Patterns of primary and specialty care among children with sickle cell anemia.

BACKGROUND AND OBJECTIVE: National guidelines recommend that children with sickle cell anemia (SCA) be seen regularly by primary care providers (PCPs) as well as hematologists to receive comprehensive, multidisciplinary care. The objective is to characterize the patterns of primary and hematology care for children with SCA in Michigan. METHODS: Using validated claims definitions, children ages 1-17 years with SCA were identified using Michigan Medicaid administrative claims from 2010 to 2018. We calculated the number of outpatient PCP and hematologist visits per person-year, as well as the proportion of children with at least one visit to a PCP, hematologist, or both a PCP and hematologist annually. Negative binomial regression was used to calculate annual rates of visits for each provider type. RESULTS: A total of 875 children contributed 2889 person-years. Of the total 22,570 outpatient visits, 52% were with a PCP and 34% with a hematologist. Annually, 87%-93% of children had a visit with a PCP, and 63%-85% had a visit with a hematologist. Approximately 66% of total person-years had both visit types within a year. The annual rate ranged from 2.3 to 2.5 for hematologist visits and from 3.7 to 4.1 for PCP visits. CONCLUSIONS: Substantial gaps exist in the receipt of annual hematology care. Given that the majority of children with SCA see a PCP annually, strategies to leverage primary care visits experienced by this population may be needed to increase receipt of SCA-specific services.

COVID-19 Immunization Coverage Among People With Sickle Cell Disease.

This cross-sectional study compares the completion of the primary COVID-19 vaccine series in Michigan residents with vs without sickle cell disease and by age group.

Common data model for sickle cell disease surveillance: considerations and implications.

Objective: Population-level data on sickle cell disease (SCD) are sparse in the United States. The Centers for Disease Control and Prevention (CDC) is addressing the need for SCD surveillance through state-level Sickle Cell Data Collection Programs (SCDC). The SCDC developed a pilot common informatics infrastructure to standardize processes across states. Materials and Methods: We describe the process for establishing and maintaining the proposed common informatics infrastructure for a rare disease, starting with a common data model and identify key data elements for public health SCD reporting. Results: The proposed model is constructed to allow pooling of table shells across states for comparison. Core Surveillance Data reports are compiled based on aggregate data provided by states to CDC annually. Discussion and Conclusion: We successfully implemented a pilot SCDC common informatics infrastructure to strengthen our distributed data network and provide a blueprint for similar initiatives in other rare diseases.

Adherence to hydroxyurea and clinical outcomes among children with sickle cell anemia.

OBJECTIVE: Hydroxyurea lowers the incidence of vaso-occlusive pain crises (VOC) and acute chest syndrome (ACS) among children with sickle cell anemia (SCA). Our objective was to assess the relationship between levels of adherence to hydroxyurea and clinical outcomes among children and adolescents with SCA. METHODS: This retrospective cohort study included Medicaid data (2005-2012) from Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. The study population consisted of children 1-17 years old with SCA enrolled in Medicaid for 3 years. Among children that initiated hydroxyurea, the medication possession ratio (MPR) was calculated as the proportion of days covered by hydroxyurea. Six months after initiation of hydroxyurea, clinical outcomes were assessed through the end of the study period: numbers of VOC-related inpatient admissions and emergency department visits, and encounters for ACS. Multivariable Poisson models were used to predict outcomes by MPR quartile adjusting for previous healthcare utilization, state, and age. RESULTS: Hydroxyurea was initiated by 515 children. The median MPR was 0.53 (interquartile range = 0.3-0.8). The annual median number of visits was 0.0 for ACS, 1.3 for VOC-related emergency department, and 1.4 for VOC-related inpatient admissions. For each outcome, the highest quartile of MPR had the lowest predicted count; this difference was significant for ACS visits when compared with the lowest quartile of MPR. CONCLUSION: This study demonstrated a high level of adherence (>75%) was essential to achieve a lower incidence of common negative clinical outcomes. Further, moderate and severe hydroxyurea nonadherence may be more common than previously appreciated among children, emphasizing the importance of developing and testing innovative strategies to increase adherence.

TCD screening and spending among children with sickle cell anemia.

OBJECTIVES: National guidelines recommend that children with sickle cell anemia receive annual transcranial Doppler (TCD) screening to assess stroke risk. Our objectives were to estimate the rate of TCD screening among privately insured children with sickle cell anemia, estimate out-of-pocket spending for TCD screening, and evaluate the association between TCD screening and enrollment in high-deductible health plans (HDHPs). STUDY DESIGN: Cross-sectional. METHODS: Using the 2009-2017 IBM MarketScan Commercial Database, we identified children aged 2 to 15 years who met a validated claims-based definition of sickle cell anemia. We calculated the proportion of children receiving annual TCD screening and out-of-pocket spending per TCD screen. Using logistic regression with generalized estimating equations, we modeled the receipt of annual TCD screening as a function of HDHP enrollment, controlling for demographics and year. RESULTS: The 2519 children in the analysis accounted for 7197 person-years of enrollment; 14% of person-years were from HDHP enrollees. During 2009-2017, the proportion of children receiving TCD screening ranged from 40% to 44%. Median out-of-pocket spending for TCD screening was $20 overall and $65 among HDHP enrollees. Out-of-pocket spending exceeded $100 for 27% of all screens and 42% of screens among HDHP enrollees. HDHP enrollment was not associated with TCD screening (adjusted odds ratio, 0.99; 95% CI, 0.85-1.15). CONCLUSIONS: Among privately insured children with sickle cell anemia, fewer than half received annual TCD screening. Out-of-pocket spending exceeded $100 for 27% of TCD screens. Although HDHP enrollment was not associated with TCD screening, additional studies are needed to assess whether cost sharing might deter this screening.

Changes in Hydroxyurea Use Among Youths Enrolled in Medicaid With Sickle Cell Anemia After 2014 Revision of Clinical Guidelines.

Importance: Youths with sickle cell anemia (SCA) are at risk of pain crises, stroke, and early death. Complications can be reduced by the oral disease-modifying medication hydroxyurea, and in 2014, the National Heart, Lung, and Blood Institute published revised guidelines that hydroxyurea should be offered to youths aged 9 months and older with SCA regardless of disease severity. Objective: To describe changes in hydroxyurea use among youths with SCA before and after release of the National Heart, Lung, and Blood Institute guidelines. Design, Setting, and Participants: This cross-sectional study was conducted using administrative data from 2010 to 2018 from Michigan and New York State (NYS) Medicaid programs. The study population included youths aged 1 to 17 years with SCA enrolled in the Michigan or NYS Medicaid programs for at least 1 year (Michigan: 2010-2018; NYS: 2012-2018). Youths with SCA were identified using validated claims-based definitions. Data were analyzed from June to October 2020. Main Outcomes and Measures: The main outcome was hydroxyurea use characterized as mean annual counts of days' supply of filled hydroxyurea prescriptions. Rates of hydroxyurea use over time were assessed using regression models (Michigan: zero-inflated negative binomial; NYS: negative binomial). Models included indicators for periods before and after guideline release. Results: A total of 4302 youths with SCA (2236 males [52.0%]; 2676 born 2005-2017 [62.2%]; 150 Hispanic [3.5%], 2929 non-Hispanic Black [68.0%], and 389 non-Hispanic White [9.0%]) contributed 12 565 person-years. The mean (SD) annual days' supply of hydroxyurea was 47.2 (93.6) days per youth in Michigan and 97.4 (137.0) days per youth in NYS. In Michigan, there was an increase in the odds of having nonzero days' supply after the guidelines were released (odds ratio, 1.52; 95% CI, 1.07-2.14). In NYS, no change was seen in the mean days' supply of filled hydroxyurea. Conclusions and Relevance: These findings suggest that hydroxyurea was substantially underused among youths with SCA, despite establishment as the primary disease-modifying therapy for SCA, and that there was incomplete clinician or patient uptake of newly released guidelines. Results suggest that expanding use of hydroxyurea may require a multifaceted approach that includes addressing multiple system- and patient-level barriers.

Considerations When Aggregating Data to Measure Performance Across Levels of the Health Care System.

BACKGROUND: Measuring quality at varying levels of the health care system requires attribution, a process of determining the patients and services for which each level is responsible. However, it is important to ensure that attribution approaches are equitable; otherwise, individuals may be assigned differentially based upon social determinants of health. METHODS: First, we used Medicaid claims (2010-2018) from Michigan to assess the proportion of children with sickle cell anemia who had less than 12 months enrollment within a single Medicaid health plan and could therefore not be attributed to a specific health plan. Second, we used the Medicaid Analytic eXtract data (2008-2009) from 26 states to simulate adapting the 30-Day Pediatric All-Condition Readmission measure to the Accountable Care Organization (ACO) level and examined the proportion of readmissions that could not be attributed. RESULTS: For the sickle cell measure, an average of 300 children with sickle cell anemia were enrolled in Michigan Medicaid each year. The proportion of children that could not be attributed to a Medicaid health plan ranged from 12.2% to 89.0% across years. For the readmissions measure, of the 1,051,365 index admissions, 22% were excluded in the ACO-level analysis because of being unable to attribute the patient to a health plan for the 30 days post discharge. CONCLUSIONS: When applying attribution models, it is essential to consider the potential to induce health disparities. Differential attribution may have unintentional consequences that deepen health disparities, particularly when considering incentive programs for health plans to improve the quality of care.

Trends in quality of care among children with sickle cell anemia.

INTRODUCTION: For decades, it has been recommended that children with sickle cell anemia (SCA) receive antibiotic prophylaxis to prevent serious infections and undergo transcranial Doppler (TCD) screening to identify those at highest risk of overt stroke. We assessed recent temporal trends in antibiotic prophylaxis prescription fills and TCD screening among children with SCA using validated quality measures. PROCEDURE: Using validated claims-based definitions, we identified children with SCA who were enrolled in Michigan or New York State (NYS) Medicaid programs (2011-2018). Among recommended age groups, two outcomes were assessed yearly: (a) filling of ≥300 days of antibiotics, and (b) receipt of greater than or equal to one TCD. The proportion of children with each outcome was calculated by state. Temporal trends in each preventive service were assessed using generalized linear models. RESULTS: A total of 1784 children were eligible for antibiotic prophylaxis (Michigan: 384; NYS: 1400), contributing 3322 person-years. Annual rates of filling ≥300 days of antibiotics ranged from 16% to 22% and were similar by state. There was no change in rates of antibiotic filling over time in Michigan (p-value: .10), but there was a decrease in NYS (p-value: .02). A total of 3439 children with SCA were eligible for TCD screening (Michigan: 710; NYS: 2729), contributing 10,012 person-years. Annual rates of TCD screening ranged from 39% to 45%, were similar by state, and did not change over time (p-values >.05). CONCLUSIONS: Most children with SCA do not receive recommended antibiotic prophylaxis and/or TCD screening. New, sustainable, and coordinated interventions across preventive services are urgently needed.

Influenza immunization coverage of children with sickle cell disease.

OBJECTIVES: To assess receipt of annual flu immunization among children living with sickle cell disease (SCD). METHODS: Receipt of flu immunization (2014-2019) by SCD status was assessed among all Michigan children <18 years of age using the statewide immunization registry. Logistic regression was used to estimate the odds of annual flu immunization by SCD status and age. RESULTS: Annual flu immunization coverage was higher among children with SCD (46.9%; n = 751) than without (23.2%; n = 2,012,846). The annual adjusted odds of flu immunization for those with SCD were 2.8 (95% CI: 2.5-3.1) times higher than for those without SCD; there were no significant differences by age among children with SCD. Among those without SCD, adolescents aged 13-17 were 2.2 (95% CI: 2.2-2.2) times less likely to receive annual flu immunization than children 6-35 months. CONCLUSIONS: Children with SCD had higher annual flu immunization rates than those without SCD, but >50% remain unimmunized.

Primary Immunization Series Coverage of Children With Sickle Cell Disease.

INTRODUCTION: Children with sickle cell disease are at increased risk of serious infections, many of which can be prevented by receipt of recommended immunizations. Study objectives were to (1) assess the primary immunization series coverage among children with sickle cell disease and (2) compare the coverage with that of those without sickle cell disease. METHODS: The Michigan Care Improvement Registry was used to obtain primary immunization series doses and sickle cell disease status for all eligible children in Michigan born in 2001-2016 (analysis was conducted in 2019). Completion of series and each individual vaccine were assessed for every child at ages 19 and 35 months. Proportions were stratified by sickle cell disease status and compared using chi-square tests. Logistic regression was used to model the odds of completing the series at each age, as predicted by sickle cell disease status and adjusting for the presence of Medicaid identification number. RESULTS: The proportion of children who completed the immunization series was higher for those with sickle cell disease than for those without sickle cell disease at 19 months (58.5% vs 48.0%) and 35 months (74.7% vs 59.6%) (both p<0.0001). The odds of completing the series were 1.4 times higher at 19 months (95% CI=1.2, 1.6) and 1.7 times higher at 35 months (95% CI=1.5, 2.0) for children with sickle cell disease than for those without, adjusting for the presence of Medicaid identification number. CONCLUSIONS: Although children with sickle cell disease had higher immunization rates than those without sickle cell disease, >40% of children with sickle cell disease did not receive all recommended immunizations by age 19 months. Immunization information systems should be utilized to improve routine immunization coverage of children with sickle cell disease.

Association Between Steroid-Sparing Therapy and the Risk of Perianal Fistulizing Complications Among Young Patients With Crohn Disease.

Importance: Perianal fistulizing complications (PFCs) develop in 15% to 30% of patients with Crohn disease (CD), are difficult to treat, worsen quality of life, increase cost of care, and commonly recur. Evidence-based strategies to prevent PFCs are lacking. Objectives: To investigate the effectiveness of medical therapy for reducing risk of PFCs among young people with CD and to test the hypothesis that steroid-sparing therapy (SST) use would be associated with reduced risk of PFC development. Design, Setting, and Participants: In this comparative effectiveness analysis of commercial administrative claims from January 1, 2001, through June 30, 2016, patients who did or did not initiate SST were matched via propensity score to adjust for all available confounders. Using Optum's Clinformatics Data Mart, a deidentified database of US commercial administrative claims, all patients aged 5 to 24 years with CD (January 1, 2001, through June 30, 2016) were identified. The index date was the CD diagnosis date. Patients with PFCs or SST use at or before CD diagnosis were excluded. The dates of analysis were October 2017 to February 2020. Exposures: The primary exposure of interest was SST initiation, including immunomodulators and/or anti-tumor necrosis factor α (anti-TNFα) medications, initiated before either PFC development or the end of the study period. Main Outcomes and Measures: The primary outcome was PFC development. Propensity score matching was used to balance baseline characteristics. Cox proportional hazards multivariable regression analyses were used to estimate hazard ratios (HRs) with 95% CIs for PFC development. Results: Among 2214 young people with CD without PFCs identified, the mean (SD) age at CD diagnosis was 17.0 (4.5) years, and 1151 (52.0%) were male. Among the cohort, 1242 patients (56.1%) initiated SST before PFC development or the end of 24-month follow-up. After propensity score matching, 972 patients remained in each treatment group. Overall, 384 of 1944 (19.8%) developed PFCs within 2 years of the index date. The use of SST was associated with a 59% decreased risk of PFC development (hazard ratio [HR], 0.41; 95% CI, 0.33-0.52; P < .001) in 2 years compared with no SST use. Among those who developed PFCs, 55% fewer SST users underwent ostomy than SST nonusers. The use of immunomodulators alone, anti-TNFα alone, and combination therapy was associated with 52% (HR, 0.48; 95% CI, 0.37-0.62; P < .001), 47% (HR, 0.53; 95% CI, 0.36-0.78; P = .001), and 83% (HR, 0.17; 95% CI, 0.09-0.30; P < .001) reductions in the risk of 2-year PFC development, respectively, compared with no SST use. Conclusions and Relevance: In this study, PFC development was common among young patients with CD. The use of SST was lower than expected. Compared with no SST, patients who initiated SST were 59% less likely to develop PFCs and fewer underwent ostomy. These results indicate that PFCs may be preventable and emphasize the importance of considering SST for all patients with CD.

The Impact of Sickle Cell Anemia and Mental Health Diagnoses on Healthcare Use and Preventive Care among Children Enrolled in Medicaid, 2005-2012.

OBJECTIVE: To examine mental health diagnoses, healthcare use, and receipt of age-appropriate preventive care, including antibiotic prophylaxis, hydroxyurea therapy, and transcranial Doppler screenings, among children with sickle cell anemia (SCA). STUDY DESIGN: Children aged 1-17 years with SCA from 6 states having 3 or more Medicaid claims with a SCA diagnosis within a year (2005-2012) were included. Children with mental health diagnoses were identified with 1 or more mental health encounters. Poisson and logistic regression models with general estimating equations assessed the relationship between mental health diagnoses, healthcare use, and receipt of age-appropriate preventive care. RESULTS: In total, 7963 children with SCA were identified (22 424 person-years); 1593 person-years (7.1%) included 1 or more mental health diagnoses. Children with a mental health diagnosis were more likely to have inpatient admissions (incidence rate ratio [IRR] 1.46, 95% CI 1.36-1.56) and outpatient (IRR 1.27, 95% CI 1.21-1.34), emergency department (IRR 1.39, 95% CI 1.30-1.48), and well-child visits (IRR 1.19, 95% CI 1.11-1.29). Those with a mental health diagnosis were more likely to receive hydroxyurea therapy (odds ration [OR] 1.17, 95% CI 1.03-1.33) and less likely to receive transcranial Doppler screenings (OR 0.79, 95% CI 0.68-0.93). CONCLUSIONS: Children with SCA do not receive adequate age-appropriate preventive care. Further research is necessary to identify key points of coordination between mental health and SCA services throughout the life course. This approach may help to increase receipt of age-appropriate preventive care and decrease reliance on acute care.

Performance of ICD-10-CM diagnosis codes for identifying children with Sickle Cell Anemia.

OBJECTIVE: To develop, test, and validate the performance of ICD-10-CM claims-based case definitions for identifying children with sickle cell anemia (SCA). DATA SOURCES: Medicaid administrative claims (2016) for children <18 years with potential SCA (any D57x diagnosis code) and newborn screening records from Michigan and New York State. STUDY DESIGN: This study is a secondary data analysis. DATA COLLECTION/EXTRACTION METHODS: Using specific SCA-related (D5700, D5701, and D5702) and nonspecific (D571) diagnosis codes, 23 SCA case definitions were applied to Michigan Medicaid claims (2016) to identify children with SCA. Measures of performance (sensitivity, specificity, area under the ROC curve) were calculated using newborn screening results as the gold standard. A parallel analysis was conducted using New York State Medicaid claims and newborn screening data. PRINCIPAL FINDINGS: In Michigan Medicaid, 1597 children had ≥1 D57x claim; 280 (18 percent) were diagnosed with SCA. Measures of performance varied, with sensitivities from 0.02 to 0.97 and specificities from 0.88 to 1.0. The case definition of ≥1 outpatient visit with a SCA-related or D571 code had the highest area under the ROC curve, with a sensitivity of 95 percent and specificity of 92 percent. The same definition also had the highest performance in New York Medicaid (n = 2454), with a sensitivity of 94 percent and specificity of 86 percent. CONCLUSIONS: Children with SCA can be accurately identified in administrative claims using this straightforward case definition. This methodology can be used to monitor trends and use of health services after transition to ICD-10-CM.

Identifying perianal fistula complications in pediatric patients with Crohn's disease using administrative claims.

BACKGROUND: Although perianal fistulas occur commonly in pediatric Crohn's disease (CD), evaluations of health services have been limited since no validated claims-based methods exist for identifying cases. OBJECTIVE: To develop and validate accurate case definitions for perianal fistulas among pediatric patients with CD from administrative claims. METHODS: Retrospective cohort study in which we developed and tested candidate case definitions for perianal fistula. Patients (age 5-21 years between 2005-2012) with CD enrolled in Michigan Medicaid with healthcare at University of Michigan were identified via claims. Medical records were obtained from all identified patients, whose entire records were abstracted. Medical record evidence for perianal fistula was considered the "gold standard" against which candidate case definitions were compared. The reference case definition of perianal fistula (ICD9 565.1) and candidate case definitions were evaluated. RESULTS: Of 843 patients identified via claims, 274 (33%) met CD criteria for inclusion. The true perianal fistula rate among CD patients was 18% (n = 49). The top-performing candidate case definition identified 15% (n = 42), had sensitivity of 77.6%, specificity of 98.2%, positive predictive value (PPV) 90.5%, negative predictive value (NPV) 95.3%, and area under receiver operator characteristic curve (ROC) of 0.88. In contrast, the reference case definition identified 9% (n = 26), sensitivity 51.0%, specificity 99.6%, PPV 96.2%, NPV 90.3%, and had an area under ROC of 0.75. CONCLUSIONS: We demonstrated that it is feasible to use administrative claims data to accurately identify pediatric patients with perianal fistula complications. Claims-based case definitions were found to be highly accurate through medical record review, providing a high degree of confidence for future studies where chart review is not feasible. These claims-based methods can be applied to claims data in other settings for the evaluation of health services utilization as well as to assess the comparative effectiveness of prevention and treatment strategies.

Incidence, demographic characteristics, and geographic distribution of sickle cell trait and sickle cell anemia births in Michigan, 1997-2014.

BACKGROUND: This study describes the incidence, demographic characteristics, and geographic distribution of sickle cell anemia (SCA) and sickle cell trait births in Michigan. METHODS: Michigan newborn screening records and birth certificates (1997-2014) were used to identify sickle cell trait and SCA births, as well as demographic characteristics and mother's residential address. Incidence was calculated overall and by county. RESULTS: During the study period, there were 592 SCA births and 33,404 sickle cell trait births in Michigan. The majority of SCA (86.3%) and trait (80.2%) cases were among children who were black. Children with SCA were born in 23% of Michigan counties; children with trait were born in 93%. CONCLUSION: Compared to SCA, sickle cell trait births occur at 50-fold greater incidence and have a substantially expanded geographic distribution. Further research is necessary to understand the most appropriate and impactful use of resources to increase the proportion of families and adults that are aware of their sickle cell trait status.

Health outcomes and services in children with sickle cell trait, sickle cell anemia, and normal hemoglobin.

The health effects of sickle cell trait among children are unknown. We compared select health outcomes and health services utilization among children with sickle cell trait, sickle cell anemia (SCA), and normal hemoglobin. Newborn screening records were used to identify children with sickle cell trait and SCA born in Michigan (1997-2014) who were enrolled in Michigan Medicaid for ≥1 year from 2012 to 2014. Each select health outcome (acute otitis media, acute respiratory infections, fever, invasive pneumococcal disease, pneumonia and influenza, renal complications, spleen problems, stroke) was defined as ≥1 claim with a diagnosis code for the respective outcome within a study year. Health services utilization was summarized as counts of emergency department, inpatient, and outpatient encounters. The relationship between hemoglobin status and each health outcome or utilization was assessed by logistic or negative binomial regression with generalized estimating equations. The study population consisted of 18 257 children with sickle cell trait, 368 with SCA, and 74 523 with normal hemoglobin (227 188 total person-years). Compared with those with normal hemoglobin, children with sickle cell trait had lower odds of acute otitis media (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.84-0.91), acute respiratory infections (OR, 0.94; 95% CI, 0.92-0.97), pneumonia and influenza (OR, 0.93; 95% CI, 0.87-0.99), and outpatient visits (incidence rate ratio, 0.95; 95% CI, 0.93-0.97). Children with SCA had higher or nonsignificant odds of all outcomes and types of health services utilization. These results indicate that children with sickle cell trait may not be at additional health risk for these outcomes. However, additional case-control studies may be necessary to identify rare events.

Hydroxyurea Initiation Among Children With Sickle Cell Anemia.

This study assesses characteristics of children with sickle cell anemia associated with hydroxyurea initiation. Medicaid administrative claims from 6 states (2005-2012) were used to identify children with sickle cell anemia enrolled in Medicaid for ≥2 years. Hydroxyurea use was defined as >30 days' supply of filled prescriptions. Children were classified as initiators (no use in year 1; use in year 2) or nonusers (no use in either year). Logistic regression was used to estimate associations between initiation, health care encounters, and demographics. A total of 4435 children were enrolled for 2 years during the study period; 885 (20.0%) initiators and 3080 (69.4%) nonusers. Children had an annual mean of 2.0 sickle cell disease-related inpatient admissions (SD = 2.2), 8.2 sickle cell disease-related outpatient visits (SD = 7.2), and 3.6 emergency department visits (SD = 3.5). The odds of initiating hydroxyurea increased with increasing health care utilization, age, and calendar year (all P values <.05).