Prolonged Survival Using Outpatient Palliative Chemotherapy in Two Children With Refractory Acute Myelogenous Leukemia.

BACKGROUND: Therapy options for relapsed/refractory acute myelogenous leukemia (AML) are limited. Palliative chemotherapy options have been explored in adult patients, but little evidence exists in children. OBJECTIVES: Describe the clinical course of 2 pediatric patients with refractory AML who transitioned to outpatient palliative chemotherapy with good disease control and quality of life on these regimens. PATIENTS AND METHODS: Patient 1 was a 2-year-old girl who received a total of 4 cycles of standard chemotherapy with multiple complications and 15% to 20% blasts on marrow subsequent evaluation. An outpatient regimen of decitabine and vorinostat was consequently chosen for her. Patient 2 was a 16-year-old boy with residual disease after induction 1 with arm A with cytarabine, daunorubicin, and etoposide. His induction 2 course was complicated by multiorgan failure secondary to multiple infections including Klebsiella pneumonia and radiographically identified pulmonary fungal disease. On recovery, the marrow showed no disease but after the toxicities of initial therapy, the patient pursued a palliative regimen with azacitidine and lenalidomide. RESULTS: Patient 1 tolerated her regimen for 14 months, requiring weekly blood products and only one hospitalization for a central-line infection. Her blast count then increased precipitously, the disease progressed, and she died comfortably while receiving hospital-based end-of-life care. Patient 2 tolerated 14 months of his regimen. On a surveillance marrow sample, he was found to have 0.02% minimal residual disease. He then elected to pursue marrow transplantation. He maintained remission until his 6-month posttransplant surveillance bone marrow biopsy, which revealed 0.04% minimal residual disease. CONCLUSION: We describe 2 pediatric patients with relapsed/refractory AML who achieved disease control and acceptable quality of life utilizing outpatient palliative chemotherapy for over 12 months. These regimens should be considered in patients who no longer desire cytotoxic chemotherapy or are ineligible for further aggressive approaches.

Sense of mastery and attitude towards illness: Examining longitudinal benefits of a medical specialty camp for youth with sickle cell disease.

Medical specialty camps can play an important role in the positive development of psychosocial outcomes for children and youth with sickle cell disease (SCD). This study examined how sense of mastery and attitude towards illness outcomes changed over 6 months for 100 campers aged 8-16 years with SCD. The outcomes were measured twice before and twice after camp. Latent growth curve modeling was used to analyze data. Results showed no changes in the outcomes for this study population. Implications for future research designs, populations, and outcomes are discussed, as are implications for communications about camp, and policy and practice.

Physical Therapy in Pediatric and Young Adult Patients With Sickle Cell Disease: Assessing Potential Benefits and Barriers.

BACKGROUND: Despite advances in the treatment of sickle cell disease (SCD) in pediatric and young adult patients, pain remains a significant cause of disease-related morbidity. Physical therapy has been shown to be useful for the treatment of pain in young patients with chronic illnesses, however, limited data exists regarding potential benefits of physical therapy in patients with SCD. MATERIALS AND METHODS: We conducted a web-based survey of health care providers and support staff in the New England area to identify potential benefits of and barriers to outpatient physical therapy in this patient population. RESULTS: Nearly 92% of survey participants felt that physical therapy had the potential to be beneficial in pediatric and young adult patients with SCD. A majority of physicians reported having referred patients with SCD for physical therapy. Perceived potential benefits included improved functional mobility, improved chronic pain symptoms, decreased opiate use, improved mood symptoms, improved acute pain symptoms, and improved adherence with medications and clinic visits. Significant perceived barriers identified included lack of transportation, time constraints, patient lack of understanding, and difficulty with insurance coverage. CONCLUSIONS: Health care providers have a positive view of the use of physical therapy in the management of this patient population. Significant barriers exist which need to be addressed.

Cost-effectiveness Analysis of Screening Extremely Low Birth Weight Children for Hepatoblastoma Using Serum Alpha-fetoprotein.

OBJECTIVES: To evaluate the cost-effectiveness of screening children born at extremely low birth weight (ELBW) for hepatoblastoma using serial serum alpha-fetoprotein measurements. STUDY DESIGN: We created a decision tree to evaluate the cost effectiveness of screening children born at ELBW between 3 and 48 months of age compared with current standard of care (no screening). Our model used discounted lifetime costs and monetary benefits in 2018 US dollars, based on estimates in the published literature. The effects of uncertainty in model parameters were also assessed using univariate sensitivity analyses, in which we changed the values for one parameter at a time to assess the effect on the estimated incremental cost-effectiveness ratio. RESULTS: For the estimated 55 699 children born at ELBW in the US each year, this screening is associated with 77.7 additional quality-adjusted life-years (QALYs) at a cost of $8.7 million. This results in an incremental cost-effectiveness ratio of about $112 000/QALY, which is considered cost effective from a US societal perspective. For children diagnosed with hepatoblastoma, our model finds that the screening regimen is associated with a 10.1% increase in survival, a 4.18% increase in expected QALYs, and a $245 184 decrease in expected cost. CONCLUSIONS: Screening ELBW children for hepatoblastoma between 3 and 48 months of age dominates the alternative and is cost effective from a societal perspective.

Newborn Screening for Hemoglobinopathies in Rhode Island, 2017.

BACKGROUND: Newborn screening (NBS) is a national initiative for early identification of serious illnesses, the clinical consequences of which can be reduced by disease-specific early interventions. The Rhode Island Department of Health (RIDOH) has been screening for sickle cell disease (SCD) since 1990. In this work the authors sought to determine the success of NBS and explore aspects of the program that could be improved. METHODS: A convenience sample of PCPs with privileges at Women and Infants Hospital of Rhode Island was surveyed by a Survey Monkey® questionnaire to determine exactly how NBS results were handled in each PCP's office and to gather information on how to improve the process as it currently stands. RESULTS: The process appeared to work efficiently. Recommendations were made to improve the service, examples of which are provided with this paper. DISCUSSION: Although NBS has a national focus, the responsibility of ensuring that babies are screened successfully and that follow-up is complete, rests with individual states. This study revealed that the screening process in Rhode Island for SCD is successful but provided suggestions for improvements. The investigators have followed up with the suggestions.

Expected Sonographic Appearance of the Spleen in Children and Young Adults With Sickle Cell Disease: An Update.

OBJECTIVES: To update the imaging literature regarding spleen appearances in young patients with sickle cell disease (SCD). METHODS: We conducted a retrospective study and included 112 patients age 0 to 21 years with SCD who had at least 1 abdominal sonogram at our institution between 1999 and 2011. Radiologic findings were compared between risk groups by χ(2) analysis. Findings were correlated with other imaging modalities when available. RESULTS: In our cohort, 35.7% of patients had autosplenectomy, and 8.0% had undergone surgical splenectomy. Only 5.0% of individuals age 0 to 5 years had autosplenectomy. In those who had not undergone surgical splenectomy or autosplenectomy, 76.2% had echogenic spleens, heterogeneous-appearing spleens, or both, and patients with the homozygous sickle cell anemia (HbSS) genotype were more likely to have an abnormal spleen echo texture. Patients treated with transfusions had echogenic spleens and had a higher frequency of splenic regeneration nodules. Most patients (80%) with splenomegaly did not require surgical splenectomy after 5.7 years of follow-up. CONCLUSIONS: Twenty years ago, children with HbSS SCD were expected to have autosplenectomy by age 5 years. There have been changes in the radiologic appearance of the spleen in patients with SDC, likely due to improved supportive care and the use of acute and chronic transfusion therapy. We found that autosplenectomy is rare by age 5 years, and during childhood and adolescence, the spleen typically appears echogenic, heterogeneous, or both, depending on disease severity.

Improving the Management of Vaso-Occlusive Episodes in the Pediatric Emergency Department.

OBJECTIVES: Vaso-occlusive episodes (VOEs) account for the majority of emergency department (ED) visits for children with sickle cell disease (SCD). We hypothesized that addressing key barriers to VOE care would improve receipt of analgesics and outcomes. METHODS: A quality improvement (QI) initiative was conducted from September 2010 to April 2014 to streamline VOE care in an urban pediatric ED. Four interventions were used: a standardized time-specific VOE protocol; intranasal fentanyl as the first parenteral pain medication; an SCD pain medication calculator; and provider and patient/family education. Data were collected for 3 outcome measures (mean time from triage to first parenteral opioid and admission/discharge decision, and proportion discharged from the ED); 1 process measure (mean time from triage to initiation of patient-controlled analgesia); and 4 balancing measures (mean time from triage to second intravenous opioid dose, 24-hour ED readmission, respiratory depression, and length of stay). RESULTS: There were 289 ED visits in the study period. Improvements were seen in mean time to: first dose of parenteral opioid (56 to 23 minutes); second opiate intravenous dose (106 to 83 minutes); admission and discharge decisions (163 to 109 minutes and 271 to 178 minutes, respectively); and initiation of patient-controlled analgesia (216 to 141 minutes). The proportion discharged from the ED increased from 32% to 48% (χ(2) = 6.5402, P = .01). No increase in 24-hour readmission, respiratory depression, or inpatient length of stay was observed. CONCLUSIONS: Using VOE-specific interventions, we significantly improved VOE care for children. Studies are needed to determine if these results can be replicated.

Implications of radiologic-pathologic correlation for gallbladder disease in children and young adults with sickle cell disease.

The purpose of this study is to describe gallbladder imaging findings in patients with sickle cell disease, and to determine how they correspond with occurrence of complications, need for cholecystectomy, and surgical pathology. This study is IRB approved and HIPAA compliant. Informed consent requirements were waived. We reviewed records of 77 children with sickle cell disease ages 0-18 years at the time of their first gallbladder imaging study. Demographics, hospital courses, and radiologic and pathologic reports were collected. Two pediatric radiologists independently and retrospectively reviewed the imaging studies. Statistical analysis was performed using kappa statistic, chi-squared test, and ANOVA F-test. Continuous variables were described with mean, median, variance, and range. Patients who underwent cholecystectomy (N = 25) were more likely than the patients who did not undergo cholecystectomy (N = 52) to have gallstones or sludge (100 versus 36.5 %, p = <0.0001) or other gallbladder or biliary abnormality (70.8 versus 1.9 %, p = <0.0001). Patients who did not undergo cholecystectomy more frequently had normal-appearing gallbladders and biliary tracts (63.5 versus 0 %, p = <0.0001). Ninety-two percent of patients with cholecystectomy had chronic cholecystitis on pathology, and 96 % had a complication, including chronic cholecystitis and sequelae of biliary obstruction. Young patients with sickle cell disease, cholelithiasis, and any other biliary imaging abnormality will almost certainly require cholecystectomy, and many will experience complications. The most common surgical pathologic diagnosis in this group is chronic cholecystitis, which has a variable radiologic appearance. Our findings support recommendations to perform elective cholecystectomy for children and young adults with sickle cell disease and cholelithiasis or gallbladder sludge.

Improvement in influenza vaccination rates in a pediatric sickle cell disease clinic.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk of complications from influenza. However, despite widespread recommendations that these patients receive an annual influenza immunization, reported vaccination rates remain very low at under 50%. PROCEDURE: Our aim was to increase the influenza vaccination rate among our pediatric patients with SCD aged 6 months to 21 years over two influenza seasons, 2012-2013 and 2013-2014, to 80%, consistent with the Health People 2020 goal. We used multiple quality improvement methods, based on the literature and our previous experience in other aspects of SCD care, including parent and provider education, enhancement of our EHR, use of a SCD patient registry and reminder and recall done by a patient navigator. RESULTS: We vaccinated 80% of our pediatric patients with SCD for influenza during the 2012-2013 season and 90% of patients in 2013-2014. Our early season vaccination rates were nearly double that of those for the general population. CONCLUSIONS: Use of quality improvement methods can increase rates of influenza vaccination for this high-risk population, suggesting that less health care utilization and lower cost might result.

Self-reported transition readiness among young adults with sickle cell disease.

BACKGROUND: A growing body of literature addresses the need for transition programs for young adults with sickle cell disease (SCD); however, studies assessing transition readiness are limited and there are few validated instruments to use. OBJECTIVE: To conduct a pilot study to assess transition readiness of patients with SCD in our transition program and to evaluate a SCD-specific assessment tool that measures 5 knowledge skill sets (medical, educational/vocational, health benefits, social, and independent living), and 3 psychological assessments (feelings, stress, and self-efficacy). RESULTS: Of the 47 SCD patients between the ages of 18 and 22 seen in our facility, 33 completed the assessment tool. The majority of patients reported good medical knowledge of SCD and said they were motivated to pursue a career despite the burden of living with the disease. We identified knowledge gaps in the area of independent living and health benefits skills sets. A majority of patients reported being worried that their SCD would prevent them from doing things in their life; however, few respondents said they were worried or anxious about their transition to adult care. CONCLUSIONS: Adolescents beginning a transition intervention program reported a high level of knowledge of their disease and demonstrated a positive attitude toward transition with good self-efficacy.

Weight status of children with sickle cell disease.

OBJECTIVE: Historically, many children and adolescents with sickle cell disease (SCD) were underweight. Treatment advances like hydroxyurea have been associated with improved growth. We hypothesized that increased hemoglobin (Hb) levels would be associated with increased weight status of children with SCD. METHODS: Investigators at 6 institutions conducted a retrospective chart review of all patients aged 2 to 19 years of age for the calendar years 2007-2009. Height, weight, baseline Hb levels, demographic information, and select comorbidities were recorded from the most recent clinic visit. Overweight and obesity were defined as ≥85th and ≥95th BMI percentiles for age and gender, respectively, and underweight was defined as <5th BMI percentile. RESULTS: Data were collected on 675 children and adolescents in 3 New England states. In this sample, 22.4% were overweight or obese, whereas only 6.7% were underweight. Overweight or obese status was associated with sickle genotypes other than Hb SS or Hb Sß(0) disease, and were associated with higher baseline Hb levels. Underweight individuals were more likely to be male, older, and have had at least 1 SCD-related complication. After adjusting for demographic factors, any SCD-related complication, SCD-directed treatments, and obesity-related conditions, there was a 36% increased odds of overweight/obesity for each 1 g/dL increase in baseline Hb levels. CONCLUSIONS: Nearly one-quarter of children and adolescents with SCD in New England are overweight or obese. Longitudinal studies are needed to determine the impact of elevated BMI on the morbidity and mortality of both children and adults with SCD.

Zinc protoporphyrin and iron deficiency screening: trends and therapeutic response in an urban pediatric center.

IMPORTANCE: Iron deficiency is the most common micronutrient deficiency among children worldwide, with iron-deficiency anemia associated with long-term adverse neurodevelopmental effects. OBJECTIVE: To understand the role of zinc protoporphyrin (ZPP) in iron deficiency screening in a low-income pediatric population, as well as to describe the prevalence and trends of abnormal ZPP and the response to iron therapy. DESIGN: Retrospective longitudinal study of data from electronic medical records collected from January 1, 2002, through December 31, 2010. SETTING: Boston Medical Center primary care center. PARTICIPANTS: A total of 2612 children with baseline routine screening results for complete blood cell count, lead, and ZPP drawn between ages 8 and 18 months and at follow-up were included. Children with sickle cell disease or lead toxicity were excluded. INTERVENTION: Documented iron prescription. MAIN OUTCOME MEASURE: Reduction of baseline abnormal ZPP at follow-up. RESULTS: Of 2612 children, 48% had an abnormal ZPP level at baseline. Among those with abnormal ZPP (n = 1254), 18% were prescribed iron. Iron prescription was significantly associated with ZPP reduction (odds ratio, 1.5; 95% CI, 1.1 to 2.0) and greater mean change in ZPP (mean difference, -4.4; 95% CI, -7.2 to -1.5). In multivariate analysis, the effect of iron prescription on the reduction of abnormal ZPP was modified by hemoglobin level. Iron prescription was significantly associated with ZPP reduction among those with anemia (odds ratio, 2.4; 95% CI, 1.1 to 5.0). Iron was rarely prescribed in children without anemia; a substantial, but not statistically significant, trend to improvement in those prescribed iron with low-normal hemoglobin was found. CONCLUSIONS AND RELEVANCE: Abnormal ZPP was common in this low-income population. Iron prescription was significantly associated with a larger reduction of ZPP. Our data suggest that ZPP may be appropriate for iron deficiency screening; further investigation is warranted to explore the role of ZPP among nonanemic children.

Management of children with sickle cell disease: a comprehensive review of the literature.

OBJECTIVE: Sickle cell disease (SCD) affects 70 000 to 100 000 people in the United States, and 2000 infants are born with the disease each year. The purpose of this study was to review the quality of the literature for preventive interventions and treatment of complications for children with SCD to facilitate the use of evidence-based medicine in clinical practice and identify areas in need of additional research. METHODS: We searched the Ovid Medline database and the Cochrane Library for articles published between January 1995 and April 2010 for English-language abstracts on 28 topics thought to be important for the care of children with SCD. We also added pertinent references cited by studies identified in our search. Each abstract was reviewed independently by 2 authors. Data from articles retrieved for full review were abstracted by using a common form. RESULTS: There were 3188 abstracts screened, and 321 articles underwent full review. Twenty-six articles (<1% of abstracts initially screened), which consisted of 25 randomized controlled trials and 1 meta-analysis, were rated as having level I evidence. Eighteen of the 28 topics selected for this review did not have level I evidence studies published. The management and prevention of pain episodes accounted for more than one-third of the level I studies. CONCLUSIONS: Although significant strides have been made in the care of children with SCD in the past 2 decades, more research needs to be performed, especially for acute events associated with SCD, to ensure that the health and well-being of children with SCD continues to improve.

Quality-of-care indicators for children with sickle cell disease.

OBJECTIVE: To develop a set of quality-of-care indicators for the management of children with sickle cell disease (SCD) who are cared for in a variety of settings by addressing the broad spectrum of complications relevant to their illness. METHODS: We used the Rand/University of California Los Angeles appropriateness method, a modified Delphi method, to develop the indicators. The process included a comprehensive literature review with ratings of the evidence and 2 rounds of anonymous ratings by an expert panel (nominated by leaders of various US academic societies and the National Heart, Lung, and Blood Institute). The panelists met face-to-face to discuss each indicator in between the 2 rounds. RESULTS: The panel recommended 41 indicators that cover 18 topics; 17 indicators described routine health care maintenance, 15 described acute or subacute care, and 9 described chronic care. The panel identified 8 indicators most likely to have a large positive effect on improving quality of life and/or health outcomes for children with SCD, which covered 6 topics: timely assessment and treatment of pain and fever; comprehensive planning; penicillin prophylaxis; transfusion; and the transition to adult care. CONCLUSIONS: Children with SCD are at risk for serious morbidities and early mortality, yet efforts to assess and improve the quality of their care have been limited compared with other chronic childhood conditions. This set of 41 indicators can be used to assess quality of care and provide a starting point for quality-improvement efforts.

Sickle cell disease-related pediatric medical expenditures in the U.S.

BACKGROUND: Although it is known that people with sickle cell disease (SCD) have relatively high utilization of medical care, most previous estimates of SCD-attributable expenditures have been limited to either inpatient care or single-state data. PURPOSE: To extend known findings by measuring the attributable or incremental expenditures per child with SCD compared to children without this illness and to thereby estimate SCD-attributable expenditures among children in the U.S. METHODS: MarketScan Medicaid and Commercial Claims databases for 2005 were used to estimate total medical expenditures of children with and without SCD. Expenditures attributable to SCD were calculated as the difference in age-adjusted mean expenditures during 2005 for children with SCD relative to children without SCD in the two databases. RESULTS: Children with SCD incurred medical expenditures that were $9369 and $13,469 higher than those of children without SCD enrolled in Medicaid and private insurance, respectively. In other words, expenditures of children with SCD were 6 and 11 times those of children without SCD enrolled in Medicaid and private insurance, respectively. CONCLUSIONS: Using a large, multistate, multipayer patient sample, SCD-attributable medical expenditures in children were conservatively and approximately estimated at $335 million in 2005.

Health care utilization and expenditures for privately and publicly insured children with sickle cell disease in the United States.

BACKGROUND: There are no current national estimates on health care utilization and expenditures for US children with sickle cell disease (SCD). PROCEDURE: We used the MarketScan Medicaid Database and the MarketScan Commercial Claims and Encounters Database for 2005 to estimate health services use and expenditures. The final samples consisted of 2,428 Medicaid-enrolled and 621 privately insured children with SCD. RESULTS: The percentage of children with SCD enrolled in Medicaid with an inpatient admission was higher compared to those privately insured (43% vs. 38%), yet mean expenditures per admission were 35% lower ($6,469 vs. $10,013). The mean number of emergency department (ED) visits was 49% higher for Medicaid-enrolled children compared to those with private insurance (1.36 vs. 0.91), but mean expenditures per ED visit were 28% lower. The mean number of non-ED outpatient visits was similar (12.6 vs. 11.5) but mean expenditures were 40% lower for the Medicaid-enrolled children ($3,557 vs. $5,908). The mean expenditures on drug claims were higher among those with Medicaid than private insurance ($1,049 vs. $531). Mean total expenditures for children with SCD enrolled in Medicaid were 25% lower than for privately insured children ($11,075 vs. $14,722). The samples were comparable with respect to SCD-related inpatient discharge diagnoses and use of outpatient blood transfusions. CONCLUSIONS: Children with SCD enrolled in Medicaid had lower expenditures than privately insured children, despite higher utilization of medical care, which indicates lower average reimbursements. Research is needed to assess the quality of care delivered to Medicaid-enrolled children with SCD and its relation to health outcomes.