In utero or early in life exposure to antibiotics and the risk of childhood atopic dermatitis, a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early life exposure of a child to antibiotics increases the risk of early onset AD. OBJECTIVE: We hypothesize that antibiotic exposure in utero or early in life (e.g., first 90 days) increases the likelihood that children develop AD. METHODS: Utilizing a large prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: The risk of AD in childhood was increased after in utero or early life antibiotic exposure. For any in utero AB exposure the HR was 1.38 (1.36,1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure, 1.43 (1.41,1.44), and for childhood exposure, 1.81(1.79,1.82). HRs were higher in children born to mothers without AD than those with AD pointing to effect modification by maternal AD status. CONCLUSION: Children born to mothers exposed to antibiotics while in utero had, depending on the mother's history of AD, approximately a 20 to 40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early-in-life had a 40 to 80% increased risk of developing AD. Our study, supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying skin microbiome.

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

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

The association between penile cancer and HIV infection: A literature review.

Penile cancer is a rare malignancy which HIV infection appears to increase the risk of. The magnitude of this risk and the pathogenesis remain unclear. A comprehensive review of the literature was undertaken using conventional search strategies. Twenty-four publications were identified by this methodology, of which nine were case reports and 15 were observational studies. These studies were highly heterogeneous, with varying study designs, populations, and objectives. The risk of penile cancer within HIV-positive individuals is significantly greater than in those without HIV (RR = 3 .7 to 5.8, 3 studies; SIR = 3.8 to 11.1, 4 studies). HIV is also shown to influence disease characteristics, with a four-fold increased risk of death from penile cancer. Moreover, progression from intraepithelial neoplasia occurs earlier in HIV, six years sooner than in HIV-negative men. HIV-positive men have a higher prevalence of HPV infection. Ethnicity is also shown to modulate the relationship between HIV and penile carcinoma, with a higher risk of cancer in Hispanic, compared with Caucasian, HIV-positive men. This review has collated data from diverse sources to improve understanding of the relationship between HIV and penile cancer. This relationship has been quantitatively and qualitatively characterised and highlights areas deserving further enquiry.

Long-term oral antibiotic use in people with acne vulgaris in UK primary care: a drug utilization study.

BACKGROUND: The inappropriate use of antibiotics is understood to contribute to antimicrobial resistance. Oral antibiotics are regularly used to treat moderate-to-severe acne vulgaris. In practice, we do not know the typical length of oral antibiotic treatment courses for acne in routine primary care and what proportion of people receive more than one course of treatment following a new acne diagnosis. OBJECTIVES: To describe how oral antibiotics are prescribed for acne over time in UK primary care. METHODS: We conducted a descriptive longitudinal drug utilization study using routinely collected primary care data from the Clinical Practice Research Datalink GOLD (2004-2019). We included individuals (8-50 years) with a new acne diagnosis recorded between 1 January 2004 and 31 July 2019. RESULTS: We identified 217 410 people with a new acne diagnosis. The median age was 17 years [interquartile range (IQR) 15-25] and median follow-up was 4.3 years (IQR 1.9-7.6). Among people with a new acne diagnosis, 96 703 (44.5%) received 248 560 prescriptions for long-term oral antibiotics during a median follow-up of 5.3 years (IQR 2.8-8.5). The median number of continuous courses of antibiotic therapy (≥ 28 days) per person was four (IQR 2-6). The majority (n = 59 010, 61.0%) of first oral antibiotic prescriptions in those with a recorded acne diagnosis were between the ages of 12 and 18. Most (n = 71 544, 74.0%) first courses for oral antibiotics were for between 28 and 90 days. The median duration of the first course of treatment was 56 days (IQR 50-93 days) and 18 127 (18.7%) of prescriptions of ≥ 28 days were for < 6 weeks. Among people who received a first course of oral antibiotic for ≥ 28 days, 56 261 (58.2%) received a second course after a treatment gap of ≥ 28 days. The median time between first and second courses was 135 days (IQR 67-302). The cumulative duration of exposure to oral antibiotics during follow-up was 255 days (8.5 months). CONCLUSIONS: Further work is needed to understand the consequences of using antibiotics for shorter periods than recommended. Suboptimal treatment duration may result in reduced clinical effectiveness or repeated exposures, potentially contributing to antimicrobial resistance.

Rates of serious clinical outcomes in survivors of hospitalisation with COVID-19 in England: a descriptive cohort study within the OpenSAFELY platform.

Background: Patients surviving hospitalisation for COVID-19 are thought to be at high risk of cardiometabolic and pulmonary complications, but quantification of that risk is limited. We aimed to describe the overall burden of these complications in people after discharge from hospital with COVID-19.   Methods: Working on behalf of NHS England, we used linked primary care records, death certificate and hospital data from the OpenSAFELY platform. We constructed three cohorts: patients discharged following hospitalisation with COVID-19, patients discharged following pre-pandemic hospitalisation with pneumonia, and a frequency-matched cohort from the general population in 2019. We studied seven outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), ischaemic stroke, myocardial infarction (MI), heart failure, AKI and new type 2 diabetes mellitus (T2DM) diagnosis. Absolute rates were measured in each cohort and Fine and Gray models were used to estimate age/sex adjusted subdistribution hazard ratios comparing outcome risk between discharged COVID-19 patients and the two comparator cohorts. Results: Amongst the population of 77,347 patients discharged following hospitalisation with COVID-19, rates for the majority of outcomes peaked in the first month post-discharge, then declined over the following four months. Patients in the COVID-19 population had markedly higher risk of all outcomes compared to matched controls from the 2019 general population. Across the whole study period, the risk of outcomes was more similar when comparing patients discharged with COVID-19 to those discharged with pneumonia in 2019, although COVID-19 patients had higher risk of T2DM (15.2 versus 37.2 [rate per 1,000-person-years for COVID-19 versus pneumonia, respectively]; SHR, 1.46 [95% CI: 1.31 - 1.63]).  Conclusions: Risk of cardiometabolic and pulmonary adverse outcomes is markedly raised following discharge from hospitalisation with COVID-19 compared to the general population. However, excess risks were similar to those seen following discharge post-pneumonia. Overall, this suggests a large additional burden on healthcare resources.

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

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: In this systematic review, a literature search was carried out using the databases Embase, MEDLINE, Cochrane, and Web of Science. They were searched using MeSH, Emtree, or other relevant terms, and followed a pre-registered protocol. METHOD: Search strategies were developed with a librarian and undertaken 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: A total of 6996 records were identified. Seventy-three 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. Weak evidence was found 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.

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

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.

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

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.

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

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.

Lack of association of biologic therapy for psoriasis with psychiatric illness: An electronic medical records cohort study.

BACKGROUND: Psoriasis and biologic therapies have been associated with psychiatric illnesses. OBJECTIVE: To determine if persons with psoriasis or those exposed to biologics are more likely to develop a psychiatric illness. METHODS: Retrospective electronic medical records cohort study. RESULTS: Individuals with psoriasis were significantly more likely to have a history of several medical (eg, cardiovascular illnesses) and psychiatric (eg, depression, suicide) illnesses than those without psoriasis. Those with psoriasis who were prescribed a biologic therapy were significantly less likely than those with psoriasis not prescribed a biologic agent to receive a psychiatric illness diagnosis (hazard ratio for any psychiatric illness 0.52, 95% confidence interval 0.51-0.53, P < .0001). With respect to any psychiatric illness, this finding was confirmed when comparing biologic therapy versus methotrexate treatment (0.80, 95% confidence interval 0.76-0.84, P < .0001). LIMITATIONS: These findings were likely attributable to treatment selection bias. CONCLUSION: Individuals with psoriasis have an increased risk of several medical and psychiatric illnesses. Individuals with psoriasis prescribed biologic agents are less likely than those not prescribed biologic agents to develop psychiatric illnesses. Most likely because of treatment selection, individuals with psoriasis prescribed biologic therapy are not currently at increased risk of a psychiatric outcome.

Trends in Oral Antibiotic Prescription in Dermatology, 2008 to 2016.

Importance: Dermatologists prescribe more oral antibiotic courses per clinician than any other specialty, and this use puts patients at risk of antibiotic-resistant infections and antibiotic-associated adverse events. Objective: To characterize the temporal trends in the diagnoses most commonly associated with oral antibiotic prescription by dermatologists, as well as the duration of this use. Design, Setting, and Participants: Repeated cross-sectional analysis of antibiotic prescribing by dermatologists from January 1, 2008, to December 31, 2016. The setting was Optum Clinformatics Data Mart (Eden Prairie, Minnesota) deidentified commercial claims data. Participants were dermatology clinicians identified by their National Uniform Claim Committee taxonomy codes, and courses of oral antibiotics prescribed by these clinicians were identified by their National Drug Codes. Exposures: Claims for oral antibiotic prescriptions were consolidated into courses of therapy and associated with the primary diagnosis from the most recent visit. Courses were stratified into those of extended duration (>28 days) and those of short duration (≤28 days). Main Outcomes and Measures: Frequency of antibiotic prescribing and associated diagnoses. Poisson regression models were used to assess for changes in the frequency of antibiotic prescribing over time. Results: Between 2008 and 2016 among 985 866 courses of oral antibiotics prescribed by 11 986 unique dermatologists, overall antibiotic prescribing among dermatologists decreased 36.6% (1.23 courses per 100 visits) from 3.36 (95% CI, 3.34-3.38) to 2.13 (95% CI, 2.12-2.14) courses per 100 visits with a dermatologist (prevalence rate ratio for annual change, 0.931; 95% CI, 0.930-0.932), with much of this decrease occurring among extended courses for acne and rosacea. Oral antibiotic use associated with surgical visits increased 69.6% (2.73 courses per 100 visits) from 3.92 (95% CI, 3.83-4.01) to 6.65 (95% CI, 6.57-6.74) courses per 100 visits associated with a surgical visit (prevalence rate ratio, 1.061; 95% CI, 1.059-1.063). Conclusions and Relevance: Continuing to develop alternatives to oral antibiotics for noninfectious conditions, such as acne, can improve antibiotic stewardship and decrease complications from antibiotic use. In addition, the rising use of postoperative antibiotics after surgical visits is concerning and may put patients at unnecessary risk of adverse events. Future studies are needed to identify the value of this practice and the risk of adverse events.

Genital contact dermatitis: a retrospective analysis.

BACKGROUND: many topical products are used in the genital region. Allergic contact dermatitis (ACD) may develop from product use or due to treatment of an underlying dermatosis. OBJECTIVES: our goal was to identify the frequency of ACD and identify top allergens in the genital region. METHODS: data were analyzed for 1,238 patients tested between January 1990 and December 2006. Fifteen allergens caused reactions at rates greater than 1%. Thirteen anatomic regions were assessed. Statistical analyses were by chi-square test and Fisher exact test. Adjusted level of significance due to multiple testing was α  =  .002. RESULTS: of individuals with genital dermatitis (n  =  37; aged 24-77 years, 48.6% female), 41% (15 of 37) had at least one positive patch-test result although only 30% (11 of 37) had a final diagnosis of relevant ACD. Mean age was 46 years for males and 41 years for females. The top five allergens were balsam of Peru (10.8%), fragrance mix I (8.1%), tolu balsam (8.1%), phenylmercuric acetate (8.1%), and neomycin (5.4%). Females were more often allergic (50%) compared to males (37%); 59.5% of patients had no positive reactions. CONCLUSION: genital dermatitis is rare; the minority tested positively for ACD. The top five allergens were present in toiletries and cosmetics used on genital skin. The top three allergens are fragrance related, underscoring the importance of using fragrance-free products on mucosal skin.

Delayed patch test reading after 5 days: the Mayo Clinic experience.

BACKGROUND: Some patients may have delayed allergic patch test reactions that are not identified with a typical 5-day reading protocol. OBJECTIVE: To identify allergens with delayed-positive reactions and to determine whether a late reading (day 7-9) can be substituted for the day-5 reading. METHODS: We retrospectively reviewed medical records of patients who underwent patch testing for suspected allergic contact dermatitis from October 1997 through December 2006 and returned for delayed readings between days 7 and 10 or beyond. (This cohort was predominantly patients with suspected allergies to metals and corticosteroids). RESULTS: A total of 36,064 individual reactions (471 allergens, 372 patients) were interpreted on day 5 and at least once during days 7 through 21. We analyzed the 170 allergens that were each tested in at least 50 patients. The 4 allergens with the highest percentage of delayed-positive reactions were gold sodium thiosulfate 0.5% (delayed-positive reactions in 22/353 patients), dodecyl gallate 0.25% (6/105), palladium chloride 2% (8/194), and neomycin sulfate 20% (10/253). We observed a low number of delayed-positive readings for p-phenylenediamine 1% (1/251) and for corticosteroids. Reactions to certain preservative and fragrance allergens dissipated after the day-5 reading. Most reactions that dissipated after day 5 were mild, whereas the reactions that became apparent after day 5 were strong. LIMITATIONS: This was a retrospective study. Most patients had suspected allergies to metals and corticosteroids. CONCLUSION: Late patch test readings (day 7 or beyond) were useful when interpreting reactions to metals and topical antibiotics, but it was not useful in the diagnosis of reactions to other allergens, including topical corticosteroids. Because reactions to certain fragrance and preservative allergens may dissipate after 5 days, patch test reactions therefore are optimally read at days 3 and 5, but an additional reading on day 7 or beyond is useful if patch tests to metals and topical antibiotics are performed.