Search

Contains fulltext : 237219.pdf (Publisher’s version ) (Open Access) Objective: To describe characteristics of randomised controlled trials (RCTs) conducted using electronic health records (EHRs), including completeness and transparency of reporting assessed against the 2021 CONSORT Extension for RCTs Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study design: MEDLINE and Cochrane Methodology Register were searched for a sample of RCTs published from 2011–2018. Completeness of reporting was assessed in a random sample using a pre-defined coding form. Results 183 RCT publications were identified; 122 (67%) used EHRs to identify eligible participants, 139 (76%) used the EHR as part of the intervention and 137 (75%) to ascertain outcomes. When 60 publications were evaluated against the CONSORT 2010 item and the corresponding extension for the 8 modified items, four items were 'adequately reported' for the majority of trials. Five new reporting items were identified for the CONSORT-ROUTINE extension; when evaluated, one was 'adequately reported', three were reported 'inadequately or not at all', the other 'partially'. There were, however, some encouraging signs with adequate and partial reporting of many important items, including descriptions of trial design, the consent process, outcome ascertainment and interpretation. Conclusion: Aspects of RCTs using EHRs are sub-optimally reported. Uptake of the CONSORT-ROUTINE Extension may improve reporting. 12 p.

A scoping review to identify methodological challenges when using routinely collected healthcare data for research.

BackgroundOral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care.AimTo describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017.Design and settingA prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK.MethodOral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone.ResultsIn total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4–24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059–6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%.ConclusionA high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place.

Indirect excess morbidity in the COVID-19 pandemic may arise from public health risk-mitigation efforts such as stay-at-home orders and re-purposing of healthcare services1 . Increased mental health disorders and shortfalls in the care of long-term conditions are described.

BACKGROUND: Emerging evidence suggests an association between common inflammatory skin diseases and chronic kidney disease (CKD). OBJECTIVES: To explore the association between CKD stages 3-5 (CKD3-5) and atopic eczema, psoriasis, rosacea and hidradenitis suppurativa. METHODS: We undertook two complementary analyses; a prevalent case-control study and a cohort study using routinely collected primary care data [UK Clinical Practice Research Datalink (CPRD)]. We matched individuals with CKD3-5 in CPRD in March 2018 with up to five individuals without CKD for general practitioner practice, age and sex. We compared the prevalence of CKD3-5 among individuals with and without each inflammatory skin disease. We included individuals in CPRD with diabetes mellitus (2004-2018) in a cohort analysis to compare the incidence of CKD3-5 among people with and without atopic eczema and psoriasis. RESULTS: Our study included 56 602 cases with CKD3-5 and 268 305 controls. Cases were more likely than controls to have a history of atopic eczema [odds ratio (OR) 1·14, 99% confidence interval (CI) 1·11-1·17], psoriasis (OR 1·13, 99% CI 1·08-1·19) or hidradenitis suppurativa (OR 1·49, 99% CI 1·19-1·85), but were slightly less likely to have been diagnosed with rosacea (OR 0·92, 99% CI 0·87-0·97), after adjusting for age, sex, practice (matching factors), index of multiple deprivation, diabetes, smoking, harmful alcohol use and obesity. Results remained similar after adjusting for hypertension and cardiovascular disease. In the cohort with diabetes (N = 335 827), there was no evidence that CKD3-5 incidence was associated with atopic eczema or psoriasis. CONCLUSIONS: Atopic eczema, psoriasis and hidradenitis suppurativa are weakly associated with CKD3-5. Future research is needed to elucidate potential mechanisms and the clinical significance of our findings.

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

Summary Background Psychological stress may reduce cellular immunity, but its role in triggering latent infections, including herpes zoster (HZ), is controversial. Objectives To examine the association between perceived psychological stress and risk of HZ. Methods In a linked registry‐based cohort study, we followed 77 310 persons aged 40 years or older who participated in the 2010 Danish National Health Survey from 1 May 2010 until HZ diagnosis, death, emigration or 1 July 2014, whichever occurred first. We computed hazard ratios (HRs) of HZ associated with Cohen’s Perceived Stress Scale (PSS) score (range 0–40) using Cox regression with age as the timescale, adjusted for sex, immunosuppressive and selected chronic conditions, immunosuppressive drugs, and sociodemographic, lifestyle and anthropometric factors. The PSS measures chronic stress perceived by an individual in response to various demands of daily life. We modelled the PSS score using quintiles and a restricted cubic spline function. Results The unadjusted rate of HZ varied from 5·53 to 7·20 per 1000 person‐years from the lowest to the highest PSS score quintile. Compared with the lowest PSS score quintile, the adjusted HR for HZ was 1·00 [95% confidence interval (CI) 0·86–1·16], 1·08 (95% CI 0·92–1·26), 1·05 (95% CI 0·90–1·23) and 1·14 (95% CI 0·97–1·34) for the second to the fifth quintile, respectively. In cubic spline analyses, PSS scores, What is already known about this topic? Psychological stress may reduce cellular immunity, but its role in triggering latent infections, such as herpes zoster (HZ), is controversial.Previous epidemiological studies have mainly focused on the effects of negative life events (e.g. bereavement) on HZ risk, and dose–response analyses are lacking.It is possible that the allostatic load (the cumulative ‘wear and tear’ on the body associated with stress) depends on the type of stress and coping mechanisms. What does this study add? In this large population‐based cohort study, we found that persons reporting the highest levels of perceived psychological stress in daily life had an increased risk of HZ.Perceived psychological stress may be a modifiable risk factor for HZ.Our study adds HZ to the growing list of potential negative health consequences of psychological stress and underscores the importance of supporting mental wellbeing and resilience in the general population. Linked Comment: A.W.M. Evers and S. van Beugen. Br J Dermatol 2021; 185:12–13.

We examined the feasibility of implementing preventive measures to prevent SARS-CoV-2 transmission across 105 English primary schools in summer 2020 via a survey and interviews with headteachers. High rates of implementation of most recommended measures were noted with the exception of requiring 2 m distance for students, fitting hand sanitizers in classrooms and introducing one-way systems in school corridors. Measures such as regular handwashing and stopping assemblies were considered easy to implement. Majorly challenging measures included distancing between individuals (for students: 51%, N = 99; for staff: 34%; N = 98; for parents: 26%, N = 100), spacing out desks (34%, N = 99), keeping same staff assigned to each student group (33%, N = 97) and staggering break times (25%, N = 99). Rapid implementation was facilitated by staff commitment and communication among stakeholders, but hampered by limitations with guidance received, physical environments, resources, parental adherence and balancing preventive measures with learning. Difficulties with distancing for younger children suggest that smaller bubbles with fewer distancing requirements within these may be a policy option. Schools require further financial, human resource and other support for effective implementation of preventive measures.

BACKGROUND: Atopic dermatitis is characterized by chronic inflammation, which is a risk factor for atrial fibrillation.OBJECTIVE: To examine the association between hospital-diagnosed atopic dermatitis and atrial fibrillation.METHODS: Using linked population-based Danish registries, we identified persons with an inpatient or outpatient hospital diagnosis of atopic dermatitis during 1977-2013 and a comparison cohort individually matched to the atopic dermatitis cohort. We followed cohorts until death, emigration, atrial fibrillation diagnosis, or end of study (January 1, 2013). We compared 35-year risk of atrial fibrillation and estimated hazard ratios with 95% confidence intervals using Cox regression, adjusting for birth year and sex. We validated 100 atopic dermatitis diagnoses from a dermatologic department through medical record review.RESULTS: We included 13,126 persons with atopic dermatitis and 124,211 comparators and followed them for a median of 19.3 years. The 35-year risk of atrial fibrillation was 0.81% and 0.67%, respectively. The positive predictive value of atopic dermatitis diagnoses was 99%. The hazard ratio was 1.2 (95% confidence interval 1.0-1.6) and remained increased after adjusting for various atrial fibrillation risk factors.LIMITATIONS: Analyses were limited to persons with moderate-to-severe atopic dermatitis, and we had no lifestyle data.CONCLUSION: Patients with hospital-diagnosed atopic dermatitis have a 20% increased long-term risk of atrial fibrillation, but the absolute risk remains low.

Introduction Two recent high-profile publications (and subsequent retractions) of pharmacoepidemiology studies reporting the effectiveness and risk of hydroxychloroquine in COVID-19 patients received international media attention. Transparent and complete reporting of these studies could have provided peer reviewers and editors with sufficient information to question the methods used and the validity of results. Since these studies used routinely collected health data, the guidelines for the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) should have been applied to ensure complete reporting of the research. Methods We evaluated the two retracted articles for completeness of reporting using the RECORD for Pharmacoepidemiology (RECORD-PE) checklist, which includes the checklists for the STengthening the Reporting of OBservational studies in Epidemiology (STROBE) and RECORD. We compared the proportion of STROBE, RECORD and RECORD-PE items adequately reported using Chi-squared statistics. Results In the article published by The Lancet, 29 of 34 STROBE items (85.3%) were adequately reported, compared with 3.5 of 13 RECORD items (26.9%) and 9.5 of 15 RECORD-PE items (63.3%)(χ2 = 14.839, P Discussion While STROBE items were generally adequately reported, RECORD and RECORD-PE items were not. Reporting guidelines should be effectively implemented in order for transparency and completeness of research manuscripts, allowing for adequate evaluation by editors and peer reviewers.

ObjectivesTo describe the development of Eczema Care Online (ECO), an online behaviour change intervention for young people with eczema (phase I); and explore and optimise the acceptability of ECO among this target group using think-aloud interviews (phase II).MethodsTheory-based, evidence-based and person-based approaches to intervention development were used. In phase I, a qualitative systematic review and qualitative interviews developed an in-depth understanding of the needs and challenges of young people with eczema. Guiding principles highlighted key intervention design objectives and features to address the needs of this target group to maximise user engagement. Behavioural analysis and logic modelling developed ECO’s hypothesised programme theory. In phase II, qualitative think-aloud interviews were carried out with 28 young people with eczema and the intervention was optimised based on their feedback.ResultsThe final intervention aimed to reduce eczema severity by supporting treatment use (emollients, topical corticosteroids/topical calcineurin inhibitors), management of irritants/triggers, emotional management and reducing scratching. Generally, young people expressed positive views of intervention content and design in think-aloud interviews. Quotes and stories from other young people with eczema and ECO’s focus on living with eczema (not just topical treatments) were valuable for normalising eczema. Young people believed ECO addressed knowledge gaps they had from childhood and the safety information about topical corticosteroids was reassuring. Negative feedback was used to modify ECO.ConclusionsA prototype of the ECO intervention was developed using rigorous and complementary intervention development approaches. Subsequent think-aloud interviews helped optimise the intervention, demonstrated ECO is likely to be acceptable to this target group, and provided support for our guiding principles including key design objectives and features to consider when developing interventions for this population. A randomised controlled trial and process evaluation of the intervention is underway to assess effectiveness and explore user engagement with the intervention’s behavioural goals.

Contains fulltext : 237435.pdf (Publisher’s version ) (Open Access) Objective: We evaluated reporting completeness and transparency in randomised controlled trials (RCTs) conducted using administrative data based on 2021 CONSORT Extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE) criteria. Study Design and Setting: MEDLINE and the Cochrane Methodology Register were searched (2011 and 2018). Eligible RCTs used administrative databases for identifying eligible participants or collecting outcomes. We evaluated reporting based on CONSORT-ROUTINE, which modified eight items from CONSORT 2010 and added five new items. Results: Of 33 included trials (76% used administrative databases for outcomes, 3% for identifying participants, 21% both), most were conducted in the United States (55%), Canada (18%), or the United Kingdom (12%). Of eight items modified in the extension; six were adequately reported in a majority (>50%) of trials. For the CONSORT-ROUTINE modification portion of those items, three items were reported adequately in >50% of trials, two in

ObjectivesTo investigate alcohol use recording in people with newly diagnosed depression in English primary care and individual characteristics associated with the recording of alcohol use.DesignA population-based cross-sectional study.SettingPrimary care data from English practices contributing to the UK Clinical Practice Research Datalink.ParticipantsWe included adults (18+ years) diagnosed with depression between 1 January 2011 and 1 January 2017 without previous antidepressant use and at least 1 year of registration before diagnosis.Primary and secondary outcome measuresWe described the proportion of individuals with alcohol use and level of alcohol use recorded at four time points (the date of depression diagnosis, 3 months before or after depression diagnosis, 12 months before or after depression diagnosis and any point pre or postdepression diagnosis). We used logistic regression to investigate individual characteristics associated with alcohol use recording in the 3 months before or after depression diagnosis.ResultsWe identified 36 424 adults with depression. 538 (2%) had alcohol use recorded in the 3 months before or after depression diagnosis using formal validated methods such as the Alcohol Use Disorders Identification Test and its abbreviated versions. At each time point, most individuals with alcohol use recorded were low risk drinkers. Alcohol use recording in the 3 months before or after depression diagnosis was associated with male sex (OR=1.38, 95% CI 1.29 to 1.48) and several other individual-level factors.ConclusionsOur study shows low levels of alcohol use recording in the 3 months before or after depression diagnosis. Levels of alcohol use recording varied depending on individual characteristics. Incentivised recording of alcohol use will increase completeness, which could improve clinical management and reduce missed opportunities for care in people with depression.

BACKGROUND One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this. OBJECTIVE This paper presents the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through implementation of school COVID-19 control measures. METHODS SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. Six bio-behavioural surveys were planned among participating students and staff during the 2020/21 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick-blood for staff and oral-fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study received approvals from the UK Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (ref:22657). RESULTS Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals: 1,891 staff and 4,654 students from 59 primary schools and 5,852 staff and 10,188 students from 97 secondary schools participated in at least one survey. On average, across survey rounds, staff and student participation rates were 45.2% and 16.4% respectively in primary schools and 30.0% and 15.2% in secondary schools. While primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (41.7% in Round 1 and 22.1% in Round 6). While staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals and from schools in the least deprived locations (in primary schools 9.6% participants were from schools in the least deprived quintile compared with 5.7% of eligible students). CONCLUSIONS We outline the study design, methods and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered, and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools, across a range of settings in England, aims to inform national guidance and public health policy for educational settings. CLINICALTRIAL

Introduction The most common cancers in the UK are keratinocyte cancers (KCs): the combined term for basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (cSCCs). Registration of KC is challenging due to high numbers and multiplicity of tumours per person. Methods We provide an updated report on the descriptive epidemiology of trends in KC incidence for the resident populations of UK countries (England, Northern Ireland, Scotland and Wales) using population‐based cancer registry and pathology report data, 2013–18. Results Substantial increases in cSCC incidence in England, Scotland and Northern Ireland can be detected for the period of 2013–18, and the incidence of cSCC also increased in Wales from 2016 to 2018. In contrast, however, the pattern of annual change in the incidence of BCC across the nations differs. In England, the incidence of BCC declined slightly from 2016 to 2018, however, the overall trend across 2013–18 is not statistically significant. In Scotland, the incidence of BCC shows some variability, declining in 2017 before increasing in 2018, and the overall trend across 2013–18 was also not statistically significant. In Northern Ireland, the incidence of BCC increased significantly over the study period, and in Wales, the incidence of BCC increased from 2016 to 2018. One in five people will develop non‐melanoma skin cancers (NMSC) in their lifetime in England. This estimate is much higher than the lifetime risk of melanoma (1 in 36 males and 1 in 47 females born after 1960 in the UK), which further highlights the burden of the disease and importance of early prevention strategies. Conclusions We highlight how common these tumours are by publishing the first ever lifetime incidence of NMSC. Additionally, the first time reporting of the age standardised incidence of KC in Wales further confirms the scale of the disease burden posed by these cancers in the UK. With approximately one in five people developing NMSC in their lifetime, optimisation of skin cancer prevention, management and research are essential.

Skin cancer is the commonest cancer in the UK. Skin cancer referrals via the two-week wait (urgent suspected cancer) pathway outnumber any other suspected malignancy.1, 2 The commonest skin cancers are keratinocyte cancers (KCs) which represents Basal Cell Carcinomas (BCC) and Cutaneous Squamous Cell Carcinomas (cSCC). Accurate KC incidence reporting is crucial for healthcare planning.

Background Lower socioeconomic position usually portends worse health outcomes, but multiple studies have found that atopic dermatitis is associated with higher socioeconomic position. The nature of this relationship remains unclear. Objective To systematically review the literature on socioeconomic position and atopic dermatitis and determine whether the association varies by patient or study characteristics. Methods A literature search was conducted in the PubMed and Embase databases. Individual-level studies addressing the association between all measures of socioeconomic position and the prevalence or incidence of atopic dermatitis were eligible for inclusion. Two independent reviewers screened all texts and extracted all data for qualitative synthesis. Results Eighty-eight studies met the inclusion criteria. Of the 88 studies, 42% (37) found a positive association between atopic dermatitis and socioeconomic position, 15% (13) found a negative association, and 43% (38) found a null or inconsistent association. Studies conducted in Europe, among children, and based on self-report of eczema were more likely to find a positive association with socioeconomic position. Limitations Studies varied both in terms of the measurement of socioeconomic position and the definition of atopic dermatitis, limiting quantitative synthesis. Conclusion The evidence of a positive association between atopic dermatitis and socioeconomic position is not consistent.

BackgroundIt is unclear if people with immune-mediated inflammatory diseases (IMIDs) (joint, bowel and skin) and on immune modifying therapy have increased risk of serious COVID-19 outcomes.MethodsWith the approval of NHS England we conducted a cohort study, using OpenSAFELY, analysingroutinely-collected primary care data linked to hospital admission, death and previously unavailable hospital prescription data. We used Cox regression (adjusting for confounders) to estimate hazard ratios (HR) comparing risk of COVID-19-death, death/critical care admission, and hospitalisation (March to September 2020) in: 1) people with IMIDs compared to the general population; and 2) people with IMIDs on targeted immune modifying drugs (e.g., biologics) compared to standard systemic treatment (e.g., methotrexate).FindingsWe identified 17,672,065 adults; of 1,163,438 (7%) with IMIDs, 19,119 people received targeted immune modifying drugs, and 200,813 received standard systemics. We saw evidence of increased COVID-19-death (HR 1.23, 95%CI 1.20, 1.27), and COVID-19 hospitalisation (HR 1.32, 95%CI 1.29, 1.35) in individuals with IMIDs overall compared to individuals without IMIDs of the same age, sex, deprivation and smoking status. We saw no evidence of increased COVID-19 deaths with targeted compared to standard systemic treatments (HR 1.03, 95%CI 0.80, 1.33). There was no evidence of increased COVID-19-related death in those prescribed TNF inhibitors, IL-12/23, IL7, IL-6 or JAK inhibitors compared to standard systemics. Rituximab was associated with increased COVID-19 death (HR 1.68, 95%CI 1.11, 2.56); however, this finding may relate to confounding.InterpretationCOVID-19 death and hospitalisation was higher in people with IMIDs. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune modifying drugs for IMIDs compared to standard systemics.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed on May 19th, 2021, using the terms “COVID-19”, “SARS-CoV-2” and “rheumatoid arthritis”, “psoriatic arthritis” “ankylosing spondylitis”, “Crohn’s disease” “ulcerative colitis” “hidradenitis suppurativa” and “psoriasis”, to identify primary research articles examining severe COVID-19 outcome risk in individuals with immune-mediated inflammatory diseases (IMIDs) and those on immune modifying therapy. The studies identified (including matched cohort studies and studies in disease-specific registries) were limited by small sample sizes and number of outcomes. Most studies did not show a signal of increased adverse COVID-19 outcomes in those on targeted therapies, with the exception of rituximab. Additionally, disease-specific registries are subject to selection bias and lack denominator populations.Added value of the studyIn our large population-based study of 17 million individuals, including 1 million people with IMIDs and just under 200,000 receiving immune modifying medications, we saw evidence that people with IMIDs had an increased risk of COVID-19-related death compared to the general population after adjusting for potential confounders (age, sex, deprivation, smoking status) (HR 1.23, 95%CI 1.20, 1.27). We saw differences by IMID type, with COVID-19-related death being increased by the most in people with inflammatory joint disease (HR 1.47, 95%CI 1.40, 1.54). We also saw some evidence that those with IMIDs were more likely, compared to the general population, to have COVID-19-related critical care admission/death (HR 1.24, 95%CI 1.21, 1.28) and hospitalisation (HR 1.32, 95%CI 1.29, 1.35).Compared to people with IMIDs taking standard systemics, we saw no evidence of differences in severe COVID-19-related outcomes with TNF inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-6 inhibitors and JAK inhibitors. However, there was some evidence that rituximab was associated with an increased risk of COVID-19-related death (HR 1.68, 95%CI 1.11, 2.56) and death/critical care admission (HR 1.92, 95%CI 1.31, 2.81). We also saw evidence of an increase in COVID-19-related hospital admissions in people prescribed rituximab (HR 1.59, 95%CI 1.16, 2.18) or JAK inhibition (HR 1.81, 95%CI 1.09, 3.01) compared to those on standard systemics, although this could be related to worse underlying health rather than the drugs themselves, and numbers of events were small.This is the first study to our knowledge to use high-cost drug data on medicines supplied by hospitals at a national scale in England (to identify targeted therapies). The availability of these data fills an important gap in the medication record of those with more specialist conditions treated by hospitals creating an important opportunity to generate insights to these conditions and these medicationsImplications of all of the available evidenceOur study offers insights into future risk mitigation strategies and SARS-CoV-2 vaccination priorities for individuals with IMIDs, as it highlights that those with IMIDs and those taking rituximab may be at risk of severe COVID-19 outcomes. Critically, our study does not show a link between most targeted immune modifying medications compared to standard systemics and severe COVID-19 outcomes. However, the increased risk of adverse COVID-19 outcomes that we saw in people with IMIDs and those treated with rituximab merits further study.

Objective: Registries are important data sources for randomised controlled trials (RCTs), but reporting of how they are used may be inadequate. The objective was to describe the current adequacy of reporting of RCTs using registries. Study Design and Setting: We used a database of trials using registries from a scoping review supporting the development of the 2021 CONSORT extension for Trials Conducted Using Cohorts and Routinely Collected Data (CONSORT-ROUTINE). Reporting completeness of 13 CONSORT-ROUTINE items was assessed. Results: We assessed reports of 47 RCTs that used a registry, published between 2011 and 2018. Of the 13 CONSORT-ROUTINE items, 6 were adequately reported in at least half of reports (2 in at least 80%). The 7 other items were related to routinely collected data source eligibility (32% adequate), data linkage (8% adequate), validation and completeness of data used for outcome assessment (8% adequate), validation and completeness of data used for participant recruitment (0% adequate), participant flow (9% adequate), registry funding (6% adequate) and interpretation of results in consideration of registry use (25% adequate). Conclusion: Reporting of trials using registries was often poor, particularly details on data linkage and quality. Better reporting is needed for appropriate interpretation of the results of these trials. Keywords: registries, CONSORT, CONSORT-ROUTINE, randomised controlled trials, reporting guideline, routinely collected data Running Title: Completeness and Transparency of Reporting of RCTs using Registries

Importance Research has highlighted associations between atopic dermatitis (AD) and mental health conditions in adults. However, literature on the development of mental health comorbidities in children is limited despite the large burden of pediatric AD worldwide. Objective To examine the association between AD and internalizing behaviors and symptoms of depression at multiple points across childhood and adolescence and to explore potential mediating factors, including asthma/rhinitis, sleep, and inflammation. Design, setting, and participants This longitudinal, population-based birth cohort study included children followed up from birth for a mean (SD) duration of 10.0 (2.9) years from the UK Avon Longitudinal Study of Parents and Children. Data were collected from September 6, 1990, to December 31, 2009. Data were analyzed from August 30, 2019, to July 30, 2020. Exposures Annual period prevalence of AD assessed at 11 points from 6 months to 18 years of age, measured by standardized questions about flexural dermatitis. Main outcomes and measures Symptoms of depression, measured using child-reported responses to the Short Moods and Feelings Questionnaire at 5 points from 10 to 18 years of age and internalizing behaviors, measured by maternal report of the Emotional Symptoms subscale of the Strength and Difficulties Questionnaire at 7 points from 4 to 16 years of age. Results Among the 11 181 children included in the analysis (5721 male [51.2%]), the period prevalence of symptoms of depression ranged from 6.0% to 21.6%; for internalizing behaviors, from 10.4% to 16.0%. Although mild to moderate AD was not associated with symptoms of depression, it was associated with internalizing behaviors as early as 4 years of age (mean increased odds of 29%-84% across childhood in adjusted models). Severe AD was associated with symptoms of depression (adjusted odds ratio, 2.38; 95% CI, 1.21-4.72) and internalizing symptoms (adjusted odds ratio, 1.90; 95% CI, 1.14-3.16). Sleep quality mediated some of this association, but it was not explained by differences in sleep duration, asthma/rhinitis, or levels of inflammatory markers (interleukin 6 and C-reactive protein). Conclusions and relevance Within this population-based birth cohort study in the UK, severe AD was associated with symptoms of depression and internalizing behaviors throughout childhood and adolescence. Risk of internalizing symptoms was increased even for children with mild AD beginning early in childhood, highlighting the importance of behavioral and mental health awareness in this population.

Importance Atopic eczema is characterized by a heterogenous waxing and waning course, with variable age of onset and persistence of symptoms. Distinct patterns of disease activity such as early-onset/resolving and persistent disease have been identified throughout childhood; little is known about patterns into adulthood. Objective This study aimed to identify subtypes of atopic eczema based on patterns of disease activity through mid-adulthood, to examine whether early life risk factors and participant characteristics are associated with these subtypes, and to determine whether subtypes are associated with other atopic diseases and general health in mid-adulthood. Design, Setting, and Participants This study evaluated members of 2 population-based birth cohorts, the 1958 National Childhood Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participant data were collected over the period between 1958 and 2016. Data were analyzed over the period between 2018 and 2020. Main Outcomes and Measures Subtypes of atopic eczema were identified based on self-reported atopic eczema period prevalence at multiple occasions. These subtypes were the outcome in models of early life characteristics and an exposure variable in models of midlife health. Results Latent class analysis identified 4 subtypes of atopic eczema with distinct patterns of disease activity among 15 939 individuals from the NCDS (51.4% male, 75.4% White) and 14 966 individuals from the BCS70 (51.6% male, 78.8% White): rare/no (88% to 91%), decreasing (4%), increasing (2% to 6%), and persistently high (2% to 3%) probability of reporting prevalent atopic eczema with age. Sex at birth and early life factors, including social class, region of residence, tobacco smoke exposure, and breastfeeding, predicted differences between the 3 atopic eczema subtypes and the infrequent/no atopic eczema group, but only female sex differentiated the high and decreasing probability subtypes (odds ratio [OR], 1.99; 95% CI, 1.66-2.38). Individuals in the high subtype were most likely to experience asthma and rhinitis, and those in the increasing subtype were at higher risk of poor self-reported general (OR, 1.29; 95% CI, 1.09-1.53) and mental (OR 1.45; 95% CI, 1.23-1.72) health in midlife. Conclusions and Relevance The findings of this cohort study suggest that extending the window of observation beyond childhood may reveal clear subtypes of atopic eczema based on patterns of disease activity. A newly identified subtype with increasing probability of activity in adulthood warrants additional attention given observed associations with poor self-reported health in midlife.

Objectives To investigate whether partner bereavement is associated with adverse cardiovascular and kidney-related events in people with reduced kidney function. Design Two parallel matched cohort studies using linked routinely collected health data. Setting England (general practices and hospitals using linked Clinical Practice Research Datalink, Hospital Episode Statistics, and Office of National Statistics) and Denmark (hospitals and community pharmacies using the Danish National Patient, Prescription and Education Registries and the Civil Registration System). Participants Bereaved people with reduced kidney function (estimated glomerular filtration rate (eGFR) 2 (England) or hospital-coded chronic kidney disease (Denmark)) and non-bereaved people with reduced kidney function similarly defined, matched on age, sex, general practice (England), and county of residence (Denmark) and followed-up from the bereavement date of the exposed person. Main outcome measures Cardiovascular disease (CVD) or acute kidney injury (AKI) hospitalization, or death. Results In people with reduced kidney function, we identified 19,820 (England) and 5,408 (Denmark) bereaved individuals and matched them with 134,828 (England) and 35,741 (Denmark) non-bereaved individuals. Among the bereaved, the rates of hospitalizations (per 1000 person-years) with CVD were 31.7 (95%-CI: 30.5–32.9) in England and 78.8 (95%-CI: 74.9–82.9) in Denmark; the rates of hospitalizations with AKI were 13.2 (95%-CI: 12.5–14.0) in England and 11.2 (95%-CI: 9.9–12.7) in Denmark; and the rates of death were 70.2 (95%-CI: 68.5–72.0) in England and 126.4 (95%-CI: 121.8–131.1) in Denmark. After adjusting for confounders, we found increased rates of CVD (England, HR 1.06 [95%-CI: 1.01–1.12]; Denmark, HR 1.10 [95%-CI: 1.04–1.17]), of AKI (England, HR 1.20 [95%-CI: 1.10–1.31]; Denmark HR 1.36 [95%-CI: 1.17–1.58]), and of death (England, HR 1.10 [95%-CI: 1.05–1.14]; Denmark HR 1.20 [95%-CI: 1.15–1.25]) in bereaved compared with non-bereaved people. Conclusions Partner bereavement is associated with an increased rate of CVD and AKI hospitalization, and death in people with reduced kidney function. Additional supportive care for this at-risk population may help prevent serious adverse events.

ObjectiveAn umbrella review summarising all safety data from systematic reviews of topical corticosteroids (TCS) in adults and children with atopic eczema.MethodsEmbase, MEDLINE, PubMed, Cochrane Database of Systematic Reviews and the Centre of Evidence Based Dermatology map of eczema systematic reviews were searched until 7 November 2018 and Epistemonikos until 2 March 2021. Reviews were included if they assessed the safety of TCS in atopic eczema and searched >1 database using a reproducible search strategy. Review quality was assessed using version 2 of 'A MeaSurement Tool to Assess systematic Reviews' (AMSTAR 2 tool).Results38 systematic reviews included, 34 low/critically low quality. Treatment and follow-up were usually short (2–4 weeks).Key findingsTCS versus emollient/vehicle: No meta-analyses identified for skin-thinning. Two 2-week randomised controlled trials (RCTs) found no significant increased risk with very potent TCS (0/196 TCS vs 0/33 vehicle in children and 6/109 TCS vs 2/50 vehicle, age unknown). Biochemical adrenal suppression (cortisol) was 3.8% (95% CI 2.4% to 5.8%) in a meta-analysis of 11 uncontrolled observational studies (any potency TCS, 522 children). Effects reversed when treatment ceased.TCS versus topical calcineurin inhibitors: Meta-analysis showed higher relative risk of skin thinning with TCS (4.86, 95% CI 1.06 to 22.28, n=4128, four RCTs, including one 5-year RCT). Eight cases in 2068 participants, 7 using potent TCS. No evidence of growth suppression.Once daily versus more frequent TCS: No meta-analyses identified. No skin-thinning in one RCT (3 weeks potent TCS, n=94) or biochemical adrenal suppression in two RCTs (up to 2 weeks very potent/moderate TCS, n=129).TCS twice/week to prevent flares (‘weekend therapy’) versus vehicle: No meta-analyses identified. No evidence of skin thinning in five RCTs. One RCT found biochemical adrenal suppression (2/44 children, potent TCS).ConclusionsWe found no evidence of harm when TCS were used intermittently ‘as required’ to treat flares or ‘weekend therapy’ to prevent flares. However, long-term safety data were limited.PROSPERO registration numberCRD42018079409.

ObjectiveThe main objective was to assess implementation of and ease of implementation of control measures in schools as reported by staff and parents.DesignCross-sectional study.SettingStaff and parents/guardian participants in the 132 primary schools and 20 secondary schools participating in sKIDs and sKIDsPLUS surveillances.Main outcome measurePrevalence of control measures implemented in Autumn 2020, parental and staff perception of ease of implementation and acceptability of conducting school surveillance studies.ResultsIn total, 56/152 (37%) schools participating in Public Health England’s sKIDs study of COVID in schools accepted the invitation to participate in the survey. By 28 December 2020, 1,953 parent and 986 staff respondents had completed the online questionnaire. While more than half the parents were positive about their children returning to school, roughly a third reported being a little anxious. 90% and 82% of primary and secondary school parents were either completely or partly reassured by the preventive measures implemented in their schools. Among staff, 80% of primary staff and 87% of secondary school staff felt that they were at higher risk of COVID-19 because of their profession; only 52% of primary school staff and 38% of secondary school staff reportedly felt safe. According to the teaching staff, most preventive measures were well-implemented apart from requiring 2-metre distancing between staff. For students, maintaining the 2-metre distance was reported to be particularly difficult. By extension, secondary schools also struggled to maintain small groups at all times or ensuring that the same staff were assigned to each student group (a problem also commonly reported by parents).ConclusionsVariable implementation of infection control measures was reported by staff and parents. Whilst the majority were not worried about returning to school, some parents and staff, were concerned about returning to school and the risks posed to children, staff and household members.Strengths and limitations of this studyStrengthsThis study is one of the few to investigate school staff and parents’ perceptions of the implementation of control measures implemented following the reopening of schools in England.The early establishment of COVID-19 surveillance in primary and secondary schools in the summer term 2020 provided a cohort to rapidly evaluate the experiences of parents and school staff during the autumn term before schools were required to close for the subsequent national lockdown.LimitationsAs the questionnaire and information provided was available in English only, there is likely to be an under-representation of families for whom English was not their main language.Some school responses were only provided by one participant so may not necessarily be representative of the whole school.Although the surveillance included schools recruited nationally, a convenience sample was used and as such may not be representative of all primary and secondary schools in England.

Background: In the UK, an estimated one third of people with dementia have not received a diagnosis. Good evidence suggests that dementia risk is increased among widowed individuals; however, it is not clear if they are being diagnosed in routine primary care.Objective: This study aimed to investigate if bereavement influenced the probability of having received a dementia diagnosis.Methods: A population-based cohort study using UK electronic health records, between 1997 and 2017, among 247,586 opposite-sex partners. Those experiencing partner bereavement were matched (age, sex, and date of bereavement) to a non-bereaved person living in a partnership. Multivariate cox regression was performed.Results: Partner bereavement was associated with an increased risk of receiving a diagnosis of dementia in the first three months (hazard ratio (HR) 1.43, 95%CI 1.20-1.71) and first six months (HR 1.24, 95%CI 1.09-1.41), while there was a small reduced risk of getting a dementia diagnosis over all follow-up (HR 0.94, 95%CI 0.89-0.98).Conclusions: Partner bereavement appears to lead to a short-term increased risk of the surviving partner receiving a diagnosis of dementia, suggesting that bereavement unmasks existing undiagnosed dementia. Over the longer term, however, bereaved individuals are less likely to have a diagnosis of dementia in their health records than non-bereaved individuals.

Background Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K. Objectives To estimate the incidence of BCC and cSCC in the U.K. Methods A cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age-standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated. Results In the U.K, the EASR of the first BCC and cSCC PPPA in 2013-15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5-11% of the true tumour count. Conclusions Based on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations. The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients. These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour-reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published. Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

La disponibilite croissante des donnees generees par les prestataires de soins de sante ainsi que par la surveillance de l’incidence des maladies et des indicateurs de l’evolution des maladies a transforme le caractere de la recherche en sante. Les donnees de sante collectees en

Background Recent studies indicate that vitamin D supplementation may decrease respiratory tract infections, but the association between vitamin D and COVID-19 is still unclear. Objective To explore the association between vitamin D status and infections, hospitalisation, and mortality due to COVID-19. Methods We used UK Biobank, a nationwide cohort of 500,000 individuals aged between 40 and 69 years at recruitment between 2006 and 2010. We included people with at least one serum vitamin D test, living in England with linked primary care and inpatient records. The primary exposure was serum vitamin D status measured at recruitment, defined as deficiency at Results We included 307,512 participants (54.9% female, 55.9% over 70 years old) in our analysis. During summertime months, weak evidence existed that the vitamin D deficiency group had a lower hazard of being diagnosed with COVID-19 (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.77–0.95). During non-summertime, the vitamin D deficiency group had a higher hazard of COVID-19 compared with the vitamin D sufficient group (HR = 1.14, 95% CI = 1.01–1.30). No evidence was found that vitamin D deficiency or insufficiency was associated with either hospitalisation or mortality due to COVID-19 in any time strata. Conclusion We found no evidence of an association between historical vitamin D status and hospitalisation or mortality due to COVID-19, along with inconsistent results for any association between vitamin D and diagnosis of COVID-19. However, studies using more recent vitamin D measurements and systematic COVID-19 testing are needed.

Background: Atopic dermatitis (AD) might adversely affect academic performance, possibly through influences on psychological functioning such as stress resilience. Objectives: To investigate the association of atopic dermatitis with stress resilience, cognitive function and educational attainment. Methods: We used data from a national cohort of men who underwent a military conscription examination at ages 17–20 years in Sweden between 1969 and 1976. All potential conscripts met a physician who assessed current or previous history of AD. Stress resilience was measured by a psychologist using a semistructured interview. The conscription assessment included a written cognitive function test. The highest level of education achieved was identified through record linkage. Results: The study population included 234 715 men, 1673 (0·7%) of whom had a diagnosis of AD. AD was associated with a greater risk of low stress resilience [adjusted relative risk ratio (RRR) 1·60, 95% confidence interval (CI) 1·38–1·86]. AD was associated with higher cognitive function (β-coefficient 0·15, 95% CI 0·05–0·24) and higher educational level (RRR 1·29, 95% CI 1·13–1·47). However, adjustment for socioeconomic characteristics of the family of origin attenuated the magnitude of the associations and eliminated the statistical significance (β-coefficient 0·06, 95% CI −0·03 to 0·15; RRR 1·16, 95% CI 1·00–1·35). Conclusions: Swedish men with AD had lower stress resilience in late adolescence but did not have lower cognitive function or poorer educational attainment. The lower stress resilience associated with AD is consistent with an increased risk of possible long-term adverse health outcomes. (Less)

BackgroundIndirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression.ObjectiveCharacterise the factors associated with worsening psoriasis in the COVID-19 pandemic, using mental health status (anxiety and depression) as the main exposure of interest.MethodsGlobal cross-sectional study using a primary outcome of self-reported worsening of psoriasis. Individuals with psoriasis completed an online self-report questionnaire (PsoProtectMe; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection Me) between May 2020 and January 2021. Each individual completed a validated screen for anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-2). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression.Results4,043 people with psoriasis (without COVID-19) from 86 countries self-reported to PsoProtectMe (mean age 47.2 years [SD 15.1]; mean BMI 27.6kg/m2 [SD 6.0], 2,684 [66.4%] female and 3,016 [74.6%] of white European ethnicity). 1,728 (42.7%) participants (1322 [77%] female) reported worsening of their psoriasis in the pandemic. A positive screen for anxiety or depression associated with worsening psoriasis in age and gender adjusted (OR 2.04, 95% CI 1.77-2.36), and fully adjusted (OR 2.01, 95% CI 1.72-2.34) logistic regression models. Female sex, obesity, shielding behaviour and systemic immunosuppressant non-adherence also associated with worsening psoriasis. The commonest reason for non-adherence was concern regarding complications related to COVID-19.ConclusionsThese data indicate an association between poor mental health and worsening psoriasis in the pandemic. Access to holistic care including psychological support may mitigate potentially long-lasting effects of the pandemic on health outcomes in psoriasis. The study also highlights an urgent need to address patient concerns about immunosuppressant-related risks, which may be contributing to non-adherence.

ObjectivesRandomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.MethodsThe development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.Results27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.ConclusionUptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using cohorts and routinely collected data.

Altres ajuts: Department of Health via the National Institute for Health Research (NIHR); St Thomas' NHS Foundation Trust; King's College London; NIHR Manchester Biomedical Research Centre; Psoriasis Association. Wellcome Senior Research Fellowship in Clinical Science (205039/Z/16/Z); Health Data Research UK (grant no. LOND1); Health Data Research UK (grant no. MR/S003126/1); UK MRC, Engineering and Physical Sciences Research Council; Economic and Social Research Council; Department of Health and Social Care (England); Chief Scientist Office of the Scottish Government Health; Social Care Directorates; Health and Social Care Research and Development Division (Welsh Government); Public Health Agency (Northern Ireland); British Heart Foundation; Wellcome Trust; NIHR Academic Clinical Lectureship through the University of Manchester; NIHR Emeritus Senior Investigator (MR/101 1808/1); NIHR Manchester Biomedical Research Centre. Background: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. Objectives: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. Conclusions: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

Background Trials of novel agents are required to improve the care of patients with rare diseases, but trial feasibility may be uncertain due to concerns over insufficient patient numbers. We aimed to determine the size of the pool of potential participants in England 2015–2017 for trials in the autoimmune blistering skin disease bullous pemphigoid. Methods The size of the pool of potential participants was estimated using routinely collected healthcare data from linked primary care (Clinical Practice Research Datalink; CPRD) and secondary care (Hospital Episode Statistics; HES) databases. Thirteen consultant dermatologists were surveyed to determine the likelihood that a patient would be eligible for a trial based on the presence of cautions or contra-indications to prednisolone use. These criteria were applied to determine how they influenced the potential pool of participants. Results Extrapolated to the population of England, we would expect approximately 10,800 (point estimate 10,747; 95% CI 7191 to 17,239) new cases of bullous pemphigoid to be identified in a three-year period. For a future trial involving oral prednisolone (standard care), the application of cautions to its use as exclusion criteria would result in approximately 365 potential participants unlikely to be recruited, a further 5332 could be recruited with caution, and 5104 in whom recruitment is still possible. 11–17% of potential participants may have pre-existing dementia and require an alternative consent process. Conclusions Routinely collected electronic health records can be used to inform the feasibility of clinical trials in rare diseases, such as whether recruitment is feasible nationally and how long recruitment might take to meet recruitment targets. Future trials of bullous pemphigoid in England may use the data presented to inform trial design, including eligibility criteria and consent processes for enrolling people with dementia.

ObjectiveNo recent large studies have described the distribution of vitamin D status in the UK. Understanding the epidemiology of vitamin D deficiency is important to inform targeted public health recommendations. This study aimed to investigate the distribution of factors associated with serum vitamin D status in a large national cohort.DesignA cross-sectional study.SettingThe UK Biobank, a prospective cohort study following the health and well-being of middle-aged and older adults recruited between 2006 and 2010.ParticipantsA total of 449 943 participants aged 40–69 years with measured serum vitamin D status were eligible for the analysis. Participants completed a questionnaire about sex, age, ethnic background, vitamin D supplementation, smoking, drinking and socioeconomic status.Primary and secondary outcome measuresWe investigated the distribution of serum vitamin D status and the association between demographic factors and vitamin D deficiency or insufficiency. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D level ResultsAsian (n=4297/8000, 53.7%) and black (n=2459/7046, 34.9%) participants had a higher proportion of vitamin D deficiency than white participants (n=50 920/422 907, 12%). During spring and winter, the proportion of vitamin D deficiency was higher across the UK and higher in the north than in the south. Male sex, abnormal body mass index, non-white ethnic backgrounds, smoking and being more socioeconomically deprived were associated with higher odds of vitamin D deficiency. Increasing age, taking vitamin D supplements and drinking alcohol were associated with lower odds of deficiency.ConclusionsVitamin D status varied among different ethnic groups and by season and geographical area within the UK. Taking supplements was associated with a lower risk of vitamin D deficiency. These findings support the vitamin D supplementation recommendations of Public Health England.

Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome data, or a combination of these purposes. This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE). The extension was developed to look at the unique characteristics of trials conducted with these types of data with the goal of improving reporting quality in the long term by setting standards early in the process of uptake of these trial designs. The extension was developed with a sequential approach, including a Delphi survey, a consensus meeting, and piloting of the checklist. The checklist was informed by the CONSORT 2010 statement and two reporting guidelines for observational studies, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement. The extension includes eight items modified from the CONSORT 2010 statement and five new items. Reporting items with explanations and examples are provided, including key aspects of trials conducted using cohorts or routinely collected data that require specific reporting considerations.

Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying, and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps for developing SPIRIT-ROUTINE, which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods: The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed, such as the Consolidated Standards of Reporting Trials (CONSORT) extension for trials conducted using cohorts and RCD (CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklist items. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of the final checklist. Conclusion: The SPIRIT-ROUTINE extension will contribute to improving design of trials using cohorts and RCD and transparency of reporting.

IntroductionEvidence indicates that people with the common inflammatory skin diseases atopic eczema or psoriasis are at increased risk of mental illness. However, the reasons for the relationship between skin disease and common mental disorders (ie, depression and anxiety) or severe mental illnesses (ie, schizophrenia, bipolar disorder and other psychoses) are unclear. Therefore, we aim to synthesise the available evidence regarding the risk factors for mental illness in adults with atopic eczema or psoriasis.Methods and analysisWe will conduct a systematic review of randomised controlled trials, cohort, case–control and cross-sectional studies. We will search the following databases from inception to March 2020: Medline, Embase, Global Health, Scopus, the Cochrane Library, Web of Science, Base, PsycInfo, the Global Resource of Eczema Trials, and the grey literature databases Open Grey, PsycExtra and the New York Academy of Medicine Grey Literature Report. We will also search the bibliographies of eligible studies and relevant systematic reviews to identify additional relevant studies. Citation searching of large summary papers will be used to further identify relevant publications. Two reviewers will initially review study titles and abstracts for eligibility, followed by full text screening. We will extract data using a standardised data extraction form. We will assess the risk of bias of included studies using the Quality in Prognosis Studies tool. We will synthesise data narratively, and if studies are sufficiently homogenous, we will consider a meta-analysis. We will assess the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework.Ethics and disseminationEthical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.PROSPERO registration numberCRD42020163941.

ObjectivesRegistry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse COVID-19 outcomes compared to patients receiving no systemic treatments. We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation.MethodsOnline surveys were completed by individuals with Rheumatic and Musculoskeletal Diseases (RMD) (UK only) or psoriasis (globally) between 4th May and 7th September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterised international variation in a mixed effects model.ResultsOf 3,720 participants (2,869 psoriasis, 851 RMD) from 74 countries, 2,262 (60.8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term ‘shielding’). A greater proportion of those receiving targeted therapies (biologics and JAK inhibitors) reported shielding compared to those receiving no systemic therapy (adjusted odds ratio [OR] 1.63, 95% CI 1.35-1.97) and standard systemic agents (OR 1.39, 95% CI 1.22-1.56). Shielding was associated with established risk factors for severe COVID-19 (male sex [OR 1.14, 95% CI 1.05-1.24], obesity [OR 1.38, 95% CI 1.23-1.54], comorbidity burden [OR 1.43, 95% CI 1.15-1.78]), a primary indication of RMD (OR 1.37, 95% CI 1.27-1.48) and a positive anxiety or depression screen (OR 1.57, 95% CI 1.36-1.80). Modest differences in the proportion shielding were observed across nations.ConclusionsGreater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk mitigation strategies and may help inform updated public health guidelines as the pandemic continues.Key messagesWhat is already known about this subject?At the beginning of the COVID-19 pandemic, patients with immune mediated inflammatory diseases (IMIDs) on targeted systemic immunosuppressive therapy were considered to be at higher risk of severe COVID-19. Subsequent registry data suggest that this may not the case.What does this study add?Here we characterise shielding behaviour in patients with IMIDs from a global survey. We identified that targeted systemic therapy associates with increased shielding behaviour, as do demographic risk factors for severe COVID-19 including male gender and obesity.Shielding behaviour varies across nations, albeit modestly when case-mix is taken into account.How might this impact on clinical practice or future developments?Variable shielding behaviour amongst patients with IMIDs may be an important confounder when considering differential COVID-19 risk between therapy types, so should be accounted for in analyses where possible.

BackgroundConcerns have been raised that the response to the UK COVID-19 pandemic may have worsened physical and mental health, and reduced use of health services. However, the scale of the problem is unquantified, impeding development of effective mitigations. We asked what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic?MethodsUsing electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (2017-2020), we calculated weekly primary care contacts for selected acute physical and mental health conditions (including: anxiety, depression, acute alcohol-related events, asthma and chronic obstructive pulmonary disease [COPD] exacerbations, cardiovascular and diabetic emergencies). We used interrupted time series (ITS) analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (‘lockdown’) compared to the period prior to their introduction in March 2020.FindingsThe overall population included 9,863,903 individuals on 1st January 2017. Primary care contacts for all conditions dropped dramatically after introduction of population-wide restrictions. By July 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels. The largest reductions were for contacts for: diabetic emergencies (OR: 0.35, 95% CI: 0.25-0.50), depression (OR: 0.53, 95% CI: 0.52-0.53), and self-harm (OR: 0.56, 95% CI: 0.54-0.58).InterpretationThere were substantial reductions in primary care contacts for acute physical and mental conditions with restrictions, with limited recovery by July 2020. It is likely that much of the deficit in care represents unmet need, with implications for subsequent morbidity and premature mortality. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people experiencing the conditions and healthcare provision. Maintaining access must be a key priority in future public health planning (including further restrictions).FundingWellcome Trust Senior Fellowship (SML), Health Data Research UK.RESULTS IN CONTEXTEvidence before this studyA small study in 47 GP practices in a largely deprived, urban area of the UK (Salford) reported that primary care consultations for four broad diagnostic groups (circulatory disease, common mental health problems, type 2 diabetes mellitus and malignant cancer) declined by 16-50% between March and May 2020, compared to what was expected based on data from January 2010 to March 2020. We searched Medline for other relevant evidence of the indirect effect of the COVID-19 pandemic on physical and mental health from inception to September 25th 2020, for articles published in English, with titles including the search terms (“covid*” or “coronavirus” or “sars-cov-2”), and title or abstracts including the search terms (“indirect impact” or “missed diagnos*” or “missing diagnos*” or “delayed diagnos*” or ((“present*” or “consult*” or “engag*” or “access*”) AND (“reduction” or “decrease” or “decline”)). We found no further studies investigating the change in primary care contacts for specific physical- and mental-health conditions indirectly resulting from the COVID-19 pandemic or its control measures. There has been a reduction in hospital admissions and presentations to accident and emergency departments in the UK, particularly for myocardial infarctions and cerebrovascular accidents. However, there is no published evidence specifically investigating the changes in primary care contacts for severe acute physical and mental health conditions.Added value of this studyTo our knowledge this is the first study to explore changes in healthcare contacts for acute physical and mental health conditions in a large population representative of the UK. We used electronic primary care health records of nearly 10 million individuals across the UK to investigate the indirect impact of COVID-19 on primary care contacts for mental health, acute alcohol-related events, asthma/chronic obstructive pulmonary disease (COPD) exacerbations, and cardiovascular and diabetic emergencies up to July 2020. For all conditions studied, we found primary care contacts dropped dramatically following the introduction of population-wide restriction measures in March 2020. By July 2020, with the exception of unstable angina and acute alcohol-related events, primary care contacts for all conditions studied had not recovered to pre-lockdown levels. In the general population, estimates of the absolute reduction in the number of primary care contacts up to July 2020, compared to what we would expect from previous years varied from fewer than 10 contacts per million for some cardiovascular outcomes, to 12,800 per million for depression and 6,600 for anxiety. In people with COPD, we estimated there were 43,900 per million fewer contacts for COPD exacerbations up to July 2020 than what we would expect from previous years.Implicatins of all the available evidenceWhile our results may represent some genuine reduction in disease frequency (e.g. the restriction measures may have improved diabetic glycaemic control due to more regular daily routines at home), it is more likely the reduced primary care conatcts we saw represent a substantial burden of unmet need (particularly for mental health conditions) that may be reflected in subsequent increased mortality and morbidity. Health service providers should take steps to prepare for increased demand in the coming months and years due to the short and longterm ramifications of reduced access to care for severe acute physical and mental health conditions. Maintaining access to primary care is key to future public health planning in relation to the pandemic.