Children's Perspectives on Food Allergy in Schools: A Qualitative Study.

Approximately 7% of children live with food allergy, a condition that requires dietary avoidance to prevent an allergic reaction. In this qualitative study, we aimed to understand food allergy-related experiences, beliefs and learning preferences among children with and without food allergies, to inform a school-based, food allergy education program. Data were analysed thematically. We virtually interviewed children in Kindergarten-Grade 8 in Manitoba, Canada, with (n = 7) and without (n = 9) parent-reported, physician-diagnosed food allergies. We identified three themes: Naive reliance on peers and school staff to assist with food allergy management; Limited food allergy knowledge; and, Recommended food allergy curricula: complementary perspective. Our findings will help inform the development of a school-based, food allergy education program, with a long-term goal of minimizing food allergy-related worries and optimizing safety for children with food allergy. Ongoing, school-based food allergy education is needed.

AUTS2 isoforms control neuronal differentiation.

Mutations in AUTS2 are associated with autism, intellectual disability, and microcephaly. AUTS2 is expressed in the brain and interacts with polycomb proteins, yet it is still unclear how mutations in AUTS2 lead to neurodevelopmental phenotypes. Here we report that when neuronal differentiation is initiated, there is a shift in expression from a long isoform to a short AUTS2 isoform. Yeast two-hybrid screen identified the splicing factor SF3B1 as an interactor of both isoforms, whereas the polycomb group proteins, PCGF3 and PCGF5, were found to interact exclusively with the long AUTS2 isoform. Reporter assays showed that the first exons of the long AUTS2 isoform function as a transcription repressor, but the part that consist of the short isoform acts as a transcriptional activator, both influenced by the cellular context. The expression levels of PCGF3 influenced the ability of the long AUTS2 isoform to activate or repress transcription. Mouse embryonic stem cells (mESCs) with heterozygote mutations in Auts2 had an increase in cell death during in vitro corticogenesis, which was significantly rescued by overexpressing the human AUTS2 transcripts. mESCs with a truncated AUTS2 protein (missing exons 12-20) showed premature neuronal differentiation, whereas cells overexpressing AUTS2, especially the long transcript, showed increase in expression of pluripotency markers and delayed differentiation. Taken together, our data suggest that the precise expression of AUTS2 isoforms is essential for regulating transcription and the timing of neuronal differentiation.

Estimating age-specific influenza-associated asthma morbidity in Ontario, Canada.

BACKGROUND: There is a need to quantify the potential benefits of influenza-focused interventions in reducing asthma morbidity at a population level. This study aims to estimate age-specific annual excess asthma morbidity attributable to influenza in Ontario, Canada. METHODS: Weekly counts of hospitalizations, emergency department (ED) visits and outpatient physician office visits for asthma were obtained from health administrative data in Ontario from 2010 to 2015, for ages 0-14, 15-59 and 60+. Asthma morbidity was modelled as a function of influenza A and B activity using linear regression, controlling for seasonal and long-term trend, mean temperature and respiratory syncytial virus. Excess asthma morbidity attributable to influenza was calculated as the difference between full model predictions and model predictions with influenza A and B variables set to 0. RESULTS: Annually, influenza was associated with the following rates of excess asthma morbidity, per 100,000 people with prevalent asthma: 12.5 hospitalizations for ages 15-59 (95% confidence interval (CI): 1.1-23.5); 35.7 hospitalizations for ages 60+ (95% CI: 3.3-67.1); 114.1 ED visits for ages 15-59 (95% CI: 46.9-181.6); 154.6 ED visits for ages 60+ (95% CI: 86.7-223.3); and 1025.7 outpatient physician office visits for ages 60+ (95% CI: 79.0-1877.3). CONCLUSIONS: Influenza was associated with excess asthma hospitalizations and ED visits for ages 15-59 and 60+ and outpatient physician office visits for ages 60+. Individuals with asthma aged 15-59 and 60+ might be important targets for influenza-focused interventions, to reduce asthma morbidity at the population level.

Patterns of health care use related to respiratory conditions in early life: A birth cohort study with linked administrative data.

OBJECTIVES: To identify distinctive patterns of respiratory-related health services use (HSU) between birth and 3 years of age, and to examine associated symptom and risk profiles. METHODS: This study included 729 mother and child pairs enrolled in the Toronto site of the Canadian Healthy Infant Longitudinal Development study in 2009-2012; they were linked to Ontario health administrative databases (2009-2016). A model-based cluster analysis was performed to identify distinct groups of children who followed a similar pattern of respiratory-related HSU between birth and 3 years of age, regarding hospitalization, emergency department (ED) and physician office visits for respiratory conditions and total health care costs (2016 Canadian dollars). RESULTS: The majority (estimated cluster weight = 0.905) showed a pattern of low and stable respiratory care use (low HSU) while the remainder (weight = 0.095) showed a pattern of high use (high HSU). From 0 to 3 years of age, the low- and high-HSU groups differed in mean trajectories of total health care costs ($783 per 6 months decreased to $114, vs $1796 to $177, respectively). Compared to low-HSU, the high-HSU group was associated with a constant risk of hospitalizations, early high ED utilization and physician visits for respiratory problems. The two groups differed significantly in the timing of wheezing (late onset in low-HSU vs early in high-HSU) and future total costs (stable vs increased). CONCLUSIONS: One in ten children had high respiratory care use in early life. Such information can help identify high-risk young children in a large population, monitor their long-term health, and inform resource allocation.

Montelukast and Neuropsychiatric Events in Children with Asthma: A Nested Case-Control Study.

OBJECTIVE: To examine the association between montelukast prescription and neuropsychiatric events in children with asthma. STUDY DESIGN: A matched, nested case-control design was used to identify cases and controls from a cohort of children aged 5-18 years with physician-diagnosed asthma from 2004 to 2015, in Ontario, Canada, prescribed an asthma maintenance medication. Cases were children with a hospitalization or emergency department visit for a neuropsychiatric event. Cases were matched to up to 4 controls on birth year, year of asthma diagnosis, and sex. The exposures were dispensed prescriptions for montelukast (yes/no) and number of dispensed montelukast prescriptions in the year before the index date. Conditional logistic regression was used to measure the unadjusted OR and aOR and 95% CIs for montelukast prescription and neuropsychiatric events. Covariates in the adjusted model included sociodemographic factors and measures of asthma severity. RESULTS: In total, 898 cases with a neuropsychiatric event and 3497 matched controls were included. Children who experienced a new-onset neuropsychiatric event had nearly 2 times the odds of having been prescribed montelukast, compared with controls (OR 1.91, 95% CI 1.15-3.18; P = .01). Most cases presented for anxiety (48.6%) and/or sleep disturbance (26.1%). CONCLUSIONS: Children with asthma who experienced a new-onset neuropsychiatric event had nearly twice the odds of having been prescribed montelukast in the year before their event. Clinicians should be aware of the association between montelukast and neuropsychiatric events in children with asthma, to inform prescribing practices and clinical follow-up.

Asthma and Chronic Obstructive Pulmonary Disease Overlap in Women. Incidence and Risk Factors.

RATIONALE: Women with asthma are at a high risk of developing chronic obstructive pulmonary disease (COPD) or asthma and COPD overlap syndrome (ACOS) as they age, which is a condition associated with a high mortality rate, low quality of life, and high healthcare costs. However, factors influencing the development of ACOS remain unclear. OBJECTIVES: To quantify the risk of developing COPD in women in Ontario with asthma and identify factors that are associated with increased risk. METHODS: Data for women in Ontario with asthma who participated in the Canadian National Breast Screening Study from 1980 to 1985 were linked to health administrative databases, and participants were followed from 1992 to 2015. A competing risks survival model was used to measure the associations between sociodemographic, lifestyle, and environmental risk factors and time to COPD incidence, accounting for death as a competing risk. RESULTS: A total of 4,051 women with asthma were included in the study, of whom 1,701 (42.0%) developed COPD. The mean age at the study end date was 79 years. Low education, high body mass index, rurality, and high levels of cigarette smoking were associated with ACOS incidence, whereas exposure to fine particulate matter, a major air pollutant, was not. CONCLUSIONS: Individual risk factors appear to play a more significant role in the development of ACOS in women than environmental factors, such as air pollution. Prevention strategies targeting health promotion and education may have the potential to reduce ACOS incidence in this population.

Asthma health services utilisation before, during and after pregnancy: a population-based cohort study.

During pregnancy, females with asthma may be at higher risk of exacerbation. The objective of this study was to determine whether females with asthma in Ontario, Canada have increased health services utilisation (HSU) during pregnancy.Rates of asthma-specific, asthma-related and non-pregnancy-related HSU were calculated in a population-based cohort of pregnant females with asthma. Poisson regression with repeated measures was used to determine adjusted rate ratios and 95% confidence intervals of HSU during and 1 year after pregnancy, compared to the year before pregnancy.The cohort consisted of 103 976 pregnant females with asthma. Compared to the year prior to pregnancy, hospitalisation rates per 100 person-months during pregnancy increased 30% for asthma (from 0.016 to 0.020), 24% for asthma-related conditions (from 0.012 to 0.015) and decreased 37% for non-pregnancy-related conditions (from 0.24 to 0.15). Emergency department visits for asthma and asthma-related conditions did not increase significantly during pregnancy. During pregnancy, physician office visits decreased 19% for asthma (from 2.20 to 1.79), 10% for asthma-related conditions (from 9.44 to 8.47) and increased 74% for non-pregnancy-related conditions (from 56.4 to 98.2).Hospitalisations for asthma and asthma-related conditions increased during pregnancy, demonstrating that the overall increase in non-pregnancy-related physician office visits may not meet the primary care needs of pregnant females with asthma.

Association Between Inhaled Corticosteroid Use and Bone Fracture in Children With Asthma.

Importance: Daily use of inhaled corticosteroids is a widely recommended treatment for mild persistent asthma in children. There is concern that, similar to systemic corticosteroids, inhaled corticosteroids may have adverse effects on bone health. Objective: To determine whether there is an increased risk of bone fracture associated with inhaled corticosteroid use in children with asthma. Design, Setting, and Participants: In this population-based nested case-control study, we used health administrative databases to identify a cohort of children aged 2 to 18 years with a physician diagnosis of asthma between April 1, 2003, and March 31, 2014, who were eligible for public drug coverage through the Ontario Drug Benefit Program (Ontario, Canada). We matched cases of first fracture after asthma diagnosis to fracture-free controls (ratio of 1 to 4) based on date of birth (within 1 year), sex, and age at asthma diagnosis (within 2 years). We used a 1-year lookback period to ascertain history of inhaled corticosteroid use. Multivariable conditional logistic regression was used to obtain an odds ratio (OR) with 95% confidence interval for fracture, comparing no inhaled corticosteroid use vs current, recent, and past use. Exposures: Inhaled corticosteroid use during the child's 1-year lookback period, measured as current user if the prescription was filled less than 90 days prior to the index date, recent user (91-180 days), past user (181-365 days), or no use. Main Outcomes and Measures: First emergency department visit for fracture after asthma diagnosis, identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Results: This study included 19 420 children (61.0% male; largest proportion of children, 31.5%, were aged 6-9 years at their index date). The multivariable regression results did not show a significant association between first fracture after asthma diagnosis and current use (OR, 1.07; 95% CI, 0.97-1.17), recent use (OR, 0.96; 95% CI, 0.86-1.07), or past use (OR, 1.00; 95% CI, 0.91-1.11) of inhaled corticosteroids, compared with no use, while adjusting for sociodemographic factors and other medication use. However, use of systemic corticosteroids in the 1-year lookback period resulted in greater odds of fracture (OR, 1.17; 95% CI, 1.04-1.33). Conclusions and Relevance: Systemic corticosteroids, but not inhaled corticosteroids, were significantly associated with increased odds of fracture in the pediatric asthma population.

Mental Health Services Claims and Adult Onset Asthma in Ontario, Canada.

BACKGROUND: Living with asthma is associated with a decrease in quality of life due to reductions in activities of daily living and increased psychological stress, both of which are associated with poor mental health outcomes. OBJECTIVE: The objective of this study was to quantify the burden of mental disorders on the adult asthma population and compare the risk of mental health services claims (MHSCs) in the 1 year before and 1 year after asthma diagnosis. METHODS: Ontario residents aged 25 to 65 years with incident physician-diagnosed asthma between April 1, 2005, and March 31, 2012, were included. MHSCs, which consisted of hospitalizations, emergency department (ED), and outpatient physician visits, were identified from universal health administrative data. Poisson regression models with repeated measures were used to estimate the relative risk (RR) of MHSCs for 2 time periods: 1 year after asthma diagnosis compared with the 1 year before and 2 years after compared with 2 years before. RESULTS: A total of 145,881 adults had incident asthma. In the 1 year after asthma diagnosis, 27% had an MHSC. The risk of ED visits for any mental disorders increased by 13% in the 1 year after asthma diagnosis compared with the 1 year before (adjusted RR [aRR], 1.13; 95% confidence interval [CI], 1.06-1.21). This increased risk of ED visits was not found when comparing 2 years after asthma diagnosis with 2 years before. The risk for outpatient physician visits for substance-related disorders increased by 21% at 1 year (aRR, 1.21; 95% CI, 1.14-1.28) and 37% at 2 years (aRR, 1.37; 95% CI, 1.28-1.46). CONCLUSIONS: The significant comorbid burden of mental disorders in adults with newly diagnosed asthma highlights the need for primary care physicians to assess mental health needs and provide appropriate care.

Frequency of health service use in the year prior to asthma death.

OBJECTIVE: High frequency health service use (HSU) is associated with poorly controlled asthma, and is a recognized risk factor for near-fatal or fatal asthma. The objective of this study was to describe the frequency of HSU in the year prior to asthma death. METHODS: Individuals aged 0-99 years who died from asthma from April 1996 to December 2011 in Ontario, Canada were identified as cases. Cases were matched to 4-5 live asthma controls by age, sex, rural/urban residence, socioeconomic status, duration of asthma and a co-diagnosis of COPD. HSU records in the year prior to death [hospitalization, emergency department (ED) and outpatient visits] were assembled. The association of prior HSU and asthma death was measured by conditional logistic regression models. RESULTS: From 1996 to 2011, 1503 individuals died from asthma. While the majority of cases did not have increased HSU as defined in the study, compared to matched live asthma controls, the cases were 8-fold more likely to have been hospitalized two or more times (OR = 7.60; 95% CI: 4.90, 11.77), 13-fold more likely to have had three or more ED visits (OR = 13.28; 95% CI: 7.55, 23.34) and 4-fold more likely to have had five or more physician visits for asthma (OR = 4.41; 95% CI: 3.58, 5.42). CONCLUSIONS: Frequency of HSU in the year prior was substantially higher in those died from asthma. Specifically, more than one asthma hospital admission, three ED visits or five physician visits increased the asthma mortality risk substantially and exponentially.

Progression from Asthma to Chronic Obstructive Pulmonary Disease. Is Air Pollution a Risk Factor?

RATIONALE: Individuals with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), have more rapid decline in lung function, more frequent exacerbations, and poorer quality of life than those with asthma or COPD alone. Air pollution exposure is a known risk factor for asthma and COPD; however, its role in ACOS is not as well understood. OBJECTIVES: To determine if individuals with asthma exposed to higher levels of air pollution have an increased risk of ACOS. METHODS: Individuals who resided in Ontario, Canada, aged 18 years or older in 1996 with incident asthma between 1996 and 2009 who participated in the Canadian Community Health Survey were identified and followed until 2014 to determine the development of ACOS. Data on exposures to fine particulate matter (PM2.5) and ozone (O3) were obtained from fixed monitoring sites. Associations between air pollutants and ACOS were evaluated using Cox regression models. MEASUREMENTS AND MAIN RESULTS: Of the 6,040 adults with incident asthma who completed the Canadian Community Health Survey, 630 were identified as ACOS cases. Compared with those without ACOS, the ACOS population had later onset of asthma, higher proportion of mortality, and more frequent emergency department visits before COPD diagnosis. The adjusted hazard ratios of ACOS and cumulative exposures to PM2.5 (per 10 µg/m(3)) and O3 (per 10 ppb) were 2.78 (95% confidence interval, 1.62-4.78) and 1.31 (95% confidence interval, 0.71-2.39), respectively. CONCLUSIONS: Individuals exposed to higher levels of air pollution had nearly threefold greater odds of developing ACOS. Minimizing exposure to high levels of air pollution may decrease the risk of ACOS.

The Annual September Peak in Asthma Exacerbation Rates. Still a Reality?

RATIONALE: Recent research suggests that the asthma epidemic observed in the 1980s and 1990s has stabilized. Changing trends in asthma may have an impact on the well-reported global phenomenon of the "asthma September peak." The 38th week of the year has been identified as the peak time for asthma exacerbations among children. OBJECTIVES: The purposes of this study were to examine the longitudinal trend of the September peak and to see if it changed over time, differed by age groups, or varied across different geographical regions. METHODS: Monthly rates of asthma emergency department (ED) and physician outpatient visits were calculated using data provided by the Ontario Asthma Surveillance Information System from 2003 to 2013 for patients of all ages. The Ontario Asthma Surveillance Information System is a population-based surveillance system with over 2 million individuals with asthma. Age-specific rates were calculated using the prevalent asthma population-asthma individuals with at least one health service claim for asthma in the respective year-as the denominator. Rates were stratified by age group and region of residence. Spatial relationships within the province were tested to examine if the September peak was more prominent in certain regions of Ontario. MEASUREMENTS AND MAIN RESULTS: The highest September peak in ED visits was observed in 2005 for children aged 0-4 years and 5-9 years (18.35 and 8.11 per 1,000 asthma prevalence, respectively). The rate of asthma ED visits of all children was consistently highest in September; however, the spike became marginally less pronounced over time. Since 2005, there has been a 51.7% decrease in the September asthma ED visit rate for all age groups. Monthly physician visits for all age groups usually peaked in October, roughly 4 weeks following the peak in ED visits. Analysis by residence showed that rates throughout Ontario were higher in September than in other months, suggesting that the spike was widespread rather than localized. CONCLUSIONS: While the magnitude of the September peak has decreased over time, the asthma ED visit rate remains significantly higher in September than in other months. Physician visits are also highest in the fall. These findings stress the importance of empowering children and families to maintain good asthma control throughout the year, including hand washing, to minimize respiratory viral infections in September.

Estimating Toronto's health services use for the 2015 Pan American and Parapan American Games.

AIMS: Ambient air temperature may exacerbate the burden of chronic diseases on Ontario's healthcare system during mass gathering events. This study aimed to estimate the impact of increasing temperature in July and August on health services use for chronic conditions in Ontario's Golden Horseshoe region during the 2015 Pan American and Parapan American Games, using environmental and health administrative data from previous years. METHOD: Negative binomial regression was used to calculate incidence risk ratios for same-day health services use (hospitalisations, emergency department visits, physician office visits) for all causes, asthma, asthma-related conditions, diabetes and hypertension associated with unit increases in daily maximum temperature from 1 May to 31 August in 2008-2010. Sensitivity analysis was performed to estimate the added burden of an increased population size, in order to model an influx of visitors during the Games. RESULTS: In July and August, on days with daily maximum temperatures of 35 °C compared to 25 °C, we estimated seeing 7,827 more physician office visits for all causes in Ontario's Golden Horseshoe region. The estimated relative increase in physician office visits for diabetes due to temperature alone was 8.4%. With an estimated 10% increase in population, the increase in physician office visits for all causes tripled to an estimated 23,590. CONCLUSION: Temperature was identified as a potential contributor to greater health services use during the Games, particularly for those living with diabetes. These results highlight the importance of strategic delivery of health services during mass gathering events, and suggest a role for educating at-risk individuals on prevention behaviours, particularly on very hot days.

Health risk of air pollution on people living with major chronic diseases: a Canadian population-based study.

OBJECTIVES: The objective of this study was to use health administrative and environmental data to quantify the effects of ambient air pollution on health service use among those with chronic diseases. We hypothesised that health service use would be higher among those with more exposure to air pollution as measured by the Air Quality Health Index (AQHI). SETTING: Health administrative data was used to quantify health service use at the primary (physician office visits) and secondary (emergency department visits, hospitalisations) level of care in Ontario, Canada. PARTICIPANTS: We included individuals who resided in Ontario, Canada, from 2003 to 2010, who were ever diagnosed with one of 11 major chronic diseases. OUTCOME MEASURES: Rate ratios (RR) from Poisson regression models were used to estimate the short-term impact of incremental unit increases in AQHI, nitrogen dioxide (NO2; 10 ppb), fine particulate matter (PM2.5; 10 µg/m(3)) and ozone (O3; 10 ppb) on health services use among individuals with each disease. We adjusted for age, sex, day of the week, temperature, season, year, socioeconomic status and region of residence. RESULTS: Increases in outpatient visits ranged from 1% to 5% for every unit increase in the 10-point AQHI scale, corresponding to an increase of about 15,000 outpatient visits on a day with poor versus good air quality. The greatest increases in outpatient visits were for individuals with non-lung cancers (AQHI:RR=1.05; NO2:RR=1.14; p<0.0001) and COPD (AQHI:RR=1.05; NO2:RR=1.12; p<0.0001) and in hospitalisations, for individuals with diabetes (AQHI:RR=1.04; NO2:RR=1.07; p<0.0001) and COPD (AQHI:RR=1.03; NO2:RR=1.09; p<1.001). The impact remained 2 days after peak AQHI levels. CONCLUSIONS: Among individuals with chronic diseases, health service use increased with higher levels of exposure to air pollution, as measured by the AQHI. Future research would do well to measure the utility of targeted air quality advisories based on the AQHI to reduce associated health service use.

Chronic disease prevalence in women and air pollution--A 30-year longitudinal cohort study.

BACKGROUND: Air pollution, such as fine particulate matter (PM2.5), can increase risk of adverse health events among people with heart disease, diabetes, asthma and chronic obstructive pulmonary disease (COPD) by aggravating these conditions. Identifying the influence of PM2.5 on prevalence of these conditions may help target interventions to reduce disease morbidity among high-risk populations. OBJECTIVES: The objective of this study is to measure the association of exposure of PM2.5 with prevalence risk of various chronic diseases among a longitudinal cohort of women. METHODS: Women from Ontario who enrolled in the Canadian National Breast Screening Study (CNBSS) from 1980 to 1985 (n = 29,549) were linked to provincial health administrative data from April 1, 1992 to March 31, 2013 to determine the prevalence of major chronic disease and conditions (heart disease, diabetes, asthma, COPD, acute myocardial infarction, angina, stroke and cancers). Exposure to PM2.5 was measured using satellite data collected from January 1, 1998 to December 31, 2006 and assigned to resident postal-code at time of entry into study. Poisson regression models were used to describe the relationship between exposure to ambient PM2.5 and chronic disease prevalence. Prevalence rate ratios (PRs) were estimated while adjusting for potential confounders: baseline age, smoking, BMI, marital status, education and occupation. Separate models were run for each chronic disease and condition. RESULTS: Congestive heart failure (PR = 1.31, 95% CI: 1.13, 1.51), diabetes (PR = 1.28, 95% CI: 1.16, 1.41), ischemic heart disease (PR = 1.22, 95% CI: 1.14, 1.30), and stroke (PR = 1.21, 95% CI: 1.09, 1.35) showed over a 20% increase in PRs per 10 µg/m(3) increase in PM2.5 after adjusting for risk factors. Risks were elevated in smokers and those with BMI greater than 30. CONCLUSIONS: This study estimated significant elevated prevalent rate ratios per unit increase in PM2.5 in nine of the ten chronic diseases studied.

Quality of asthma care under different primary care models in Canada: a population-based study.

BACKGROUND: Previous research has shown variations in quality of care and patient outcomes under different primary care models. The objective of this study was to use previously validated, evidence-based performance indicators to measure quality of asthma care over time and to compare quality of care between different primary care models. METHODS: Data were obtained for years 2006 to 2010 from the Ontario Asthma Surveillance Information System, which uses health administrative databases to track individuals with asthma living in the province of Ontario, Canada. Individuals with asthma (n=1,813,922) were divided into groups based on the practice model of their primary care provider (i.e., fee-for-service, blended fee-for-service, blended capitation). Quality of asthma care was measured using six validated, evidence-based asthma care performance indicators. RESULTS: All of the asthma performance indicators improved over time within each of the primary care models. Compared to the traditional fee-for-service model, the blended fee-for-service and blended capitation models had higher use of spirometry for asthma diagnosis and monitoring, higher rates of inhaled corticosteroid prescription, and lower outpatient claims. Emergency department visits were lowest in the blended fee-for-service group. CONCLUSIONS: Quality of asthma care improved over time within each of the primary care models. However, the amount by which they improved differed between the models. The newer primary care models (i.e., blended fee-for-service, blended capitation) appear to provide better quality of asthma care compared to the traditional fee-for-service model.

Asthma deaths in a large provincial health system. A 10-year population-based study.

RATIONALE: Individuals with asthma are more likely to die from chronic conditions than the general population. Measuring only mortality with asthma listed as the primary cause of death may lead to an underestimation of total asthma mortality. OBJECTIVES: To examine mortality patterns in the asthma population over 10 years, including asthma as the primary cause of death (asthma-specific mortality) and asthma as a secondary, contributing cause of death (asthma-contributing mortality). METHODS: Health administrative data from Ontario, Canada were used to identify mortality rates and cause of death in subjects 0 to 99 years of age. Mortality rates were calculated in the asthma and general population from 1999 to 2008. Total asthma mortality was estimated by adding rates of asthma-specific and asthma-contributing mortality for years 2003 to 2008. MEASUREMENTS AND MAIN RESULTS: Asthma-specific mortality rates per 100,000 asthma population decreased by 54.4% from 13.6 in 1999 to 6.2 in 2008. In 2008, the asthma population had higher all-cause mortality compared with the general population (rate ratio, 1.3), asthma-specific mortality rates were 60% higher among those in the lowest compared with highest socioeconomic status, and total asthma mortality was fourfold higher than asthma-specific mortality alone (21.6 vs. 5.4 per 100,000). CONCLUSIONS: All-cause mortality rates have decreased substantially over the past decade. Compared with the general population, the asthma population has higher all-cause mortality and is more likely to die from comorbid conditions. Total asthma mortality was fourfold higher than asthma-specific mortality, highlighting the importance of comprehensive measurement approaches that include asthma-specific and asthma-contributing mortality.

Smoking initiation among young adults in the United States and Canada, 1998-2010: a systematic review.

INTRODUCTION: Young adults have the highest smoking rate of any age group in the United States and Canada, and recent data indicate that they often initiate smoking as young adults. The objective of this study was to systematically review peer-reviewed articles on cigarette smoking initiation and effective prevention efforts among young adults. METHODS: We searched 5 databases for research articles published in English between 1998 and 2010 on smoking initiation among young adults (aged 18-25) living in the United States or Canada. We extracted the following data from each study selected: the measure of initiation used, age range of initiation, age range of study population, data source, target population, sampling method, and sample size. We summarized the primary findings of each study according to 3 research questions and categories of data (eg, sociodemographic) that emerged during the data extraction process. RESULTS: Of 1,072 identified studies, we found 27 articles that met our search criteria, but several included a larger age range of initiation (eg, 18-30, 18-36) than we initially intended to include. Disparities in young adult smoking initiation existed according to sex, race, and educational attainment. The use of alcohol and illegal drugs was associated with smoking initiation. The risk of smoking initiation among young adults increased under the following circumstances: exposure to smoking, boredom or stress while serving in the military, attending tobacco-sponsored social events while in college, and exposure to social norms and perceptions that encourage smoking. Effective prevention efforts include exposure to counter-marketing, denormalization campaigns, taxation, and the presence of smoke-free policies. CONCLUSION: Much remains to be learned about young adult smoking initiation, particularly among young adults in the straight-to-work population. Dissimilar measures of smoking initiation limit our knowledge about smoking initiation among young adults. We recommend developing a standardized measure of initiation that indicates progression to regular established smoking.

Leishmania major: effect of protein kinase A and phosphodiesterase activity on infectivity and proliferation of promastigotes.

Effect of modulators on protein kinase A (PKA) activity, promastigote growth and their ability to infect peritoneal macrophages was monitored. PKA inhibitors reduced [Protein Kinase Inhibitor (PKI) - 56%; H89 - 54.5%] kemptide phosphorylation by Leishmania major promastigote lysates, while activators increased phosphorylation (8-CPT-cAMP - 88%; Sp-cAMPS-AM - 152%). Activation was specifically inhibited by PKI. Phosphodiesterase inhibitors also increased kemptide phosphorylation (dipyridamole - 171%; rolipram - 106%; and 3-isobutyl-1-methyl-xanthine - 154%). Parasite proliferation was significantly retarded (200 nM H89; 100 microM myristoylated-PKI) or completely inhibited (500 nM H89) by culturing with PKA inhibitors. Incubation with dipyridamole or Sp-cAMPS-AM also inhibited proliferation. Brief treatment (2h) with either H89, myristoylated-PKI, dipyridamole or Sp-cAMPS-AM reduced initial macrophage infection at days 1 and 2 (>40%) and on day 3 (>78% only for 100 microM myr-PKI). Characterization of leishmanial cAMP mediated signal transduction pathways will serve as the basis for the new drug design.