title: Decreased fetal hemoglobin over time among youth with sickle cell disease on hydroxyurea is associated with higher urgent hospital use.
abstract: Hydroxyurea (HU) induces dose-dependent increased fetal hemoglobin (HbF) for sickle cell disease (SCD). Large deviation from historical personal best (PBest) HbF, a clinic-based version of maximum dose, may identify a subset with suboptimal HU adherence over time.
  
  
  
  Retrospective clinical data from youth ages 10-18 years prescribed HU at two centers were extracted from medical records at three time points: pre-HU initiation, PBest and a recent assessment. Decrease from PBest HbF of 20% or more at recent assessment despite stable dosing was designated as high deviation from PBest. Acute hospital use was compared between 1-year periods, pre-HU and ±6 months for PBest and recent assessment. Groups were compared using descriptive and bivariate nonparametric statistics.
  
  
  
  Seventy-five youth, mean HU duration 5.9 years, met eligibility criteria. Mean ages of HU initiation, PBest and recent assessment were 8.0, 10.9 and 13.9 years, respectively. Despite stable dosing, average HbF of 19.5% at PBest overall declined by 31.8% at recent assessment. PBest HbF declined by 11.7 and 40.1% in two groups, the latter comprised 70.7% of the sample, had lower pre-HU and recent HbF and higher dosing. They experienced more urgent hospital use during the year framing recent assessment than during PBest; these findings were supported by sensitivity analysis.
  
  
  
  Decline from PBest HbF is a novel approach to assess HU effectiveness, is common among youth and may represent suboptimal adherence. Larger prospective studies using additional adherence measures are needed to confirm our approach of tracking HbF deviation over time and to define an appropriate cutoff.
authors: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York. nsg11@columbia.edu.
authors: Nancy S
authors: NS
authors: Green
authors: Division of Pediatric Hematology-Oncology, Department of Pediatrics, Albert Einstein Medical School and Montefiore Hospital, New York, New York.
authors: Deepa
authors: D
authors: Manwani
authors: Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors: Mahvish
authors: M
authors: Qureshi
authors: Division of Pediatric Hematology-Oncology, Department of Pediatrics, Albert Einstein Medical School and Montefiore Hospital, New York, New York.
authors: Karen
authors: K
authors: Ireland
authors: Division of Pediatric Hematology-Oncology, Department of Pediatrics, Albert Einstein Medical School and Montefiore Hospital, New York, New York.
authors: Arpan
authors: A
authors: Sinha
authors: School of Nursing, Columbia University Medical Center, New York, New York.|College of Dental Medicine, CUMC.
authors: Arlene M
authors: AM
authors: Smaldone
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy*; D000986:Antisickling Agents / Q000627:therapeutic use*; D002648:Child; D004636:Emergency Service, Hospital; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use*; D007902:Length of Stay; D008297:Male; D012189:Retrospective Studies
chemical_list: D000986:Antisickling Agents; D005319:Fetal Hemoglobin; D006918:Hydroxyurea
keywords: fetal hemoglobin; hydroxyurea; medication adherence; sickle cell disease