Publications by authors named "Sinead Langan"

105 Publications

Is there an association between long-term antibiotics for acne and subsequent infection sequelae and antimicrobial resistance? A systematic review.

Br J Gen Pract 2021 Mar 4. Epub 2021 Mar 4.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Background: Antimicrobial resistance (AMR) is a global health priority. Acne vulgaris is a common skin condition for which antibiotic use ranges from a few months to years of daily exposure.

Aim: To systemically search for and synthesise evidence on the risk of treatment-resistant infections, and other evidence of AMR, following long-term oral antibiotic use for acne.

Design & Setting: Embase, MEDLINE, Cochrane and Web of Science databases were searched using MeSH, EMTREE or other relevant terms and following a pre-registered protocol.

Method: Search strategies were developed with a librarian and run in July 2019. All searches date from database inception. The primary outcome was antibiotic treatment failure or infection caused by a resistant organism. Secondary outcomes included detection of resistant organisms without an infection, rate of infection, or changes to flora.

Results: 6,996 records were identified. 73 full-text articles were shortlisted for full review, of which five were included. Two investigated rates of infection and three resistance or changes to microbial flora. Three studies had 35 or fewer participants (range 20-118,496). Three studies had a 'serious' or 'high' risk of bias, one 'moderate' and one a 'low' risk of bias. We found weak evidence for an association between antibiotic use for acne and subsequent increased rates of upper respiratory-tract infections and pharyngitis.

Conclusion: There is a lack of high-quality evidence on the relationship between oral antibiotics for acne treatment and subsequent AMR sequelae. This needs to be urgently addressed with rigorously conducted studies.
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http://dx.doi.org/10.3399/BJGPO.2020.0181DOI Listing
March 2021

Indirect acute effects of the COVID-19 pandemic on physical and mental health in the UK: a population-based study.

Lancet Digit Health 2021 Feb 18. Epub 2021 Feb 18.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK; Health Data Research UK, London, UK.

Background: There are concerns that the response to the COVID-19 pandemic in the UK might 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 aimed to ascertain what has happened to general practice contacts for acute physical and mental health outcomes during the pandemic.

Methods: Using de-identified electronic health records from the Clinical Research Practice Datalink (CPRD) Aurum (covering 13% of the UK population), between 2017 and 2020, we calculated weekly primary care contacts for selected acute physical and mental health conditions: anxiety, depression, self-harm (fatal and non-fatal), severe mental illness, eating disorder, obsessive-compulsive disorder, acute alcohol-related events, asthma exacerbation, chronic obstructive pulmonary disease exacerbation, acute cardiovascular events (cerebrovascular accident, heart failure, myocardial infarction, transient ischaemic attacks, unstable angina, and venous thromboembolism), and diabetic emergency. Primary care contacts included remote and face-to-face consultations, diagnoses from hospital discharge letters, and secondary care referrals, and conditions were identified through primary care records for diagnoses, symptoms, and prescribing. Our overall study population included individuals aged 11 years or older who had at least 1 year of registration with practices contributing to CPRD Aurum in the specified period, but denominator populations varied depending on the condition being analysed. We used an interrupted time-series analysis to formally quantify changes in conditions after the introduction of population-wide restrictions (defined as March 29, 2020) compared with the period before their introduction (defined as Jan 1, 2017 to March 7, 2020), with data excluded for an adjustment-to-restrictions period (March 8-28).

Findings: The overall population included 9 863 903 individuals on Jan 1, 2017, and increased to 10 226 939 by Jan 1, 2020. Primary care contacts for almost all conditions dropped considerably after the introduction of population-wide restrictions. The largest reductions were observed for contacts for diabetic emergencies (odds ratio 0·35 [95% CI 0·25-0·50]), depression (0·53 [0·52-0·53]), and self-harm (0·56 [0·54-0·58]). In the interrupted time-series analysis, with the exception of acute alcohol-related events (0·98 [0·89-1·10]), there was evidence of a reduction in contacts for all conditions (anxiety 0·67 [0·66-0·67], eating disorders 0·62 [0·59-0·66], obsessive-compulsive disorder [0·69 [0·64-0·74]], self-harm 0·56 [0·54-0·58], severe mental illness 0·80 [0·78-0·83], stroke 0·59 [0·56-0·62], transient ischaemic attack 0·63 [0·58-0·67], heart failure 0·62 [0·60-0·64], myocardial infarction 0·72 [0·68-0·77], unstable angina 0·72 [0·60-0·87], venous thromboembolism 0·94 [0·90-0·99], and asthma exacerbation 0·88 [0·86-0·90]). By July, 2020, except for unstable angina and acute alcohol-related events, contacts for all conditions had not recovered to pre-lockdown levels.

Interpretation: There were substantial reductions in primary care contacts for acute physical and mental conditions following the introduction of restrictions, with limited recovery by July, 2020. Further research is needed to ascertain whether these reductions reflect changes in disease frequency or missed opportunities for care. Maintaining health-care access should be a key priority in future public health planning, including further restrictions. The conditions we studied are sufficiently severe that any unmet need will have substantial ramifications for the people with the conditions as well as health-care provision.

Funding: Wellcome Trust Senior Fellowship, Health Data Research UK.
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http://dx.doi.org/10.1016/S2589-7500(21)00017-0DOI Listing
February 2021

Lifestyle and Anthropometric Factors and Risk of Herpes Zoster: A Nationwide Population-Based Cohort Study.

Am J Epidemiol 2021 Feb 11. Epub 2021 Feb 11.

Research Unit for General Practice, Aarhus University, Aarhus, Denmark.

The role of lifestyle in development of herpes zoster remains unclear. We examined whether smoking status, alcohol consumption, body mass index (BMI), or physical activity were associated with zoster risk. We followed a population-based cohort of 101,894 respondents to the 2010 Danish National Health Survey (baseline May 1, 2010) until zoster diagnosis, death, emigration, or July 1, 2014, whichever occurred first. We computed hazard ratios for zoster associated with each exposure, using Cox regression with age as the time-scale and adjusting for potential confounders. Compared with never smokers, hazards for zoster were increased in former smokers [1.17; 95% confidence interval (CI): 1.06, 1.30], but not in current smokers (1.00; 95% CI: 0.89, 1.13). Compared with low-risk alcohol consumption, neither intermediate-risk (0.95; 95% CI: 0.84, 1.07) nor high-risk alcohol consumption (0.99; 95% CI: 0.85, 1.15) were associated with zoster. We also found no increased hazard associated with weekly binge drinking vs. not (0.93; 95% CI: 0.77, 1.11). Risk of zoster varied little by BMI (referent=normal weight) and physical activity levels (referent=light level), with HRs between 0.96 and 1.08. We observed no dose-response association between the exposures and zoster. The examined lifestyle and anthropometric factors thus were not risk factors for zoster.
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http://dx.doi.org/10.1093/aje/kwab027DOI Listing
February 2021

Supporting self-care for eczema: protocol for two randomised controlled trials of ECO (Eczema Care Online) interventions for young people and parents/carers.

BMJ Open 2021 Feb 5;11(2):e045583. Epub 2021 Feb 5.

School of Primary Care, Population Health and Medical Education, University of Southampton, Southampton, UK.

Introduction: Eczema care requires management of triggers and various treatments. We developed two online behavioural interventions to support eczema care called ECO (Eczema Care Online) for young people and ECO for families. This protocol describes two randomised controlled trials (RCTs) aimed to evaluate clinical and cost-effectiveness of the two interventions. METHODS AND ANALYSIS: : Two independent, pragmatic, unmasked, parallel group RCTs with internal pilots and nested health economic and process evaluation studies. : Participants will be recruited from general practitioner practices in England. : Young people aged 13-25 years with eczema and parents and carers of children aged 0-12 years with eczema, excluding inactive or very mild eczema (five or less on Patient-Oriented Eczema Measure (POEM)). : Participants will be randomised to online intervention plus usual care or to usual eczema care alone. : Primary outcome is eczema severity over 24 weeks measured by POEM. Secondary outcomes include POEM 4-weekly for 52 weeks, quality of life, eczema control, itch intensity (young people only), patient enablement, health service and treatment use. Process measures include treatment adherence, barriers to adherence and intervention usage. Our sample sizes of 303 participants per trial are powered to detect a group difference of 2.5 (SD 6.5) in monthly POEM scores over 24 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up. Cost-effectiveness analysis will be from a National Health Service and personal social service perspective. Qualitative and quantitative process evaluation will help understand the mechanisms of action and participant experiences and inform implementation.

Ethics And Dissemination: The study has been approved by South Central Oxford A Research Ethics Committee (19/SC/0351). Recruitment is ongoing, and follow-up will be completed by mid-2022. Findings will be disseminated to participants, the public, dermatology and primary care journals, and policy makers.

Trial Registration Number: ISRCTN79282252.
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http://dx.doi.org/10.1136/bmjopen-2020-045583DOI Listing
February 2021

Atopic eczema in adulthood and mortality: UK population-based cohort study, 1998-2016.

J Allergy Clin Immunol 2021 Jan 21. Epub 2021 Jan 21.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; Health Data Research UK, London, United Kingdom. Electronic address:

Background: Atopic eczema affects up to 10% of adults and is becoming more common globally. Few studies have assessed whether atopic eczema increases the risk of death.

Objective: We aimed to determine whether adults with atopic eczema were at increased risk of death overall and by specific causes and to assess whether the risk varied by atopic eczema severity and activity.

Methods: The study was a population-based matched cohort study using UK primary care electronic health care records from the Clinical Practice Research Datalink with linked hospitalization data from Hospital Episode Statistics and mortality data from the Office for National Statistics from 1998 to 2016.

Results: A total of 526,736 patients with atopic eczema were matched to 2,567,872 individuals without atopic eczema. The median age at entry was 41.8 years, and the median follow-up time was 4.5 years. There was limited evidence of increased hazard for all-cause mortality in those with atopic eczema (hazard ratio = 1.04; 99% CI = 1.03-1.06), but there were somewhat stronger associations (8%-14% increased hazard) for deaths due to infectious, digestive, and genitourinary causes. Differences on the absolute scale were modest owing to low overall mortality rates. Mortality risk increased markedly with eczema severity and activity. For example, patients with severe atopic eczema had a 62% increased hazard (hazard ratio = 1.62; 99% CI = 1.54-1.71) for mortality compared with those without eczema, with the strongest associations for infectious, respiratory, and genitourinary causes.

Conclusion: The increased hazards for all-cause and cause-specific mortality were largely restricted to those with the most severe or predominantly active atopic eczema. Understanding the reasons for these increased hazards for mortality is an urgent priority.
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http://dx.doi.org/10.1016/j.jaci.2020.12.001DOI Listing
January 2021

Vitamin D Deficiency or Supplementation and the Risk of Human Herpesvirus Infections or Reactivation: A Systematic Review and Meta-analysis.

Open Forum Infect Dis 2021 Jan 22;8(1):ofaa570. Epub 2020 Dec 22.

Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Background: Vitamin D may protect against respiratory virus infections, but any association with herpesviruses is unclear.

Methods: We undertook a systematic review of vitamin D deficiency or supplementation and the risk of 8 human herpesviruses. Six databases and 4 gray literature databases were searched for relevant cohort studies, case-control studies, and clinical trials.

Results: Ten studies were included, all conducted among immunosuppressed patients. There was no evidence that vitamin D deficiency is associated with cytomegalovirus (CMV) disease (pooled risk ratio, 1.06; 95% CI, 0.66-1.7), herpes zoster after transplantation (1 study), or HHV-8 among HIV patients (1 study). Vitamin D supplementation may decrease herpes zoster among hemodialysis patients (1 study) or CMV disease after renal transplantation (1 study), but supplementation was not associated with reduced EBV viral load among multiple sclerosis patients (1 study).

Conclusions: Any association between vitamin D and herpesviruses remains inconclusive. Further studies in the general population are needed.
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http://dx.doi.org/10.1093/ofid/ofaa570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817081PMC
January 2021

Distribution of vitamin D status in the UK: a cross-sectional analysis of UK Biobank.

BMJ Open 2021 Jan 6;11(1):e038503. Epub 2021 Jan 6.

Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, UK.

Objective: No 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.

Design: A cross-sectional study.

Setting: The UK Biobank, a prospective cohort study following the health and well-being of middle-aged and older adults recruited between 2006 and 2010.

Participants: A 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 Measures: We 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 <25 nmol/L. Multivariable logistic regression was used to assess the association between demographic factors and vitamin D status.

Results: Asian (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.

Conclusions: Vitamin 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.
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http://dx.doi.org/10.1136/bmjopen-2020-038503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789460PMC
January 2021

Retraction of COVID-19 Pharmacoepidemiology Research Could Have Been Avoided by Effective Use of Reporting Guidelines.

Clin Epidemiol 2020 21;12:1403-1420. Epub 2020 Dec 21.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

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 , 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%)(χ = 14.839, P <0.001). Similarly, the article published in reported 24 of 34 STROBE items (70.6%), two of 13 RECORD items (15.4%), and 7.5 of 15 RECORD-PE items (50.0%) (χ = 11.668, P = 0.003). Important aspects of the methods unique to research using routinely collected health data were not reported, including variables used to identify exposure, outcome and confounders, validation of the coding or algorithms, a description of the underlying database population and the accuracy of data linkage methods.

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.
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http://dx.doi.org/10.2147/CLEP.S288677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762449PMC
December 2020

Risk factors for mental illness in adults with atopic eczema or psoriasis: protocol for a systematic review.

BMJ Open 2020 12 28;10(12):e038324. Epub 2020 Dec 28.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Introduction: Evidence 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 Analysis: We 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 Dissemination: Ethical 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 Number: CRD42020163941.
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http://dx.doi.org/10.1136/bmjopen-2020-038324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772326PMC
December 2020

Factors associated with adverse COVID-19 outcomes in patients with psoriasis-insights from a global registry-based study.

J Allergy Clin Immunol 2021 01 16;147(1):60-71. Epub 2020 Oct 16.

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, United Kingdom. Electronic address:

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited.

Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization.

Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors.

Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94).

Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates.
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http://dx.doi.org/10.1016/j.jaci.2020.10.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566694PMC
January 2021

Pyoderma gangrenosum.

Nat Rev Dis Primers 2020 10 8;6(1):81. Epub 2020 Oct 8.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that presents with rapidly developing, painful skin ulcers hallmarked by undermined borders and peripheral erythema. Epidemiological studies indicate that the average age of PG onset is in the mid-40s, with an incidence of a few cases per million person-years. PG is often associated with a variety of other immune-mediated diseases, most commonly inflammatory bowel disease and rheumatoid arthritis. The cause of PG is not well understood, but PG is generally considered an autoinflammatory disorder. Studies have focused on the role of T cells, especially at the wound margin; these cells may support the destructive autoinflammatory response by the innate immune system. PG is difficult to diagnose as several differential diagnoses are possible; in addition to clinical examination, laboratory tests of biopsied wound tissue are required for an accurate diagnosis, and new validated diagnostic criteria will facilitate the process. Treatment of PG typically starts with fast-acting immunosuppressive drugs (corticosteroids and/or cyclosporine) to reduce inflammation followed by the addition of more slowly acting immunosuppressive drugs with superior adverse event profiles, including biologics (in particular, anti-tumour necrosis factor (TNF) agents). Appropriate wound care is also essential. Future research should focus on PG-specific outcome measures and PG quality-of-life studies.
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http://dx.doi.org/10.1038/s41572-020-0213-xDOI Listing
October 2020

How "benign" is cutaneous mastocytosis? A Danish registry-based matched cohort study.

Int J Womens Dermatol 2020 Sep 1;6(4):294-300. Epub 2020 Jun 1.

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

Background: There are limited estimates of the incidence rates (IRs) of mastocytosis, and only a few studies have addressed the long-term consequences of living with these diagnoses. Previous reports have shown that systemic mastocytosis is associated with leukemic transformations and an increased risk of death as opposed to cutaneous mastocytosis (CM) and indolent systemic mastocytosis (ISM), which have benign diagnoses with life expectancy rates similar to those of the background population.

Objective: This study aimed to analyze the incidence and mortality of mastocytosis.

Methods: A population-based matched cohort study of patients with mastocytosis between 1 January 1, 1977 and 31 December 31, 2014 was identified from the Danish National Health Registries. IRs of CM, ISM, and pediatric mastocytosis were highlighted. Survival estimates were compared with those of a healthy background population, using a Cox proportional hazard model.

Results: A total of 1461 patients with mastocytosis were identified. The annual IR of overall mastocytosis was 1.1 per 100,000 person years (95% confidence interval [CI], 1.0-1.2). Among children, the IR was 1.8 per 100,000 person years (95% CI, 1.6-2.1). The prevalence of any comorbidity was twice as high among patients with mastocytosis compared with the population without mastocytosis (odds ratio: 2.1; 95% CI, 1.8-2.5). The Charlson Comorbidity Index-adjusted mortality among adult patients with mastocytosis was HR 1.2 (95% CI, 0.8-1.9), HR 1.9 (95% CI 1.4-2.5), and HR 4.2 (95%, CI 1.9-9.4), respectively.

Conclusion: Based on an entire nation, with free health care at the point of access, we estimated an annual IR of mastocytosis and its subgroups. We discovered that patients with ISM had an increased risk of death compared with the general population. Our data supported the overall benign nature of CM diagnosed after age 2 years.
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http://dx.doi.org/10.1016/j.ijwd.2020.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522902PMC
September 2020

Personalized prediction of daily eczema severity scores using a mechanistic machine learning model.

Clin Exp Allergy 2020 11 9;50(11):1258-1266. Epub 2020 Sep 9.

Department of Bioengineering, Imperial College London, London, UK.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease with periods of flares and remission. Designing personalized treatment strategies for AD is challenging, given the apparent unpredictability and large variation in AD symptoms and treatment responses within and across individuals. Better prediction of AD severity over time for individual patients could help to select optimum timing and type of treatment for improving disease control.

Objective: We aimed to develop a proof of principle mechanistic machine learning model that predicts the patient-specific evolution of AD severity scores on a daily basis.

Methods: We designed a probabilistic predictive model and trained it using Bayesian inference with the longitudinal data from two published clinical studies. The data consisted of daily recordings of AD severity scores and treatments used by 59 and 334 AD children over 6 months and 16 weeks, respectively. Validation of the predictive model was conducted in a forward-chaining setting.

Results: Our model was able to predict future severity scores at the individual level and improved chance-level forecast by 60%. Heterogeneous patterns in severity trajectories were captured with patient-specific parameters such as the short-term persistence of AD severity and responsiveness to topical steroids, calcineurin inhibitors and step-up treatment.

Conclusions: Our proof of principle model successfully predicted the daily evolution of AD severity scores at an individual level and could inform the design of personalized treatment strategies that can be tested in future studies. Our model-based approach can be applied to other diseases with apparent unpredictability and large variation in symptoms and treatment responses such as asthma.
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http://dx.doi.org/10.1111/cea.13717DOI Listing
November 2020

Atopic dermatitis.

Lancet 2020 08;396(10247):345-360

Department of Dermatology and Allergy, University Hospital Schleswig-Holstein, Kiel, Germany.

Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.
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http://dx.doi.org/10.1016/S0140-6736(20)31286-1DOI Listing
August 2020

Validation study of bullous pemphigoid and pemphigus vulgaris recording in routinely collected electronic primary healthcare records in England.

BMJ Open 2020 07 14;10(7):e035934. Epub 2020 Jul 14.

Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, UK.

Objectives: The validity of bullous pemphigoid and pemphigus vulgaris recording in routinely collected healthcare data in the UK is unknown. We assessed the positive predictive value (PPV) for bullous pemphigoid and pemphigus vulgaris primary care Read codes in the Clinical Practice Research Datalink (CPRD) using linked inpatient data (Hospital Episode Statistics (HES)) as the diagnostic benchmark.

Setting: Adult participants with bullous pemphigoid or pemphigus vulgaris registered with HES-linked general practices in England between January 1998 and December 2017. Code-based algorithms were used to identify patients from the CPRD and extract their benchmark blistering disease diagnosis from HES.

Primary Outcome Measure: The PPVs of Read codes for bullous pemphigoid and pemphigus vulgaris.

Results: Of 2468 incident cases of bullous pemphigoid and 431 of pemphigus vulgaris, 797 (32.3%) and 85 (19.7%) patients, respectively, had a hospitalisation record for a blistering disease. The PPV for bullous pemphigoid Read codes was 93.2% (95% CI 91.3% to 94.8%). Of the bullous pemphigoid cases, 3.0% had an HES diagnosis of pemphigus vulgaris and 3.8% of another blistering disease. The PPV for pemphigus vulgaris Read codes was 58.5% (95% CI 48.0% to 68.9%). Of the pemphigus vulgaris cases, 24.7% had an HES diagnosis of bullous pemphigoid and 16.5% of another blistering disease.

Conclusions: The CPRD can be used to study bullous pemphigoid, but recording of pemphigus vulgaris needs to improve in primary care.
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http://dx.doi.org/10.1136/bmjopen-2019-035934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365488PMC
July 2020

Is there an association between long-term antibiotics for acne and subsequent infection sequelae and antimicrobial resistance? A systematic review protocol.

BMJ Open 2020 07 2;10(7):e033662. Epub 2020 Jul 2.

Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, UK.

Introduction: Antimicrobial resistance (AMR) is a global health emergency. Acne vulgaris is a highly prevalent condition and the dominant role antibiotics play in its treatment is a major concern. Antibiotics are widely used in the treatment of acne predominantly for their anti-inflammatory effect, hence their use in acne may not be optimal. Tetracyclines and macrolides are the two most common oral antibiotic classes prescribed, and their average use can extend from a few months to several years of intermittent or continuous use. The overall aim of this systematic review is to elucidate what is known about oral antibiotics for acne contributing to antibiotic treatment failure and AMR.

Methods And Analysis: A systematic review will be conducted to address the question: What is the existing evidence that long-term oral antibiotics used to treat acne in those over 8 years of age contribute towards antibiotic treatment failure or other outcomes suggestive of the impact of AMR? We will search the following databases: Embase, MEDLINE, the Cochrane Library and Web of Science. Search terms will be developed in collaboration with a librarian by identifying keywords from relevant articles and by undertaking pilot searches. Randomised controlled trials, cohort and case-controlled studies conducted in any healthcare setting and published in any language will be included. The searches will be re-run prior to final analyses to capture the recent literature. The Cochrane tool for bias assessment in randomised trials and ROBINS-I for the assessment of bias in non-randomised studies will be used to assess the risk of bias of included studies. GRADE will be used to make an overall assessment of the quality of evidence. A meta-analysis will be undertaken of the outcome measures if the individual studies are sufficiently homogeneous. If a meta-analysis is not possible, a qualitative assessment will be presented as a narrative review.

Ethics And Dissemination: Ethical approval is not required for this systematic-review. The results will be published in a peer-reviewed journal and any deviations from the protocol will be clearly documented in the published manuscript of the full systematic-review.

Prospero Registration Number: CRD42019121738.
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http://dx.doi.org/10.1136/bmjopen-2019-033662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333805PMC
July 2020

Association Between Atopic Eczema and Cancer in England and Denmark.

JAMA Dermatol 2020 Jun 24. Epub 2020 Jun 24.

Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Importance: Associations between atopic eczema and cancer are unclear, with competing theories that increased immune surveillance decreases cancer risk and that immune stimulation increases cancer risk. Establishing baseline cancer risk in people with atopic eczema is important before exploring the association between new biologic drugs for atopic eczema and cancer risk.

Objective: To investigate whether atopic eczema is associated with cancer.

Design, Setting, And Participants: Matched cohort studies were conducted from January 2, 1998, to March 31, 2016, in England and from January 1, 1982, to June 30, 2016, in Denmark. We conducted our analyses between July 2018 and July 2019. The setting was English primary care and nationwide Danish data. Participants with atopic eczema (adults only in England and any age in Denmark) were matched on age, sex, and calendar period (as well as primary care practice in England only) to those without atopic eczema.

Exposure: Atopic eczema.

Main Outcomes And Measures: Overall cancer risk and risk of specific cancers were compared in people with and without atopic eczema.

Results: In England, matched cohorts included 471 970 individuals with atopic eczema (median [IQR] age, 41.1 [24.9-60.7] years; 276 510 [58.6%] female) and 2 239 775 individuals without atopic eczema (median [IQR] age, 39.8 [25.9-58.4] years; 1 301 074 [58.1%] female). In Denmark, matched cohorts included 44 945 individuals with atopic eczema (median [IQR] age, 13.7 [1.7-21.1] years; 22 826 [50.8%] female) and 445 673 individuals without atopic eczema (median [IQR] age, 13.5 [1.7-20.8] years; 226 323 [50.8%] female). Little evidence was found of associations between atopic eczema and overall cancer (adjusted hazard ratio [HR], 1.04; 99% CI, 1.02-1.06 in England and 1.05; 99% CI, 0.95-1.16 in Denmark) or for most specific cancers. However, noncutaneous lymphoma risk was increased in people with atopic eczema in England (adjusted HR, 1.19; 99% CI, 1.07-1.34 for non-Hodgkin lymphoma [NHL] and 1.48; 99% CI, 1.07-2.04 for Hodgkin lymphoma). Lymphoma risk was increased in people with greater eczema severity vs those without atopic eczema (NHL adjusted HR, 1.06; 99% CI, 0.90-1.25 for mild eczema; 1.24; 99% CI, 1.04-1.48 for moderate eczema; and 2.08; 99% CI, 1.42-3.04 for severe eczema). Danish point estimates also showed increased lymphoma risk in people with moderate to severe eczema compared with those without atopic eczema (minimally adjusted HR, 1.31; 99% CI, 0.76-2.26 for NHL and 1.35; 99% CI, 0.65-2.82 for Hodgkin lymphoma), but the 99% CIs were wide.

Conclusions And Relevance: The findings from 2 large population-based studies performed in different settings do not support associations between atopic eczema and most cancers. However, an association was observed between atopic eczema and lymphoma, particularly NHL, that increased with eczema severity. This finding warrants further study as new immunomodulatory systemic therapeutics are brought to market that may alter cancer risk.
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http://dx.doi.org/10.1001/jamadermatol.2020.1948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315391PMC
June 2020

Risk of herpes zoster after exposure to varicella to explore the exogenous boosting hypothesis: self controlled case series study using UK electronic healthcare data.

BMJ 2020 01 22;368:l6987. Epub 2020 Jan 22.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, WC1E7HT, UK.

Objective: To assess the magnitude and duration of any hypothesised protective effect of household exposure to a child with varicella on the relative incidence of herpes zoster in adults.

Design: Self controlled case series.

Setting: UK general practices contributing to Clinical Practice Research Datalink.

Participants: 9604 adults (≥18 years) with a diagnosis of herpes zoster (in primary care or hospital records) between 1997 and 2018, who during their observation period lived with a child (<18 years) with a diagnosis of varicella.

Main Outcome Measures: Relative incidence of herpes zoster in the 20 years after exposure to a child with varicella in the household compared with baseline time (all other time, excluding the 60 days before exposure).

Results: 6584 of the 9604 adults with herpes zoster (68.6%) were women. Median age of exposure to a child with varicella was 38.3 years (interquartile range 32.3-48.8 years) and median observation period was 14.7 (11.1-17.7) years. 4116 adults developed zoster in the baseline period, 433 in the 60 days before exposure and 5055 in the risk period. After adjustment for age, calendar time, and season, strong evidence suggested that in the two years after household exposure to a child with varicella, adults were 33% less likely to develop zoster (incidence ratio 0.67, 95% confidence interval 0.62 to 0.73) compared with baseline time. In the 10-20 years after exposure, adults were 27% less likely to develop herpes zoster (0.73, 0.62 to 0.87) compared with baseline time. A stronger boosting effect was observed among men than among women after exposure to varicella.

Conclusions: The relative incidence of zoster was lower in the periods after exposure to a household contact with varicella, with modest but long lasting protective effects observed. This study suggests that exogenous boosting provides some protection from the risk of herpes zoster, but not complete immunity, as assumed by previous cost effectiveness estimates of varicella immunisation.
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http://dx.doi.org/10.1136/bmj.l6987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190015PMC
January 2020

Atopic eczema and fracture risk in adults: A population-based cohort study.

J Allergy Clin Immunol 2020 02 19;145(2):563-571.e8. Epub 2019 Nov 19.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom; Health Data Research UK, London, United Kingdom.

Background: Limited evidence suggests increased fracture risk in people with atopic eczema. Any link could have substantial effect; atopic eczema is common, and fractures have associated morbidity and mortality.

Objective: We sought to examine whether atopic eczema is associated with fracture and whether fracture risk varies with eczema severity.

Methods: We performed a matched cohort study set in primary care (Clinical Practice Research Datalink GOLD 1998-2016) and linked hospital admissions data (Hospital Episode Statistics), including adults (≥18 years old) with atopic eczema matched (by age, sex, general practice, and cohort entry date) with up to 5 individuals without eczema. We estimated hazard ratios (HRs) from stratified Cox regression comparing risk of major osteoporotic (hip, pelvis, spine, wrist, and proximal humerus) fractures individually and any fracture in those with and without atopic eczema.

Results: We identified 526,808 people with atopic eczema and 2,569,030 people without atopic eczema. Those with eczema had increased risk of hip (HR, 1.10; 99% CI, 1.06-1.14), pelvic (HR, 1.10; 99% CI, 1.02-1.19), spinal (HR, 1.18; 99% CI, 1.10-1.27), and wrist (HR, 1.07; 99% CI, 1.03,-1.11) fractures. We found no evidence of increased proximal humeral (HR, 1.06; 99% CI, 0.97-1.15) fracture risk. Fracture risk increased with increasing eczema severity, with the strongest associations in people with severe eczema (compared with those without) for spinal (HR, 2.09; 99% CI, 1.66-2.65), pelvic (HR, 1.66; 99% CI, 1.26-2.20), and hip (HR, 1.50; 99% CI, 1.30-1.74) fractures. Associations persisted after oral glucocorticoid adjustment.

Conclusions: People with atopic eczema have increased fracture risk, particularly major osteoporotic fractures.
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http://dx.doi.org/10.1016/j.jaci.2019.09.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014587PMC
February 2020

Vitamin D deficiency or supplementation and the risk of human herpesvirus infections or reactivation: a systematic review protocol.

BMJ Open 2019 10 7;9(10):e031867. Epub 2019 Oct 7.

Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine Faculty of Epidemiology and Population Health, London, UK

Introduction: Human herpesviruses induce lifelong latent infections and may reactivate as the immune system deteriorates. Recent studies have suggested that vitamin D, an essential element of bone health, may have some effect of protecting against infections, but investigations of its potential to prevent herpesvirus infection or reactivation are limited. We will review the current literature examining vitamin D and the risk of herpesvirus infections or reactivation.

Methods And Analysis: Our systematic review will address two research questions: (1) Do deficient/insufficient serum vitamin D levels increase the risk of herpesvirus infections and (2) Does vitamin D supplementation protect against herpesvirus infections? We will include only intervention studies with control groups, cohort studies and case-control studies. We will use subject headings and keywords to search for synonyms of 'vitamin D' and 'herpesviruses' (including herpes simplex virus type 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesviruses type 6, 7 and 8) in Medline, Embase, Global Health, Web of Science, Scopus and Cochrane Central Register of Controlled Trials, and the grey literature databases Open Grey, EThOS and BASE from inception to 31 August 2019. References to the included articles and relevant systematic reviews will also be examined. Two reviewers will independently screen the study titles and abstracts, and examine the full texts to decide the final eligibility. They will independently extract data from the studies and assess bias using the Cochrane Collaboration approach. A third researcher will solve any discrepancies. The results will be narratively synthesised; if an adequate number of studies is included and the homogeneity between studies is acceptable, a meta-analysis will be performed. We will assess the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation framework, and display the results in a summary of findings table.

Ethics And Dissemination: Ethical review is not required for a systematic review. We will publish the results in a peer-review journal. Any amendments to the protocol will be recorded in the supplementary section.

Prospero Registration Number: CRD42019130153.
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http://dx.doi.org/10.1136/bmjopen-2019-031867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797410PMC
October 2019

Partner Bereavement and Detection of Dementia: A UK-Based Cohort Study Using Routine Health Data.

J Alzheimers Dis 2019 ;72(2):653-662

London School of Hygiene & Tropical Medicine, London, UK.

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.
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http://dx.doi.org/10.3233/JAD-190571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918907PMC
November 2020

Atopic Eczema in Adulthood and Risk of Depression and Anxiety: A Population-Based Cohort Study.

J Allergy Clin Immunol Pract 2020 01 31;8(1):248-257.e16. Epub 2019 Aug 31.

Department of Non-Communicable Disease Epidemiology, Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom; St John's Institute of Dermatology, Guy's & St Thomas' Hospital National Health Service (NHS) Foundation Trust and King's College London, London, United Kingdom; Health Data Research UK, London, United Kingdom.

Background: Atopic eczema is a common and debilitating condition associated with depression and anxiety, but the nature of this association remains unclear.

Objective: To explore the temporal relationship between atopic eczema and new depression/anxiety.

Methods: This matched cohort study used routinely collected data from the UK Clinical Practice Research Datalink, linked to hospital admissions data. We identified adults with atopic eczema (1998-2016) using a validated algorithm, and up to 5 individuals without atopic eczema matched on date of diagnosis, age, sex, and general practice. We estimated the hazard ratio (HR) for new depression/anxiety using stratified Cox regression to account for age, sex, calendar period, Index of Multiple Deprivation, glucocorticoid treatment, obesity, smoking, and harmful alcohol use.

Results: We identified 526,808 adults with atopic eczema who were matched to 2,569,030 without. Atopic eczema was associated with increased incidence of new depression (HR, 1.14; 99% CI, 1.12-1.16) and anxiety (HR, 1.17; 99% CI, 1.14-1.19). We observed a stronger effect of atopic eczema on depression with increasing atopic eczema severity (HR [99% CI] compared with no atopic eczema: mild, 1.10 [1.08-1.13]; moderate, 1.19 [1.15-1.23]; and severe, 1.26 [1.17-1.37]). A dose-response association, however, was less apparent for new anxiety diagnosis (HR [99% CI] compared with no atopic eczema: mild, 1.14 [1.11-1.18]; moderate, 1.21 [1.17-1.26]; and severe, 1.15; [1.05-1.25]).

Conclusions: Adults with atopic eczema are more likely to develop new depression and anxiety. For depression, we observed a dose-response relationship with atopic eczema severity.
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http://dx.doi.org/10.1016/j.jaip.2019.08.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947493PMC
January 2020

Atopic dermatitis and risk of atrial fibrillation or flutter: A 35-year follow-up study.

J Am Acad Dermatol 2020 Dec 20;83(6):1616-1624. Epub 2019 Aug 20.

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

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.
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http://dx.doi.org/10.1016/j.jaad.2019.08.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704103PMC
December 2020

Clinical onset of atopic eczema: Results from 2 nationally representative British birth cohorts followed through midlife.

J Allergy Clin Immunol 2019 09 28;144(3):710-719. Epub 2019 Jun 28.

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Atopic eczema onset is described primarily in early childhood, and the frequency and characteristics of adult-onset disease remain controversial.

Objective: We sought to determine the proportion of subjects who report atopic eczema symptoms between birth and midadulthood and to examine demographic, immunologic, and genetic factors associated with period of symptom onset.

Methods: We conducted a longitudinal study using data from 2 nationally representative community-based birth cohorts from the United Kingdom: the British Cohort Studies 1958 and 1970. Subjects were followed from birth through age 42 to 50 years. The primary outcome was the age period of self-reported atopic eczema symptom onset based on repeated measures of self-reported atopic eczema at each survey wave.

Results: The annual period prevalence of atopic eczema ranged from 5% to 15% in 2 cohorts of more than 17,000 participants each followed from birth through middle age. There was no clear trend in prevalence by age, and among adults reporting active atopic eczema during a given year, only 38% had symptom onset reported in childhood. When compared with subjects whose eczema started in childhood, those with adult-onset disease were more likely to be women, from Scotland or Northern England, of lower childhood socioeconomic group, smokers in adulthood, and less likely to have a history of asthma. In a subanalysis using data from the 1958 cohort only, genetic mutations previously associated with atopic eczema, including filaggrin-null mutations, and allergen-specific IgE were more common among those with childhood-onset disease.

Conclusion: Rates of self-reported atopic eczema remain high after childhood, and adult-onset atopic eczema has different risk factor associations than childhood-onset eczema.
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http://dx.doi.org/10.1016/j.jaci.2019.05.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721832PMC
September 2019

La déclaration RECORD-PE (Reporting of Studies Conducted Using Observational Routinely Collected Health Data Statement for Pharmacoepdemiology) : directives pour la communication des études realisées à partir de données de santé observationelles collectées en routine en pharmacoépidémiologie.

CMAJ 2019 06;191(25):E689-E708

Faculty of Epidemiology and Population Health (Langan, Wing, Smeeth), London School of Hygiene and Tropical Medicine, Londres, Royaume-Uni ; Département d'épidémiologie clinique (Schmidt, Ehrenstein, Petersen, Sørensen), université d'Aarhus, Aarhus, Danemark ; Institut de recherche de l'Hôpital d'Ottawa (Nicholls, Moher) ; École d'épidémiologie et de santé publique (Nicholls), Université d'Ottawa, Ottawa, Ont. ; Département d'épidémiologie, de bio-statistique et de santé au travail (Filion), Université McGill ; Centre d'épidémiologie clinique (Filion), Institut Lady Davis, Hôpital général juif, Montréal, Qué. ; Division of Pharmacoepidemiology and Clinical Pharmacology (Klungel), Utrecht Institute for Pharmaceutical Sciences, université d'Utrecht, Utrecht, Pays-Bas ; Department of Primary Care and Population Health (Petersen), University College London, Londres, Royaume-Uni ; Arthritis Research UK Centre for Epidemiology (Dixon), Division of Musculoskeletal and Dermatological Sciences, School of Biological Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester, Royaume-Uni ; ICES (Guttmann, Benchimol) ; Department of Paediatrics (Guttmann), The Hospital for Sick Children, université de Toronto, Toronto, Ont. ; Population, Policy and Practice Programme (Harron), Great Ormond Street Institute of Child Health, University College London, Londres, Royaume-Uni ; Basel Institute for Clinical Epidemiology and Biostatistics (Hemkens), Department of Clinical Research, University Hospital of Basel, université de Basel, Basel, Suisse ; Division of Pharmacoepidemiology and Pharmacoeconomics (Schneeweiss, Wang), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Mass. ; Julius Global Health (Sturkenboom), University Medical Center Utrecht, Utrecht, Pays-Bas ; Cochrane Suisse (von Elm), Institut de médecine sociale et préventive, Université de Lausanne, Lausanne, Suisse ; Département de pédiatrie et École d'épidémiologie et de santé publique (Benchimol), Université d'Ottawa ; Institut de recherche du Centre hospitalier pour enfants de l'est de l'Ontario (Benchimol), Ottawa, Ont.

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http://dx.doi.org/10.1503/cmaj.190347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6592814PMC
June 2019

Assessment of Sleep Disturbances and Exhaustion in Mothers of Children With Atopic Dermatitis.

JAMA Dermatol 2019 05;155(5):556-563

Department of Dermatology Program for Clinical Research, University of California, San Francisco.

Importance: The well-being and development of children is strongly influenced by parents' physical and psychosocial health. Data from small, clinic-based studies suggest that sleep loss may be common in parents of children with atopic dermatitis (AD), but longitudinal population-based studies are lacking.

Objectives: To compare sleep disturbances over time between mothers of children with and without AD and to determine whether these disturbances are associated with the child's disease severity and the child's sleep disturbances.

Design, Setting, And Participants: In the ongoing Avon Longitudinal Study of Parents and Children, all pregnant women residing in Avon, United Kingdom, with an expected delivery date between April 1, 1991, and December 31, 1992, were recruited. Analyses for this study, a secondary analysis of this cohort, were performed from September 2017 to September 2018. Mother-child pairs were followed up with a time-varying measure of child AD activity and severity and self-reported maternal sleep measures repeated at multiple time points between child ages 6 months and 11 years.

Main Outcomes And Measures: Time-varying binary measures of maternal sleep duration (<6 vs ≥6 hours per night), difficulty falling asleep, early morning awakening, subjectively insufficient sleep, and daytime exhaustion.

Results: The study followed up 13 988 mother-child pairs from birth for a median duration of 11 (interquartile range, 7-11) years. Among the cohort, 11 585 of 13 972 mothers (82.9%) were aged 21 to 34 years and 12 001 of 12 324 (97.4%) were of white race/ethnicity; 7220 of 13 978 children (51.7%) were male. Sleep duration (adjusted odds ratio [AOR], 1.09; 95% CI, 0.90-1.32) and early morning awakenings (AOR, 1.16; 95% CI, 0.93-1.46) were similar between mothers of children with and without AD. In contrast, mothers of children with AD were more likely to report difficulty falling asleep (AOR, 1.36; 95% CI, 1.01-1.83), subjectively insufficient sleep (AOR, 1.43; 95% CI, 1.24-1.66), and daytime exhaustion (AOR, 1.41; 95% CI, 1.12-1.78) independent of the child's comorbid asthma and/or allergic rhinitis. For all measures, worse child AD severity was associated with worse maternal sleep outcomes. The magnitude and significance of the associations were largely unchanged after adjustment for child sleep disturbances.

Conclusions And Relevance: Mothers of children with AD reported difficulty falling asleep, subjectively insufficient sleep, and daytime exhaustion throughout the first 11 years of childhood. However, child sleep disturbances did not fully explain maternal sleep disturbances, and future research should investigate other mechanisms. In caring for children with AD, clinicians should consider maternal sleep disturbances and caregiver fatigue.
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http://dx.doi.org/10.1001/jamadermatol.2018.5641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506883PMC
May 2019

Engaging the Patient's Perspective in Clinical Trials Research.

J Invest Dermatol 2019 06 14;139(6):1217-1220. Epub 2019 Mar 14.

Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2019.02.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540938PMC
June 2019

Association of Atopic Dermatitis With Sleep Quality in Children.

JAMA Pediatr 2019 05 6;173(5):e190025. Epub 2019 May 6.

Department of Dermatology Program for Clinical Research, University of California, San Francisco, San Francisco.

Importance: Pruritus, a hallmark of atopic dermatitis (AD), is thought to disrupt sleep, yet little is known about how variations in disease activity and severity of this common childhood condition may be associated with sleep patterns over time.

Objective: To determine whether children with active AD have impaired sleep duration and quality at multiple time points throughout childhood and whether disease severity affects sleep outcomes.

Design, Setting, And Participants: This longitudinal cohort study used data of children enrolled in the Avon Longitudinal Study of Parents and Children, a population-based birth cohort in Avon, United Kingdom. Participants were children (N = 13 988) alive at 1 year and followed up with repeated measures of self-reported AD and sleep through 16 years of age. This study was based on data collected from 1990 to 2008. Data analysis was performed from September 2017 to September 2018.

Main Outcomes And Measures: Standardized measure of sleep duration and composite measure of sleep quality, including nighttime awakenings, early morning awakenings, difficulty falling asleep, and nightmares, were repeated at multiple time points between 2 and 16 years of age.

Results: The study sample comprised 13 988 children (7220 male [51.6%]) followed up for a median (interquartile range [IQR]) duration of 11 (5-14) years. Of this total, 4938 children (35.3%) met the definition of having atopic dermatitis between 2 and 16 years of age. Total sleep duration was similar between children with active AD and without AD at all ages, and the average estimated difference across childhood was a clinically negligible difference of 2 minutes less per day for children with AD (95% CI, -4 to 0 minutes). In contrast, children with active AD were more likely to report worse sleep quality at all time points, with a nearly 50% higher odds of experiencing more sleep-quality disturbances (adjusted odds ratio [aOR], 1.48; 95% CI, 1.33 to 1.66). Children with more severe active disease (quite bad or very bad AD: aOR, 1.68; 95% CI, 1.42 to 1.98) and with comorbid asthma or allergic rhinitis (aOR, 1.79; 95% CI, 1.54 to 2.09) had worse sleep quality. However, even children with mild AD (OR, 1.40; 95% CI, 1.27 to 1.54) or inactive AD (OR, 1.41; 95% CI, 1.28 to 1.55) had statistically significantly increased odds of impaired sleep quality.

Conclusions And Relevance: Atopic dermatitis appeared to be associated with impaired sleep quality throughout childhood; thus, it is suggested that clinicians should consider sleep quality among all children with AD, especially those with comorbid asthma or allergic rhinitis and severe disease, and that interventions to improve sleep quality are needed.
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http://dx.doi.org/10.1001/jamapediatrics.2019.0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503516PMC
May 2019

La déclaration RECORD (Reporting of Studies Conducted Using Observational Routinely Collected Health Data) : directives pour la communication des études réalisées à partir de données de santé collectées en routine.

CMAJ 2019 02;191(8):E216-E230

Institut de recherche du Centre hospitalier pour enfants de l'est de l'Ontario (Benchimol) ; Département de pédiatrie (Benchimol), Université d'Ottawa ; École d'épidémiologie et de santé publique (Benchimol, Moher), Université d'Ottawa, Ottawa, Ont. ; ICES (Benchimol, Guttmann), Toronto, Ont. ; London School of Hygiene and Tropical Medicine (Smeeth, Harron, Langan), Londres, Royaume-Uni ; Department of Paediatrics (Guttmann), The Hospital for Sick Children; Institute of Health Policy, Management and Evaluation (Guttmann), University of Toronto, Toronto, Ont. ; Institut de recherche de l'Hôpital d'Ottawa (Moher), Ottawa, Ont. ; Département de soins primaires et santé publique (Petersen), University College London, Londres, Royaume-Uni ; Département d'épidémiologie clinique (Sørensen), université d'Aarhus, Aarhus, Danemark ; Management des organisations de santé (EA 7348 MOS) (Januel), Institut du Management, École des hautes études en santé publique, Rennes, France ; Chaire d'excellence en Management de la santé (Januel), Université Sorbonne Paris Cité, Paris, France ; Cochrane Suisse (von Elm), Institut universitaire de médecine sociale et préventive, Université de Lausanne, Lausanne, Suisse

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http://dx.doi.org/10.1503/cmaj.181309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389451PMC
February 2019

Atopic eczema and major cardiovascular outcomes: A systematic review and meta-analysis of population-based studies.

J Allergy Clin Immunol 2019 05 18;143(5):1821-1829. Epub 2018 Dec 18.

Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: Atopic eczema is a common inflammatory skin disease. Various inflammatory conditions have been linked to cardiovascular disease, a major cause of global mortality and morbidity.

Objective: We sought to systematically review and meta-analyze population-based studies assessing associations between atopic eczema and specific cardiovascular outcomes.

Methods: MEDLINE, Embase, and Global Health were searched from inception to December 2017. We obtained pooled estimates using random-effects meta-analyses. We used a multivariate Bayesian meta-regression model to estimate the slope of effect of increasing atopic eczema severity on cardiovascular outcomes.

Results: Nineteen relevant studies were included. The effects of atopic eczema reported in cross-sectional studies were heterogeneous, with no evidence for pooled associations with angina, myocardial infarction, heart failure, or stroke. In cohort studies atopic eczema was associated with increased risk of myocardial infarction (n = 4; relative risk [RR], 1.12; 95% CI, 1.00-1.25), stroke (n = 4; RR, 1.10; 95% CI, 1.03-1.17), ischemic stroke n = 4; RR, 1.17; 95% CI, 1.14-1.20), angina (n = 2; RR, 1.18; 95% CI, 1.13-1.24), and heart failure (n = 2; RR, 1.26; 95% CI, 1.05-1.51). Prediction intervals were wide for myocardial infarction and stroke. The risk of cardiovascular outcomes appeared to increase with increasing severity (mean RR increase between severity categories, 1.15; 95% credibility interval, 1.09-1.21; uncertainty interval, 1.04-1.28).

Conclusion: Significant associations with cardiovascular outcomes were more common in cohort studies but with considerable between-study heterogeneity. Increasing atopic eczema severity was associated with increased risk of cardiovascular outcomes. Improved awareness among stakeholders regarding this small but significant association is warranted.
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http://dx.doi.org/10.1016/j.jaci.2018.11.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497108PMC
May 2019