The Quadrivalent human papillomavirus (HPV) Vaccine Evaluation Study with Addition of the Nonavalent Vaccine Study (QUEST-ADVANCE) aims to provide insight into the long-term immunogenicity and effectiveness of one, two and three HPV vaccine doses. Here, we describe the protocol for QUEST-ADVANCE.

QUEST-ADVANCE is an observational cohort study including males and females who are unvaccinated or vaccinated with the quadrivalent or nonavalent HPV vaccine in British Columbia, Canada. Female participants who are unvaccinated or vaccinated with 1–3 doses of the quadrivalent or nonavalent HPV vaccine at 9–14 years of age will be recruited approximately 5 or 12 years postvaccination eligibility. Male participants who are unvaccinated or vaccinated with 1 or 2 doses of the nonavalent HPV vaccine at 9–14 years of age will be recruited at approximately 5 years postvaccination eligibility. The study involves a maximum of four visits over a period of 4–5 years for female participants, and two visits over a 12-month period for male participants. At each visit, self-collected swabs (cervico-vaginal or penile) and questionnaire data will be collected. In each study group, a subset of participants will be invited to participate in a substudy evaluating the long-term humoral immunogenicity of the HPV vaccine. Additional blood samples will be collected from participants who are part of the immunogenicity substudy. The total required sample size is 7180 individuals. The primary objectives are (1) to examine vaccine effectiveness in males and females against prevalent genital HPV infections for one, two and three doses of the HPV vaccine compared with unvaccinated participants and (2) to evaluate if there is non-inferior immunogenicity as indicated by type-specific antibody response of one dose of the HPV vaccine in 20–27-year-old females vaccinated at 9–14 years of age compared with historical data of three doses of the HPV vaccine females vaccinated at 16–26 years of age up to 12 years postvaccination.

QUEST-ADVANCE was approved by the Research Ethics Board of the University of British Columbia/Children’s and Women’s Health Centre of British Columbia (H20-02111). Individual electronic informed consent or assent will be obtained from each participant before any study-specific procedures are undertaken. Results will be published in an international peer-reviewed journal and on the study website.

A retrospective cohort study.

A large multispecialty, tertiary referral and teaching hospital in England, UK.

The study included 3175 consecutive adult ICU UPAs from hospital wards over a 6-year period (2014–2019).

Ward-based management of deterioration prior to ICU admission was assessed by the RRT, using a scored checklist—the UPA score. Admissions were compared in two groups according to their exposure to an RRT review in the 72 hours before ICU admission. Associations with in-hospital cardiac arrest within 24 hours before ICU admission and all-cause in-hospital mortality were estimated, using unadjusted and adjusted odds ratios (aORs) with 95%CI.

RRT review occurred in 1413 (44.5%) admissions and was associated with reduced odds of in-hospital cardiac arrest (aOR 0.51; 95% CI 0.36 to 0.78; p

An RRT review in the 72 hours prior to ICU admission was associated with reduced odds of in-hospital cardiac arrest but did not impact in-hospital mortality. Higher UPA scores were associated with increased incidence of both in-hospital cardiac arrest and in-hospital mortality. In addition, this study describes a novel and adaptable RRT scoring tool (the UPA score) for safety monitoring and quality improvement.

The objective of this scoping review is to map and synthesise existing literature on interventions aimed at promoting healthy screen use among adolescents. This review identifies the types, functions and settings of interventions, explores the diversity of targeted outcomes and highlights equity considerations and research gaps.

We conducted a scoping review in accordance with the Arksey and O’Malley framework and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines.

We systematically searched Medline, PsycINFO and ERIC from January 2013 to June 2024. Reference lists of included studies were also manually screened.

We included peer-reviewed experimental, quasi-experimental, observational and qualitative studies reporting on interventions designed to promote healthy screen use among adolescents aged 10–19 years.

One author extracted data using a structured charting form, and a second author verified all entries. Results were synthesised descriptively across key themes including target populations, theoretical frameworks, intervention components and reported outcomes.

From 6433 records, we identified 93 articles on 81 interventions, mainly conducted in high school settings in the USA and Australia. Most examined short-term interventions targeting recreational screen time. Outcomes included media literacy, cyberbullying, internet and gaming addiction, safe internet use, social media use and mental and sexual health. Seventy-eight per cent of interventions attempted to educate adolescents, while 34% offered training activities (eg, educational sessions to elevate risk awareness and skill-based training to enhance digital literacy and self-regulation). Interventions targeting external influences were used less frequently. About 20% of studies showed no statistically significant findings, highlighting the need to promote evidence-based interventions.

This review identifies a need for broader, multilevel strategies that account for contextual factors and social determinants in influencing screen use and its related health issues. Future research should explore long-term effectiveness while examining the potential moderating and mediating effects of social determinants. Equity considerations were not a primary focus of most interventions, underscoring an important gap in this literature. Future interventions could incorporate equity-focused design and evaluation to ensure they respond to the needs of diverse adolescent populations.

To explore the challenges experienced by people with intellectual disability, their carers and health and social care professionals when using and managing medication.

A synthesis of qualitative research using meta-ethnography.

We searched seven databases: MEDLINE, Embase, CINAHL, Science, Social Science and Conference Proceedings Citation Indices (Web of Science), Cochrane Library, PsycINFO and Proquest Dissertations and Theses from inception to September 2022 (updated in July 2023).

We included studies exploring the challenges and perceptions of people with intellectual disability, their carers and health and social care professionals regarding medication management and use.

We reviewed 7593 abstracts and 475 full texts, resulting in 45 included papers. Four major themes were identified: (1) Medication-related issues, (2) navigating autonomy and relationships, (3) knowledge and training needs and (4) inequalities in the healthcare system. We formulated a conceptual framework centred around people with intellectual disability and described the interconnectedness between them, their carers and health and social care professionals in the process of managing and using medication. We identified challenges that could be associated with the person, the medication and/or the context, along with a lack of understanding of these challenges and a lack of capability or resources to tackle them. We developed an overarching concept of ‘collective collaboration’ as a potential solution to prevent or mitigate problems related to medication use in people with intellectual disability.

The effective management of medication for people with intellectual disability requires a collaborative and holistic approach. By fostering person-centred care and shared decision-making, providing educational and practical support, and nurturing strong relationships between all partners involved to form a collective collaboration surrounding people with intellectual disability, improved medication adherence and optimised therapeutic outcomes can be achieved.

CRD42022362903.

Although as many as 92% of survivors of physical intimate partner violence (IPV) report impacts to the head and/or non-fatal strangulation (NFS) that raise clinical suspicion of brain injury (BI), there are no evidence-based methods to document and characterise BI in this vulnerable population, limited clinical practice guidelines and insufficient understanding about long-term risks for conditions including Alzheimer’s Disease and Related Dementias (ADRD). This leaves most survivors of IPV-caused BI (IPV-BI), overwhelmingly women, without adequate access to medical care and support, safe housing, back-to-school/work accommodations or follow-up care for long-term neurocognitive health. Although traumatic brain injury (TBI) is an established ADRD risk factor, little is known about the attributable risk of ADRD due to IPV-BI, particularly in women.

Our overarching objectives are to (1) use plasma biomarkers as novel tools to assist clinicians to improve diagnosis of IPV-BI at the acute, subacute and chronic stages in a manner sensitive to the needs of this vulnerable population and (2) raise awareness of the importance of considering IPV-BI as a potential ADRD risk factor. A prospective observational study funded by the US Department of Defense (HT9425-24-1-0462), Brain Canada (6200) and the Canadian Institutes of Health Research (523320-NWT-CAAA-37499) leverages collaborative research at multiple clinical sites in British Columbia to maximise equity, diversity and inclusion among participants, with a target enrolment of n=600 participants.

The Advocates, Academics, Survivors and Clinicians to END Intimate Partner Violence Biomarkers study, which is predicated on pre-specified research questions, represents one of the most significant community-based studies on plasma biomarkers affected by an IPV-BI incident. Of particular significance is the fact our study uses robust biomarker approaches being applied in the TBI and ADRD fields to determine how the biomarker profile after IPV-BI compares to typical TBI and the early stage of neurodegenerative disorders.

This study was approved by the University of British Columbia Clinical Research Ethics Board (H24-01990, H22-02241 and H16-02792) and the Island Health Research Ethics Board (H22-03510). Upon publication of primary papers, de-identified data and biospecimens will be made widely available, including the US Federal Interagency Traumatic Brain Injury Research (FITBIR) federated database. Our data and integrated knowledge translation activities with persons with lived experience of IPV-BI and those working in the healthcare sector will be synthesised into co-designed and implemented knowledge tools to improve outcomes for survivors of IPV-BI.

The standard treatment of oral cavity cancers (OCC) relies on surgery and postoperative radiotherapy (poRT) for advanced stages or poor factors. In more than 75% of cases, reconstructive surgery with a flap aims to restore the function lost with tumour resection. Current poRT planning and delineation guidelines omit the presence of a flap. It may be assumed that poRT with flap sparing may allow for reducing radio-induced toxicities and improving functional outcomes, without impairing local primary control. The OPTIFLAP trial assesses non-inferior locoregional control using flap sparing compared with conventional flap-agnostic radiotherapy in patients with OCC, while reducing treatment-related toxicity and improving functional outcomes.

The OPTIFLAP study is a French, multicentre, 1:1 randomised, phase III, controlled trial. It will recruit 348 patients with OCC with a flap. Recruitment is active with the first enrolment on 2 July 2025 and is planned over 48 months. The primary outcome is non-inferior 2-year locoregional control rate using flap sparing compared with flap-agnostic radiotherapy (as per standard routine practice) in completely resected OCCs undergoing poRT. Key secondary outcomes include rates of toxicities, locoregional relapse-free survival, progression-free survival, overall survival, quality of life, functional outcomes (assessed by the Performance Status Scales for Head and Neck Cancer, the MD Anderson Dysphagia Inventory (self-questionnaire) and the Phonation Handicap Index (self-questionnaire)), flap doses and outcomes between arms depending on dosimetric parameters. The trial incorporates translational ancillary studies addressing individual radiosensitivity, salivary microbiome evolution, radiomics and dosiomics of flap changes, as well as medico-economic evaluation.

The study protocol has been approved by the Medical Ethics Committee East III (January 2025; Ref 24.05832.000442) and the French Agency for Medical and Health Products Safety (December 2024; ID-RCB: 2024-A01764-43) and was validated by review boards of all participating centres. Written informed consent will be obtained from all participants. Study results will be published in international peer-reviewed scientific journals and presented at relevant scientific conferences.

NCT06798922.

The development of effective vaccines targeting human papillomavirus (HPV) has significantly contributed to disease prevention, highly relevant in immunosuppressed patients who have higher incidence of HPV-related cancers than their non-immunosuppressed counterparts. However, the acceptance and uptake of the HPV vaccine among immunosuppressed individuals pose unique challenges. Immunocompromised patients’ acceptance of the HPV vaccine is influenced by multifaceted factors, including concerns about safety and effectiveness, interactions with immunosuppressive medications and uncertainties due to their compromised immunity. This systematic review aims to identify the main factors influencing HPV vaccine acceptance among immunosuppressed patients.

A comprehensive search strategy will be executed across databases such as MEDLINE/PubMed, Embase, Scopus, Web of Science, ScienceDirect, Latin American and Caribbean Literature in Health Sciences, Cumulative Index to Nursing and Allied Health Literature and Cochrane Database. The review will encompass the three WHO-endorsed HPV vaccines (quadrivalent, bivalent and nonavalent) and will consider studies related to HPV vaccines and their administration. The scope includes study focusing on immunosuppressed patients who received organ transplants, cancer treatments or are HIV-positive. No temporal restrictions will be applied, and searches will be conducted until December 2025. Observational studies, including retrospective/prospective cohorts, case–control and cross-sectional studies, reporting factors influencing HPV vaccination in immunosuppressed populations will be included. Studies with overlapping patient populations will be excluded. Data extraction will include study details, demographics, vaccine type, risk/protective factors, outcomes and medical history. Validation and cross-verification will ensure data accuracy. Risk of bias will be assessed using ROBINS-I (Risk Of Bias In Non-randomised Studies of Interventions), and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will rate evidence certainty. Meta-analysis, guided by Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, will employ fixed/random-effects models, assessing heterogeneity using I² statistics.

This research will analyse previously published data, so ethical approval is not required. The results of the systematic review will be submitted for publication in a peer-reviewed journal.

CRD42023452537.

Overexpression of p16 has been documented in a variety of human tumours. Nonetheless, the association between p16 overexpression and the clinicopathological characteristics of patients with cervical cancer remains a subject of debate. This meta-analysis sought to systematically assess the relationship between p16 expression and the clinicopathological features of patients with cervical cancer.

Systematic review and meta-analysis.

The PubMed, Embase, Cochrane Library (Central), Web of Science (SCI Expanded), and Chinese databases (CNKI, VIP, Wanfang and CBM) were searched through 1 March 2024.

Case-control studies examining the association between p16 expression and cervical cancer were analysed to evaluate whether p16 expression was correlated with the clinicopathological characteristics of patients with cervical cancer.

Two independent reviewers employed standardised methods to search, screen and code the included studies. The risk of bias was evaluated using the Cochrane Collaboration tools and the Newcastle-Ottawa Scale. Statistical analyses and data processing were conducted using Review Manager V.5.4, which included heterogeneity tests and sensitivity analyses. Additionally, STATA V.16.0 was used for further sensitivity analyses of the included studies, and publication bias was assessed using Begg’s test.

The p16 protein is strongly associated with the onset and progression of cervical cancer and serves as a valuable biomarker for its early detection and diagnosis.

CRD42024546241.

To address the lack of accurate and accessible mental health medicines-information resources for children, young people and their parents/guardians using design thinking to co-design free-to-use, video resources tailored to this audience.

A multiphase qualitative case study using the Double Diamond model of Design Thinking: Discover, Define, Develop and Deliver. This included iterative prototyping, thematic analysis and public and patient involvement throughout.

Dublin, Ireland with online distribution of the final resources internationally through a free, open-access platform.

A multidisciplinary co-design team including two specialist mental health pharmacists, two academic pharmacists, five consultant psychiatrists, a psychiatric nurse, a youth content specialist, three youth activists and a parent representative.

26 co-designed, medicines-information videos were created, including versions for children (voiced by children), parents/guardians and young people. Videos feature storytelling formats with Bitmoji characters. Feedback from youth and parent collaborators guided design and content. Since launch, www.youthmed.info has had over 25 000 website views and more than 30 000 video views, with engagement from over 91 countries. The resources are also linked on national and international clinical and charity platforms.

Youth Med.Info addresses a gap in accessible, accurate mental health medicines-information by placing users – children, young people, parents/guardians and clinicians—at the centre of its design.

The management of bleeding and coagulation after total knee arthroplasty (TKA) has long been recognised as a significant challenge for orthopaedic surgeons. Despite the notable success of empirical anticoagulation in preventing venous thromboembolism (VTE) following TKA, the increased risk of postoperative bleeding has also raised extensive concern. Ecchymosis, as one of the most common manifestations indicating postoperative bleeding, holds the potential to indicate the balance of bleeding and hypercoagulation. However, there is still a lack of evidence-based medical research to determine the importance of postoperative ecchymosis and related personalised anticoagulation therapy. Therefore, we have designed a randomised controlled trial aimed at assessing the safety and efficacy of personalised delayed anticoagulation strategies in the management of postoperative bleeding in TKA patients.

This is a prospective, randomised, controlled trial. Patients diagnosed with end-stage knee osteoarthritis will be grouped based on the presence of ecchymosis after TKA. Those without ecchymosis will receive standard anticoagulation therapy, while those with ecchymosis will be randomised in a 1:1 ratio into either the standard anticoagulation group or the delayed anticoagulation group. The primary outcomes will compare the blood routine examination, coagulogram, thromboelastography and the incidence of VTE. The secondary outcomes will include surgical-related complications. Additionally, patient baseline data and surgery-related data will also be recorded and analysed.

Ethics approval has been obtained from The First Affiliated Hospital of Chongqing Medical University (2024-194-01). The results will be disseminated at international conferences and in peer-reviewed publications.

ChiCTR2400084440.

Difficulty with walking can lead to reduced quality of life for people with Parkinson’s disease (pwPD); improving walking is considered a treatment priority. Drug therapies can control PD symptoms; however, pwPD often still experience mobility problems.

Functional electrical stimulation (FES) induces movement in weak muscles via external electrical stimulation. FES is used in stroke and multiple sclerosis patients to correct dropped foot by stimulating the common peroneal nerve and is associated with improved quality of life and mobility. The randomised feasibility study preceding this definitive study showed that daily FES can produce a clinically meaningful improvement in walking speed in pwPD; this was sustained 4 weeks after FES was withdrawn. STEPS II is the first definitive randomised controlled trial, with blinded outcome assessment, aiming to determine the efficacy of FES in pwPD.

STEPS II is a two-group, parallel, assessor-blinded, superiority randomised controlled trial with an internal pilot, designed to compare FES plus usual care versus usual care alone. 234 participants will be randomised across eight UK sites. Telephone pre-screening and face-to-face screening will determine eligibility. The intervention group will attend four unblinded FES visits to receive the device and assess walking with and without FES. All participants have blinded assessments at baseline and weeks 2, 6, 18 and 22. The primary objective is to compare whole body bradykinesia at 18 weeks post-baseline via changes in 10m walking speed. Secondary objectives will assess the wider effects of FES on Parkinsonian gait and quality of life. An embedded qualitative component will explore wider experiences of FES.

This study received ethical approval from the Yorkshire and The Humber-Sheffield Research Ethics Committee (reference 23/YH/0193). A Data Monitoring Committee and Trial Steering Committee will provide independent oversight. Dissemination will be via publications, conferences and social media. FES intervention and training materials will be made open access.

ISRCTN13120555.

Many cancer treatments can result in reduced fertility, impacting survivors’ opportunities for biological parenthood. Fertility preservation (FP) methods for boys and young men, such as cryopreservation of testicular tissue or sperm, offer hope but are currently underused among young male patients with cancer. Despite guidelines recommending early discussion of fertility implications, many newly diagnosed males do not receive FP counselling or referral to fertility services. Male cancer survivors face a higher likelihood of infertility than their peers, yet focused FP decision-making support is lacking. This study aims to address this gap by developing and evaluating the first dedicated patient decision aid (PtDA) for boys and young male patients with cancer aged 11–25 years old, to help them make informed FP decisions before receiving cancer treatment.

The current study follows a multistage process: developing the PtDA, alpha testing for acceptability with former patients, parents and healthcare professionals, and beta testing in clinical settings to ensure effective integration into routine care. Using a combination of interviews and questionnaire data, this research will assess the PtDA’s acceptability and impact on decision-making.

This study has been prospectively registered on the Research Registry (10273). Ethics approval has been obtained from Leeds Beckett University and the National Health Service/Health Research Authority before undertaking data collection. The final resource will be disseminated widely and made freely available online via our dedicated Cancer, Fertility and Me website, for use in clinical and research practice.

The harmful health effects of children’s exposure to secondhand smoke (SHS) are well established. Most SHS exposure now occurs in the home, in low-income households. Previous research suggests that using nicotine replacement therapy (NRT) in the home can help with temporary smoking abstinence and could reduce smoking indoors. This pilot randomised controlled trial tests the feasibility of providing parents, carers and relatives with posted-to-home nicotine replacement therapy alongside fortnightly telephone support to reduce children’s exposure to SHS.

100 participants are being recruited through existing National Health Service (NHS) Lanarkshire initiatives and social media. Parents/carers who are at least 18 years old, smoke in the home and care for one or more children aged 0–16 years are eligible to take part. Participants are randomised to either the intervention (Group A) or control (Group B) arm. Group A receives NRT posted to their home for 12 weeks free of charge, alongside fortnightly telephone calls and materials to support them in reducing children’s exposure to SHS. Group B is signposted to the Scottish Government’s ‘Take it Right Outside’ website which provides interactive advice on creating a smoke-free home. To quantify the child’s exposure to SHS, participants instal an air quality monitor to measure fine particulate matter (PM_2.5) concentrations in their living room for 7 days at baseline and 12-week follow-up and/or collect and post saliva samples from their youngest child (age 5 or over) for cotinine analysis. Qualitative interviews explore intervention experience, NRT use and adherence and changes to home-smoking behaviours/smoking-related expenditure. Descriptive data analyses will be performed to address the feasibility of recruitment, randomisation, retention and adherence, data collection and intervention delivery. Analysis will also include pre/post changes (paired t-test) in both child’s salivary cotinine and PM_2.5 levels to provide preliminary data on intervention effectiveness and difference between the intervention and control arms of the study. Health economics and resource use data will be collected and assessed for completeness, to test the process of data collection and estimate mean cost of both study arms.

NHS ethical approval has been obtained by the West of Scotland Research Ethics Service (15 December 2023, ref 23/WS/0153; 13 December 2024, ref AM01). The findings will be disseminated to participants, funders, NHS Lanarkshire and other health services, and in peer-reviewed journals and academic conferences. Findings will inform new approaches that are timely and important, providing valuable evidence to help reduce children’s exposure to SHS in the home in Scotland and elsewhere.

ISRCTN79307718.

To investigate discrepancies in perceptions regarding the accessibility and availability of rest and relaxation (R&R) spaces between hospital doctors in Scotland and NHS Scotland regional health boards (HBs), with the intention of informing best practices for organisational policy on the provision of R&R spaces both now and in the future.

A qualitative study, through an inhabited institutionalism (II) lens, of semi-structured interviews of hospital doctors across the career continuum in Scotland and all NHS regional HBs in Scotland providing written information relating to R&R space provision.

NHS Scotland during the COVID-19 pandemic and beyond.

Hospital doctors (n=30) who had participated in a larger qualitative study and provided specific insights on R&R spaces. All NHS Scotland regional HBs (n=14).

Although HBs reported the provision of R&R spaces, numerous doctors reported R&R spaces had been removed, relocated or were inaccessible. Furthermore, limited awareness of their availability attributed to inadequate communication, compounded the issue. This divergence between institutional reporting and front-line experience can be interpreted through the lens of II, which posits that institutional polices are often interpreted and implemented differently.

This study emphasises how crucial R&R spaces are to promoting doctors’ well-being especially during the time of high stress. HBs must not only guarantee the accessibility and physical availability of R&R spaces but also enhance their communication regarding the provision.

Tuberculosis (TB) remains the leading cause of infectious disease deaths, particularly among people living with HIV (PWH). Despite being preventable, TB preventive therapy (TPT) uptake is low in high-burden regions like South Africa, where new guidelines have expanded TPT eligibility and introduced shorter, more effective regimens like 3 months of weekly rifapentine and isoniazid (3HP). As differentiated service delivery models for HIV care have proven effective, there is increasing recognition that decentralising TPT delivery may improve coverage and completion. This study explores whether a community-based TPT delivery strategy can enhance uptake and completion of TPT compared with traditional clinic-based services.

We will conduct a household-randomised, non-blinded, controlled trial. Persons eligible for TPT will be recruited from the TB TRIAGE+Trial study, a community-based household TB screening study. Households containing at least one person eligible for TPT will be randomised 1:1 to either community-based TPT or standard-of-care clinic referral for TPT. At enrolment, all participants will be provided with a 2-week supply of TPT in the community. Participants randomised to the community arm will receive the entire course of TPT in a single dispense (12 weeks of 3HP or 6 months of isoniazid, if 3HP is contraindicated). Clinic-arm participants will be referred to their local clinic for the remainder of their course of TPT and will collect TPT refills on the clinic-determined schedule. Our primary outcome is the proportion of participants who complete a course of TPT. Secondary outcomes include overall adherence to TPT, predictors of adherence with TPT, participant satisfaction with the assigned TPT delivery method and adverse events.

The study and its tools were approved by the Human Sciences Research Councils Research Ethics Committee (approval number: 2/25/10/23), based in Pretoria, Gauteng, South Africa, as well as the University of Washington Institutional Review Board (Study 00018448). Study findings will be shared through the community advisory group and local stakeholder meetings, relevant international and local meetings/conferences and peer-reviewed publications.

NCT06214910. Date and version: 3.0, 30 July 2024.

Rare diseases (RD) are collectively common and often genetic. Families value and can benefit from precise molecular diagnoses. Prolonged diagnostic odysseys exacerbate the burden of RD on patients, families and the healthcare system. Genome sequencing (GS) is a near-comprehensive test for genetic RD, but existing care models—where consultation with a medical geneticist is a prerequisite for testing—predate GS and may limit access or delay diagnosis. Evidence is needed to guide the optimal positioning of GS in care pathways. While initiating GS prior to geneticist consultation has been trialled in acute care settings, there are no data to inform the utility of this approach in outpatient care, where most patients with RD seek genetics services. We aim to evaluate the diagnostic yield, time to diagnosis, clinical and personal utility and incremental cost-effectiveness of GS initiated at the time of referral triage (pre-geneticist evaluation) compared with standard of care.

200 paediatric patients referred to one of two large genetics centres in Ontario, Canada, for suspected genetic RD will be randomised into a 1:1 ratio to the intervention (GS first) or standard of care (geneticist first) arm. An unblinded, permuted block randomisation design will be used, stratified within each recruitment site by phenotype and prior genetic testing. The primary outcome measure is time to genetic diagnosis or to cessation of active follow-up. Survival analysis will be used to analyse time-to-event data. Additional measures will include patient-reported and family-reported measures of satisfaction, understanding and perceived test utility, clinician-reported measures of perceived test utility and management impact, and healthcare system utilisation and costs.

This study was approved by Clinical Trials Ontario. Results will be disseminated, at minimum, via peer-reviewed journals, professional conferences and internal reports to funding bodies. Efforts will be made to share aggregated study results with participants and their families.

NCT06935019.

Reducing sedentary behaviour (SB) in older adults is a promising strategy to promote healthy ageing. However, to develop more effective interventions, more in-depth information is needed on how existing interventions work. The present realist review aims to identify the working mechanisms and contextual preconditions to guide the development of future interventions.

A realist review was conducted following the iterative process of Pawson and Tilley and reported following the RAMESES publication standards.

Evidence was searched in four databases: EMBASE, PubMed, Web of Science and Scopus, and in the grey literature.

All study types and designs were included. Studies conducted in older adults with a mean age of 60 years or older, providing information on the context, mechanisms and/or outcomes of interventions aimed at the reduction of SB were eligible for inclusion and appraised for relevance and rigour.

All data were coded by two independent reviewers. Sections that contained relevant information to refine, refute or confirm the initial programme theory were given a code. Based on these codes, context-mechanism-outcome configurations were made, and a final programme theory was developed.

In total, 58 studies, from 61 articles, were eligible. The review revealed three important contexts for changes in SB: the (1) motivation, (2) opportunities and (3) capabilities of older adults. Depending on the context, other behaviour change techniques should be used to trigger specific mechanisms and, in turn, reduce SB. Especially, the impact of the underlying automatic processes of SB on the effectiveness of SB interventions became clear. Existing interventions primarily focus on the reflective processes guiding SB, without taking into account that SB is often an automatic response that occurs unconsciously, with little reasoning.

The effectiveness of SB interventions in older adults highly depends on the context in which the interventions occur. In particular, the context of automatic motivation should receive more attention to break the ingrained habit of SB in older adults.

SARS-CoV-2 is now endemic and expected to remain a health threat, with new variants continuing to emerge and the potential for vaccines to become less effective. While effective vaccines and natural immunity have significantly reduced hospitalisations and the need for critical care, outpatient treatment options remain limited, and real-world evidence on their clinical and cost-effectiveness is lacking. In this paper, we present the design of the Canadian Adaptive Platform Trial of Treatments for COVID in Community Settings (CanTreatCOVID). By evaluating multiple treatment options in a pragmatic adaptive platform trial, this study will generate high-quality, generalisable evidence to inform clinical guidelines and healthcare decision-making.

CanTreatCOVID is an open-label, individually randomised, multicentre, national adaptive platform trial designed to evaluate the clinical and cost-effectiveness of therapeutics for non-hospitalised SARS-CoV-2 patients across Canada. Eligible participants must present with symptomatic SARS-CoV-2 infection, confirmed by PCR or rapid antigen testing (RAT), within 5 days of symptom onset. The trial targets two groups that are expected to be at higher risk of more severe disease: (1) individuals aged 50 years and older and (2) those aged 18–49 years with one or more comorbidities. CanTreatCOVID uses numerous approaches to recruit participants to the study, including a multifaceted public communication strategy and outreach through primary care, outpatient clinics and emergency departments. Participants are randomised to receive either usual care, including supportive and symptom-based management, or an investigational therapeutic selected by the Canadian COVID-19 Outpatient Therapeutics Committee. The first therapeutic arm evaluates nirmatrelvir/ritonavir (Paxlovid), administered two times per day for 5 days. The second therapeutic arm investigates a combination antioxidant therapy (selenium 300 µg, zinc 40 mg, lycopene 45 mg and vitamin C 1.5 g), administered for 10 days. The primary outcome is all-cause hospitalisation or death within 28 days of randomisation.

The CanTreatCOVID master protocol and subprotocols have been approved by Health Canada and local research ethics boards in the participating provinces across Canada. The results of the study will be disseminated to policy-makers, presented at conferences and published in peer-reviewed journals to ensure that findings are accessible to the broader scientific and medical communities. This study was approved by the Unity Health Toronto Research Ethics Board (#22-179) and Clinical Trials Ontario (Project ID 4133).

NCT05614349

Gestational diabetes is a common metabolic disorder in pregnancy which identifies a substantial increased risk of future diabetes. Despite this risk, many individuals are not screened for dysglycaemia in the postpartum period. Continuous glucose monitoring (CGM) is an evolving technology that provides details of an individual’s glucose levels throughout the day; however, it has not yet been evaluated as a screening tool for postpartum dysglycaemia. To address this gap, this prospective cohort study will examine the use of CGM in the early postpartum period to predict the risk of maternal dysglycaemia after delivery.

The Predicting Dysglycaemia in Individuals with Gestational Diabetes Immediately Postpartum using CGM (PREDISPOSE) study is a prospective cohort study designed to assess the ability of a CGM device (Freestyle Libre 2) worn in the postpartum period to detect persistent dysglycaemia in individuals with gestational diabetes. The study will recruit 240 individuals with gestational diabetes. Each participant will wear the CGM immediately postpartum and before attending routine postpartum diabetes screening, consisting of a 75-gram oral glucose tolerance test (OGTT) and related blood work (haemoglobin A1c (HbA1c), complete blood count and lipid profile). The primary outcome is the accuracy of the area under the curve for all glucose measurements from the first CGM wear to detect postpartum dysglycaemia. We will perform sensitivity and specificity analyses to determine optimal CGM cut-offs to diagnose diabetes or prediabetes. Secondary outcomes include the incidence of postpartum dysglycaemia (based on 75-gram OGTT and/or HbA1c), incidence of postpartum dyslipidaemia, patient acceptability of CGM testing, data variability from CGM and cardiometabolic health outcomes diagnosed in years one, two and five after delivery.

All participating sites have received ethics approval of the current protocol and have started recruitment of participants to the study. The ethics boards that approved this study are the Biomedical Research Ethics Board at the University of Manitoba, the Conjoint Health Research Ethics Board at the University of Calgary, the Mount Sinai Hospital Research Ethics Board at Mount Sinai Hospital and the Comité d'éthique de la Recherche at Université Laval. Study results will be disseminated through conference presentations and publication in a peer-reviewed journal, regardless of study findings.

NCT04972955. Registration date: 28 June 2021.

Latin American countries have long struggled with socioeconomic inequalities and health equity. In 2007, Ecuador implemented a health reform to address these issues by making public health services free, coordinating finances between subsystems and increasing the state’s health budget. This study evaluates whether Ecuador’s health system reform (2007–2017) reduced out-of-pocket (OOP) health spending, catastrophic health spending (CHS) and socioeconomic inequalities in CHS.

Cross-sectional study.

Secondary data available of households from the 2006 and 2014 National Living Standards Measurement surveys.

Descriptive statistics (means and medians) and log-binomial regression were applied to assess prevalence of OOP and socioeconomic inequalities (residence, region, health insurance status and wealth) in catastrophic health expenditure (CHE) for each period and over time.

Overall, there was a significant reduction of 14% points in the proportion of households with OOP healthcare expenditure. The prevalence of CHE decreased from 17% to 10% and within each socioeconomic group over time. Significant reductions in relative risk were observed in all socioeconomic variables. The inequality in CHE decreased significantly in households placed in rural areas (relative difference (RD): 0.88; 95% CI: 0.79 to 0.97) and poorest (RD: 0.82; 95% CI: 0.69 to 0.97); however, it increased within regions (RD: 0.58; 95% CI: 0.44 to 0.76) and for uninsured households (RD: 1.39; 95% CI: 0.95 to 2.04).

This study suggests that recent health reform effectively reduced OOP healthcare expenditure, CHE and some socioeconomic inequalities. Future reforms should further invest in key areas, expand health insurance for the most disadvantaged and monitor progress towards universal health coverage to address persistent inequalities.