secondary analysis of prospective cohort study data.

Setting
Data for the study were collected from 54 clinical sites across Ontario, Canada, between May 2018 and January 2023.

Participants
To be included in the present study, participants had to be at least 16 years of age, have provided written informed consent and be receiving either MMT or bup/nal therapy for OUD. This study includes data from 2601 participants, of whom 2068 were receiving MMT and 533 were receiving bup/nal for OUD. The mean age of participants was 39.4 years (SD: 10.9), and 45% were female.

Interventions
MMT or bup/nal treatment for OUD.

Outcome measures
We employed a propensity score matched analysis to compare treatment outcomes among patients receiving MMT compared with bup/nal. We used ongoing illicit opioid use as an indicator of treatment outcome. We considered participants with >50% of urine drug screens in the past 12 months positive for non-prescribed opioids to be ‘non-responders’. We conducted subgroup analyses to identify whether treatment type was associated with ongoing non-prescribed opioid use among patients with and without a history of intravenous drug use (IVDU), and whether treatment type was associated with retention in treatment.

Results
Eight per cent of patients on bup/nal were considered non-responders, compared with 11.9% of patients on MMT. We did not find a statistically significant association between treatment type and treatment response. However, we did find that patients on MMT were more likely to stay in treatment for 12 months (OR 1.79, 95% CI 1.45 to 2.22, p

Objectives
Unplanned pneumonia readmissions increase patient morbidity, mortality and healthcare costs. Among pneumonia patients, the middle-aged and elderly (≥45 years old) have a significantly higher risk of readmission compared with the young. Given that the 14-day readmission rate is considered a healthcare quality indicator, this study is the first to develop survival machine learning (ML) models using emergency department (ED) data to predict 14-day readmission risk following pneumonia-related admissions.

Design
A retrospective multicentre cohort study.

Setting
This study used the Taipei Medical University Clinical Research Database, including data from patients at three affiliated hospitals.

Participants
11 989 hospital admissions for pneumonia among patients aged ≥45 years admitted from 2014 to 2021.

Primary and secondary outcome measures
The dataset was randomly split into training (80%), validation (10%) and independent test (10%) sets. Input features included demographics, comorbidities, clinical events, vital signs, laboratory results and medical interventions. Four survival ML models—CoxNet, Survival Tree, Gradient Boosting Survival Analysis and Random Survival Forest—were developed and compared on the validation set. The best performance model was tested on the independent test set.

Results
The RSF model outperformed the other models. Validation on an independent test set confirmed the model’s robustness (C-index=0.710; AUC=0.693). The most important predictive features included creatinine levels, age, haematocrit levels, Charlson Comorbidity Index scores, and haemoglobin levels, with their predictive value changing over time.

Conclusions
The RSF model effectively predicts 14-day readmission risk among pneumonia patients. The ED data-based model allows clinicians to estimate readmission risk before ward admission or discharge from the ED, enabling timely interventions. Accurately predicting short-term readmission risk might also further support physicians in designing the optimal healthcare programme and controlling individual medical status to prevent readmissions.

This JAMA Insights explores the use of different types of peripheral nerve blocks as an opioid-sparing pain strategy in the treatment of adults with hip fractures.

An important aspect of caring for patients with complex chronic illness, especially older adults with cancer, is understanding how treatment is tolerated. Yet barriers to seeking this information are many, including the debilitation caused by not only illness but also the adverse effects of treatment itself, which can effectively silence patients. In “Treatment Tolerability,” poetry becomes a vehicle for addressing these challenges, and imagining what patients may experience when receiving treatment (in this case, multiple transfusions). Immediately noticeable is the lack of capitalization and punctuation throughout the poem, which suggests the subordination of patients to the imperatives of urgent treatment in the quest for a cure. Adverse effects, such as confusion and weakness, are then conveyed by the haphazard rhyming in the poem; breathlessness, perhaps, is felt in the short, enjambed lines. Even the vague nursery rhyme feel of the poem seems a caution against how clinicians might infantilize and speak down to patients when attempting to assess treatment tolerability. That the poem’s speaker is not the patient but an observer seems to underscore the risk, even with the best of intentions, of supplanting the patient’s voice with our own. Finally, the speaker’s recognition of the inescapability of these concerns, and the frustration, shared by clinicians, that often accompanies them, are deftly expressed in the searching lines, “blindfolded in a fog of pain/covering everything/with a god-like fabric/because no mercy/is bright enough to pass/this fatigue onto another.”

Introduction
Kidney stones constitute a major global healthcare problem and are characterised by high recurrence rates. Thiazide and thiazide-like diuretics (thiazides) have been the standard medical treatment for the prevention of kidney stone recurrence. This clinical routine has recently been challenged by the findings of the large NOSTONE trial that failed to show superiority of hydrochlorothiazide at doses up to 50 mg daily over placebo in preventing a composite of clinical or radiological recurrence in patients at high risk of kidney stone recurrence. If these results also apply to the longer-acting and more potent thiazides indapamide and chlorthalidone remains unknown. No head-to-head comparison of different thiazides for kidney stone recurrence prevention or for the established proxies of recurrence risk, urine relative supersaturation ratios, has ever been conducted.

Methods and analysis
INDAPACHLOR is a single-centre, randomised, double-blind, cross-over trial evaluating the efficacy of indapamide or chlorthalidone compared with hydrochlorothiazide in lowering urine relative supersaturation ratios for calcium oxalate and calcium phosphate in individuals with idiopathic calcium kidney stones. Participants will be allocated to indapamide 2.5 mg once daily, chlorthalidone 25 mg once daily and hydrochlorothiazide 50 mg once daily in a random sequence. The three consecutive active treatment periods of 28 days each will be separated by wash-out periods of 28 days. Inclusion criteria are age ≥18 years and ≥2 stone episodes in the last 10 years with calcium-containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients with secondary causes of calcium kidney stones are excluded. The primary outcomes are the changes in the relative supersaturation ratios of calcium oxalate and calcium phosphate from baseline to day 28 of each treatment period. Secondary outcomes include changes in 24 hours urine and blood parameters from baseline to day 28 of each treatment period. The study targets enrolment of 99 participants to achieve 80% power for detecting a 20% reduction in the relative supersaturation ratios of calcium oxalate and calcium phosphate when treated with indapamide or chlorthalidone and hydrochlorothiazide.

Ethics and dissemination
The study was approved by the Ethics Commission Bern, Switzerland, and the Competent Authority Swissmedic. Results will be disseminated through peer-reviewed publications and conference presentations.

Trial registration numbers
ClinicalTrials.gov (NCT06111885) and Swiss National Clinical Trials Portal (SNCTP000006156).

Protocol version
Version 4.0, 29 November 2024.