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The "Adacel (Tdap5) Pregnancy Registry" was used to identify 1182 women who received the tetanus, diphtheria, acellular pertussis [5 components] (Tdap5) vaccine during pregnancy from 2005 to 2016. To evaluate the safety and use of prenatal Tdap5, we calculated the rate of maternal, obstetrical, pregnancy and neonatal outcomes following Tdap5 pregnancy exposure and assessed vaccine uptake by year and trimester of exposure. The most commonly reported maternal adverse events included injection site reactions (2.6%; 95% Confidence Interval 1.8%, 3.7%), nervous system events (1.3%; 0.8%, 2.1%) and musculoskeletal events (1.1%; 0.6%, 1.9%). The most commonly reported complications of pregnancy were hypertension/preeclampsia (5.5%; 3.3%, 8.9%) and gestational diabetes (2.5%; 1.1%, 5.3%), while those for labor and delivery were premature labor (2.9%; 1.4%, 5.7%) and premature membrane rupture (1.5%; 0.4%, 3.8%). These rates were similar to, or lower than those reported for the general population of pregnant women. Among pregnancies with known birth outcomes (N = 275), 90.4% (86.2%, 93.4%) resulted in a live birth, 5.9% (3.6%, 9.5%) in spontaneous abortion, 3.0% (1.4%, 5.8%) in stillbirth, and 0.7% (0.0%, 2.8%) in ectopic pregnancies. Most newborns had normal APGAR scores and birth weights (98.1% and 93.0%, respectively), and only two reported a congenital anomaly (0.7%; 0.0%, 2.8%). An influx of reports in 2012 with third trimester Tdap5 exposure coincided with the 2012 updated Advisory Committee on Immunization Practices recommendations. This analysis did not identify any safety concerns across the continuum of maternal, obstetrical, pregnancy, and neonatal outcomes in women who received Tdap5 vaccination during pregnancy.

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OBJECTIVE: The Ontario Government funded the development and implementation of a standardized adult emergency department (ED) asthma care pathway (EDACP). We aimed to describe baseline patterns of ED use by adults for asthma in Ontario, Canada, and determine site characteristics associated with the EDACP implementation workshop attendance and subsequent pathway implementation. METHODS: All Ontario EDs were offered EDACP implementation workshops by the Lung Assocation-Ontario between 2008 and 2011, and were surveyed regarding site implementation status as of October, 2013. Survey data were linked by site to Ontario's administrative health databases. Logistic regression models investigated the association between site and patient characteristics and: a) workshop attendance; b) pathway implementation. RESULTS: In the 2 years prior to EDACP implementation, there were 41 143 asthma visits to 167 sites by adults (62.3% female). Asthma-related return visits within 72 h varied by hospital type (teaching 2.1%, community 2.8%, small 4.0%; p < 0.05). Implementation workshops were attended by staff from 122 sites (72.6%). Implementation status was known for 108 sites and varied by hospital type (p < 0.001), but not workshop attendance (p = 0.11). By 2013, 47% of all hospitals were using or planning to use the EDACP. Uptake was more likely in community hospitals. CONCLUSIONS: Ontario adult asthma ED visitors are more often women. Asthma-related return visits are uncommon, but significantly higher in small community hospitals. This provincial QI initiative reached almost 75% of Ontario EDs, and achieved almost 50% implementation rate within 2 years. Factors other than workshop attendance, such as hospital size, were associated with EDACP implementation.

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BACKGROUND: Impaired symptom perception is often listed as a risk factor for life-threatening asthma, but there is limited evidence to support this. OBJECTIVE: We aimed to determine whether impaired perception of bronchoconstriction (BC) and/or dynamic hyperinflation (DH) are risk factors for severe asthma exacerbations. METHODS: In this prospective cohort study, individuals with asthma underwent high-dose methacholine challenge testing. Changes in forced expiratory volume in 1 second (FEV1) (% predicted) and inspiratory capacity (IC) (% predicted) were measured to assess the degree of BC and DH, respectively, during high-dose methacholine bronchoprovocation. Participants rated dyspnea intensity during testing and were categorized as poor, normal, and over perceivers of BC and DH based on perception scores at standardized changes (20%, 30%, and 40%) in FEV1 (% predicted) and IC (% predicted). We compared the rates of severe asthma exacerbations (defined as one of emergency department [ED] visit or hospitalization) between groups, using Ontario's administrative health databases. RESULTS: Poor perceivers had higher rates of ED visits and hospitalizations as compared with normal perceivers at 4 of 6 threshold decreases in FEV1 and IC studied. Poor perceivers of severe DH had a 6-fold increase in asthma exacerbations (odds ratio, 5.7; 95% confidence interval, 1.31-25.03). CONCLUSIONS: Health services utilization is increased in individuals with asthma who have poor perception of BC and DH. Poor perceivers of severe DH appear to be at the highest risk of exacerbations.

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BACKGROUND: Melanoma is a serious, potentially lethal disease. It is one of very few common cancers whose incidence is rising in North America. OBJECTIVES: The objective of this study was to examine trends in melanoma incidence in Ontario, Canada's most populous province, over the past 20 years. METHODS: Using data from the Ontario Cancer Registry (OCR), this retrospective cohort examined all incident cases of melanoma in Ontario from 1990 to 2012. Generalized linear modeling was used to evaluate changes in melanoma incidence over time, adjusting for age and sex using direct standardization with the 1991 Canadian census population. Tests for trend for changes in the distribution of cases by age, sex, socioeconomic status, and rurality status were also calculated. RESULTS: Our results show a statistically significant increasing incidence of melanoma in Ontario from 9.3 cases per 100 000 in 1990 to 18.0 cases per 100 000 in 2012 ( P for trend <.001, adjusted for age and sex). Incidence rates show stabilization from 2010 to 2012. CONCLUSION: Our study reveals a marked increase in melanoma incidence in Ontario, more than doubling over the past 20 years but with a stabilization more recently. Adequate availability of dermatology services may be important to ensure satisfactory care for the increased caseload and to ensure that cases may detected at an early stage with a good prognosis.

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BACKGROUND: Despite demonstrated effectiveness in real-world settings, concerns persist regarding the safety of the quadrivalent human papillomavirus (HPV4) vaccine. We sought to assess the risk of autoimmune disorders following HPV4 vaccination among grade 8 girls eligible for Ontario's school-based HPV vaccination program. METHODS: We undertook a population-based retrospective cohort study using Ontario's administrative health and vaccination databases from 2007 to 2013. The self-controlled case series method was used to compare the rate of a composite end point of autoimmune disorders diagnosed during days 7-60 post-vaccination ("exposed" follow-up) to that at any other time ("unexposed"). The analysis was repeated to assess the effect of a history of immune-mediated diseases and time since vaccination. We also conducted an exploratory analysis of individual autoimmune disorders. Rate ratios and 95% confidence intervals (CIs) were estimated using conditional Poisson regression, adjusted for age, seasonality, concomitant vaccinations and infections. RESULTS: The study cohort consisted of 290 939 girls aged 12-17 years who were eligible for vaccination between 2007 and 2013. There was no significant risk for developing an autoimmune disorder following HPV4 vaccination (n = 681; rate ratio 1.12, 95% CI 0.85-1.47), and the association was unchanged by a history of immune-mediated disorders and time since vaccination. Exploratory analyses of individual autoimmune disorders found no significant risks, including for Bell palsy (n = 65; rate ratio 1.73, 95% CI 0.77-3.89), optic neuritis (n = 67; rate ratio 1.57, 95% CI 0.74-3.33) and Graves disease (n = 47; rate ratio 1.55, 95% CI 0.92-2.63). INTERPRETATION: We did not observe an increased risk of autoimmune disorders following HPV4 vaccination among teenaged girls. These findings should reassure parents and health care providers.

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The benefit of oral bisphosphonates in reducing fracture risk in glucocorticoid-induced osteoporosis is controversial. We aimed to estimate the effectiveness of oral bisphosphonates in reducing fracture risk in a cohort of new chronic oral glucocorticoid users. We created three matched cohorts using health care administrative data from Ontario, Canada. We included residents aged 66 years and older initiating chronic oral glucocorticoids (≥450 mg prednisone equivalent and ≥2 glucocorticoid prescriptions within a 6-month window) between January 1998 and September 2014. Exposed patients were those who initiated an oral bisphosphonate (alendronate, etidronate, or risedronate) within the first 6 months of starting chronic oral glucocorticoid therapy. Exposed cohorts (3945 alendronate, 5825 risedronate, and 8464 etidronate) were each matched 1:1 to unexposed patients on glucocorticoid exposure, fracture risk factors, and propensity score. We examined incident hip (primary outcome), vertebral, forearm, and humerus fractures using Cox proportional hazard models. Alendronate (hazard ratio [HR] = 0.46, 95% confidence interval [CI] 0.25-0.80) and risedronate (HR = 0.58, 95% CI 0.36-0.90) were associated with reduced hip fracture risk. Alendronate (HR = 0.52, 95% CI 0.39-0.68), etidronate (HR = 0.59, 95% CI 0.48-0.73) and risedronate (HR = 0.47 95% CI 0.36-0.60) were associated with reduced vertebral fracture risk. No risk reduction in forearm or humerus fractures was apparent for any bisphosphonate. Among older chronic glucocorticoid initiators, all oral bisphosphonates reduced vertebral fracture risk, yet only alendronate and risedronate reduced hip fracture risk. Results were similar between men and women. We provided compelling evidence that early initiation of oral bisphosphonates during chronic oral glucocorticoid therapy is beneficial to prevent osteoporotic fractures. © 2017 American Society for Bone and Mineral Research.

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Background: The regression discontinuity design (RDD) is a quasi-experimental approach used to avoid confounding bias in the assessment of new policies and interventions. It is applied specifically in situations where individuals are assigned to a policy/intervention based on whether they are above or below a pre-specified cut-off on a continuously measured variable, such as birth date, income or weight. The strength of the design is that, provided individuals do not manipulate the value of this variable, assignment to the policy/intervention is considered as good as random for individuals close to the cut-off. Despite its popularity in fields like economics, the RDD remains relatively unknown in epidemiology where its application could be tremendously useful. Methods: In this paper, we provide a practical introduction to the RDD for health researchers, describe four empirically testable assumptions of the design and offer strategies that can be used to assess whether these assumptions are met in a given study. For illustrative purposes, we implement these strategies to assess whether the RDD is appropriate for a study of the impact of human papillomavirus vaccination on cervical dysplasia. Results: We found that, whereas the assumptions of the RDD were generally satisfied in our study context, birth timing had the potential to confound our effect estimate in an unexpected way and therefore needed to be taken into account in the analysis. Conclusions: Our findings underscore the importance of assessing the validity of the assumptions of this design, testing them when possible and making adjustments as necessary to support valid causal inference.

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BACKGROUND: Isotretinoin, a teratogen, is widely used to treat cystic acne. Although the risks of pregnancy during isotretinoin therapy are well recognized, there are doubts about the level of adherence with the pregnancy prevention program in Canada. Our objective was to evaluate the effectiveness of the Canadian pregnancy prevention program in 4 provinces: British Columbia, Saskatchewan, Manitoba and Ontario. METHODS: Using administrative data, we identified 4 historical cohorts of female users of isotretinoin (aged 12-48 yr) for the period 1996 to 2011. We defined pregnancy using International Statistical Classification of Diseases and billing codes. One definition included only cases with documented pregnancy outcomes (high-specificity definition); the other definition also included individuals recorded as receiving prenatal care (high-sensitivity definition). We studied new courses of isotretinoin and detected pregnancies in 2 time windows: during isotretinoin treatment only and up to 42 weeks after treatment. Live births were followed for 1 year to identify congenital malformations. RESULTS: A total of 59 271 female patients received 102 308 courses of isotretinoin. Between 24.3% and 32.9% of participants received prescriptions for oral contraceptives while they were taking isotretinoin, compared with 28.3% to 35.9% in the 12 months before isotretinoin was started. According to the high-specificity definition of pregnancy, there were 186 pregnancies during isotretinoin treatment (3.1/1000 isotretinoin users), compared with 367 (6.2/1000 users) according to the high-sensitivity definition. By 42 weeks after treatment, there were 1473 pregnancies (24.9/1000 users), according to the high-specificity definition. Of these, 1331 (90.4%) terminated spontaneously or were terminated by medical intervention. Among the 118 live births were 11 (9.3%) cases of congenital malformation. Pregnancy rates during isotretinoin treatment remained constant between 1996 and 2011. INTERPRETATION: Adherence to the isotretinoin pregnancy prevention program in Canada was poor during the 15-year period of this study.

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UNLABELLED: We identified significantly slower uptake, and consistently lower proportions of new oral bisphosphonate formulations dispensed in rural regions compared to urban regions of Ontario. Further research examining regional differences in outcomes may provide insight as to whether urban-rural differences in prescribing translate into health disparities between regions. PURPOSE: The aim of this study was to examine urban-rural differences in the uptake of new oral bisphosphonate formulations available on the Ontario drug formulary: alendronate + vitamin D3 (January 2007), monthly risedronate (June 2009), and risedronate delayed-release (February 2012). METHODS: We plotted the monthly proportion of new formulation claims of all claims with the same drug molecule, from their formulary listing date until March 2014. Results were stratified by major urban, nonmajor urban, and rural regions as defined by the Rurality Index of Ontario. We compared the rate of uptake over the first year of formulary availability using linear regression, and compared proportions dispensed between regions using chi-squared tests. RESULTS: We identified a regional gradient in uptake for alendronate + vitamin D3 and monthly risedronate; major urban regions had the fastest uptake, followed by nonmajor urban regions, and rural regions had the slowest uptake. Rural regions also had the slowest uptake of risedronate delayed-release; however, uptake in major urban and nonmajor urban regions were similar. Rural regions dispensed the lowest proportions for all new formulations 1 year after formulary availability: alendronate + vitamin D3 (32% major urban, 23% nonmajor urban, 12% rural), monthly risedronate (26% major urban, 21% nonmajor urban, 16% rural), and risedronate delayed-release (21% major urban, 22 % nonmajor urban, 13% rural). This pattern persisted throughout our study. CONCLUSION: We identified significantly slower uptake and lower proportions of new formulations dispensed in rural regions compared to urban regions. Further research examining regional differences in outcomes may demonstrate whether urban-rural differences in prescribing translate into health disparities between regions.

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AIM: To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. METHODS: We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. RESULTS: The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. CONCLUSION: Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

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BACKGROUND: Nurse prescribing is a practice that has evolved and will continue to evolve in response to emerging trends, particularly in primary care. The goal of this study was to describe the trends and patterns in medication prescription to adults 65 years of age or older in Ontario by nurse practitioners over a 10-year period. METHODS: We conducted a population-based descriptive retrospective cohort study. All nurse practitioners registered in the Corporate Provider Database between Jan. 1, 2000, and Dec. 31, 2010, were identified. We identified actively prescribing nurse practitioners through linkage of dispensed medications to people aged 65 years or older from the Ontario Drug Benefit database. For comparison, all prescription medications dispensed by family physicians to a similar group were identified. Geographic location was determined based on site of nurse practitioner practice. RESULTS: The number and proportion of actively prescribing nurse practitioners prescribing to older adults increased during the study period, from 44/340 (12.9%) to 888/1423 (62.4%). The number and proportion of medications dispensed for chronic conditions by nurse practitioners increased: in 2010, 9 of the 10 top medications dispensed were for chronic conditions. There was substantial variation in the proportion of nurse practitioners dispensing medication to older adults across provincial Local Health Integration Networks. INTERPRETATION: Prescribing by nurse practitioners to older adults, particularly of medications related to chronic conditions, increased between 2000 and 2010. The integration of nurse practitioners into primary care has not been consistent across the province and has not occurred in relation to population changes and perhaps population needs.

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Thiazide diuretics (TDs) are a cost-effective first-line therapy for uncomplicated hypertension; however, they are less prescribed than other options. The authors aimed to assess the noninferiority of TDs relative to different classes of antihypertensive medications in relation to central blood pressure. Cross-sectional data from the Quebec CARTaGENE project was used. Nondiabetic hypertensive participants on monotherapy for hypertension were studied. Separate adjusted models were constructed to establish noninferiority of TDs to non-TD antihypertensive medications for central blood pressure measurements. Models included a set of potential confounders. Of the 1194 hypertensive participants, 7.4% were taking TDs. We found that TDs were comparable with non-TD antihypertensive medications for central systolic blood pressure (adjusted regression coefficient, 0.45; 95% confidence interval, -1.61 to 2.50). No differences in other central measurements were noted. The results provide additional support that TDs are at least as effective as other first-line medications for treating uncomplicated hypertension.

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OBJECTIVES: To describe the use and reporting of interrupted time series methods in drug utilization research. STUDY DESIGN AND SETTING: We completed a systematic search of MEDLINE, Web of Science, and reference lists to identify English language articles through to December 2013 that used interrupted time series methods in drug utilization research. We tabulated the number of studies by publication year and summarized methodological detail. RESULTS: We identified 220 eligible empirical applications since 1984. Only 17 (8%) were published before 2000, and 90 (41%) were published since 2010. Segmented regression was the most commonly applied interrupted time series method (67%). Most studies assessed drug policy changes (51%, n = 112); 22% (n = 48) examined the impact of new evidence, 18% (n = 39) examined safety advisories, and 16% (n = 35) examined quality improvement interventions. Autocorrelation was considered in 66% of studies, 31% reported adjusting for seasonality, and 15% accounted for nonstationarity. CONCLUSION: Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration.

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BACKGROUND: Despite widespread promotion of quadrivalent human papillomavirus (qHPV) vaccination for young girls, there is limited information on the vaccine's real-world effectiveness and none on the effectiveness of qHPV vaccination programs. We assessed the impact of the qHPV vaccine and Ontario's grade 8 qHPV vaccination program on cervical dysplasia and anogenital warts (AGW). METHODS: By using administrative health databases of Ontario, Canada, we identified a population-based retrospective cohort of girls in grade 8 before (2005/2006-2006/2007) and after (2007/2008-2008/2009) program implementation. Vaccine exposure was ascertained in grades 8 to 9 and outcomes in grades 10 to 12. A quasi-experimental approach known as regression discontinuity was used to estimate absolute risk differences (RDs), relative risks (RRs), and 95% confidence intervals (CIs) attributable to vaccination and program eligibility (intention-to-treat analysis). RESULTS: The cohort comprised 131,781 ineligible and 128,712 eligible girls (n = 260,493). We identified 2436 cases of dysplasia and 400 cases of AGW. Vaccination significantly reduced the incidence of dysplasia by 5.70 per 1000 girls (95% CI -9.91 to -1.50), corresponding to a relative reduction of 44% (RR 0.56; 95% CI 0.36 to 0.87). Program eligibility also had a significant protective effect on dysplasia: RD -2.32/1000 (95% CI -4.02 to -0.61); RR 0.79 (95% CI 0.66 to 0.94). Results suggested decreases in AGW attributable to vaccination (RD -0.83/1000, 95% CI -2.54 to 0.88; RR 0.57, 95% CI 0.20 to 1.58) and program eligibility (RD -0.34/1000, 95% CI -1.03 to 0.36; RR 0.81, 95% CI 0.52 to 1.25). CONCLUSIONS: This study provides strong evidence of the early benefits of qHPV vaccination among girls aged 14 to 17 years, offering additional justification for not delaying vaccination.

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BACKGROUND: Suboptimal human papillomavirus (HPV) vaccine coverage in some jurisdictions is partly attributed to fears that vaccination may increase risky sexual behaviour. We assessed the effect of HPV vaccination on clinical indicators of sexual behaviour among adolescent girls in Ontario. METHODS: Using Ontario's administrative health databases, we identified a population-based cohort of girls in grade 8 in the 2 years before (2005/06 and 2006/07) and after (2007/08 and 2008/09) implementation of Ontario's grade 8 HPV vaccination program. For each girl, we then obtained data on vaccine receipt in grades 8 and 9 and data on indicators of sexual behaviour (pregnancy and non-HPV-related sexually transmitted infections) in grades 10-12. Using a quasi-experimental method known as regression discontinuity, we estimated, for each outcome, the risk difference (RD) and relative risk (RR) attributable to vaccination and to program eligibility. RESULTS: The cohort comprised 260 493 girls, of whom 131 781 were ineligible for the program and 128 712 were eligible. We identified 15 441 (5.9%) cases of pregnancy and sexually transmitted infection and found no evidence that vaccination increased the risk of this composite outcome: RD per 1000 girls -0.61 (95% confidence interval [CI] -10.71 to 9.49) and RR 0.96 (95% CI 0.81 to 1.14). Similarly, we found no discernible effect of program eligibility: RD per 1000 girls -0.25 (95% CI -4.35 to 3.85) and RR 0.99 (95% CI 0.93 to 1.06). The findings were similar when outcomes were assessed separately. INTERPRETATION: We present strong evidence that HPV vaccination does not have any significant effect on clinical indicators of sexual behaviour among adolescent girls. These results suggest that concerns over increased promiscuity following HPV vaccination are unwarranted and should not deter from vaccinating at a young age.

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BACKGROUND: Clinical practice guidelines recommend that all patients starting chronic oral glucocorticoid (GC) therapy receive bone mineral density (BMD) testing and osteoporosis pharmacotherapy. OBJECTIVE: We completed a systematic review of observational studies to examine the proportion of patients on chronic oral GC therapy who receive osteoporosis management. METHODS: Two independent reviewers completed a systematic search of Ovid MEDLINE® and EMBASE® to identify all English language articles that examined the prevalence of osteoporosis management among chronic oral GC users. Clinical trials, abstracts, reviews, commentaries, and letters to the editor were excluded. Study methods and results (use of BMD testing and osteoporosis pharmacotherapy) were abstracted and summarized by year and region. RESULTS: We identified 29 eligible studies published between 1999 and October 2013: 17 were conducted in North America, 5 in Europe, and 7 in other regions. Heterogeneity between patient populations and methods used to define chronic GC use precluded the direct comparison of results between regions, or over time. Over 80% of studies identified that < 40% of chronic oral GC users received BMD testing or osteoporosis pharmacotherapy. When results of these studies were plotted by year, there was little evidence of improvement in osteoporosis management over time. CONCLUSIONS: Despite consistent recommendations to target osteoporosis prevention at the onset of chronic oral GC therapy, osteoporosis is undermanaged among chronic oral GC users. Targeted interventions are needed to help reduce the burden of fracture-related morbidity associated with GC-induced osteoporosis.

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BACKGROUND: Proper administration of the human papillomavirus (HPV) vaccine (three doses at 0, 2, and 6 months) will likely influence the vaccine's effectiveness and the impact of vaccination programs on health outcomes. Therefore, we assessed HPV vaccine series completion and on-time dosing in Canada's largest publicly funded, school-based HPV vaccination program. METHODS: Using administrative health and immunization databases, we identified a population-based cohort of girls eligible for Ontario's Grade 8 HPV vaccination program in the 2007/08-2009/10 program years who received at least one dose of the vaccine. We determined the number of doses received and calculated the percentage of girls that completed the three-dose series in Grade 8 and Grades 8-9. To assess on-time dosing, the number of days between doses 1-2, 2-3, and 1-3 was calculated and categorized (e.g., too short, on schedule, too long) based on the manufacturer's recommendations. Analyses were also stratified by program year. RESULTS: We identified a cohort of 55,798 girls who initiated the vaccination series. Series completion was high in the Grade 8 window (81.8%) and increased by approximately 6% in Grade 9. Series completion was similar across the three program years. 70.8%, 98.5%, and 86.1% of girls were classified as 'on schedule' for dosing intervals 1-2, 2-3, and 1-3, respectively; 70.0% of girls received all three doses in perfect accordance with dosing recommendations. Stratification revealed that on-time dosing was highest in the first two years of the program (85.6% and 80.6%), but dropped to 42.1% in the 2009/10 year when H1N1 vaccination programs were prioritized. CONCLUSIONS: Our study demonstrates that delivery of the HPV vaccine through a free, school-based program is an effective method of ensuring high completion and on-time dosing, but may not be sufficient to guarantee high coverage.

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BACKGROUND: Studies on the determinants of human papillomavirus (HPV) vaccine use have generally focused on individual-level characteristics, despite the potentially important influence of regional-level characteristics. Therefore, we undertook a population-based, retrospective cohort study to identify individual- and regional-level determinants of HPV vaccine refusal (non-receipt) in Ontario's (Canada) Grade 8 HPV Immunization Program. METHODS: Ontario's administrative health and immunization databases were used to identify girls eligible for free HPV vaccination in 2007-2011 and to ascertain individual-level characteristics of cohort members (socio-demographics, vaccination history, health care utilization, medical history). The social and material characteristics of the girl's region (health unit) were derived from the 2006 Canadian Census. Generalized estimating equations (binomial distribution, logit link) were used to estimate the population-average effects of individual- and regional-level characteristics on HPV vaccine refusal. RESULTS: Our cohort consisted of 144,047 girls, 49.3% of whom refused HPV vaccination. Factors associated with refusal included a previous diagnosis of Down's syndrome (OR = 1.37, 95% CI 1.16-1.63) or autism (OR = 1.60, 95% CI 1.34-1.90), few physician visits (OR = 1.45, 95% CI 1.35-1.55), and previous refusal of mandatory (OR = 2.23, 95% CI 2.07-2.40) and optional (OR = 3.96, 95% CI 3.87-4.05) vaccines. Refusal was highest among the lowest and highest income levels. Finally, a previous diagnosis of obesity and living in an area of high deprivation were associated with lower refusal (OR = 0.87, 95% CI 0.83-0.92 and OR = 0.82 95%, CI 0.79-0.86, respectively). CONCLUSIONS: Studies on HPV vaccine determinants should consider regional-level factors. Efforts to increase HPV vaccine acceptance should include vulnerable populations (such as girls of low income) and girls with limited contact with the healthcare system.

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INTRODUCTION: Frequent emergency department (ED) users are inconsistently defined and poorly studied in Canada. The purpose of this study was to develop uniform definitions, quantify ED burden, and characterize adult frequent users of a suburban community ED. METHODS: We retrospectively reviewed the administrative database of the WestView ED in Alberta for patients ≥ 18 years of age presenting during the fiscal year of 2010. Adult frequent users and extreme frequent users were defined as patients with yearly visit numbers greater than the 95th and 99th percentiles, respectively. Demographic information including age, sex, ED length of stay, diagnoses, Canadian Triage and Acuity Scale (CTAS) level, and disposition were collected and stratified by ED frequency of use categories. RESULTS: The study included 22,333 ED visits by 14,223 patients. Frequent users represented 3.1% of patients and 13.8% of visits. Extreme frequent users represented 0.8% of patients, 5.4% of visits, and 568,879 cumulative ED minutes (395 days). Nonfrequent users had one to four, frequent users had five or more, and extreme frequent users had eight or more visits over a 12-month period. Frequent users and extreme frequent users had a significantly longer ED length of stay overall and in most age categories. Alcohol-related behavioural disorders, anxiety, nausea/vomiting, and chronic obstructive pulmonary disease were prominent diagnoses, suggesting that psychiatric, somatic, and chronic illnesses may underlie recurrent visits. Admission rates were significantly higher for frequent compared to nonfrequent users. CONCLUSIONS: We propose reproducible definitions for adult frequent and extreme frequent ED users and provide information on the characteristics and burden of care of these groups at a community Canadian suburban ED. Adoption of these definitions would allow comparison across centres in future research and facilitate targeted interventions for frequent and extreme frequent ED users.

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