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About 30% of depressed patients suffer from a protracted course in which the disorder continues to cause significant burden despite treatment efforts. While originally developed for relapse prevention, mindfulness-based cognitive therapy (MBCT) has increasingly been investigated in depressed patients with such ‘difficult-to-treat’ courses. This is a protocol for an individual participant data (IPD) meta-analysis aiming to determine efficacy and potential moderators of MBCT treatment effects in this group based on evidence from randomised controlled trials.
Systematic searches in PubMed, Web of Science, Scopus, PsycINFO, EMBASE and the Cochrane Controlled Trials Register for randomised controlled trials were completed on 17 June 2024. Authors of identified studies have contributed IPD, and data extractions have been completed. An update search will be conducted immediately before the start of data analyses. We will investigate the following outcomes: (a) self-reported and observer-reported severity of depression symptomatology, (b) remission and (c) clinically meaningful improvement and deterioration. One-stage and two-stage IPD-MA will be conducted with one-stage models using the observed IPD from all studies simultaneously as the primary approach. One-stage IPD models will include stratified study intercepts and error terms as well as random effects to capture between-study heterogeneity. Moderator analyses will test treatment-covariate interactions for both individual patient-level and study-level characteristics.
The results will inform understanding of the use of MBCT in patients with current ‘difficult-to-treat’ depression and will contribute to arguments in favour of or against implementing MBCT as a treatment for this group. They will be published in a peer-reviewed journal and made available to stakeholders in accessible formats. No local ethical review was necessary following consultation with the Ethics and Governance Board of the University of Surrey. Guidance on patient data storage and management will be adhered to throughout.
CRD42022332039.
Osteogenesis imperfecta (OI) is the most common inherited cause of bone fragility (approximately 1 in 16 000). People with OI suffer bone fragility causing fractures, pain and deformity; sarcopenia causing fatigue and poor endurance; aortic root dilatation and hearing loss. No drug currently has market authorisation to treat OI in Europe. Current standard-of-care is multidisciplinary, with pharmacological interventions—primarily bisphosphonates—directed at increasing bone mass; however, such interventions are of equivocal efficacy. The structural damage that can accumulate as a result of repeated fractures over time may not be reversible. The lack of a treatment with clearly defined efficacy in terms of reducing fracture frequency or the sarcopenia, that is increasingly recognised in this condition, leads to the consideration of alternatives based on what is known about the molecular pathophysiology of the condition. For reasons that are currently unclear, transforming growth factor beta (TGFβ) pathway signalling is increased in OI, and both studies in mouse models and more recently also in humans suggest that reducing TGFβ pathway signalling could be of benefit in OI. This demonstrator project tests the hypothesis that losartan, an antihypertensive agent known to reduce circulating TGFβ, will reduce bone turnover and bone loss and have a positive effect on muscle function and quality of life in adults and older adolescents with OI.
This is a phase 2/pilot, open-label, dose-escalating study. This study aims to identify the effective dose for losartan in this population to inform the design of a pivotal phase III study. The study aims to recruit 30 adolescents and adults aged 16 years and above with OI across secondary care study sites in the UK and Italy. Participants will be recruited from the patient populations attending for treatment of OI at the participating hospital sites or referred by clinicians at the Participant Identification Centres (PIC sites). Participants will be randomised to one of three ‘final doses’—25, 50 or 75 mg losartan once daily. All participants will start on 25 mg once daily. Those assigned to higher ‘final doses’ will increase in 25 mg once daily increments on day 8 and day 15 following safety assessments. The primary outcome measures are to establish the effective dose of losartan in OI patients, based on maximal reduction in the bone resorption marker carboxy-terminal crosslink of type I collagen telopeptide (CTX) over the 24-week period of the study.
Secondary outcome measures are to determine the changes in proxy efficacy outcomes for bone (turnover, mass, architecture and strength) using blood tests, high-resolution peripheral quantitative CT (HRpQCT), dual-energy X-ray absorptiometry (DXA) and muscle (strength) using the ‘Timed Up and Go’ test. In addition, the changes in quality of life, including pain and fatigue, will be evaluated by using a disease-specific tool (OI-QOL) and a validated generic tool (EQ-5D-5L-VAS).
In the UK, the study protocol and amendments have been approved by the London Bridge Research Ethics Committee (REC reference: 23/LO/015) and by the Medicines and Healthcare products Regulatory Agency (MHRA). In Italy, the study protocol and amendments have been approved by the Italian and European ethics and regulatory authorities (Clinical Trials Information System European Union (CTIS EU) portal according to EU Regulation 536/2014). Final version of study protocol: Version 3.2, 05.03.2025. Final results will be disseminated in peer-reviewed journals through local OI, orthopaedic and other relevant clinical networks and at national and international meetings. Sheffield Children’s National Health Service Foundation Trust (UK) and Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Istituto Ortopedico Rizzoli (Italy) are the joint study sponsors.
ISRCTN (ISRCTN13317811).
To evaluate the clinical effectiveness of a Nurse Practitioner led procedural support service for children with procedural anxiety, and identify facilitators and barriers to its sustained implementation and optimisation.
An effectiveness–implementation hybrid type 3 study used a prospective mixed methods evaluation approach.
From December 2022 to May 2023, data were collected from children, parents and clinicians using a nurse practitioner-led service at a quaternary paediatric hospital in Brisbane, Australia. A prospective audit assessed clinical outcomes, while qualitative interviews explored implementation barriers and facilitators.
The clinical audit (n = 40) confirmed the service was effective and safe, ensuring procedural completion with minimal distress. Descriptive statistics indicated low pain and anxiety scores. There was a moderate negative relationship between pain scores and the use of distraction techniques. Interviews with thirty-three participants showed the service improved access to procedural care, reduced the need for physical restraint and general anaesthesia, and enhanced clinical workflow through preadmission assessments.
Utilising a Nurse Practitioner support service represents a safe and effective strategy to enhance access for paediatric patients with procedural anxiety.
This study underscores the significance of specialised nursing roles in managing paediatric procedural anxiety, offering a replicable model to enhance procedural outcomes and mitigate medical trauma across healthcare settings.
Minimising pain and distress is important in all clinical encounters with children to reduce the risk of medical-related trauma and the future avoidance of healthcare.
The report of study outcomes was guided by the Standards for Reporting Implementation Studies (StaRI) initiative.
Patients or the public were not included in the design, conduct or reporting of the study.
Although some research supports the maintenance of positive outcomes from cardiac rehabilitation Phase II (CR II) up to 12 months, the barriers to maintaining physical activity and risk factor management during CR maintenance (CR III) are well known.
To investigate participants' ability to sustain clinical, quality-of-life (QOL), and behavioral outcomes and share their experiences 6 months after CR II completion.
Longitudinal explanatory sequential pre-CR/post-CR study in a community hospital within a large health system. A convenience sample of 155 participants completed a reassessment of health outcomes. Participants also completed an online survey about barriers and facilitators during and after CR II. Analysis methods included MANOVA and summative content analysis.
The sample was mostly male, white, non-Hispanic, and college educated, with a mean age of 67.9 years. CR II participants sustained most behavioral outcomes, but not all clinical outcomes. Outcomes that improved/maintained were physical activity, tobacco status, diet, and QOL. Outcomes that worsened/returned to pre-CR II were weight, blood pressure, and depression. Participants described their motivation for staying healthy, top concerns, goals, barriers, and strengths/resources. Common responses included exercise, weight, diet, quality of life, family, and friends.
Our findings suggest the need for the implementation of innovative strategies during CR II that may extend past discharge into CR III. These include the introduction of digital technology and eHealth to provide value-added service to patients and a solid foundation for future maintenance and a structured, behavioral weight loss intervention. Establishing these tools, in addition to developing a support system will help patients to initiate maintenance care before program completion.
by Amanda E. Hewes, Cassandra Fieldson, Maude W. Baldwin, William A. Buttemer, Alejandro Rico-Guevara
Honeyeaters (Aves, Meliphagidae) are a speciose clade of nectarivorous birds, and there is immense diversity in the degree to which different species within the family rely on nectar. Honeyeater tongues are commonly described as similar to a paintbrush, with this morphology being interpreted as an adaptation for increasing nectar extraction efficiency. However, there has been limited work documenting the degree of interspecific diversity in tongue morphology across the family or the extent to which such diversity correlates with dependance on nectar. This information is also lacking for the hyoid bones, the structures responsible for moving the tongue in and out of the mouth. We aimed to fill this knowledge gap by examining honeyeater tongues and hyoids from across the family. We found that there are six distinct tongue types across the Meliphagidae, and that certain genera such as Acanthorhynchus and Phylidonyris have a unique tongue morphologies. Using phylogenetic generalized least square regressions, we found that tongue length (not size corrected) and the proportion of tongue that is bristled were both positively correlated to degree of nectarivory, while tongue length (relative to bill length), tongue depth (relative to bill depth) and tongue width (relative to bill width) were not correlated to nectarivory. Finally, we found no correlation between hyoid length (relative to bill length) and nectarivory, suggesting that the capacity for further tongue protrusion is unrelated to nectar dependence in honeyeaters. Similar studies should be conducted across other groups of avian nectarivores to expand our understanding of dietary ecomorphology beyond bill shape, which has been the focus of the majority of research on food handling adaptations in birds thus far.To identify the assessments, diagnostic criteria and outcome measures reported in peer-reviewed literature for children with growing pains and persistent lower limb pain in the presence of restless leg syndrome (RLS).
Scoping review completed in line with Joanna Briggs Institute methodological guidance
Five online databases were searched—MEDLINE, Embase, CINAHL, PsycINFO and AMED—for records up to 14 October 2024.
Records reporting on the use of assessments, diagnostic criteria or outcome measures in children (aged 0–18 years) with growing pains or persistent lower limb pain in the presence of RLS. Articles were required to have a sample size of ≥10 and be available in English language.
Data were extracted by two independent reviewers and analysed using descriptive statistics.
Following review of 19 806 records, 61 unique records were included. Most were observational cross-sectional or case–control designs. Assessments were varied and primarily focused on body functions and pain characteristics rather than activities and participation. There were 15 unique diagnostic criteria reported for growing pains with limited consistency and sometimes conflict between included items. Outcomes measures were only reported in eight records and typically measured pain presence and intensity.
Assessment and subsequent diagnosis of growing pains and persistent pain in the presence of RLS lack consistency. Outcome measures were seldom used as most records were not designed to measure change over time. Standardised practices for assessment and management of these conditions may benefit clinicians and optimise patient care.
Limited literature has focused on people with cancers' preference for care providers in scenarios where trade-offs may have to be made.
To report the results of a comprehensive search and synthesis of discrete choice experiments or best-worst scaling studies (± willingness to pay estimates) in scenarios involving cancer nurses, with a focus on: (1) preferred care provider; and (2) relative importance of attributes of care provision for people with cancer.
A search was conducted across: CINAHL, Cochrane Central Register of Controlled Trials, EconLit, Medline, PsycINFO, Scopus, Web of Science Core Collection, and Google Scholar for discrete choice experiments published between January and July 2025. Data were extracted and appraised by two authors. Results were narratively synthesised.
Of 461 studies screened, 11 were included, published in Australia (n = 3), UK (n = 3), and China (n = 5) including people with breast (n = 4), gastric (n = 4), prostate (n = 1), or mixed cancers (n = 2). In six studies exploring scenarios of follow-up care (i.e., survivorship/surveillance), cancer medical specialists were the preferred care provider, followed by cancer nurses, and then general practitioners. In four of the five studies of supportive care scenarios (i.e., diet and exercise advice, anxiety and depression screening), cancer nurses were the preferred care provider, followed by allied health professionals, then cancer medical specialists. The highest WTP estimate was $US226.15 for a medical specialist to provide follow-up care. For supportive care, the highest WTP was $US137.52 for a cancer nurse to provide diet-based lifestyle advice post-treatment for breast cancer.
Cancer nurses are highly valued by people with cancer, particularly for supportive care provision. Opportunities exist for an increase in cancer nurse specialists with expanded scope of practice, to support the preference of people with cancer to have cancer medical specialists, or cancer nurse specialists provide expert cancer follow-up care.
Employees of a cancer patient advocacy group were involved in the design of the study, interpretation of the data, and the preparation of the manuscript. No patients were involved in this work. However, this systematic review prioritized patient voices by including studies that reported on the preferences of people with cancer.
To develop an updated core dataset for acute stroke care in Ireland, informed by international audit benchmarking and national stakeholder consensus, for integration into the Irish National Audit of Stroke (INAS).
Scoping review and three-round Delphi process.
Medline Ovid, Embase, CINAHL EBSCOhost, Google Scholar, audit websites and grey literature (2010–2024). Additional audit documentation was obtained via direct author contact.
National stroke audits or registries with a country-wide scope, ≥1 year of continuous data collection and active in 2021 were eligible. Only audits covering acute stroke care were included in this study phase. All records were screened for inclusion.
Audit documentation (data dictionaries, item definitions and contextual metadata) was retrieved from eligible audits. Acute stroke care items were extracted, charted and benchmarked against existing INAS items and each other to identify commonalities and gaps. Frequently collected international items (appearing in ≥4 audits/registries) were shortlisted. A three-round Delphi process with 24 national stakeholders (clinicians, nurses, allied health professionals, researchers, policymakers and patient representatives) was conducted to audit and refine the dataset through structured, anonymised item rating, iterative feedback and consensus-building discussions.
Twenty-one eligible international stroke audits/registries were identified, yielding ~4500 audit items. Benchmarking against existing INAS items (n=103), frequently collected international items (n=97) and expert-suggested items (n=22) informed the Delphi consultation. The final dataset expanded INAS by 18 items, totalling 86 acute care and 35 thrombectomy-specific items. New additions included stroke-related complications and risk factor documentation.
This structured, consensus-led process resulted in an internationally benchmarked, stakeholder-informed core dataset to enhance standardised stroke auditing in Ireland. The expanded dataset supports enhanced clinical monitoring, quality improvement and health system planning. This approach may inform audit development and research efforts in other contexts.
This study examined cultural, contextual and psychological risk and protective factors for suicide risk (i.e., suicide ideation, planning and attempting in the past year) in a cross-sectional sample of nursing students in the United States.
A cross-sectional study design was employed.
Nursing students (n = 9871) were selected from the national 2020–2021 Healthy Minds Study (HMS). Students reported their demographics, suicidality and non-suicidal self-injurious behaviour (NSSIB). They also completed validated self-report measures of depression, belonging and flourishing.
Logistic regressions revealed that racial minority nursing students were at risk for suicidal ideation and attempts, and sexual minority students were at risk for suicidal ideation. Nursing students with a history of mental illness severe enough to seek treatment and those who reported more NSSIB also evidenced greater odds of reporting all forms of suicide risk. Specifically, the odds of suicidal ideation and attempts were more than three times greater for nursing students who reported NSSIB. Additionally, positive elements of flourishing only marginally protected against suicidal ideation, and belonging was not associated with any form of suicide risk.
Findings highlight the high number of nursing students at risk for suicidality and highlight potential demographic and psychological targets for suicide interventions. Impact: Early intervention during nursing school could impact suicide risk throughout a nurse's educational and professional journey. Thus, nurse educators should consider implementing suicide and mental health interventions in their programmes.
No direct patient or public contribution.
by Emmanuel Timmy Donkoh, Iddrisu Wahab Abdul, Abraham Kwadzo Ahiakpa, Isaac Williams, Rita Nyaaba Akologo, Stephen Danyo, Chrysantus Kubio, Kofi Effah, Joseph Emmanuel Amuah
BackgroundCervical cancer, though preventable, remains the second most diagnosed cancer and the primary cause of cancer-related deaths among females in Sub-Saharan Africa. The significance of coordinated screening programmes for reducing the burden of cervical cancer in Africa is not well documented. This systematic review will summarize published reports from key databases, grey literature and programme reports to assess the performance of cervical cancer prevention programmes in Ghana.
MethodsTo be eligible for inclusion, interventions must target Ghanaian women with cervical cancer screening and prevention strategies using methods such as visual inspection with acetic acid (VIA), mobile colposcopy, HPV DNA testing, cytology (Pap smear), and treatment approaches such as cryotherapy, thermal ablation, loop electrosurgical excision procedure (LEEP). A comprehensive electronic search strategy will be used to identify studies published since database inception, and indexed in MEDLINE, EMBASE, CINAHL and Web of Science. The search strategy will include MeSH terms (and synonyms) relevant to cervical cancer, screening/treatment methods, geographic focus and implementing institution. We will include searches for grey literature, recognizing the value of programmatic and governmental reports that might not appear in traditional databases. Search results will be summarized in line with PRISMA guidelines. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach will be used to evaluate and document evidence certainty for all outcomes, internal validity of included reports, inconsistency, indirectness, imprecision, and publication bias. Where sufficient homogeneity exists among included studies in terms of interventions, study designs, populations, and outcome measures, we will perform a meta-analysis to calculate pooled effect estimates and their corresponding 95% confidence intervals.
SignificanceThis systematic review will assess the performance and impact of cervical cancer screening and prevention programmes conducted in Ghana to date and identify what contextual strategies have delivered the most impact as well as highlight what gaps remain in our understanding of how a nationwide screening programme can be properly construed for maximum impact.
by Seung-Schik Yoo, Anvita Reddy, William Carroll, Kanyapat Ploypradith
Pharmacological removal of amyloid beta protofibrils has emerged as a promising therapeutic strategy to delay the onset of Alzheimer’s disease (AD) symptoms. As a non-pharmacological and noninvasive alternative, transcranial application of low-intensity ultrasound through intact skull can induce convective acoustic streaming, which has been shown to enhance cerebrospinal fluid solute transport and facilitate the clearance of interstitial solutes. This has led to the development of device-based approaches aimed at removing the precursors of amyloid beta (Aβ) plaques and mitigating cognitive decline in AD. We applied non-thermal, non-cavitational ultrasound (400 kHz frequency) in a pulsed mode (75 ms pulse duration, 2 Hz repetition rate) to the hippocampal region of male 5xFAD mice for 30 minutes weekly, starting at 10 weeks of age and continuing for 15 weeks (until 6 months of age). Spatial and recognition memory performance was assessed monthly using the Y-maze spontaneous alternation (SA) and novel object recognition (NOR) tests. A control group of age-matched mice underwent the same procedures with receiving zero acoustic output. Mice subjected to transcranial ultrasound (tUS) treatment maintained both SA and NOR performance throughout the entire experimental period, whereas mice that received sham tUS exhibited a progressive decline in memory beginning at 3–4 months of age. Congo Red staining of the brain sections revealed a significant (> 40%) reduction in Aβ plaques in the sonicated group. Histological analysis confirmed that repeated ultrasound exposure did not cause any detectable tissue damage. These findings suggest that low intensity tUS may serve as a novel, noninvasive therapeutic strategy to delay the onset of AD symptoms through the reduction of Aβ burden.by Claire Verkuyl, Ari Belotserkovsky, Thomas Zerbes, Declan Williams, Medha R. Krishnan, Sabrina Zhu, Sophie Grunnesjӧ, Shehab Eid, Cunjie Zhang, Wenda Zhao, Leo Xu, Eleanore Lin, Teaghan O’Shea, Benjamin Draper, Andreas Jungman, Patrick Most, Gerold Schmitt-Ulms
Any strategy that can selectively and persistently lower the brain levels of the cellular prion protein (PrPC) is expected to extend survival in prion diseases. Recent advances in the virus-mediated delivery of gene therapies prompted us to explore if a recombinant adeno-associated virus (rAAV) vector delivering a CRISPR-Cas-based gene editor can be devised that induces a functional knockout of the prion gene. Whereas the eventual objective is to assess the therapeutic potency of an optimized vector in prion-infected mice, in this proof-of-concept study, we evaluated tools and methods that are suited to achieve this goal. The result of these efforts is a first-generation all-in-one rAAV vector that codes for a prion gene-specific guide RNA and a small Cas9 endonuclease, whose expression is controlled by a truncated neural cell adhesion molecule 1 (NCAM1) promoter that is active in PrPC expressing cells. We also constructed a second rAAV vector coding for a prion gene-specific ‘traffic light reporter’ (TLR). The TLR can be used to monitor prion gene-editing efficacy by coding for red and green fluorescent proteins separated by a segment of the prion gene that is targeted by the gene editor. For the purification of AAVs, we adopted a robust and scalable rAAV vector assembly pipeline and undertook proof-of-concept prion gene editing experiments in human cells and mice, which to date yielded prion gene editing rates of approximately 20% and 5%, respectively. Finally, we compared brain distributions of rAAV vectors following intrathalamic versus retro-orbital injection, and selected the 9P31 capsid for future studies based on a 7.5-fold higher heterologous gene expression level as compared to the PHP.eB capsid.To compare costs and health consequences and to assess the cost-effectiveness of using low-dose oral long-acting morphine in people with chronic breathlessness.
Within-trial planned cost-consequences and cost-effectiveness analysis of data from a multisite, parallel-group, double-blind, randomised, placebo-controlled trial of low-dose, long-acting morphine.
11 hospital outpatients across the UK.
Consenting adults with chronic breathlessness due to long-term cardiorespiratory conditions.
5–10 mg two times a day oral long-acting morphine with a blinded laxative for 56 days.
Mean and SD of healthcare resource use (HRU) by trial arm; mean differences and 95% CI of costs between trial arms.
Mean differences in 28- and 56-day quality-adjusted life years (QALYs based on EuroQol five-dimension five-level score), Short Form-six dimensional scores and ICEpop CAPability-Supportive Care Measure scores; cost-utility of long-acting morphine for chronic breathlessness.
143 participants (75 morphine and 67 placebo) were randomised; 140 (90% power, males 66%, mean age 70.5 (SD 9.4)) formed the modified intention-to-treat population (participants receiving at least one dose of study medication). There were more inpatient and fewer outpatient services used by the morphine group versus the placebo. In the base-case analysis at 56 days, long-acting morphine was associated with similar mean per-patient costs and QALYs. There was an increase of £24 (95% CI –£395 to £552) and 0.002 (95% CI –0.004 to 0.008) QALYs. Hospitalisations were the main driver of cost differences. The corresponding incremental cost-effectiveness ratio was £12 000/QALY, with a probability of cost-effectiveness of 54% at a £20 000 willingness-to-pay threshold. In the scenario analysis that excluded costs of adverse events considered unrelated to long-acting morphine by site investigators and researchers, the probability of cost-effectiveness increased to 73%.
Oral morphine for chronic breathlessness is likely to be a cost-effective intervention provided adverse events are minimised, but the effect on outcome is small and cautious interpretation is warranted.
Intraoperative anaesthesia handoffs represent a risk point in the care of surgical patients. Although often necessary to prevent fatigue, improve vigilance and optimise operational efficiency, critical information can be lost, potentially leading to postoperative complications. Structured handoffs can increase the transfer of knowledge during intraoperative anaesthesia handoffs, improving their quality. We therefore propose to test the primary hypothesis that a semi-structured intraoperative anaesthesia handoff cognitive aid reduces the number of serious 30-day complications in surgical patients.
We will enrol adults having non-cardiac surgery who are scheduled to have an intraoperative anaesthesia handoff for operational reasons. We plan a cluster randomised trial (enrolling over 18 months, anticipated sample size approximately 4500 patients) that will compare the Epic Electronic Health Record intraoperative anaesthesia handoff cognitive aid to routine handoffs. Our primary outcome will be the number of serious postoperative complications within 30 days. Our secondary outcomes will be: (1) the number of minor complications; and (2) the duration of postoperative hospitalisation. Bayesian analysis with generalised linear multilevel modelling will be used to estimate the effect of structured handoffs on the primary and secondary outcomes.
This study has been approved by the local institutional review board with a waiver of informed consent. Results will be disseminated in the medical literature with de-identified data available on request.
by Kazuya Takahashi, Michalina Lubiatowska, Huma Shehwana, James K. Ruffle, John A. Williams, Animesh Acharjee, Shuji Terai, Georgios V. Gkoutos, Humayoon Satti, Qasim Aziz
BackgroundThe exact mechanisms underlying paediatric abdominal pain (AP) remain unclear due to patient heterogeneity. This preliminary study aimed to identify AP phenotypes and develop predictive models to explore associated factors, with the goal of guiding future research.
MethodsIn 13,790 children from a large birth cohort, data on paediatric and maternal demographics and comorbidities were extracted from general practitioner records. Machine learning (ML) clustering was used to identify distinct AP phenotypes, and an ML-based predictive model was developed using demographics and clinical features.
Results1,274 children experienced AP (9.2%) (average age: 8.4 ± 1.1 years, male/female: 615/659), who clustered into three distinct phenotypes: Phenotype 1 with an allergic predisposition (n = 137), Phenotype 2 with maternal comorbidities (n = 676), and Phenotype 3 with minimal other comorbidities (n = 340). As the number of allergic diseases or maternal comorbidities increased, so did the frequency of AP, with 17.6% of children with ≥ 3 allergic diseases and 25.6% of children with ≥ 3 maternal comorbidities. The predictive model demonstrated moderate performance in predicting paediatric AP (AUC 0.67), showing that a child’s ethnicity, paediatric allergic diseases, and maternal comorbidities were key predictive factors. When stratified by ML-predicted probability, observed AP rates were 18.9% in the 60% group.
ConclusionsThis study identified distinct AP phenotypes and key risk factors using ML. Furthermore, the predictive ML model enabled risk stratification for paediatric AP. These analyses provide valuable insights to guide future investigations into the mechanisms of AP and may facilitate research aimed at identifying targeted interventions to improve patient outcomes.
by Brandon Hergert, Kristin M. Whitworth, Devorah C. Goldman, Lisa Moreau, Kelsey McQueen, Kalindi Parmar, Alan D’Andrea, Melissa S. Samuel, Kevin D. Wells, Randall S. Prather, Craig Dorell, Markus Grompe, William H. Fleming
Although small animal models of Fanconi anemia (FA) are useful, they do not faithfully replicate many of the clinical features seen in FA patients. We reasoned that a porcine model of FA with its similar physiology and a relatively long lifespan would produce a phenotype more similar to human FA. Targeting FANCA in domestic swine resulted in skeletal abnormalities and extreme sensitivity to interstrand DNA cross-linking agents. In addition, FANCA disruption followed by mitomycin C treatment resulted in a > 10-fold increase in chromosomal radials, a finding that is considered diagnostic for human FA. Bone marrow derived, hematopoietic progenitor cells from a FANCA null pig showed a 75% reduction in colony forming activity compared to wild type. Evaluation of steady state hematopoiesis in the peripheral blood revealed the gradual development of red cell macrocytosis and a reduction in circulating neutrophils. Targeting of FANCD2 failed to produce any biallelic animals demonstrating the loss of FANCD2 function is embryonic lethal in pigs. These results indicate that a porcine model of FANCA holds promise for the development of strategies to prevent the development of bone marrow failure and malignancies in patients with FA.Cellulitis is a common bacterial skin infection causing significant pain, swelling and impact on daily activities, frequently leading to emergency department presentations and hospital admissions. While antibiotics are the mainstay of treatment, they do not directly address inflammation, often resulting in persisting or worsening symptoms in the initial days. Corticosteroids, with their potent anti-inflammatory effects, have shown benefit in other acute infections but are not currently standard care for patients with cellulitis. This trial aims to determine if adjunctive oral dexamethasone can reduce pain and improve outcomes in adults with cellulitis presenting to UK urgent secondary care settings.
This is a pragmatic, multicentre, double-blind, placebo-controlled, randomised, parallel group, phase 3 superiority trial, with an internal pilot and parallel health economic evaluation. Adult patients (≥16 years) with a clinical diagnosis of cellulitis (at any body site except the orbit) presenting to urgent secondary care will be screened for eligibility. 450 participants will be randomised (1:1) to receive either two 8 mg doses of oral dexamethasone or matched placebo, administered approximately 24 hours apart, in addition to standard antibiotic therapy. The primary outcome is total pain experienced over the first 3 days postrandomisation, calculated using the standardised area under the curve from pain scores (Numerical Rating Scale 0–10) across up to seven timepoints. Secondary outcomes include health-related quality of life (EuroQol 5 Dimension 5 Level), patient global impression of improvement, analgesia and antibiotic usage, hospital (re)admissions, complications, unscheduled healthcare use, cellulitis recurrence and cost-effectiveness at 90 days. The primary estimand will apply a treatment policy approach to intercurrent events.
The trial has received ethical approval from South Central—Oxford B Research Ethics Committee (reference: 24/SC/0289) and will be conducted in compliance with Good Clinical Practice and applicable regulations. Informed consent will be obtained from all participants. A model consent form can be seen in . Findings will be disseminated through peer-reviewed publications and conference presentations, and to patient groups and relevant clinical guideline committees.
Persistent pain is common among older people living with frailty and can impact on their daily living, mobility, social interactions and sleep. However, healthcare support to mitigate impact is lacking in this population. The Pain in Older People with Frailty (POPPY) study is a multiphase, mixed-methods study that addresses how pain management services for older people with frailty should be organised and delivered.
For this phase (POPPY-Q), we used qualitative methods: semi-structured interviews with a grounded theory approach to analysis.
Community-dwelling older people (≥75 years) with persistent pain and frailty were invited to participate in two qualitative interviews (in-person/remotely) 10 weeks apart. Interviews took place in varied geographical locations across England between July 2022 and August 2023 and explored experiences of living with pain and access to and engagement with services and healthcare professionals (HCPs) and support and treatments received for pain.
Twenty-six people (77–91 years) with pain and frailty (from mild to severe) consented and were interviewed; 24 completed a second interview. Three interviews included a spouse/family member. Themes were general health and well-being; pain and its impact; acceptance of living with pain; support-seeking decisions; experience of accessing support; and perception/experience of pain support and treatment. This paper focuses on pain acceptance and support-seeking; other themes are used contextually, and accessing support was rare. Many participants were stoical about pain; some prioritised other health conditions; some preferred self-management; some were resigned and had lost hope of effective treatment; some expressed concern about burdening healthcare resources.
HCPs should be aware of the stances of older people with frailty about seeking support for pain and should be proactive, asking about pain. Longer appointments for complex cases may allow general practitioners to address pain, offer reassurance, provide information or referral or arrange a follow-up consultation focused on pain management.
Cystic fibrosis (CF) is an inherited condition, affecting approximately 150 000 people worldwide. Physical activity (PA) is an integral component in the management of CF. However, it is estimated that only a third of young people (with and without CF) achieve UK Chief Medical Officer guideline recommended levels of activity. The aim of this research was to use the person-based approach to develop an intervention supporting families with young people (aged 6–12 years) with CF to incorporate PA as a sustainable habit in their lives to increase the likelihood of sustained PA levels going into adolescence and adulthood.
Using the person-based approach, intervention content was created and iteratively adapted. This was initially guided by relevant literature; the guiding principles, logic model and preliminary content were developed via co-production with patient and public involvement (PPI) representatives (n=8) with lived experience of CF. The intervention was further refined/optimised using qualitative think-aloud and retrospective interviews, the results of the preliminary evaluation are reported. Think-aloud interviews were rapidly analysed using a table of changes analysis and used to inform adaptations to content. Retrospective interviews were analysed thematically.
Community settings in the UK.
Participants included six families with a child with CF aged between 6 years and 12 years old.
Intervention content consisted of nine sections and was delivered as a printable PDF file. Informed by the Capability, Opportunity, Motivation and Behaviour framework and self-determination theory, content focused on promotion of PA as a family activity that is fun, enjoyable, quick and achievable. It promoted ‘movement to make you feel good"’ and in short bursts of activity. Promotion of PA as medicine was avoided. The final intervention was considered to be engaging and acceptable.
Qualitative methods and PPI facilitated the development of a family-focused intervention supporting the integration of PA into daily life. This was viewed as acceptable and engaging among families of people with CF. Future research now needs to explore the effectiveness of the intervention for increasing PA behaviour.
FreshRSS 