Archives of Disease in Childhood

BackgroundAn upsurge in Streptococcus pyogenes infections 2022-2023 highlighted potential benefits of point-of-care tests (POCT) to support clinical pathways, prevent outbreaks, and optimise antibiotic use. ObjectivesWe conducted a pilot research study in a west London paediatric emergency department (ED) to determine whether a molecular POCT had potential to alter management in children who were also having a conventional throat swab taken for culture. MethodsChildren <16 years presenting to ED who had a throat swab requested by a clinician were invited to have a second swab taken for research purposes only. Clinical management was unaffected by the research swab result, which was processed using a molecular POCT that was not approved for use in the host NHS Trust. ResultsPrevalence of streptococcal infection was low during the study (May 2023-June 2025); swab positivity in symptomatic children was 12.8% (6/47). Overall, 38/49 (77.6%) participants who had throat swabs received antibiotics. Of those children recommended to receive antibiotics, 29/38 (76.3%) had a negative POCT. Mean time to reporting of positive throat swab culture results was 3.67 days (range 3-5 days) leading to occasional delay in treatment, although POCT identified positive results within minutes. ConclusionAntibiotic use was frequent and could be avoided or stopped by use of a rule out POCT in over three-quarters of children in the ED, if suspicion of S. pyogenes is the main driver for prescribing. POCT were easy to process and produced immediate results compared with culture, in theory enabling timely decision-making and avoiding treatment delay.

Objective The decline of the perinatal demise rate is slowing and demises are often unexplained. Significant research has been done regarding diagnostic yield and genetic causes of demise, but little is known about how Geneticist involvement impacts outcomes. The goal of the study was to evaluate post-mortem genetic testing practices and effects of the geneticists involvement. Methods Retrospective data from 111 perinatal demise cases was examined, including rates of prenatal genetic counseling, post-delivery genetics consult, genetic testing, and autopsy investigation. Results In this cohort 54% received genetic testing and 25% received a genetics consult. When compared to those without, cases with genetic specialist involvement were associated with significant increases in testing uptake (p=0.007), diagnostic yield (p<0.001), and patient education (p<0.001). Second trimester stillbirths and those with fewer ultrasound (US) abnormalities were less likely to receive genetic testing (both p values <0.001) and consults (p<0.001, p=0.020). Conclusion Though it was not possible to avoid ascertainment bias, this data demonstrates that geneticist involvement correlates with a higher rate of testing, greater diagnostic yield, and more thorough counseling. These findings underscore the importance of integrating genetics providers into perinatal postmortem healthcare teams.

Recognizing the challenges faced by primary caregivers regarding the health of children with congenital craniofacial anomalies (CCAs) contributes to strengthening healthcare programs according to patient[s] and families differential needs. This qualitative study presents the experiences of 25 caregivers of children with CCAs from Bogota and Cali, Colombia, identified from care registries and consultation statistics provideed from public high-complexity healthcare institutions. Grounded in Giorgis descriptive phenomenology and employing thematic analysis, this research utilized semi-structured interviews and focus groups to explore the diagnostic process and its impact, experiences with healthcare services, and the caregivers role and daily care activities. Data were analyzed using MAXQDA(R) qualitative software. Findings highlighted the emotional complexity of caring for childre[n]s health. Challenges included late diagnoses, pessimistic views of the children with CCAs condition by healthcare team members; lack of effective support, information, and guidance from health staff; absence of clear care and referral protocols, and limited access to specific adaptations and timely specialized care for children with CCAs. There were also reduced therapeutic services, and a pronounced gendered caregiving burden when responsibilities fall almost exclusively on mothers. System fragmentation, reflected in deficiencies in communication and a lack of clear, coordinated, and timely pathways of care, as well as the absence of adequate psychosocial support for families, emerged as common structural problems in healthcare services in both geographic settings where this research has been conducted. Gender-sensitive strategies focused on alleviating emotional concerns and the burden of caregiving from diagnosis onward within a patient and family-centered care model are decisive. Improving comprehensive CCAs training for healthcare personnel and making adjustments to care pathways are suggested to contribute to the implementation of inclusive health programs that address the diverse needs of children and their families.

Background Childhood 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. Methods We 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. Results: These 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. Conclusions The 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.

Objective: To describe the clinical characteristics of term neonates with neonatal bacterial meningitis (NBM) and explore the association between different pathogens and imaging complications, providing clinical evidence for early identification and individualized management. Methods: A retrospective study was conducted on 531 term neonates diagnosed with NBM admitted to the Capital Institute of Pediatrics from 2013 to 2025. Demographics, clinical manifestations, laboratory parameters, etiological results, imaging complications and treatment measures were collected. Patients were divided into favorable/adverse discharge outcome groups and pathogen-positive/negative groups. Statistical analyses were performed using appropriate tests, and Cramers V coefficient was used to analyze the association between pathogens and imaging complications. Results: (1) The most common clinical manifestations were abnormal body temperature (79.85%), altered consciousness (55.18%) and jaundice (46.52%). CSF/blood culture was positive in 133 cases (25.05%), with Escherichia coli (27.07%), group B streptococcus (17.29%) and Staphylococcus species (16.54%) as predominant pathogens. The overall incidence of imaging complications was 22.22%, mainly hydrocephalus (5.84%), subdural effusion (4.90%) and encephalomalacia (2.64%). (2) Adverse discharge outcomes occurred in 107 cases (20.15%). Compared with the favorable group, the adverse group had higher incidences of convulsions, altered consciousness, anterior fontanelle bulging, abnormal muscle tone and primitive reflexes (all P<0.001), more obvious laboratory abnormalities (higher CRP, CSF leukocytes and protein, lower CSF glucose, all P<0.05), higher culture positive rates and greater need for adjuvant therapy (all P<0.001). (3) Pathogen-positive patients had higher imaging complication rates. Gram-negative infections were associated with higher hydrocephalus and subdural effusion rates, while Gram-positive infections had higher brain abscess risk. Specifically, Escherichia coli correlated with hydrocephalus and subdural effusion; group B streptococcus with cerebral infarction and encephalomalacia; LM with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). Conclusion: Term NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens are Escherichia coli, group B streptococcus and Staphylococcus species, with hydrocephalus and subdural effusion as common imaging complications. Adverse outcomes are associated with severe symptoms, obvious laboratory abnormalities and higher pathogen positivity. Specific pathogens correlate with distinct imaging complications.

Background Individuals experiencing or at risk of homelessness face substantial barriers to preventive eye care that are poorly addressed by standard service models. Interdisciplinary optometry-social work collaboration offers a rights-based approach to improving engagement and continuity of care. Methods A convergent mixed-methods study was conducted between February and August 2024 at a multidisciplinary community centre. Clients experiencing or at risk of homelessness received integrated optometry and social work assessment and were prioritised as high, medium, or low based on combined clinical and social risk. Social work follow-up was guided by the Triple Mandate and W-Questions framework. Quantitative data were summarised using mean (SD), median [IQR], or n (%). Qualitative case notes were analysed using content analysis with inductive coding and secondary review for consistency. Results A total of 165 clients had priority categories coded (high: 68; medium: 47; low: 154). Demographic data were available for 132 clients (60% male; mean age 49.5 years [SD 16]); 27% had not completed high school, 89% reported weekly income below AUD 1000, and 28% had vision impairment. Two hundred forty-five case-note entries were consolidated into 146 unique records. SMS (46%) and phone calls (38%) were the most documented contact methods, although only 21% of calls were answered; missed calls (13%) and disconnected numbers (7%) were common. Multi-modal contact was more frequently documented for higher-priority clients. Appointment assistance was the most recorded facilitator (71%), while rights-based supports, including interpreter and transport assistance, were infrequently documented (<=5%). Qualitative analysis identified unstable communication, reliance on informal supports, and service fragmentation as key influences on recall outcomes. Conclusion This study supports an interdisciplinary, rights-based optometry-social work model to address barriers to preventive eye care among people experiencing or at risk of homelessness. Embedding structured handovers and tiered recall processes within community-based services may strengthen continuity and accountability for high-priority clients. Future implementation should evaluate outcomes related to equity of reach, service integration, and sustained engagement in care.

BackgroundPaediatric liquid medicines (PLMs) routinely contain sucrose to improve palatability, yet their cariogenic potential is well established. Healthcare professionals awareness and prescribing practices regarding sugar-free PLMs have received limited study in India, particularly in Uttarakhand. MethodsA descriptive cross-sectional study was conducted among 500 healthcare professionals aged [&ge;]25 years, using a pilot-tested structured questionnaire (Cronbachs = 0.85), administered online and in person across Uttarakhand districts (January-March 2024). After excluding 69 incomplete responses, 431 participants were analysed (response rate: 86.2%), comprising general medicine practitioners (49%, n = 211), paediatricians (27%, n = 116), and dental practitioners (24%, n = 104). Descriptive statistics and chi-square tests were applied (p < 0.05). ResultsPrescription decisions were primarily driven by childs age and weight (58%), cost (40%), and pharmaceutical brand (37%). While 88% recognised PLM sweetness and 67% were aware of pH-dental harm links, only 20% associated PLMs with dental caries. Overall awareness of hidden sugars was 73%. Eighty-three percent knew of sugar-free alternatives (50% local availability), yet 80% found them less palatable and 85% costlier. Only 48% routinely provided oral health advice. A statistically significant association was found between specialty and sugar-free PLM awareness (p = 0.03), with dental practitioners recording the highest awareness (90%). ConclusionsHealthcare professionals demonstrated variable levels of knowledge, attitudes, and practices regarding PLMs, with critical gaps in caries recognition (20%) and oral health counselling (48%). Despite high sugar-free PLM awareness, uptake is constrained by perceived cost and palatability barriers. Targeted continuing medical education and policy measures, including sucrose-free labelling promotion, are needed to improve paediatric oral health outcomes in Uttarakhand. KEY MESSAGESO_LIOnly 20% of healthcare professionals in Uttarakhand associated pediatric liquid medicines (PLMs) with dental caries, representing a critical knowledge gap despite 88% recognising their sweetness. C_LIO_LIOverall awareness of hidden sugars in PLMs was 73%, yet only 48% routinely provided post-prescription oral health counsellingsubstantially below international benchmarks. C_LIO_LIEighty-three percent were aware of sugar-free PLM alternatives, but adoption was constrained by perceived inferior palatability (80%) and higher cost ([~]10% premium, cited by 85%). C_LIO_LIDental practitioners demonstrated significantly higher sugar-free PLM awareness than general practitioners and pediatricians (p = 0.03), supporting the case for interprofessional oral health education in medical training. C_LIO_LITargeted continuing medical education (CME) and policy measuresincluding sucrose-free labelling mandates and institutional formulary inclusionare needed to convert awareness into prescribing practice change. C_LI

BackgroundSouth Africas public healthcare system serves most of the population through approximately 3,900 primary healthcare clinics characterised by long waiting times and high volumes of repeat-prescription visits. No published pre-arrival digital triage system operates across all 11 official South African languages while aligning with the South African Triage Scale (SATS). This paper reports the design and preliminary safety validation of BIZUSIZO, a hybrid deterministic-AI WhatsApp triage system. MethodsBIZUSIZO delivers SATS-aligned triage via WhatsApp, combining AI-assisted free-text classification (Claude Haiku 4.5) with a Deterministic Clinical Safety Layer (DCSL) that overrides AI output for 53 clinical discriminator categories (14 RED, 19 ORANGE, 20 YELLOW) coded in all 11 official languages and independent of AI availability. A five-domain risk factor assessment can only upgrade triage level. One hundred and twenty clinical vignettes in patient language (English, isiZulu, isiXhosa, Afrikaans; 30 per language) were scored against a developer-assigned gold standard with independent blinded nurse review. A 121-vignette multilingual DCSL safety consistency check across all 11 languages and a 220-call post-hoc framing sensitivity evaluation (110 paired vignettes) were also conducted. ResultsUnder-triage was 3.3% (4/120; 95% CI: 0.9%-8.3%) with no RED under-triage; exact concordance was 80.0% (96/120) and quadratic weighted kappa 0.891 (95% CI: 0.827-0.932). One two-level under-triage was observed on a non-RED presentation (V072, isiXhosa burns vignette, ORANGEGREEN); one two-level over-triage was observed (V054, isiZulu deep laceration, YELLOWRED). In the framing sensitivity evaluation, AI-only classification achieved 50.9% RED invariance under adversarial framing; full-pipeline classification achieved 95.0% in four validated languages, with the DCSL rescuing 18 of 23 AI drift cases. ConclusionsA hybrid deterministic-AI triage system with DCSL-based emergency detection achieved zero RED under-triage and consistent RED detection across all 11 official languages. The 16.7% over-triage rate falls within published South African SATS ranges (13.1-49%). A single two-level under-triage event was observed on an isiXhosa burns vignette (ORANGEGREEN) and is discussed in Limitations. Findings are preliminary; prospective validation against independent nurse triage is the necessary next step.

ObjectivesTo evaluate the effect of surgical hubs on the volume of surgeries, patient waiting times, and length of hospital stay for elective hip and knee replacements in the English NHS. DesignA retrospective longitudinal study using a difference-in-differences approach to compare changes in outcomes at NHS trusts that opened surgical hubs with those that did not. SettingThe study was set in the English NHS, using administrative data from NHS acute trusts providing elective hip and knee replacements between April 2014 and September 2024. ParticipantsThe study included 76 NHS trusts. The treatment group consisted of 29 trusts that opened a surgical hub for trauma and orthopaedic surgery during the study period. The control group consisted of 47 trusts that did not. 48 trusts that performed fewer than 1,000 relevant procedures over the ten-year period or that reported data for fewer than 41 of the 42 quarters in the sample period were excluded. InterventionThe phased introduction of surgical hubs dedicated to elective procedures at 29 NHS trusts between Q1 2020 and Q3 2024. Main outcome measuresThe three main outcomes were, measured at the trust-quarter level: the total number of elective primary hip and knee replacements (surgical volume), the average length of stay in hospital, and the average waiting time from being added to the waiting list to hospital admission. ResultsThe opening of a surgical hub was associated with an increase of 43.75 hip and knee replacement surgeries per quarter (95% CI: 22.22 to 65.28), which represents a 19.1% increase compared to the pre-hub mean. Length of stay was reduced by 0.32 days (95% CI: - 0.48 to -0.16), a 7.8% reduction. There was no statistically significant effect on average waiting times (-14.96 days, 95% CI: -33.11 to 3.19). ConclusionsSurgical hubs appear to be effective at increasing the number of hip and knee replacements and reducing the time patients spend in hospital. However, in this study, they did not lead to a statistically significant reduction in waiting times overall.

BackgroundAccess to safe, equitable, and affordable surgical and anesthesia care is critical to reducing the burden of surgical diseases in Africa. To understand the state of access in South Sudan, we conducted a baseline assessment of surgical services in Central Equatoria State (CES) in May 2024. ObjectivesThis study aimed to survey public healthcare facilities in CES capable of providing essential surgical services. We used the capacity to perform cesarean section, laparotomy, and open fracture management--Bellwether procedures--as a proxy for assessing workforce, infrastructure, financing, information management, and service delivery. MethodsWe used a validated and contextualized Surgical Assessment Tool developed by the Harvard Program on Global Surgery and Social Change and the World Health Organization. Data were collected at the facility level and summarized descriptively using percentages, means (standard deviations), medians (minimum, maximum), and visualized in graphs, charts, and tables. ResultsAll three public health facilities assessed could perform Bellwether procedures for their catchment populations. However, workforce availability, financing, and surgical infrastructure were major constraints. The surgical workforce density was 2.27 surgical, anesthesia, and obstetric specialists per 100,000 population. Specialized procedures--such as repair of cleft lip and palate, clubfoot, and hydrocephalus shunt--were unavailable at all sites. None had magnetic resonance imaging (MRI) machines. The total average annual facility budget was $918,850, ranging from $3,960 to $800,000 at the teaching hospital--insufficient for proper operations. ConclusionWhile Bellwether procedures are routinely performed, access to quality and affordable care is compromised by deficits in workforce, financing, and infrastructure. We recommend that the Ministry of Health scale this survey nationally and develop a surgical policy and strategic plan focused on improving infrastructure, workforce, and financing for surgical and anesthesia care in South Sudan.

Objectives Concerns about COVID-19 were a key driver of infection-prevention behaviour during the pandemic. The aim of this study was to gain an in-depth longitudinal understanding of the type and frequency of concerns experienced throughout the first two years of the COVID-19 pandemic. Design Content analysis of qualitative descriptions provided in a prospective longitudinal online survey as part of the COVID-19 UK Public Experiences (COPE) Study. Method At baseline (March/April 2020), when the UK entered its first national lockdown, 11,113 adults completed the COPE survey. Follow-up surveys were conducted at 3, 12, 18 and 24 months. Participants were recruited via the HealthWise Wales research registry and social media. Baseline surveys collected demographic and health data, and all waves included an open-ended question about COVID-19 concerns. Content analysis was used to identify the type and frequency of concerns at each time point. Results A total of 41,564 open-text responses were coded into six categories: personal harm (n=16,353), harm to others (n=11,464), social/economic impact (n=6,433), preventing transmission (n=4,843), government/media (n=1,048), and general concerns (n=1,423). The proportion of respondents reporting any concern declined from 75.3% at baseline to 65.8% at 24 months. Over time, concerns about personal harm increased (baseline 41.8% vs. 24-months 52.7%) whereas concerns about harm to others decreased (baseline 48.5% vs. 24-months 28.6%). Concerns about harm were also expressed in relation to clinical vulnerability, lack of trust in government/media, and perceived lack of adherence by others. These were balanced against concerns about wider social and economic impacts of restrictions. Conclusions Public concerns about COVID-19 evolved substantially over the first two years of the pandemic, reflecting changing perceptions of risk and responsibility. Monitoring concerns longitudinally is vital to help guide effective communication and behavioural interventions during future pandemics.

Although the co-occurrence of diarrhea and malnutrition is well documented, research has largely focused on the acute management of diarrheal illness. Despite its importance, longitudinal evidence characterizing post-diarrheal recovery trajectories is sparse. We sought to characterize post-diarrheal nutritional recovery trajectories among children aged 6-35 months who were malnourished at enrollment using data from the Enterics for Global Health (EFGH) Shigella Surveillance study (2022-2024). EFGH enrolled children aged 6-35 months presenting with medically-attended diarrhea and followed them at 4 weeks and 3 months post-enrollment. This analysis included children with baseline wasting, stunting, or underweight (z-score < -2) and complete anthropometric follow-up. Latent class mixed-effects models were used to identify distinct post-diarrheal growth trajectories based on changes in anthropometric z-scores over time. Multinomial modified Poisson regression models examined associations between baseline factors and trajectory membership. Among 9,480 enrolled children, 16.5% (n=1,561) were wasted, 22.7% (n=2,155) stunted, and 21.0% (n=1,994) underweight at baseline. Wasting showed greater recovery potential (80.8%) compared with stunting (38.5%) and underweight (40.3%). Recovery was shaped by factors across multiple levels. Clinical severity markers ( prolonged diarrhea, dehydration, and hypoxemia) increased the risk of nutritional failure. Age also influenced outcomes: infants were more likely to worsen, whereas older toddlers more often experienced stagnation. Interventions including exclusive breastfeeding, oral rehydration therapy, appropriate antibiotics, and zinc supplementation, improved outcomes, while unimproved sanitation undermined recovery. These findings highlight the need for integrated strategies combining infection control, nutritional rehabilitation, and water, sanitation, and hygiene interventions tailored to the childrens developmental stage. Key MessagesO_LIPost-diarrheal nutritional recovery is highly heterogeneous, with wasting showing the greatest potential for improvement, while stunting and underweight often result in persistent growth stagnation. C_LIO_LIBaseline anthropometric deficits alone are insufficient to predict recovery, highlighting the need for dynamic monitoring and individualized management. C_LIO_LIInfants are particularly vulnerable to acute nutritional deterioration, while older toddlers frequently experience growth stagnation. C_LIO_LIModifiable protective factors including exclusive breastfeeding, ORS, zinc, and appropriate antibiotics, improved outcomes, whereas poor sanitation undermined recovery. C_LIO_LIIntegrated strategies, tailored to a childs developmental stage, combining clinical care, nutrition, and environmental interventions are critical to support sustained child growth and development. C_LI

Background: Acute necrotizing encephalopathy (ANE) is a rare and severe neurologic complication of viral infection in children, thought to result from a hyperacute cytokine storm causing blood-brain barrier disruption and central nervous system injury. Despite characteristic clinical and radiologic features, ANE remains poorly understood at the molecular level, with no validated biomarkers or targeted therapies. We aimed to determine whether genetic predisposition to ANE due to RANBP2 variants is associated with a distinct immunologic signature. Methods: We conducted a prospective biological study of familial ANE (ANE1, NCT06731790). We included 23 heterozygous carriers of the RANBP2 c.1754C>T (p.Thr585Met) variant from 10 families, and 28 noncarriers (median age, 40 years [range, 4-72]). Soluble immune mediators, transcriptomic analyses, multiparameter flow cytometry, and cellular imaging were analysed in peripheral blood mononuclear cells (PBMCs) and monocytes. Baseline and resiquimod stimulated immune responses were analysed within the same statistical model, with genetic status as the primary predictor. Findings: The RANBP2 Thr585Met mutation was associated with a dysregulated inflammatory phenotype characterized by reduced basal mediator production and exaggerated TNF- responses following stimulation (estimated difference, +2,098 pg/mL; 95% CI, 1,121 to 3,076; P=0.0001). Transcriptomic and flow cytometry analyses showed broad reprogramming of myeloid cells with enrichment of CXCR3-high CD14-high subsets. Expansion of these populations was associated with increased long-term disease burden. The RANBP2 variant was the only independent factor associated this inflammatory phenotype. Interpretation: RANBP2-associated ANE is characterised by a distinct immunological signature that can inform disease stratification and support the development of targeted immunotherapeutic approaches.

ObjectivesTo estimate current, and 5- and 10-year projected, number of cases of cancer per year in transgender and gender diverse (TGD) people in England, overall and by tumour type, accounting for uptake of gender affirming care (GAC). DesignPopulation-based epidemiological modelling study using an age-stratified Monte Carlo simulations approach and the NORDPRED method for predictions. SettingModels estimating cancer case numbers for TGD people in England based on publicly available 2023 cancer surveillance data and survey-based 2025 GAC access, and predicted at 5 and 10 years hence. ParticipantsTGD people aged 15 years and above. Main outcome measuresPrimary cancer cases per year overall, by gender, age group, tumour type, and current and planned GAC. ResultsThe estimated TGD population size in England is 441547 (95% uncertainty interval (UI) 429207- 452890). Total cases per year of cancer in TGD people is expected to be 966 (95% UI 882-1069) excluding non-melanoma skin. Most cases are expected to occur in people aged 60-64. The top 5 expected cancers in TGD people are breast (19%, n = 187, 95% UI 149-241), colorectal (12%, n = 117, 95% UI 106-129), lung (11%, n = 108, 95% UI 96-122), melanoma (7.1%, n = 69, 95% UI 64-74) and urinary (6.2%, n = 60, 95% UI 54-67). Total cases of cancer in TGD people are estimated to be 1740 (95% UI 1584-1934) in 5 years and 2258 (95% UI 2066-2507) in 10 years (excluding non-melanoma skin). If TGD people were able to access their planned level of GAC, this would reduce these figures to 1555 (95% CI 1386-1766) and 2012 (95% CI 1797-2282) respectively. ConclusionsThis study provides prediction of cancer cases in TGD people in England, supporting the planning of service provision and training. This is vital, as with increasing disclosure, and long wait times for GAC, cancer cases in TGD people are predicted to increase. Summary BoxesO_ST_ABSWhat is already known on this topicC_ST_ABSThe annual number of cases of cancer in transgender and gender diverse (TGD) people in England is currently unknown as gender incongruence is not collected as part of the National Cancer Registration and Analysis Service. Some gender-affirming care (GAC) interventions are known to modulate cancer risk. Use of testosterone and chest reconstruction for transmasculine people is known to reduce their incidence of breast cancer compared to cisgender women. Use of oestradiol alongside medical or surgical androgen suppression has been shown to reduce the incidence of prostate cancer in transfeminine people while increasing their risk of breast cancer, compared to cisgender men. What this study addsThis study found that there are likely to be approximately 966 cases of cancer (excluding non-melanoma skin) in TGD people per year in the UK. Though total annual cases of cancer in TGD people are expected to be 2258 in 10 years, improved access to gender-affirming care could reduce total cases to 2012 (a 11% reduction). These figures provide additional justification for funding to improve access to GAC via the National Health Service (NHS), as well as for training on the oncological needs of this population.

Abstract Background Spontaneous coronary artery dissection (SCAD) is a well-recognised cause of acute coronary syndrome particularly among women without conventional cardiovascular risk factors. Increasing evidence indicates a genetic contribution; however, the underlying genetic architecture of SCAD remains insufficiently understood. Objective The aim of this study was to assess the prevalence of rare variants in previously reported SCAD associated genes and to explore the potential presence of novel genetic alterations in well-characterised Swedish patients with SCAD. Methods The study comprised 201 patients enrolled in SweSCAD, a national project examining the clinical characteristics, aetiology, and outcomes of SCAD. All individuals had a confirmed diagnosis based on invasive coronary angiography. Comprehensive exome sequencing was performed to identify rare variants contributing to disease susceptibility. Results Genetic variants that have been associated with SCAD according to current clinical genetics practice for variant reporting were identified in approximately 4 % of patients. In addition, rare potentially relevant variants were detected in almost 60 % of patients in genes associated with vascular integrity and vascular remodelling. Conclusion This study supports SCAD as a genetically complex arteriopathy, driven by rare high?impact variants together with broader polygenic susceptibility. Variants in collagen, vascular extracellular matrix, and oestrogen?responsive pathways provide biologically plausible links to female?predominant disease. Although the diagnostic yield of clearly actionable variants is modest, these findings support broader genomic evaluation beyond overt syndromic presentations and highlight the need for larger integrative genomic and functional studies to refine risk stratification and management.

Background: Lung cancer screening can reduce lung cancer mortality through early detection, but uptake of the NHS Targeted Lung Health Check (TLHC) programme remains low. Behaviourally informed invitation messages have been proposed as a low-cost approach to increase attendance, but evidence of their effectiveness in lung cancer screening is mixed. Few intervention studies used evidence-based behaviour change frameworks, and rarely tailored invitation strategies to empirically identified barriers and enablers. Methods: In an online experiment, 3,274 adults aged 55-74 years and with a history of smoking were randomised to see one of four behaviourally informed invitation messages or a control message. Participants then rated their intention to attend a TLHC appointment, and selected barriers and enablers to attending from a pre-defined list, which were classified according to the Theoretical Domains Framework. Invitation messages were mapped to Behaviour Change Techniques using the Theory and Techniques Tool. Message conditions were compared on intention to attend TLHC using bootstrapped ANOVA followed by pairwise comparisons. Exploratory counterfactual mediation analyses examined the role of fear in intention to attend. Results: Behaviourally informed invitation messages did not meaningfully increase intention to attend TLHC compared with the control message. While a GP-endorsed message showed a small potential benefit relative to the other conditions, this finding was not robust after adjustment for multiple comparisons. Participants most frequently reported barriers related to Emotion (particularly fear), Social Influence, and Knowledge, while Beliefs about Consequences emerged as the primary enabler of attendance. Only around half of reported barriers and enablers were addressed by the invitation messages. Exploratory analyses found that fear was associated with lower intention to attend a TLHC appointment, yet none of the behaviourally informed messages appeared to reduce fear compared to the control message. Conclusions: Improving lung cancer screening uptake will likely require invitation messages that directly address emotional concerns, particularly fear, alongside credible recommendations. These findings highlight the importance of systematically aligning invitation message content with empirically identified behavioural influences when designing scalable interventions to improve lung cancer screening uptake.

BackgroundPolygenic embryo screening (PES) has recently become available to in-vitro fertilization (IVF) patients, allowing them to evaluate the genetic risk of each of their embryos for polygenic conditions such as heart attack or diabetes. Initial modeling predicted that transferring the embryo with the lowest genetic risk for one or more diseases would substantially reduce prevalence in the next generation, with relative risk reductions up to 50%. However, these models assumed the availability of a prespecified number of embryos and that the embryo with the most favorable polygenic risk is born once transferred to the uterus. In reality, a large percentage of embryo transfers do not lead to live births, and IVF frequently results in no or only a single live birth. MethodsTo quantify the expected risk reduction in the context of IVF, we used two datasets: 6944 ovarian stimulation cycles from 4452 Italian infertility patients and 2138 stimulation cycles of egg donors. In both datasets, we simulated the hypothetical application of PES in these cycles by assigning patients and their embryos randomly drawn polygenic risk scores for a given disease, assuming that embryos have been transferred in increasing order of their risk, and tracing their birth outcomes. We then compared the risk of the embryo born after hypothetical PES to the risk of an embryo born without PES. We either considered only completed cycles or integrated over possible birth outcomes of non-transferred embryos in incomplete cycles. ResultsIn stimulation cycles in infertility patients in which all embryos have been transferred and at least one child was born, we estimate that PES will result in relative risk reductions of just {approx}1-3%. In an intention-to-screen analysis of all completed cycles (regardless of birth outcomes), relative risk reductions are under 0.5%. The risk reductions increase, as expected, with more euploid blastocysts and with younger maternal age. Including incomplete cycles (in which not all embryos have been transferred) increases risk reductions to {approx}2-5%, due to the availability of more euploid blastocysts and a higher live birth rate per transfer in these cycles. Pooling all embryos from all cycles of the same patient increases risk reductions to {approx}5-10%. Relative risk reductions in egg donor cycles reach {approx}20% even with a single stimulation cycle per donor. ConclusionsWith the exception of particularly good-prognosis patients or cycles, typical infertility patients would benefit little from PES. In fertile patients, as represented by egg donors, PES is predicted to achieve greater relative risk reductions. However, even though these reductions are still substantially lower than prior estimates that did not account for realistic live birth rates. Ethical, social, and clinical issues associated with offering PES in the general population should be prioritized in future research.

Background Regulatory inconsistency across African countries contributes to duplicative scientific assessments, prolonged approval timelines, and delayed access to essential medical products. To inform the operationalisation of the African Medicines Agency (AMA), the African Medicines Regulatory Harmonisation (AMRH) programme implemented Africa's first continental pilot study for the scientific evaluation and listing of human medicinal products. This study evaluates the pilot's procedural performance and examines how continental scientific opinions were translated into national regulatory decisions through reliance mechanisms. Methods and Findings A mixed-methods programme evaluation was conducted using regulatory datasets generated during the pilot study. Quantitative data included assessment timelines, GMP inspection outcomes and national post-listing regulatory actions. Retrospective qualitative thematic analysis was applied to governance documents and National Regulatory Authority (NRA) feedback to identify legal, institutional and procedural determinants influencing uptake. Of 64 expressions of interest, 24 products progressed to full evaluation and 12 received positive continental scientific opinions. Ten met the predefined performance target of [&le;]210 working days. Twenty-four GMP inspections identified no critical deficiencies and aligned with global regulatory benchmarks. National uptake demonstrated active reliance: full reliance (continental opinion as primary basis for national approval) for 7 products (58%); sequential reliance (continental assessment supplemented with targeted national queries) for 3 products (25%); and supplemented national review (separate national assessment undertaken) for 2 products (17%). Products with broader market strategies achieved registration in up to 23 African countries within a median of 77 working days post-listing. Variability in uptake reflected national legal authority, administrative requirements, and applicant submission strategies Conclusions The pilot study demonstrates the feasibility of a continent-wide regulatory assessment mechanism capable of producing trusted scientific outputs and enabling reliance-based national decision-making in Africa. While reliance was widely applied, heterogeneity in national procedures and administrative sequencing affected time to national registration. Findings provide empirical evidence to inform the AMA scale-up, highlighting the need for harmonised reliance pathways, streamlined administrative processes, and coordinated digital regulatory infrastructure.

BackgroundDespite advances in therapy, optimal management of juvenile idiopathic arthritis (JIA) remains challenging. The ability to predict disease progression in JIA can improve personalized treatment decisions, but few reliable clinical predictors have been identified. We developed machine learning approaches to predict disease trajectories in children with JIA. MethodsUsing data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry (years 2015-2024), we developed machine learning models to predict attainment of inactive disease in children with non-systemic JIA. We applied Dynamic Bayesian Networks (DBN) to model temporal dependencies and causal relationships, and Convolutional Neural Networks (CNN) to capture complex non-linear patterns. Model input included demographic factors, longitudinal clinical factors, and medication use in the preceding 12 months. FindingsA total of 8,093 participants were included. When tested on an independent test cohort, both DBN (AUC:0.76; precision:0.73; recall:0.83; F1-score:0.78; accuracy:0.71) and CNN (AUC:0.76; precision:0.71; recall:0.63; F1-score:0.67; accuracy:0.70) models achieved comparable performance in predicting inactive disease. Disease activity levels in the preceding 12 months, presence of enthesitis and uveitis were the strongest predictors. Causal relationships captured in the DBN model revealed suboptimal care patterns, likely shaped by insurance constraints and a predominantly reactive approach to JIA management. InterpretationOur study demonstrates that machine learning approaches can predict disease trajectories in JIA with good discriminative performance. Unlike prior studies that predict outcomes at single timepoints, our models are the first to predict inactive disease longitudinally. However, suboptimal care patterns in retrospective data limit models capacity to learn treatment-outcome relationships, underscoring critical opportunities to improve JIA care and the need for prospective comparative studies to better inform prediction models. FundingPatient-Centered Outcomes Research Institute (PCORI) Award (ME-2022C2-25573-IC). RESEARCH IN CONTEXT Evidence before this studyNumerous studies have sought to identify clinical predictors of JIA progression and outcomes. However, few reliable predictors have emerged and existing prediction models demonstrate limited performance. As a result, our ability to personalize treatment decisions based on individual risk of severe disease course remains limited. Added value of this studyWe developed novel machine learning models that predict individualized disease trajectories in children with polyarticular and oligoarticular JIA using data from their preceding 12-month clinical course. These models demonstrated strong discriminative performance and outperformed previously published machine learning approaches in JIA. Unlike prior studies limited to single time-point predictions, our models are the first to predict inactive disease longitudinally, enabling a patient-specific projection of disease progression over time. Importantly, our findings also bright to light patterns of suboptimal care, likely driven by insurance constraints and a reactive treatment paradigm, underscoring critical opportunities to improve JIA management. Implications of all the available evidenceOur models have the potential to support clinical decision-making by enabling early identification of children with JIA at risk for unfavorable disease trajectories. In addition, the suboptimal care patterns and systems-level barriers identified through our analyses highlight priority areas for quality improvement initiatives and policy interventions to reduce gaps in JIA care delivery.

This updated systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and obesity related complications. Medline and Embase were searched up to 21 November 2025 for randomized controlled trials comparing OMMs versus placebo or active comparators in adults. The primary endpoint was percentage total body weight loss (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and 3 years, anthropometric, metabolic, mental health and quality of life outcomes, cardiovascular morbidity and mortality, remission of obesity related complications, serious adverse events and all cause mortality. Sixty six RCTs (66 comparisons) were identified: orlistat (22), semaglutide (18), liraglutide (11), tirzepatide (8), naltrexone/bupropion (5) and phentermine/topiramate (2), enrolling 63,909 patients (34,861 and 29,048 with active compound and placebo, respectively). All OMMs showed significantly greater TBWL% versus placebo; tirzepatide and semaglutide exceeded 10% TBWL and showed the most favourable glycaemic effects. Semaglutide reduced major adverse cardiovascular events and all cause mortality. In dedicated complication specific trials, semaglutide and tirzepatide showed benefit on heart failure related outcomes; tirzepatide was associated with improved obstructive sleep apnoea syndrome and semaglutide with knee osteoarthritis pain remission. Tirzepatide and semaglutide were associated with improvements in metabolic dysfunction-associated steatohepatitis remission, and semaglutide with improvement in liver fibrosis. No OMMs were associated with an increased risk of serious adverse events. These updated results reinforce the need to individualize OMMs selection according to weight loss efficacy, complication profile and safety.