To translate and culturally adapt six self-report measures for depression, anxiety, post-traumatic stress disorder (PTSD) and somatic symptom disorder into Hindi and determine their diagnostic accuracy against a diagnostic clinical interview.

Cross-sectional validation study.

Rural Kangra, Himachal Pradesh, northern India.

480 perinatal (pregnant or within 12 months postpartum) and non-perinatal (not currently pregnant and not given birth within 12 months) women at one tertiary hospital and district-level Anganwadi (community health) centres.

Symptom endorsement; and discriminant validity, sensitivity, specificity, positive and negative predictive values and area under the receiver operating characteristic curve (AUROC) of the Kessler Scale of Psychological Distress (K10), Patient Health Questionnaire (PHQ9), Edinburgh Postnatal Depression Scale (EPDS), Generalised Anxiety Disorder Scale (GAD7), Perinatal Anxiety Screening Scale (PASS), PTSD Checklist (PCL-5) and Scale for the Assessment of Somatic Symptoms (SASS).

Complete data were available for 443 participants. Tiredness and body weakness were the most commonly endorsed symptoms among participants with common mental disorders. Among perinatal participants, the AUROC was highest for the GAD7 (0.88, 95% CI 0.79 to 0.96) and SASS (0.84, 95% CI 0.71 to 0.96). Among non-perinatal participants, the AUROC was highest for the SASS (0.92, 95% CI 0.88 to 0.97) and PHQ9 (0.91, 95% CI 0.86 to 0.96).

Measures which assess for fatigue, tiredness and somatic symptoms may help to identify women experiencing common mental disorders in this setting. Small numbers of participants with clinically diagnosed mental disorders in our sample mean results must be interpreted cautiously.

NCT05485701.

A significant proportion of infants born at ≤29+6 weeks’ gestation develop lung disease during the neonatal period, thus putting them at risk of developing prematurity-associated lung disease in childhood and adulthood. After discharge from the neonatal unit, pre-existing lung disease in preterm-born infants is exacerbated by (often frequent) respiratory viral infections requiring greater health utilisation, including hospital admissions, than their term-born equivalents. Opportunities to prevent viral infections in infancy are largely limited to anti-respiratory syncytial virus (RSV) antibody prophylaxis and recently maternal RSV immunisation, but in term-born infants, trained immunity-based vaccines such as Bactek (MV130, Inmunotek, Spain) are increasingly used. Bactek provides a promising therapeutic avenue for preterm-born infants to target postdischarge respiratory viral infection in this vulnerable group of infants. The BALLOON study aims to assess this treatment in a very/extremely preterm-born population and determine if treatment with the trained immunity-based vaccine Bactek decreases the risk of unscheduled visits to healthcare professionals for lower respiratory tract infections, when compared with placebo. Included infants are born at ≤29+6 weeks’ gestation and treated daily from term-equivalent (37–43 weeks’ postmenstrual age, PMA) or from discharge, if earlier, up to 1 year of corrected age.

542 infants are being recruited prior to discharge by neonatal units in the UK. They are being randomised to receive Bactek or placebo, once daily dose of 2 sprays (each 0.1 mL) of IMP (300 Formazin Turbidity Units), from 37 to 43 weeks’ PMA or discharge if earlier up to 1 year of corrected age. The primary objective is to assess if sublingual Bactek spray decreases the risk of health professional diagnosed lower respiratory tract infections (LRTIs) (unscheduled visits to general practitioners, accident and emergency departments and hospital admissions) between enrolment and 1 year of corrected age. Secondary outcomes include the number of parent-reported, health professional-confirmed unscheduled visits for LRTIs, the time to first parent-reported, health professional-confirmed unscheduled visit for LRTI, parent-reported wheeze episodes (identification aided by WheezeScan (Omron, Japan)), parent-reported use of respiratory medications, growth (weight, length and head circumference), parent(s)/guardian(s) reported time missed from work and/or nursery time missed for the infant and volume of adverse reactions. Viruses associated with LRTIs will also be identified.

Ethics permission has been granted by the Wales Research Ethics Committee 3 (Ref 24/WA/0181), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (CTA reference 21323/0063/001-0004). The study is registered on ISRCTN (ISRCTN14019493). Findings will be disseminated via national and international peer-reviewed journals, and conferences. Oversight of the study is being provided by an Independent Data Monitoring Committee and an independent Trial Steering Committee (TSC). The Trial Management Group (TMG) meets every month.

ISRCTN14019493.

Poor access to surgical wound swabbing in the community often results in delayed or inappropriate antibiotic prescribing for surgical site infections. This delay can contribute to prolonged wound healing and poor antimicrobial stewardship. Patient self-swabbing at home could improve access to diagnostic testing, but its feasibility and acceptability remain unexplored.

TREASURE is a multicentre, mixed-methods feasibility study. A total of 40 patient participants and 10 staff stakeholders will be included. 40 adult patients undergoing cardiac surgery via median sternotomy will be recruited from Harefield Hospital (n=25) and the Royal Sussex County Hospital (n=15). Eligible participants will receive a coproduced self-swabbing set of instructions and kit at discharge and perform wound swabbing at home within 1–21 days, observed remotely by a researcher via Microsoft Teams. Swabs will be couriered to a central laboratory for bacterial culture with antimicrobial susceptibility testing for pathogens.

The primary feasibility outcome is the proportion of patients successfully completing self-swabbing at home to obtain usable culture swabs with samples received at the laboratory within 24 hours and deemed suitable for processing. Secondary safety and acceptability outcomes include usability of the kit and instructions; patient satisfaction; viability of samples for laboratory analysis; and recruitment and retention rates. A 30-day follow-up will capture wound complications, antibiotic prescribing and healthcare utilisation via patient questionnaires, case note review, general practitioner confirmation and patient interviews. 10 staff stakeholders will be interviewed to inform pathway development.

Quantitative data will be analysed descriptively, with proportions reported alongside 95% CIs. Qualitative data from patients will undergo thematic analysis, and stakeholder interviews will be coded using Normalisation Process Theory. An early health economic model will be developed to explore resource use, costs and proportions of appropriate and timely antibiotic use between current pathways and a proposed pathway, including self-swabbing.

West of Scotland Research Ethics Service has reviewed and approved the study (REC reference: 25/WS/0079). Findings will be disseminated through the study website, a webinar, peer-reviewed publications, conference presentations, patient and public involvement-led activities and engagement with National Health Service (NHS) stakeholders.

NCT07200401, ISRCTN28466609.

Within the UK there are 33 deaths every day from prostate cancer, second only to lung cancer as the most common cause of cancer death in males in the UK. Of the 55 000 new cases each year, up to 50% of these patients will receive radiotherapy either alone or after prostatectomy. Although there have been significant improvements in the accuracy of radiotherapy delivery leading to better tumour targeting and a reduction in dose to normal tissues, significant permanent genito-urinary or gastrointestinal-related side effects are all too common. With nearly 80% of patients with prostate cancer surviving for 10 years or more, minimising life-limiting radiation damage to normal tissues is vitally important. However, at present, it is not possible to identify which patients will suffer a poorer outcome after radiotherapy. The aim of this study, improving radiotherapy in PROState cancer using EleCtronic population-based healthCAre data (PROSECCA), is to do this by using the existing information in a patient’s digital healthcare record. By linking primary, secondary and tertiary clinical data, including digital image information, with radiotherapy treatment plans and outcome data, the PROSECCA study will identify de novo predictive biomarkers of radiation response and provide clinicians with a tool to individualise a radiotherapy dose and plan to maximise cure and minimise toxicity.

The PROSECCA study is a large multidisciplinary project, the purpose of which is to analyse healthcare records from up to 15 000 patients with prostate cancer who underwent radiotherapy in the treatment of their cancer in Scotland between 2010 and 2022. Through the linkage of data obtained specifically for radiotherapy and data held within each patient’s unique electronic health record (EHR), the factors that indicate why some patients have a poor response to treatment, or an increased risk of side effects from radiation, will be identified. This will be made possible by the use of artificial intelligence and machine learning (AL/ML), which will help to identify at-risk patients earlier and allow adaptation of their treatment accordingly.

The study is being conducted in accordance with the ethical principles set out in the Declaration of Helsinki and Good Clinical Practice that respects and protects the rights, and maintains confidentiality, of all trial participants. The study protocol (V.1.0) was reviewed by the South Central Oxford A Research Ethics Committee (REC) on 13 December 2021 and received a favourable opinion subject to each National Health Service (NHS) organisation confirming permission for patients treated within their area. Approval for the use of unconsented healthcare record data for patients included in the study and treated at one of the five Scottish Cancer Centres required an application to the NHS Scotland Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP). Full approval from the HSC-PBPP panel was received on 1 July 2024, which covered the use of pseudoanonymised EHR data for all patients participating in the study. The study is publicly listed on the NHS Health Research Authority site, with IRAS ID 306245 and REC reference 21/SC/0402. Dissemination of the study findings will take place through field-leading cancer, radiation oncology and medical physics journals. All manuscripts will be approved by the main study team and authorship determined by mutual agreement.

NCT06714630.

Meperidine, once viewed as relatively safe, is now discouraged in clinical settings due to its associated risks. Previous studies have identified a significant decrease in meperidine distribution across the USA from 2000 to 2021. Regional disparities accompanied this decline. The goal of this study was to investigate if the decrease in meperidine distribution has continued in recent years, 2019–2023, and if regional variations persist. This investigation also aimed to identify correlates of meperidine distribution, including adult obesity prevalence and annual income, to provide insight into the regional variation.

Retrospective observational study using data from the Automation of Reports and Consolidated Orders System Drug Retail Summary Reports by the Drug Enforcement Administration (DEA), the Centers for Disease Control and Prevention (CDC) and the US Census Bureau.

USA, including Puerto Rico.

US population.

The primary outcome was the meperidine distribution across the US between 2019 and 2023. Secondary outcomes included associations between meperidine distribution and adult obesity prevalence and median household income.

Total meperidine distribution across the USA dropped by 57.8% from 2019 to 2023. A substantial geographic variation was found with southern states accounting for the second, third and fourth highest in meperidine use per capita in 2023, only behind Puerto Rico. In contrast, northeastern states accounted for four of the five lowest states. A significant relationship was found between annual income and meperidine distribution in 2022 (r(49) = –0.38, p

Our study revealed a continued decrease in meperidine distribution and sustained presence of geographical variation from 2019 to 2023. Furthermore, novel relationships were identified between meperidine distribution, annual income and adult obesity prevalence.

Shared decision-making is widely advocated in policy and practice, but how it is to be applied in a high-stakes clinical decision such as major lower limb amputation due to chronic limb-threatening ischaemia or diabetic foot is unclear. The aim of this study was to explore the communication, consent, risk prediction and decision-making process in relation to major lower limb amputation.

A qualitative study (done as part of a broader mixed-methods study) using semi-structured interviews. Interview transcriptions were analysed using thematic analysis.

Vascular centres in three large National Health Service hospitals in Wales and England, UK, between 1 October 2020 and 30 September 2022.

A purposive sample of 18 patients for whom major lower limb amputation was considered as a treatment option/carried out, with interviews conducted before or within 4 months of amputation and 4–6 months after amputation. A further purposive sample of 20 healthcare professionals (including eight surgeons) involved in supporting or conducting major lower limb amputation decision-making.

Five major categories were identified that highlighted the challenges of ensuring shared decision-making associated with major lower limb amputation: (i) patients’ limited understanding, (ii) variable patient attitudes to decision-making, (iii) healthcare professionals’ perceived challenges to sharing decision-making, (iv) surgeons’ paternalism and (v) patients’ and healthcare professionals’ decisional regret/possible consequences of challenges.

Amputation is a life-changing decision for both patients and healthcare professionals, with huge consequences. Despite being considered the gold standard, our findings highlight several challenges to effective shared decision-making for major lower limb amputation. Shared decision-making training for healthcare professionals is paramount if these limitations are to be addressed and patients are to feel confident in being adequately informed about the treatment decisions that they make.

NCT04903756.

For people whose stroke risk would be reduced by taking a long-term oral anticoagulant (OAC), it is important to implement effective strategies to support medication initiation, adherence and persistence. To do this, a better understanding of the factors associated with implementation of interventions to optimise OAC management is needed.

This scoping review aimed to summarise the evidence-based characteristics associated with implementing interventions designed to optimise long-term OAC adherence.

Primary research (published post-2000) evaluating any intervention designed to optimise implementation of long-term OAC for stroke prevention by way of change in OAC services, staff or patient behaviour.

Five databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Cochrane Library) were searched from 1 January 2000 to 4 August 2023 using a combination of terms relating to population, intervention and study design.

Titles/abstracts were screened by at least one reviewer. Data from each full text were abstracted (with 20% double-checked for accuracy) and its implementation content reviewed, guided by the Expert Recommendations for Implementing Change strategies.

216 studies were included, with varying descriptive reporting of implementation strategies, and only 61 (28%) self-identifying as an implementation study. The median number of implementation strategies used was three, with recently published studies (2015 onwards), those including patients receiving either direct OACs (DOACs) or vitamin K antagonists (VKAs) and those including multiple intervention targets (service, staff or patients) associated with using more implementation strategies. ‘Train and educate stakeholders’ strategies were the most commonly used, and ‘Adapt and tailor to the context’ strategies were the least used by included studies. Conversely, self-defined implementation studies were less likely to use ‘Train and educate stakeholders’ strategies, although they were positively associated with use of ‘Adapt and tailor to the context’. ‘Use evaluative & iterative’ strategies were used more frequently in studies where patients used either VKAs or DOACs, or were published more recently.

Studies need to self-define as implementation studies, improve implementation strategy reporting and be transparently registered, alongside conducting process evaluations or more richly describing implementation processes. Future research could explore why some implementation strategies are used more than others and whether aligning strategy clusters with intervention targets results in clinically significant differences in patient care.

Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.

The primary objective of this clinical trial is to determine the clinical and cost-effectiveness of psychoeducation and emotional stabilisation (PES), together with eye movement desensitisation and reprocessing (EMDR) plus treatment-as-usual (TAU) in reducing symptoms of post-traumatic stress disorder (PTSD) among adults with intellectual disabilities compared with TAU. Secondary objectives include: (1) determining whether PES/EMDR plus TAU is superior to TAU in improving mental health problems and quality of life (QoL) among adults with intellectual disabilities who had a diagnosis of PTSD and (2) completing a process evaluation to examine intervention implementation and acceptability.

This is a two-arm parallel single-blind randomised controlled trial comparing PES-EMDR+TAU to TAU including an internal pilot phase. Outcome data will be captured prior to randomisation, and at 4 (after PES), 8 (after EMDR) and 14 months postrandomisation by masked assessors. 144 adults with intellectual disabilities with a diagnosis of PTSD will be allocated (1:1) randomly using minimisation from National Health Service (NHS) community and inpatients services for adults with intellectual disabilities in England. Participants are eligible to take part in this trial if: (1) they are aged 18 or older, but younger than 66, (2) have a Full Scale IQ

The primary outcome will be assessed using an intention-to-treat analysis. Baseline characteristics will be compared between arms to determine whether any potentially influential imbalance occurred. The primary outcome will be analysed by analysis of covariance, adjusting for baseline values of the outcome and any variables used in the randomisation process. Secondary outcomes will be analysed using linear or logistic regression models as appropriate reflecting the distribution of the outcome variable. The treatment effect will be estimated as an adjusted difference between sample means, presented with 95% CIs and p values. A complier average causal effect analysis will be considered should the data availability be sufficient to estimate the impact of non-compliance. A series of subgroup analyses on the primary outcomes will be considered considering differences in the Impact of Event Scale–Intellectual Disabilities scores at 14 months for (1) differing levels of general intellectual functioning and (2) PTSD versus complex PTSD.

This clinical trial was designed to allow for conclusions about whether PES/EMDR+TAU is efficacious in reducing symptoms of PTSD, relative to TAU, for adults with intellectual disabilities. A favourable ethical opinion has been received from an NHS ethics committee in the UK. The findings from this trial will be published within peer-reviewed journals and shared at national and international conferences. We will also aim to record and distribute podcasts detailing our findings together with our partners.

ISRCTN35167485.

Global migration has steadily risen, with 16% of the UK population born abroad. Migrants (defined here as foreign-born individuals) face unique health risks, including potential higher rates and delays in diagnosis of infectious and non-communicable diseases, compounded by significant barriers to healthcare. UK Public Health guidelines recommend screening at-risk migrants, but primary care often faces significant challenges in achieving this, exacerbating health disparities. The Health Catch-UP! tool was developed as a novel digital, multidisease screening and catch-up vaccination solution to support primary care to identify at-risk adult migrants and offer individualised care. The tool has been shown to be acceptable and feasible and to increase migrant health screening in previous studies, but to facilitate use in routine care requires the development of an implementation package. This protocol describes the development and optimisation of an implementation package for Health Catch-UP! following the person-based approach (PBA), a participatory intervention development methodology, and evaluates our use of this methodological approach for migrant participants.

Through engagement with both migrants and primary healthcare professionals (approximately 80–100 participants) via participatory workshops, focus groups and think-aloud interviews, the study aims to cocreate a comprehensive Health Catch-UP! implementation package. This package will encompass healthcare professional support materials, patient resources and potential Health Catch-UP! care pathways (delivery models), developed through iterative refinement based on user feedback and behavioural theory. The study will involve three linked phases (1) planning: formation of an academic–community coalition and cocreation of guiding principles, logic model and intervention planning table, (2) intervention development: focus groups and participatory workshops to coproduce prototype implementation materials and (3) intervention optimisation: think-aloud interviews to iteratively refine the final implementation package. An embedded mixed-methods evaluation of how we used the PBA will allow shared learning from the use of this methodology within the migrant health context.

Ethics approval granted by the St George’s University Research Ethics Committee (REC reference: 2024.0191). A community celebration event will be held to recognise contributions and to demonstrate impact.

Peripheral arterial disease (PAD) commonly coexists with chronic kidney disease (CKD). Patients with symptomatic PAD often require endovascular revascularisation to relieve pain or salvage limbs. However, the iodinated intra-arterial contrast routinely used in these procedures is nephrotoxic, placing patients with CKD at increased risk of acute kidney injury (AKI) and long-term renal decline. Carbon dioxide (CO₂) delivered via automated injection is a potential alternative imaging contrast medium. This trial will evaluate whether using CO₂ instead of iodinated contrast reduces the risk of AKI and short-term renal function decline in this high-risk group.

This is a multicentre, open-label, prospective randomised controlled trial across six secondary-care National Health Service (NHS) vascular surgery centres. A total of 174 patients with PAD and CKD undergoing endovascular intervention will be randomised 1:1 to receive iodinated contrast (standard of care) or CO₂ via automated injector (Angiodroid). All perioperative care will follow local NHS protocols.

The primary outcome is log serum creatinine at 2, 30 and 90 days postprocedure. Key secondary outcomes include: incidence and severity of AKI within 48 hours postprocedure, major adverse kidney events (death, dialysis or >25% estimated glomerular filtration rate decline) by 90 days, inpatient length of stay, procedural pain, quality of life, procedural success, reinterventions, acceptability and feasibility (patient/practitioner questionnaires) of using CO₂, and cost-effectiveness (healthcare resource use analysis). A mixed-methods process evaluation will be undertaken with patients and clinicians.

The trial has been approved by an NHS ethical review committee (24/WA/0332) and patients have been involved in trial design. Findings will be disseminated to participants, clinicians and the wider public through patient groups, lay summaries, social media, conferences, peer-reviewed journals and NHS policy channels.

ISRCTN23564393.

When deciding acute healthcare delivery location, multiple factors should be considered, including risks associated with potential care locations and the willingness of decision stakeholders to take those risks. Individual risk tolerance potentially informs these choices. We therefore aimed to investigate the risk tolerance of staff, patients and carers in front-door and ambulatory care units.

Several variants of the ‘multiple price list’ method of risk tolerance assessment were employed. The different variants covered financial and health outcomes, and known and unknown odds in the ‘risky’ options. For financial outcomes, participants made seven choices between a guaranteed (eg, £70) and risky (eg, chance of £20 or £160) outcome, with the higher quantity in the risky outcome increasing with each choice, in six ‘lottery sets’. For health outcomes, participants made choices between a guaranteed and risky outcome measured in number of healthy days.

Staff, patients and carers were recruited from front-door and ambulatory care units in the UK.

Risk tolerance was the primary outcome measure and was established in two ways—number of times the guaranteed option was chosen, and the point where participants switched from the guaranteed to the risky option.

Among 338 participants, a wide range of risk tolerance levels were demonstrated, and three key findings were identified—participants were less risk tolerant in health-based than financial decisions; older people had a more dichotomised approach to health risk-taking than younger people; and patients could engage in informed, structured discussions about risk, including when acutely unwell.

These findings suggest that, while stakeholders in location-of-care decisions may have different risk tolerance levels, they can engage in structured discussions about risk, which should inform shared decision-making. Additionally, older patients, who constitute a significant proportion of hospital attendees, may be more willing to take health-based risks than younger people. Future work may benefit from formal exploration of people’s rationale for their decisions and may be considered in other clinical settings.

To develop and validate a polycystic ovary syndrome (PCOS) case definition using administrative health data sources.

A validation study.

Secondary care centre outpatient gynaecology clinic in Calgary, Alberta, Canada.

3951 electronic health records of women aged 18–45 years who presented to a gynaecology clinic in Calgary, Canada, between January 2014 and December 2019 were reviewed. We identified 180 patients with PCOS using the Rotterdam criteria. Participants were excluded if they were biologically male, pregnant at the time of the consultation, did not meet the date criteria or if their consultation note was missing. The chart data were connected to the Practitioner Claims and the Discharge Abstract Database by personal health number.

Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 68 case definitions for PCOS were estimated. Case definition performance was graded.

Of the 68 case definitions tested, none had high validity. The best performing case definitions were: (1) ≥3 instances of International Classification of Diseases-9 code 256.4 (polycystic ovaries) with exclusion codes (sensitivity 23.89%, specificity 99.59%, PPV 74.14%, NPV 96.35%) and (2) 626.X (irregular menstruation), 704.1 (hirsutism) and ≥3 instances of code 256.4 with exclusion codes (sensitivity 2.78%, specificity 99.97%, PPV 83.33%, NPV 95.40%).

We identified several case definitions for PCOS of moderate validity with high PPV (>70%) for case ascertainment in PCOS research in jurisdictions with similar administrative health data. These case definitions are limited by low sensitivity, which should be considered when interpreting research findings.

The incidence of anal carcinoma is increasing, with the current gold standard treatment being chemoradiotherapy. There is currently a wide range in the radiotherapy dose used internationally which may lead to overtreatment of early-stage disease and potential undertreatment of locally advanced disease.

PLATO is an integrated umbrella trial protocol which consists of three trials focused on assessing risk-adapted use of adjuvant low-dose chemoradiotherapy in anal margin tumours (ACT3), reduced-dose chemoradiotherapy in early anal carcinoma (ACT4) and dose-escalated chemoradiotherapy in locally advanced anal carcinoma (ACT5), given with standard concurrent chemotherapy.

The primary endpoints of PLATO are locoregional failure (LRF)-free rate for ACT3 and ACT4 and LRF-free survival for ACT5. Secondary objectives include acute and late toxicities, colostomy-free survival and patient-reported outcome measures. ACT3 will recruit 90 participants: participants with removed anal tumours with margins ≤1 mm will receive lower dose chemoradiotherapy, while participants with anal tumours with margins >1 mm will be observed. ACT4 will recruit 162 participants, randomised on a 1:2 basis to receive either standard-dose intensity modulated radiotherapy (IMRT) in combination with chemotherapy or reduced-dose IMRT in combination with chemotherapy. ACT5 will recruit 459 participants, randomised on a 1:1:1 basis to receive either standard-dose IMRT in combination with chemotherapy, or one of two increased-dose experimental arms of IMRT with synchronous integrated boost in combination with chemotherapy.

This study has been approved by Yorkshire & The Humber – Bradford Leeds Research Ethics Committee (ref: 16/YH/0157, IRAS: 204585), July 2016. Results will be disseminated via national and international conferences, peer-reviewed journal articles and social media. A plain English report will be shared with the study participants, patients’ organisations and media.

ISRCTN88455282.

Distal radius fractures are the most common fractures seen in the emergency department in children in the USA. However, no established or standardised guidelines exist for the optimal management of completely displaced fractures in younger children. The proposed multicentre randomised trial will compare functional outcomes between children treated with fracture reduction under sedation versus children treated with simple immobilisation.

Participants aged 4–10 years presenting to the emergency department with 100% dorsally translated metaphyseal fractures of the radius less than 5 cm from the distal radial physis will be recruited for the study. Those patients with open fractures, other ipsilateral arm fractures (excluding ulna), pathologic fractures, bone diseases, or neuromuscular or metabolic conditions will be excluded. Participants who agree to enrol in the trial will be randomly assigned via a minimal sufficient balance algorithm to either sedated reduction or in situ immobilisation. A sample size of 167 participants per arm will provide at least 90% power to detect a difference in the primary outcome of Patient-Reported Outcomes Measurement Information System Upper Extremity computer adaptive test scores of 4 points at 1 year from treatment. Primary analyses will employ a linear mixed model to estimate the treatment effect at 1 year. Secondary outcomes include additional measures of perceived pain, complications, radiographic angulation, satisfaction and additional procedures (revisions, refractures, reductions and reoperations).

Ethical approval was obtained from the following local Institutional Review Boards: Advarra, serving as the single Institutional Review Board, approved the study (Pro00062090) in April 2022. The Hospital for Sick Children (Toronto, ON, Canada) did not rely on Advarra and received separate approval from their local Research Ethics Board (REB; REB number: 1000079992) on 19 July 2023. Results will be disseminated through publication in peer-reviewed journals and presentations at international conference meetings.

NCT05131685.

Persistent pain is common among older people living with frailty and can impact on their daily living, mobility, social interactions and sleep. However, healthcare support to mitigate impact is lacking in this population. The Pain in Older People with Frailty (POPPY) study is a multiphase, mixed-methods study that addresses how pain management services for older people with frailty should be organised and delivered.

For this phase (POPPY-Q), we used qualitative methods: semi-structured interviews with a grounded theory approach to analysis.

Community-dwelling older people (≥75 years) with persistent pain and frailty were invited to participate in two qualitative interviews (in-person/remotely) 10 weeks apart. Interviews took place in varied geographical locations across England between July 2022 and August 2023 and explored experiences of living with pain and access to and engagement with services and healthcare professionals (HCPs) and support and treatments received for pain.

Twenty-six people (77–91 years) with pain and frailty (from mild to severe) consented and were interviewed; 24 completed a second interview. Three interviews included a spouse/family member. Themes were general health and well-being; pain and its impact; acceptance of living with pain; support-seeking decisions; experience of accessing support; and perception/experience of pain support and treatment. This paper focuses on pain acceptance and support-seeking; other themes are used contextually, and accessing support was rare. Many participants were stoical about pain; some prioritised other health conditions; some preferred self-management; some were resigned and had lost hope of effective treatment; some expressed concern about burdening healthcare resources.

HCPs should be aware of the stances of older people with frailty about seeking support for pain and should be proactive, asking about pain. Longer appointments for complex cases may allow general practitioners to address pain, offer reassurance, provide information or referral or arrange a follow-up consultation focused on pain management.

The development of the target trial emulation (TTE) methodology has enhanced the conduct of non-randomised studies. By leveraging readily available routinely collected data, TTEs offer opportunities for complementing randomised controlled trials (RCTs), providing more precise estimates and improving the external validity of RCTs. To explore this potential, we selected a successfully completed RCT as a case study. In the FIRST-line support for Assistance in Breathing in Children (FIRST-ABC) step-up RCT, high flow nasal cannula (HFNC) was found to be non-inferior to continuous positive airway pressure (CPAP) in terms of time to liberation from respiratory support in the paediatric critical care setting. We will emulate the FIRST-ABC step-up trial using routinely collected data from the Paediatric Intensive Care Audit Network (PICANet) database.

This is a protocol for a TTE that will use longitudinally collected data from the PICANet database. The study aims to emulate the FIRST-ABC step-up RCT using an observational study design in a frequentist framework. We will benchmark the results against the published trial. The study will apply a new-user design by selecting children admitted to paediatric intensive care units that started HFNC or non-invasive ventilatory support (as a surrogate for CPAP). The eligibility criteria and selected outcomes will reflect those of FIRST-ABC within the constraints of the available routinely collected data. We will use advanced quantitative doubly robust methods to minimise the impact of confounding by indication and allow for heterogeneity according to child characteristics. The analysis will be repeated using a Bayesian approach for follow-up research.

The research received ethics approval from the London School of Hygiene & Tropical Medicine Research Ethics Committee. This study will expand the findings from the FIRST-ABC step-up RCT, providing additional insight from a large representative sample using real-world data. The frequentist and Bayesian approaches will enable a discussion about the advantages and drawbacks of the two strategies. The results will be disseminated to the research and clinical community and made accessible to the public. In addition, the study results will be used in future research, which aims to supplement RCTs with additional evidence from a TTE.