Pilot assessment of omega-3 fatty acids and potassium thiocyanate in sickle cell anemia patients with conditional peak systolic cerebral artery blood velocity.

OBJECTIVE: The purpose of this pilot study was to explore the effect of omega-3 fatty acids and potassium thiocyanate on conditional peak systolic cerebral artery blood velocity in children with sickle cell anemia (SCA). METHODS: Transcranial doppler ultrasonography (TCD) was done on 232 SCA children, and 21 found with conditional peak systolic blood velocity (PSV) of 200-249 cm/s in internal carotid, middle or anterior cerebral arteries. These were randomized to receive omega-3 fatty acids and potassium thiocyanate with standard treatment of SCA (test group, N = 14), or standard treatment only (control group, N = 7). After 3 months of treatment, PSV was measured again. RESULTS: Right middle cerebral artery PSV was significantly reduced in the test relative to the control groups (p = 0.04). PSV returned to normal in 79% of the test versus 43% of the control group; and increased to abnormal in one member of the control group, but none of the test group. CONCLUSIONS: The pilot data suggest that in SCA, omega-3 fatty acids and potassium thiocyanate might reduce conditional blood velocity to normal, or prevent progression to abnormal values. A larger, randomized, clinical trial is required to further address the current gap in management of conditional TCD blood velocity.

Quality of life assessments in a cohort of Mozambican children with sickle cell disease.

INTRODUCTION: sickle cell disease (SCD) has significant pediatric morbidity and mortality in sub-Saharan Africa, where access to therapies such as hydroxyurea and opioids is often limited. Poor disease control and Pain management adversely affects the well-being and mental health of affected children. Questionnaires have been utilized in other regions to report the quality of life (QOL) in children with SCD, but assessments from Africa are lacking. METHODS: children age 2-14 years with SCD presenting for routine outpatient consultations at Hospital Central de Maputo from June-August 2017 were offered participation. After informed consent, the Pediatric QOL Inventory (PedsQL) SCD Module was administered to all caregivers and children > 5 years. Responses were scored from 0-100, with higher scores representing better QOL. RESULTS: a total of 14 children were included, with six (43%), four (29%), two (14%), and two (14%) from the age groups of 2-4, 5-7, 8-12, and 13-14 years, respectively. Mean overall patient QOL was 65.3 and 56.0 in child and caregiver respondents. In patients > 5 years, the difference in mean overall QOL for those on/not on hydroxyurea was 0.6 (66.5-64.9) in child respondents and 15.8 (68.4-52.6) in caregiver respondents. Domains related to worry/emotions and communication scored lower in QOL than Pain-related domains for both patient and caregiver respondents. CONCLUSION: SCD has a negative impact on QOL as reported by this cohort of Mozambican pediatric patients and caregivers, with Pain being less of a concern than emotional and interpersonal issues. A comprehensive, child-focused care approach with robust psychosocial support is needed.

Pain in Children and Adolescents With Sickle Cell Disease: Multidimensional Assessment.

BACKGROUND: Patients with sickle cell disease (SCD) suffer from recurrent painful vaso-occlusive episodes with a significant impact on their quality of life. The aim of this study was to perform a multidimensional assessment of pain in Portuguese children and adolescents with SCD. METHODS: Subjects were children and adolescents and their parents recruited from the outpatient pediatric hematology clinic in a Portuguese Hospital. Pain frequency and a broader multidimensional evaluation was performed using the Pediatric Pain Questionnaire (PedsQL) (that includes Visual Analog Scales, color indicators, qualitative descriptors of pain [open question] and body diagram) and a structured questionnaire (PQ2), that included a term list of the Adolescent Pediatric Pain Tool, among other questions. RESULTS: Included 60 children and adolescents (36 boys and 24 girls) with a mean age of 11±4.0 years (range, 5 to 18). The majority of children (83.1%) reported no present pain and 57.6% reported pain last month, with several degrees of pain intensity. Abdomen, thorax, and limbs were the most frequent localizations. Red was the color most chosen to describe "severe pain," whereas blue and green were more used to describe "no pain." The number of pain descriptors is different using an open-ended question (2.1±1.5) than a given list of terms (15.3±8.1). The most frequent terms used in the open question were "strong/very strong," "hurts a lot," "makes cry," and "horrible." Parents used similar pain descriptors. "Makes cry," "horrible," "tiring," "unbearable," and "uncomfortable" were the most frequent terms chosen in the PQ2. Pain interfered variably with daily activities for most of the patients. CONCLUSION: Pain experienced in SCD has a broad range of intensity levels, localization, and frequency. There are a number of pain descriptors and socio-emotional factors related to the pain experience. A comprehensive multidimensional assessment that includes both child's and parents' perspective seem to be the most adequate strategy to assess pain.

Vaso-occlusive crises and costs of sickle cell disease in patients with commercial, Medicaid, and Medicare insurance - the perspective of private and public payers.

AIM: To characterize vaso-occlusive crises (VOCs) and describe healthcare costs among commercially-insured, Medicaid-insured, and Medicare-insured patients with sickle cell disease (SCD). MATERIALS AND METHODS: The IBM Truven Health MarketScan Commercial (2000-2018), Medicaid Analytic eXtract (2008-2014), and Medicare Research Identifiable Files (2012-2016) databases were used to identify patients with ≥2 SCD diagnoses. Study measures were evaluated during a 12-month follow-up period, stratified by annual number of VOCs (i.e. 0, 1, and ≥2). RESULTS: Among 16,092 commercially-insured patients (mean age = 36.7 years), 35.3% had 1+ VOCs. Mean annual total all-cause healthcare costs were $15,747, $27,194, and $64,555 for patients with 0, 1, and 2+ VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 31.0%, 1 VOC = 53.1%, 2+ VOCs = 65.4%) and SCD-related costs (0 VOC = 56.4%, 1 VOC = 78.4%, 2+ VOCs = 93.9%). Among 18,287 Medicaid-insured patients (mean age = 28.5 years, fee-for-service = 50.2%), 63.9% had 1+ VOCs. Mean annual total all-cause healthcare costs were $16,750, $29,880, and $64,566 for patients with 0, 1, and 2+ VOCs, respectively. Inpatient costs (0 VOC = 37.2%, 1 VOC = 64.3%, 2+ VOCs = 72.9%) and SCD-related costs (0 VOC = 60.9%, 1 VOC = 73.8%, 2+ VOCs = 92.2%) accounted for a significant proportion of total all-cause healthcare costs. Among 15,431 Medicare-insured patients (mean age = 48.2 years), 55.1% had 1+ VOCs. Mean annual total all-cause healthcare costs were $21,877, $29,250, and $58,308 for patients with 0, 1, and ≥2 VOCs, respectively. Total all-cause healthcare costs were mainly driven by inpatient (0 VOC = 47.9%, 1 VOC = 54.9%, 2+ VOCs = 67.5%) and SCD-related costs (0 VOC = 74.9%, 1 VOC = 84.4%, 2+ VOCs = 95.3%). LIMITATIONS: VOCs managed at home were not captured. Analyses were descriptive in an observational setting; thus, no causal relationships can be inferred. CONCLUSIONS: A high proportion of patients experienced VOCs across payers. Furthermore, inpatient and SCD-related costs accounted for a significant proportion of total all-cause healthcare costs, which increased with VOC frequency.

Confined filaments in soft vesicles - the case of sickle red blood cells.

Abnormal shapes of red blood cells (RBC) have been associated with various diseases. Diverse RBC shapes have also been intriguing for membrane biophysics. Here we focus on sickle shaped RBC which form due to abnormal growth of semi-rigid hemoglobin (HbS) fibers confined in RBC. Using the area difference elasticity (ADE) model for RBC and worm-like chain model for the confined HbS fibers, we explore shape deformations at equilibrium using Monte-Carlo simulations. We show that while a single HbS fiber is not rigid enough to produce sickle like deformation, a fiber bundle can do so. We also consider multiple disjoint filaments and find that confinement can generate multipolar RBC shapes and can even promote helical filament conformations which have not been discussed before. We show that the same model, when applied to microtubules confined in phospholipid vesicles, predicts vesicle tubulation. In addition we reproduce the tube collapse transition and tennis racket type vesicle shapes, as reported in experiments. We conclude that with a decrease in the surface area to volume ratio, and membrane rigidity, the vesicles prefer tubulation over sickling. The highlight of this work is several important non-axisymmetric RBC and vesicle shapes, which have never been explored in simulations.

Screening for neuropathic pain in patients with sickle cell disease: is a single assessment scale sufficient?

BACKGROUND: The objectives of this study were to delineate the clinical-epidemiological profile of patients with neuropathic pain (NP) in the groups of SCD patients, from each of the three questionnaires used DN-4, painDETECT - PDQ, LANSS and to compare these three questionnaires in NP evaluation in SCD carriers. This cross-sectional study evaluated 83 patients with symptomatic SCD, aged 14 years or older. Clinical and laboratory data were extracted from the patients' charts and from information obtained from the patients during the interview before the application of the questionnaire. The calculations were performed using the statistical software Epi InfoTM 7. Pearson's correlation coefficient was used to compare the neuropathic pain evaluation scales with the software BioEstat 5.3. RESULTS: The use of two or more questionnaires may increase the suspicion of NP in patients with SCD and, with a confirmed diagnosis, adequate treatments will benefit patients.

ASSESSMENT OF MACULAR VASCULATURE OF CHILDREN WITH SICKLE CELL DISEASE COMPARED TO THAT OF HEALTHY CONTROLS USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: This study aims at describing the macular vascular features of the eyes of pediatric patients with the homozygous form of sickle cell disease (SCD) using optical coherence tomography angiography. METHODS: This is a retrospective case series of eyes of pediatric patients with SCD, race- and age-matched to those of healthy individuals. Using optical coherence tomography angiography images of superficial capillary plexus and deep capillary plexus, the nonflow area, vascular density, and foveal avascular zone were measured. The remodeled microvascular foveal architectures obtained on optical coherence tomography angiography and fluorescein angiography were compared. RESULTS: A total of 19 eyes of patients with SCD and 18 eyes of race-matched healthy controls were examined. The best-corrected visual acuity ranged from 75 to 85 letters in all cases. In the SCD series, 8 eyes displayed signs of retinopathy on funduscopy. The foveal avascular zone was significantly enlarged, the foveal vascular density was 8% lower, and there were more perifoveal vascular alterations in the eyes of patients with SCD compared to those of controls. CONCLUSION: The foveal vascular density was significantly reduced and area of the foveal avascular zone was significantly increased in the eyes of patients with SCD. Consistent architectural changes in the perifoveal capillaries were also observed in the pediatric patients with SCD.

Características socioeconômicas e nutricionais de crianças e adolescentes com anemia falciforme: uma revisão sistemática / Socioeconomic and nutritional characteristics of children and adolescents with sickle cell anemia: a systematic review

RESUMO Objetivo: Descrever as características socioeconômicas e nutricionais de crianças e adolescentes com anemia falciforme. Fonte de dados: Estudo de revisão sistemática da literatura baseado em artigos publicados em revistas científicas. As buscas foram realizadas na base de dados eletrônica da National Library of Medicine, National Institutes of Health- PubMed.Foram realizadas duas buscas de artigos publicados nos últimos 20anos e sem limitação de idioma. Aprimeira partiu do Descritor em Ciências da Saúde "Anemia Falciforme" associado com "Fatores Socioeconômicos"; e a segunda partiu do descritor "Anemia Falciforme" associado com "Antropometria". Asbuscas foram direcionadas para pesquisas realizadas em seres humanos na faixa etária de 0 a 18anos. Síntese dos dados: A seleção final foi composta por 11artigos referentes às características socioeconômicas e 21 referentes às características nutricionais. Asamostras estudadas foram de crianças e adolescentes de ambos os sexos, com idade de 0 a 18anos e com predomínio de populações negras. Famílias de crianças e adolescentes com anemia falciforme eram predominantemente de baixo nível socioeconômico. Ospais apresentaram níveis educacionais inferiores, quando comparados a pais de crianças e adolescentes saudáveis. Asmedidas corporais (peso e estatura) e os indicadores antropométricos de crianças com anemia falciforme foram frequentemente menores, quando comparados com os dos grupos saudáveis ou das populações de referência. Conclusão: Crianças e adolescentes com anemia falciforme apresentam limitações socioeconômicas e piores condições nutricionais, quando comparados às populações de referência. Essas limitações podem implicar pior crescimento e maior ocorrência de possíveis complicações, que podem prejudicar sua qualidade de vida.

ABSTRACT Objective: To describe the socioeconomic and nutritional characteristics of children and adolescents with sickle cell anemia. Data sources: The present study is a systematic literature review based on published scientific articles. The searches were carried out using the electronic database of the National Library of Medicine, National Institutes of Health- PubMed. Two searches of articles published in the last 20years and without limitation of language were carried out. Thefirst one started from the Medical Subject Headings term "Anemia, Sickle Cell" associated with "Socioeconomic Factors"; and the second started from the term "Anemia, Sickle Cell" associated with "Anthropometry". Thesearches were directed to research conducted on humans in the age group from 0 to 18years. Data synthesis: The final selection was composed by 11 articles on socioeconomic characteristics and 21articles on nutritional characteristics. Allstudies included children and adolescents with sickle cells disease (age range 0-18years), both genders, and most of them of black ethnicity. Families of children and adolescents with sickle cell anemia were of predominantly low socioeconomic status. Parents had lower educational levels when compared to parents of healthy children and adolescents. Body measurements (weight and height) and anthropometric indicators of children with sickle cell anemia were often lower when compared to healthy groups or reference populations. Conclusions: Children and adolescents with sickle cell anemia have socioeconomic limitations and worse nutritional conditions, when compared to reference populations. These limitations may lead to worse growth and greater occurrence of possible complications that can impair their quality of life.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD. METHODS: A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments. RESULTS: The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach's α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified. CONCLUSIONS: The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

Predictive Ability of Intermittent Daily Sickle Cell Pain Assessment: The PiSCES Project.

Background: Pain diary assessment in sickle cell disease (SCD) may be expensive and impose a high respondent burden. Objective: To report whether intermittent assessment could substitute for continuous daily pain assessment in SCD. Design: Prospective cohort study. Setting: Academic and community practices in Virginia. Patients. A total of 125 SCD patients age 16 years or older in the Pain in Sickle Cell Epidemiology Study. Measurements. Using pain measures that summarized all diaries as the gold standard, we tested the statistical equivalence of four alternative strategies that summarized diaries only from the week prior or the month prior to study completion; one week per month; or one day per week (random day). Summary measures included percent pain days, percent crisis days (self-defined), mean pain (0-9 Likert scale) on all days, and mean pain on pain days. Equivalence tests included comparisons of means, regression intercepts, and slopes, as well as measurement of R2. Results: Compared with the gold standard, the one-day-per-week and one-week-per-month strategies yielded statistically equivalent means of six summary pain measures, and the week prior and month prior yielded equivalent means as some of the measures. Regression showed statistically equivalent slopes and intercepts to the gold standard using one-day-per-week and one-week-per-month strategies for percent pain days and percent crisis days, but almost no other equivalence. R2 values ranged from 0.64 to 0.989. Conclusions: It is possible to simulate five- to six-month daily assessment of pain in SCD. Either one-day-per-week or one-week-per-month assessment yields an equivalent mean and fair regression equivalence.

Assessment of cerebral blood flow with magnetic resonance imaging in children with sickle cell disease: A quantitative comparison with transcranial Doppler ultrasonography.

Introduction: Transcranial Doppler ultrasonography (TCD) is a clinical tool for stratifying ischemic stroke risk by identifying abnormal elevations in blood flow velocity (BFV) in the middle cerebral artery (MCA). However, TCD is not effective at screening for subtle neurologic injury such as silent cerebral infarcts. To better understand this disparity, we compared TCD measures of BFV with tissue-level cerebral blood flow (CBF) using arterial spin-labeling MRI in children with and without sickle cell disease, and correlated these measurements against clinical hematologic measures of disease severity. Methods: TCD and MRI assessment were performed in 13 pediatric sickle cell disease patients and eight age-matched controls. Using MRI measures of MCA diameter and territory weight, TCD measures of BFV in the MCA [cm/s] were converted into units of CBF [ml min-1100 g-1] for comparison. Results: There was no significant association between TCD measures of BFV in the MCA and corresponding MRI measures of CBF in patients (r = .28, p = .39) or controls (r = .10, p = .81). After conversion from BFV into units of CBF, a strong association was observed between TCD and MRI measures (r = .67, p = .017 in patients, r = .86, p = .006 in controls). While BFV in the MCA showed a lack of correlation with arterial oxygen content, an inverse association was observed for CBF measurements. Conclusions: This study demonstrates that BFV in the MCA cannot be used as a surrogate marker for tissue-level CBF in children with sickle cell disease. Therefore, TCD alone may not be sufficient for understanding and predicting subtle pathophysiology in this population, highlighting the potential clinical value of tissue-level CBF.

Magnetic Resonance Imaging Assessment of Kidney Oxygenation and Perfusion During Sickle Cell Vaso-occlusive Crises.

BACKGROUND: Our understanding of the pathophysiologic processes underlying sickle cell nephropathy remains incomplete. We performed a pilot study to investigate the potential value of magnetic resonance imaging (MRI) for the assessment of kidney oxygenation and detection of potential changes to tissue perfusion and cellular integrity during a vaso-occlusive crisis. STUDY DESIGN: A case-control study. SETTING & PARTICIPANTS: 10 homozygous patients with sickle cell disease (SCD), without kidney disease (based on estimated glomerular filtration rate and albuminuria), underwent renal MRI during a vaso-occlusive crisis episode. The imaging data obtained were compared with those for a second MRI performed at steady state (median, 56 [IQR, 37-72] days after the vaso-occlusive crisis MRI). The control group consisted of 10 apparently healthy individuals. MEASUREMENTS: Deoxyhemoglobin level assessed by R2* value was calculated using the blood oxygen level-dependent technique. The intravoxel incoherent motion diffusion-weighted imaging technique was used to calculate D, D*, and F parameters. RESULTS: Median medullary R2* values on steady-state MRI were significantly higher for patients with SCD than for controls (P=0.01) and did not change significantly during the vaso-occlusive crisis. No significant differences in median cortical R2* values were observed. Both cellular integrity (D) and local perfusion (D* and F) were significantly altered in medullary and cortical areas during vaso-occlusive crises in comparison to steady state in patients with SCD. These parameters did not differ significantly between patients with SCD assessed at steady state and the control group. LIMITATIONS: Small sample size, estimation of glomerular filtration rate according to CKD-EPI creatinine equation without adjustment for race. CONCLUSIONS: Deoxyhemoglobin levels in the medullary area are higher in patients with SCD, during vaso-occlusive crises and at steady state, than in controls. Alterations to the tissue perfusion and cellular integrity of renal parenchyma are a common finding during vaso-occlusive crises that provide additional evidence that a vaso-occlusive crisis may be associated with subclinical kidney injury detectable on MRI.

Managing an invisible disease.

Sickle cell disease is a life-limiting and sometimes life-threatening condition that most healthcare professionals will encounter at some point in their career.

Longitudinal assessment of lung function in children with sickle cell disease.

OBJECTIVES: To prospectively assess longitudinal lung function in children with sickle cell disease (SCD). WORKING HYPOTHESIS: Lung function in SCD children deteriorates with increasing age and the decline is more marked in younger children who have recently suffered ACS episodes. STUDY DESIGN: Two prospective longitudinal studies. PATIENT-SUBJECT SELECTION: Two cohorts of SCD children and age and ethnic matched controls were recruited. Cohort One (47 SCD and 26 controls) had a median age of 8.8 years and follow up of 2 years and Cohort Two (45 SCD and 26 controls) a median age of 10.2 years and follow up of 10 years. METHODOLOGY: Forced expiratory volume in one second (FEV1 ), vital capacity (VC), forced expiratory flow between 25% and 75% of VC (FEF 25-75 ), total lung capacity (TLC) and residual volume (RV) were measured on two occasions. RESULTS: In both groups of SCD children, lung function declined significantly, but in neither control group. ACS episodes were more frequent during the follow up period in Cohort One than Cohort Two (P < 0.0001). The rate of decline was greater in Cohort One than Cohort Two for FEV1 (P = 0.008), VC (P = 0.001), FEF25-75 (P = 0.030), TLC (P = 0.004), and RV (P = 0.043). In Cohort Two restrictive abnormalities were more common at follow up (P = 0.006). CONCLUSIONS: Lung function deteriorated with increasing age in SCD children and the rate of decline was greater in younger children in whom ACS episodes were more common. Pediatr Pulmonol. 2016;51:717-723. © 2015 Wiley Periodicals, Inc.

The Challenges and Opportunities Associated with Sickle Cell Disease Prevention, Education, and Management.

Sickle cell disease (SCD) is a hereditary blood disorder affecting the shape of the red blood cells that block blood vessels leading to organ damage and frequent erratic painful episodes. SCD is a global public health issue affecting millions of people throughout the world. This article explores (a) what SCD is; (b) the physical and psychosocial impacts of the disease;

Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis.

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model.

An analysis of the NIH-supported sickle cell disease research portfolio.

Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease.

Doppler assessment of renal hemodynamic alterations in homozygous sickle cell disease and sickle Beta-thalassemia.

We evaluated the renal vascular indices in children and adolescents with sickle cell disease (SCD) using Doppler ultrasonography. We also assessed the renal hemodynamics alterations in patients with homozygous SCD and sickle beta-thalassemia (sickle ß-thalassemia). We studied 75 patients (age range = 3-20 years; M = 9.95 ± 4.15) with SCD: 42 patients suffering from homozygous SCD and 33 patients diagnosed with sickle ß-thalassemia. Thirty, age- and sex-matched, normal subjects were also included as a control group. Both patients and control groups had Doppler assessment of pulsatility (PI) and resistivity (RI) indices of main renal, segmental, interlobar, and arcuate arteries. Both PIs and RIs were significantly higher in SCD patients, compared with the control group. Among patients, PIs and RIs in the main renal, segmental, interlobar, and arcuate arteries were significantly higher in patients with homozygous SCD as compared with those with sickle ß-thalassemia (p values <0.01, <0.001, <0.001, and <0.001 for PIs and <0.001, <0.001, <0.001, and <0.01 for RIs, respectively). We concluded that renal vascular resistance is raised in children and adolescents with SCD. This is more pronounced in patients with homozygous SCD as compared with those with sickle ß-thalassemia.

Capacity building and stroke risk assessment in Nigerian children with sickle cell anaemia.

BACKGROUND: Transcranial Doppler ultrasonography (TCD) measures blood flow velocities in the large cerebral vessels and thus, detects the risk of stroke. This report describes a capacity building program which enabled the use of TCD for detecting stroke risk and also describes the pattern of non-imaging TCD examinations seen in Nigerian children with sickle cell anaemia (SCA). PROCEDURE: Ten university graduates were trained on the use of TCD in a 5-day capacity building workshop after which, the three best candidates were employed to provide a 5-day a week TCD screening service in Lagos. Data from TCD examination collected between March 2011 and September 2013 were analysed and reported. RESULT: Between March 2011 and September 2013, 2,331 children with SCA aged 2-16 years had TCD studies. TCD's findings were classified as normal (standard risk) in 70.4%, conditional in 19% and abnormal (high risk) in 9.3%. The majority of children (76.9%) in the high risk category were aged 2-8 years. TCD study was inadequate for risk categorisation in 1.3% of the patients. CONCLUSION: Effective capacity building of middle level manpower is feasible and can provide a credible TCD screening service to communities with a high demand and a shortage of trained professionals. The pattern of TCD abnormalities seen in Africa are comparable to those obtained in several previous worldwide reports.