eClinicalMedicine

BACKGROUND Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy associated with disability, morbidity and mortality. Impairment of health-related quality of life (HRQoL) in ENL has been reported using the Dermatology Life Quality Index (DLQI) and the 36-Item Short Form Health Survey (SF-36), the latter validated in people affected by leprosy. Understanding the correlation between these measures is important to determine whether the shorter dermatology-specific DLQI provides a valid and practical measure of HRQoL in ENL. OBJECTIVES To examine the relationship between DLQI and SF-36 scores in individuals with ENL using data from the Methotrexate and Prednisolone study in ENL (MaPs in ENL). METHODS A post-hoc analysis of prospectively collected HRQoL data from the trial sites in India, Indonesia, and Nepal of the MaPs in ENL multicentre randomised clinical trial was performed. HRQoL was assessed using the DLQI and SF-36 at enrolment and at weeks 24, 48 and 60. Associations between DLQI and SF-36 physical (PCS) and mental (MCS) component summary scores were evaluated using correlation analyses and multivariable linear regression at enrolment, and linear mixed-effects models during follow-up adjusted for age, sex, recruiting centre and enrolment SF-36 scores. RESULTS A total of 383 paired HRQoL assessments from 129 participants were analysed. At enrolment, HRQoL impairment was substantial (median DLQI 19, IQR 15-21; mean PCS 30.3 + - 7.3; mean MCS 33.3 + - 8.4). DLQI scores improved markedly during follow-up. Across all timepoints, DLQI was strongly inversely correlated with PCS and MCS (both p<0.001). In adjusted analyses, higher DLQI scores were consistently associated with lower PCS and MCS. At enrolment, each 1-point increase in DLQI was associated with a 0.66-point reduction in PCS and a 0.51-point reduction in MCS (both p<0.001). These associations remained strong during follow-up, with no evidence that they varied over time. CONCLUSIONS DLQI scores were strongly and consistently associated with SF-36 physical and mental health scores. These findings support the use of the DLQI as a practical patient reported outcome measure to assess the HRQoL associated with ENL and its change following treatment.

Background: Global guidelines recommend strengthening and integrating health services for skin diseases, yet evidence for strategies remains scarce. We evaluated a decentralised approach to the care of skin disease through integration within routine primary care, by assessing uptake, equity, alignment with skin disease burden and associated treatment costs. Methods and findings: A before-and-after intervention study was conducted across all 17 public health facilities in Atwima Mponua district, Ghana from November 2023 to September 2024 (intervention period). We analysed routine health facility records to compare uptake of primary care for skin diseases pre-intervention (January to October 2023) and during the intervention. We assessed the burden of skin disease through a community-based two-stage cross-sectional dermatological survey, and estimated patient and provider costs for skin disease through post-care questionnaires and health facility surveys. We compared uptake to disease burden and assessed catastrophic expenditure and factors associated with higher treatment costs. Uptake of primary care for skin disease doubled during the intervention period relative to the pre-intervention period (adjusted incidence rate ratio (aIRR) 2.0, 95% CI 1.92-2.09), with greatest increases amongst school-age children (aIRR 2.70, 2.46-2.97) and individuals residing within very rural communities (aIRR 2.79, 2.47-3.15). Amongst 42,801 individuals surveyed, odds of any skin disease were greater amongst males (adjusted odds ratio (aOR) 1.25; 1.13-1.38), pre-school age children (aOR=1.80, 1.61-2.80), and residents of very rural communities (aOR=1.68, 1.09-2.61). Males and school-age children remained underrepresented amongst those who sought care during the intervention period relative to those diagnosed during the survey. Amongst patients seeking care for skin NTDs and complex wounds, 4% experienced catastrophic expenditure, driven largely by costs prior to visiting an intervention health facility. Conclusions: Greater integration within primary care substantially increased uptake of care for skin disease, but populations at greatest risk remained underrepresented amongst those accessing care. These findings highlight the need for deliberate strategies to address persistent barriers to care, with lessons for integration efforts across primary health systems.

Background There are no licensed treatments for patients with mild to moderate patchy alopecia areata (AA). Objectives To evaluate the efficacy, safety and dose response of STS01, a novel nanoparticle controlled release, topical formulation of dithranol/Prosilic. Methods In a phase 2, double blind study, adult patients with mild to moderate AA (guideline 10% to 50% of scalp hair loss) were randomly assigned to STS01 at doses of 0.25%, 0.5%, 1%, 2% or placebo, daily for 6 months. The primary endpoints included the proportion of patients achieving a >=30% improvement in Severity of Alopecia Tool (SALT) score, and percentage change from baseline in SALT score. This minimum level of improvement is generally accepted as an indicator of the population likely to progress to complete regrowth Results A total of 155 patients were randomized and treated (placebo, n=32; STS01 groups, n=30 to 31). STS01 1% met the primary efficacy endpoint of >=30% SALT score improvement compared to placebo: 75.9% (95% CI, 60.3 to 91.4%) vs 36.7% (95% CI, 19.4 to 53.9%) at 6 months; p=0.0037. The least squares (LS) mean percentage change in SALT score from baseline to end of treatment showed a clear dose response relationship; STS01 0.5% was the minimally effective dose and 2% the maximum tolerated dose, and there was a statistically significant improvement in the STS01 1% group (minus 55.0% vs +0.6% with placebo; p<0.01). Significant improvements (p<0.05) in LS mean percentage changes from baseline in SALT scores were demonstrated in the STS01 1% group at 2 months (-28.6% vs 12.8%), 4 months (-57.2% vs 1.5%), and 6 months (minus 67.0% vs 0.6%). Clinical Global Impression improvement was reported in 72.0% of patients with STS01 1% vs 41.7% with placebo (p<0.05). The most commonly reported treatment emergent adverse events were skin irritation reactions, but were mostly mild (STS01: 56.7% to 71.0%; placebo: 21.9%) or moderate (STS01:13.3% to 35.5%; placebo: 0%) and manageable by reduced frequency of application. There were 15 skin-related discontinuations with STS01 (12.2%) and 2 (6.3%) with placebo. Conclusions STS01 demonstrated a clear dose response, with STS01 1% dose optimally more effective than placebo for hair regrowth with minimal tolerance concerns in mild to moderate patchy AA. Skin irritation reactions were generally manageable and there were no new safety signals. Further characterisation of the STS01 1% dose is planned in a phase 3 study. Chief Investigator AGM reports fees from Soterios Ltd. Chief Statistician DMF is an employee of Soterios Ltd. All other authors were Principal Investigators in the trial and their clinics were reimbursed for the work involved. Most also had sponsorship in the form of consultancies, investigational roles or lecturing roles on behalf of other Dermatological pharmaceutical companies

Mental health problems, including emotional problems, are linked to adverse educational outcomes among children and adolescents. This study examines the association between early onset of mental health problems generally, and emotional problems specifically, at ages 5-14, and outcomes from the General Certificate of Secondary Education (GCSE), a secondary education qualification, at age 16 for 4,783 students in England, using the Millennium Cohort Study dataset linked to the National Pupil Database. We found that the onset of mental health problems at ages 5, 7, 11 and 14 had a significant and negative association with all GCSE outcomes. We also found negative associations between early onset emotional problems and GCSE outcomes, although results were most stark for emotional problems that onset at age 11, with statistically significant negative associations with all GCSE outcomes. School absence was identified as a potential mediator of the negative association. Furthermore, this study found that the potential loss of productivity related to mental health problems in general and emotional problems in particular was over 23,000 sterling and 11,000 sterling per affected individual, respectively, which could translate into approximately 2.57 billion sterling and 1.6 billion sterling, respectively at the population level for England. These findings highlight the importance of early intervention for children and adolescents with mental health problems to improve educational and future outcomes.

BackgroundThe COVID-19 pandemic was associated with increased child developmental concerns in Scotland. However, it is not known whether this increase was uniform across social groups, and there is particular concern that children from low-income households, urban areas and ethnic minority groups may have been disproportionately affected. This retrospective, population-based, cohort study aimed to examine whether the pandemic was associated with changes in developmental inequalities in Scotland. Study designWe linked national birth records, the COVID-19 in Pregnancy in Scotland (COPS) dataset, and 13-15 month and 27-30 month child health review records, covering all children born in Scotland who undertook reviews between January 2019 and August 2023 and had full developmental data. Logistic regression models estimated inequalities in odds of developmental concerns, before, during and after the pandemic and across Scottish Index of Multiple Deprivation (SIMD) quintiles, parental National Statistics Socioeconomic Classification (NS-SEC), urban-rural classification, child ethnicity and child sex. Interaction analysis formally tested for any significant changes in inequalities. FindingsThe analyses included 254,367 children, covering 13-15 month child health review records for 183,439 children and 27-30 month child health review records for 184,689 children. Children in more deprived SIMD quintiles and lower parental NS-SEC categories had significantly higher odds of developmental concerns, as did African and Asian children (at 27-30 months only). Children who were female and in rural areas (27-30 months only) had significantly lower odds of developmental concerns. Developmental inequalities were broadly consistent at each time point and interaction analysis suggested that there was no widening of inequalities during or after the pandemic. ConclusionsDevelopmental inequalities in Scotland did not widen during or after the COVID-19 pandemic. However, substantial pre-existing inequalities persist, underscoring the need for interventions to reduce disparities and support national policy goals on child development.

Introduction Care home (CH) influenza vaccination of staff improves resident health, yet uptake remains low at just over 11% (England, 2025/2026). We report an economic evaluation (EE) of "FluCare", an intervention to increase staff influenza vaccination through: vaccination clinics at CHs; promotional materials; and CH financial incentives. Method Seventy-five CHs were randomised to FluCare or control. A cost-consequence analysis took the influenza vaccination programme funder perspective, but also extended to the National Health Service (NHS) and CH perspective. Costs included: influenza vaccination; administration fee; FluCare components; CH resident NHS utilisation. Outcomes were: staff influenza vaccination rates; staff sickness; and resident mortality. Sensitivity analyses excluded intervention CHs that did not host vaccination clinics. Results Compared to control CHs, adjusted analysis found intervention homes with a mean absolute increase in vaccination rates of 1.8% (95% CI: -6.0%, 10.8%; p=0.572) at an increased cost of {pound}451 (95% CI: {pound}239, {pound}675; p<0.001) to the vaccination programme funders: {pound}249 per additional percentage point (PAPP) per CH. Vaccination clinics were delivered late in the influenza season, with 80% taking place from February 2023. Including only intervention CHs that hosted staff flu vaccination clinics (23/35), increases the mean difference to 10.1% (95% CI: 0.9%, 21.9%; p=0.018) and costs to {pound}805 (95% CI: {pound}603, {pound}1,079; p<0.001): {pound}79 PAPP per CH. Differences between trial arms in other costs and outcomes were marginal and generally non-significant. Conclusions FluCare delivered little improvement when staff flu vaccination clinics did not occur and had little impact on other costs/outcomes. Cost-effectiveness depends on willingness-to-pay for increased staff vaccination, but cost PAPP per CH improved from {pound}249 to {pound}79 when only CHs hosting clinics were considered. Late implementation, likely reduced impact by limiting clinic delivery, as reflected in sensitivity analysis. Future evaluations should implement FluCare earlier in the season.

BackgroundChildhood sensory and intellectual disabilities represent significant yet under-recognized barriers to learning and human capital development. This study analyzes prevalence and severity of these conditions among 149.3 million children aged 5-19 years across 25 countries in Latin America and the Caribbean (LAC) using Global Burden of Disease 2023 data. MethodsWe extracted GBD 2023 estimates for vision loss, hearing loss, and intellectual disability across 25 LAC countries, stratified by age, sex, and severity. Regional estimates were calculated using population-weighted averages. Severity distributions were compared with OECD countries to contextualize regional patterns. ResultsThese conditions are estimated to affected 9,282,921 children (6.22%; 95% UI: 5.89-6.54%). Hearing loss was predominant, affecting an estimated 5.42 million (3.63%, 3.41-3.86), with 87.6% mild-to-moderate. Intellectual disability estimated to affected 2.56 million (1.71%, 1.58-1.85), with 61.7% borderline-to-mild. Vision loss estimated to affected 1.30 million (0.87%, 0.79-0.96), with 89% that can be effectively addressed with spectacles. Prevalence increased with age across all conditions. Male predominance was consistent for intellectual disability (2.00% vs 1.42%). Annual economic cost totaled US$19.3-29.0 billion, while comprehensive interventions would require US$9.45-14.23 billion with benefit-cost ratios of 2:1 to 15:1. ConclusionsThe distribution of children across milder levels of difficulty underscores the opportunity for education and public health systems to provide timely and accessible support. With approximately 88% of sensory impairments addressable through established technologies, investments in inclusive services can yield strong social and economic returns.

Background Smartphone ownership among UK adolescents is near universal. Teachers report phones increasingly being involved in classroom disruption, and misuse during school hours is among the more common serious behavioural issues in secondary schools. Evidence on whether restrictive policies improve behaviour, attainment, or wellbeing remains limited. Objectives The primary objective is to assess the impact of a lockable smartphone pouch on educational attainment and behaviour. Secondary objectives are to assess impacts on general functioning, psychological wellbeing, and school level indicators such as exclusions, and to examine whether effects differ for pupils who may be most at risk. Methods We will conduct a mixed methods cohort study in secondary schools across Northern Ireland and England during the 2025 to 2026 academic year. The quantitative component uses a serial cross sectional design. Students will complete an online questionnaire at 0, 4 weeks, and 8 weeks, covering homework completion, classroom disruption, participation in PE and extracurricular activities, peer interaction during break, and patterns of smartphone use. Measures include the Strengths and Difficulties Questionnaire (SDQ), the Revised Child Anxiety and Depression Scale (RCADS), the short form of the Smartphone Addiction Scale (SAS SV), and the Bergen Social Media Addiction Scale (BSMAS). Each participating school will also supply half termly aggregate data on exclusions, detentions, CAMHS referrals, counsellor visits, and parent visits between September 2023 and May 2026. Assuming 90% power, a two-sided type 1 error of 0.05, an intracluster correlation of 0.02, and 25% loss to follow up, we aim to recruit a minimum of 3,200 students from six or more schools to detect a small effect (Cohen's d = 0.2) on SDQ hyperactivity score. Continuous outcomes will be analysed with linear regression and binary outcomes with logistic regression. Prespecified subgroup analyses cover SEN or neurodivergent status, area level deprivation, and which phone policy is in place at each school. Qualitative analyses comprise focus groups with students and staff at each participating school and semi-structured interviews with school leads. Transcripts will be coded both inductively and deductively and analysed thematically with Braun and Clarke's six phase approach. Ethics and Dissemination The study has been approved by the King's College London Research Ethics Committee. A Data Protection Impact Assessment has been agreed with the Northern Ireland Department of Education. Findings will be published in peer reviewed journals and shared with participating schools, parents, and policy makers to inform smartphone policy in schools.

IntroductionThe link between Human Papillomavirus (HPV) and cancer is well-established. In Singapore, bivalent HPV vaccines are subsidised for females, but not males. Economic analysis of HPV vaccination has generally assessed the costs to the health system, but this may not be as relevant to individual decision-making as potential lost income. We estimated the impact of bivalent HPV 16/18 vaccination on sick leave, unemployment, and premature mortality as a function of age and sex to understand the broader impact of HPV-related cancers. MethodsWe developed a population-level economic model to estimate lifetime income losses by diagnosis age, sex and cancer type. We applied sex- and cancer-specific Cox regressions to the Singapore Cancer Registry for annual predicted survival from 1992 to 2022. These were combined with census and employment data to estimate HPV-associated income losses in Singapore. Attributable fractions and vaccine effectiveness data for HPV 16/18 from the literature were used to estimate the effectiveness of bivalent HPV vaccination. Structural sensitivity analysis examined the role of 80% population coverage conferring herd immunity. ResultsThe registry contained 17,294 individuals with an HPV-associated cancer diagnosis. Lost income was greatest for cervical cancer due to its high prevalence, however the losses per diagnosis were highest for oropharyngeal cancer. Bivalent HPV vaccination led to income benefits of $SGD1,397 [$895 to $1,838] in girls and -$62 [- $76 to -$48] in boys. A gender-neutral HPV vaccination of 80% of 15-year-old Singaporeans, conferring herd immunity, would have lifetime income protective benefits of $24.4m [$14.2m, $33.7m] per cohort, a five-fold return on investment. ConclusionsIn addition to avoiding healthcare costs and lost quality of life, parents should consider vaccination as a means of avoiding potential income losses. A national policy of gender-neutral HPV vaccination could deliver substantial income protection due to both individual vaccine protection and herd immunity.

BackgroundNon-segmental vitiligo(NSV) shows marked heterogeneity in activity, progression, and treatment response. Reliable clinical markers that predict prognosis and patient-reported outcomes are lacking. ObjectivesTo identify clinicodemographic and clinical predictors of disease extent, progression, repigmentation, treatment dependency, noticeability, and psychosocial impact in NSV. MethodsIn this prospective cohort study, 275 patients with NSV were followed for 12 months. Sixteen baseline variables, including demographic features, autoimmune history, and clinical markers (koebnerization, confetti and trichrome patterns, leukotrichia, mucosal, acral, and periorificial involvement), were recorded. Outcomes included body surface area(BSA), progression, repigmentation, treatment dependency, Vitiligo Noticeability Scale(VNS), and quality-of-life indices(VIS-22, DLQI, C-DLQI, F-VIS). Multivariable analyses and cluster analysis were performed at 6 and 12 months. ResultsMarkers of disease activity leukotrichia, trichrome and confetti lesions, koebnerization, and mucosal, acral, and periorificial involvement were strongly associated with greater BSA, poor repigmentation, higher noticeability, and treatment dependency. Leukotrichia was consistent predictor of poor repigmentation and high VNS. Family history of autoimmunity predicted progression and treatment dependency. Early-onset vitiligo showed lower disease extent but greater family-related psychosocial burden. Cluster analysis identified severe, intermediate, and mild phenotypes with distinct therapeutic responses. ConclusionsSimple clinical markers can stratify NSV patients into prognostic subgroups, enabling individualized treatment and counseling. Plain Language SummaryVitiligo behave variably in different people, some people may have slow-spreading course, while others develop widespread or persistent patches. In this study, we followed 275 people with non-segmental vitiligo for one year to find signs on the skin that could predict how the disease would behave and how it would affect daily life. We found that features such as white hair within patches (leukotrichia), speckled (confetti) or three-colored lesions (trichrome), new patches appearing after injury (koebnerization), and involvement of the lips, mouth, hands, feet were linked to more severe disease, poorer response to treatment, and greater cosmetic concern. A family history of autoimmune disease increased the risk of worsening vitiligo. Patients who developed vitiligo early in life had less skin involvement but greater emotional and family-related impact. These easily recognized signs can help doctors and patients plan treatment and set realistic expectations. Significance of the studyNon-segmental vitiligo (NSV) has a heterogeneous and unpredictable clinical course with variable progression and response to therapy. However, robust prospective data linking these markers with long-term outcomes and patient-reported measures remain limited. In our prospective cohort of 275 patients, clinical markers such as leukotrichia, trichrome and confetti lesions, koebnerization, and acral/mucosal/periorificial involvement, were strongly associated with greater disease extent, poorer repigmentation, higher treatment dependency, and increased noticeability. Leukotrichia consistently predicted poor repigmentation. Thereby, prognostic stratification can also improve patient counselling regarding expected repigmentation, treatment duration, and psychosocial burden.

Background Early onset obesity in children, almost always accompanied by significant health complications, may be driven by rare genetic variants that influence appetite, metabolism, and nutrient absorption. Traditional treatment approaches are usually insufficient for those with monogenic obesity of this type. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, and related drugs such as melanocortin 4 receptor agonists, have emerged as promising first-line treatments for severe obesity. There is no established protocol or pathway in England for identifying children with monogenic obesity who could benefit from these and similar treatments Methods We undertook early economic modelling to examine the cost-effectiveness, from a health service perspective, of implementing a new pharmacotherapeutic care pathway for the identification and treatment of monogenic obesity in children. We modelled a hypothetical population of children with hyperphagia and body mass index (BMI) three standard deviations above mean values for age and sex. We evaluated the clinical decision to initiate the pathway using a decision tree model with patient quality-adjusted life years (QALYs) and NHS healthcare costs 12 months from an initial clinic visit as outcomes, and calculated incremental cost effectiveness ratios and a cost-effectiveness acceptability curve. Results Both costs and QALYs were higher under further investigation (GBP3,247 and 0.47 QALYs) compared to no further investigation (GBP1,589 and 0.24 QALYs). The incremental cost-effectiveness ratio in the base case was GBP7,133 per QALY. Further examination of these children was therefore likely to be cost effective in this model. Conclusion A decision-tree model suggested that further investigation of severely obese children potentially eligible for treatment with semaglutide is likely to be cost-effective for the NHS. However, this result is associated with uncertainty arising from a lack of evidence for many key model parameters.

Hidradenitis suppurativa (HS) is a chronic, debilitating, inflammatory skin disorder. Medications have been reported in association with cases of new-onset HS or exacerbation of existing disease; however, the extent of this risk is unclear. We queried the FDA adverse event reporting system (FAERS) from 2003-2023 to identify drug-specific reporting signals for HS. We stratified reports by whether HS was listed as an indication (Drug-Worsened, DW) or not (Drug-Induced, DI) to distinguish disease flares from de novo disease. Primary suspect drugs with > 3 HS reports were included. Disproportionality was quantified using reporting odds ratio (ROR) with Wald 95% confidence intervals (CI). Time-to-onset was also evaluated. We identified 5,529 HS reports: 3,725 DW and 1,804 DI. Females comprised 63% (mean age 41) and the US was the top reporting country (81.8% DW; 53.66% DI). In the DI group, statistically significant signals were observed for immunomodulators also used to treat HS including adalimumab (n=506, ROR= 12.6 [11.3-14.0]) infliximab (n=108, ROR=8.2 [6.7-10.0]), and secukinumab (n=79, ROR=6.6 [5.2-8.2]), consistent with paradoxical reactions. Median time-to-onset was 22 days for secukinumab, compared to 312 and 319 days for adalimumab and infliximab. Signals were also identified for isotretinoin (n=28, ROR= 6.2 [4.2-8.9]), and for antineoplastic agents including cytarabine (n=25, ROR= 24.7 [16.6-36.6]) and omacetaxine (n=8; ROR= 7416 [CI 2923-18816]), which may reflect reported eccrine hidradenitis. In the DW group, adalimumab (n=2967), secukinumab (n=67), and infliximab (n=57) predominated but displayed lower RORs (0.72-1.4), likely reflecting indication bias. While mechanisms of drug-associated HS require further clarification, our findings demonstrate significant associations and highlight the importance of dermatologic monitoring when initiating certain agents.

Background Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes-borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions. Methods We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when comparable effect estimates were available (PROSPERO #CRD420251124994). Findings 51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12-4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76-0.89]) and composite outcomes (RR:0.88 [0.82-0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01-1.78]), dementia (HR:1.61 [1.10-2.35]), autoimmune (RR:1.39 [1.17-1.67]), cardiovascular (HR:1.51 [1.27-1.80]), psychiatric (HR:1.17 [1.07-1.28]), and any sequelae (HR:1.19 [1.13-1.25]) versus those without prior infection. Interpretations Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.

IntroductionSpinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) are progressive genetic neuromuscular disorders imposing substantial caregiving demands on families. In Pakistan, where disease-modifying therapies remain largely inaccessible, care is predominantly supportive, frequently resulting in psychological distress and diminished caregiver confidence. An individuals belief in their capacity to execute required behaviours, self-efficacy, is a recognised determinant of caregiving quality, yet evidence on caregiver self-efficacy in SMA and DMD within low-resource settings remains sparse. This study aims to evaluate the effect of a multicomponent, digitally delivered intervention on self-efficacy among primary caregivers of children with SMA and DMD in Pakistan. Methods and AnalysisThis single-group, pre-post study will recruit 30 primary caregivers of children with SMA or DMD enrolled in the Treat-NMD Registry of Pakistan. An eight-week intervention will be delivered via online support groups, comprising educational video clips, expert-led live sessions, pictorial guides, and progressively tapering audio reminders. The primary outcome, self-efficacy, will be measured using a culturally adapted, content-validated Urdu version of the DMD Caregiver Self-Efficacy Scale (DMD-CSES), assessed at baseline (T0) and eight weeks post-intervention (T1). Pre-post scores will be compared using a paired t-test or Wilcoxon signed-rank test depending on data distribution, with analyses conducted in STATA Version 17. Ethics and DisseminationEthical approval has been granted by the Ethics Review Committee of Aga Khan University (2025-11875-37040). Verbal informed consent will be obtained from all participants, with confidentiality maintained throughout. Findings will be disseminated via peer-reviewed publication, conference presentations, and shared with the Treat-NMD registry network. Trial registration numberNCT07356063, Date of registration: 11/January/2026

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 Lifestyle interventions can increase the probability of remission of prediabetes to normal glucose tolerance, but their economic value remains unclear. We assessed the within-trial and lifetime-horizon modeled cost-effectiveness of intensive and conventional lifestyle interventions in risk-stratified participants with prediabetes. Methods A health economic evaluation was conducted alongside the 12-month multicenter PLIS trial (n=1,105). High-risk participants were randomized to intensive (HR-INT) or conventional (HR-CONV); low-risk participants to conventional lifestyle intervention (LR-CONV) or control (only short single consultation; LR-CTRL) with risk stratification based on insulin secretion, insulin sensitivity, and liver fat content. Within-trial analyses estimated incremental costs per additional remission to normoglycemia and per quality-adjusted life year (QALY). Lifetime cost-effectiveness was modelled using a four-state Markov Model. Findings At 12 months, HR-INT and LR-CONV increased remission compared with their respective comparators. The incremental cost per additional remission was {euro}7,081 (95% CI: dominated-47,277) for HR-INT and {euro}4,278 (1,312-11,793) for LR-CONV from a health insurance perspective. A willingness-to-pay of {euro}22,000 (HR-INT) and {euro}7,500 (LR-CONV) per additional remission corresponded to 90% probability of cost-effectiveness. Neither intervention was cost-effective in terms of QALYs gained within the 12-months period. Lifetime modelling suggested that both HR-INT and LR-CONV are not only cost-effective, but also cost-saving, relative to HR-CONV and LR-CTRL, respectively. Also in the probabilistic sensitivity analysis, most simulations indicated dominance (71.7% for HR and 88% for LR). Interpretation Based on short-term economic evaluation, the interventions assessed were cost-effective regarding additional participants with remission, not for incremental QALYs gained. Lifetime modelling suggests cost savings for both risk groups. Targeting populations with lifestyle interventions to achieve prediabetes remission seems to generate good value for money in the long term.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of lepromatous leprosy characterised by recurrent inflammatory episodes often requiring prolonged immunosuppression. The severity of ENL can be quantified using the validated and reliable ENLIST ENL Severity Scale (EESS). The longitudinal course of ENL and how it is captured using standardised severity measures has not been well described. We prospectively evaluated the changes in ENL severity over time using the EESS in a randomised clinical trial. Methods We conducted a post-hoc analysis of participants enrolled in the Methotrexate and Prednisolone Study in ENL, an international multicentre randomised controlled trial conducted in Ethiopia, India, Indonesia, and Nepal. Adults with severe ENL (EESS score [&ge;]9) were followed for 60 weeks with repeated EESS assessments. Longitudinal trajectories were analysed using mixed-effects regression models. Item-level analyses characterised the clinical phenotype captured by the scale. Associations between EESS score, prednisolone exposure, and dermatology-specific health-related quality of life measured using the Dermatology Life Quality Index (DLQI) were examined. Findings A total of 135 participants contributed 1,958 EESS assessments. Mean EESS declined rapidly during the first four weeks of treatment (-2.10 points/week; 95% CI -2.36 to -1.84; p<0.001), increased modestly during reduction in corticosteroid dose (weeks 4-20), and gradually declined thereafter. Severe ENL (EESS score [&ge;]9) occurred in 20.6% of visits and was characterised primarily by pain and cutaneous inflammatory manifestations. Participants who required additional prednisolone had persistently higher EESS scores and showed limited improvement compared with those who did not receive additional prednisolone. Longitudinal EESS scores were strongly correlated with the DLQI score (Spearmans {rho}=0.75; p<0.001). Conclusion The EESS captures clinically meaningful changes in ENL severity, aligns with treatment decisions, and reflects patient-reported severity over time. These findings support the use of the EESS as a robust tool for monitoring ENL severity in both clinical research and routine care.

Objective: To independently audit vendor-reported performance claims of health AI systems deployed in Nigeria and assess discrepancies, clinical consequences, equity impacts, and implications for safe AI deployment in low- and middle-income countries. Methods and analysis: We conducted a mixed-methods longitudinal audit (October 2024-March 2026) of six health AI systems (chest X-ray interpretation, TB screening, symptom triage, maternal health risk prediction, patient history intake, and health chatbots) across 73 diverse health facilities in six Nigerian states, involving 52,000 patients and 45 key informant interviews conducted with stakeholders. All data were sourced from integrated facility-level records, and no database linkage was performed. Vendor claims were abstracted from documentation, white papers, and validation studies. Independent performance was verified by an independent third party through system logs, patient records, clinical outcomes, and stakeholder interviews. Performance gaps were quantified as absolute percentage-point differences; clinical harms were estimated using patient volume and bootstrap confidence intervals; equity impacts were assessed across vulnerability dimensions (geography, age, income, comorbidities, infrastructure) using interaction terms in mixed-effects models and an Equity Harm Index (EHI). Results: Vendor-reported accuracy averaged 91.5%, while independently measured real-world accuracy averaged 67.3%, yielding a mean performance gap of 24.2 percentage points (95% CI: 21.5 to 26.9; p<0.001) across systems. Gaps ranged from 17 to 35 percentage points and were statistically significant for all systems. These discrepancies translated to substantial preventable harm, including an estimated 1,247 undetected TB cases (186 preventable deaths) and 342 misclassified high-risk pregnancies annually. Performance gaps were 28-38% larger among vulnerable groups (e.g., rural patients showed 38% higher EHI). Gaps were classified as systematic, context-dependent, or population-dependent. Conclusion: Vendor-reported performance metrics substantially overstated the real-world effectiveness of health AI in Nigeria, leading to preventable patient harm and widening inequities. Mandatory independent post-deployment verification, analogous to pharmaceutical Phase IV surveillance, is essential to ensure safe, equitable AI use in resource-constrained settings. Donors and regulators should prioritize verification over trust-based deployment.

BackgroundClinical and genetic evidence on the association between atopic dermatitis (AD) and subsequent psoriasis remains conflicting, and it is unclear whether this risk is modified by systemic treatments. Recent reports suggest type 2-targeted biologics may unmask psoriasis in AD patients, but data are limited. We thus aimed to assess whether AD is associated with incident psoriasis and whether this risk differs by systemic treatment, particularly biologics versus conventional systemic immunosuppressants (cvIS). MethodsScoping analyses informed a locked analytic design, preregistration at OSF, and confirmatory execution. Propensity score-matched analyses compared AD with non-AD controls and biologics with cvIS. Sensitivity analyses, Cox model triangulation, and control outcomes assessed robustness. FindingsAmong [~]300,000 matched pairs, AD was associated with increased psoriasis risk (primary HR 3.81, 95% CI 3.35-4.34), consistent across all 8 sensitivity analyses and model triangulation. Biologic treatment was associated with reduced psoriasis risk versus cvIS (primary HR 0.20, 95% CI 0.11-0.35), consistent across 6 of 7 evaluable sensitivity analyses and Cox triangulation. Positive and negative control outcomes showed expected directional patterns. InterpretationAcknowledging limitations including residual confounding and coding misclassification, AD was associated with increased psoriasis risk and biologics with lower psoriasis risk than cvIS. FundingDFG (EXC2167, SFB1526, LU877/25-1), Schleswig-Holstein Excellence-Chair Program, Swedish Society for Dermatology and Venereology, and the Tore Nilson Foundation. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAtopic dermatitis (eczema) and psoriasis are the two most common chronic inflammatory skin diseases worldwide. For a long time, doctors and researchers assumed these two conditions could not occur in the same person, as they were thought to involve opposing immune responses. However, this view has been challenged over the past decade. Some large studies, including population-based cohorts from Taiwan and the United Kingdom, have found that people with eczema may be at higher risk of developing psoriasis over time, while other studies, including genetic analyses, have suggested the opposite: that the two diseases may actually protect against each other. This conflicting picture has left clinicians uncertain about the true relationship between the two diseases in everyday clinical practice. A separate but related concern has emerged with the introduction of a new class of highly effective treatments for eczema, biologics, particularly dupilumab. Case reports and observational studies, including a large study published in JAMA Dermatology in 2025, have raised the possibility that these medications might trigger psoriasis in some patients, potentially by shifting the immune system from one inflammatory pattern to another. However, prior studies on this question had important methodological limitations: they were not pre-planned and registered before data collection, they did not always tightly link treatment use to an eczema diagnosis, and critically, none compared biologic treatment directly against conventional immunosuppressant medications, the most relevant clinical comparator. Added value of this studyThis study is a large and methodologically rigorous investigation of both questions: whether eczema itself increases the risk of developing psoriasis, and whether the type of systemic treatment used for eczema influences that risk. Using a database of over 110 million electronic health records from across the United States, we matched approximately 300,000 patients with eczema to 300,000 patients without eczema and followed them for up to seven years. We also compared nearly 5,500 patients treated with biologics to an equal number treated with conventional immunosuppressants. Crucially, our study was pre-registered before any data were analyzed, meaning the research questions, methods, and analyses were locked in advance and could not be adjusted based on what the data showed. We also used a range of additional analyses to test whether our findings were robust, including checks using outcomes that should not be affected by eczema or its treatment (such as appendectomy and hearing loss), which confirmed that our results were not likely explained by bias alone. We found that eczema was associated with an increased risk of developing psoriasis, but that this risk was substantially influenced by the choice of comparison group, ranging from approximately 1.4-fold to nearly 4-fold depending on the analytical approach. More strikingly, we found that patients treated with biologics had a markedly lower risk of developing psoriasis compared with those treated with conventional immunosuppressants, the opposite of what prior reports had suggested. This finding was consistent across nearly all additional analyses performed. Implications of all the available evidenceTaken together with existing evidence, these findings suggest two important conclusions. First, clinicians should be aware that eczema, particularly moderate-to-severe eczema requiring systemic treatment, may carry an elevated risk of developing psoriasis over time. This does not mean that all patients with eczema need to be screened for psoriasis routinely, but it does support clinical awareness and monitoring in higher-risk patients. Second, and perhaps most importantly for treatment decisions, biologics do not appear to increase the risk of psoriasis compared with conventional immunosuppressants and may in fact be associated with a lower risk. This provides reassurance for patients and clinicians considering biologic therapy and challenges the narrative that these medications trigger psoriasis. Future research should aim to confirm these findings in other populations, investigate the biological mechanisms underlying the relationship between eczema and psoriasis, and examine whether specific biologic agents differ from one another in their effects on psoriasis risk.

Background Erythema nodosum leprosum (ENL) is a severe inflammatory complication of leprosy that often requires prolonged corticosteroid therapy which is associated with adverse effects. Methotrexate is an affordable immunomodulatory agent with limited evidence for its use in ENL treatment. We evaluated whether weekly oral methotrexate in additional to prednisolone reduces the need for additional prednisolone in adults with severe ENL. Methods and Findings We performed an international, multicentre, double-blind, randomised, placebo-controlled trial conducted at five leprosy referral centres in Ethiopia, India, Indonesia, and Nepal. Adults aged 18-60 years with severe ENL were randomised to receive oral methotrexate and prednisolone, or matching placebo and prednisolone. All participants received an identical prednisolone regime over 20 weeks and were followed for 60 weeks. The primary outcome was time to first ENL flare requiring additional prednisolone, assessed over 24 and 48 weeks. Between January 2023 and June 2024, 231 individuals were screened and 137 were randomised (68 methotrexate and prednisolone; 69 placebo and prednisolone). By 24 weeks, 85/137 (62.0%) participants experienced an ENL flare requiring additional prednisolone; the adjusted hazard ratio (HR) for methotrexate versus placebo was 0.98 (95% CI 0.62-1.54). By 48 weeks, 102/137 (74.5%) experienced an ENL flare; adjusted HR 0.95 (95% CI 0.62-1.43). Secondary outcomes were similar: methotrexate did not reduce ENL severity at first flare, flare frequency, or severity of subsequent flares. Health-related quality of life improved substantially in both groups with no evidence of a differential treatment effect. Methotrexate was generally well tolerated. The trial was registered at ClinicalTrials.gov (NCT03775460). Conclusions Oral methotrexate added to prednisolone did not reduce the requirement for additional prednisolone or delay ENL flares compared to placebo and prednisolone, and our study does not support the use of methotrexate for severe ENL.