Search

Background: Atopic dermatitis is a prevalent condition in children and can be effectively managed with medications such as topical calcineurin inhibitors (pimecrolimus or tacrolimus). A key unresolved safety concern is whether use of topical calcineurin inhibitors is associated with cancer. We systematically reviewed the risk of cancer in patients with atopic dermatitis exposed to topical calcineurin inhibitors., Methods: As part of the 2022 American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters atopic dermatitis guidelines, we searched MEDLINE, Embase, the Latin American and Caribbean Health Sciences Literature database, the Índice Bibliográfico Espanhol de Ciências da Saúde database, the Global Resource of Eczema Trials database, WHO's International Clinical Trials Registry Platform, the US Food and Drug Administration database, the European Medicines Agency database, company registers, and relevant citations from inception to June 6, 2022. We included randomised controlled trials and comparative and non-comparative non-randomised studies in any language addressing cancer risk in patients with atopic dermatitis using topical calcineurin inhibitors. We excluded split-body studies and studies with less than 3 weeks of follow-up. Paired reviewers independently screened records, extracted data, and assessed risk of bias in duplicate. We used Bayesian models to estimate the probability for cancer due to topical calcineurin inhibitor exposure and the GRADE approach to determine the certainty of the evidence. Patients, advocacy groups, and care providers set a priori thresholds of important effects. This study is registered with Open Science Framework, https://osf.io/v4bfc., Findings: We identified and analysed 110 unique studies (52 randomised controlled trials and 69 non-randomised studies [11 were non-randomised study extensions of randomised controlled trials]) including 3·4 million patients followed up for a mean of 11 months (range 0·7-120). The absolute risk of any cancer with topical calcineurin inhibitor exposure was not different from controls (absolute risk 4·70 per 1000 with topical calcineurin inhibitors vs 4·56 per 1000 without; odds ratio 1·03 [95% credible interval 0·94-1·11]; moderate certainty). For all age groups and using data from observational studies and randomised controlled trials, the use of pimecrolimus (OR 1·05 [95% credible interval 0·94-1·15]) or tacrolimus (0·99 [0·89-1·09]) is likely to have had little to no association with cancer compared with no topical calcineurin inhibitor exposure. For pimecrolimus versus tacrolimus, the finding was similar (0·95 [95% credible interval 0·83-1·07]). Findings were similar in infants, children, and adults, and robust to trial sequential, subgroup, and sensitivity analyses., Interpretation: Among individuals with atopic dermatitis, moderate-certainty evidence shows that topical calcineurin inhibitors do not increase the risk of cancer. These findings support the safe use of topical calcineurin inhibitors in the optimal treatment of patients with atopic dermatitis., Funding: American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma and Immunology via the Joint Task Force on Practice Parameters., Competing Interests: Declarations of interests LS reports, outside of the submitted work, consulting fees from Leo Pharma and Sanofi; payments to her institution for study support from Pfizer and Regeneron; participation on the data safety monitoring board for the US National Institute of Allergy and Infectious Diseases, Syneos for Alladapt Immunotherapeutics; participation on the scientific advisory board for Food Allergy Research and Education, Biothera Theapeutics, and Ukko; and stock or stock options in Ukko. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Study Objectives: To identify patient characteristics associated with nocturnal emergency department (ED) visits for asthma., Methods: Asthmatic patients 18 to 55 years of age who visited Ontario EDs between April 1, 2003 and March 31, 2004, were identified through an administrative clinical database. Patients' time of ED presentation was analyzed for circadian pattern using histogram and polynomial regression. Risk of nocturnal visit (presentation at the ED between midnight and 8 AM) was modeled through generalized estimating equations with patient age, gender, and asthma severity level as covariates. The effect of nocturnal visit on return rate to the ED within 14 days after the initial visit was determined through Cox regression., Results: During study period there were 31,490 ED visits for asthma made by 23,253 patients. Their time of ED visits displayed a distinct circadian pattern with peak between 7 and 8 PM, and trough at 5 AM. Approximately 22% of visits (6,868) occurred at night. Men had higher odds of presenting at night than women (OR 1.61; 1.49-1.73). Patients with mild asthma were significantly less likely to visit the ED at night than patients with moderate or severe asthma. Nocturnal presentation was not associated with higher odds of subsequent returns to the ED (HR 1.00; 0.89-1.14)., Conclusion: Higher odds of nocturnal visits in men suggest the existence of gender-differences in health-seeking behavior in asthmatics. Although nocturnal visits are associated with more severe asthma, they do not lead to higher return rates.

Background: To investigate if fetal gender (1) affects the risk of having an emergency department (ED) visit for asthma; and (2) is associated with adverse pregnancy outcomes among women who had at least one visit to the ED for asthma during pregnancy., Methods: We linked two provincial administrative databases containing records on in-patient deliveries and ED visits. The study sample included women who delivered a live singleton baby between April 2003 and March 2004. Pregnant women who made at least one ED visit for asthma were counted as cases and the rest of the women as control subjects. We performed a multivariable analysis using logistic regression to model the risk of having an ED visit for asthma, with fetal gender being one of the predictors. In addition, a series of multivariable logistic regressions were also constructed separately for cases and controls for the following adverse delivery outcomes: low birth weight baby, preterm delivery, and delivery via Caesarian section., Results: Among 109,173 live singleton deliveries, 530 women had visited ED due to asthma during pregnancy. While having an ED visit for asthma was positively associated with teenage pregnancy, low income, and presence of pregnancy-induced hypertension, it was not associated with fetal gender (OR 1.01, 95% CI 0.85-1.19). Fetal gender was not a significant predictor of adverse pregnancy outcomes among women who had an asthma ED visit during pregnancy., Conclusion: Fetal gender does not affect the risk of having an ED visit for asthma during pregnancy, and it is not associated with adverse pregnancy outcomes among women who had an asthma-related ED during pregnancy.

Background: Women represent the majority of adult patients hospitalized for asthma. Analyzing the course of emergency department (ED) visits before hospital admission can help understanding of the mechanisms behind the excess of hospitalizations in women., Objective: To investigate sex differences in hospital admission rates in adult patients with asthma visiting EDs in Ontario., Methods: Asthmatic patients 18 to 55 years old who visited Ontario EDs between April 1, 2003, and March 31, 2004, were identified using the Canadian Institute for Health Information's National Ambulatory Care Reporting System. The generalized estimating equations for binary outcome were used to model rates of hospital admission with sex, age, and triage (severity) score as covariates. Analysis was further stratified by the ED volume., Results: Women represented 62.2% of all ED visits. They were on average older than men, but both groups had similar distributions of triage scores. Female patients accounted for more hospital admissions than male patients (7.4% vs 4.5%). After adjusting for age and triage score, women were more likely to be admitted than men (odds ratio, 1.64; 95% confidence interval, 1.41-1.90). The interaction found between sex and triage level indicates that hospitalized women may have less severe asthma than hospitalized men. Analysis by ED volume did not significantly alter the results., Conclusion: The higher admission rates in women may be related to sex differences in the subjective perception of dyspnea, management of asthma by ED physician, or inadequate ambulatory care strategies in women and thus merit further investigation.

Objective: To examine the pattern and strength of seasonal fluctuations in emergency department (ED) visits due to asthma, by month and day of the week, by the patient's age, gender, and severity of asthma attack., Methods: Time series analysis of ED visits was conducted among patients with asthma aged from 18 to 55 years who visited Ontario EDs between April 1, 2001 and March 31, 2004. Autoregressive regression models with months and days of the week as predictors were fitted for (1) all patients; (2) females and males separately; (3) each combination of gender and age group, and (4) each combination of gender and level of severity. The strength of seasonality in each group of patients was estimated from the R2-statistic derived from autoregression models., Results: For all patient groups, the highest number of ED visits occurred in October and December, and on Sundays and Mondays. Month of January and Fridays were associated with a decreased number of visits. The strength of seasonality was similar in men and women (R2 = 0.52), was the highest in young patients and decreased with age, in men more rapidly than in women. Severe cases of asthma attacks exhibited weaker seasonality (R2 = 0.30) compared to mild (R2 = 0.45) or moderate (R2 = 0.53) cases., Conclusion: The strength of seasonal patterns of asthma ED visits is influenced by age and the severity of attack, and to a lesser extent, gender. Understanding the significance of seasonal precipitants of asthma in different patients subgroups could lead to better management strategies.