BMJ Open Respiratory Research

Objective: Several endotypes contribute to the development of Obstructive Sleep Apnea (OSA). However, efforts to measure these endotypes have been challenging. In this paper, we propose a new method that overcomes some of these challenges. Methods: To test the feasibility of this new method, data from the Sleep Heart Health Study (SHHS) were analyzed and two oxygen-based endotypes were identified and plotted on a graphical model: the steady-state SpO2 and the SpO2 arousal threshold. The first is the oxygen saturation that would occur during sleep if there were no arousals, and it is a measure of upper airway collapsibility (a more collapsible airway produces a lower SpO2). The latter is the oxygen saturation that triggers arousals. These endotypes were validated by assessing their ability to detect positional and state-related changes in airway collapsibility and arousal threshold. Results: The study showed that it was feasible to measure oxygen-based endotypes in 95% of SHHS participants. As expected, steady-state SpO2 was lower during supine vs. non-supine sleep, as well as during REM vs. NREM sleep. Also, the SpO2 arousal threshold was similar between supine and non-supine sleep. However, SpO2 arousal threshold was not lower in REM sleep vs. NREM sleep. Therefore, in 3 of the 4 conditions, the oxygen-based endotypes moved in the expected direction due to positional or sleep state changes. Conclusion: Although further validation experiments are required, this study indicates that OSA endotyping using the pulse oximetry signal is feasible. The oxygen-based endotypes could be used to aid therapeutic decision making.

Purpose: The purpose of this study was to examine the barriers and facilitators experienced by non-U.S. born persons during the diagnosis and treatment of latent tuberculosis infection (LTBI) in primary care settings, including the impact of culturally and linguistically congruent care navigation. Design: 25 interviews with non-U.S. born patients, along with focus groups and surveys with 31 primary care team members and leadership, were conducted. Setting: The study was conducted within a network of Federally Qualified Health Center (FQHC) clinics. Participants: Participants were adult non-U.S. born patients with LTBI and FQHC care team members. A purposefully selected subsample of randomized participants was interviewed. Intervention: Care navigators followed participants randomized to receive care navigation after a positive test for tuberculosis (TB) infection and offered health navigation and education about the importance of TB screening and treatment. Method: Data collection was followed by thematic analysis guided by a critical ideological paradigm. Results: Culturally and linguistically congruent navigation emerged as central to potentially reducing barriers, fostering trust, and improving treatment continuity. Participants without navigation support reported confusion and disengagement from care, while those with culturally aligned navigators described clarity and comfort, with influence overall by intrinsic motivation, relational support, and culturally shaped beliefs about care. Conclusion: Care navigation that includes culturally and linguistically congruent navigators whenever possible may help increase LTBI treatment completion among non-U.S. born populations. Limitations of the study include the potential influence of cultural norms, power dynamics, and selection bias.

Background. Capillary refill time is a resuscitation target in septic shock,1-4 but bedside measurement is examiner-dependent. An ICU monitor co-records a photoplethysmogram on the pulse oximeter and intermittent noninvasive blood pressure cuff cycles; if the probe and the cuff share a limb, each cycle is an unplanned vascular occlusion test on the distal microvascular bed. Standard practice places the two on opposite limbs. Objective. To measure how often, in MIMIC-IV-WDB v0.1.0, charted cuff cycles show the photoplethysmographic morphology expected of a same-limb cuff and probe, and to characterize the candidate capillary refill-like signal when that morphology is present. Methods. MIMIC-IV-WDB v0.1.05 was linked to the MIMIC-IV clinical database.6 A pre-registered rule-based detector identified candidate occlusion-reperfusion signatures on the 1-Hz perfusion-index envelope around each charted cuff timestamp. The primary endpoint was the proportion of cuff cycles suitable for analysis that were detector-positive at a 15-second reperfusion threshold, with 95% confidence intervals estimated by resampling patients at a fixed seed. A secondary analysis used a locally hosted multimodal language model (a Gemma-3 derivative on a non-device server) to adjudicate the same signature on perfusion-index plots; no MIMIC-IV-WDB content left the workstation. Results. Of 9,224 charted cuff cycles, 8,909 had a usable pulse-oximeter waveform, and 268 cycles in 15 patients (4.30% of the 6,236 cuff cycles suitable for analysis, 95% CI 2.60 to 6.03) met the primary 15-second threshold. The language model adjudicated the same cycles and called 1,367 of the 8,909 cycles with a usable waveform (15.34%) signature-present, roughly five times the detectors count. Because no laterality ground truth exists, agreement with a single blinded reader served as the comparator rather than accuracy. The two methods were about equally concordant with the reader: precision was 0.25 (95% CI 0.14 to 0.39) for the detector and 0.24 (95% CI 0.10 to 0.35) for the language model, although reweighting to the full population of cycles with a usable waveform lowered the language model to 0.030 (95% CI 0.009 to 0.053). These estimates are reference-limited: a blinded re-read of a 150-card subsample showed only moderate intra-rater reliability (Cohen {kappa} 0.46 to 0.59) with systematic undercalling on the first pass, and rescoring against the corrected re-read roughly doubled precision for both methods. Conclusions. Opportunistic extraction of capillary refill-like signals from archived ICU pulse oximetry is limited in two distinct ways. First, sensor geometry limits how often the signal is recordable: cuff cycles rarely show the morphology expected of a same-limb cuff and probe pair, consistent with opposite-limb placement, so the bottleneck is geometry rather than signal processing. Second, the modest reliability of morphology adjudication limits how well any single flagged cycle can be confirmed: against a blinded reader the detector is a usable screen but a noisy confirmer, the reference is itself only moderately reliable, and the language model is no more concordant despite flagging many more cycles. The minority of cycles in which the morphology appears contain a candidate signal that may merit prospective study under controlled placement with laterality recorded.

Background Chronic pain is common in adults aged 85 years and older (85+) and is associated with detrimental outcomes. Chronic pain guidelines advise first line management with non-pharmacological measures; paracetamol and non-steroidal anti-inflammatory drugs are the preferred analgesics. Challenges in accessing non-pharmacological therapies for adults aged 85+, and the presence of multimorbidity and polypharmacy, mean that opioid medication is often prescribed for chronic pain despite the potential for opioid-related adverse effects and guidance identifying long-term opioids for chronic pain as a potentially inappropriate prescription. Aim This study aims to explore patient, caregiver, and healthcare professional perspectives on the prescription of opioid medications for pain management for chronic pain in adults aged 85+ to support development of resources for optimising opioid prescribing. Design and Setting In this qualitative study, participants were recruited through primary care, in the community or in care home settings. Method 36 semi-structured interviews were conducted with care home residents and community dwellers aged 85+ (n=12), caregivers (informal and care home staff) (n=12), and healthcare professionals (n=12). Interviews were transcribed and analysed using reflexive thematic analysis. Results Four themes were developed: contextual complexity, satellite influences, balancing act, and pragmatic prescribing. Using opioids in adults aged 85+ is a balancing act to support patients best possible quality of life within their unique circumstances whilst using the pain management tools available. Conclusion Opioids continue to have an important role in pain management in adults aged 85+ largely due to paucity of alternatives and the drive to support quality of life.

Background Sierra Leones neonatal mortality rate is among the highest in the world. Koidu Government Hospital opened a Special Care Baby Unit (SCBU) in 2020. To increase knowledge of the SCBU health care providers (HCPs), a neonatal curriculum was implemented to facilitate HCP education on management of neonatal conditions. The aim of this study was to understand the effect of the curriculum on knowledge acquisition and the perception of the teaching methodologies among participating HCPs. Methods US-based mentors facilitated a two-phase, flipped classroom, virtual neonatal medicine curriculum between October 2024 and April 2025, followed by one-week in-person education sessions with SCBU HCPs. With each phase, participants completed pre- and post-test educational assessments. At the end of the curriculum, they completed a subjective assessment to capture perceptions related to the quality of teaching methodologies integrated within the curriculum. Wilcoxon signed rank test was used to assess pre- versus post-test change. Descriptive statistics were used to analyse the subjective assessment. Results Thirty-eight participants completed the educational assessments, 30 (79%) took all four pre- and post-tests; 25/38 (65.8%) were female, 27 (71.1%) were nurses. Median correct answers for both phases increased from the pre- to post-test for individual learners [Phase 1, pre-test 14/27 (51.9%), post-test 23/27 (85.2%), p<0.001], [Phase 2, pre-test 14/25 (56.0%), post-test 23/25 (92.0%), p <0.001]. Thirty-one participants completed the subjective assessment, of whom 96.8% (30/31) rated the curriculum to be "very effective." All 31 participants indicated that the in-person instruction was "very helpful." Through open text responses, they offered valuable insight into challenges, strengths, and next steps. Conclusion This neonatal curriculum resulted in significantly increased knowledge and was well regarded. Adapting this curriculum or similar curricula show promise to improve the quality of care for small and/or sick neonates in low resource settings.

Aim: Healthy Heart Actions Right Time (HHART) is a multi-phased research project that seeks to identify, implement and evaluate strategies to connect community and clinical activities to reduce the burden of heart disease for Aboriginal and Torres Strait Islander people. The aim in Phase One was to identify priority activities for two participating services. Background: The ongoing effects of colonisation drive a disproportionate burden of heart disease for Aboriginal and Torres Strait Islander people. Clinical and community groups both have established strengths in reducing the risk of heart disease, but these are not always well connected. Methods: Using a case study methodology in two locations we partnered in a 12-month co-design process to identify priority activities to connect clinical and community activities. Findings: Three priorities emerged from the Phase One co-design process: (i) community-led gardening as a strategy to promote heart health through connection and healthy lifestyles; (ii) community days to increase engagement in heart checks and strengthen community-clinic relationship; and (iii) clinic-led development of culturally relevant education resources to promote clinician confidence and community heart health knowledge.

Background: 48,XXYY syndrome is a rare sex chromosome aneuploidy (SCA) characterized by neurodevelopmental deficits and medical comorbidities. The limited information available in the literature is almost exclusively limited to postnatally diagnosed cases. This study aims to describe the early medical and developmental features of prenatally identified 48,XXYY infants, with comparisons to 47,XYY, 47,XXY cohorts, and typical populations, as well as previously reported postnatally diagnosed 48,XXYY cases. Methods: The eXtraordinarY Babies Study prospectively follows children prenatally identified to be at high risk for SCA with annual medical and neurodevelopmental evaluations. Data presented herein include the prevalence of medical conditions, developmental milestones, developmental and adaptive functioning assessment scores, and therapy utilization in participants confirmed to have 48,XXYY. Comparisons were made between this cohort and the typical population, infants with 47,XYY and 47,XXY also enrolled in the eXtraordinarY Babies Study, and a 2008 cohort of individuals postnatally identified 48,XXYY. Results: Infants with 48,XXYY exhibited a range of early medical features, including high rates of feeding and GI disorders (breastfeeding difficulties, gastroesophageal reflux, and eosinophilic esophagitis), allergic disorders (food allergies and environmental allergies), and hypotonia. Developmental and adaptive functioning scores indicated delays in motor, communication, and social domains, with nearly all infants receiving speech therapy, physical and/or occupational therapy. Comparisons with the 47,XYY and 47,XXY cohorts revealed more medical and developmental challenges in the 48,XXYY group, however there was variability and some overlap with both the general population and sex chromosome trisomy conditions. Additionally, comparison to the 2008 postnatally identified 48,XXYY cohort indicated that while prenatal diagnosis allowed for earlier intervention, developmental outcomes in the first years of life were similar between the two groups. Conclusions: 48,XXYY diagnosed prenatally facilitates early monitoring, anticipatory guidance, and proactive referrals for medical evaluations and intervention, given developmental delays and medical challenges are more common in infancy and early childhood compared to the general population and trisomy SCAs. These findings provide valuable insights for genetic counselors and healthcare providers, emphasizing the spectrum of medical and developmental findings and importance of early and proactive care to support individual outcomes. Prospective study of this prenatally identified cohort will provide important natural history and phenotypic variability in XXYY, as well as identification of predictors of health and developmental outcomes.

Objectives People with mental health conditions experience increased rates of diagnostic errors and delays in acute treatment. While causes such as diagnostic overshadowing (misattribution of physical symptoms to mental health conditions) are well documented, less attention has been paid to the organisational and structural conditions that shape diagnostic work. This study examines how physical illness is diagnosed in patients with mental health conditions in emergency departments (EDs), with a focus on the structural conditions that enable or constrain safe diagnostic practice. Method We conducted a multi-site ethnography across three purposively selected EDs in England between April 2023 and April 2024, varying in size, population demographics, and local service configuration. Data were collected through 284 hours of non-participant observation and 20 semi-structured interviews with ED staff. Results Our analysis identified four recurring structural gaps that shaped the conditions under which physical health diagnosis took place for patients with mental health conditions: a design gap, whereby targets and physical layouts constrained diagnostic reasoning; a preparedness gap, reflecting the lack of structural support to allow staff to act on their existing knowledge and skills; a coordination gap, reflecting fragmented ownership and the challenges of joint assessment across mental and physical healthcare teams; and an expectation gap, whereby unmet need elsewhere in the system increased demand for ED services that were beyond its formal scope. These gaps made diagnostic errors and delay more likely for patients with mental health conditions seeking physical healthcare in the ED. Conclusions As new dedicated mental health EDs are introduced in England, there is an opportunity to avoid reproducing these structural gaps in new settings. Our study suggests that improving physical healthcare for patients with mental health conditions requires changes to how EDs are designed, resourced and supported, and how they connect with the wider health and care system. Keywords: mental health, diagnostic inequality, emergency departments

Purpose In deprescribing studies, a prescription-free gap is typically used to determine if patients discontinued their treatment. An appropriate gap depends on the typical time between prescriptions during continued use. This work aims to characterise the interval between prescriptions of chronic drugs using different methods for a cohort of older people in primary care in Ireland. Methods The empirical prescription interval was analysed for 38,154 patients for the twenty most common drug classes and the association between covariates and the interval was analysed using a multi-level model. Estimates were also compared to those obtained from the parametric waiting time distribution (pWTD) approach. Results Available covariates had consistent relationships with prescription intervals across drug classes. For example, each additional prescription issue was associated with an increase in the interval by 5.0 (NSAIDs) to 19.7 days ("Other antidepressants"). Full public health cover was associated with a -29.0 day (inhaled adrenergics) to -11.0 day (opioids) change relative to partial cover, while other/private cover had a -17.9 day (benzodiazepines and associated drugs) to -7.1 day (SSRI and SNRIs) change relative to partial cover. The pWTD also produced consistent estimates of the population interval for most drugs. Conclusions The interval varied substantially within drug classes, due to a mixture of patient, practice and unmodelled factors. Variation between practices was effectively explained, with residual variation between patients and within patients. The pWTD approach is useful for describing complex distributions of intervals, and may be more appropriate for inferring a gap than summarising truncated data.

OBJECTIVE: Bladder cancer (BC) is predominantly a disease of older, comorbid adults, and radical cystectomy (RC), which is the gold standard treatment, carries considerable morbidity. We sought to determine the impact of baseline dementia and frailty on the care trajectory beyond the immediate postoperative period. We hypothesized that frail patients and those with dementia undergoing RC for BC will have poorer care trajectories. METHODS AND MATERIALS: We identified Medicare beneficiaries [&ge;] 66 years old who underwent RC for BC in 2017 with 12 months of pre- and post-RC enrollment. Frailty and dementia were characterized using validated, claims-based measures. Associations between baseline frailty and dementia with postoperative care trajectory outcomes were determined using Fine-Gray competing risk models. RESULTS: We identified 3,600 beneficiaries of whom 11.6% were frail and 3.4% met criteria for dementia. Patients with dementia were more likely to be frail, comorbid, and not receive standard-of-care neoadjuvant chemotherapy. Frailty was independently associated with [&ge;] 2 transitions in care level after index discharge from RC and skilled nursing facility (SNF) admissions within 1 year of RC, exposure to intensive post-RC interventions, including dialysis and feeding tube placement, and poorer survival. Dementia remained associated with SNF admissions regardless of frailty level. CONCLUSIONS: Among a contemporary cohort of older adults undergoing RC for BC, preoperative dementia and frailty were independently associated with poorer care trajectory beyond the immediate postoperative period after RC. Our work highlights a role for preoperative geriatric assessment in identifying and optimizing patients at greatest risk.

Background One in four surgical patients carries a drug allergy label, of which an estimated 90% are incorrect. Avoidance of first-choice drug therapies may lead to worse postoperative outcomes. We sought to determine the nature and extent of any association between drug allergy labels and postoperative complications. Methods A multicentre observational study in 21 NHS hospitals. Eligible patients were 18 years or older, undergoing common surgical procedures: primary hip or knee replacement; internal fixation of closed long bone fracture; colorectal resection; trans-urethral resection of prostate or bladder tumour; caesarean section; hysterectomy. Exclusion criteria: use of antibiotics in the two weeks prior to surgery, previous participation in the study. Primary outcome was postoperative complications within 30 days following surgery, a composite outcome comprising: all postoperative infections, anastomotic leak, acute respiratory distress syndrome, myocardial infarction, postoperative bleed, pulmonary embolism, stroke, antimicrobial side effects, death. Results Among 13,646 patients, 3924 (29%) carried greater than or equal to1 drug allergy labels. Labelled patients were more likely to develop postoperative complications (989/3924 (25%) vs 1926/9722 (20%); OR 1.21 [1.10-1.34]; p<0.001). They were more likely to develop surgical site infections (337/3924 (9%) vs 760/9722 (8%); OR 1.19 [1.03 -1.38]; p<0.018), and any postoperative infection (750/3924 (19%) vs 1472/9722 (15%); OR 1.24 [1.11-1.38] p<0.001). Labelled patients experienced increased risk of allergic drug reactions (31/3924 (0.01%) vs 29/9722 (<0.01%); OR 3.00 [1.77-5.09]; p<0.001), but no increase in mortality. Conclusions Drug allergy labels are common, but often incorrect. Labelled patients experience worse postoperative outcomes, including infective and non-infective complications and increased risk of allergic drug reactions. Trial registration Registered with ISRCTN registry, ISRCTN15775657.

Introduction: Hypertension is the world's leading cause of death, and depression its leading cause of disability. Control rates for these noncommunicable diseases (NCDs) are low in low and middle-income countries (LMICs). Many LMICs have programs to screen and treat underserved communities for infectious diseases, but evidence to adapt them to treat NCDs is limited. We developed and tested a non-communicable disease program through Ghana's Community-Based Health Planning and Services (CHPS) primary care initiative. Methods: We trained 8 CHPS nurses to diagnose and treat hypertension and depression through door-to-door screening and pharmacotherapy. Physician assistants provided telehealth supervision. We combined this treatment with volunteer counseling to boost medication adherence, improve mood, and change health behaviors. We called the 90-day intervention the CHPS Opportunity for Mentally and Behaviorally Integrated NCD Engagement (COMBINE). Results: We recruited 60 adults from 580 screened: 37 with hypertension (mean blood pressure (BP) of 149/91 mm Hg) and 23 with depression (mean physician health questionnaire (PHQ-9) score of 13.3). After 90 days, 57/60 (95%) completed the intervention: 32/37 (86%) achieved blood pressure control (mean BP 122/75 mm Hg), and 19 of 20 (95%) achieved depression control (mean PHQ-9 score 2.0). After 12 months, 51/60 were retained: 33/37 with hypertension (89%) and 18/23 with depression (78%), with a mean BP of 121/75 and PHQ-9 score of 1.4 respectively. All 51 (100%) achieved disease control at 12 months. 5 persons left by migration and 4 by escalation to higher-level care. Conclusions: The COMBINE model achieved high levels of diagnosis, care retention, and disease control, with minimal adverse events, in a remote setting with limited usual NCD care. This model suggests a novel means to improve the care cascade for these and other noncommunicable diseases through existing non-physician care models in LMICs, warranting further controlled testing at scale.

Background. Tobacco smoke exposure, quantified by serum cotinine, is associated with cardiovascular, metabolic, and sleep-related health risks. The relationship between biomarker-verified tobacco smoke exposure and objectively measured, free-living wrist-worn ambient light patterns has not been examined in a nationally representative U.S. adult sample. Methods. We analyzed NHANES 2011-2014 cross-sectional data from 6,937 adults aged >20 years with valid serum cotinine and wrist-worn Physical Activity Monitor (PAM) ambient light data. Seven light outcomes were modeled using survey-weighted linear regression with log2(cotinine+1) as the continuous exposure across four covariate adjustment levels. Benjamini-Hochberg false discovery rate (FDR) correction was applied across the 7 outcomes within each model. Results. In Model 2 (adjusted for age, sex, race/ethnicity, education, poverty-income ratio, BMI, and survey cycle; N = 6,350), higher serum cotinine was associated with significantly higher nighttime light (beta = +0.024, 95% CI: 0.010, 0.038; p-FDR = 0.014) and lower evening light (beta = -0.031, 95% CI: -0.055, -0.008; p-FDR = 0.042). In exploratory behavioral models without alcohol (Model 3a; N = 5,766), both nighttime and evening associations remained FDR-significant. After additional adjustment for alcohol, which substantially reduced the sample due to 37.6% missingness (Model 3b; N = 3,866), the nighttime association attenuated below the FDR threshold, while the evening association remained FDR-significant. Categorical analyses showed progressively higher nighttime light across cotinine groups, and a hypothesis-generating sex interaction was identified (p-interaction = 0.001). Conclusions. Higher serum cotinine concentrations were associated with higher nighttime and lower evening ambient light after sociodemographic adjustment. Attenuation after behavioral adjustment and the cross-sectional design preclude causal inference. Longitudinal studies with formal mediation analyses are needed to clarify the temporal ordering and mechanisms linking tobacco smoke exposure, smoking-related behaviors, and personal light-dark cycle patterns.

Background: Olfactory dysfunction (OD) in children remains underdiagnosed and poorly characterised. Despite its known impacts on nutrition, quality of life, safety awareness, and psychosocial development, no standardised diagnostic or management pathway currently exists for paediatric OD. This study aimed to characterise global practice patterns and identify diagnostic and therapeutic challenges unique to paediatric care. Methodology/Principal: A 44-item cross-sectional online survey was distributed to a verified international network of paediatric otolaryngologists across 36 countries via a closed professional platform. The survey assessed five domains: diagnostic practices, management protocols, technology and innovation, education and training, and barriers to effective care. Regional grouping was used to facilitate meaningful statistical comparisons. Categorical variables were evaluated using chi-square tests, with odds ratios and 95% confidence intervals reported for significant findings. Results: Of 351 potential participants, 167 responded (47.6% response rate). Most respondents (83%) reported seeing children with OD, yet 95% saw fewer than ten such patients annually. Psychophysical testing was never performed by 54.8% of respondents, while 88.4% routinely ordered cross-sectional imaging. Testing frequency increased significantly with patient age (Cochran's Q p<0.001). The most common barriers to objective testing were insufficient training (44.3%), time constraints (29.9%), and funding limitations (28.1%). Multidisciplinary collaboration was negligible. Significant regional variation was observed across most practice domains. Conclusions: Paediatric OD care is characterised by functional underinvestigation, fragmented multidisciplinary collaboration, and systemic educational gaps. These findings support urgent development of standardised clinical guidelines, age-appropriate validated assessment tools, and formal interdisciplinary care pathways.

Background: Obesity is globally recognized as a complex, multifactorial chronic disease, with biological, psychological, environmental and behavioural factors involved in both disease pathogenesis and maintenance. Although previous group-based studies demonstrated involvement of each of these factors, there is large inter-individual variability in the factors contributing to disease development as well as intervention outcomes, causing limited translatability to the individual level. This heterogeneity in treatment effectiveness might be due to differential causal and maintenance factors of obesity. To enable the transition from a one-size-fits-all approach to a more personalized approach for individuals with overweight or obesity, this study aims to investigate if and how the degree of weight loss and changes in daily life behaviour after a combined lifestyle intervention depend on individual baseline profiles comprising of person characteristics, biological, psychological, environmental and behavioural factors. Methods: This study will include 600 individuals varying in BMI, 200 participants with a healthy BMI (18.5-24.9kg/m2), 200 with overweight (BMI 25.0-29.9kg/m2), and 200 with obesity (BMI [&ge;]30.0kg/m2). For all participants, a comprehensive individual baseline profile is created, including person characteristics, biological, psychological, environmental and behavioural factors. A clustering method is applied to identify clusters of participants with similar characteristics. Next, we examine if and how these clusters are linked to bodyweight indicators measured at baseline, and how they relate to daily lifestyle behaviour, as measured by ecological momentary assessment (EMA) using a smartphone app and sensor technology (3-week measurements). Individuals with overweight or obesity will be randomized to the intensive lifestyle intervention or a lifestyle information condition, to determine if treatment response can be predicted based on cluster characteristics, how daily lifestyle behaviour changes after an intervention, and how changes in daily lifestyle behaviour relate to treatment response. Discussion: The End of Average study aims to characterize a large set of individuals varying in body weight to predict intervention effectiveness measured as changes in body weight indicators and in daily lifestyle behaviours. If reliable predictors of treatment success can be identified, these can be applied in personalized lifestyle interventions to improve lifestyle behaviour, body weight management and overall health.

Background: Adults with severe mental health conditions (often referred to as severe mental illness, SMI) experience 15 to 20 year mortality gap relative to the general population, with lung cancer a significant contributor. National cancer policy targets earlier diagnosis but does not explicitly address how pathways function for this group. Aims: This study aimed to describe lung cancer risk, prevalence, screening eligibility, referral activity and diagnostic pathway performance for adults with SMI in South East London (SEL), and to examine where along the pathway inequalities arise. Methods: Co-designed with experts with lived experience and voluntary sector, this exploratory mixed-methods service evaluation combined quantitative analysis of routinely collected data from the Quality Outcomes Framework (QOF), SMI Register and Cancer Waiting Times Record (April 2023-March 2024) with semi-structured qualitative interviews (n=11 clinical staff) and focus groups (n=6 adults with lived experience of SMI). Quantitative and qualitative data were analysed using descriptive statistics and framework-based thematic analysis respectively, and findings were integrated using a joint display approach, organised by the Consolidated Framework for Implementation Research (CFIR). Results: Lung cancer prevalence was approximately double among adults with SMI (0.17% vs 0.09% in the general population). Despite Urgent Suspected Cancer (USC) referral rates being more than twice as high in the SMI population (63 vs 28 per 100,000), fewer cancers were detected via planned general practice (GP) routes (11% vs 20%), the 28-day Faster Diagnosis Standard was not met for any SMI patient diagnosed with lung cancer during the study period; overall FDS performance was 76% in the SMI population compared with 84% in the general population; and appointment non-attendance was more than double that in the general population (6% vs 3%). Qualitative findings identified individual, service and system-level mechanisms, including stigma, diagnostic overshadowing, fragmented coordination, and rigid pathway protocols, that compound disadvantage across lung cancer pathway stages. Conclusions: Inequality in lung cancer outcomes for adults with SMI accumulates across the pathway rather than arising at a single point of failure. Addressing this requires proportionate adaptations within existing cancer pathways, alongside routine reporting of cancer outcomes stratified by SMI population. Keywords: severe mental health conditions, lung cancer, health inequalities, cancer screening, diagnostic pathway, mixed methods

Background Tobacco smoking during pregnancy increases the risk of preterm birth, small for gestational age (SGA), stillbirth, and longer-term adverse health outcomes. Globally, reducing smoking in pregnancy is a key public health priority, yet the organisation, accessibility, and effectiveness of cessation support varies substantially between countries and healthcare systems. Differences in policy implementation, resource allocation, and integration of cessation services into antenatal care influence uptake and success rates across diverse settings. In England, pregnant women are entitled to free smoking cessation support, however, service delivery varies across regions with mixed efficacy. While tobacco smoking is more prevalent in deprived communities, there is limited understanding of how, why, for whom, and under what circumstances these services are most effective, particularly in areas of social deprivation, such as the North East and Yorkshire. Objective To conduct a realist evaluation to understand how smoking cessation services support pregnant women in areas of social deprivation to stop smoking and reduce adverse perinatal outcomes. Methods This multi-site realist evaluation will be conducted across three NHS maternity services in West Yorkshire, England. The study comprises four iterative stages: (1) development of initial programme theories through realist-informed literature scoping and stakeholder consultation; (2) case study data collection including qualitative interviews with pregnant women (approximately 15-30) and staff (approximately 15-30); (3) analysis of routine anonymised maternity and neonatal electronic data collected over a one-year period; and (4) realist analysis to refine context-mechanism-outcome (CMO) configurations. Qualitative data will be analysed using realist logic supported by NVivo software. Quantitative data will be analysed using descriptive and inferential statistics to explore associations between smoking cessation engagement and perinatal outcomes. Ethics and dissemination Ethical approval was obtained through the UK Health Research Authority and a Research Ethics Committee prior to study commencement (IRAS 364173; REC reference number 26/SC/0020). Findings will inform recommendations to improve smoking cessation support for pregnant women in deprived areas. Results will be disseminated through peer-reviewed publications, conference presentations, and stakeholder engagement.

Background Tuberculosis remains the leading infectious cause of death worldwide. In the WHO African region, declining incidence has coincided with antiretroviral therapy (ART) scale-up, though whether this reflects reduced progression to disease or reduced transmission is unclear. We evaluated how ART and symptom status influence within-household Mycobacterium tuberculosis complex (MTBC) transmission risk. Methods We conducted a case-contact household study in rural South Africa, enrolling index adults with bacteriologically-confirmed pulmonary tuberculosis. MTBC immunoreactivity was measured in all child household contacts (aged 2-14 years) as a proxy measure of within-household transmission. We assessed the influence of index person ART status and symptom status, and explored effect-measure modification of the association between index person HIV status and transmission risk by sex. Results Among 755 child contacts of 296 index persons, effective ART was not associated with within-household MTBC transmission risk (risk ratio [RR], 1.07; 95% CI, 0.66-1.74). Among PLHIV engaged in ART care, WHO TB four-symptom screen (WHO4SS) status was not associated with transmission risk (RR, 0.80; 95% CI, 0.43-1.47), although absence of reported cough reduced risk (RR, 0.61; 95% CI, 0.38-0.96). A pronounced interaction between sex and HIV status was observed: HIV-negative women had the highest within-household MTBC transmission risk (30.5% vs. 14.3% in women with HIV) whereas risks were similar between HIV-positive and HIV-negative men. Conclusions We found no evidence that effective ART or WHO4SS status influenced within-household MTBC transmission risk, though confidence intervals were wide. Absence of reported cough was associated with lower risk, and transmission risk was highest among child contacts of HIV-negative women. These findings suggest reported cough is a useful marker of transmission risk and that routine tuberculosis screening within ART care may reduce transmission from PLHIV; intensified efforts are nonetheless needed to achieve earlier tuberculosis detection in HIV-negative individuals.

Introduction Reducing delays in leprosy case detection is essential for achieving global leprosy targets. Accurate measurement of these delays and their determinants relies largely on patient-reported data, as routine health records are often inadequate. The leprosy case detection delay (CDD) questionnaire, developed under the Post Exposure Prophylaxis for Leprosy (PEP4LEP) project, has been validated in Ethiopia, Mozambique, Tanzania, and Indonesia. However, it has not been adapted or validated for Nigeria or any major Nigerian indigenous language. This study aimed to culturally adapt and validate the CDD questionnaire for Igbo-speaking populations in Nigeria. Methodology/Principal Findings The CDD questionnaire underwent a standardized cross-cultural adaptation process. Content validity was assessed using item- and scale-level content validity indices, while construct validity was evaluated through hypothesis testing. Reproducibility was assessed using test-retest and inter-rater reliability; agreement using the Bland-Altman method and the Wilcoxon Signed-Rank test; reliability using Spearmans rank correlation coefficient and the Intraclass Correlation Coefficient (ICC); and internal consistency using Cronbachs alpha. Data were collected through face-to-face interviews with persons affected by leprosy at two time points separated by at least two weeks. Participants (n=100) had a mean age of 45.1 years (SD=18.7). Mean CDD was 77.2 months at baseline and 77.9 months at retest. The instrument demonstrated excellent content validity (I-CVI/S-CVI: 0.90-1.00), good internal consistency (Cronbachs =0.77), and excellent test-retest reliability (ICC=0.996, 95% CI: 0.994-0.997). Test and retest measurements were highly correlated ({rho}=0.985, p<0.001), with no evidence of systematic change over time (p=0.864). Seventy-two percent of participants reported identical CDD values across assessments. All items from the original English version were retained without modification. Conclusion/Significance The Igbo version of the CDD questionnaire demonstrated good validity and reliability and is suitable for assessing leprosy case detection delay among Igbo-speaking populations in Nigeria

Objectives To explore caregiver and clinicians perspectives on implementing mental health conversations and supports for caregivers of children with chronic conditions in paediatric outpatient clinics. Specifically, views were sought on (a) screening approaches and measures (phase 1) and (b) how feedback and support could be provided to caregivers experiencing mental health difficulties (phase 2). Methods Caregivers and clinicians from two outpatient clinics (neuromuscular and diabetes) at a tertiary paediatric hospital in Melbourne, Australia participated in online focus groups in July and August 2024. Caregivers were recruited from outpatient clinics and clinicians were recruited via email. Both groups were combined for phase 1 before separating into breakout rooms for phase 2. Two authors conducted reflexive thematic analysis of transcripts using NVivo. Results Sixteen participants (caregivers n = 8; and clinicians n = 8) took part in in two semi-structured focus groups. Analysis generated two overarching domains, each comprising multiple themes. Domain 1, Addressing caregiver mental health, captured themes of overwhelm and invisibility, diverse caregiving roles, and the need for time and resources to support wellbeing conversations. Domain 2, Housing the mental health conversation, encompassed themes of screening preferences, caregiver agency in confidentiality, delivery of feedback, and access to tailored supports. Conclusions Caregivers and clinicians support routine caregiver mental health discussions in paediatric outpatient settings. Caregivers favour screening at diagnosis and key transitions, with clear, and actionable feedback delivered away from the child. Questions about record-keeping warrant further exploration, as do the perspectives of fathers.