A randomized, controlled clinical trial established the efficacy and safety of short-term use of hydroxyurea in adult sickle cell anemia. To examine the risks and benefits of long-term hydroxyurea usage, patients in this trial were followed for 17.5 years during which they could start or stop hydroxyurea. The purpose of this follow-up was to search for adverse outcomes and estimate mortality. For each outcome and for mortality, exact 95% confidence intervals were calculated, or tests were conducted at a 5 0.05 level (P-value <0.05 for statistical significance). Although the death rate in the overall study cohort was high (43.1%; 4.4 per 100 person-years), mortality was reduced in individuals with long-term exposure to hydroxyurea. Survival curves demonstrated a significant reduction in deaths with long-term exposure. Twenty-four percent of deaths were due to pulmonary complications; 87.1% occurred in patients who never took hydroxyurea or took it for <5 years. Stroke, organ dysfunction, infection, and malignancy were similar in all groups. Our results, while no longer the product of a randomized study because of the ethical concerns of withholding an efficacious treatment, suggest that long-term use of hydroxyurea is safe and might decrease mortality. Am. J. Hematol. 85:403-408, 2010. V

Context Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. Objective To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. Design, Setting, and Participants Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level ≤10 mg/dL) aged 19 to 55 years and of African descent (n=149) or community controls (Hb AA and normal hemoglobin level) (n=47). Participants were stratified on age, sex, and education. Main Outcome Measures The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. Results The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, −5.50; 95% confidence interval {CI}, −9.55 to −1.44]; P =.008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, −5.19; 95% CI, −9.24 to −1.13]; P =.01), working memory (90.75 vs 95.25 [mean difference, −4.50; 95% CI, −8.55 to −0.45]; P =.03), processing speed (86.50 vs 97.95 [mean difference, −11.46; 95% CI, −15.51 to −7.40]; P <.001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. Conclusion Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.

Key Points ATLL presents more aggressively in US Afro-Caribbean than Japanese patients and continues to have a poor outcome despite modern therapies. AZT-IFN is a reasonable up-front option for aggressive, nonbulky, leukemic ATLL subtypes, resulting in long PFS after a complete response.

No abstract

The objective of this study is to identify risk factors for meconium aspiration syndrome (MAS) in newborns born through meconium-stained amniotic fluid (MSAF). From May 27, 1994 to June 9, 1997 maternal and neonatal data were prospectively collected on all infants born through MSAF. Development of MAS was the primary outcome. Using bivariate and logistic regression analysis we identified risk factors for MAS. There were 8,967 births during this period: 7.9% (708 of 8,967) were delivered through MSAF. Respiratory symptoms developed in 6.8% (48 of 708) of births. Of these, 50% (24 of 48) were excluded due to the diagnosis of transient tachypnea of the newborn (17), respiratory distress syndrome (4), group B streptococcus pneumonia (1), congenital cytomegalic inclusion disease (1), and supraventricular tachycardia (1). Of the 24 infants with respiratory symptoms consistent with MAS, 45.8% (11 of 24) required ventilatory support, one required extracorporeal-membrane oxygenation. Bivariate analysis identified six risk factors ( p <0.05): Apgar <7 at 1 minute, Apgar <7 at 5 minutes, thick meconium, fetal distress, suction of infant's stomach by delivery room team at <5 minutes of age, and need for resuscitation. Tracheal meconium was very prevalent in our population at 74% of all intubated infants, and was not significantly associated with MAS. Logistic regression analysis identified four independent risk factors. Looking at multiple prediction models, an infant with fetal distress, Apgar <7 at 1 and 5 minutes and thick meconium has a 79.8% probability of developing respiratory symptoms. If these risk factors are not present, there is a 0.8% risk. In our cohort, this group had 16.7% positive predictive value (4 of 24) and 99.6% negative predictive value (657 of 660). In meconium deliveries, infants with thick meconium, fetal distress, and Apgar scores <7 at 1 and 5 minutes are at high risk for development of respiratory symptoms. Infants delivered in the absence of all of these risk factors are at low risk for development of MAS.