Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring : A Cohort Study.

BACKGROUND: There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD). OBJECTIVE: To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 ("swine flu") during pregnancy. DESIGN: Population-based cohort study using nationwide registers. SETTING: Seven health care regions in Sweden. PARTICIPANTS: Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed. MEASUREMENTS: Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD). RESULTS: Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, -0.09% to 0.17%) for ASD and 0.02% (CI, -0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD). LIMITATION: Data on H1N1 influenza infection are lacking. CONCLUSION: This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring. PRIMARY FUNDING SOURCE: Swedish Research Council.

A general score-independent test for order-restricted inference.

In the analysis of ordered categorical data, the categories are often assigned a set of subjectively chosen order-restricted scores. To overcome the arbitrariness involved in the assignment of the scores, several score-independent tests have been proposed. However, these methods are limited to 2 × K contingency tables, where K is the number of ordered categories. We present an efficiency robust score-independent test that is applicable to more general situations. The test is embedded into a flexible framework for conditional inference and provides a natural generalization of many familiar tests involving ordered categorical data, such as the generalized Cochran-Mantel-Haenszel test for singly or doubly ordered contingency tables, the Page test for randomized block designs and the Tarone-Ware trend test for survival data. The proposed method is illustrated by several numerical examples.

Allergy or tolerance in children sensitized to peanut: prevalence and differentiation using component-resolved diagnostics.

BACKGROUND: Not all peanut-sensitized children develop allergic reactions on exposure. OBJECTIVE: To establish by oral food challenge the proportion of children with clinical peanut allergy among those considered peanut-sensitized by using skin prick tests and/or IgE measurement, and to investigate whether component-resolved diagnostics using microarray could differentiate peanut allergy from tolerance. METHODS: Within a population-based birth cohort, we ascertained peanut sensitization by skin tests and IgE measurement at age 8 years. Among sensitized children, we determined peanut allergy versus tolerance by oral food challenges. We used open challenge among children consuming peanuts (n = 45); others underwent double-blind placebo-controlled challenge (n = 34). We compared sensitization profiles between children with peanut allergy and peanut-tolerant children by using a microarray with 12 pure components (major peanut and potentially cross-reactive components, including grass allergens). RESULTS: Of 933 children, 110 (11.8%) were peanut-sensitized. Nineteen were not challenged (17 no consent). Twelve with a convincing history of reactions on exposure, IgE > or =15 kUa/L and/or skin test > or =8mm were considered allergic without challenge. Of the remaining 79 children who underwent challenge, 7 had > or =2 objective signs and were designated as having peanut allergy. We estimated the prevalence of clinical peanut allergy among sensitized subjects as 22.4% (95% CI, 14.8% to 32.3%). By using component-resolved diagnostics, we detected marked differences in the pattern of component recognition between children with peanut allergy (n = 29; group enriched with 12 children with allergy) and peanut-tolerant children (n = 52). The peanut component Ara h 2 was the most important predictor of clinical allergy. CONCLUSION: The majority of children considered peanut-sensitized on the basis of standard tests do not have peanut allergy. Component-resolved diagnostics may facilitate the diagnosis of peanut allergy.

Development and Validation of a Novel Risk Score for In-Hospital Major Bleeding in Acute Myocardial Infarction:-The SWEDEHEART Score.

Background Bleeding risk stratification in acute coronary syndrome is of highest clinical interest but current risk scores have limitations. We sought to develop and validate a new in-hospital bleeding risk score for patients with acute myocardial infarction. Methods and Results From the nationwide SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register, 97,597 patients with acute myocardial infarction enrolled from 2009 until 2014 were selected. A full model with 23 predictor variables and 8 interaction terms was fitted using logistic regression. The full model was approximated by a model with 5 predictors and 1 interaction term. Calibration, discrimination, and clinical utility was evaluated and compared with the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Ad verse Outcomes With Early Implementation of the ACC /AHA Guidelines) scores. Internal and temporal validity was assessed. In-hospital major bleeding, defined as fatal, intracranial, or requiring surgery or blood transfusion, occurred in 1356 patients (1.4%). The 5 predictors in the approximate model that constituted the SWEDEHEART score were hemoglobin, age, sex, creatinine, and C-reactive protein. The ACTION and CRUSADE scores were poorly calibrated in the derivation cohort and therefore were recalibrated. The SWEDEHEART score showed higher discriminative ability than both recalibrated scores, overall ( C-index 0.80 versus 0.73/0.72) and in all predefined subgroups. Decision curve analysis demonstrated consistently positive and higher net benefit for the SWEDEHEART score compared with both recalibrated scores across all clinically relevant decision thresholds. The original ACTION and CRUSADE scores showed negative net benefit. Conclusions The 5-item SWEDEHEART score discriminates in-hospital major bleeding in patients with acute myocardial infarction and has superior model performance compared with the recalibrated ACTION and CRUSADE scores.

Physical activity, sleep and risk of respiratory infections: A Swedish cohort study.

OBJECTIVES: Previous studies found higher levels of physical activity to be protective against infections and that short and long sleep negatively affects the immune response. However, these relationships remain debatable. We aimed to investigate if physical activity and sleep habits affect incidence of upper respiratory tract infections (URTI) in a prospective cohort study. METHODS: A total of 2,038 adults aged 25-64 years served as a random sample of the gainfully employed population of an industrial town in Sweden. Physical activity and sleep habits were estimated through self-reported questionnaires. Physical activity was expressed as metabolic energy turnover hours per day. Sleep was assessed as number of hours slept per night and its perceived quality. URTI outcome was prospectively self-reported during a 9-month follow-up period. Associations of physical activity and sleep with URTI were estimated using hurdle regression models adjusted for potential confounders. RESULTS: During 1,583 person-years 1,597 URTI occurred, resulting in an incidence of 1.01 infections/person-year (95% CI 0.96-1.06). The fitted regression models did not provide support for an association with physical activity or sleep habits. Factors positively associated with experiencing URTI were having children ≤ 6 years, female gender, higher education and treatment for allergy, asthma or lung cancer. Having children ≤ 6 years and female gender were related to a higher number of URTI among those experiencing URTI. CONCLUSIONS: We did not find any association between physical activity, sleep duration or sleep quality and the occurrence of upper respiratory tract infections in adult Swedish population.