Mortality of New York children with sickle cell disease identified through newborn screening.

PURPOSE: Long-term follow-up of newborn screening for conditions such as sickle cell disease can be conducted using linkages to population-based data. We sought to estimate childhood sickle cell disease mortality and risk factors among a statewide birth cohort with sickle cell disease identified through newborn screening. METHODS: Children with sickle cell disease identified by newborn screening and born to New York residents in 2000-2008 were matched to birth and death certificates. Mortality rates were calculated (using numbers of deaths and observed person-years at risk) and compared with mortality rates for all New York children by maternal race/ethnicity. Stratified analyses were conducted to examine associations between selected factors and mortality. RESULTS: Among 1,911 infants with sickle cell disease matched to birth certificates, 21 deaths were identified. All-cause mortality following diagnosis was 3.8 per 1,000 person-years in the first 2 years of life and 1.0 per 1,000 person-years at ages 2-9 years. The mortality rate was significantly lower among children of foreign-born mothers and was significantly higher among preterm infants with low birth weight. The mortality rates were not significantly higher for infants after 28 days with sickle cell disease than for all New York births, but they were 2.7-8.4 times higher for children 1 through 9 years old with homozygous sickle cell disease than for those of all non-Hispanic black or Hispanic children born to New York residents. CONCLUSION: Estimated mortality risk in children with homozygous sickle cell disease remains elevated even after adjustment for maternal race/ethnicity. These results provide evidence regarding the current burden of child mortality among children with sickle cell disease despite newborn screening.Genet Med 17 6, 452-459.

State-based surveillance for selected hemoglobinopathies.

PURPOSE: The lack of an ongoing surveillance system for hemoglobinopathies in the United States impedes the ability of public health organizations to identify individuals with these conditions, monitor their health-care utilization and clinical outcomes, and understand the effect these conditions have on the health-care system. This article describes the results of a pilot program that supported the development of the infrastructure and data collection methods for a state-based surveillance system for selected hemoglobinopathies. METHODS: The system was designed to identify and gather information on all people living with a hemoglobinopathy diagnosis (sickle cell diseases or thalassemias) in the participating states during 2004-2008. Novel, three-level case definitions were developed, and multiple data sets were used to collect information. RESULTS: In total, 31,144 individuals who had a hemoglobinopathy diagnosis during the study period were identified in California; 39,633 in Florida; 20,815 in Georgia; 12,680 in Michigan; 34,853 in New York, and 8,696 in North Carolina. CONCLUSION: This approach provides a possible model for the development of state-based hemoglobinopathy surveillance systems.

Patient reports of health outcome for adults living with sickle cell disease: development and testing of the ASCQ-Me item banks.

BACKGROUND: Providers and patients have called for improved understanding of the health care requirements of adults with sickle cell disease (SCD) and have identified the need for a systematic, reliable and valid method to document the patient-reported outcomes (PRO) of adult SCD care. To address this need, the Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me) was designed to complement the Patient Reported Outcome Measurement Information System (PROMIS®). Here we describe methods and results of the psychometric evaluation of ASCQ-Me item banks (IBs). METHODS: At seven geographically-disbursed clinics within the US, 556 patients responded to questions generated to assess cognitive, emotional, physical and social impacts of SCD. We evaluated the construct validity of the hypothesized domains using exploratory factor analysis (EFA), parallel analysis (PA), and bi-factor analysis (Item Response Theory Graded Response Model, IRT-GRM). We used IRT-GRM and the Wald method to identify bias in responses across gender and age. We used IRT and Cronbach's alpha coefficient to evaluate the reliability of the IBs and then tested the ability of summary scores based on IRT calibrations to discriminate among tertiles of respondents defined by SCD severity. RESULTS: Of the original 140 questions tested, we eliminated 48 that either did not form clean factors or provided biased measurement across subgroups defined by age and gender. Via EFA and PA, we identified three subfactors within physical impact: sleep, pain and stiffness impacts. Analysis of the resulting six item sets (sleep, pain, stiffness, cognitive, emotional and social impacts of SCD) supported their essential unidimensionality. With the exception of the cognitive impact IB, these item sets also were highly reliable across a broad range of values and highly significantly related to SCD disease severity. CONCLUSION: ASCQ-Me pain, sleep, stiffness, emotional and social SCD impact IBs demonstrated exceptional measurement properties using modern and classical psychometric methods of evaluation. Further development of the cognitive impact IB is required to improve its sensitivity to differences in SCD disease severity. Future research will evaluate the sensitivity of the ASCQ-Me IBs to change in SCD disease severity over time due to health interventions.

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain.

To address the global burden of sickle cell disease (SCD) and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to: patient-reported outcomes (PROs), pain (non-PROs), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the PROs, pain, and brain panels, as well as relevant findings and recommendations from the biomarkers panel. The panels identify end points, where there were supporting data, to use in clinical trials of SCD. In addition, the panels discuss where further research is needed to support the development and validation of additional clinical trial end points.

Standard measures for sickle cell disease research: the PhenX Toolkit sickle cell disease collections.

Standard measures and common data elements for sickle cell disease (SCD) will improve the data quality and comparability necessary for cross-study analyses and the development of guidelines that support effective treatments and interventions. In 2014, the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) funded an Administrative Supplement to the PhenX Toolkit (consensus measures for Phenotypes and eXposures; https://www.phenxtoolkit.org/) to identify common measures to promote data comparability across SCD research. An 11-member Sickle Cell Disease Research and Scientific Panel provided guidance to the project, establishing a core collection of SCD-related measures and defining the scope of 2 specialty collections: (1) cardiovascular, pulmonary, and renal complications, and (2) neurology, quality-of-life, and health services. For each specialty collection, a working group of SCD experts selected high-priority measures using a consensus process that included scientific community input. The SCD measures were released into the Toolkit in August 2015. The 25 measures included in the core collection are recommended for use by all NHLBI-funded investigators performing human-subject SCD research. The 10 neurology, quality-of-life, and health services measures and 14 cardiovascular, pulmonary, and renal measures are recommended for use within these specialized research areas. For SCD and other researchers, PhenX measures will promote collaborations with clinicians and patients, facilitate cross-study analysis, accelerate translational research, and lead to greater understanding of SCD phenotypes and epigenetics. For clinicians, using PhenX measures will help elucidate the etiology, progression, and treatment of SCD, leading to improved patient care and quality of life.

Quality of care in sickle cell disease: Cross-sectional study and development of a measure for adults reporting on ambulatory and emergency department care.

Documented deficiencies in adult sickle cell disease (SCD) care include poor access to knowledgeable providers and inadequate treatment in emergency departments (EDs).The aim of this study was to create patient-reported outcome measures of the quality of ambulatory and ED care for adults with SCD.We developed and pilot tested SCD quality of care questions consistent with Consumer Assessments of Healthcare Providers and Systems surveys. We applied psychometric methods to develop scores and evaluate reliability and validity.The participants of this study were adults with SCD (n = 556)-63% aged 18 to 34 years; 64% female; 64% SCD-SS-at 7 US sites.The measure used was Adult Sickle Cell Quality of Life Measurement information system Quality of Care survey.Most participants (90%) reported at least 1 severe pain episode (pain intensity 7.8 ±â€Š2.3, 0-10 scale) in the past year. Most (81%) chose to manage pain at home rather than the ED, citing negative ED experiences (83%). Using factor analysis, we identified Access, Provider Interaction, and ED Care composites with reliable scores (Cronbach α 0.70-0.83) and construct validity (r = 0.32-0.83 correlations with global care ratings). Compared to general adult Consumer Assessments of Healthcare Providers and Systems scores, adults with SCD had worse care, adjusted for age, education, and general health.Results were consistent with other research reflecting deficiencies in ED care for adults with SCD. The Adult Sickle Cell Quality of Life Measurement Quality of Care measure is a useful self-report measure for documenting and tracking disparities in quality of SCD care.

Enhancing measurement in health outcomes research supported by Agencies within the US Department of Health and Human Services.

Many of the Institutes, Agencies and Centers that make up the US Department of Health and Human Services (DHHS) have recognized the need for better instrumentation in health outcomes research, and provide support, both internally and externally, for research utilizing advances in measurement theory and computer technology (informatics). In this paper, representatives from several DHHS agencies and institutes will discuss their need for better instruments within their discipline and describe current or future initiatives for exploring the benefits of these technologies. Together, the perspectives underscore the importance of developing valid, precise, and efficient measures to capture the full burden of disease and treatment on patients. Initiatives, like the Patient-Reported Outcomes Measurement Information System (PROMIS) to create health-related quality of life item banks, represent a trans-DHHS effort to develop a standard set of measures for informing decision making in clinical research, practice, and health policy.

Hematology grants workshop.

Uppermost among the many concerns of young researchers is acquiring funding for beginning a career as a clinician-scientist. This chapter is targeted specifically at those individuals considering an academic physician-scientist career and those on the verge of becoming independent researchers. In Section I, Drs. Poncz and Iannone discuss the Mentored Career Development Award (K08). They summarize the application process, highlighting the critical components of a successful application and what the review process entails. In Section II, Dr. Werner discusses what applicants need to know about the NIH Institutes' program, review, and grants management function; the different NIH staff whom applicants should contact during the various stages of the grants process; and the important sections and key phrases in NIH Program Announcements for career development awards.