Biomedical subjects

Winfred C Wang

Publications and source records attributed to Winfred C Wang.

At least 19 recordsLinked to original sources

PubMed2008

Impact of proximity to comprehensive sickle cell center on utilization of healthcare services among children with sickle cell disease.

BACKGROUND: The impact of comprehensive care on utilization of healthcare services by children with sickle cell disease (SCD) has not been fully evaluated. We compared the medical care utilization and mortality in children less than 20 years of age with SCD in four regions in the state of Tennessee with and without a comprehensive sickle cell center (CSCC). METHODS: Rates of hospitalizations, outpatient and emergency department (ED) visits, and deaths were measured in a cohort of children aged <20 years with SCD, enrolled in TennCare, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. The patients were classified into one of four regions based on their residential address on the day of their hospitalization or outpatient visit. RESULTS: The cohort consisted of 1,214 children with 6,393 person-years of follow-up. Fifty-six percent of patients resided in the region with the CSCC. This region had the highest overall rates of hospitalization for all children (P < 0.001), while ED and outpatient visits were higher in other areas. The death rates ranged from 1.8 to 4.3 per 1,000 person-years in the four regions and did not represent statistically significant differences. CONCLUSION: No clear pattern of improved utilization of medical care services were identified in relation to proximity of residence to a CSCC. This cohort was not large enough to detect small differences in death rates. In addition, other outcomes that incorporate quality of life measures may be more sensitive to differences in medical care.

Adolescent↗

PubMed2007

Pseudoscore-based estimation from biased observations.

There are many practical situations where observation of the primary variable Y for individuals in a population is incomplete and depends on some auxiliary variables X that are potentially correlated with Y. We consider parameter estimation for the distribution of Y with the incomplete data, without specifying the underlying association between Y and X. The approach is based on a class of pseudoscore functions using available information of X. We demonstrate the consistency and asymptotic normality of the estimators and study their finite-sample properties in various situations via simulation. The methodology is illustrated by an example involving kindergarten readiness skills in children with sickle cell disease.

Anemia, Sickle Cell↗

PubMed2006

Hemoglobinopathies mimicking Hb S/beta-thalassemia: Hb S/S with alpha-thalassemia and Hb S/Volga.

There are approximately 1200 known natural mutations of the human globin genes. In most clinical laboratories, the diagnosis of hemoglobin disorders is based on blood counts, hemoglobin electrophoresis, or column chromatography, which can identify common variant hemoglobins such as Hb S, C, and E, but are unable to definitively diagnose most other hemoglobin variants and thalassemia mutations. We report two unrelated cases, both thought initially to have Hb S/beta-thalassemia. Subsequent mutational analyses revealed that one is Hb S/S with compound heterozygosity for nondeletional alpha-thalassemia mutations. The other is the first reported case of compound heterozygosity for Hb S and an unstable hemoglobin, Hb Volga. Correct diagnoses of these hereditary disorders are needed for prognosis and proper management and also for genetic counseling. These studies underscore the importance to correlate clinical course with laboratory diagnosis and to make DNA-based diagnostics more widely available for patients with unusual or complicated hemoglobin disorders.

Adolescent↗

PubMed2005

Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study.

The long-term efficacy and toxicity of hydroxyurea for infants are undefined, and its role in preventing organ dysfunction is unknown. Short-term feasibility of hydroxyurea administration, toxicities, hematologic effects, and effect on spleen function in infants with sickle cell anemia (SCA) were reported (Hydroxyurea Safety and Organ Toxicity [HUSOFT] trial). These infants completing 2 years of hydroxyurea therapy (20 mg/kg/d) were offered study extension with dose escalation to 30 mg/kg/d. Patients were monitored with laboratory tests and biannual imaging studies. Hematologic indices were compared with predicted age-specific values and event rates compared with historic rates. All 21 subjects completing the original trial enrolled in the extension study: median age, 3.4 years old (range, 2.6 to 4.4 years); 12 females; 20 with Hb SS, 1 with Hb S/beta0-thalassemia. Seventeen patients completed 4 years of hydroxyurea, and 11 completed 6 years. After 4 years, hydroxyurea was associated with increased hemoglobin concentration, percentage of fetal hemoglobin (Hb F), and mean corpuscular volume (MCV) and decreased reticulocytes, white blood cells (WBCs), and platelets (P < .01). Patients experienced 7.5 acute chest syndrome (ACS) events per 100 person-years, compared with 24.5 events per 100 person-years among historic controls (P = .001). Treated patients had better spleen function than expected and improved growth rates. Infants with SCA tolerate prolonged hydroxyurea therapy with sustained hematologic benefits, fewer ACS events, improved growth, and possibly preserved organ function.

Anemia, Sickle Cell↗

PubMed2005

A case of hemoglobin SC disease with cold agglutinin-induced hemolysis.

Children with sickle cell disease commonly require red blood cell (RBC) transfusion. We report the first case of hemoglobin (Hb) SC disease with development of severe anemia induced by cold agglutinin hemolysis after Mycoplasma infection. Complete blood count (CBC) showed falsely decreased RBC count and hematocrit and falsely elevated MCV and MCHC. Peripheral blood smear showed RBC clumping at room temperature; this disappeared after warming to 37 degrees C. Anti C3b-C3d was present on red cells, and indirect antiglobulin test revealed a circulating cold agglutinin. Furthermore, anti-Mycoplasma pneumoniae IgM antibody was detected in serum. Careful evaluation of CBCs and peripheral blood smears is required in cases of worsening anemia among sickle cell patients and consideration should be given to cold hemagglutinin disease as an etiology.

Adolescent↗

PubMed2005

Medical care utilization and mortality in sickle cell disease: a population-based study.

The purpose of this study was to evaluate the pattern of medical care utilization and mortality in children and adults with sickle cell disease (SCD) in the state of Tennessee. Rates of hospitalization, emergency department visits, and deaths were measured in a cohort of adults and children with SCD enrolled in TennCare, Tennessee's Medicaid managed health care program, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. For children less than 5 years of age, the mortality rate was similar to that of other black Tennessee children (P = 0.71). Among children, the death rate was highest in 10-19 years of age and was 8-fold higher than Tennessee's race- and age-specific rate. Among 20- to 49-year-old patients with SCD, mortality was significantly higher in males than in females (P < 0.001). As compared to the black population without SCD in TennCare, patients with SCD had 7-30 times higher rate of hospitalization and 2-6 times higher rates of emergency department visits (P < 0.001). The death rate in adolescents and young adults with SCD continues to be much higher than population-specific rates. Interventions to prevent morbidity and mortality related to SCD are urgently needed.

Adolescent↗

PubMed2005

Effect of long-term transfusion on growth in children with sickle cell anemia: results of the STOP trial.

OBJECTIVE: To determine whether long-term transfusion improves growth in children with sickle cell anemia. STUDY DESIGN: In the Stroke Prevention Trial for Sickle Cell Anemia Study, patients were randomized to receive long-term transfusion (CTX) or standard care (STC). Transfusions were administered every 3 to 5 weeks, and hemoglobin S levels were maintained at 30% pretransfusion for an average of 2 years. Serial height and weight measurements (obtained every 3 months), body mass index (BMI) values, and growth z-scores were analyzed. RESULTS: Children in the CTX (n=53) and STC (n=41) groups were similar at baseline. After 24 months, the z-scores for height, weight, and BMI of those receiving CTX had improved significantly, whereas no changes occurred in the STC group. Patients in the CTX group approached normal height-for-age and weight-for-age z-scores. Patients from a large historical control group had significantly lower weight and height growth velocities than patients in the CTX group. CONCLUSIONS: Patients in the Stroke Prevention Trial for Sickle Cell Anemia Study who received CTX had improved height and weight and BMI over a 2-year period. Higher hemoglobin levels resulting from transfusion may improve growth by lowering energy expenditure. In addition to the prevention of vasoocclusive events, CTX results in significant improvement in the growth of children with sickle cell disease.

Adolescent↗

PubMed2005

Pyogenic hepatic abscess after percutaneous liver biopsy in a patient with sickle cell disease.

Liver abscess is a rare complication of liver biopsy but has not been reported in a patient with sickle cell disease (SCD) undergoing this procedure. The authors report the case of a child with SCD, on treatment with chronic transfusions and desferrioxamine, who developed a delayed liver abscess after a liver biopsy in which Avitene, a topical hemostatic agent, was used. This is the first description of a liver abscess as a possible complication of liver biopsy in a child with SCD. The presence of a hepatic abscess should be considered in the differential diagnosis of atypical abdominal pain in patients with SCD.

Abdominal Pain↗

PubMed2004

Natural history of moderate aplastic anemia in children.

BACKGROUND: Moderate aplastic anemia (MAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We evaluated the rate of progression to SAA. METHODS: We reviewed the records of 136 children referred for evaluation of bone marrow failure from 1978 to 2002 at St. Jude Children's Research Hospital. MAA was defined by a hypocellular bone marrow (<50%) and 2 or 3 cytopenias (absolute neutrophil count <1,500/mm(3), absolute reticulocyte count <40,000/mm(3), platelet count <100,000/mm(3)) lasting at least 6 weeks. RESULTS: Twenty-four patients met the criteria for MAA. At a median follow-up of 66 months (range, 10-293), 16 patients (67%) progressed to SAA, 5 (21%) had persistent MAA, and 3 (12%) had complete resolution of MAA. No risk factors for progression could be identified. CONCLUSIONS: When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

Adolescent↗

PubMed2003

Brain imaging findings in pediatric patients with sickle cell disease.

PURPOSE: To determine prevalence of imaging abnormalities in the brain of children with sickle cell disease (SCD) and to identify clinical and methodological factors that influence prevalence estimate. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiographic findings for 185 patients with SCD examined at St Jude Children's Research Hospital since 1993 were reviewed. At least two readers independently reviewed images. Standard MR imaging criteria were used to identify lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy. Patients were assigned grades to indicate limited or extensive abnormalities. Standard MR angiographic criteria were used to identify arterial tortuosity (limited vasculopathy) and stenosis or occlusion (extensive vasculopathy). Findings were evaluated as a function of patient clinical status (including stroke) and diagnosis. Recent methods (T1- and T2-weighted MR imaging plus fluid-attenuated inversion recovery [FLAIR] at 3-mm section thickness) were compared with older methods (T1- and T2-weighted MR imaging without FLAIR at 5-mm section thickness). RESULTS: At mean age of 10 years, overall prevalence of infarction, ischemia, or atrophy in patients with SCD was 44% (82 of 185), and prevalence of vasculopathy was 55% (102 of 185), without evidence of a significant referral bias. Twenty-six of 27 patients with clinical stroke had abnormal findings at imaging, but even if patients with stroke were excluded, 35% (56 of 158) had a "silent infarction" (MR imaging-visible injury without clinical stroke), and 49% (78 of 158) had abnormal findings at MR angiography. Patients with clinically severe disease had more abnormalities at MR imaging (P <.001) and MR angiography (P <.004) than did patients with milder disease. Severe vasculopathy was more prevalent in patients with hemoglobin SS than in those with hemoglobin SC (P <.001). Recent imaging methods showed more abnormalities than did older methods (P <.01). With newer methods, 43% (29 of 67) of patients had extensive abnormalities, whereas with older methods, 28% (33 of 116) had extensive abnormalities. CONCLUSION: Prevalence of ischemic brain injury in pediatric patients with SCD is substantially higher than was previously reported, in part because of improvements in imaging methods.

Anemia, Sickle Cell↗

PubMed2003

Prospective brain imaging evaluation of children with sickle cell trait: initial observations.

PURPOSE: To determine whether sickle cell trait (hemoglobin AS) is associated with abnormalities in the brain of asymptomatic children. MATERIALS AND METHODS: Magnetic resonance (MR) imaging and MR angiography were performed prospectively in 26 siblings (eight girls, 18 boys; mean age, 10.5 years) of patients with sickle cell disease. Two neuroradiologists, blinded as to whether a child had hemoglobin AS or AA, reviewed images obtained in siblings. With MR imaging, lacunae, loss of white matter volume, encephalomalacia, or leukoencephalopathy was identified. With MR angiography, arterial stenosis, occlusion, or tortuosity was identified. Images with definite or possible abnormalities were mixed with randomly selected images and were referred to a third neuroradiologist for a completely blinded review. In cases in which all neuroradiologists concurred, a score was assigned that indicated the sibling had an abnormality. MR angiographic findings were assigned a score for tortuosity with a new quantitative scale. RESULTS: Among 26 siblings screened, 21 children had sickle cell trait. Among these 21 children, two had mild abnormalities at MR imaging (sample prevalence rate, 10% [95% CI: 1%, 29%]), and four had arterial tortuosity (sample prevalence rate, 19% [95% CI: 5%, 42%]). When children with sickle cell trait were compared with 31 control subjects without the trait, arterial tortuosity was significantly more common in children with sickle cell trait (P =.014). Among children with sickle cell trait, percentage of hemoglobin S was significantly greater in children who had tortuosity than percentage of hemoglobin S in children who had normal blood vessels at MR angiography (P <.03). CONCLUSION: Findings suggest that greater percentage of hemoglobin S is associated with mild vasculopathy. This vasculopathy may explain some of the excess risk of stroke among African Americans.

Adolescent↗

PubMed2003

Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination.

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.

Anemia, Sickle Cell↗

PubMed2003

Resolution of chronic hepatic sequestration in a patient with homozygous sickle cell disease receiving hydroxyurea.

Hepatic sequestration is an uncommon complication in patients with homozygous sickle cell disease. Although transfusion therapy has been effective for the acute condition, no definitive treatment of chronic hepatic sequestration has been identified. We describe a 17-year-old male patient with hemoglobin SS and chronic hepatic sequestration who was treated with long-term (60 months) hydroxyurea. After 36 months of HU therapy, the patient had both an excellent hematologic response and a resolution of hepatic sequestration, as evidenced by disappearance of clinical hepatomegaly, normalization of liver volume on serial computed tomography scans, as well as decreased sinusoidal dilatation and congestion and red blood cell sickling on liver biopsy. The findings in this case suggest that hydroxyurea may benefit patients who have unusual complications of sickle cell disease, such as chronic erythrocyte sickling in the liver.

Adolescent↗

PubMed2002

Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease.

Children with sickle cell anemia (HbSS) are at high risk for neurologically overt cerebral infarcts associated with stroke and neurologically silent cerebral infarcts correlated with neuropsychometric deficit. We used complete magnetic resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19 years, who were enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) to examine silent infarct prevalence, localization, recurrence, and progression. We report a baseline prevalence of 21.8%, marginally higher than previously reported due to improved imaging technologies. Although we observed no overall sex difference in prevalence, most lesions in girls occurred before age 6, whereas boys remained at risk until age 10. Silent infarcts were significantly smaller and less likely to be found in the frontal or parietal cortex than were infarcts associated with stroke. Children with silent infarct had an increased incidence of new stroke (1.03/100 patient-years) and new or more extensive silent infarct (7.06/100 patient-years) relative to stroke incidence among all children in our cohort (0.54/100 patient-years). Both events were substantially less frequent than the risk of stroke recurrence among children not provided chronic transfusion therapy. Although chronic transfusion is known to decrease occurrence of new silent infarcts and strokes in children with elevated cerebral arterial blood flow velocity, further study is required to determine its risk-benefit ratio in children with silent infarct and normal velocities. Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities.

Adolescent↗

PubMed2002

Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy.

In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF). To identify predictors of the HbF response to hydroxyurea therapy, baseline clinical and laboratory values (age, sex, hemoglobin concentration, %HbF, reticulocytes, white blood cell [WBC], platelets, and serum chemistries), as well as treatment variables (number of toxicities, noncompliance, MTD dose, and MTD blood counts) were analyzed in 53 HUG-KIDS children who achieved MTD. Baseline %HbF values (P =.001), baseline hemoglobin concentration (P =.01), MTD dose (P =.02), and compliance (P =.02) were significantly associated with a higher %HbF at MTD; in contrast, age, sex, number of toxicities, and other baseline hematologic parameters were not. After adjusting for variations in baseline %HbF, the baseline reticulocyte count (P =.05) and baseline WBC count (P =.05) were also significantly associated with a higher %HbF at MTD. Hydroxyurea-induced increases in the hemoglobin concentration and mean corpuscular volume (both higher absolute values at MTD and larger positive changes from baseline values), as well as hydroxyurea-induced decreases in reticulocytes and WBC count, were significantly associated with a higher %HbF at MTD. These data suggest that selected baseline laboratory parameters, a higher MTD dose with attention to compliance, and greater therapy-related changes in blood counts may predict the HbF response to hydroxyurea therapy for children with sickle cell anemia. The HbF response to hydroxyurea is variable and complex, however, and even children with low baseline %HbF values can develop substantial increases in %HbF at MTD.

Anemia, Sickle Cell↗

PubMed2002

Effect of hydroxyurea on growth in children with sickle cell anemia: results of the HUG-KIDS Study.

OBJECTIVES: Although hydroxyurea is effective in treating adults with sickle-cell anemia (SCA), there is concern that it may adversely affect growth in children. We report the growth characteristics of patients in the Phase I-II pediatric hydroxyurea trial (HUG-KIDS) before and during treatment at the maximum tolerated dose for one year. STUDY DESIGN: Children and adolescents with SCA (n = 68), aged 5 to 16 years at baseline, reached the maximum tolerated dose and had serial height, weight, and Tanner stage measurements. Data from the Cooperative Study of Sickle Cell Disease (CSSCD) were used for comparison. Mixed-effects models were used to compare serial measurements as a function of age and group. RESULTS: In girls, there were no significant differences in height or weight among the pretreatment, on-treatment, and CSSCD groups. Compared with the CSSCD group, HUG-KIDS boys were heavier starting at age 9 years, and pretreatment HUG-KIDS boys were taller starting at age 7 years. The Tanner stage transitions took place at appropriate ages. CONCLUSIONS: Hydroxyurea treatment had no adverse effect on height or weight gain or pubertal development in school-aged children with SCA.

Adolescent↗

PubMed2002

Hydroxyurea therapy associated with declining serum levels of magnesium in children with sickle cell anemia.

OBJECTIVE: To obtain quantitative serum levels of total and ionized magnesium (Mg(2+)) in children with homozygous sickle cell anemia (SCA) undergoing therapy with hydroxyurea. STUDY DESIGN: Five children, ages 11 to 14 years with homozygous SCA, were enrolled in a dose-escalating trial of hydroxyurea over an 18-month period. Serum levels of total and ionized magnesium together with ionized K(+), Na(+), and Ca(2+) were measured before hydroxyurea and every 6 months during hydroxyurea therapy. RESULTS: Before treatment, 4 of the 5 patients had low or below-normal serum concentrations of Mg(2+) (normal range, 0.51-0.67 mmol/L). All 5 became Mg(2+)-deficient during hydroxyurea therapy, with no indication of recovery until after 12 to 18 months of drug administration (P <.05). Similar changes were noted for total magnesium concentrations. Mean serum levels of K(+), Na(+), and Ca(2+) remained consistently within normal ranges. CONCLUSIONS: These findings warrant a controlled study of the effects of magnesium supplementation in patients with SCA receiving hydroxyurea. Potentially, such therapy could alleviate or prevent vaso-occlusive crises.

Adolescent↗

PubMed2002

Equation to estimate resting energy expenditure in adolescents with sickle cell anemia.

BACKGROUND: Basal energy requirements are higher in adolescents with sickle cell anemia (SCA) than in healthy control subjects. However, no equation is available to accurately predict their energy needs. OBJECTIVE: Our objective was to develop a clinically useful equation to estimate resting energy expenditure (REE) in adolescents with SCA. DESIGN: REE and other components of total energy expenditure were measured in adolescents with SCA (n = 37) and in control subjects (n = 23) for 24 h in a whole-room indirect calorimeter. Multiple linear regression analysis was used to describe the relations of REE with independent variables such as sex, weight, height, fat-free mass, fat mass, age, and hemoglobin concentration in adolescents with SCA. The Bland-Altman comparison technique was used to compare values predicted by existing equations with measured REE values. RESULTS: Mean (+/-SD) measured REEs were 7746 +/- 974 and 6332 +/- 869 kJ/d in the male and female subjects with SCA, respectively, and these values were 16% higher than those in the healthy control subjects. Standard equations underestimated REE by 12% (P </= 0.001) in adolescents with SCA and overestimated REE by 4% in control subjects (P = 0.01-0.29). Several REE regression equations for SCA were developed. The most parsimonious equation for males was REE (kJ/d) = 5461 + 77.7.weight (kg) - 233.2.hemoglobin (g/dL), or REE (kcal/d) = 1305 + 18.6.weight (kg) - 55.7.hemoglobin (g/dL). For females, the most parsimonious equation was REE (kJ/d) = 4603 + 55.6.weight (kg) - 126.2.hemoglobin (g/dL), or REE (kcal/d) = 1100 + 13.3.weight (kg) - 30.2.hemoglobin (g/dL). CONCLUSION: The new equations have better agreement with the basal metabolic needs of adolescents with SCA than do standard predictive equations.

Adolescent↗