Growth patterns in children with sickle cell anemia during puberty.

BACKGROUND: Previous studies of children with homozygous sickle cell anemia (SCA) show impaired growth and maturation. The correlation of this suboptimal growth with metabolic and hematological factors during puberty is poorly understood. PROCEDURE: We studied a group of pre-adolescent children with SCA (19 males, 14 females) and healthy controls (16 males, 15 females) matched for race, sex, body size, and pubertal development. Height, weight, body mass index (BMI), and body composition changes were longitudinally assessed over a 2-year period and compared between the groups and with Z scores based on US growth charts. These changes were correlated with hemoglobin (Hgb) concentration and with energy expenditure (EE) measured using indirect whole-room calorimetry. RESULTS: Children with SCA progressed through puberty slower than control children. While, after 2 years, pubertal males with SCA were shorter, their annual increases in weight were not different from controls. The mean fat free mass (FFM) increments were significantly less in males and females with SCA than in control children. In males with SCA, growth in height declined over time and was significantly slower than in matched controls (P < 0.05). CONCLUSION: Growth delays were present during puberty in children with SCA. Decreased growth velocity in children with SCA was independently associated with decreased Hgb concentration and increased total EE.

Pneumocystis pneumonia in children receiving chemotherapy.

Pneumocystis pneumonia (PCP) is a serious complication of chemotherapy-induced immunosuppression. Trimethoprim-sulfamethoxazole (TMP-SMZ) given twice daily, 3 days every week is considered the best form of prophylaxis for PCP. We evaluated PCP prophylaxis in all children up to 18 years of age undergoing cancer chemotherapy over a 2-year period. Four children were diagnosed with PCP over 24 months. Two of 12 children on intravenous pentamidine, 1 of 143 on TMP-SMZ and 1 of 36 on dapsone for PCP prophylaxis developed PCP. Intravenous pentamidine may not be as effective as previously considered and should be used with caution.

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.

Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine.

BACKGROUND: We sought to determine the incidence of invasive pneumococcal disease (IPD) among individuals with sickle cell disease (SCD) before and after the introduction of the pneumococcal conjugate vaccine (PCV). METHODS: Individuals with SCD who were enrolled in Tennessee Medicaid from January 1995 through December 2004 were identified using SCD-specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Population-based surveillance data were used to identify individuals with IPD and were linked to patients with SCD in the Tennessee Medicaid database to determine incidence rates of IPD. Clinical data were collected on all subjects with IPD, and antibiotic susceptibility testing and serotyping were performed on all available pneumococcal isolates. RESULTS: We identified 2026 individuals with SCD, who constituted 13,687 person-years of follow-up. During the study period, 37 individuals with SCD developed IPD, and 21 of these patients were aged <5 years. In a comparison of the pre-PCV period (1995-1999) with the post-PCV period (2001-2004), the rate of IPD decreased by 90.8% in children aged <2 years (from 3630 to 335 cases per 100,000 person-years; P<.001) and by 93.4% in children aged <5 years (from 2044 to 134 cases per 100,000 person-years; P<.001). Rates of IPD for patients with SCD who were aged >or=5 years decreased from 161 cases per 100,000 person-years during the pre-PCV period to 99 cases per 100,000 person-years during the post-PCV period (P=.36). CONCLUSION: The rate of IPD among children with SCD who are aged <5 years has decreased markedly since the introduction of routine administration of PCV to young children.

Health care utilization by adult long-term survivors of hematopoietic cell transplant: report from the Bone Marrow Transplant Survivor Study.

The high intensity of therapy and prolonged immune suppression after hematopoietic cell transplantation (HCT) increase the risk of long-term complications and health care needs among survivors. The aim of this study was to evaluate the current status of health care utilization by long-term HCT survivors and to identify factors associated with lack of utilization. A total of 845 individuals who had undergone HCT between 1974 and 1998 at age 21 years or older and survived 2 or more years after HCT participated in the study. Health care utilization was assessed through a mailed questionnaire in three domains: general contact with health care system, general physical examination, and cancer/HCT-related visit. The median age at HCT was 38.2 years, and the median length of follow-up was 6.4 years. Overall, 98% of allogeneic and 94% of autologous HCT survivors reported medical contact 11+ years after HCT. Cancer/HCT-related visits decreased with increasing time from HCT (allogeneic HCT, 98-57%; autologous HCT, 94-63%). The prevalence of general physical examination increased with time (allogeneic HCT, 56-74%; autologous HCT, 72-81%). Primary care physicians provide health care for an increasing number of adult long-term survivors of HCT, emphasizing the need for increased awareness of the long-term follow-up needs of the HCT survivors by the health care providers.

Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy.

Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) is a serious opportunistic infection in children and adolescents with cancer. It was the most common cause of death among children receiving chemotherapy prior to the inclusion of PCP prophylaxis as part of standard care for children with leukemia. The incidence of PCP has decreased significantly since initiation of prophylaxis; however, breakthrough cases continue to occur. Hematologic malignancies, brain tumors necessitating prolonged corticosteroid therapy, hematopoietic stem cell transplantation, prolonged neutropenia, and lymphopenia are the most important risk factors for PCP in children not infected with HIV. Of children with leukemia, 15-20% may develop PCP in the absence of prophylaxis. Infection with P. jiroveci occurs early in life in most individuals. However, clinically apparent disease occurs almost exclusively in immunocompromised persons. Dyspnea, cough, hypoxia, and fever are the most common presenting symptoms of PCP. Chest radiography and high-resolution CT scans of the chest demonstrate a characteristic ground-glass pattern. Induced sputum analysis and bronchoalveolar lavage are the diagnostic procedures of choice. Gomori's methenamine-silver stain, Geimsa or Wright's stain, and monoclonal immunofluorescent antibody stains are most commonly used to make a diagnosis. However, identification of P. jiroveci DNA using polymerase chain reaction assays in bronchoalveolar lavage fluid is more sensitive. Trimethoprim-sulfamethoxazole (TMP-SMZ; cotrimoxazole) is the recommended drug for the treatment of PCP. Patients who are intolerant of TMP-SMZ or who have not responded to treatment after 5-7 days of therapy with TMP-SMZ should be treated with pentamidine. A short course of corticosteroids is recommended for moderate to severe cases of PCP within the first 72 hours after diagnosis. Mutations in the dihydropteroate synthetase gene may confer resistance to TMP-SMZ; however, the clinical relevance of these mutations is not well established. TMP-SMZ is the most commonly used agent for prophylaxis. Myelosuppression is the most important adverse effect of TMP-SMZ and the most frequent cause for choosing alternative prophylactic agents in children undergoing chemotherapy. Alternative agents for chemoprophylaxis include dapsone, aerosolized pentamidine, and atovaquone. Alternative prophylactic agents must be used in patients developing myelosuppression secondary to TMP-SMZ or dapsone.

Defects in postabsorptive plasma homeostasis of fatty acids in sickle cell disease.

BACKGROUND: The chronic hemolytic anemia experienced by sickle cell disease (SCD) patients leads to adverse effects on oxygen transport by the blood and to a decrease in oxygen availability for peripheral tissues. Limited tissue oxygen availability has the potential to modify events of intracellular metabolism and, thus, alter lipid homeostasis. METHODS: The impact of SCD on plasma fatty acid homeostasis was determined in 8 African American SCD patients and in 6 healthy African American control subjects under postabsorptive conditions and during a 3-hour IV infusion of a nutrient solution containing lipid, glucose, and amino acids. RESULTS: SCD patients had higher fasting levels of plasma nonesterified fatty acids (NEFA), triglycerides, and phospholipids than healthy controls. Similarly, SCD patients had higher fasting levels of fatty acids in plasma triglycerides and phospholipids than healthy controls. Infusion of nutrients resulted in equivalent plasma NEFA profiles, total NEFA, and triglycerides in SCD patients and controls. However, the plasma phospholipid concentrations and fatty acid composition of plasma triglycerides and phospholipids were significantly higher in SCD patients; in particular, plasma pools of oleic acid were consistently increased in SCD. Plasma free oleic acid levels were elevated basally, leading to increased oleic acid content in triglycerides and phospholipids both post absorptively and during nutrient infusion. CONCLUSIONS: There is an underlying defect in lipid metabolism associated with SCD best manifested during the fasting state. This abnormality in lipid homeostasis has the potential to alter red blood cell (RBC) membrane fluidity and function in SCD patients.

Health care utilization by adult Hispanic long-term survivors of hematopoietic stem cell transplantation: report from the Bone Marrow Transplant Survivor Study.

BACKGROUND: Long-term hematopoietic cell transplantation (HCT) survivors have a high prevalence of severe and chronic health conditions, placing significant demands on the healthcare system. The objective of the current study was to evaluate and compare the healthcare utilization by adult Hispanic and non-Hispanic white long-term survivors of HCT. METHODS: A mailed questionnaire was used to assess self-reported healthcare utilization in 3 domains: general contact with healthcare system, general physical examination outside cancer center (GPE), and cancer/HCT center visit. Eligible individuals had undergone HCT between 1974 and 1998, at age > or =21 years, and had survived > or =2 years after HCT. RESULTS: The cohort included 681 non-Hispanic white and 137 Hispanic survivors. The median age at HCT was 38.3 years, and the median length of follow-up was 6.6 years. Hispanic survivors had lower family income and education and were more likely to lack health insurance. The prevalence of GPE increased significantly over time among non-Hispanic whites (67% at 2-5 years to 76% at 11+ years) but remained unchanged among Hispanics (66% to 61%). Cancer/HCT center visits declined over time among both Hispanics and non-Hispanic whites, but a higher proportion of Hispanics reported cancer/HCT center visits at 11+ years after HCT (81% vs 54%). CONCLUSIONS: Compared with non-Hispanic whites, Hispanic survivors are less likely to establish contact with primary care providers years after HCT and to continue to receive care at cancer/HCT centers. Future studies of this population are needed to establish the factors responsible for this pattern of healthcare utilization.

Monitoring for cardiovascular disease in survivors of childhood cancer: report from the Cardiovascular Disease Task Force of the Children's Oncology Group.

Curative therapy for childhood cancer has improved significantly in the last 2 decades such that, at present, approximately 80% of all children with cancer are likely to survive > or = 5 years after diagnosis. Prevention, early diagnosis, and treatment of long-term sequelae of therapy have become increasingly more significant as survival rates continue to improve. Cardiovascular disease is a well-recognized cause of increased late morbidity and mortality among survivors of childhood cancer. The Children's Oncology Group Late Effects Committee and Nursing Discipline and Patient Advocacy Committee have recently developed guidelines for follow-up of long-term survivors of pediatric cancer. A multidisciplinary task force critically reviewed the existing literature to evaluate the evidence for the cardiovascular screening recommended by the Children's Oncology Group guidelines. In this review we outline the clinical manifestations of late cardiovascular toxicities, suggest modalities and frequency of monitoring, and address some of the controversial and unresolved issues regarding cardiovascular disease in childhood cancer survivors.

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.

Use of air displacement plethysmography in the determination of percentage of fat mass in african american children.

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate percentage of fat mass (%FM) in African American children. %FM was determined in 21 boys and 13 girls (11.0 +/- 1.4 y, 18.6 +/- 4.2 kg/m(2) [mean +/- SD]) by ADP (using six published densitometric equations) and dual-energy x-ray absorptiometry (DXA). Measures were done within 2 h of one another, in random order. Regardless of equation, %FM(ADP) was significantly correlated with %FM(DXA) (R(2) = 0.67-0.71, all p < 0.001). %FM(ADP) using the equation of Siri (%FM(ADP-Siri) 20.3 +/- 9.0) agreed most closely with %FM(DXA) (20.0 +/- 10.2, difference p = 0.729). Together, surface area artifact and bone mineral content per unit of bone-free fat-free mass accounted for 29% of the variance in the residual between methods. The correlation between %FM(ADP-Siri) and %FM(DXA) was not significant for those <35 kg (n = 10; R(2) = 0.084, p = 0.417). There was a trend toward %FM(ADP-Siri) underestimating %FM(DXA) in girls (-1.46 +/- 3.0%FM; p = 0.103) but not in boys (1.43 +/- 6.4%FM; p = 0.315). Predicted lung volume was 40.1% higher than measured lung volume (p < 0.001). %FM(ADP-Siri) determined using predicted lung volume was 23.5 +/- 8.9, higher than that using measured lung volume (p < 0.001) and higher than %FM(DXA) (p = 0.001). We conclude that in 9- to 14-y-old African American children and provided lung volume is measured, %FM using ADP with Siri's equation approximates that obtained by DXA. Body composition results determined by ADP in children <35 kg should be interpreted with caution.