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Adherence to hydroxyurea and clinical outcomes among children with sickle cell anemia
Authors:Sarah L. Reeves  Kevin J. Dombkowski  Hannah K. Peng  Hanna Phan  Giselle Kolenic  Susan E. Creary  Brian Madden  Lynda D. Lisabeth
Affiliation:1. Department of Pediatrics, Susan B Meister Child Health Evaluation and Research (CHEAR) Center, University of Michigan, Ann Arbor, MI, United 2. States;3. States

College of Pharmacy, University of Michigan, Ann Arbor, MI, United 4. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United 5. Center for Child Health Equity and Outcomes Research, Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH, United 6. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, United 

Abstract:

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.
Keywords:acute care  hydroxyurea  sickle cell disease
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