Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.

BACKGROUND: Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on presence and severity of symptoms reported in questionnaires (Severe-Frequent, Moderate-Frequent, Moderate-Declining, Mild-Intermittent, Unaffected/Rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inferring subtypes from EHRs alone, which would enable their study in large primary care databases. OBJECTIVES: 1. Explore if presence and number of AD records in EHRs agrees with AD symptom and severity reports from ALSPAC; 2. Explore if EHRs agree with ALSPAC-derived AD subtypes; 3. Construct models to classify ALSPAC-derived AD subtype using EHRs. METHODS: We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g., diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models tuning hyperparameters and evaluating performance in the testing set (ROC AUC, accuracy, sensitivity, and specificity). RESULTS: 8,828 individuals out of a total 13,898 had both been assigned an AD subtype and had linked EHRs. The number of AD-related codes in EHRs generally increased with severity of AD subtype, however not all with the Severe-Frequent subtypes had AD in EHRs, and many with the Unaffected/Rare subtype did have AD in EHRs. When predicting ALSPAC AD subtype using EHRs, the best tuned model had ROC AUC of 0.65, sensitivity of 0.29 and specificity of 0.83 (both macro averaged); when different sets of predictors were used, individuals with missing EHR coverage excluded, and subtypes combined, sensitivity was not considerably improved. CONCLUSIONS: ALSPAC and EHRs disagreed not just on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered as having AD in one source may not be considered as having AD in another.

Common mental health disorders in adults with inflammatory skin conditions: nationwide population-based matched cohort studies in the UK.

BACKGROUND: Psoriasis and atopic eczema are common inflammatory skin diseases. Existing research has identified increased risks of common mental disorders (anxiety, depression) in people with eczema and psoriasis; however, explanations for the associations remain unclear. We aimed to establish the risk factors for mental illness in those with eczema or psoriasis and identify the population groups most at risk. METHODS: We used routinely collected data from the UK Clinical Practice Research Datalink (CPRD) GOLD. Adults registered with a general practice in CPRD (1997-2019) were eligible for inclusion. Individuals with eczema/psoriasis were matched (age, sex, practice) to up to five adults without eczema/psoriasis. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for hazards of anxiety or depression in people with eczema/psoriasis compared to people without. We adjusted for known confounders (deprivation, asthma [eczema], psoriatic arthritis [psoriasis], Charlson comorbidity index, calendar period) and potential mediators (harmful alcohol use, body mass index [BMI], smoking status, and, in eczema only, sleep quality [insomnia diagnoses, specific sleep problem medications] and high-dose oral glucocorticoids). RESULTS: We identified two cohorts with and without eczema (1,032,782, matched to 4,990,125 without), and with and without psoriasis (366,884, matched to 1,834,330 without). Sleep quality was imbalanced in the eczema cohorts, twice as many people with eczema had evidence of poor sleep at baseline than those without eczema, including over 20% of those with severe eczema. After adjusting for potential confounders and mediators, eczema and psoriasis were associated with anxiety (adjusted HR [95% CI]: eczema 1.14 [1.13-1.16], psoriasis 1.17 [1.15-1.19]) and depression (adjusted HR [95% CI]: eczema 1.11 [1.1-1.12], psoriasis 1.21 [1.19-1.22]). However, we found evidence that these increased hazards are unlikely to be constant over time and were especially high 1-year after study entry. CONCLUSIONS: Atopic eczema and psoriasis are associated with increased incidence of anxiety and depression in adults. These associations may be mediated through known modifiable risk factors, especially sleep quality in people with eczema. Our findings highlight potential opportunities for the prevention of anxiety and depression in people with eczema/psoriasis through treatment of modifiable risk factors and enhanced eczema/psoriasis management.

Factors associated with depression, anxiety and severe mental illness among adults with atopic eczema or psoriasis: a systematic review and meta-analysis.

BACKGROUND: Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. OBJECTIVES: To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. METHODS: We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case-control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. RESULTS: We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety - one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09-2.40, 95% prediction intervals (PIs) 0.62-4.23, I2 = 24.90%, τ2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56-3.25, 95% PI 0.21-24.23, I2 = 0.00%, τ2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32-5.07, 95% PI 0.00-3956.27, I2 = 61.90%, τ2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33-2.94, I2 = 0.00%, τ2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05-1.25, I2 0.00%, τ2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). CONCLUSIONS: Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear.

Seasonality of acute kidney injury phenotypes in England: an unsupervised machine learning classification study of electronic health records.

BACKGROUND: Acute Kidney Injury (AKI) is a multifactorial condition which presents a substantial burden to healthcare systems. There is limited evidence on whether it is seasonal. We sought to investigate the seasonality of AKI hospitalisations in England and use unsupervised machine learning to explore clustering of underlying comorbidities, to gain insights for future intervention. METHODS: We used Hospital Episodes Statistics linked to the Clinical Practice Research Datalink to describe the overall incidence of AKI admissions between 2015 and 2019 weekly by demographic and admission characteristics. We carried out dimension reduction on 850 diagnosis codes using multiple correspondence analysis and applied k-means clustering to classify patients. We phenotype each group based on the dominant characteristics and describe the seasonality of AKI admissions by these different phenotypes. RESULTS: Between 2015 and 2019, weekly AKI admissions peaked in winter, with additional summer peaks related to periods of extreme heat. Winter seasonality was more evident in those diagnosed with AKI on admission. From the cluster classification we describe six phenotypes of people admitted to hospital with AKI. Among these, seasonality of AKI admissions was observed among people who we described as having a multimorbid phenotype, established risk factor phenotype, and general AKI phenotype. CONCLUSION: We demonstrate winter seasonality of AKI admissions in England, particularly among those with AKI diagnosed on admission, suggestive of community triggers. Differences in seasonality between phenotypes suggests some groups may be more likely to develop AKI as a result of these factors. This may be driven by underlying comorbidity profiles or reflect differences in uptake of seasonal interventions such as vaccines.

Description of Plasmodium falciparum infections in central Gabon demonstrating high parasite densities among symptomatic adolescents and adults.

BACKGROUND: Malaria remains a public health issue, particularly in sub-Saharan Africa with special features of seriousness in young children and pregnant women. Adolescents and adults are reported to have acquired a semi-immune status and, therefore, present with low parasitaemia. Children are understood to present with a much higher parasitaemia and severe malaria. It is a concern that effective malaria control programmes targeting young children may lead to a delay in the acquisition of acquired immunity and, therefore, causing a shift in the epidemiology of malaria. Prevalence and parasitaemia were explored in adolescents and adults with Plasmodium falciparum infections compared to young children in the area of Lambaréné, Gabon as an indicator for semi-immunity. METHODS: A cross-sectional study was conducted at the Centre de Recherches Médicales de Lambaréné (CERMEL) during a 6-month period in 2018. Symptomatic patients, of all ages were screened for malaria at health facilities in Lambaréné and Fougamou and their respective surrounding villages in the central region of Gabon. Plasmodium falciparum infections were determined either by rapid diagnostic test (RDT) or by microscopy. Descriptive analysis of data on parasite densities, anaemia, and fever are presented. RESULTS: 1589 individuals screened were included in this analysis, including 731 (46%) adolescents and adults. Out of 1377 assessed, the proportion of P. falciparum positive RDTs was high among adolescents (68%) and adults (44%), compared to young children (55%) and school children (72%). Out of 274 participants assessed for malaria by microscopy, 45 (16%) had a parasite count above 10,000/µl of which 9 (20%) were adults. CONCLUSION: This study shows a high rate of P. falciparum infections in adolescents and adults associated with high-level parasitaemia similar to that of young children. Adolescents and adults seem to be an at-risk population, suggesting that malaria programmes should consider adolescents and adults during the implementation of malaria prevention and case management programmes with continuous care, since they also act as reservoirs for P. falciparum.

Implementation of a Taxonomy-Based Framework for the Selection of Appropriate Drugs and Outcomes for Real-World Data Signal Detection Studies.

INTRODUCTION: For signal detection studies investigating either drug safety or method evaluation, the choice of drug-outcome pairs needs to be tailored to the planned study design and vice versa. While this is well understood in hypothesis-testing epidemiology, it should be as important in signal detection, but this has not widely been considered. There is a need for a taxonomy framework to provide guidance and a systematic reproducible approach to the selection of appropriate drugs and outcomes for signal detection studies either investigating drug safety or assessing method performance using real-world data. OBJECTIVE: The aim was to design a general framework for the selection of appropriate drugs and outcomes for signal detection studies given a study design of interest. As a motivating example, we illustrate how the framework is applied to build a reference set for a study aiming to assess the performance of the self-controlled case series with active comparators. METHODS: We reviewed criteria presented in two published studies which aimed to provide practical advice for choosing the appropriate signal evaluation methodology, and assessed their relevance for signal detection. Further characteristics specific to signal detection were added. The final framework is based on: the application of study design requirements, the database(s) of interest, and the clinical importance of the drug(s) and outcome(s) under consideration. This structure was applied by selecting drug-outcome pairs as a reference set (i.e. list of drug-outcome pairs classified as positive or negative controls) for which the method is expected to work well for a signal detection study aiming to assess the performance of self-controlled case series. Eight criteria were used, related to the application of self-controlled case series assumptions, choice of active comparators, coverage in the database of interest and clinical importance of the outcomes. RESULTS: After application of the framework, two classes of antibiotics (seven drugs) were selected for the study, and 28 outcomes from all organ classes were chosen from the drug labels, out of the 273 investigated. In total, this corresponds to 104 positive controls (drug-outcome pairs) and 58 negative controls. CONCLUSIONS: We proposed and applied a framework for the selection of drugs and outcomes for both drug safety signal detection and method assessment used in signal detection to optimise their performance given a study design. This framework will eliminate part of the bias relating to drugs and outcomes not being suited to the method or database. The main difficulty lies in the choice of the criteria and their application to ensure systematic selection, especially as some information remains unknown in signal detection, and clinical judgement was needed on occasions. The same framework could be adapted for other methods.

Anxiety and Depression in People with Eczema or Psoriasis: A Comparison of Associations in UK Biobank and Linked Primary Care Data.

Introduction: Previous research has shown associations between eczema and psoriasis and anxiety and depression. We investigated whether associations are consistent across different settings of ascertainment for depression and anxiety, including interview and survey responses from UK Biobank (a large longitudinal cohort recruiting individuals aged 40-69 years between 2006-2010), and linked primary care data, with the aim of drawing more reliable conclusions through triangulation. Methods: In cross-sectional studies, we estimated associations between eczema or psoriasis and anxiety or depression, defining anxiety or depression as 1) self-reported previous diagnosis at UK Biobank recruitment interview; 2) PHQ-9/GAD-7 score indicating depression or anxiety from a UK Biobank mental health follow-up survey in 2016; and 3) diagnosis in linked primary care electronic health record data. Results: We analysed 230,047 people with linked Biobank and primary care data. We found poor agreement between the data sources for eczema, psoriasis, anxiety, and depression. Eg, 9474 had a previous eczema diagnosis in primary care data, 4069 self-reported previous eczema diagnosis at the UK biobank interview, and 1536 had eczema in both data sources (for depression 40,455; 13,320; and 9588 respectively). Having eczema or psoriasis (recorded in primary care or baseline interview) was associated with higher odds of anxiety and depression. Eg, the adjusted odds ratio for depression comparing those with eczema to those without was greater than 1 when defining the outcome from 1) the recruitment interview (1.36, 95% confidence interval 1.27-1.45); 2) the follow-up survey (1.24, 1.09-1.39), and 3) primary care records (1.56, 1.50-1.62). Discussion: Our findings support increased prevalence of mental illness in people with psoriasis and eczema across multiple data sources, which should be considered in planning of mental health services. However, we found poor agreement in disease ascertainment between settings, with implications for data interpretation in electronic health records.

Association of Different Prescribing Patterns for Oral Corticosteroids With Fracture Preventive Care Among Older Adults in the UK and Ontario.

Importance: Identifying and mitigating modifiable gaps in fracture preventive care for people with relapsing-remitting conditions such as eczema, asthma, and chronic obstructive pulmonary disease who are prescribed high cumulative oral corticosteroid doses may decrease fracture-associated morbidity and mortality. Objective: To estimate the association between different oral corticosteroid prescribing patterns and appropriate fracture preventive care, including treatment with fracture preventive care medications, among older adults with high cumulative oral corticosteroid exposure. Design, Setting, and Participants: This cohort study included 65 195 participants with UK electronic medical record data from the Clinical Practice Research Datalink (January 2, 1998, to January 31, 2020) and 28 674 participants with Ontario, Canada, health administrative data from ICES (April 1, 2002, to September 30, 2020). Participants were adults 66 years or older with eczema, asthma, or chronic obstructive pulmonary disease receiving prescriptions for oral corticosteroids with cumulative prednisolone equivalent doses of 450 mg or higher within 6 months. Data were analyzed October 22, 2020, to September 6, 2022. Exposures: Participants with prescriptions crossing the 450-mg cumulative oral corticosteroid threshold in less than 90 days were classified as having high-intensity prescriptions, and participants crossing the threshold in 90 days or more as having low-intensity prescriptions. Multiple alternative exposure definitions were used in sensitivity analyses. Main Outcomes and Measures: The primary outcome was prescribed fracture preventive care. A secondary outcome was major osteoporotic fracture. Individuals were followed up from the date they crossed the cumulative oral corticosteroid threshold until their outcome or the end of follow-up (up to 1 year after index date). Rates were calculated for fracture preventive care and fractures, and hazard ratios (HRs) were estimated from Cox proportional hazards regression models comparing high- vs low-intensity oral corticosteroid prescriptions. Results: In both the UK cohort of 65 195 participants (mean [IQR] age, 75 [71-81] years; 32 981 [50.6%] male) and the Ontario cohort of 28 674 participants (mean [IQR] age, 73 [69-79] years; 17 071 [59.5%] male), individuals with high-intensity oral corticosteroid prescriptions had substantially higher rates of fracture preventive care than individuals with low-intensity prescriptions (UK: 134 vs 57 per 1000 person-years; crude HR, 2.34; 95% CI, 2.19-2.51, and Ontario: 73 vs 48 per 1000 person-years; crude HR, 1.49; 95% CI, 1.29-1.72). People with high- and low-intensity oral corticosteroid prescriptions had similar rates of major osteoporotic fractures (UK: crude rates, 14 vs 13 per 1000 person-years; crude HR, 1.07; 95% CI, 0.98-1.15 and Ontario: crude rates, 20 vs 23 per 1000 person-years; crude HR, 0.87; 95% CI, 0.79-0.96). Results from sensitivity analyses suggested that reaching a high cumulative oral corticosteroid dose within a shorter time, with fewer prescriptions, or with fewer or shorter gaps between prescriptions, increased fracture preventive care prescribing. Conclusions: The results of this cohort study suggest that older adults prescribed high cumulative oral corticosteroids across multiple prescriptions, or with many or long gaps between prescriptions, may be missing opportunities for fracture preventive care.

Severe Mental Illness Among Adults with Atopic Eczema or Psoriasis: Population-Based Matched Cohort Studies within UK Primary Care.

Background: Existing research exploring associations between atopic eczema (AE) or psoriasis, and severe mental illness (SMI - ie, schizophrenia, bipolar disorder, other psychoses) is limited, with longitudinal evidence particularly scarce. Therefore, temporal directions of associations are unclear. We aimed to investigate associations between AE or psoriasis and incident SMI among adults. Methods: We conducted matched cohort studies using primary care electronic health records (January 1997 to January 2020) from the UK Clinical Practice Research Datalink GOLD. We identified two cohorts: 1) adults (≥18 years) with and without AE and 2) adults with and without psoriasis. We matched (on age, sex, general practice) adults with AE or psoriasis with up to five adults without. We used Cox regression, stratified by matched set, to estimate hazard ratios (HRs) comparing incident SMI among adults with and without AE or psoriasis. Results: We identified 1,023,232 adults with AE and 4,908,059 without, and 363,210 with psoriasis and 1,801,875 without. After adjusting for matching variables (age, sex, general practice) and potential confounders (deprivation, calendar period) both AE and psoriasis were associated with at least a 17% increased hazard of SMI (AE: HR=1.17,95% CI=1.12-1.22; psoriasis: HR=1.26,95% CI=1.18-1.35). After additionally adjusting for potential mediators (comorbidity burden, harmful alcohol use, smoking status, body mass index, and, in AE only, sleep problems and high-dose glucocorticoids), associations with SMI did not persist for AE (HR=0.98,95% CI=0.93-1.04), and were attenuated for psoriasis (HR=1.14,95% CI=1.05-1.23). Conclusion: Our findings suggest adults with AE or psoriasis are at increased risk of SMI compared to matched comparators. After adjusting for potential mediators, associations with SMI did not persist for AE, and were attenuated for psoriasis, suggesting that the increased risk may be explained by mediating factors (eg, sleep problems). Our research highlights the importance of monitoring mental health in adults with AE or psoriasis.

Atopic Eczema-Associated Fracture Risk and Oral Corticosteroids: A Population-Based Cohort Study.

BACKGROUND: Evidence suggests adults with atopic eczema have increased fracture risk. However, it is unclear whether oral corticosteroids explain the association. OBJECTIVE: To assess to what extent oral corticosteroids mediate the relationship between atopic eczema and fractures. METHODS: We conducted a cohort study using English primary care (Clinical Practice Research Datalink) and hospital admissions (Hospital Episode Statistics) records (1998-2016) including adults (18 years old and older) with atopic eczema matched (age, sex, and general practice) with up to 5 adults without atopic eczema. We used Cox regression to estimate hazard ratios (HRs) for specific major osteoporotic fractures (hip, spine, pelvis, or wrist) and for any-site fracture comparing individuals with atopic eczema with those without, adjusting for 6 different definitions of time-updated oral corticosteroid use (ever any prescription, ever high-dose, and recent, cumulative, current, or peak dose). RESULTS: We identified 526,808 individuals with atopic eczema and 2,569,030 without. We saw evidence of an association between atopic eczema and major osteoporotic fractures (eg, spine HR 1.15, 99% CI 1.08-1.22; hip HR 1.11, 99% CI 1.08-1.15) that remained after additionally adjusting for oral corticosteroids (eg, cumulative corticosteroid dose: spine HR 1.09, 99% CI 1.03-1.16; hip HR 1.09, 99% CI 1.06-1.12). Fracture rates were higher in people with severe atopic eczema than in people without even after adjusting for oral corticosteroids (eg, spine HR [99% CI]: confounder-adjusted 2.31 [1.91-2.81]; additionally adjusted for cumulative dose 1.71 [1.40-2.09]). CONCLUSIONS: Our findings suggest that little of the association between atopic eczema and major osteoporotic fractures is explained by oral corticosteroid use.

Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.

Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.

Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. Methods: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). Findings: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL­23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49). Interpretation: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. Funding: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.

Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, "high-cost drugs" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.

A randomized controlled trial comparing the effectiveness of individual versus household treatment for Scabies in Lambaréné, Gabon.

BACKGROUND: It is unclear whether individual treatment of scabies is similarly effective compared to household treatment. This study compared these two treatment strategies with topical benzyl benzoate for treating scabies in Lambaréné, Gabon. METHODS: Participants presenting with uncomplicated scabies were randomized into either the Individual Treatment group, where only the affected participants received treatment, or the Household Treatment group, where all family members were treated in parallel to the affected participants regardless of signs and symptoms. The primary endpoint was clinical cure after 28 days; the secondary endpoint was the proportion of affected household members per household after 28 days. RESULTS: After 28 days, from a total of 79 participants assessed, 67% (n = 53) were clinically cured; 59% (20/34) in the Individual Treatment group and 73% (33/45) in the Household Treatment group. Participants in the Household Treatment group had about twice the odds of being cured (odds ratio 1.9, 95% confidence interval: 0.8-4.9; p = 0.17). For the secondary outcome, an effect of similar size was observed. CONCLUSIONS: Our findings show that treating close contacts of persons affected by scabies may be beneficial to patients and contacts, however, the benefit was less pronounced than anticipated and further research is needed to definitively answer this question.