Transitions From Heart Disease to Cancer as the Leading Cause of Death in US States, 1999-2016.

INTRODUCTION: Heart disease has been the leading cause of death in the United States since 1910 and cancer the second leading cause of death since 1933. However, cancer emerged recently as the leading cause of death in many US states. The objective of this study was to provide an in-depth analysis of age-standardized annual state-specific mortality rates for heart disease and cancer. METHODS: We used population-based mortality data from 1999 through 2016 to compare 2 underlying cause-of-death categories: diseases of heart (International Classification of Diseases, 10th Revision [ICD-10] codes I00-I09, I11, I13, and I20-I51) and malignant neoplasms (ICD-10 codes C00-C97). We calculated age-standardized annual state-specific mortality rate ratios (MRRs) as heart disease mortality rate divided by cancer mortality rate. RESULTS: In 1999, age-standardized heart disease mortality exceeded that for cancer in all 50 states. Median state-specific MRR in 1999 was 1.26 (interquartile range [IQR], 1.17-1.34; range, 1.03-1.56), indicating predominance of heart disease mortality nationwide. Median state-specific MRR decreased annually through 2010, reaching a low of 1.00 (IQR, 0.95-1.07; range, 0.71-1.25), indicating that predominance of heart disease mortality prevailed in approximately half of states. Median state-specific MRR increased to 1.03 (IQR, 0.97-1.12; range, 0.77-1.31) in 2016. In 2016, age-standardized cancer mortality exceeded that for heart disease in 19 states. State-level transitions were most apparent for people aged 65 to 84 and affected men, women, and all racial/ethnic groups. CONCLUSION: State-level data indicated heterogeneity across US states in the predominance of heart disease mortality relative to cancer mortality. Timing and magnitude of transitions toward cancer mortality predominance varied by state.

Respiratory syncytial virus immunoprophylaxis in high-risk infants and development of childhood asthma.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection is implicated in asthma development. RSV immunoprophylaxis during infancy is efficacious in preventing RSV-related hospitalizations and has been associated with decreased wheezing in the first years of life. OBJECTIVE: We investigated whether greater adherence to immunoprophylaxis in infants at high risk for severe RSV would be associated with decreased childhood asthma. METHODS: We conducted a retrospective cohort investigation including children born from 1996-2003 who were enrolled in Kaiser Permanente Northern California or Tennessee Medicaid and eligible to receive RSV immunoprophylaxis. Asthma was defined at 4.5 to 6 years of age by using asthma-specific health care visits and medication fills. We classified children into immunoprophylaxis eligibility groups and calculated adherence (percentage receipt of recommended doses). We used a set of statistical strategies (multivariable logistic regression and propensity score [PS]-adjusted and PS-matched analyses) to overcome confounding by medical complexity because infants with higher adherence (≥70%) have higher prevalence of chronic lung disease, lower birth weight, and longer nursery stays. RESULTS: By using multivariable logistic regression and PS-adjusted models in the combined group, higher adherence to RSV immunoprophylaxis was not associated with decreased asthma. However, in PS-matched analysis, treated children with 70% or greater adherence had decreased odds of asthma compared with those with 20% or less adherence (odds ratio, 0.62; 95% CI, 0.50-0.78). CONCLUSIONS: This investigation of RSV immunoprophylaxis in high-risk children primarily found nonsignificant associations on prevention of asthma in specific preterm groups. Our findings highlight the need for larger studies and prospective cohorts and provide estimates of potential preventive effect sizes in high-risk children.

Identifying and Reducing Disparities in Mental Health Outcomes Among American Indians and Alaskan Natives Using Public Health, Mental Healthcare and Legal Perspectives.

The purpose of this paper was to investigate disparities in mental healthcare delivery in American Indian/Alaska Native populations from three perspectives: public health, legal policy and mental healthcare and provide evidence-based recommendations toward reducing those disparities. Data on mental health funding to tribes were obtained from the Substance Abuse and Mental Health Services Administration. As a result of analysis of these data, vital statistics and current literature, we propose three recommendations to reduce mental health disparities. First, where possible, increase mental health funding opportunities for federally-recognized tribes. Second, model funding practices on principles of tribal self-determination. Finally, support diverse interventions that are culturally-based and culturally-appropriate.

Interference Between Respiratory Syncytial Virus and Human Rhinovirus Infection in Infancy.

BACKGROUND: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. METHODS: To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses. RESULTS: Among 3263 respiratory tract samples, 24.5% (798) and 37.3% (1216) were RSV and HRV positive, respectively. The odds of HRV infection were significantly lower in RSV-infected infants in all cohorts, with adjusted odds ratios of 0.30 (95% confidence interval [CI], .22-.40 in the INSPIRE study, 0.18 (95% CI, .11-.28) in the TCRI (adjusted for disease severity), and 0.34 (95% CI, .16-.72) in the MAKI trial. HRV infection was significantly more common among infants administered RSV immunoprophylaxis, compared with infants who did not receive immunoprophylaxis (OR, 1.65; 95% CI, 1.65-2.39). CONCLUSIONS: A negative association of RSV on HRV codetection was consistently observed across populations, seasons, disease severity, and geographical regions. Suppressing RSV infection by RSV immunoprophylaxis might increase the risk of having HRV infection.

Applications of GPS-tracked personal and fixed-location PM(2.5) continuous exposure monitoring.

UNLABELLED: Continued development of personal air pollution monitors is rapidly improving government and research capabilities for data collection. In this study, we tested the feasibility of using GPS-enabled personal exposure monitors to collect personal exposure readings and short-term daily PM2.5 measures at 15 fixed locations throughout a community. The goals were to determine the accuracy of fixed-location monitoring for approximating individual exposures compared to a centralized outdoor air pollution monitor, and to test the utility of two different personal monitors, the RTI MicroPEM V3.2 and TSI SidePak AM510. For personal samples, 24-hr mean PM2.5 concentrations were 6.93 µg/m³ (stderr = 0.15) and 8.47 µg/m³ (stderr = 0.10) for the MicroPEM and SidePak, respectively. Based on time-activity patterns from participant journals, exposures were highest while participants were outdoors (MicroPEM = 7.61 µg/m³, stderr = 1.08, SidePak = 11.85 µg/m³, stderr = 0.83) or in restaurants (MicroPEM = 7.48 µg/m³, stderr = 0.39, SidePak = 24.93 µg/m³, stderr = 0.82), and lowest when participants were exercising indoors (MicroPEM = 4.78 µg/m³, stderr = 0.23, SidePak = 5.63 µg/m³, stderr = 0.08). Mean PM(2.5) at the 15 fixed locations, as measured by the SidePak, ranged from 4.71 µg/m³ (stderr = 0.23) to 12.38 µg/m³ (stderr = 0.45). By comparison, mean 24-h PM(2.5) measured at the centralized outdoor monitor ranged from 2.7 to 6.7 µg/m³ during the study period. The range of average PM(2.5) exposure levels estimated for each participant using the interpolated fixed-location data was 2.83 to 19.26 µg/m³ (mean = 8.3, stderr = 1.4). These estimated levels were compared with average exposure from personal samples. The fixed-location monitoring strategy was useful in identifying high air pollution microclimates throughout the county. For 7 of 10 subjects, the fixed-location monitoring strategy more closely approximated individuals' 24-hr breathing zone exposures than did the centralized outdoor monitor. Highlights are: Individual PM(2.5) exposure levels vary extensively by activity, location and time of day; fixed-location sampling more closely approximated individual exposures than a centralized outdoor monitor; and small, personal exposure monitors provide added utility for individuals, researchers, and public health professionals seeking to more accurately identify air pollution microclimates. IMPLICATIONS: Personal air pollution monitoring technology is advancing rapidly. Currently, personal monitors are primarily used in research settings, but could they also support government networks of centralized outdoor monitors? In this study, we found differences in performance and practicality for two personal monitors in different monitoring scenarios. We also found that personal monitors used to collect outdoor area samples were effective at finding pollution microclimates, and more closely approximated actual individual exposure than a central monitor. Though more research is needed, there is strong potential that personal exposure monitors can improve existing monitoring networks.

Investigation of spatio-temporal cancer clusters using residential histories in a case-control study of non-Hodgkin lymphoma in the United States.

BACKGROUND: Non-Hodgkin lymphoma (NHL) is an enigmatic disease with few known risk factors. Spatio-temporal epidemiologic analyses have the potential to reveal patterns that may give clues to new risk factors worthy of investigation. We sought to investigate clusters of NHL through space and time based on life course residential histories. METHODS: We used residential histories from a population-based NHL case-control study of 1300 cases and 1044 controls with recruitment centers in Iowa, Detroit, Seattle, and Los Angeles, and diagnosed in 1998-2000. Novel methods for cluster detection allowing for residential mobility, called Q-statistics, were used to quantify nearest neighbor relationships through space and time over the life course to identify cancer clusters. Analyses were performed on all cases together and on two subgroups of NHL: Diffuse large B-cell lymphoma and follicular lymphoma. These more homogenous subgroups of cases might have a more common etiology that could potentially be detected in cluster analysis. Based on simulation studies designed to help account for multiple testing across space and through time, we required at least four significant cases nearby one another to declare a region a potential cluster, along with confirmatory analyses using spatial-only scanning windows (SaTScan). RESULTS: Evidence of a small cluster in southeastern Oakland County, MI was suggested using residences 10-18 years prior to diagnosis, and confirmed by SaTScan in a time-slice analysis 20 years prior to diagnosis, when all cases were included in the analysis. Consistent evidence of clusters was not seen in the two histologic subgroups. CONCLUSIONS: Suggestive evidence of a small space-time cluster in southeastern Oakland County, MI was detected in this NHL case-control study in the USA.

Ecogeographic genetic epidemiology.

Complex diseases such as cancer and heart disease result from interactions between an individual's genetics and environment, i.e. their human ecology. Rates of complex diseases have consistently demonstrated geographic patterns of incidence, or spatial "clusters" of increased incidence relative to the general population. Likewise, genetic subpopulations and environmental influences are not evenly distributed across space. Merging appropriate methods from genetic epidemiology, ecology and geography will provide a more complete understanding of the spatial interactions between genetics and environment that result in spatial patterning of disease rates. Geographic information systems (GIS), which are tools designed specifically for dealing with geographic data and performing spatial analyses to determine their relationship, are key to this kind of data integration. Here the authors introduce a new interdisciplinary paradigm, ecogeographic genetic epidemiology, which uses GIS and spatial statistical analyses to layer genetic subpopulation and environmental data with disease rates and thereby discern the complex gene-environment interactions which result in spatial patterns of incidence.

Whole genome association study of brain-wide imaging phenotypes for identifying quantitative trait loci in MCI and AD: A study of the ADNI cohort.

A genome-wide, whole brain approach to investigate genetic effects on neuroimaging phenotypes for identifying quantitative trait loci is described. The Alzheimer's Disease Neuroimaging Initiative 1.5 T MRI and genetic dataset was investigated using voxel-based morphometry (VBM) and FreeSurfer parcellation followed by genome-wide association studies (GWAS). One hundred forty-two measures of grey matter (GM) density, volume, and cortical thickness were extracted from baseline scans. GWAS, using PLINK, were performed on each phenotype using quality-controlled genotype and scan data including 530,992 of 620,903 single nucleotide polymorphisms (SNPs) and 733 of 818 participants (175 AD, 354 amnestic mild cognitive impairment, MCI, and 204 healthy controls, HC). Hierarchical clustering and heat maps were used to analyze the GWAS results and associations are reported at two significance thresholds (p<10(-7) and p<10(-6)). As expected, SNPs in the APOE and TOMM40 genes were confirmed as markers strongly associated with multiple brain regions. Other top SNPs were proximal to the EPHA4, TP63 and NXPH1 genes. Detailed image analyses of rs6463843 (flanking NXPH1) revealed reduced global and regional GM density across diagnostic groups in TT relative to GG homozygotes. Interaction analysis indicated that AD patients homozygous for the T allele showed differential vulnerability to right hippocampal GM density loss. NXPH1 codes for a protein implicated in promotion of adhesion between dendrites and axons, a key factor in synaptic integrity, the loss of which is a hallmark of AD. A genome-wide, whole brain search strategy has the potential to reveal novel candidate genes and loci warranting further investigation and replication.

Genetic pathway-based hierarchical clustering analysis of older adults with cognitive complaints and amnestic mild cognitive impairment using clinical and neuroimaging phenotypes.

Hierarchical clustering is frequently used for grouping results in expression or haplotype analyses. These methods can elucidate patterns between measures that can then be applied to discerning their validity in discriminating between experimental conditions. Here a hierarchical clustering method is used to analyze the results of an imaging genetics study using multiple brain morphology and cognitive testing endpoints for older adults with amnestic mild cognitive impairment (MCI) or cognitive complaints (CC) compared to healthy controls (HC). The single nucleotide polymorphisms (SNPs) are a subset of those included on a larger array that are found in a reported Alzheimer's disease (AD) and neurodegeneration pathway. The results indicate that genetic models within the endpoints cluster together, while there are 4 distinct sets of SNPs that differentiate between the endpoints, with most significant results associated with morphology endpoints rather than cognitive testing of patients' reported symptoms. The genes found in at least one cluster are ABCB1, APBA1, BACE1, BACE2, BCL2, BCL2L1, CASP7, CHAT, CST3, DRD3, DRD5, IL6, LRP1, NAT1, and PSEN2. The greater associations with morphology endpoints suggests that changes in brain structure can be influenced by an individual's genetic background in the absence of dementia and in some cases (Cognitive Complaints group) even without those effects necessarily being detectable on commonly used clinical tests of cognition. The results are consistent with polygenic influences on early neurodegenerative changes and demonstrate the effectiveness of hierarchical clustering in identifying genetic associations among multiple related phenotypic endpoints.

Geospatial and Temporal Associations between Increases in Opioid Deaths, Socioeconomics, and Rates of Sexually Transmitted Infections in the Northeast United States 2012-2017.

With the introduction of fentanyl to illegal markets in 2013 and an overall rise in rates of synthetic opioid use, opioid-related deaths have increased significantly. A similar trend has been observed for sexually transmitted infections, homicides, and poor mental health outcomes. In this paper, we explore the spatiotemporal relationship between opioid death rates and sexually transmitted infection (STI) rates in counties from the Northeast region of the United States between the years 2012-2017. We hypothesized that rates for gonorrhea, chlamydia, and human immunodeficiency virus (HIV) would all be positively associated with opioid death rates and that there would be a similar association between the STI rates and later time periods relative to earlier time periods. A negative binomial mixed-effects regression model was employed to assess these associations. Contrary to the study hypothesis, opioid death rates were not found to be significantly associated with the STI rates after accounting for other demographic and socioeconomic variables, with the exception of opioid deaths and gonorrhea in urban counties. Additionally, the regression demonstrated a significant association between infection rate and time period beyond the included socioeconomic variables and opioid deaths. Overall, this study indicates that declining sexual health outcomes may parallel rising opioid death, though both trends may be explained by similar underlying factors related to time period.

Political and personal reactions to COVID-19 during initial weeks of social distancing in the United States.

OBJECTIVE: To examine perceptions, behaviors, and impacts surrounding COVID-19 early in the pandemic response. MATERIALS AND METHODS: A cross-sectional survey of 1,030 U.S. adults was administered on March 31st, 2020. This survey examined attitudes toward media, government, and community responses to COVID-19 by political ideology and sociodemographic factors. Knowledge, anxieties, and impacts of COVID-19 were also assessed. RESULTS: Conservatives were more likely to report that COVID-19 was receiving too much media coverage and people were generally overreacting; liberals were more likely to report the government had not done enough in response to the pandemic. Females and those with lower income experienced more COVID-19 related economic anxieties. Those working and with children at home reported higher social, home, and work disruption. Social distancing behaviors were more common among liberals and were associated with increases in depressive symptoms. General knowledge about COVID-19 was widely exhibited across the sample, however, Black and Hispanic respondents were less likely to correctly answer questions about the availability of a vaccine and modes of transmission. CONCLUSIONS: Public health experts should consider the political climate in crafting messaging that appeals to the values of those across the political spectrum. Research on the COVID-19 pandemic should continue to monitor the effects of social distancing on mental health and among vulnerable populations.

Comparative Seasonal Respiratory Virus Epidemic Timing in Utah.

Previous studies have found evidence of viral interference between seasonal respiratory viruses. Using laboratory-confirmed data from a Utah-based healthcare provider, Intermountain Health Care, we analyzed the time-specific patterns of respiratory syncytial virus (RSV), influenza A, influenza B, human metapneumovirus, rhinovirus, and enterovirus circulation from 2004 to 2018, using descriptive methods and wavelet analysis (n = 89,462) on a local level. The results showed that RSV virus dynamics in Utah were the most consistent of any of the viruses studied, and that the other seasonal viruses were generally in synchrony with RSV, except for enterovirus (which mostly occurs late summer to early fall) and influenza A and B during pandemic years.

Modeling the effects of atmospheric pressure on suicide rates in the USA using geographically weighted regression.

Low atmospheric pressure may increase depression and suicide through inducing hypoxia. Previous studies have not evaluated the geographic variation of this relationship across the United States. Analyses were based on three groupings of age-adjusted completed suicide rates (all suicide, firearm-related suicide, non-firearm-related suicide) from 2286 counties in the United States. Multiple regression was used to determine the overall relationship between atmospheric pressure and completed suicide rates. Geographically weighted regression (GWR) models were used to obtain local coefficient estimates. A negative correlation between atmospheric pressure and completed suicide rates was observed for all three suicide groupings (p-value <0.0001). Significant, negative GWR coefficient estimates were located in the West and Northeast for the all suicides and firearm-related suicides, and in the Midwest for non-firearm-related suicides.

Personal exposure to fine particulate air pollution while commuting: An examination of six transport modes on an urban arterial roadway.

Traffic-related air pollution in urban areas contributes significantly to commuters' daily PM2.5 exposures, but varies widely depending on mode of commuting. To date, studies show conflicting results for PM2.5 exposures based on mode of commuting, and few studies compare multiple modes of transportation simultaneously along a common route, making inter-modal comparisons difficult. In this study, we examined breathing zone PM2.5 exposures for six different modes of commuting (bicycle, walking, driving with windows open and closed, bus, and light-rail train) simultaneously on a single 2.7 km (1.68 mile) arterial urban route in Salt Lake City, Utah (USA) during peak "rush hour" times. Using previously published minute ventilation rates, we estimated the inhaled dose and exposure rate for each mode of commuting. Mean PM2.5 concentrations ranged from 5.20 µg/m3 for driving with windows closed to 15.21 µg/m3 for driving with windows open. The estimated inhaled doses over the 2.7 km route were 6.83 µg for walking, 2.78 µg for cycling, 1.28 µg for light-rail train, 1.24 µg for driving with windows open, 1.23 µg for bus, and 0.32 µg for driving with windows closed. Similarly, the exposure rates were highest for cycling (18.0 µg/hr) and walking (16.8 µg/hr), and lowest for driving with windows closed (3.7 µg/hr). Our findings support previous studies showing that active commuters receive a greater PM2.5 dose and have higher rates of exposure than commuters using automobiles or public transportation. Our findings also support previous studies showing that driving with windows closed is protective against traffic-related PM2.5 exposure.

Elemental analysis of infant airborne particulate exposures.

Air pollution is hypothesized to have negative impacts on infant pulmonary health because of infants' increased rates of respiration and ongoing lung development. The severity and type of impact may differ depending on elemental concentrations. We conducted a study of 21 infants <6 months old whose parents carried a small personal particulate monitoring device (RTI MicroPEM) and GPS unit with the infant for 7 days in January and February 2015. The study area was Utah County, UT, USA. Real-time particulate exposure levels, as well as optical density and elemental analysis of the particulate matter (PM), were compared with levels from an outdoor stationary monitor. Infants spent an average of 87.4% of their time indoors. PM levels varied widely by infant and time of day (average=19.07 µg/m3, range=0.63-170.25 µg/m3). Infant particulate exposures were not well approximated by the outdoor monitor. Infants had lower exposures to Sb, Mn, Pb, W and Fe than the outdoor monitor and higher exposures to Cd, Ni and Na. Differences were most pronounced for Na. Brown carbon was only detected by personal monitors and not by the outdoor monitor. Further research is needed to understand the potential implications of indoor elemental exposures on early respiratory development.

Seasonal Timing of Infant Bronchiolitis, Apnea and Sudden Unexplained Infant Death.

Rates of Sudden Unexplained Infant Death (SUID), bronchiolitis, and central apnea increase in winter in temperate climates. Though associations between these three conditions are suggested, more work is required to establish if there is a causal pathway linking bronchiolitis to SUID through inducing central apnea. Utilizing a large population-based cohort of infants studied over a 20-year period (n = 834,595, from birth years 1989-2009)), we analyzed ecological associations between timing of SUID cases, bronchiolitis, and apnea healthcare visits. Data were analyzed between 2013 and 2015. We used a Cox Proportional Hazards model to analyze possible interactions between maternal smoking and maternal asthma with infant bronchiolitis on time to SUID. SUID and bronchiolitis both occurred more frequently in winter. An increase in bronchiolitis clinical visits occurred within a few days prior to apnea visits. We found a temporal relationship between infant bronchiolitis and apnea. In contrast, no peak in SUID cases was seen during peaks of bronchiolitis. Among those without any bronchiolitis visits, maternal smoking was associated with an increased risk of SUID: Hazard Ratio (HR) of 2.38 (95% CI: 2.11, 2.67, p-value <0.001). Maternal asthma was associated with an increased risk of SUID among infants with at least one bronchiolitis visit: HR of 2.40 (95% CI: 1.04, 5.54, p-value = 0.04). Consistent trends between bronchiolitis, apnea, and SUID were not established due to small numbers of SUID cases. However, interaction analysis revealed potential differential associations of bronchiolitis and SUID by maternal smoking, maternal asthma status.

Space-time analysis of testicular cancer clusters using residential histories: a case-control study in Denmark.

Though the etiology is largely unknown, testicular cancer incidence has seen recent significant increases in northern Europe and throughout many Western regions. The most common cancer in males under age 40, age period cohort models have posited exposures in the in utero environment or in early childhood as possible causes of increased risk of testicular cancer. Some of these factors may be tied to geography through being associated with behavioral, cultural, sociodemographic or built environment characteristics. If so, this could result in detectable geographic clusters of cases that could lead to hypotheses regarding environmental targets for intervention. Given a latency period between exposure to an environmental carcinogen and testicular cancer diagnosis, mobility histories are beneficial for spatial cluster analyses. Nearest-neighbor based Q-statistics allow for the incorporation of changes in residency in spatial disease cluster detection. Using these methods, a space-time cluster analysis was conducted on a population-wide case-control population selected from the Danish Cancer Registry with mobility histories since 1971 extracted from the Danish Civil Registration System. Cases (N=3297) were diagnosed between 1991 and 2003, and two sets of controls (N=3297 for each set) matched on sex and date of birth were included in the study. We also examined spatial patterns in maternal residential history for those cases and controls born in 1971 or later (N= 589 case-control pairs). Several small clusters were detected when aligning individuals by year prior to diagnosis, age at diagnosis and calendar year of diagnosis. However, the largest of these clusters contained only 2 statistically significant individuals at their center, and were not replicated in SaTScan spatial-only analyses which are less susceptible to multiple testing bias. We found little evidence of local clusters in residential histories of testicular cancer cases in this Danish population.

Reactive versus proactive patterns of inhaled corticosteroid use.

For patients with persistent asthma, inhaled corticosteroids (ICS) are a mainstay of controller therapy. These medications are usually prescribed to be taken daily and have been shown to be associated with decreased asthma morbidity. Adherence to daily treatment is very low in many populations in the United States. The purpose of this study is to evaluate the seasonal use of ICS prescription filling as reactive behavior primarily after an asthma exacerbation in a pediatric population. The study population is a subgroup of the Tennessee Asthma and Bronchiolitis Study. The children in this study were enrolled in Tennessee Medicaid (TennCare). The subjects had asthma and were 6 to 9 years of age during the years 2005 to 2010. Prescription filling was determined using claims data, and asthma exacerbations were defined by use of systemic rescue corticosteroids (RCS). In this cohort of 13,114 children with asthma, ICS and RCS filling were highly seasonal and trended with fall and winter peaks in asthma exacerbations. Prescription refilling was very low, with an average of three ICS fills per child who filled at least one during the study period. Among these children, 54.1% (7,096) had an asthma exacerbation during the study period. Among ICS users, 68.5% (3,441/5,020) had a disease exacerbation. ICS filling occurred overwhelmingly on the same day as RCS fills. The seasonal filling patterns of ICS coincide with asthma exacerbations. ICS adherence is low and inconsistent in this population of children with asthma. Increased adherence to ICS, particularly before the seasonal virus epidemics, could greatly reduce asthma morbidity.