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INTRODUCTION - Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD.
Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries.
© 2015 Wiley Periodicals, Inc.
The completion of the Multicenter Silent Infarct Transfusion Trial demonstrated that children with pre-existing silent cerebral infarct and sickle cell anemia (SCA) who received regular blood transfusion therapy had a 58% relative risk reduction of infarct recurrence when compared to observation. However, the total benefit of blood transfusion therapy, as assessed by the parents, was not measured against the burden of monthly blood transfusion therapy. In this planned ancillary study, we tested the hypothesis that a patient centered outcome, health-related quality of life (HRQL), would be greater in participants randomly assigned to the blood transfusion therapy group than the observation group. A total of 89% (175 of 196) of the randomly allocated participants had evaluable entry and exit HRQL evaluations. The increase in Change in Health, measured as the child's health being better, was significantly greater for the transfusion group than the observation group (difference estimate = -0.54, P ≤ 0.001). This study provides the first evidence that children with SCA who received regular blood transfusion therapy felt better and had better overall HRQL than those who did not receive transfusion therapy.
© 2014 Wiley Periodicals, Inc.
BACKGROUND - Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care.
METHODS - In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct.
RESULTS - A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P=0.04).
CONCLUSIONS - Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.).
BACKGROUND - The HeartWare (HW) (Framingham, MA) and the HeartMate II (HM II) (Thoratec Inc, Pleasanton, CA) continuous-flow left ventricular assist devices (CF-LVADs) are commonly used to bridge patients to transplantation. We hypothesized that there are differences in perioperative blood product (BP) use and chest tube (CT) output between CF-LVAD types.
METHODS - We retrospectively evaluated BP use in 71 patients who were implanted with a CF-LVAD (HM II = 38; HW = 33) by median sternotomy for bridge to transplantation (BTT) indications from 2009 to 2013. Detailed BP use data were collected during the intraoperative and postoperative periods and included packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate.
RESULTS - Preoperative characteristics (age, left ventricular ejection fraction, previous sternotomy, ischemic cause), and risk stratification scores (Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS]) profile, Leitz-Miller score, Kormos score) were comparable between groups (all p > 0.05). Total average intraoperative and postoperative BP use was different between device types: HW = 8.3 ± 13 versus HM II = 12.6 ± 14.0 units (p = 0.002) and HW = 6.1 ± 12.0 units compared with HM II = 13.5 ± 24.1 units (p = 0.022), respectively. Average postoperative CT output for HW (3,231 ± 3,648 mL) and HM II (3,463 ± 3,050) (p < 0.008) were different between device types. Multivariate analysis revealed that a higher preoperative Leitz-Miller score, implantation of an HM II CF-LVAD, previous sternotomy, and a longer duration of cardiopulmonary bypass (CPB) time were independently associated with increased need for BP use, whereas only use of the HM II device and a longer bypass time predicted a greater CT output.
CONCLUSIONS - Compared with HM II, implantation of the HW CF-LVAD was associated with reduced intraoperative and postoperative BP use and decreased CT output. Increased awareness of device-related differences in bleeding and BP use may improve CF-LVAD patient outcomes.
Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Few studies have investigated factors influencing participation rates for minority children with a chronic disease in clinical trials. The Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial provides an opportunity to study the impact of demographic and socio-economic factors on randomization in a clinical trial among Black children. Our primary objective was to characterize the factors associated with successful randomization of children with sickle cell disease (SCD) and silent cerebral infarct (SCI) in the SIT Trial after initial consent.
PROCEDURE - Differences in socio-economic and demographic variables, family history and disease-related variables were determined between eligible participants who were successfully randomized and those who were not randomized following initial consent. Head of household educational level and family income were examined separately for US versus non-US sites.
RESULTS - Of 1,176 children enrolled in the SIT Trial, 1,016 (86%) completed screening. Of 208 (20%) children with qualifying SCI on pre-randomization MRI, 196 (94%) were successfully randomized. There were no differences in socio-economic, demographic, or disease-related variables between children who were or were not randomized. Participants from non-US sites were more likely to be randomized (22% vs. 12%, P = 0.011); although, randomization by country was associated with neither head of household education nor family income.
CONCLUSION - In the SIT Trial, acceptance of random allocation was not associated with socio-economic or demographic factors. Although these factors may represent barriers for some participants, they should not bias investigators caring for children with SCD in their approach to recruitment for clinical trial participation.
© 2014 Wiley Periodicals, Inc.