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Ofelia Alvarez,
Scott T Miller,
Winfred C Wang,
Zhaoyu Luo,
M Beth McCarville,
George J Schwartz,
Bruce Thompson,
Thomas Howard, Rathi V Iyer,
Sohail R Rana,
Zora R Rogers,
Sharada A Sarnaik,
Courtney D Thornburg,
Russell E Ware
[show abstract]
[hide abstract]
ABSTRACT: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration.
193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function.
At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P = 0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR.
Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function.
Pediatric Blood & Cancer 01/2012; 59(4):668-74. · 1.89 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Clinical complications of sickle cell anemia begin in infancy. BABY HUG (ClinicalTrials.gov, NCT00006400) was a NHLBI-NICHD supported randomized phase III placebo-controlled trial of hydroxyurea (HU) in infants (recruited at 9-18 months) unselected for clinical severity with sickle cell anemia. This secondary analysis of data from BABY HUG examines the influence of anemia on the incidence of sickle cell related complications, and the impact of hydroxyurea therapy in altering these events by comparing children with lower (<25th percentile) and higher (>75th percentile) hemoglobin concentrations at study entry.
Infants were categorized by: (1) age-adjusted hemoglobin quartiles as determined by higher (Hi) and lower (Lo) hemoglobin concentrations at study entry (9-12 months old: <8.0 and >10.0 gm/dL; 12-18 months old: <8.1 and >9.9 gm/dL) and (2) treatment arm (hydroxyurea or placebo). Four subgroups were created: placebo (PL) LoHb (n = 25), PL HiHb (n = 27), hydroxyurea (HU) LoHb (n = 21), and HU HiHb (n = 18). The primary and secondary endpoints of BABY HUG were analyzed by subgroup.
Infants with lower hemoglobin at baseline were more likely to have a higher incidence of clinical events (acute chest syndrome, pain crisis, fever) as well as higher TCD velocities and lower neuropsychological scores at study exit. Hydroxyurea reduced the incidence of these findings.
Infants with more severe anemia are at risk for increased clinical events that may be prevented by early initiation of hydroxyurea.
Pediatric Blood & Cancer 12/2011; 59(4):675-8. · 1.89 Impact Factor
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Michael R DeBaun,
Sharada A Sarnaik,
Mark J Rodeghier,
Caterina P Minniti,
Thomas H Howard, Rathi V Iyer,
Baba Inusa,
Paul T Telfer,
Melanie Kirby-Allen,
Charles T Quinn, [......],
Corina E Gonzalez,
Suzanne L Saccente,
Karen A Kalinyak,
John J Strouse,
Jason M Fixler,
Mae O Gordon,
J Phillip Miller,
Michael J Noetzel,
Rebecca N Ichord,
James F Casella
[show abstract]
[hide abstract]
ABSTRACT: The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSβ° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.
Blood 11/2011; 119(16):3684-90. · 9.90 Impact Factor
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Russell E Ware,
William H Schultz,
Nancy Yovetich,
Nicole A Mortier,
Ofelia Alvarez,
Lee Hilliard, Rathi V Iyer,
Scott T Miller,
Zora R Rogers,
J Paul Scott,
Myron Waclawiw,
Ronald W Helms
[show abstract]
[hide abstract]
ABSTRACT: Stroke occurs in 5-10% of children with sickle cell anemia (SCA) and has a high (>50%) risk of recurrence without therapy. Chronic monthly erythrocyte transfusions effectively prevent recurrent stroke, but their long-term use is limited by serious side effects, including iron overload. An alternative to transfusion for secondary stroke prevention in SCA is needed, especially one that also improves the management of iron overload.
Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) is an NHLBI-sponsored Phase III multicenter randomized controlled clinical trial for children with SCA, stroke, and iron overload (NCT00122980). The primary goal of SWiTCH is to compare 30 months of alternative therapy (hydroxyurea and phlebotomy) with standard therapy (transfusions and chelation) for the prevention of secondary stroke and reduction of transfusional iron overload.
SWiTCH has several distinctive study features including novel methodological and design components: (1) composite primary endpoint including both stroke recurrence rate and iron burden; (2) non-inferiority design with an "acceptable" increased stroke risk; (3) transfusion goals based on current academic community practices; (4) special oversight for the enrollment and randomization process; (5) overlap treatment period within the alternative treatment arm; (6) masking of the overall trial Principal Investigator to treatment results; (7) inclusive independent stroke adjudication process for all suspected new neurological events; and (8) periodic therapeutic phlebotomy program to alleviate iron overload.
Investigation of alternative treatments in SWiTCH could lead to changes in the management of cerebrovascular disease for selected patients with SCA, stroke, and iron overload.
Pediatric Blood & Cancer 08/2011; 57(6):1011-7. · 1.89 Impact Factor
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Winfred C Wang,
Russell E Ware,
Scott T Miller, Rathi V Iyer,
James F Casella,
Caterina P Minniti,
Sohail Rana,
Courtney D Thornburg,
Zora R Rogers,
Ram V Kalpatthi, [......],
Sharada A Sarnaik,
Thomas H Howard,
Lynn W Wynn,
Abdullah Kutlar,
F Daniel Armstrong,
Beatrice A Files,
Jonathan C Goldsmith,
Myron A Waclawiw,
Xiangke Huang,
Bruce W Thompson
[show abstract]
[hide abstract]
ABSTRACT: Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects.
This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400.
96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m(2), p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia.
On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia.
The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.
The Lancet 05/2011; 377(9778):1663-72. · 38.28 Impact Factor
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Zora R Rogers,
Winfred C Wang,
Zhaoyu Luo, Rathi V Iyer,
Eglal Shalaby-Rana,
Stephen D Dertinger,
Barry L Shulkin,
John H Miller,
Bea Files,
Peter A Lane,
Bruce W Thompson,
Scott T Miller,
Russell E Ware
[show abstract]
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ABSTRACT: We evaluated spleen function in 193 children with sickle cell anemia 8 to 18 months of age by (99m)Tc sulfur-colloid liver-spleen scan and correlated results with clinical and laboratory parameters, including 2 splenic biomarkers: pitted cell counts (PIT) and quantitative Howell-Jolly bodies (HJB) enumerated by flow cytometry. Loss of splenic function began before 12 months of age in 86% of infants in association with lower total or fetal hemoglobin and higher white blood cell or reticulocyte counts, reinforcing the need for early diagnosis and diligent preventive care. PIT and HJB correlated well with each other and liver-spleen scan results. Previously described biomarker threshold values did define patients with abnormal splenic function, but our data suggest that normal spleen function is better predicted by PIT of ≤1.2% or HJB ≤55/10(6) red blood cells and absent function by PIT ≥4.5% or HJB ≥665/10(6). HJB is methodologically advantageous compared with PIT, but both are valid biomarkers of splenic function. This trial was registered at www.clinicaltrials.gov as #NCT00006400.
Blood 01/2011; 117(9):2614-7. · 9.90 Impact Factor
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MS Courtney D. Thornburg MD,
Zora R. Rogers MD,
Michael R. Jeng MD,
Sohail R. Rana MD, Rathi V. Iyer MD,
Lane Faughnan RN, BSN, CCRP,
Leann Hassen MPH,
Jennifer Marshall RN, ADN, CLNC,
Roy P. McDonald MPH,
Winfred C. Wang MD,
Xiangke Huang MD,
Renée C. Rees PhD
[show abstract]
[hide abstract]
ABSTRACT: Background
Subject retention and adherence are essential to maintain the power and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We designed a study to assess adherence with study medication administration and study visits and to evaluate socioeconomic factors (SES) that may influence these measurements of adherence. These data are important for assessing impact of adherence on BABY HUG trial outcome and defining impact of SES on adherence.Methods
Each subject's median study medication (MedAd) and mean visit adherence (VAd) were evaluated. We examined associations of adherence with SES of participating families.ResultsMedAd data were available on 153 of the 191 subjects who started randomized study medication. MedAd was 101.7% of volume prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were available on 185 of the 191 subjects who started randomized study medication. VAd was 97.3%, with 82.2% of subjects having no missed visits. During dose titration, subjects had on average 12.9% higher medication adherence than subjects who were on a stable dose and had less frequent study visits. MedAd and VAd were not significantly associated with SES.Conclusion
Subjects in the BABY HUG trial have had excellent adherence. SES was not associated with adherence, suggesting that SES should not be used as a criterion for enrolment in clinical trials. Additional efforts are needed to maintain medication adherence, particularly when the interval between scheduled visits increases. (ClinicalTrials.gov number, NCT00006400). Pediatr Blood Cancer 2010;54:260–264. © 2009 Wiley-Liss, Inc.
Pediatric Blood & Cancer 01/2010; 54(2):260 - 264. · 1.89 Impact Factor
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Russell E Ware,
Renee C Rees,
Sharada A Sarnaik, Rathi V Iyer,
Ofelia A Alvarez,
James F Casella,
Barry L Shulkin,
Eglal Shalaby-Rana,
C Frederic Strife,
John H Miller,
Peter A Lane,
Winfred C Wang,
Scott T Miller
[show abstract]
[hide abstract]
ABSTRACT: To examine the feasibility and accuracy of glomerular filtration rate (GFR) measurements in infants with sickle cell anemia (SCA).
The NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled trial (BABY HUG) tests the hypothesis that hydroxyurea can prevent chronic organ damage in SCA. GFR elevation is a coprimary endpoint, measured quantitatively by technetium 99m-labeled diethylenetriaminepentaacetic acid (DTPA) plasma clearance and estimated by the Schwartz equation with height and creatinine.
Baseline DTPA GFR measurement was attempted in 191 infants; 176 of 184 completed studies (96%) were interpretable. Average age (mean +/- 1SD) was 13.7 +/- 2.6 months. Average DTPA GFR was 125.2 +/- 34.4 (range 40.2-300.9, normal 91.5 +/- 17.8 mL/min/1.73m(2)), while Schwartz estimates were higher at 184.4 +/- 55.5 mL/min/1.73m(2). DTPA GFR was correlated with Schwartz GFR (r(2) = 0.0658, P = .0012); also with age, weight, height, and kidney volume (all P < .002); but not with hemoglobin, HbF, white blood cell count, reticulocytes, medical events, or splenic function.
Quantitative GFR measurement is feasible but variable among infants with SCA. Schwartz GFR estimates are not highly correlated with quantitative DTPA GFR values. Baseline GFR measurements suggest that renal dysfunction in SCA, evidenced by glomerular hyperfiltration, begins during infancy.
The Journal of pediatrics 10/2009; 156(1):66-70.e1. · 4.02 Impact Factor
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Bruce W Thompson,
Scott T Miller,
Zora R Rogers,
Renee C Rees,
Russell E Ware,
Myron A Waclawiw, Rathi V Iyer,
James F Casella,
Lori Luchtman-Jones,
Sohail Rana,
Courtney D Thornburg,
Ram V Kalpatthi,
Julio C Barredo,
R Clark Brown,
Sharada Sarnaik,
Thomas H Howard,
Lori Luck,
Winfred C Wang
[show abstract]
[hide abstract]
ABSTRACT: Evidence of the laboratory benefits of hydroxyurea and its clinical efficacy in reducing acute vaso-occlusive events in adults and children with sickle cell anemia has accumulated for more than 15 years. A definitive clinical trial showing that hydroxyurea can also prevent organ damage might support widespread use of the drug at an early age. BABY HUG is a randomized, double-blind placebo-controlled trial to test whether treating young children ages 9-17 months at entry with a liquid preparation of hydroxyurea (20 mg/kg/day for 2 years) can decrease organ damage in the kidneys and spleen by at least 50%. Creation of BABY HUG entailed unique challenges and opportunities. Although protection of brain function might be considered a more compelling endpoint, preservation of spleen and renal function has clinical relevance, and significant treatment effects might be discernable within the mandated sample size of 200. Concerns about unanticipated severe toxicity and burdensome testing and monitoring requirements were addressed in part by an internal Feasibility and Safety Pilot Study, the successful completion of which was required prior to enrolling a larger number of children on the protocol. Concerns over recruitment of potentially vulnerable subjects were allayed by inclusion of a research subject advocate, or ombudsman. Finally, maintenance of blinding of research personnel was aided by inclusion of an unblinded primary endpoint person, charged with transmitting endpoint data and monitoring blood work locally for toxicity (ClinicalTrials.gov number, NCT00006400).
Pediatric Blood & Cancer 10/2009; 54(2):250-5. · 1.89 Impact Factor
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Courtney D Thornburg,
Zora R Rogers,
Michael R Jeng,
Sohail R Rana, Rathi V Iyer,
Lane Faughnan,
Leann Hassen,
Jennifer Marshall,
Roy P McDonald,
Winfred C Wang,
Xiangke Huang,
Renée C Rees
[show abstract]
[hide abstract]
ABSTRACT: Subject retention and adherence are essential to maintain the power and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We designed a study to assess adherence with study medication administration and study visits and to evaluate socioeconomic factors (SES) that may influence these measurements of adherence. These data are important for assessing impact of adherence on BABY HUG trial outcome and defining impact of SES on adherence.
Each subject's median study medication (MedAd) and mean visit adherence (VAd) were evaluated. We examined associations of adherence with SES of participating families.
MedAd data were available on 153 of the 191 subjects who started randomized study medication. MedAd was 101.7% of volume prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were available on 185 of the 191 subjects who started randomized study medication. VAd was 97.3%, with 82.2% of subjects having no missed visits. During dose titration, subjects had on average 12.9% higher medication adherence than subjects who were on a stable dose and had less frequent study visits. MedAd and VAd were not significantly associated with SES.
Subjects in the BABY HUG trial have had excellent adherence. SES was not associated with adherence, suggesting that SES should not be used as a criterion for enrolment in clinical trials. Additional efforts are needed to maintain medication adherence, particularly when the interval between scheduled visits increases. (ClinicalTrials.gov number, NCT00006400).
Pediatric Blood & Cancer 10/2009; 54(2):260-4. · 1.89 Impact Factor
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Steven G Pavlakis,
Renée C Rees,
Xiangke Huang,
R Clark Brown,
James F Casella, Rathi V Iyer,
Ram Kalpatthi,
Judy Luden,
Scott T Miller,
Zora R Rogers,
Courtney D Thornburg,
Winfred C Wang,
Robert J Adams
[show abstract]
[hide abstract]
ABSTRACT: Transcranial Doppler ultrasonography (TCD) is used to predict stroke risk in children with sickle cell anemia (SCA), but has not been adequately studied in children under age 2 years.
TCD was performed on infants with SCA enrolled in the BABY HUG trial. Subjects were 7-17 months of age (mean 12.6 months). TCD examinations were successfully performed in 94% of subjects (n = 192).
No patient had an abnormal TCD as defined in the older child (time averaged maximum mean TAMM velocity > or =200 cm/sec) and only four subjects (2%) had velocities in the conditional range (170-199 cm/sec). TCD velocities were inversely related to hemoglobin (Hb) concentration and directly related to increasing age.
Determination of whether the TCD values in this very young cohort of infants with SCA can be used to predict stroke risk later in childhood will require analysis of exit TCD's and long-term follow-up, which is ongoing (ClinicalTrials.gov number, NCT00006400).
Pediatric Blood & Cancer 10/2009; 54(2):256-9. · 1.89 Impact Factor
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Thomas V Adamkiewicz,
Miguel R Abboud,
Carole Paley,
Nancy Olivieri,
Melanie Kirby-Allen,
Elliott Vichinsky,
James F Casella,
Ofelia A Alvarez,
Julio C Barredo,
Margaret T Lee, [......],
Abdullah Kutlar,
Kathleen M McKie,
Virgil McKie,
Nadine Odo,
Beatrice Gee,
Janet L Kwiatkowski,
Gerald M Woods,
Thomas Coates,
Winfred Wang,
Robert J Adams
[show abstract]
[hide abstract]
ABSTRACT: Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% +/- 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% +/- 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% +/- 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% +/- 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.
Blood 08/2009; 114(21):4632-8. · 9.90 Impact Factor
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Sharada A. Sarnaik,
James F. Casella,
Bruce A Barton,
Michele Afif,
Gladstone Airewele,
Brian W. Berman,
Francoise Bernaudin,
Thomas Coates,
Beng Fuh,
Helge Hartung, [......],
Charles T. Quinn,
Rupa Redding-Lallinger,
Melissa M. Rhodes,
Hernan Sabio,
Suzanne Saccente,
Charles Scher,
Paul Telfer,
Alexis A Thompson,
Gerald M Woods,
Michael R. DeBaun
[show abstract]
[hide abstract]
ABSTRACT: Abstract 262 IntroductionThe most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and MethodsIn this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta{degrees} thalassemia and no history of overt strokes or seizure were evaluated. ResultsA total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. [IMG] /small/bld0010900030002.gif" ALT="Figure 1"> Figure. Joint effect of fetal hemoglobin and systolic blood -pressure on odds of silent cerebral infarct in 542 children with hemoglobin SS or S-beta{degrees}-thalassemia between 5 and 15 years of age. ConclusionSBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. DisclosuresNo relevant conflicts of interest to declare.
Blood (ASH Annual Meeting Abstracts). 01/2009; 114(22):262-.
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Thomas V Adamkiewicz,
Sharada Sarnaik,
George R Buchanan, Rathi V Iyer,
Scott T Miller,
Charles H Pegelow,
Zora R Rogers,
Elliott Vichinsky,
John Elliott,
Richard R Facklam,
Katherine L O'Brien,
Benjamin Schwartz,
Chris A Van Beneden,
Michael J Cannon,
James R Eckman,
Harry Keyserling,
Kevin Sullivan,
Wing-Yen Wong,
Winfred C Wang
[show abstract]
[hide abstract]
ABSTRACT: Rates and severity of pneumococcal infections in children with sickle cell disease were examined before licensure of pneumococcal-conjugated vaccine (PVC). Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per 1000 person-years, respectively (>10 and 100 times as frequent as in the general population). Overall, 71% of serotyped isolates (n=80) were PVC serotypes and 71% of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation in children with hemoglobin SS (n=71; more with hypotension) and hemoglobin SC (n=18; more with acute chest syndrome, otitis media) differed. Penicillin nonsusceptibility (38% of isolates) varied between geographic study sites. Penicillin prophylaxis appeared less effective against intermediate and resistant strains. Of all infected children, meningitis developed in 20% and 15% died (hemoglobin SS, n=15 and 11; hemoglobin SC, n=1 each). Factors associated with death included age >4 years (58%), serotype 19F, and not being followed by a hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4% effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with sickle cell disease of all ages may benefit from PVC boosted with polysaccharide vaccination.
Journal of Pediatrics 10/2003; 143(4):438-44. · 4.11 Impact Factor
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Deborah Dean,
Lynne Neumayr,
Dana M Kelly,
Samir K Ballas,
Klara Kleman,
Shanda Robertson, Rathi V Iyer,
Russell E Ware,
Mabel Koshy,
Wayne R Rackoff,
Chuck H Pegelow,
Peter Waldron,
Lennette Benjamin,
Elliott Vichinsky
[show abstract]
[hide abstract]
ABSTRACT: PURPOSE Few studies address the association of Chlamydia pneumoniae infection with pulmonary disease and outcome in patients with underlying pathology such as sickle cell disease (SCD). SCD patients are susceptible to the pulmonary disorder known as acute chest syndrome (ACS), where the etiology remains ill defined. The purpose of this study was to analyze the clinical course and outcome of C. pneumoniae-associated ACS among SCD patients as part of the National Acute Chest Syndrome Study.
This was a longitudinal study of SCD patients presenting with ACS to multiple U.S. medical centers. Two hundred ninety-six SCD patients who developed ACS were tested by PCR for C. pneumoniae and by standard techniques for other respiratory pathogens. These infections were evaluated for association with ACS, clinical course, and complications.
Forty-one (14%) patients with first episodes of ACS were PCR positive for C. pneumoniae. Compared with other infections, C. pneumoniae-infected patients were older, were more likely to present with chest pain, and had higher hemoglobin levels at diagnosis. Both groups had similar rates of respiratory failure and prolonged hospitalization. Of the 89 patients with single-pathogen infections, 27 (30%) were due to C. pneumoniae, 21% to Mycoplasma pneumoniae, 10% to RSV, 4% to Staphylococcus aureus, and 3% to Streptococcus pneumoniae.
C. pneumoniae was the most prevalent pathogen in this study of ACS and was responsible for significant morbidity. Additional research is required to develop effective treatment guidelines for ACS.
Journal of Pediatric Hematology/Oncology 02/2003; 25(1):46-55. · 1.16 Impact Factor
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Gerald M. Woods,
James H. Jorgensen,
Myron A. Waclawiw,
Clarice Reid,
Winfred Wang,
Charles H. Pegelow,
Zora R. Rogers, Rathi V. Iyer,
C. Tate Holbrook,
Thomas R. Kinney,
Elliott Vichinsky,
Michael R. DeBaun,
Neil J. Grossman,
Marilyn D. Thomas,
John M. Falletta
[show abstract]
[hide abstract]
ABSTRACT: Purpose: To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia.
Methods: Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb Sβ° thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents.
Results: Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant.
Conclusions: The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.
Journal of Pediatric Hematology/Oncology 06/1997; 19(4):327-333. · 1.16 Impact Factor
