eClinicalMedicine

ObjectivesTo compare the co-administration of an Ayurvedic drug AYUSH 64 as an adjunct to standard of care (SOC) and SOC for efficacy and safety in the management of COVID-19. DesignMulticentre, parallel efficacy, randomized, controlled, open label, assessor blind, exploratory trial with a convenience sample. Patients followed to complete 12 weeks of study duration. SettingCOVID-19 dedicated non-intensive care wards at 1 government hospital, 1 medical college teaching hospital and 1 medical university teaching hospital Participants140 consenting, eligible, hospitalized adult patients suffering from mild and moderate symptomatic COVID-19 and confirmed by a diagnostic (SARS-CoV-2) RT-PCR assay on nasal and throat swab were randomized to SOC or SOC plus AYUSH 64. To be withdrawn if disease becomes severe. InterventionsTwo tablets of AYUSH 64, 500 mg each, twice daily after meals, and continued till study completion. SOC (symptomatic and supportive) as per national guidelines of India for mild and moderate disease. Main outcome measuresTime period to clinical recovery (CR) from randomization baseline and proportion with CR within 28 days time frame; CR defined in the protocol Results140 patients randomized (70 in each arm); 138 patients with CR qualified for analysis. Both groups were matched at baseline. The mean time to CR from randomization was significantly superior in AYUSH 64 group (95% CI -3.03 to 0.59 days); a higher proportion (69.7%) in the first week (p=0.046, Chi-square). No significant differences observed for COVID-19 related blood assays (such as D-Dimer). AYUSH 64 arm showed significant (p<0.05) superior persistent improvement in general health, quality of life, fatigue, anxiety, stress, sleep and other psychosocial metrics. 1 patient on SOC required critical care. 48 adverse events (AE) reported in each group. Barring three SAE (in SOC), AE were mild and none were drug related. 22 participants (8 on AYUSH) were withdrawn. No deaths were reported. ConclusionsAYUSH 64 hastened recovery, reduced hospitalization and improved overall health in mild and moderate COVID-19 when co-administered with SOC under medical supervision. It was safe and well tolerated. Further studies are warranted. Trial registrationThe Clinical Trials Registry India Number CTRI/2020/06/025557 FundingCCRAS, Ministry of AYUSH, Government of India

OBJECTIVEChildhood immunisation rates in the UK have recently fallen to their lowest level in 14 years. There is currently a lack of temporal evidence on parental attitudes to childhood immunisations and how they have evolved in response to the Covid-19 pandemic, limiting our ability to assess the impact of the pandemic on population-level attitudes to non-Covid vaccines. This study aims to assess trends in parental confidence in childhood immunisations between 2020 and 2022 at varying spatial scales in the UK, while also identifying the socio-demographic factors associated with vaccine perceptions and how these have shifted over time. DESIGNThree cross-sectional surveys in 2020, 2021, and 2022. SETTINGUnited Kingdom. PARTICIPANTS14,720 adults responsible for decisions surrounding the vaccination of children. MAIN OUTCOME MEASURESThe percentage of parents indicating past or future refusal for the MMR, HPV, and influenza vaccines for their child in 2020, 2021, and 2022 as well as Covid-19 vaccine refusal for their child in 2022. A combined metric (refusal) is created to measure parental refusal for any childhood vaccine. Associations between these primary outcome measures and socio-demographic variables are investigated via multiple logistic regression, with effects reported via odds ratios. Additionally, the extent to which parental and caregiver perceptions in giving children immunisations since the start of the pandemic is examined using data from 2022. RESULTSAcross the UK overall refusal decreased from 16.2% in 2020 to 14.0% in 2021 (p<0.001) before increasing to 20.8% in 2022 (p<0.001 compared to 2020). This loss was driven by relatively high rates of parental refusal of the Covid-19 vaccine for their children in 2022, rather than perceptions towards other childhood vaccines. A marked negative change in perceptions towards giving childhood vaccines is found among parents who had not themselves received at least three doses of a Covid-19 vaccine, signalling a strong spillover effect of Covid-19 vaccine hesitancy onto routine childhood vaccines. Many parental socio-demographic factors were found to be informative of vaccine refusal, with younger age groups, individuals living in Greater London, Hindus, and Muslims exhibiting higher rates of refusal. Interestingly, however, 18-- 34-year-olds, Hindus, Muslims, and Black / Black British respondents report becoming more positive towards giving about giving their children vaccines in 2022 compared to the start of the pandemic. CONCLUSIONSThe available evidence suggests that parental refusal of routine childhood immunisations has decreased between 2020 and 2022 and remains low across the UK. Encouragingly, many socio-demographic groups with historically low confidence in childhood immunisations appear to be more positive about giving their children vaccines in 2022 compared to the beginning of the pandemic. While these findings are cautiously optimistic, there is still a mismatch between these reported increases in vaccine confidence and uptake rates of routine immunisations across the UK. Parents who did not receive at least three doses of a Covid-19 vaccine feel much less positive about giving their children vaccines since the start of the pandemic compared to those who did receive at least three doses. This group represents an important cohort for targeted outreach and tailored interventions to address lingering concerns and support vaccine uptake.

BackgroundTreatment responsiveness of dermatophytosis has decreased considerably in recent past in India. We compared effectiveness of oral terbinafine daily (Terb) (active control) versus itraconazole daily (Itra) versus terbinafine plus itraconazole daily (TI) versus terbinafine daily plus itraconazole pulse (TIp) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial. MethodsNinety-two microscopically confirmed patients were allocated to Terb (6 mg/kg/day), Itra (5 mg/kg/day), TI (terbinafine 6 mg/kg/day, itraconazole 5 mg/kg/day), or TIp (terbinafine 6 mg/kg/day, itraconazole 10 mg/kg/day for 1 week in 4 weeks) group by concealed block randomization and treated for 8 weeks or cure. ResultsCure rates were similar at 4 weeks (P=0.768). At 8 weeks, 5 (21.7%), 18 (78.3%), 16 (69.6%), and 16 (69.6%) patients were cured in Terb, Itra, TI, and TIp groups, respectively. All experimental regimens (Itra, TI, TIp) were more effective than Terb (P[&le;]0.0027). All experimental regimens had similar effectiveness (P[&ge;]0.738). Relapse rates 4 and 8 weeks after cure were similar (P=0.869 and 0.314, respectively). Number-needed-to-treat (NNT) was 2 for Itra, 3 for TI, and 3 for TIp. ConclusionsOral itraconazole given daily (NNT=2) is the most effective treatment and combining it with terbinafine does not increase effectiveness. One Sentence SummaryCombination of oral terbinafine and itraconazole is not more effective than itraconazole alone in current epidemic of altered dermatophytosis in India.

BackgroundCommon diagnostic tools for atopic dermatitis (AD) often perform worse in skin-of-colour (SOC) populations. The objective of this review is to map the prevalence, validation, and effectiveness of clinician-based and patient-reported tools for diagnosing AD in SOC groups across all ages. MethodsThis review followed PRISMA-ScR guidelines and searched Embase, Scopus, PubMed, MEDLINE, Web of Science, and MedRxiv for articles published January 2015 through December 2023. Eligible studies were observational, randomized, or review articles evaluating clinician-rated scales or patient-reported measures with self-identified race or ethnicity. We excluded non-English publications, case reports/series, guidelines, editorials, and studies lacking stratification. After de-duplication, two reviewers screened titles, abstracts, and full texts with conflicts resolved by a third reviewer. Data extraction captured study design, population demographics, tools evaluated, and key findings on accuracy and reliability in SOC cohorts. Results28 articles (total n = 20 332) met inclusion criteria. 24 assessed clinician-rated scales, most often EASI (n = 16), SCORAD (n = 10), and o-SCORAD (n = 8). These tools frequently underestimate AD severity in Fitzpatrick IV-VI skin types. Five studies examined alternative clinician tools (vIGA-AD, IGAxBSA). Rajka-Langeland and ADSI scores were each assessed once. Patient-reported outcomes (PROs) were dominated by POEM (n = 17), which had only 14% SOC participants during initial validation. PO-SCORAD (a PRO based on SCORAD) was also assessed (n = 10). Nine newer PRO tools (RECAP, ADCT, PSAAD, ADSEQ, CEQ, DFI, CADIS, QoLIAD, PIQoL-AD) appeared in single studies. Adjunctive measures and technological approaches (body-surface area alone, photo guides, AI-assisted analysis, remote assessment) featured in five studies but lack multi-center validation. ConclusionsMost diagnostic tools remain validated in lighter-skinned cohorts and underrepresent SOC populations. Patient-reported measures show promise but require wider validation. Adjunctive and technology-driven methods may improve equity but need rigorous testing. Future research should prioritize multiethnic cohorts, age-specific validation, and consensus-driven adaptation of both clinician and patient-reported tools to ensure reliable assessment for all skin types.

BackgroundHealthcare system disparities have a significant impact on chronic disease management in conflict-affected settings. Vitiligo, a stigmatizing dermatological condition, requires sustained care, yet limited evidence exists regarding how healthcare sector differences affect patient outcomes in Afghanistan. This study addresses this critical knowledge gap in a post-conflict, resource-limited setting. The main objectives of this study were to compare socio-demographic profiles, clinical characteristics, psychological burden, and health-related quality of life (HRQoL) between vitiligo patients attending public versus private hospitals in Kandahar, Afghanistan. MethodsA cross-sectional analytical study was conducted from March 2023 to January 2024 with 402 vitiligo patients (153 [38.1%] from three public hospitals and 249 [61.9%] from five private hospitals). Comprehensive assessment included socio-demographic variables, clinical severity (Vitiligo Area Severity Index [VASI]), psychological distress (General Health Questionnaire-12 [GHQ-12]), anxiety (Hamilton Anxiety Rating Scale [HAM-A]), depression (Quick Inventory of Depressive Symptomatology [QIDS-SR16]), and HRQoL (Dermatology Life Quality Index [DLQI]). Stratified analyses, multivariable linear regression, and interaction testing were performed. ResultsCompared to public hospitals, patients visiting private hospitals were younger (69.3% aged 18- 29 years, {chi}2=21.4, p<0.001), more rural (65.5%, {chi}2=12.7, p<0.001), and less educated (63.9% illiterate, {chi}2=15.2, p<0.001). However, clinical severity (VASI: public M=6.58{+/-}7.47; private M=6.84{+/-}4.64; t=-0.427, p=0.670), psychological burden, and HRQoL showed no significant differences between sectors. Interaction analyses revealed moderating effects: disease severity impacted HRQoL more strongly in public hospitals (VASIxhospital type: B=-0.168, 95%CI: - 0.258 to -0.077, p<0.001, {beta}=-0.515), while psychological distress affected HRQoL more in private settings (GHQxhospital type: B=0.440, 95%CI: 0.094 to 0.785, p=0.013, {beta}=0.442). ConclusionWhile demographic disparities exist in healthcare access, clinical and psychological outcomes are similar across sectors. However, pathways to HRQoL impairment differ significantly, suggesting sector-specific mechanisms requiring tailored interventions. These findings highlight the need for equitable, context-sensitive vitiligo care that addresses both universal and sector-specific determinants of patient well-being in conflict-affected settings.

The dominance of the COVID-19 Delta variant has renewed questions about the impact of K12 school policies, including the role of masks, on disease burden.1 A recent study showed masks and testing could reduce infections in students, but failed to address the impact on the community,2 while another showed masking is critical to slow disease spread in communities, but did not consider school openings under Delta.3 We project the impact of school-masking on the community, which can inform policy decisions, and support healthcare system planning. Our findings indicate that the implementation of masking policies in school settings can reduce additional infections post-school opening by 23-36% for fully-open schools, with an additional 11-13% reduction for hybrid schooling, depending on mask quality and fit. Masking policies and hybrid schooling can also reduce peak hospitalization need by 71% and result in the fewest additional deaths post-school opening. We show that given the current vaccination rates within the community, the best option for children and the general population is to employ consistent high-quality masking, and use social distancing where possible.

BackgroundSkin disease affects 4.7-4.9 billion individuals globally; however, little is known about access to dermatological care. MethodsWe conducted a multinational, cross-sectional survey of dermatological care across 194 WHO member states and three additional geographic areas in 2024-2025. Primary outcomes included dermatologist density per 100,000 population and number of dermatologists globally. Secondary outcomes included training programme density, workforce distribution, perceived access to care, and health system characteristics. Descriptive statistics and nonparametric tests compared outcomes across World Bank Income (WBI) levels and WHO regions. FindingsResponses were obtained from 158 countries. Mean dermatologist density was 2.66 per 100,000, ranging from 0.37 in low-income (LICs) to 5.05 in high-income countries (HICs). There are estimated 175,633 dermatologists globally (95% CI: 173,598-177,668). Forty-two percent of countries reported inadequate or extremely poor access to dermatological care. There was significant variation (p < 0.001) in access to all types of subspecialty care (paediatric, surgical, dermatopathology) across WBI levels, with consistently worse access in lower-income countries. Dermatologists are primarily based in urban centres (79%). Twenty-one percent of countries lack dermatology training programs, with training varying by WBI level (p < 0.001). Non-dermatologist healthcare workers bear a substantial responsibility for management of skin disease. InterpretationSignificant global disparities exist in access to dermatological care, particularly in lower resource settings. Achieving skin health equity will require global commitment to expanding/funding training programmes, incentivizing decentralization of dermatology practice, and optimizing alternative care delivery including upskilling front-line healthcare workers. FundingInternational League of Dermatological Societies and LOreal Dermatological Beauty.

UK-based quantitative research on the health and education outcomes of Unaccompanied Asylum-Seeking Children (UASC) remains limited, especially at national level. Linked administrative data provide an unprecedented opportunity to study these outcomes among UASC. This paper lays a foundation for further research, particularly examining the influence of socio-demographic, legal and environmental factors on UASCs health and educational outcomes. We described the UASC population with a first recorded episode of local authority care between 1st April 2005 and 31st March 2021 in ECHILD, which gathers national records for England, by age, gender, ethnicity, region, and placement type. We calculated linkage rates between the social care and educational dataset, estimating how many UASC were recorded as being enrolled in state-funded schools. We also assessed how many of those linked to the school dataset was linked to National Health Service (NHS) datasets. Finally, we explored how linkage rates between social care, education, and NHS datasets vary by socio-demographic factors and placement type. There were 37,170 UASC recorded in the ECHILD of which 32,570 (88%) were male and 24,290 (65%) aged 16 - 17 years. We found 7,740 (21%) UASC recorded as being enrolled in state funded schools, of whom 6,690 (88%) were also linked to NHS data. The linkage rate for UASC in the social care to health datasets was therefore 19%. Of those 16-17 years at entry in social care, 4% (1,060/24,290) were recorded as enrolled in school compared to 50% (6,390/12,880) under 16 years. Linkage to the school, and subsequently to the NHS dataset, wholly depends on enrolled state-funded education, excluding College and Sixth-form education. Despite this limitation, we characterised a national cohort of 6,890 UASC in England whose social care, education, and health outcomes can be examined.

BackgroundThere are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the 18 to 45-year age-group began in April 2021 when seropositivity rates in the general population were rising due to the Delta wave in April-May 2021. MethodsBetween 30 June 2021 and 28 January 2022, we enrolled 691 participants in the 18-45 age group across 4 clinical sites in India. In this non-randomized and laboratory blinded study, participants received either two doses of Covaxin(R) 4 weeks apart or two doses of Covishield 12 weeks apart per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titer (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination. FindingsWhen compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield elicited higher antibody responses than Covaxin(R) as measured by seroconversion rate (98.3% vs 74.4%, p<0.0001 in seronegative individuals; 91.7% vs 66.9%, p<0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 BAU/ml, p<0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p<0.0001 in seropositive individuals). Not all sites recruited at the same time, therefore site-specific immunogenicity was impacted by the timing of vaccination relative to the Delta and Omicron waves. Surrogate neutralizing antibody responses against variants-of-concern were higher in Covishield recipients than in Covaxin(R) recipients and in seropositive than in seronegative individuals after both vaccination and asymptomatic Omicron infection. T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the Omicron wave. In seronegative individuals, Covishield elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin(R) elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals. InterpretationCovishield elicited immune responses of higher magnitude and breadth than Covaxin(R) in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of the majority of the vaccinated Indian population.

ObjectiveThanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis health outcomes have improved. This paper evaluates the costs and the health-related quality of life implications of these guidelines. Design and settingA sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015. Study participantsData for patients aged [&ge;]16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months. Primary and secondary outcome measuresPatient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS), and the EuroQoL; health care costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life years (QALYs) were calculated from the EQ-5D utility scores. Cost-utility analysis was performed using the NHS and Social Scare perspective. ResultsA total of 49 patients were included, 35 treated within 48 hours "early" (median [IQR] 8.25 [3.7-20.5]) and 14 treated after 48 hours (median [IQR] 93.9 [66.7 - 100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0-3) compared to 4 (29%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p<0.000). After adjusting for age and symptom duration at admission, early treatment incurred a lower average cost at discharge, {pound}23,086 (95% CI: {pound}15,186 to {pound}30,987) vs {pound}42,405 (95% CI: {pound}25,457 to {pound}59,354) [p<0.04]. A -{pound}20,218 (95% CI: -{pound}52,173 to {pound}11,783) cost difference was observed at 12-month follow-up post discharge. ConclusionsThis study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment. Article SummaryO_ST_ABSStrengths and limitations of this studyC_ST_ABS- Admissions to acute hospitals with suspected encephalitis, using predetermined inclusion criteria were recruited across 29 hospitals in the UK within a 3-year period, giving the largest cohort of prospectively recruited HSV encephalitis cases in the UK to date. - Precise definitions to characterise those individuals with proven HSV encephalitis were applied thus ensuring accurate diagnoses. - Individuals were followed up systematically for 12 months after discharge for clinical, and quality of life data providing the first study to assess the effect of treatment delays on health care resources, costs and health related quality of life. - The analysis is limited by its relatively small sample size due to it being a rare disease, and the case record forms although thorough may not capture all health care costs incurred. This is particularly so for primary care and community care contact outside of the study hospitals.

ObjectiveTo assess the early vaccine administration coverage and vaccine effectiveness and outcome data across an integrated care system of eight CCGs leveraging a unique population-level care dataset DesignRetrospective cohort study. SettingIndividuals eligible for COVID 19 vaccination in North West London based on linked primary and secondary care data. Participants2,183,939 individuals eligible for COVID 19 vaccination ResultsDuring the NWL vaccine programme study time period 5.88% of individuals declined and did not receive a vaccination. Black or black British individuals had the highest rate of declining a vaccine at 16.14% (4,337). There was a strong negative association between deprivation and rate of declining vaccination (r=-0.94, p<0.01) with 13.5% of individuals declining vaccination in the most deprived postcodes compared to 0.98% in the least deprived postcodes. In the first six days after vaccination 344 of 389587 individuals tested positive for COVID-19 (0.09%). The rate increased to 0.13% (525/389,243) between days 7 and 13, before then gradually falling week on week. At 28 days post vaccination there was a 74% (HR 0.26 (0.19-0.35)) and 78% (HR 0.22 (0.18-0.27)) reduction in risk of testing positive for COVID-19 for individuals that received the Oxford/Astrazeneca and Pfizer/BioNTech vaccines respectively, when compared with unvaccinated individuals. After vaccination very low rates of hospital admission were seen in individuals testing positive for COVID-19 (0.01% of all patients vaccinated). ConclusionsThis study provides further evidence that a single dose of either the Pfizer/BioNTech vaccine or the Oxford/Astrazeneca vaccine is effective at reducing the risk of testing positive for COVID-19 up to 60 days across all adult age groups, ethnic groups, and risk categories in an urban UK population. There was no difference in effectiveness up to 28 days between the Oxford/Astrazeneca and Pfizer/BioNtech vaccines. In those declining vaccination higher rates were seen in those living in the most deprived areas and in Black and Black British groups. There was no definitive evidence to suggest COVID-19 was transmitted as a result of vaccination hubs during vaccine the administration roll-out in NWL, and the risk of contracting COVID-19 and/or becoming hospitalised after vaccination has been demonstrated to be very low in the vaccinated population.

BackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine plus griseofulvin versus terbinafine alone in tinea corporis, tinea cruris and tinea faciei in a randomized pragmatic open trial. MethodsOne hundred and thirty two microscopy confirmed patients were randomly allocated (ratio 1:1) to two groups, terbinafine (T) and terbinafine plus griseofulvin (T+G). Doses given were as follows: T, oral terbinafine (6 mg/kg/day, maximum 500 mg/day, once daily); T+G, terbinafine (as above) plus oral griseofulvin (children [<18 years] 10 mg/kg/day, adults [18 years or more] 10 mg/kg/day, but not <500 mg and not >1000 mg per day, in two divided doses). Patients were treated for 8 weeks or cure, whichever occurred earlier. ResultsAt 4 weeks, none of the patients were cured in both groups. At 6 weeks, 1(1.5%) and 4 (6.1%) patients were cured in T and T+G groups, respectively (P=0.417). At 8 weeks, 17 (25.8%) and 19 (28.8%) patients were cured in T and T+G groups, respectively (P=0.845). For cure rate at 8 weeks, number needed to treat (NNT) for T+G (versus T), was 33. ConclusionsAddition of griseofulvin to terbinafine does not increase effectiveness of terbinafine in current epidemic of altered dermatophytosis in India.

BackgroundMachine learning (ML) models are widely used to predict body mass index (BMI), yet their fairness across socioeconomic and caste groups remains uncertain, especially in countries with structure inequalities. This study evaluated the accuracy and fairness of ML models in predicting underweight, overweight, and central adiposity, examined the impact of socioeconomic and household factors, identified key predictive features, and assessed the effect of bias mitigation techniques on model performance. MethodsThis study analysed data from the nationally representative Longitudinal Ageing Study in India (LASI) with over 55,000 individuals aged 45 and older. We applied ML models (Random Forest, XGBoost, Gradient Boosting, LightGBM, DNN, DCN) alongside logistic regression. Model were trained (80%) and tested (20%), evaluated using AUROC, accuracy, sensitivity, specificity, and precision. Fairness assessment included subgroup analyses across socioeconomic and caste groups, equity-based fairness (e.g. Equalized Odds, Demographic Parity). Feature importance was examined using SHAP values. Bias mitigation techniques were applied at three stages: pre-processing (Disparate Impact Remover, Reweighting), in-processing (Exponential Gradient Reduction), and post- processing (Calibrated Equalized Odds, Reject Option Classification). Prediction density analysis assessed class separability across subgroup. ResultsTree-based models--especially LightGBM and Gradient Boosting--along with Logistic Regression, consistently delivered the highest AUROC scores in predicting underweight, overweight, and high waist circumference outcomes (AUROC= 0.79-0.84). Incorporating socioeconomic and health-related variables gradually enhanced model performance; for example, the AUROC for underweight prediction increased from 0.74 to 0.78. However, our analysis revealed notable fairness issues: models performed worse for scheduled tribes and lower socioeconomic groups, as evidenced by reduced sensitivity and specificity in these subgroups. Feature importance analysis using SHAP values indicated that variables such as grip strength, gender, and residence were the key drivers of prediction differences; specifically, lower grip strength and rural residence were linked to underweight, whereas higher grip strength, urban residence, and female gender were associated with overweight and central adiposity. Regarding bias mitigation, techniques like Reject Option Classification and Equalized Odds Postprocessing showed some potential for reducing subgroup disparities by aligning the performance of low- and high-performing groups. Nevertheless, these adjustments sometimes came with trade-offs, and other methods--such as Exponentiated Gradient Reduction and Adversarial Debiasing--resulted in substantial declines in overall performance. While approaches like Disparate Impact Remover, Reweighting, and the Stratified Subgroup Best Model produced only modest changes relative to the unmitigated model, our findings highlight persistent fairness challenges. ConclusionsML models can effectively predict obesity and adiposity risks in India, but addressing biases is critical for equitable application. There are needs to further refinement of fairness awareness ML approaches in public health, particularly in the context of Indias diverse population for more inclusive and effective policy decisions. AUTHOR SUMMARYIndia now faces the paradox of widespread under-nutrition alongside a rising tide of obesity among its older population. We asked whether state-of-the-art machine-learning models could accurately identify individuals at highest risk of under-weight, overweight-obesity, and central adiposity while treating all social groups equitably. Using nationally representative data on more than 55,000 adults aged 45 years and above, we compared gradient-boosted decision trees, random forests, logistic regression, and other approaches with conventional regression techniques. Overall, the modern algorithms produced the strongest predictions. Yet a closer look revealed systematic shortfalls for scheduled tribes, scheduled castes, and the lowest income quintile--even when the models achieved excellent accuracy in the population as a whole. We then applied several well-established bias-mitigation strategies, such as re-weighting the training data and post-processing the decision thresholds. These interventions reduced the performance gap for disadvantaged groups, albeit at a modest cost to overall accuracy. By combining careful fairness audits with Shapley-based interpretation of feature importance, we illuminate how socioeconomic and caste-related factors shape both nutritional risk and prediction error. Our findings underscore that fair, trustworthy decision support systems in public health must be designed explicitly with equity objectives, rather than assuming that technical excellence alone will guarantee just outcomes.

ObjectiveThe objective of this systematic review is to assess the impact of oxymetazoline in patients with moderate to severe rosacea. Data SourcesWe will conduct a comprehensive search in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Lilacs, the International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, US National Institutes of Health (NIH) and grey literature, to identify all relevant randomized controlled trials regardless of language or publication status (published, unpublished, in press and in progress). Eligibility criteria for selecting studies and methodsWe will include randomized trials evaluating the effect of oxymetazoline in patients with moderate to severe rosacea. Two reviewers will independently screen each study for eligibility, data extraction, and assess the risk of bias. We will pool the results using meta-analysis and will apply the GRADE [1] system to assess the certainty of the evidence for each outcome. Ethics and DisseminationNo ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media. Protocol and RegistrationThis protocol was adapted to the specificities of the question assessed in this review and registered to PROSPERO with the ID CRD42020150262.

BackgroundNanocovax is a recombinant severe acute respiratory syndrome coronavirus 2 subunit vaccine composed of full-length prefusion stabilized recombinant SARS-CoV-2 spike glycoproteins (S-2P) and aluminum hydroxide adjuvant. In a Phase 1 and 2 studies, (NCT04683484) the vaccine was found to be safe and induce a robust immune response in healthy adult participants. MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled study to evaluate the safety, immunogenicity, and protective efficacy of the Nanocovax vaccine against Covid-19 in approximately 13,007 volunteers aged 18 years and over. The immunogenicity was assessed based on Anti-S IgG antibody response, surrogate virus neutralization, wild-type SARS-CoV-2 neutralization and the types of helper T-cell response by intracellular staining (ICS) for interferon gamma (IFNg) and interleukin-4 (IL-4). The vaccine efficacy (VE) was calculated basing on serologically confirmed cases of Covid-19. FindingsUp to day 180, incidences of solicited and unsolicited adverse events (AE) were similar between vaccine and placebo groups. 100 serious adverse events (SAE) were observed in both vaccine and placebo groups (out of total 13007 participants). 96 out of these 100 SAEs were determined to be unrelated to the investigational products. 4 SAEs were possibly related, as determined by the Data and Safety Monitoring Board (DSMB) and investigators. Reactogenicity was absent or mild in the majority of participants and of short duration. These findings highlight the excellent safety profile of Nanocovax. Regarding immunogenicity, Nanocovax induced robust IgG and neutralizing antibody responses. Importantly, Anti S-IgG levels and neutralizing antibody titers on day 42 were higher than those of natural infected cases. Nanocovax was found to induce Th2 polarization rather than Th1. Post-hoc analysis showed that the VE against symptomatic disease was 51.5% (95% confidence interval [CI] was [34.4%-64.1%]. VE against severe illness and death were 93.3% [62.2-98.1]. Notably, the dominant strain during the period of this study was Delta variant. InterpretationNanocovax 25 microgram (mcg) was found to be safe with the efficacy against symptomatic infection of Delta variant of 51.5%. FundingResearch was funded by Nanogen Pharmaceutical Biotechnology JSC., and the Ministry of Science and Technology of Vietnam; ClinicalTrials.gov number, NCT04922788.

BackgroundDexamethasone, a widely available glucocorticoid, was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial; however, evidence is still needed to support its real-world effectiveness in patients with a wide range of comorbidities and in diverse care settings. ObjectivesTo conduct a comparative effectiveness analysis of dexamethasone use with and without remdesivir in hospitalized COVID-19 patients using electronic health record data. MethodsWe conducted a retrospective real-world effectiveness analysis using the harmonized, highly granular electronic health record data of the National COVID Cohort Collaborative (N3C) Data Enclave. Analysis was restricted to COVID-19 patients in an inpatient setting, prior to vaccine availability. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome as defined by use of ECMO or mechanical ventilation during stay. Missing data were imputed with single imputation. Matching of dexamethasone-treated patients to non-dexamethasone-treated controls was accomplished using propensity score (PS) matching, stratified by remdesivir treatment and based on demographics, baseline laboratory values, and comorbidities. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS. ResultsRegression analysis revealed a statistically significant association between dexamethasone use and reduced risk of in-hospital mortality for those not receiving remdesivir (OR=0.77, 95% CI: 0.62 to 0.95, p=0.017), and a borderline statistically significant risk for those receiving remdesivir (OR=0.74, 95% CI: 0.53 to 1.02, p=0.054). Treatment also showed secondary outcome benefit. In sensitivity analyses, treatment effect size generally remained similar with some heterogeneity of benefit across strata of PS. ConclusionsWe add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.

Parental mental health has a long-lasting impact on developmental outcomes for infants and children through its impact on the family environment. Targeted parenting interventions should address both parental health and parenting skills. However, data is limited on how interventions perform in Central Asian populations. Using routine evaluation data from n=194 participants, we modelled the effectiveness of the Mellow Babies (MB) programmes, delivered to mothers from Tajikistan and their children as part of a community support approach. Pre-post intervention changes were measured on depression, anxiety, parenting stress, quality of life, and child behaviour outcomes. Demographics were modelled as covariates. Participation in MB was associated with improvements in maternal mental health, parenting stress, quality of life and child behaviour. Demographic factors moderated interactions between pre and post intervention outcomes, including urban/rural differences, parental employment, marital status and child disability status. Our findings suggest that MB is acceptable, effective and potentially scalable as a parenting intervention in Tajikistan. Future replication using implementation designs and replication of MB in other global settings is merited.

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

BackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine daily plus fluconazole weekly (TFw) and terbinafine daily plus fluconazole daily (TFd) versus oral terbinafine daily (T) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial. MethodsOne hundred and seventeen microscopy confirmed patients were allocated to T (6 mg/kg/day), TFw (terbinafine 6 mg/kg/day+fluconazole 12 mg/kg once weekly), or TFd (terbinafine 6 mg/kg/day+fluconazole 6 mg/kg/day) groups by concealed randomization and treated for 8 weeks or cure. Each group included 39 patients. ResultsAt 4 weeks, 9 (23.1%), 8 (20.5%) and 14 (35.9%) patients were cured in T, TFw and TFd groups, respectively (P=0.279). At 8 weeks, number of patients cured was as follows: T 13 (33.3%), TFw 18 (46.2%) and TFd 25 (64.1%). TFd was more effective than T (P=0.012), other comparisons were not significantly different. However, effect size as calculated by number needed to treat (NNT) (versus terbinafine) was 8 for TFw and 4 for TFd. Relapse rates one month after cure were similar in all groups (P=0.664). ConclusionsIn view of cure rates and NNT, terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India. One Sentence SummaryTerbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.