Background Sickle cell anaemia (SCA) is associated with significant morbidity from acute complications and organ dysfunction beginning in the first year of life. In the first multicenter randomised double-blinded trial in very young children with SCA, the impact of hydroxyurea (hydroxycarbamide) therapy on organ dysfunction, clinical complications, and laboratory findings, and its toxicity, were examined. Methods Eligible subjects had HbSS or Sβ0thalassaemia, were age 9–18 months at randomisation, and were not selected for clinical severity. Subjects received liquid hydroxyurea, 20 mg/kg/day, or placebo for two years. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional evaluations included: blood counts, HbF, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every two to four weeks. Findings Ninety-six subjects received hydroxyurea and 97 placebo; 86% completed the study. Significant differences were not seen for the primary endpoints, but suggestive benefit was noted in quantitative measures of spleen function. Hydroxyurea significantly decreased pain and dactylitis with trends for decreased acute chest syndrome, hospitalisation and transfusion. Hydroxyurea increased haemoglobin and HbF and decreased WBC count. Toxicity was limited to mild-moderate neutropaenia. Interpretation Although hydroxyurea treatment did not reduce splenic and renal dysfunction assessed by primary endpoint measures, it resulted in major clinical benefit because of diminished acute complications, favorable haematologic results, and a lack of unexpected toxicities. Based on the safety and efficacy data from this trial, hydroxyurea can now be considered for all very young children with SCA.

The purpose of the study was to analyze clinical and/or autopsy findings at the time of death among adults with sickle cell disease (SCD) at Howard University in Washington, DC over a 25-year period. A single physician recorded circumstances of death among 141 adult SCD patients he treated and knew well from 1976 to 2001. These findings were determined by autopsy report and/or clinical assessment. In a subset of 31 patients, autopsy records were reviewed for reports of iron deposition in liver and heart and of organ pathology. One hundred and fourteen (80.9%) of the patients had SS phenotype and 66 (46.8%) were female. The mean ± SD age at death was 36 ± 11 years. Leading circumstances of death included pulmonary hypertension (PHT) (26.2%), sudden death (23.4%), renal failure (22.6%), infection (18.4%), thromboembolism (14.9%), cardiac diagnoses (12.0%), cirrhosis (11.3%), pneumonia or acute chest syndrome (9.9%), bleeding (7.8%), and iron overload (7.0%). When circumstances of deaths that occurred after 1991 (n = 69) were compared to those that occurred in 1991 or earlier (n = 72), PHT (36.2% vs. 16.6%; P < 0.01) was significantly more common in 1992 or later. Significant associations were found between PHT and thromboembolism and between cirrhosis and iron overload. In this proportional mortality study of adults with SCD, PHT was the leading finding at the time of death. Thromboembolism was associated with PHT, and iron overload was associated with cirrhosis. Am. J. Hematol. 81:858-863, 2006. V V C 2006 Wiley-Liss, Inc.

Limited phenotype matching would have prevented all alloantibodies in 53.3 percent of the patients who formed alloantibodies. This protocol requires RBCs that are readily available. Extended phenotype matching would have prevented alloimmunization in 70.8 percent of patients who formed alloantibodies. However, this would require phenotypes that are 22.7 times less prevalent among random blood donors and is therefore impractical for a long-term strategy.

Although nonadherence to prescribed therapies is widespread, it is particularly problematic with highly active antiretroviral therapy for HIV infection. This review of >50 studies in the area of pediatric HIV infection revealed varying methods for assessing antiretroviral adherence with a wide range of estimates of adherence. Correlates of adherence could be grouped as those relating to the medication, the patient, and the caregiver/family, with many conflicting findings and a lack of theory guiding the research. Only 8 studies, mainly small feasibility or pilot investigations, evaluated highly active antiretroviral therapy adherence interventions in pediatric populations. We conclude with specific recommendations for assessment and clinical management of adherence and discuss directions for future research in this area. KeywordsHIV/AIDS; adherence; compliance; interventions; pediatric Adherence to therapy, or the extent to which a patient's behaviors coincide with medical advice mutually negotiated between the health professional and the patient, is a universal HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript challenge with all illnesses and in all age groups. 1 Each year in the United States, 500 000 physicians write 1.8 billion prescriptions involving 55 000 pharmacies. 2 However, many of these prescribed medications are never taken, with rates of nonadherence ranging from 15% to 93%. 3 Among persons with chronic illnesses, nonadherence is especially problematic, occurring in up to 82% of cases. [4][5][6] The effects of nonadherence range from individual disability (eg, unrelieved pain) to global threat (eg, development of treatment-resistant bacteria or viruses). The yearly monetary costs of nonadherence exceed $100 billion. 7Adherence is particularly critical with highly active antiretroviral therapy (HAART) in the treatment of pediatric HIV infection. The data on HAART for pediatric HIV infection, although scarcer than for adults, suggest that medication adherence is a strong predictor of therapeutic impact. 8,9 For example, Wiener et al 10 observed that among children with an HIV-1 RNA viral load (VL) < 10 000, 75% had taken 100% of their medication doses in the previous week, whereas among those with a VL of ≥10 000, only 36% reported taking all of their medication.Despite the benefits of HAART in treating pediatric HIV infection [11][12][13][14][15] and the adverse consequences of nonadherence, adherence is reportedly suboptimal among children. [16][17][18][19][20] It is likely thwarted by multiple barriers 21,22 and complicated because, unlike with many other chronic illnesses, most children who are born with HIV in the United States are ethnic/racial minorities who live in chronic poverty with limited resources and face discrimination, family disruption, substance abuse, and the stressors of life in the inner city. 23 In addition, stigma is greater for HIV/AIDS than other chronic illnesses, which often leads caregivers to conceal the child's diagnosis a...