Claims-Based vs Agency-Reported Patient Outcomes Among Home Health Agencies, 2013-2019.

Importance: Given the growth of home health agency (HHA) care, it is important to understand whether quality reporting programs, such as star ratings, are associated with improved patient outcomes. Objective: To assess the immediate and long-term association of the introduction of HHA star ratings with patient-level quality outcomes, comparing claims-based and agency-reported measures. Design, Setting, and Participants: This cross-sectional study used Medicare HHA claims and agency-reported assessments to identify sequential patient episodes (ie, spells) among US adults with traditional Medicare who received HHA care (2013-2019). An interrupted time series (ITS) model was used to measure changes in trends and levels before and after the introduction of star ratings. Statistical analysis was performed from November 2022 to September 2023. Exposure: The exposure was the introduction of HHA star ratings. The postexposure period was set as starting January 1, 2016, to account for the period when both star ratings (quality of patient care and patient satisfaction rating) were publicly reported. Main Outcomes and Measures: The main outcomes included claims-based hospitalization measures (both during the patient spell and 30 days after HHA discharge) and agency-reported functional measures, such as improvement in ambulation, bathing, and bed transferring. There was also a measure to capture timely initiation of care among post-acute care HHA users, defined as HHA care initiated within 2 days of inpatient discharge. Results: This study identified 22 958 847 patient spells to compare annual changes over time; 9 750 689 patient spells were included during the pre-star ratings period from January 1, 2013, to December 31, 2015 (6 067 113 [62.2%] female; 1 100 145 [11.3%] Black, 512 487 [5.3%] Hispanic, 7 845 197 [80.5%] White; 2 656 124 [27.2%] dual eligible; mean [SD] patient spell duration, 70.9 [124.9] days; mean [SD] age, 77.4 [12.0] years); 13 208 158 patient spells were included during the post-star ratings period from January 1, 2016, to December 31, 2019 (8 104 69 [61.4%] female; 1 385 180 [10.5%] Black, 675 536 [5.1%] Hispanic, 10 664 239 [80.7%] White; 3 318 113 [25.1%] dual eligible; mean [SD] patient spell duration, 65.3 [96.2] days; mean [SD] age, 77.7 [11.6] years). Results from the ITS models found that the introduction of star ratings was associated with an acceleration in the mean [SE] hospitalization rate during the spell (0.39% [0.05%] per year) alongside functional improvements in ambulation (2.40% [0.29%] per year), bed transferring (3.95% [0.48%] per year) and bathing (2.34% [0.19%] per year) (P < .001). This occurred alongside a 1.21% (0.12%) per year reduction in timely initiation of care (P < .001). Conclusions and Relevance: This cross-sectional study found an observed improvement in agency-reported functional measures, which contrasted with slower increases in more objective measures such as hospitalization rates and declines in timely initiation of care. These findings suggest a complex picture of HHA quality of care after the introduction of star ratings.

Sex-Based Disparities in Acute Myocardial Infarction Treatment Patterns and Outcomes in Older Adults Hospitalized Across 6 High-Income Countries: An Analysis From the International Health Systems Research Collaborative.

BACKGROUND: Sex differences in acute myocardial infarction treatment and outcomes are well documented, but it is unclear whether differences are consistent across countries. The objective of this study was to investigate the epidemiology, use of interventional procedures, and outcomes for older females and males hospitalized with ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction (NSTEMI) in 6 diverse countries. METHODS: We conducted a serial cross-sectional cohort study of 1 508 205 adults aged ≥66 years hospitalized with STEMI and NSTEMI between 2011 and 2018 in the United States, Canada, England, the Netherlands, Taiwan, and Israel using administrative data. We compared females and males within each country with respect to age-standardized hospitalization rates, rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery within 90 days of hospitalization, and 30-day age- and comorbidity-adjusted mortality. RESULTS: Hospitalization rates for STEMI and NSTEMI decreased between 2011 and 2018 in all countries, although the hospitalization rate ratio (rate in males/rate in females) increased in virtually all countries (eg, US STEMI ratio, 1.58:1 in 2011 and 1.73:1 in 2018; Israel NSTEMI ratio, 1.71:1 in 2011 and 2.11:1 in 2018). Rates of cardiac catheterization, percutaneous coronary intervention, and coronary artery bypass graft surgery were lower for females than males for STEMI in all countries and years (eg, US cardiac catheterization in 2018, 88.6% for females versus 91.5% for males; Israel percutaneous coronary intervention in 2018, 76.7% for females versus 84.8% for males) with similar findings for NSTEMI. Adjusted mortality for STEMI in 2018 was higher for females than males in 5 countries (the United States, Canada, the Netherlands, Israel, and Taiwan) but lower for females than males in 5 countries for NSTEMI. CONCLUSIONS: We observed a larger decline in acute myocardial infarction hospitalizations for females than males between 2011 and 2018. Females were less likely to receive cardiac interventions and had higher mortality after STEMI. Sex disparities seem to transcend borders, raising questions about the underlying causes and remedies.

Diabetes-Focused Health Care Utilization Among Adolescents and Young Adults With Type 1 Diabetes.

OBJECTIVE: To describe the current rates of health services use with various types of providers among adolescents and young adults (AYA) with type 1 diabetes (T1D) and evaluate which patient factors are associated with rates of service use from different provider types. METHODS: Using 2012-16 claims data from a national commercial insurer, we identified 18,927 person-years of AYA with T1D aged 13 to 26 years and evaluated the frequency at which: 1) AYA skipped diabetes care for a year despite being insured; 2) received care from pediatric or non-pediatric generalists or endocrinologists if care was sought; and 3) received annual hemoglobin A1c (HbA1c) testing as recommended for AYA. We used descriptive statistics and multivariable regression to examine patient, insurance, and physician characteristics associated with utilization and quality outcomes. RESULTS: Between ages 13 and 26, the percentage of AYA with: any diabetes-focused visits declined from 95.3% to 90.3%; the mean annual number of diabetes-focused visits, if any, decreased from 3.5 to 3.0; receipt of ≥2 HbA1c tests annually decreased from 82.3% to 60.6%. Endocrinologists were the majority providers of diabetes care across ages, yet the relative proportion of AYA whose diabetes care was endocrinologist-dominated decreased from 67.3% to 52.7% while diabetes care dominated by primary care providers increased from 19.9% to 38.2%. The strongest predictors of diabetes care utilization were younger age and use of diabetes technology (pumps and continuous glucose monitors). CONCLUSIONS: Several provider types are involved in the care of AYA with T1D, though predominate provider type and care quality changes substantially across age in a commercially-insured population.

Steatosis drives monocyte-derived macrophage accumulation in human metabolic dysfunction-associated fatty liver disease.

Background & Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common complication of obesity with a hallmark feature of hepatic steatosis. Recent data from animal models of MAFLD have demonstrated substantial changes in macrophage composition in the fatty liver. In humans, the relationship between liver macrophage heterogeneity and liver steatosis is less clear. Methods: Liver tissue from 21 participants was collected at time of bariatric surgery and analysed using flow cytometry, immunofluorescence, and H&E microscopy. Single-cell RNA sequencing was also conducted on a subset of samples (n = 3). Intrahepatic triglyceride content was assessed via MRI and tissue histology. Mouse models of hepatic steatosis were used to investigate observations made from human liver tissue. Results: We observed variable degrees of liver steatosis with minimal fibrosis in our participants. Single-cell RNA sequencing revealed four macrophage clusters that exist in the human fatty liver encompassing Kupffer cells and monocyte-derived macrophages (MdMs). The genes expressed in these macrophage subsets were similar to those observed in mouse models of MAFLD. Hepatic CD14+ monocyte/macrophage number correlated with the degree of steatosis. Using mouse models of early liver steatosis, we demonstrate that recruitment of MdMs precedes Kupffer cell loss and liver damage. Electron microscopy of isolated macrophages revealed increased lipid accumulation in MdMs, and ex vivo lipid transfer experiments suggested that MdMs may serve a distinct role in lipid uptake during MAFLD. Conclusions: The human liver in MAFLD contains macrophage subsets that align well with those that appear in mouse models of fatty liver disease. Recruited myeloid cells correlate well with the degree of liver steatosis in humans. MdMs appear to participate in lipid uptake during early stages of MALFD. Impact and implications: Metabolic dysfunction associated fatty liver disease (MAFLD) is extremely common; however, the early inflammatory responses that occur in human disease are not well understood. In this study, we investigated macrophage heterogeneity in human livers during early MAFLD and demonstrated that similar shifts in macrophage subsets occur in human disease that are similar to those seen in preclinical models. These findings are important as they establish a translational link between mouse and human models of disease, which is important for the development and testing of new therapeutic approaches for MAFLD.

Variation in care for patients presenting with hip fracture in six high-income countries: A cross-sectional cohort study.

BACKGROUND: Hip fractures are costly and common in older adults, but there is limited understanding of how treatment patterns and outcomes might differ between countries. METHODS: We performed a retrospective serial cross-sectional cohort study of adults aged ≥66 years hospitalized with hip fracture between 2011 and 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. We examined mortality, hip fracture treatment approaches (total hip arthroplasty [THA], hemiarthroplasty [HA], internal fixation [IF], and nonoperative), and health system performance measures, including hospital length of stay (LOS), 30-day readmission rates, and time-to-surgery. RESULTS: The total number of hip fracture admissions between 2011 and 2018 ranged from 23,941 in Israel to 1,219,696 in the US. In 2018, 30-day mortality varied from 3% (16% at 1 year) in Taiwan to 10% (27%) in the Netherlands. With regards to processes of care, the proportion of hip fractures treated with HA (range 23%-45%) and THA (0.2%-10%) differed widely across countries. For example, in 2018, THA was used to treat approximately 9% of patients in England and Israel but less than 1% in Taiwan. Overall, IF was the most common surgery performed in all countries (40%-60% of patients). IF was used in approximately 60% of patients in the US and Israel, but only 40% in England. In 2018, rates of nonoperative management ranged from 5% of patients in Taiwan to nearly 10% in England. Mean hospital LOS in 2018 ranged from 6.4 days (US) to 18.7 days (England). The 30-day readmission rate in 2018 ranged from 8% (in Canada and the Netherlands) to nearly 18% in England. The mean days to surgery in 2018 ranged from 0.5 days (Israel) to 1.6 days (Canada). CONCLUSIONS: We observed substantial between-country variation in mortality, surgical approaches, and health system performance measures. These findings underscore the need for further research to inform evidence-based surgical approaches.

Specialist use among privately insured children with disabilities.

OBJECTIVE: To investigate primary care practice ownership and specialist-use patterns for commercially insured children with disabilities. DATA SOURCES AND STUDY SETTING: A national commercial claims database and the Health Systems and Provider Database from 2012 to 2016 are the data sources for this study. STUDY DESIGN: This cross-sectional, descriptive study examines: (1) the most visited type of pediatric primary care physician and practice (independent or system-owned); (2) pediatric and non-pediatric specialist-use patterns; and (3) how practice ownership relates to specialist-use patterns. DATA COLLECTION/EXTRACTION METHODS: This study identifies 133,749 person-years of commercially insured children with disabilities aged 0-18 years with at least 24 months of continuous insurance coverage by linking a national commercial claims data set with the Health Systems and Provider Database and applying the validated Children with Disabilities Algorithm. PRINCIPAL FINDINGS: Three-quarters (75.9%) of children with disabilities received their pediatric primary care in independent practices. Nearly two thirds (59.6%) used at least one specialist with 45.1% using nonpediatric specialists, 28.8% using pediatric ones, and 17.0% using both. Specialist-use patterns varied by both child age and specialist type. Children with disabilities in independent practices were as likely to see a specialist as those in system-owned ones: 57.1% (95% confidence interval [95% CI] 56.7%-57.4%) versus 57.3% (95% CI 56.6%-58.0%), respectively (p = 0.635). The percent using two or more types of specialists was 46.1% (95% CI 45.4%-46.7%) in independent practices, comparable to that in systems 47.1% (95% CI 46.2%-48.0%) (p = 0.054). However, the mean number of specialist visits was significantly lower in independent practices than in systems-4.0 (95% CI 3.9%-4.0%) versus 4.4 (95% CI 4.3%-4.6%) respectively-reaching statistical significance with p < 0.0001. CONCLUSIONS: Recognizing how privately insured children with disabilities use pediatric primary care from pediatric and nonpediatric primary care specialists through both independent and system-owned practices is important for improving care quality and value.

Differences in Treatment Patterns and Outcomes of Acute Myocardial Infarction for Low- and High-Income Patients in 6 Countries.

Importance: Differences in the organization and financing of health systems may produce more or less equitable outcomes for advantaged vs disadvantaged populations. We compared treatments and outcomes of older high- and low-income patients across 6 countries. Objective: To determine whether treatment patterns and outcomes for patients presenting with acute myocardial infarction differ for low- vs high-income individuals across 6 countries. Design, Setting, and Participants: Serial cross-sectional cohort study of all adults aged 66 years or older hospitalized with acute myocardial infarction from 2013 through 2018 in the US, Canada, England, the Netherlands, Taiwan, and Israel using population-representative administrative data. Exposures: Being in the top and bottom quintile of income within and across countries. Main Outcomes and Measures: Thirty-day and 1-year mortality; secondary outcomes included rates of cardiac catheterization and revascularization, length of stay, and readmission rates. Results: We studied 289 376 patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and 843 046 hospitalized with non-STEMI (NSTEMI). Adjusted 30-day mortality generally was 1 to 3 percentage points lower for high-income patients. For instance, 30-day mortality among patients admitted with STEMI in the Netherlands was 10.2% for those with high income vs 13.1% for those with low income (difference, -2.8 percentage points [95% CI, -4.1 to -1.5]). One-year mortality differences for STEMI were even larger than 30-day mortality, with the highest difference in Israel (16.2% vs 25.3%; difference, -9.1 percentage points [95% CI, -16.7 to -1.6]). In all countries, rates of cardiac catheterization and percutaneous coronary intervention were higher among high- vs low-income populations, with absolute differences ranging from 1 to 6 percentage points (eg, 73.6% vs 67.4%; difference, 6.1 percentage points [95% CI, 1.2 to 11.0] for percutaneous intervention in England for STEMI). Rates of coronary artery bypass graft surgery for patients with STEMI in low- vs high-income strata were similar but for NSTEMI were generally 1 to 2 percentage points higher among high-income patients (eg, 12.5% vs 11.0% in the US; difference, 1.5 percentage points [95% CI, 1.3 to 1.8 ]). Thirty-day readmission rates generally also were 1 to 3 percentage points lower and hospital length of stay generally was 0.2 to 0.5 days shorter for high-income patients. Conclusions and Relevance: High-income individuals had substantially better survival and were more likely to receive lifesaving revascularization and had shorter hospital lengths of stay and fewer readmissions across almost all countries. Our results suggest that income-based disparities were present even in countries with universal health insurance and robust social safety net systems.

Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy.

Tumor-associated macrophages (TAMs) are abundant in pancreatic ductal adenocarcinomas (PDACs). While TAMs are known to proliferate in cancer tissues, the impact of this on macrophage phenotype and disease progression is poorly understood. We showed that in PDAC, proliferation of TAMs could be driven by colony stimulating factor-1 (CSF1) produced by cancer-associated fibroblasts. CSF1 induced high levels of p21 in macrophages, which regulated both TAM proliferation and phenotype. TAMs in human and mouse PDACs with high levels of p21 had more inflammatory and immunosuppressive phenotypes. p21 expression in TAMs was induced by both stromal interaction and/or chemotherapy treatment. Finally, by modeling p21 expression levels in TAMs, we found that p21-driven macrophage immunosuppression in vivo drove tumor progression. Serendipitously, the same p21-driven pathways that drive tumor progression also drove response to CD40 agonist. These data suggest that stromal or therapy-induced regulation of cell cycle machinery can regulate both macrophage-mediated immune suppression and susceptibility to innate immunotherapy.

Association of Medicare Advantage vs Traditional Medicare With 30-Day Mortality Among Patients With Acute Myocardial Infarction.

Importance: Medicare Advantage health plans covered 37% of beneficiaries in 2018, and coverage increased to 48% in 2022. Whether Medicare Advantage plans provide similar care for patients presenting with specific clinical conditions is unknown. Objective: To compare 30-day mortality and treatment for Medicare Advantage and traditional Medicare patients presenting with acute myocardial infarction (MI) from 2009 to 2018. Design, Setting, and Participants: Retrospective cohort study that included 557 309 participants with ST-segment elevation [acute] MI (STEMI) and 1 670 193 with non-ST-segment elevation [acute] MI (NSTEMI) presenting to US hospitals from 2009-2018 (date of final follow up, December 31, 2019). Exposures: Enrollment in Medicare Advantage vs traditional Medicare. Main Outcomes and Measures: The primary outcome was adjusted 30-day mortality. Secondary outcomes included age- and sex-adjusted rates of procedure use (catheterization, revascularization), postdischarge medication prescriptions and adherence, and measures of health system performance (intensive care unit [ICU] admission and 30-day readmissions). Results: The study included a total of 2 227 502 participants, and the mean age in 2018 ranged from 76.9 years (Medicare Advantage STEMI) to 79.3 years (traditional Medicare NSTEMI), with similar proportions of female patients in Medicare Advantage and traditional Medicare (41.4% vs 41.9% for STEMI in 2018). Enrollment in Medicare Advantage vs traditional Medicare was associated with significantly lower adjusted 30-day mortality rates in 2009 (19.1% vs 20.6% for STEMI; difference, -1.5 percentage points [95% CI, -2.2 to -0.7] and 12.0% vs 12.5% for NSTEMI; difference, -0.5 percentage points [95% CI, -0.9% to -0.1%]). By 2018, mortality had declined in all groups, and there were no longer statically significant differences between Medicare Advantage (17.7%) and traditional Medicare (17.8%) for STEMI (difference, 0.0 percentage points [95% CI, -0.7 to 0.6]) or between Medicare Advantage (10.9%) and traditional Medicare (11.1%) for NSTEMI (difference, -0.2 percentage points [95% CI, -0.4 to 0.1]). By 2018, there was no statistically significant difference in standardized 90-day revascularization rates between Medicare Advantage and traditional Medicare. Rates of guideline-recommended medication prescriptions were significantly higher in Medicare Advantage (91.7%) vs traditional Medicare patients (89.0%) who received a statin prescription (difference, 2.7 percentage points [95% CI, 1.2 to 4.2] for 2018 STEMI). Medicare Advantage patients were significantly less likely to be admitted to an ICU than traditional Medicare patients (for 2018 STEMI, 50.3% vs 51.2%; difference, -0.9 percentage points [95% CI, -1.8 to 0.0]) and significantly more likely to be discharged to home rather than to a postacute facility (for 2018 STEMI, 71.5% vs 70.2%; difference, 1.3 percentage points [95% CI, 0.5 to 2.1]). Adjusted 30-day readmission rates were consistently lower in Medicare Advantage than in traditional Medicare (for 2009 STEMI, 13.8% vs 15.2%; difference, -1.3 percentage points [95% CI, -2.0 to -0.6]; and for 2018 STEMI, 11.2% vs 11.9%; difference, 0.6 percentage points [95% CI, -1.5 to 0.0]). Conclusions and Relevance: Among Medicare beneficiaries with acute MI, enrollment in Medicare Advantage, compared with traditional Medicare, was significantly associated with modestly lower rates of 30-day mortality in 2009, and the difference was no longer statistically significant by 2018. These findings, considered with other outcomes, may provide insight into differences in treatment and outcomes by Medicare insurance type.

Variation in revascularisation use and outcomes of patients in hospital with acute myocardial infarction across six high income countries: cross sectional cohort study.

OBJECTIVES: To compare treatment and outcomes for patients admitted to hospital with a primary diagnosis of ST elevation or non-ST elevation myocardial infarction (STEMI or NSTEMI) in six high income countries with very different healthcare delivery systems. DESIGN: Retrospective cross sectional cohort study. SETTING: Patient level administrative data from the United States, Canada (Ontario and Manitoba), England, the Netherlands, Israel, and Taiwan. PARTICIPANTS: Adults aged 66 years and older admitted to hospital with STEMI or NSTEMI between 1 January 2011 and 31 December 2017. OUTCOMES MEASURES: The three categories of outcomes were coronary revascularisation (percutaneous coronary intervention or coronary artery bypass graft surgery), mortality, and efficiency (hospital length of stay and 30 day readmission). Rates were standardised to the age and sex distribution of the US acute myocardial infarction population in 2017. Outcomes were assessed separately for STEMI and NSTEMI. Performance was evaluated longitudinally (over time) and cross sectionally (between countries). RESULTS: The total number of hospital admissions ranged from 19 043 in Israel to 1 064 099 in the US. Large differences were found between countries for all outcomes. For example, the proportion of patients admitted to hospital with STEMI who received percutaneous coronary intervention in hospital during 2017 ranged from 36.9% (England) to 78.6% (Canada; 71.8% in the US); use of percutaneous coronary intervention for STEMI increased in all countries between 2011 and 2017, with particularly large rises in Israel (48.4-65.9%) and Taiwan (49.4-70.2%). The proportion of patients with NSTEMI who underwent coronary artery bypass graft surgery within 90 days of admission during 2017 was lowest in the Netherlands (3.5%) and highest in the US (11.7%). Death within one year of admission for STEMI in 2017 ranged from 18.9% (Netherlands) to 27.8% (US) and 32.3% (Taiwan). Mean hospital length of stay in 2017 for STEMI was lowest in the Netherlands and the US (5.0 and 5.1 days) and highest in Taiwan (8.5 days); 30 day readmission for STEMI was lowest in Taiwan (11.7%) and the US (12.2%) and highest in England (23.1%). CONCLUSIONS: In an analysis of myocardial infarction in six high income countries, all countries had areas of high performance, but no country excelled in all three domains. Our findings suggest that countries could learn from each other by using international comparisons of patient level nationally representative data.

Development of a Generic Physiologically-Based Pharmacokinetic Model for Lactation and Prediction of Maternal and Infant Exposure to Ondansetron via Breast Milk.

Ondansetron is commonly used in breastfeeding mothers to treat nausea and vomiting. There is limited information in humans regarding safety of ondansetron exposure to nursing infants and no adequate study looking at ondansetron pharmacokinetics during lactation. We developed a generic physiologically-based pharmacokinetic lactation model for small molecule drugs and applied this model to predict ondansetron transfer into breast milk and characterize infant exposure. Drug-specific model inputs were parameterized using data from the literature. Population-specific inputs were derived from a previously conducted systematic literature review of anatomic and physiologic changes in postpartum women. Model predictions were evaluated using ondansetron plasma and breast milk concentration data collected prospectively from 78 women in the Commonly Used Drugs During Lactation and infant Exposure (CUDDLE) study. The final model predicted breast milk and plasma exposures following a single 4 mg dose of intravenous ondansetron in 1,000 simulated women who were 2 days postpartum. Model predictions showed good agreement with observed data. Breast milk median prediction error (MPE) was 18.4% and median absolute prediction error (MAPE) was 53.0%. Plasma MPE was 32.5% and MAPE was 43.2%. The model-predicted daily and relative infant doses were 0.005 mg/kg/day and 3.0%, respectively. This model adequately predicted ondansetron passage into breast milk. The calculated low relative infant dose indicates that mothers receiving ondansetron can safely breastfeed. The model building blocks and population database are open-source and can be adapted to other drugs.

Medication use and spending trends among children with ADHD in Florida's Medicaid program, 1996-2005.

OBJECTIVE: How the introduction of new pharmaceuticals affects spending for treatment of children with attention-deficit hyperactivity disorder (ADHD) is unknown. This study examined trends in use of pharmaceuticals and their costs among children with ADHD from 1996 to 2005. METHODS: This observational study used annual cohorts of children ages three to 17 with ADHD (N=107,486 unique individuals during the study period) from Florida Medicaid claims to examine ten-year trends in the predicted probability for medication use for children with ADHD with and without psychiatric comorbidities as well as mental health spending and its components. Additional outcome measures included average price per day and average number of days filled for medication classes. RESULTS: Overall, the percentage of children with ADHD treated with ADHD drugs increased from 60% to 63%, and the percentage taking antipsychotics more than doubled, from 8% to 18%. In contrast, rates of antidepressant use declined from 21% to 15%, and alpha agonist use was constant, at 15%. Mental health spending increased 61%, with pharmaceutical spending representing the fastest-rising component (up 192%). Stimulant spending increased 157%, mostly because of increases in price per prescription. Antipsychotic spending increased 588% because of increases in both price and quantity (number of days used). By 2005, long-acting ADHD drugs accounted for over 90% of stimulant spending. CONCLUSIONS: Long-acting ADHD drugs have rapidly replaced short-acting stimulant use among children with ADHD. The use of antipsychotics as a second-tier agent in treating ADHD has overtaken traditional agents such as antidepressants or alpha agonists, suggesting a need for research into the efficacy and side effects of second-generation antipsychotics among children with ADHD.