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Intermittent fasting and chronic pain: Protocol for a systematic review of randomised controlled trials

Por: Bruton · A. M. · Staab · C. · Gray · O. · Chua · W. R. · Alsakhita · N. · Goldenberg · J. · Roberts · J. L.
Introduction

Chronic pain is a leading public health problem, impacting over 1.5 billion people worldwide. Standard-of-care includes pharmaceutical medication, surgery and physical therapy, yet many patients experience continued symptoms. Investigation into lifestyle-based approaches such as dietary interventions has increased in recent years, including intermittent fasting, due to known impacts on inflammation and neurotransmitters.

Methods and analysis

This systematic review and meta-analysis will be conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search will include the PubMed/MEDLINE, Embase (Ovid), Web of Science (Core Collection) and LILACS (VHL) databases. The Google Scholar, ClinicalTrials.gov, PROSPERO, Open Science Forum and MedRXiv platforms will also be searched. Randomised, controlled trials investigating the impact of intermittent fasting interventions in adult humans with any chronic pain condition will be included. The primary outcomes will be self-reported pain or function and the secondary outcome will be rescue medication use. Study screening, data extraction and risk of bias assessment will be conducted independently in duplicate. The Cochrane Risk of Bias-2 tool will be used to assess bias at the study level, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines will be used to assess bias at the outcome level. The meta-analysis will use random effects, with heterogeneity assessed using the I2 statistic. For studies that report rescue medication use, we will analyse the impact of intermittent fasting on pain or function, adjusting for rescue medication use, using established methods. Subgroup and sensitivity analyses will be conducted to explore heterogeneity.

Ethics and dissemination

As this project involves analysis of publicly available data, no ethical oversight was or is required. The results of this review will be disseminated by publication in a peer-reviewed journal.

PROSPERO registration number

CRD #420261395061.

Corneal and tear film immunology in anterior uveitis: protocol for a systematic review and meta-analysis

Por: Ye · J. L. · Tong · J. · Wu · C. Y. · Fraser · A. S. · McGuinness · M. B. · Lim · L. L. · Downie · L. E.
Introduction

Anterior uveitis is an intraocular inflammatory condition that can lead to vision impairment without appropriate and timely treatment. Determining its aetiology can be difficult due to its heterogeneous clinical presentations, which challenges effective treatment. The primary aim of this systematic review is to comprehensively identify and synthesise evidence on the immunological features of anterior uveitis in the human cornea and tear film, as a foundation for considering the utility of such features as biomarkers for disease classification, prognosis and monitoring treatment responsiveness.

Methods and analysis

Comprehensive electronic database searches will be performed in Ovid MEDLINE, Ovid Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) without date restrictions. Two independent review authors will screen retrieved titles and abstracts in Covidence relative to predefined study eligibility criteria. Studies judged eligible or potentially eligible for inclusion will undergo full-text review using a similar method. Disagreements will be resolved by consensus. For each included study, risk of bias will be assessed using validated tools appropriate to the study design. Where sufficient and appropriate data are available, meta-analyses will be performed. For outcomes where a meta-analysis is not possible, a narrative synthesis will be provided. This review will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement.

Ethics and dissemination

Ethics approval is not applicable for this review as no original data will be collected. The results of this review are expected to be disseminated through a peer-reviewed publication and/or scientific conference presentations.

PROSPERO registration number

CRD420261339682.

Endovascular thrombectomy alone versus intravenous thrombolysis plus endovascular thrombectomy on acute basilar artery occlusion (ATTENTION IV): study protocol for a multicentre randomised controlled trial

Por: Li · R. · Nguyen · T. N. · Tao · C. · Sun · J. · Xu · P. · Luo · C. · Wang · L. · Liu · T. · Song · J. · Jing · X. · Wang · A. · Qureshi · A. I. · Abdalkader · M. · Saver · J. L. · Nogueira · R. G. · Hu · W.
Introduction

The DEVT and DIRECT-MT trials showed that endovascular thrombectomy (EVT) alone is non-inferior to intravenous thrombolysis (IVT) followed by EVT in achieving 90-day functional independence for stroke patients with large-vessel occlusion (LVO). However, it is unclear whether EVT alone is non-inferior to IVT followed by EVT among patients with acute basilar artery occlusion (BAO). Therefore, additional studies are needed to explore the potential benefits of EVT alone in these patients.

Methods and analysis

The ATTENTION IV trial is a prospective, multicentre, non-inferiority, blinded endpoint assessment, randomised controlled clinical trial to assess the effect of EVT alone compared with IVT plus EVT in acute BAO patients within 4.5 hours of symptom onset. Patients will be randomised in a 1:1 ratio to either the EVT-alone group or the IVT-plus-EVT group. A score of 0–2 on the 90-day modified Rankin Scale (mRS) was designated as the primary outcome for this study. Primary analysis will follow the intention-to-treat principle with a 15% non-inferiority margin. Secondary outcomes encompass functional status (mRS shift, excellent/good/fair outcomes), quality of life, early neurological recovery and radiological outcomes alongside safety endpoints of intracerebral haemorrhage and mortality.

Ethics and dissemination

This study has been approved by the Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (2023KY-055) and will be conducted following the Declaration of Helsinki. Study results will be published in peer-reviewed academic journals.

Trial registration number

ClinicalTrials.gov (NCT05827042).

READYCOM: protocol for a 2-year prospective natural history and cross-sectional muscle-fatigability study for improving trial readiness in congenital myopathies

Por: van de Camp · S. A. J. H. · Brenninkmeijer · R. · van Doorn · J. L. M. · de Laat · E. C. M. · Pomp · L. · Stinissen · L. · Cameron · D. · Groothuis · J. T. · van Alfen · N. · Jungbluth · H. · Erasmus · C. E. · Bartels · B. · Wadman · R. I. · Voet · N. B. M. · van der Pol · W. L. · Vo
Introduction

Congenital myopathies (CMYO) are a group of rare hereditary muscle diseases defined by characteristic abnormalities on muscle biopsy. Several types, including the core myopathies central core disease and multi-minicore disease, nemaline myopathy and centronuclear myopathy, have been identified based on the characteristic histopathological changes and attributed to various genetic backgrounds. The most prominent clinical features are generalised muscle weakness often pronounced axially, variable cardiorespiratory and bulbar impairment, and skeletal and joint involvement. Currently, no curative therapies are available for CMYOs; however, a few phase I and II trials have been performed or are expected in the near future. To reach trial readiness, an informed understanding of the disease course and a selection of relevant and sensitive clinical and functional outcome measures, and blood and imaging biomarkers is necessary. Furthermore, additional symptoms such as muscle fatigability have been recognised but not investigated systematically yet. The lack of understanding muscle fatigability in CMYO in particular calls for a cross-sectional study as this feature may be a treatment target.

Methods and analysis

In collaboration with patient representatives, two studies have been designed: (1) a prospective cohort study with five 6-monthly visits over a 2-year period; and (2) a cross-sectional study on muscle fatigability. For both studies, patients from the same study population will be included. We aim to include 45 patients in study 1 and 75 in study 2. Patients are invited to participate in both studies. In study 1, we will perform a range of assessments covering patient-reported outcomes, clinical and functional outcome measures, and blood and imaging biomarkers. For study 2, we will assess the muscle fatigability and neuromuscular junction transmission. Baseline data will be analysed using descriptive statistics and correlation analysis. To assess disease progression, mixed models will be used. Multiple linear regressions will be used to explore the relationship between potential disease-modifying variables and disease severity.

Ethics and dissemination

This study was approved by the Central Committee on Research Involving Human Subjects (CCMO, registration number NL83069.000.23). Findings will be shared with the participating patients and the funder. It will be presented at conferences and shared through peer-reviewed publications.

Trial registration number

NCT06157268.

Rationale and design of a prospective cohort study and biobank of the offspring born to mothers with a solid organ transplant: protocol for the TransplantLines Next Generation study

Introduction

Successful pregnancies with healthy newborns have been reported after all types of solid organ transplantation (SOT). Limited data in young children suggest similar development and health compared with the general population. However, fetal development may be influenced by factors such as immunosuppressive medication and the increased incidence of pregnancy complications, and forthcoming health problems may only become apparent later in the life of the offspring. To allow for better investigation of the long-term health of offspring born after SOT, we designed the Transplantlines Next Generation biobank and cohort study. This study will be the first with detailed data on overall health status at later age in offspring born to mothers after kidney, liver, pancreas (including pancreas islet), heart and lung transplantation (KTx, LiTx, PTx, HTx and LuTx, respectively).

Methods and analysis

Transplantlines Next Generation is a descriptive, prospective cohort study and biobank. It includes offspring aged≥16 years born after KTx or LiTx. Because of the scarcity of pregnancies after (solo) PTx, HTx and LuTx worldwide, and as a consequence the lack of information about these pregnancies, we want to include all offspring, at any age, born after (solo) PTx, HTx and/or LuTx in the Netherlands. Participants will attend a one-time visit for questionnaires, physical tests (for participants≥16 years including kidney ultrasound and 24-hour ambulatory blood pressure) and biological sample collection (urine, blood, faeces) for participants≥16 years of age for biobanking. Reference values and values from existing birth cohorts will serve as controls. Primary endpoints are cardiovascular and kidney health, assessed through growth charts, physical tests (eg, body composition, blood pressure, kidney ultrasound) and metabolic and kidney function biomarkers. Secondary aims include immunological status, microbiome analysis, quality of life and overall development.

Ethics and dissemination

Ethical approval has been obtained from the local medical ethical committee; the Institutional Review Board METc UMC Groningen (METc 2023/610). The study will be conducted according to the Declaration of Helsinki and in accordance with the Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts including the General Data Protection Regulation (GDPR). All participants will give written informed consent upon enrolment. TransplantLines Next Generation is designed to deliver pioneering insights into the health of offspring born after SOT. This knowledge will help optimise care and available information for families with a pregnancy wish after SOT and provide a rationale for future studies. The results of this study are planned to be submitted for publication in relevant peer-reviewed journals and will be presented at national and international conferences.

Trial registration number

NCT07291258.

Development and acceptability of gist-based decision aids for prostate and breast cancer screening: a two-phase qualitative interview study in an online setting

Por: Nalavenkata · S. · Bergengren · O. · Lynch · K. · Emard · N. · Austria · M. · Martin · S. · Ogbennaya · G. · Dualeh · K. · Stevanovic · K. · Patel · M. I. · Gonsky · J. · Vickers · A. · Fagerlin · A. · Hamilton · J. G. · Hay · J. L. · Carlsson · S.
Background

Traditional approaches to designing decision aids have focused on providing completeness of information and quantitative detail. An alternative approach based on psychological research emphasises understanding the essence or ‘gist’ of the decision. Few gist-based decision aids exist. The objective of this study was to develop novel gist-based decision aids for prostate and breast cancer screening and evaluate their acceptability.

Methods

Men aged 40–60 years and women aged 40–49 years eligible for prostate or breast cancer screening were recruited from ResearchMatch (National Institutes of Health) and a public hospital located in New York City. Three rounds of semistructured interviews were performed to determine self-reported comprehensibility and acceptability, with iterative modifications after each phase, including: Phase 1: initial feedback; Phase 2, Round 1: evaluating our modifications; and Phase 2, Round 2: confirming final content.

Results

A total of 80 participants were involved in the two-phase qualitative interview process; Phase 1 and Phase 2 included 32 and 48 participants, respectively. Racial distribution was 50% white, 30% black and 10% Asian; 9% of participants were Hispanic or Latino. Most participants were highly educated. Interview themes established content validity of the final decision aids. In a quantitative analysis of the final decision aids using a questionnaire with fixed response options, acceptability was high, with two-thirds finding the length and amount of information of the decision aid to be optimal. The majority found the decision aid visually appealing, easy to read and easy to get through, and indicated that it held their interest and did not require much mental effort to read. One-quarter said the tool made them feel somewhat nervous, and three-quarters not at all. Most participants could understand and relate to the images, graphs and patient stories in the decision aid. After Phase 2, 45 of the 48 participants (94%) said they would find the decision aid helpful when making a decision.

Conclusion

This study describes the iterative development and pilot testing of a novel gist-based decision aid for cancer screening, demonstrating high acceptability. Our findings provide a foundation for randomised trials comparing gist-based and traditional tools.

Outcomes at school-age of children born extremely preterm or extremely low birth weight in Victoria, Australia: protocol for the 8-9 years follow-up of the prospective, longitudinal Victorian Infant Collaborative Study (VICS) 2016-2017 cohort

Por: Cheong · J. L. Y. · Nguyen · T.-N.-N. · Olsen · J. E. · Pigdon · L. · Du Berry · C. · Howlin · L. · Mainzer · R. M. · Anderson · P. J. · Spittle · A. J. · Doyle · L. W. · The Victorian Infant Collaborative Study Group · Abraham · Alarcon-Martinez · Anderson · Axford · Boland · Ch
Introduction

Children born extremely preterm (EP;

Methods and analysis

This is a follow-up of the VICS 2016–2017 cohort, a prospective longitudinal cohort study of children born EP/ELBW and a contemporaneous group of term-born controls born in the state of Victoria, Australia. Children were previously assessed at 2 years’ corrected age.

Follow-up at 8–9 years’ corrected age includes a comprehensive assessment of cognitive, motor, social and behavioural development and lung function.

Follow-up at 8–9 years’ corrected age includes a comprehensive assessment of cognitive, motor, social and behavioural development and lung function.

Ethics and dissemination

The study has approval from the Royal Children’s Hospital Human Research Ethics Committee, Melbourne, Australia. The findings will be disseminated via peer-reviewed journal publications, conference presentations, digital and print media and through parent support/network groups.

Long-term disparities and mediators of psychological distress in mothers with and without out-of-home care experience: analysis of prospective cohort data

Por: Park · J. · Hiller · R. M. · Shelton · K. · Carter · B. · Sprecher · E. A. · Mckeaveney · E. · Damman · J. L. · Robinson · C. · Ramsay-Patel · T. · Holmes · L.
Objectives

Care-experienced individuals are at elevated risk of mental health difficulties, yet less is known about their mental health needs in motherhood. This study aims to explore (a) disparities in trajectories of psychological distress in care-experienced versus non-care-experienced mothers as they raise their child from age 3 to 14, and (b) putative postpartum-associated pathways shaping disparities in maternal distress at child age 14.

Design and setting

We conducted longitudinal secondary data analysis using the prospective United Kingdom Millennium Cohort Study data.

Participants

11 252 mothers and their children were included in the analysis, including mothers who experienced out-of-home care in their childhood (N=156).

Outcomes

The primary outcomes were psychological distress of mothers at child ages 3, 5, 7, 11 and 14.

Results

Relative to non-care-experienced mothers, care-experienced mothers were consistently more likely to experience distress across child ages 3–14 (coefficient (B)=1.36 (95% CI 0.85 to 1.87) pp=0.005), lower locus of control (B=0.31 (95% CI 0.11 to 0.51) p=0.002), lower income (B=0.28 (95% CI 0.15 to 0.41) pp=0.006) in their child’s infancy.

Conclusions

Our evidence underscores the potential value of holistically considering postpartum mental health, psychosocial and financial resources in maternal and early childhood public health interventions to disrupt the cumulative inequity likely faced by care-experienced mothers and prevent their mental ill-health in the long term.

Diagnostic stewardship in emergency departments using the UNTIE framework: a stepped-wedge cluster randomised study protocol

Por: Chandru · P. · Gunja · N. · Poon · S. · Mallows · J. L. · Nguyen · K. · McNulty · R. · Teixeira-Pinto · A. · Loy · C.
Introduction

Pathology testing accounts for over half of non-labour costs in Australian Emergency Departments (EDs), yet up to one-fifth of tests are unnecessary. Despite national guidance from the Australasian College for Emergency Medicine (ACEM) and the Royal College of Pathologists of Australasia (RCPA), variation in test ordering persists across departments and across clinical presentations. The Unnecessary Tests in Emergency (UNTIE) study aims to evaluate whether audit and feedback using a novel indicator can reduce unnecessary pathology testing.

Methods and analysis

UNTIE is a multicentre, stepped-wedge cluster randomised trial conducted across five metropolitan EDs in New South Wales, Australia. All adult ED presentations that fall within the 29 clinical conditions covered by the 2023 ACEM–RCPA guideline will be included. Presentations were identified using routinely collected ED triage diagnoses. Because the ACEM–RCPA pathology guideline specifies clinical presentations rather than diagnostic codes, a mapping process was developed to align triage terms used in the electronic medical record with the guideline categories. Approximately 100 common triage diagnoses were reviewed by a panel of emergency physicians and mapped to the 29 eligible presentations. This mapping dictionary was used to automatically classify all ED encounters during data extraction. Ambiguous or unmapped triage terms were reviewed and assigned by consensus.

The intervention comprises a multifaceted audit-feedback programme—combining local champions, education sessions, visual prompts and electronic dashboards. Two automated indicators will be generated for every eligible ED encounter: UNTIE-U (Unnecessary Testing Index) representing the proportion of tests performed but not recommended and UNTIE-N (Necessary Testing Index) representing the proportion of guideline-recommended tests performed. The primary outcome is change in UNTIE-U before and after intervention; the secondary outcome is change in UNTIE-N.

Ethics and dissemination

Ethics approval has been granted by the Western Sydney Local Health District Human Research Ethics Committee (HREC/17/WMEAD/274, 2022/STE03249). All analyses will use de-identified data. Findings will be disseminated through peer-reviewed publication, conference presentation and feedback to participating EDs.

Trial registration number

Australian New Zealand Clinical Trials Registry: ACTRN12623001130651, UTN: U1111-1297-0386

Dialogic reading at age 2 is linked to frontal activation related to executive function at age 5: An fNIRS study

by Ming Yean Sia, Chia-Feng Lu, Ovid J. L. Tzeng, Shinmin Wang

This study investigates the relationship between children’s dialogic reading (DR) experiences with parents at age 2 and their frontal neural responses related to executive function (EF) at age 5. To assess how the intensity of DR influences brain development, we quantitatively measured parental engagement in DR when children are at 2 years of age. Neural activations in frontal regions associated with EF were evaluated using functional near-infrared spectroscopy when children reached age 5. Our results reveal a significant positive correlation between parental dialogic interaction during shared book reading at age 2 and the activation of key brain regions related to EF – the bilateral dorsolateral prefrontal cortex and the bilateral inferior frontal gyrus – during a Dimensional Change Card Sort (DCCS) task at age 5. This correlation persisted even after controlling for maternal education and children’s expressive vocabulary, indicating a robust relationship between early DR experiences and subsequent neural correlates of EF. The results suggest that early DR may help cultivate the neural infrastructure necessary for EF development. By focusing on DR at a young age and assessing neural activity during a classic EF task, the DCCS, our findings contribute additional evidence regarding the role of DR in shaping neural development associated with EF. These results highlight the importance of encouraging interactive DR practices in early childhood, as they not only support language development but also strengthen the neural pathways crucial for cognitive skills essential for academic success.

The LIFE study: a cross-sectional study protocol for LIfestyle risk Factors for chronic disease across the stagEs of reproductive ageing

Por: Pernoud · L. E. · Noll · J. L. · Gardiner · P. A. · Dean · M. · Broadhouse · K. M. · Walker · M. A. · Wright · H. H. · Villani · A. · Scott · J. · Metse · A. P. · Schaumberg · M. A.
Introduction

The dynamic physiological and hormonal changes through the menopause transition predispose women to an increased risk of chronic diseases including cardiovascular disease, metabolic disease, depression and dementia. The underlying mechanisms remain unclear, yet it is thought that chronic systemic inflammation and changes to lifestyle behaviours play important roles. The LIfestyle risk Factors for chronic disease across the stagEs of reproductive ageing (LIFE study) is a cross-sectional study aimed to characterise how hormonal and lifestyle (physical activity, diet and sleep) differences across pre, peri and postmenopause influence chronic systemic inflammation, visceral adiposity, cognitive function and sleep health.

Methods and analysis

Women aged between 40 and 65 years were recruited and classified into pre, peri or postmenopausal groups. Body composition measures and blood samples were collected. Sleep and physical activity were objectively measured using activPAL4 and ActiGraph GT9X link accelerometer over 7 days. Participants were also provided with a sleep diary. Physical function was assessed using the Short Physical Performance Battery. Cognitive function was evaluated using Addenbrooke’s Cognitive Examination-III and Cambridge Neuropsychological Test Automated Battery. Participants completed a series of questionnaires: Depression, Anxiety and Stress Scale-21, RuSATED, Berlin Questionnaire, Insomnia Severity Index, Activities-specific Balance Confidence Scale and the Australian Eating Survey.

Ethics and dissemination

Ethical approval was received from the relevant University Human Research Ethics Committee (ethics approval number #S221718) prior to the commencement of the research project. Data collection is ongoing and expected to be completed by April 2026. Results are expected to be available from July 2026. Findings will be disseminated in national and international conferences and in peer-reviewed journals and expected to inform how differences in lifestyle behaviours across menopause influence chronic systemic inflammation, visceral adiposity and cognitive function. Understanding and characterising the links between lifestyle behaviours and menopausal symptoms will inform targeted strategies to improve long-term well-being, heart, brain and metabolic health.

Electronic nicotine delivery systems versus nicotine replacement therapies and risk of smoking relapse: evidence from a US nationwide prospective cohort (Cancer Prevention Study-3)

Por: Westmaas · J. L. · Landry · M. · Nighbor · T. · Xue · Z. · Diver · R. W. · Patel · A. · Kondo · K. K. · Asare · S. · Lori · A. · Bandi · P. · Nargis · N.
Objective

To compare use of electronic nicotine delivery systems (ENDS) with nicotine replacement therapies (NRTs) on risk of cigarette smoking relapse by people who had already quit cigarettes.

Design

Prospective cohort study.

Setting

The American Cancer Society Cancer Prevention Study-3, a nationwide US cohort with follow-up every 3 years beginning in 2015.

Participants

Adults who in 2015 had already quit smoking (n=3112) or were smoking (n=1018) and who in 2018 reported past or current exclusive use of ENDS or NRT and provided smoking status.

Outcome measures

Relapse to cigarette smoking in 2018 among people who were already quit in 2015, and abstinence from cigarettes in 2018 among people who were smoking in 2015.

Results

Among respondents who had already quit in 2015, the unadjusted risk of relapse in 2018 was approximately three times greater for those who reported past exclusive ENDS versus past exclusive NRT use (11.2% vs 3.9%; relative risk (RR)=2.90, 95% CI 2.12 to 3.98). This association remained significant in a multivariable-adjusted model (RR=2.09, 95% CI 1.49 to 2.92). Among those smoking in 2015, the unadjusted likelihood of abstinence in 2018 was higher for those who reported current ENDS versus NRT use (RR=1.35, 95% CI 1.01 to 1.80), but the multivariable model adjusted for smoking frequency indicated no difference in abstinence (RR=1.38; 95% CI 0.93 to 2.05).

Conclusions

ENDS use was associated with greater relapse risk than NRT among people who had already quit. Although ENDS may support shorter-term cessation, further long-term observational research is needed to clarify relapse risks associated with ENDS relative to NRT.

Polyneuropathy in kidney transplant recipients: a cross-sectional study in Groningen, the Netherlands

Por: Nolte · S. · Moes · H. R. · Bakker · S. J. L. · Oldag · C. · Lange · F. · de Greef · B. T. A. · Nolte · I. M. · Van Londen · M. · Elting · J.-W. J. · Faber · C. G. · Van Doorn · P. A. · Berger · S. P. · Drost · G.
Objectives

To determine the prevalence and clinical characteristics associated with polyneuropathy in kidney transplant recipients (KTRs).

Design

Cross-sectional study.

Setting

SENS study at the University Medical Center Groningen, the Netherlands, December 2021–May 2023.

Participants

KTR, participating in the ongoing TransplantLines Biobank and Cohort Study, ≥12 months post-transplantation.

Main outcome measures

Participants underwent a structured neurological assessment including history taking, neurological examination, quantitative sensory testing and nerve conduction studies. An expert panel classified participants into no/possible, probable/definite large fibre polyneuropathy or small fibre neuropathy. Large-fibre subtypes included axonal or demyelinating, pure sensory, pure motor and sensorimotor. To assess potential associations with clinical characteristics, logistic regression analysis was conducted.

Results

We included 160 KTRs with a mean age of 59.8±11.6 years at a median of 6.1 (95% CI 3.9 to 13.1) years post-transplantation, with 16 KTRs (10%) diagnosed with polyneuropathy before study inclusion. In total, 84 KTRs (53%) were identified with large fibre polyneuropathy and 7 KTRs (4%) with small fibre neuropathy. KTRs with large fibre polyneuropathy presented with either sensor-predominant polyneuropathy (40 KTR (48%)) or sensorimotor polyneuropathy (44 KTR (52%)). We found no neurophysiological characteristics of demyelination. Overall, 18% (95% CI 11% to 27%) of KTRs with large fibre polyneuropathy were asymptomatic. Higher age (OR=1.04 (1.01 to 1.08), p=0.01), male sex (OR=2.55 (1.19 to 5.60), p=0.02), diabetes (OR=5.58 (1.36 to 38.14), p=0.03) and elevated urea levels (OR=1.12 (1.04 to 1.23), p=0.01) were significantly associated with polyneuropathy in KTR.

Conclusions

In contrast with previous studies, axonal sensory or sensorimotor polyneuropathy is highly prevalent and often underdiagnosed in KTR. Next to higher age and male sex, it was independently associated with diabetes and higher urea levels. Further research is needed to reveal the aetiology and course of polyneuropathy in KTRs.

Trial registration number

NCT04664426.

Association between joint tenderness, patient-reported joint pain and ultrasound abnormalities in anti-CCP positive individuals at risk of rheumatoid arthritis: a cross-sectional study from a Leeds (UK) cohort

Por: Garcia-Montoya · L. · Kang · J. · Duquenne · L. · Di Matteo · A. · Harnden · K. · Nam · J. L. · Chowdhury · R. · Wakefield · R. J. · Mankia · K. S. · Emery · P.
Objectives

In individuals at-risk of rheumatoid arthritis (RA), to investigate how joint tenderness and patient-reported joint pain (PRJP) relate to ultrasound abnormalities and assess whether these exploratory results could be used to assist future evaluation of symptom/signs-guided ultrasound scanning approaches in this population.

Methods

This is a cross-sectional analysis from a Leeds (UK) cohort of anti-cyclic citrullinated peptide (anti-CCP) positive individuals with new musculoskeletal complaints and no clinical arthritis. Assessments included physical examination, a mannequin where participants ticked joints that were painful and ultrasound scans of wrists, metacarpo-phalangeal joints 1–5 (MCPs1-5), proximal interphalangeal joints 1–5 (PIPs1-5), elbows, knees, ankles, metatarso-phalangeal joints 1–5 (MTPs1-5), finger flexor tendons (2-5) and extensor carpi ulnaris. Grey scale (GS), power Doppler (PD), tenosynovitis and erosions were assessed. A generalised estimating equations model was used to evaluate potential associations between tenderness/PRJP and ultrasound findings at the joint-level, adjusting for age and sex. Positive and negative predictive values for ultrasound changes were calculated.

Results

323 participants were analysed. Joint tenderness was associated with ultrasound abnormalities, predominantly PD in wrists, MCPs, PIPs, elbows, knees and MTPs. GS and erosions were also associated with tenderness, but to a lesser degree. Association of PRJP with ultrasound abnormalities was more inconsistent and mostly for GS in the feet (all p0.05). Absence of symptoms and signs had a negative predictive value between 97% and 100% in all joints, except in wrists; which was slightly lower.

Conclusions

In anti-CCP positive individuals at risk of RA, tenderness, predominantly in the small joints, was associated with local inflammatory changes on ultrasound. The association of PRJP and ultrasound was limited. In the absence of tenderness, the presence of PD, tenosynovitis or erosions was uncommon. These findings may inform future studies evaluating symptom/sign-guided ultrasound assessment approaches in at-risk populations.

Trial registration number

NCT02012764.

Cost of emergency hospital admissions to acute general wards for mental health problems among children and young people in England, 2012-2022: a retrospective observational study

Por: Pilvar · H. · Cornaglia · F. · Ward · J. L. · Vazquez-Vazquez · A. · Phillips · K. · Settle · K. · Gibson · F. · Nicholls · D. · Roland · D. · Roberts · H. · Viner · R. M. · Hudson · L. D.
Objectives

To examine trends in the frequency and costs of emergency hospital admissions in acute wards for mental health conditions among children and young people in England between 2012 and 2022 and to assess socioeconomic and geographic disparities in these costs.

Design

Retrospective observational cohort study using routinely collected administrative data.

Setting

Secondary care acute wards; analysis includes all National Health Service (NHS) hospital admissions in England.

Participants

All emergency hospital admissions in acute wards for individuals aged 5–18 years with a primary or secondary mental health diagnosis recorded between 2012 and 2022. Exclusion criteria included admissions without a mental health diagnosis or outside the defined age range.

Primary and secondary outcome measures

Primary outcomes were the annual number and total cost of mental health-related emergency admissions. Secondary outcomes included length of stay, diagnostic categories contributing to cost, and variation by socioeconomic deprivation and geographic location.

Results

Between 2012 and 2022, the total cost of emergency admissions for mental health among children and young people rose markedly, driven by increases in both admission rates and length of stay. Children from the most socioeconomically deprived areas experienced higher admission rates and greater associated costs. Substantial regional variation in the financial burden was also observed. Eating disorders and self-harm were the main diagnostic categories contributing to the rise in costs. Following the COVID-19 pandemic, total admission numbers declined, but overall costs remained high due to a shift in diagnostic mix towards conditions associated with longer hospital stays and higher per-admission costs.

Conclusions

The increasing financial burden of paediatric mental health crises highlights the urgency of addressing upstream drivers of poor mental health. Policies should prioritise early intervention, reduce regional and socioeconomic disparities, and ensure equitable allocation of mental health resources. Further research should explore the effectiveness of community-based alternatives to hospital care.

Screening for hyperglycaemia in pregnancy and pregnancy outcomes among Aboriginal women in remote communities of the Northern Territory, Australia: a retrospective cohort study

Por: Wood · A. J. · OHara · C. · Joyce-Tubb · A. · Webster · V. · Wicks · M. · Van Dokkum · P. · Maple-Brown · L. J. · Hare · M. J. L.
Background

Aboriginal women in the remote Northern Territory (NT) experience high rates of adverse pregnancy outcomes related to hyperglycaemia in pregnancy. Oral glucose tolerance test (OGTT) screening was recommended in early pregnancy but barriers to uptake exist.

Objectives

To examine uptake of screening for hyperglycaemia in pregnancy among Aboriginal women in remote NT communities and explore adverse pregnancy outcome rates among women who did not have early OGTT screening compared with women who did undergo screening in early pregnancy and those with pre-existing diabetes.

Design

Retrospective observational cohort study of pregnancies among Aboriginal women in remote NT clinics from January 2017 to December 2019. Screening for hyperglycaemia in pregnancy included having an early OGTT (

Results

Among 1191 pregnancies in 52 remote communities, pre-existing type 2 diabetes (T2D) was diagnosed in 6.4% (n=76) and gestational diabetes mellitus (GDM) was diagnosed in 13% (154/1191). Excluding women with pre-existing diabetes, 226 (20%) had an early OGTT. Guideline-directed screening (with either (a) an early OGTT diagnosing GDM or (b) a negative early OGTT followed by a routine OGTT) occurred in 14% of pregnancies (n=158). Compared with women who had an early pregnancy OGTT, the combined adverse pregnancy outcome was more common among women with pre-existing T2D (89% vs 54%, adjusted OR 6.06 (95% CI 2.75 to 13.35)) and similar among women who did not undergo early OGTT (50%, adjusted OR 0.97 (95% CI 0.71 to 1.32)).

Conclusion

Uptake of guideline-directed screening in Aboriginal women in remote NT was low, although there was no difference in pregnancy outcomes for women who were and were not screened with an early OGTT. Rates of adverse pregnancy outcomes were concerningly high in women with pre-existing T2D, highlighting a need to strengthen diabetes care for these women.

Comparison of iloprost therapy versus non-iloprost therapy for severe frostbite: a retrospective cohort study of two Canadian cities

Por: ODochartaigh · D. · Douma · M. J. · Picard · C. · Violato · E. · Poole · A. · Gauthier · J. · Armour · A. · Tiwana · D. · Harrigan · T. · Gabriel · V. · Brown · J. · Ghosh · S. M. · MacNairn · I. · Khangura · J. · Boucher · H. · Robinson · L. · Watt · L. · Van Nest · J. · Bown · J. l. · Mage
Objectives

Frostbite is a common reason for emergency department (ED) presentations in Canada. Iloprost, a prostacyclin analogue, has been investigated to reduce the risk of amputation with its use expanding. Two Canadian cities implemented iloprost over different times leading to a practice variation that allowed for treatment comparison. Our objective is to evaluate the effectiveness of iloprost compared with non-iloprost treatment. Secondary objectives include assessing the impact of iloprost dosage and homelessness.

Methods

A retrospective cohort study was conducted on adult severe frostbite cases presenting to EDs in Calgary and Edmonton between November 2021 and April 2024. Data were abstracted from clinical databases and analysed for demographic and injury characteristics, treatment and amputation outcomes.

Results

Of 1812 total ED encounters for frostbite, 257 patients with grades 2–4 extremity frostbite were included for analysis. Logistic regression found that overall patients receiving iloprost were associated with reduced likelihood of any amputation (OR=0.49, 95% CI 0.25 to 0.96) and fewer digit amputations (p

Conclusions

Iloprost infusion was associated with a reduction in amputation rates in grade 3 and 4 frostbite with the greatest association seen in grade 3 cases. Greater iloprost dosage was associated with improved digit salvage. Homelessness was associated with delayed ED presentation.

Advancing sustainable medication use in healthcare: a Delphi study on (de)prescribing interventions

Por: Smale · E. M. · van der Giessen · J. L. · Appels · C. W. Y. · Leegwater · E. · Dietz · M. · van den Bemt · P. M. L. A. · Coenradie · S. · Kool · R. B. · Kwint · H.-F. · Ista · E. · Hunfeld · N.
Objective

To identify and prioritise the most appropriate (de)prescribing interventions in inpatient and outpatient hospital care to advance environmentally sustainable healthcare.

Design

A modified RAND Delphi study.

Setting

Inpatient and outpatient hospital care in the Netherlands.

Participants

The Delphi panel consisted of 63 participants, comprising 36 physicians and 27 pharmacists working in Dutch hospitals.

Primary and secondary outcome measures

Consensus on the appropriateness of (de)prescribing interventions for frequently used medications in inpatient and outpatient hospital care to advance environmentally sustainable healthcare and the prioritisation of interventions per care setting (inpatient/outpatient) and intervention type (deprescribing/sustainable dosage form), culminating in a top 20.

Results

51 (de)prescribing interventions were identified for 18 medication classes, for which consensus on appropriateness was reached for 42 (82%). The top 20 highest ranked interventions were identified, starting with switching from intravenous to oral administration of paracetamol, stopping chronically used proton pump inhibitors without indication and initiating antibiotics orally in case of good bioavailability.

Conclusions

Most (de)prescribing interventions were considered appropriate for advancing sustainable medication use, highlighting support for their potential implementation to reduce the environmental burden of healthcare.

Effectiveness of interventions involving parents on childrens eating behaviours: protocol for a systematic review and meta-analysis

Por: Khorramrouz · F. · Rae · S. · Kucab · M. · Uleryk · E. M. · Maguire · J. L. · Pechlivanoglou · P. · Thorpe · K. E. · Comelli · E. M. · Birken · C. S.
Background

Parents play a pivotal role in shaping their children’s food environment and eating behaviours. Involving parents in interventions designed to promote nutritional outcomes such as dietary intake in children has been shown to improve parental feeding practices. However, it remains unclear how such interventions influence children’s eating behaviour outcomes. This protocol describes the methods of a systematic review evaluating the effectiveness of interventions involving parents in improving the eating behaviours of healthy children aged 0–12 years.

Methods and analysis

Electronic databases including MEDLINE, EMBASE, CENTRAL, APA PsycINFO, CINAHL, Scopus and Web of Science will be searched from inception to September 2025. A search strategy is developed to identify randomised controlled trials directly involving parents and reporting eating behaviours in children as either primary or secondary outcomes. Two independent reviewers will screen identified records and extract data on study, participant and intervention characteristics. Study results relevant to our primary and secondary outcomes will also be extracted using a prepiloted standardised data extraction form. We will use the Revised Cochrane Risk of Bias tool (RoB2) and Grading of Recommendations Assessment, Development and Evaluation approach to assess risk of bias and certainty of evidence, respectively. Where possible, meta-analysis using random-effects models will be performed; otherwise a qualitative summary will be provided.

Ethics and dissemination

Ethics approval is not required for this study as no primary data will be collected. The findings will provide valuable insights for stakeholders to inform and optimise public health policies and practices aimed at empowering families to promote healthy eating behaviours early in childhood. The results will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD420251076540.

Randomised controlled trial comparing antibiotic cement bead pouch versus negative pressure wound therapy for the management of severe open tibia fracture wounds: Beads versus VAC (BvV) protocol

Por: Marchand · L. S. · Slobogean · G. · OHara · N. N. · Harris · A. D. · Grainger · D. W. · Thabane · L. · Bhandari · M. · Della Rocca · G. J. · Kellam · P. J. · Zura · R. D. · Marvel · D. · Wells · J. L. · Gitajn · I. L. · Jeray · K. J. · OToole · R. V. · Working · Z. M. · Natoli · R. M.
Introduction

Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds.

Methods and analysis

BvV is a multicentre, pragmatic, parallel arm randomised controlled trial that aims to enrol 312 adult patients admitted to a participating centre with a severe open tibia fracture requiring multiple irrigation and debridement surgeries. Participants will be randomly allocated on a 1:1 basis to either antibiotic cement bead pouch or negative pressure wound therapy. The primary outcome will be a composite outcome to evaluate clinical status 6 months after randomisation. Using the win ratio approach, we will hierarchically assess the composite outcome in the following order: (i) all-cause mortality, (ii) injury-related amputation of the lower extremity, (iii) unplanned reoperation to manage wound complications, an infection or promote fracture healing and (iv) clinical fracture healing assessed using the Functional IndeX for Trauma (FIX-IT) instrument.

Ethics and dissemination

The BvV trial has been approved by a central institutional review board (IRB) (Advarra) for clinical sites in the USA, the ethics board at the coordinating centre at McMaster University (Hamilton Integrated Research Ethics Board), and participating sites not using the central institutional IRB (Fraser Health Research Ethics Board, The University of British Columbia Clinical Research Ethics Board, Newfoundland and Labrador Health Research Ethics Board, University of Manitoba Biomedical Research Ethics Board). Additional clinical sites who are in the start-up phase, as well as any new selected clinical sites, will obtain local approvals prior to initiating trial activities. This will include a clinical site in the UK who is in the process of obtaining the necessary approvals. Recruitment began in November 2023. Both interventions are frequently used to manage severe open fracture wounds, ensuring that the trial results can be easily transitioned into clinical practice. The results of this trial will be disseminated to national and international partners through peer-reviewed publications, academic conferences and stakeholder engagement activities.

Trial registration number

NCT05615844.

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