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Development of a resource use measure to capture costs related to unpaid care for people living with non-memory led dementia: a modified Delphi study

Por: Cullen · K. · Brotherhood · E. V. · Hayes · O. · Mansfield · V. · Suarez-Gonzalez · A. · Zimmermann · N. · Stott · J. · Fitzsimmons · D.
Objectives

To determine the personal, National Health Service and wider societal resource use in relation to caring responsibilities for carers of people living with non-memory led dementias (NMLDs); and to design a resource use measure (RUM) that can be delivered in the Better Living with Non-memory-led Dementia (BELIDE) randomised controlled trial, part of the Rare Dementia (RD) - TALK research programme.

Design

The first stage was to identify and review any existing RUMs that could be used or adapted to the trial population and setting. If no measures were identified, the second stage was initial informal discussions with healthcare professionals (HCPs) and the programme patient and public involvement representatives to inform the perspective, settings of care and main resource items to develop a new RUM. In the third stage, a first draft of the RUM was tested for content and face validity in a modified Delphi study comprising HCPs and carers. The measure was revised and, in the final stage, piloted in the first 3 months of the BELIDE trial to assess acceptability and feasibility of collecting the economic outcomes and the completeness of data collection. The key drivers of resource use and costs were assessed, and appropriate face validity checks were applied to ensure accurate description of the treatment pathways.

Participants and setting

Carers and family of people living with NMLD recruited from Rare Dementia Support members in the UK, and a broad range of HCPs with experience of working with people who have NMLD to capture the different dimensions of experience, grade and skill mix.

Results

In total, 20 people participated in the modified Delphi study, 11 HCPs and 9 carers. Rare Dementia Support groups and 1:1 calls were highly rated, as were general practitioner appointments. The greatest consensus was in the productivity and carer tasks; all caring tasks were highly rated. Healthcare practitioners rated healthcare items as higher importance than carers themselves.

Conclusions

Unpaid carers and HCPs are the experts in the resource impact of caring for someone with NMLD and have been underserved in research to date. This research, as part of preparatory stages of the BELIDE trial, has enabled the timely development of a comprehensive and valid RUM for unpaid carers of people with NMLD.

PROSPERO registration number

CRD42022356943.

Trial registration number

NCT06241287.

Start4All protocol for a Bayesian cost-effectiveness model of tuberculosis screening and diagnosis in seven high burden low-income and middle-income countries

Introduction

High costs of screening and diagnostic tests remain a major barrier to timely tuberculosis (TB) identification in resource-limited settings. Evidence on the cost-effectiveness of scalable screening algorithms is limited. Start4All is a research project aimed at developing and evaluating algorithmic approaches to TB screening and diagnosis, with the goal of optimising technical and allocative efficiency when expanding diagnostic coverage to primary healthcare and community settings.

Methods and analysis

Five screening and diagnostic tests will be evaluated: a capillary blood-based assay (C-reactive protein (CRP)), sputum-based rapid molecular tests (PCR; individual and pooled Xpert MTB/RIF Ultra assay (Xpert Ultra, Cepheid®, California, USA)), a lateral-flow urine-based test for lipoarabinomannan (LF-LAM), and digital chest X-rays with artificial intelligence-based computer-aided detection (CXR-CAD). A microbiological reference standard of positive culture using the mycobacteria growth indicator tube will be used to confirm TB disease.

We will compare the cost and effectiveness of concurrent and sequential positive serial combinations (screening algorithms) of CRP, CXR-CAD, LF-LAM, individual and pooled Xpert Ultra. Diagnostic performance will be estimated using sensitivity, specificity, predictive values and proportions of positive results, with Bayesian inference used to derive these estimates. The analysis will include adults (15 years and older) only and will be stratified by HIV status and level of care, including facility and community-based case finding. Effectiveness will be assessed based on the number of people with TB detected. Cost analysis will be conducted from the provider perspective, incorporating commodity and implementation costs. A decision tree model will be developed to assess the cost per number of persons with confirmed TB detected across all countries. Probabilistic sensitivity analysis will be conducted to account for uncertainty in model parameters, incorporating willingness-to-pay and willingness-to-accept thresholds.

Ethics and dissemination

WHO ethical review committee approval ERC.0003921. Data will be available on reasonable request to the principal investigator of the consortium.

Trial registration number

NCT05845112.

Social determinants of health and risk of lower extremity amputation in patients with peripheral artery disease in Canada: protocol for a systematic review and meta-analysis

Por: Chowdhury · A. · Sheikh · F. · Azab · S. M. · de Souza · R. J. · Banfield · L. · Balakrishnan · N. · Anand · S. S.
Introduction

Peripheral artery disease (PAD) affected approximately 800 000 Canadians aged 25 years or older in 2015 and it poses a substantial risk of lower extremity amputation (LEA). While clinical risk factors for amputation are well-established, the impact of social determinants of health (SDoH) on amputation risk remains unclear, particularly in a Canadian context.

Objectives

This systematic review aims to: (1) synthesise evidence on the associations between multilevel SDoH domains and LEA (both major and/or minor) risk in Canadian PAD patients including intersectional effects of race and ethnicity with another SDoH domain, and (2) evaluate the statistical methodologies used in the researched literature to inform future study design and analysis approaches.

Methods and analysis

We will systematically search MEDLINE, Embase, EmCare, Global Health, Cumulative Index to Nursing and Allied Health Literature and Web of Science for studies examining SDoH and LEA in Canadian patients with PAD (including chronic limb-threatening ischaemia which is a severe form of PAD). Date limits for each database will be from inception through December 2025. SDoH will be categorised using a modified Healthy People 2030 SDoH framework under six domains: economic stability, education, food, neighbourhood and physical environment, healthcare system and community and social context. Two reviewers will independently screen titles, abstracts and full texts, with discrepancies resolved by a third reviewer. Data will be extracted on study characteristics, SDoH measures, outcomes and statistical methods. Risk of bias will be assessed using RoB 2 for randomised trials, ROBINS-I for non-randomised studies of interventions and ROBINS-E for studies investigating exposures. A narrative synthesis, and where data permit, a Bayesian hierarchical meta-analysis using both effect size and contingency table approaches will be conducted. Statistical heterogeneity will be explored through subgroup analyses and meta-regression, examining study design, SDoH measurement approaches and population characteristics.

Ethics and dissemination

As a systematic review and meta-analysis, ethics approval is not required. For institutional oversight, we provide the contact of Dr Sonia Anand (Associate Vice-President, Global Health, McMaster University; anands@mcmaster.ca). Results will be reported following PRISMA guidelines and disseminated through a peer-reviewed publication.

PROSPERO registration number

CRD420251115759.

Are equity, diversity and inclusion considered in early-phase studies evaluating innovative and developing surgical procedures? Protocol for a scoping review

Por: Etemadi · M. · Macefield · R. · Avery · K. · Elliott · D. · Dawson · S. · Blencowe · N. S. · Coyle · M. · Richards · H. S. · Graham · B. · Jones · E. · Torkington · A. · Chatfield · K. · Malik · H. · Garlick · M. · Blazeby · J.
Introduction

Increased risks and concerns regarding patient safety in early-phase studies exist because knowledge about the new intervention is still accumulating. This means that narrow eligibility criteria are needed. However, if early-phase studies are narrow in their inclusion, for example, by not including diverse populations, there is a potential risk that new therapies have insufficient relevant efficacy and safety data. Existing research has explored equity, diversity and inclusion (EDI) factors in early-phase pharmaceutical studies, but it has not been possible to find studies that have systematically examined whether EDI factors have been considered in surgical studies reporting innovative procedures. We aim to examine how EDI factors are considered in early-phase surgical studies and surgical innovation reports to explore how this may impact on later-phase evaluation and inclusive intervention implementation.

Methods and analysis

A scoping review following the JBI (Joanna Briggs Institute) and Arksey and O’Malley’s five-step process is being conducted. We will search Scopus, PubMed and Web of Science for surgical early-phase studies. A two-step screening process for eligibility is being used. Independent double screening will take place for 20% of the papers. Eligible articles will report early evaluation of an innovative surgical/invasive procedure. Excluded will be comparative and later-phase studies and early evaluations of pharmaceutical products even in a surgical setting. Data on article details, patient eligibility and whether protected characteristics are reported and considered will be extracted. Information about EDI considerations reported in the introduction or discussion of the papers will also be extracted. Findings will be discussed with a patient advisory group. A content synthesis approach will be undertaken and descriptive summaries presented.

Ethics and dissemination

This study does not require ethical approval being a secondary analysis. The findings will be disseminated through academic journal publications and oral presentations.

Adult survivors of sickle cell disease, transfusion-dependent beta-thalassaemia and childhood acute leukaemia in England: protocol for a mixed methods data linkage and health-related quality of life survey study

Por: Ahmed · K. · Holloway · I. · Absolom · K. · Mason · S. J. · Mujica-Mota · R. · Gkountouras · G. · Martin · A. · Flannery · T. · Richards · M. · Astwood · E. · Ackroyd · S. · Greystoke · B. · Greenfield · D. M. · Hill · Q. · James · B. · Kwok- Williams · M. · Murray · R. D. · Samuelson · C
Introduction

Recent advances in treatment and care have improved survival rates for children and young adults with severe blood disorders such as sickle cell disease (SCD), transfusion-dependent beta-thalassaemia (TDT) and acute leukaemia. However, their quality of life and reproductive and psychosocial outcomes are not yet well studied. For SCD and TDT, robust survival data are mainly limited to North America. Thus, there is a need to fill these knowledge gaps to guide improvements in care, address unmet clinical needs and rigorously assess the efficacy of emerging novel therapies.

Methods and analysis

This is an observational population-based mixed-methods study of individuals diagnosed with SCD, TDT or acute leukaemia when under the age of 18 in England, involving a data linkage component and a patient-reported outcomes measures survey. Data linkage-eligible participants will be identified from national and regional databases, including the Hospital Episode Statistics, Yorkshire Specialist Register of Cancer in Children & Young People and the National Congenital Anomaly and Rare Diseases Registration Service. Data linkage will be processed within the NHS England and the University of Leeds’ secure, trusted research environments. Data will be accessed without consent under section 251 and approval by the confidentiality advisory group. It will assess survival rates for SCD and TDT as well as clinical, educational and mental health outcomes for SCD, TDT and acute leukaemia diagnosed in childhood.

Survey-eligible participants for SCD, TDT and acute leukaemia cohorts will be checked for their suitability to participate by the North of England clinical care teams. An NHS-approved survey provider will facilitate data checks with the NHS National Data Opt-Out Service. Consent is required for participation in the survey and for subsequent data linkage to existing databases. Surveys are conducted in various formats (online, paper and phone), with reminders sent after 21 days. The survey will assess quality of life and psychosocial and reproductive outcomes. Participants can withdraw at any time, and support is available via telephone helplines.

Ethics and dissemination

The study has received ethical and information governance approval from the Health Research Authority (Reference 24/YH/0186) and the Confidentiality Advisory Group (CAG 24/CAG/0138) to process identifiable data without consent. Study results will be available to patients, physicians, researchers, stakeholders and others through open-access publishing, results sharing via media platforms and presentations at conferences and meetings.

Pathogenic bacterial species and the microbiome of cat fleas (<i>Ctenocephalides felis</i>) inhabiting flea-infested homes

by Taylor E. Gin, Charlotte O. Moore, Trey Tomlinson, Grace Wilson, Amiah Gray, Cameron Sutherland, Kamilyah Miller, Krista Li, Michael Canfield, Brian Herrin, Erin Lashnits, Benjamin Callahan

Background

Ctenocephalides felis is a common ectoparasite of dogs and cats and can transmit a variety of pathogens including Bartonella and Rickettsia species. These bacteria, along with the known endosymbiont Wolbachia, are well-documented members of the C. felis microbiome, but species-level information is limited. Additionally, little is known about the variation in the C. felis microbiome in fleas from different sources and when different sequencing methods are applied to the same samples.

Objective

This study aimed to characterize the flea microbiome using both short-read (V3/V4) and long-read (full-length) 16S rRNA gene sequencing, determine whether long-read sequencing improves species-level identification especially in known pathogenic genera, and evaluate differences in microbial composition between fleas collected from cats, dogs, and environmental traps.

Methods

Fleas were collected from cats, dogs, and traps in flea-infested homes in Florida, pooled by source, and sequenced using short- (V3/V4) and long-read (full-length) 16S rRNA gene sequencing. Microbial prevalence and abundance were compared across sequencing approaches. Community composition was evaluated for differences between sources and houses. Candidate members of the flea microbiome were identified based on a combination of prevalence, abundance, and statistical signatures of potential contaminant origin. For Rickettsia and Bartonella, species-level taxonomic assignments were refined using a phylogenetic approach.

Results

Wolbachia, Rickettsia, and Bartonella were the most prevalent and abundant taxa. Spiroplasma was identified as a fourth core member of the flea microbiome. Long-read sequencing enabled better, but not perfect, species-level classification of Bartonella and Rickettsia compared to short-read sequencing. Important relationships between specific ASVs and flea sources were identified, for example fleas from cats harbored higher abundances of B. clarridgeiae and B. henselae than fleas from traps.

How Classmates Experience Visiting Their Hospitalised Peer During Cancer Treatment: A RESPECT Study

ABSTRACT

Aim

To explore how classmate ‘ambassadors’ experienced and engaged in social interaction while visiting a hospitalised peer undergoing cancer treatment.

Design

A phenomenological-hermeneutic inspired exploratory study.

Methods

Using on-the-go semi-structured interviews and participant observations from January to December 2023 in Denmark, we included 27 school-aged ambassadors aged 6–18 years old; 18 participated in pre- and post-visit interviews, while all 27 took part in observations during 19 visits. Van Manen's phenomenological-hermeneutic approach guided thematic analysis.

Results

Six themes emerged: (1) visiting the hospital, (2) being supportive, (3) aligning expectations, (4) being unsure, (5) safeguarding the relationship and (6) leaving the hospital. Ambassadors were eager to visit, seeking to be good friends by offering social, emotional and physical support. They were mindful of the information shared to prevent the hospitalised children from feeling excluded. Social interactions often involved allowing the hospitalised children to take on decision-making roles, recognising their well-being as a priority.

Conclusion

Ambassadors found hospital visits meaningful as they wanted to make a difference and sought to support their hospitalised peers. Their role was shaped by their understanding of friendship and the disease trajectory. Social interactions were largely conflict-free due to the pre-visit alignment of expectations.

Implications for Profession or Patient Care

Classmates found visits meaningful and wished to make a difference. Healthcare professionals should facilitate visits to strengthen social connections between the hospitalised child and their surroundings as a part of family-centred care within paediatric oncology.

Impact

Problem: Cancer treatment often causes social disruption for children with cancer, making the transition to everyday life more difficult post-treatment.

Main Findings

Classmates were eager to visit hospitalised peers, demonstrating awareness of cancer and a desire to support them.

Research Impact

Facilitating classmate visits may enhance classmates' understanding of cancer and aid hospitalised children's reintegration into everyday life.

Reporting Method

The COREQ checklist was used.

Patient or Public Contribution

Ambassadors contributed to designing the interview guides.

Global Clinical Contribution

Enhances knowledge of supporting social relationships between hospitalised children and their classmates during cancer treatment. However, the RESPECT study is rooted in the Danish cultural context, where it is common to attend local volunteer activities after school. Although getting diagnosed with a life-threatening illness such as cancer may be difficult to talk about with peers and even a taboo in some countries, we do expect that interventions with structured possibilities for social interactions are an important step towards normalisation of communicating about childhood cancer.

Research on Eating and Adolescent Lifestyle (REAL) 2.0: 15-year follow-up study of eating disorders and weight-related trajectories, mental health and substance use health from early adolescence to early adulthood--a Canadian cohort profile

Por: Obeid · N. · Buchholz · A. · Bradley · A. H. · Mistry · N. · Vaillancourt · T. · Colman · I. · Tasca · G. A. · Corace · K. · Maras · D. · Goldfield · G.
Purpose

Few studies have examined how psychosocial risk and protective factors in adolescence shape mental health outcomes and other multimorbid conditions in adulthood, particularly among Canadian youth. The Research on Eating and Adolescent Lifestyle (REAL) 2.0 study was a 15-year follow-up cohort study designed to investigate how early etiological factors, including body image and disordered eating symptoms in adolescence, contribute to the development of eating, weight-related concerns, mental health and substance use health problems in early adulthood. In this paper, we describe the REAL 2.0 cohort’s demographic and clinical characteristics alongside an overview of the study procedures, laying the groundwork for collaboration on future learnings with this unique data.

Participants

The cross-sectional REAL study initially surveyed middle and high school students from 2004 to 2010 (n=3043) across 43 schools in the Ottawa, Canada region. Of those, respondents in grade 7 or 9 (n=1197 from 25 of the 43 original schools) were asked to participate in a longitudinal arm of the study that consisted of yearly follow-ups. From the longitudinal cohort, there were 278 participants (29.1% male; Mage=28.6) from those who consented to be re-contacted (n=912), who completed the REAL 2.0 survey electronically (30.4%), providing comprehensive data on demographic, clinical, eating and weight-related behaviour, psychological, social, environmental and substance use health factors in adulthood.

Findings to date

9.4% of REAL 2.0 participants met DSM-5 criteria for an eating disorder, while 17.6% met criteria for disordered eating. Moderate to severe anxiety was reported by 28% of participants, while 21.6% experienced moderate to severe depressive symptoms. Regarding substance use, 16.9% engaged in hazardous drinking, 16.9% used cannabis daily or almost daily, and 4.3% reported daily tobacco use.

Future plans

REAL 2.0 has the potential to answer multiple research questions about several mental health outcomes, but its priority focus is to answer questions related to risk and protective factors of multimorbidity in adulthood. Additionally, profiling work, linked to health service utilisation data for systems planning work and predictive modelling studies are secondary goals. By leveraging the Health Data Nexus (HDN) platform, we welcome collaboration with interested researchers who would like to utilise the breadth of data both in adolescence and adulthood to answer other pertinent aetiological questions in mental health and substance use health outcomes. Future plans to conduct additional follow-ups remain feasible.

A Novel Murine Model for Studying Impaired Wound Healing in Diabetes

ABSTRACT

A lack of murine models that mimic impaired wound healing in people with type 2 diabetes has hindered research. The commonly used leptin-receptor knockout model (db/db) fails to accurately reflect the pathophysiology of human disease. This study aimed: (i) to investigate whether our novel murine model of diabetes, whilst less hyperglycaemic and obese than db/dbs, effectively demonstrated impaired wound healing, and (ii) to identify the most robust methods for quantifying wound closure. C57BL/6J mice were high-fat diet fed for a total of 11 weeks and injected with three doses of streptozotocin (65 mg/kg body weight) at week 5 with chow-fed mice as controls. All mice received four excisional wounds and were euthanised at day-4 or day-10 post-wounding (n = 8/group/timepoint). Wound healing was evaluated by digital planimetry, histology, Micro-CT, and tensiometry. Histological analysis was the most sensitive method for identifying impaired wound healing. Our high-fat diet/low-dose streptozotocin model had significantly higher non-fasting blood glucose (25.7 ± 5.4 mmol/L vs. 8.7 ± 0.8 mmol/L) and lower wound quality scores (day-4 post-wounding: 2.6 ± 1.9 vs. 4.4 ± 0.8) than healthy controls (both p < 0.05). At day-10 post-wounding, a linear trend in wound healing was observed between healthy controls, our novel model and the db/db model, indicating that our diabetic murine model may be clinically relevant for studying diabetes-related wound healing.

Evaluating the clinical care, quality of life and overall experiences of patients with primary biliary cholangitis (PBC) during the pandemic: A Canadian mixed-methods study

by Elizabeth Baguley, Madelyn Knaub, Jessica VanDyke, Gideon Hirschfield, Mark G. Swain, Gail Wright, Deirdre McCaughey, Abdel Aziz Shaheen

Pandemic restrictions impacted healthcare, particularly during the first year. We evaluated the impact of the pandemic on quality of life and clinical care among patients with primary biliary cholangitis (PBC). This mixed-methods study administered quality of life surveys (Fear of COVID-19 Scale [FCV-19S], EuroQol 5-dimension 3-level [EQ-5D-3L], 29-item Patient-Reported Outcomes Measurement Instrument Survey [PROMIS-29]) and a PBC Care Delivery questionnaire to 348 Canadian PBC patients, followed by two focus groups with patients (n = 14) and stakeholders (n = 3). Quality of life scores were compared among sub-groups (i.e., care delays and pandemic appointment type) and with various reference populations. Most participants were female (94.0%) and Caucasian (88.2%), with a median age of 63.0 years (IQR: 55.9–71.2). During the pandemic, 75.8% had the majority (≥ 50%) of their hepatologist appointments virtually, but only 22.4% preferred to continue with virtual care post-pandemic. Participants with care delays had worse scores on the FCV-19S (p = 0.014), EQ-5D-3L (p = 0.009), and PROMIS-29 (i.e., fatigue, anxiety, sleep disturbance, ability to participate in social roles and activities, p p 

Intelligent monitoring to predict atrial fibrillation (NOTE-AF): clinical study 1 for the 'Health virtual twins for the personalised management of stroke related to atrial fibrillation (TARGET) project - a protocol for a prospective cohort analysis

Por: Essa · H. · Johnston · B. · Lip · G. Y. H. · Ortega-Martorell · S. · Williams · K. · Welters · I. D. · TARGET Consortium · Ortega-Martorell · Olier · Mistry · Knowles · Bellfield · Aikodon · Lotto · Jones · Dawson · Thijssen · Maganaris · Baltzopoulos · McDowell · Smith · Ohlsson
Introduction

Atrial Fibrillation (AF) is the most common arrhythmia worldwide affecting an estimated 5% of people over the age of 65 and is a leading cause of stroke and heart failure. Identification of patients at risk allows preventative measures and treatment before these complications occur. Conventional risk prediction models are static, do not have flexibility to incorporate dynamic risk factors and possess only modest predictive value. Artificial intelligence and machine learning-powered health virtual twin technology offer transformative methods for risk prediction and guiding clinical decisions.

Methods and analysis

In this prospective observational study, 1200 patients will be recruited in two tertiary centres. Patients hospitalised with acute illnesses (sepsis, heart failure, respiratory failure, stroke or critical illness) and patients having undergone high-risk surgery (major vascular surgery, upper gastrointestinal surgery and emergency surgery) will be monitored with a patch-based remote wireless monitoring system for up to 14 days. Clinical and electrocardiographic data will be used for modelling the risk of new-onset AF. The primary outcome is episodes of AF >30 s and will be described as ratio of episodes/patient and as percentage of patients having episodes of AF. Secondary outcomes include 30-day and 90-day readmission rates and complications of AF.

The aim of this study is to generate data for the development and validation of health virtual twins predicting onset of AF in an at-risk population. The intelligent monitoring to predict atrial fibrillation (NOTE-AF) study is part of the TARGET project, a Horizon Europe funded programme which includes risk prediction, diagnosis and management of AF-related stroke (https://target-horizon.eu/).

Ethics and dissemination

The study has received approval by the Health Research Authority and the National Research Ethics Service (REC reference 24/NW/0170, IRAS project ID: 342528) in the UK and has been registered on clinicaltrials.gov (NCT06600620). Results will be disseminated as outlined in the TARGET protocol to communicate project ideas, activities and results to diverse audiences.

Trial registration number

NCT06600620.

Surgery versus conservative management for severe pectus excavatum (RESTORE): protocol for a multicentre, randomised, controlled superiority trial

Por: Maier · R. · Dunning · J. · Wason · J. · Chadwick · T. · Bryant · A. · Fernandez-Garcia · C. · Vale · L. · Danjoux · G. R. · Wallace · G. · Levett-Renton · A. · Naidu · B. · Pryor · C. · McCulloch · P. · Thursfield · R. · Wyllie · J. · Chang · L. · Marsay · L. · Akowuah · E.
Introduction

Severe pectus excavatum (PE) may impair cardiopulmonary and physical function. The effectiveness of surgical treatment to correct PE and restore physical function is widely debated due to a lack of high-quality comparative evidence. The RESTORE trial aims to determine the clinical and cost-effectiveness of corrective surgery for severe PE compared with conservative management for the first time in a randomised controlled trial (RCT).

Methods and analysis

RESTORE is a pragmatic, multicentre, RCT with an embedded observational cohort. 200 participants aged ≥12 years with severe PE will be recruited at around 12 National Health Service cardiothoracic surgical centres in England. Participants will be randomised 1:1 to receive either surgery within 3 months of randomisation (intervention arm) or no surgery until after the primary outcome measurement at 1 year (comparator arm). The primary outcome is change in physical functioning from baseline to 1 year as measured by the Short Form Health Survey (SF-36v2) physical function score. The primary economic outcome is cost-effectiveness. The key secondary outcome is change in % predicted VO2peak at 1 year measured by cardiopulmonary exercise test (CPET). Outcomes will be assessed at 1 year post-randomisation in the comparator arm and 1 year post-surgery in the intervention arm. The primary analyses will be undertaken on an intention-to-treat population using a linear mixed-effects model, adjusted for stratification variables via a binary covariate. Other secondary outcomes will include change from baseline of cardiopulmonary function (CPET and spirometry), health-related quality of life using the EuroQol 5 Dimension 5 Level (EQ-5D-5L) and SF-36v2 questionnaires, Hospital Anxiety and Depression Scale and disease specific symptoms (Phoenix Comprehensive Assessment for Pectus Excavatum Symptoms and Pectus Excavatum Evaluation Questionnaire). Adverse events, complications from surgery and operative technical success (Haller and Compression Indices from preoperative and postoperative CT scans) will also be assessed. Health economic analysis will estimate the incremental cost per quality adjusted life year at 1 year.

Ethics and dissemination

The trial was approved by East of Scotland Research and Ethics Service (24/ES/0034). Participants who are ≥16 years of age will be required to provide written informed consent. For participants

Trial registration number

ISRCTN11359779.

Health literacy scale for English-speaking children: translation and validation of the HLS-Child-Q15-EN

Por: Drake-Brockman · T. F. E. · Locke · V. · Hauser · N. · Sommerfield · D. · Evans · D. · Sommefield · A. · Khan · N. · von Ungern-Sternberg · B. S.
Objective

To translate and validate the HLS-Child-Q15, a relatively short questionnaire for assessing health literacy in children originally validated in German, into English to make it accessible to a large population of English-speaking children.

Design

We translated the HLS-Child-Q15 into English following established methods, including forward and backward translation, using multiple translators. We incorporated clinician and consumer input into the translation process. We conducted a qualitative pre-test to assess comprehension and a validation to assess psychometric properties and test-retest reliability.

Setting

Perth Children’s Hospital, Perth, Western Australia

Patients

We recruited English-speaking children aged 8 to 15 years.

Main outcome measures

Qualitative analysis of pre-test interviews, Cronbach’s α coefficient for internal consistency and intraclass correlation coefficient for test-retest reliability.

Results

The translation process yielded an acceptable translation. A qualitative pre-test conducted with 10 children demonstrated good comprehension of questionnaire items and resulted in small changes to increase item clarity. Validation with 207 participants demonstrated that questionnaire output score increased with age, school year, self-efficacy score, parental educational level and home literacy environment score. Internal consistency was assessed, with a Cronbach’s α coefficient of 0.854 (95% CI 0.812 to 0.887). Test-retest reliability was moderate, with an intraclass correlation coefficient of 0.612 (95% CI 0.402 to 0.761).

Conclusions

The translated HLS-Child-Q15 was well understood by children. Validation of the translated questionnaire demonstrated adequate psychometric properties, consistent with the original German questionnaire. The translated HLS-Child-Q15 is suitable for use with English-speaking children.

Data availability statement

Data are available on reasonable request and in compliance with institutional ethics and governance requirements.

Trial registration number

ACTRN12622001499774

Effectiveness of digital physiotherapy interventions in patients with knee osteoarthritis: a systematic review and meta-analysis of randomised controlled trials

Por: Cheung · T. H. R. · Elliott · M. T. · Stephens · G. · Mansfield · M.
Objectives

This systematic review and meta-analysis aims to provide an overview of the effectiveness of digital physiotherapy interventions on pain, physical functions and quality of life for patients with knee osteoarthritis.

Design

Systematic review and meta-analysis using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

Data sources

A systematic search of electronic databases, including MEDLINE, EMBASE, Web of Science, PsycInfo, CINAHL, Scopus and Cochrane Library, was conducted on 19 February 2025.

Eligibility criteria for selecting studies

We included randomised controlled trials which compared digital physiotherapy interventions to standard physiotherapy care for patients with knee osteoarthritis. Main outcomes included pain, physical functions and quality of life.

Data extraction and synthesis

25 studies met the inclusion criteria, and 18 studies were eligible for meta-analysis. The primary author conducted the initial search, selected articles and extracted data from eligible studies, which were independently checked by a second reviewer. Risk of bias (ROB) was assessed by Cochrane ROB-2 tool. Quality of evidence was evaluated by the GRADE approach.

Results

Overall, digital physiotherapy was associated with a small but statistically significant improvement in physical function (SMD=0.24, 95% CI 0.13 to 0.35); an overall meta-analysis was not performed for pain and quality of life due to considerable heterogeneity. Subgroup analyses revealed both video-conferencing and app- or web-based physiotherapy significantly reduced pain (SMD=–0.53, 95% CI –1.06 to –0.01 and SMD=–0.47, 95% CI –0.70 to –0.25, respectively) and physical function (SMD=0.32, 95% CI 0.10 to 0.54 and SMD=0.30, 95% CI 0.09 to 0.50 respectively). Digital physiotherapy interventions with individualised exercise components also reduced pain (SMD=–0.43, 95% CI –0.66 to –0.21) and improved physical function (SMD=0.30, 95% CI 0.17 to 0.43), when compared with non-exercise interventions.

Conclusion

There was moderate-quality evidence to support the use of digital physiotherapy interventions in improving pain and function in patients with knee osteoarthritis. Subgroup analyses revealed low-to-moderate quality evidence in using video-conferencing and app-/web-based physiotherapy and interventions with exercise components to treat patients with knee osteoarthritis. Overall, there were limited high-quality trials in drawing a robust conclusion. High ROB and huge heterogeneity were observed across studies. Further research should minimise the ROB and investigate the effect of different digital modalities, intervention components and length of follow-up.

Morphological diversity in the honeyeater hyolingual apparatus and its relationship with nectarivory

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.

The cost-effectiveness of penicillin allergy assessment pathway (PAAP): a decision analysis

Por: Yang · M. · Bestwick · R. · Howdon · D. · Ahmed · S. · Powell · N. · Armitage · K. F. · Fielding · J. · Porter · C. E. · Savic · S. · West · R. M. · Howard · P. · Galal · U. · Pavitt · S. · Sandoe · J. A. · Mujica-Mota · R. E.
Objective

To evaluate the cost-effectiveness of implementing a penicillin allergy assessment pathway (PAAP) versus usual care within the NHS.

Design

A decision tree analysis over a 5-year time-period, informed by a randomised controlled trial (RCT) of PAAP and systematic review. Value of information analysis was also conducted to estimate the value of conducting a new trial.

Data sources

Model inputs were informed by the ALABAMA RCT participants included in the primary analysis, 811 adults with penicillin allergy labels and recent antibiotic prescriptions, and data from published literature.

Interventions

Participants in the ALABAMA trial included in the primary analysis: PAAP (n=401) and usual care (n=410).

Primary and secondary outcome measures

Costs are presented in GBP (£) at 2022–2023 prices, quality-adjusted life years (QALYs), incremental cost-effectiveness ratio, incremental net monetary benefit (INMB), the probability of cost-effectiveness at the £20,000 and £30,000 per QALY threshold, and the cost effectiveness of a new follow-on trial.

Results

PAAP had incremental costs of £–83 (probability of cost saving 47.5%) and incremental QALYs of 0.036 (probability of positive benefits 47.5%). The INMBs (probability of cost-effectiveness) were £806 (48%) and £1167 (48%) under the decision thresholds of £20,000 and £30,000 per QALY, respectively. PAAP was more cost-effective among females, people aged >65 years, and more frequent antibiotic users. A new follow-on trial involving 1267 participants was estimated to cost £2.4 million and, by reducing uncertainty in the evidence, would avoid £19.6 million in costs of incorrect management decisions for eligible patients over the next 10 years.

Conclusion

The PAAP was considered cost-effective, but significant uncertainty remained. Future trials with adequate power and longer follow-up are needed to determine the most cost-effective models for penicillin allergy testing.

Trial registration number

ISRCTN20579216.

Prevalence of sexually transmitted infections among military personnel: a systematic review protocol

Por: Shoemaker · E. S. · Sandstrom · E. · Dangerfield · C. D. · Linton · J. · Cholette · F. · McClarty · L. M. · Lazarus · L. · Herpai · N. · Pavlova · D. · Pickles · M. · Becker · M.
Introduction

Military personnel are a unique population with heightened vulnerability to sexually transmitted infections (STIs), often exhibiting higher prevalence rates than civilians due to demographic, environmental and occupational factors. These vulnerabilities underscore the need for global prevalence estimates to guide effective, evidence-based interventions. This study aims to quantify the global burden of STIs among military personnel, providing a comprehensive and up-to-date assessment.

Methods and analysis

This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines (2020). Using the CoCoPop (Condition, Context, and Population) framework, a comprehensive search strategy will be conducted in MEDLINE, Embase, Global Health and Scopus to retrieve peer-reviewed records published between January 2010 and June 2025. Eligible studies will report numerical STI prevalence data among military personnel. Studies with insufficient information to calculate prevalence or those relying on self-reported STI data will be excluded. Data extraction will include study details, military descriptors, STI prevalence and diagnostic methods. Risk of bias will be assessed using the Joanna Briggs Institute critical assessment tool for prevalence and incidence studies. Prevalence estimates with 95% CIs will be reported for each STI and, where appropriate, pooled for curable STIs. Subgroup analyses will stratify prevalence by geographic region, service status, deployment status and socioeconomic factors. Heterogeneity will be evaluated within predefined subgroups using the I² statistic. Data will be presented in comprehensive tables and visualised with graphical tools, including forest plots for subgroup analyses and pooled estimates.

Ethics and dissemination

Ethical approval is not required for this review. The results will be disseminated through a peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42023472113.

Use of electronic point-of-care resources by early-career general practitioners and associations with their use during consultations: A cross-sectional analysis of consultation data.

Por: Mitchell · B. · Magin · P. · van Driel · M. L. · Tapley · A. · Ralston · A. · Davey · A. · Holliday · E. · Dizon · J. · Moad · D. · Fielding · A. · Fisher · K. · Clarke · L. · Spurling · G.
Objectives

To determine the use, frequency and factors linked to the use of any electronic point of care resources (ePOC resources) used by early-career general practitioners (GPs in training, otherwise known as GP residents or registrars) during consultations; and the frequency, and factors linked to the use of evidence-based clinical summaries.

Design

Cross-sectional analysis of data collected as part of the Registrar Clinical Encounters in Training (ReCEnT) project from 2018 to 2022. Every 6 months, GP trainees record 60 consecutive consultations, including information about their use of resources.

Setting

Australian training general practices.

Participants

3024 GP trainees in community-based vocational training.

Primary and secondary outcome measures

The primary outcome was the use of ePOC resources, and the secondary outcome was the use of evidence-based ePOC summaries.

Results

A total of 3024 GP trainees accessed electronic resources during patient encounters for 67 651/628 855 (10.8%) of diagnoses/problems. Use of ePOC resources increased 4% per year over the study period. Therapeutic Guidelines was accessed most often (27 435/79 536, 34.7% of all ePOC use) followed by Australian Medicines Handbook (7507, 9.4%) and HealthPathways (6965, 8.7%). Various factors were associated with increased use of ePOC resources, including increasing patient age, diagnosis/problem type, increasing years of experience prior to GP training and stage of training. GP trainees rarely accessed dedicated evidence-based clinical summaries.

Conclusions

Australian GP trainees use a range of resources to answer their clinical questions, mostly from Therapeutic Guidelines and prescribing compendiums, but also system specific resources that are free to access.

Singing interventions for people living with Parkinsons: a systematic review and meta-analysis

Por: Irons · J. Y. · Sheffield · D.
Objectives

To evaluate the effects of singing interventions on well-being, mental health and communication, motor and respiratory functions through meta-analysis and to examine the practices used in the singing interventions.

Design

Systematic review and meta-analysis.

Inclusion criteria

Both randomised and non-randomised studies, involving participants living with Parkinson’s and receiving singing interventions.

Data sources

Four databases (CINAHL, Medline, PsycINFO, Web of Science) and Google Scholar were searched. The last search was conducted on 3 April 2025.

Primary and secondary outcome measures

Eligible studies reported on the following outcomes: quality of life, voice-related acoustic measures, respiratory function, mental health and motor function. The risk of bias was assessed using the Downs and Black Quality checklist for controlled studies and national heart, lung, blood institute study quality assessment tool for non-controlled studies.

Analysis

Meta-analyses were conducted to pool effect sizes across included studies using random-effects models. All analyses were performed using Meta-Essentials. Additionally, key elements of singing practices were narratively synthesised.

Results

23 studies (3 randomised controlled trials (RCTs), 20 non-RCTs) involving 540 participants were included in the analysis. Common elements of singing intervention practices included breathing exercises, vocal warm-ups and singing participants’ preferred songs, which are largely led by music therapists.Three meta-analyses based on RCTs were conducted on clinical outcome measures; results suggest that singing was favoured in only one outcome measure, vocal loudness during sustained vowel production (standard mean difference (SMD)=0.67, 95% CI 0.29 to 1.05, I2=0%). However, the certainty of this evidence is very low due to a high risk of bias, imprecision and indirectness. Further, when combining results from RCTs and non-RCTs, positive changes for three further outcome measures were observed: maximum phonation time (k=11, n=157, SMD=0.38, 95% CI 0.18 to 0.59, I2=23.48%), vocal loudness of sustained vowel (k=8, n=99, SMD=0.50, 95% CI 0.14 to 0.86, I2=50.96%) and a respiratory function measure of maximal inspiration pressure (k=4, n=65, SMD=0.46, 95% CI 0.07 to 0.85, I2=0%). However, these findings are largely based on non-controlled studies with very low quality of evidence.

Conclusions

Singing interventions may support people living with Parkinson’s, but due to insufficient high-quality evidence, we are unable to determine the effects of singing interventions. We discuss implications for future work and practice, emphasising that more robust RCTs are needed.

Perceptions of an AI-based clinical decision support tool for prescribing in multiple long-term conditions: a qualitative study of general practice clinicians in England

Por: dElia · A. · Morris · S. G. · Cooper · J. · Nirantharakumar · K. · Jackson · T. · Marshall · T. · Fitzsimmons · L. · Jackson · L. J. · Crowe · F. · Haroon · S. · Greenfield · S. · Hathaway · E.
Background

Artificial intelligence (AI)-based clinical decision support systems (CDSSs) are currently being developed to aid prescribing in primary care. There is a lack of research on how these systems will be perceived and used by healthcare professionals and subsequently on how to optimise the implementation process of AI-based CDSSs (AICDSSs).

Objectives

To explore healthcare professionals’ perspectives on the use of an AICDSS for prescribing in co-existing multiple long-term conditions (MLTC), and the relevance to shared decision making (SDM).

Design

Qualitative study using template analysis of semistructured interviews, based on a case vignette and a mock-up of an AICDSS.

Setting

Healthcare professionals prescribing for patients working in the English National Health Service (NHS) primary care in the West Midlands region.

Participants

A purposive sample of general practitioners/resident doctors (10), nurse prescribers (3) and prescribing pharmacists (2) working in the English NHS primary care.

Results

The proposed tool generated interest among the participants. Findings included the perception of the tool as user friendly and as a valuable complement to existing clinical guidelines, particularly in a patient population with multiple long-term conditions and polypharmacy, where existing guidelines may be inadequate. Concerns were raised about integration into existing clinical documentation systems, medicolegal aspects, how to interpret findings that were inconsistent with clinical guidelines, and the impact on patient-prescriber relationships. Views differed on whether the tool would aid SDM.

Conclusion

AICDSSs such as the OPTIMAL tool hold potential for optimising pharmaceutical treatment in patients with MLTC. However, specific issues related to the tool need to be addressed and careful implementation into the existing clinical practice is necessary to realise the potential benefits.

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