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Word count: 3490At a Glance Commentary: Scientific Knowledge on the Subject: Ambient fine particulate matter (PM2.5) exposure in utero has been associated with the development of childhood asthma. However, little is known regarding the impact of ambient ultrafine particles (<0.1 μm) (UFPs) on childhood asthma development What this Study Adds to the Field: Our findings suggest that UFPs exposure during the second trimester of pregnancy was associated with an increased risk of developing asthma in children before age 6 independent of other air pollutants including NO2 and PM2.5. These findings highlight the need for further research on the effects of UFPs during the perinatal period on respiratory health in children. Online Data Supplement: This article has an online data supplement, which is accessible from this issue's table of content online at www.atsjournls.org 1 ABSTRACT Rationale: Little is known regarding the impact of ambient ultrafine particles (<0.1 μm) (UFPs) on childhood asthma development. Objective: To examine the association between prenatal and early postnatal life exposure to UFPs and development of childhood asthma. Methods: A total of 160,641 singleton live births occurring in the City of Toronto, Canada between April 1 st 2006and March 31 st 2012 were identified from a birth registry. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6) were estimated using random-effects Cox proportional hazards models, adjusting for personal-and neighborhood-level covariates. We investigated both single-and multi-pollutant models accounting for co-exposures to PM2.5 and NO2. Measurements and Main Results: We identified 27,062 children with incident asthma diagnosis during the follow-up. In adjusted models, second trimester exposure to UFPs (Hazard Ratio (HR) per interquartile (IQR) increase = 1.09, 95% CI: 1.06 -1.12) was associated with asthma incidence. In models additionally adjusted for PM2.5 and NO2, UFPs exposure during the second trimester of pregnancy remained positively associated with childhood asthma incidence (HR per IQR increase = 1.05, 95% CI: 1.01 -1.09). Conclusion: This is the first study to evaluate the association between perinatal exposure to UFPs and the incidence of childhood asthma. Exposure to UFPs during a critical period of lung development was linked to the onset of asthma in children, independent of PM2.5 and NO2. Abstract word count: 229

Objective To determine whether any association exists between exposure to 2009 pandemic H1N1 (pH1N1) influenza vaccination during pregnancy and negative health outcomes in early childhood. Design Retrospective cohort study. Setting Population based birth registry linked with health administrative databases in the province of Ontario, Canada. Participants All live births from November 2009 through October 2010 (n=104 249) were included, and children were followed until 5 years of age to ascertain study outcomes. Main outcome measures Rates of immune related (infectious diseases, asthma), non-immune related (neoplasms, sensory disorders), and non-specific morbidity outcomes (urgent or inpatient health services use, pediatric complex chronic conditions) were evaluated from birth to 5 years of age; under-5 childhood mortality was also assessed. Propensity score weighting was used to adjust hazard ratios, incidence rate ratios, and risk ratios for potential confounding. Results Of 104 249 live births, 31 295 (30%) were exposed to pH1N1 influenza vaccination in utero. No significant associations were found with upper or lower respiratory infections, otitis media, any infectious diseases, neoplasms, sensory disorders, urgent and inpatient health services use, pediatric complex chronic conditions, or mortality. A weak association was observed between prenatal pH1N1 vaccination and increased risk of asthma (adjusted hazard ratio 1.05, 95% confidence interval 1.02 to 1.09) and decreased rates of gastrointestinal infections (adjusted incidence rate ratio 0.94, 0.91 to 0.98). These results were unchanged in sensitivity analyses accounting for any potential differential healthcare seeking behavior or access between exposure groups. Conclusions No associations were observed between exposure to pH1N1 influenza vaccine during pregnancy and most five year pediatric health outcomes. Residual confounding may explain the small associations observed with increased asthma and reduced gastrointestinal infections. These outcomes should be assessed in future studies.

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Background There may be less primary health care engagement among people who use drugs (PWUD) than among the general population, even though the former have greater comorbidity and more frequent use of emergency department care. We investigated factors associated with primary care engagement among PWUD. Methods The Participatory Research in Ottawa: Understanding Drugs (PROUD) cohort study meaningfully engaged and trained people with lived experience to recruit and survey marginalized PWUD between March–December 2013. We linked this survey data to provincial-level administrative databases held at ICES. We categorized engagement in primary care over the 2 years prior to survey completion as: not engaged (< 3 outpatient visits to the same family physician) versus engaged in care (3+ visits to the same family physician). We used multivariable logistic regression to determine factors associated with engagement in primary care. Results Characteristics of 663 participants included a median age of 43 years, 76% men, and 67% living in the two lowest income quintile neighborhoods. Despite high comorbidity and a median of 4 (interquartile range 0–10) primary care visits in the year prior to survey completion, only 372 (56.1%) were engaged in primary care. Engagement was most strongly associated with the following factors: receiving provincial benefits, including disability payments (adjusted odds ratio [AOR] 4.14 (95% confidence interval [CI] 2.30 to 7.43)) or income assistance (AOR 3.69 (95% CI 2.00 to 6.81)), having ever taken methadone (AOR 3.82 (95% CI 2.28 to 6.41)), mental health comorbidity (AOR 3.43 (95% CI 2.19 to 5.38)), and having stable housing (AOR 2.09 (95% CI 1.29 to 3.38)). Conclusions Despite high comorbidity, engagement in primary care among PWUD was low. Our findings suggest that social care (housing, disability, and income support) and mental health care are associated with improved primary care continuity; integration of these care systems with primary care and opioid substitution therapy may lessen the significant morbidity and acute care use among PWUD.

Background: Almost 1% of Canadians are hepatitis C (HCV)-infected. The liver-specific complications of HCV are established but the extra-hepatic comorbidity, multimorbidity, and its relationship with HCV treatment, is less well known. We describe the morbidity burden for people with HCV and the relationship between multimorbidity and HCV treatment uptake and cure in the pre-and post-direct acting antiviral (DAA) era. Methods: We linked adults with HCV at The Ottawa Hospital Viral Hepatitis Program as of April 1, 2017 to provincial health administrative data and matched on age and sex to 5 Ottawa-area residents for comparison. We used validated algorithms to identify the prevalence of mental and physical health comorbidities, as well as multimorbidity (2+ comorbidities). We calculated direct age-and sex-standardized rates of comorbidity and comparisons were made by interferon-based and interferon-free, DAA HCV treatments. Results: The mean age of the study population was 54.5 years (SD 11.4), 65% were male. Among those with HCV, 4% were HIV co-infected, 26% had liver cirrhosis, 47% received DAA treatment, and 57% were cured of HCV. After accounting for age and sex differences, the HCV group had greater multimorbidity (prevalence ratio (PR) 1.38, 95% confidence interval (CI) 1.20 to 1.58) and physical-mental health multimorbidity (PR 2.71, 95% CI 2.29-3.20) compared to the general population. Specifically, prevalence ratios for people with HCV were significantly higher for diabetes, renal failure, cancer, asthma, chronic obstructive pulmonary disease, substance use disorder, mood and anxiety disorders and liver failure. HCV treatment and cure were not associated with multimorbidity, but treatment prevalence was significantly lower among middle-aged individuals with substance use disorders despite no differences in prevalence of cure among those treated. Conclusion: People with HCV have a higher prevalence of comorbidity and multimorbidity compared to the general population. While HCV treatment was not associated with multimorbidity, people with substance use disorder were less likely to be treated. Our results point to the need for integrated, comprehensive models of care delivery for people with HCV.

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