Mary M. Hulihan

Public health implications of sickle cell trait: a report of the CDC meeting.

Although the issue of whether sickle cell trait (SCT) is clinically benign or a significant health concern has not yet been resolved, the potential health risk to affected individuals is of vital importance and represents a tremendous challenge in protecting, promoting, and improving the health of the approximately 300 million people worldwide and 3 million people in the U.S. who possess the trait. In response to a request by the Sickle Cell Disease Association of America, in December 2009, the CDC convened a meeting of partners, stakeholders, and experts to identify the gaps in public health, clinical health services, epidemiologic research, and community-based outreach strategies and to develop an agenda for future initiatives. Through facilitated discussion and presentations in four topic areas, participants discussed pertinent issues, synthesized clinical research findings, and developed a coherent framework for establishing an agenda for future initiatives. A primary outcome of the meeting was to provide the first step of an iterative process to move toward agreement regarding appropriate counseling, care, and, potentially, treatment of people with SCT.

The use of US health insurance data for surveillance of rare disorders: hereditary hemorrhagic telangiectasia.

Purpose:To assess the utility of US health insurance data for surveillance of hereditary hemorrhagic telangiectasia, an autosomal-dominant blood vasculature disorder with an estimated prevalence of 1.5–2.0 per 10,000 persons worldwide.Methods:We used 2005–2010 MarketScan Research Databases to identify individuals with employer-sponsored health insurance and International Classification of Disease, 9th Revision, Clinical Modification codes of 448.0 present in either one inpatient claim or two outpatient claims 30 days apart to define hereditary hemorrhagic telangiectasia. We examined frequencies of International Classification of Disease, 9th Revision, Clinical Modification codes for conditions that are complications of hereditary hemorrhagic telangiectasia among individuals with hereditary hemorrhagic telangiectasia and the general population to identify combinations of codes associated with hereditary hemorrhagic telangiectasia.Results:Excluding observations from one state, the average prevalence of hereditary hemorrhagic telangiectasia was 0.3 per 10,000 persons. The reported prevalence rose with age from ~0.1 per 10,000 at ages <30 years to 1.0–1.1 per 10,000 at ages 70 years and above. The condition codes that were most specific to presumed hereditary hemorrhagic telangiectasia were lung arteriovenous malformations and upper gastrointestinal angiodysplasia. Combinations of those codes and codes for brain arteriovenous malformation and epistaxis were highly predictive of reporting of hereditary hemorrhagic telangiectasia, with 20–57% of enrollees with those codes also meeting the study definition for hereditary hemorrhagic telangiectasia.Conclusion:Hereditary hemorrhagic telangiectasia is underrecognized in US administrative data. Administrative health data can be used to identify individuals with combinations of signs that are suggestive of hereditary hemorrhagic telangiectasia. Studies are needed to test the hypothesis that referral for evaluation of individuals with administrative records suggestive of undiagnosed hereditary hemorrhagic telangiectasia could lead to diagnosis and access to life-saving treatments for both them and affected family members.Genet Med 16 1, 33–39.

The impact of chelation therapy on survival in transfusional iron overload: a meta-analysis of myelodysplastic syndrome.

Elevated iron has been linked to increased morbidity and mortality in the general population (Mainous et al, 2004). In addition, iron overload can occur as an iatrogenic consequence of red blood cell (RBC) transfusions. Transfusional iron overload is not an uncommon consequence in patients who are chronically transfused to treat severe anaemia (de Ville de Goyet et al, 2013), as can occur in patients with myelodysplastic syndrome (MDS). Transfusion-dependent patients have increased mortality (de Ville de Goyet et al, 2013). Iron chelation therapy (ICT) is a strategy to address transfusional iron overload in MDS and utilizes drugs that remove iron as the drug is excreted.

Sickle cell disease incidence among newborns in New York State by maternal race/ethnicity and nativity

Purpose:Sickle cell disease is estimated to occur in 1:300–400 African-American births, with higher rates among immigrants from Africa and the Caribbean, and is less common among Hispanic births. This study determined sickle cell disease incidence among New York State newborns stratified by maternal race/ethnicity and nativity.Methods:Newborns with confirmed sickle cell disease born to New York State residents were identified by the New York State newborn screening program for the years 2000–2008 and matched to birth records to obtain birth and maternal information. Annual incidence rates were computed and bivariate analyses were conducted to examine associations with maternal race/ethnicity and nativity.Results:From 2000 to 2008, 1,911 New York State newborns were diagnosed with sickle cell disease and matched to the birth certificate files. One in every 1,146 live births was diagnosed with sickle cell disease. Newborns of non-Hispanic black mothers accounted for 86% of sickle cell disease cases whereas newborns of Hispanic mothers accounted for 12% of cases. The estimated incidence was 1:230 live births for non-Hispanic black mothers, 1:2,320 births for Hispanic mothers, and 1:41,647 births for non-Hispanic white mothers. Newborns of foreign-born non-Hispanic black mothers had a twofold higher incidence of sickle cell disease than those born to US-born non-Hispanic black mothers (P < 0.001).Conclusion:This study provides the first US estimates of sickle cell disease incidence by maternal nativity. Women born outside the United States account for the majority of children with sickle cell disease born in New York State. Such findings identify at-risk populations and inform outreach activities that promote ongoing, high-quality medical management to affected children.Genet Med 2013:15(3):222–228

Uric Acid as a Potential Cue to Screen for Iron Overload

Background: It is suggested that targeted screening for hemochromatosis and iron overload may be worthwhile. The aim of this study was to examine uric acid as a potential indicator of the presence of iron overload. Methods: We analyzed adults aged 20 and older in the National Health and Nutrition Examination Survey 1999 to 2002. We computed logistic regressions controlling for age, sex, race/ethnicity, liver or kidney condition, and alcohol use to see the relationship between combinations of uric acid and ferritin with the outcomes of elevated liver enzymes and proteinuria. Results: In unadjusted analyses, 20.7% of individuals with high uric acid had high ferritin levels versus 8.8% of individuals with low uric acid levels (P < .001). Individuals with both elevated uric acid and elevated ferritin levels had significantly higher liver enzymes than individuals with either elevated uric acid or ferritin. With low uric acid and low ferritin as the reference category, individuals with high uric acid and high ferritin were significantly more likely to also have proteinuria (odds ratio, 2.66; 95% CI, 1.82–3.91). Conclusions: Elevated levels of uric acid is associated with elevated ferritin levels and may serve as a risk stratification variable for presence of iron overload and hemochromatosis.

Telomere length and elevated iron: The influence of phenotype and HFE genotype

Elevated body iron stores are associated with morbidity and mortality due to oxidative stress. Hereditary hemochromatosis, a common condition caused by HFE gene mutations, can lead to excess iron storage and disease but clinical penetrance of HFE gene mutations is low and many people with elevated iron stores lack HFE mutations. We analyzed data from the Hemochromatosis and Iron Overload Screening Study to assess the relationship among HFE genotype (individuals with either homozygous or compound heterozygous status for C282Y and/or H63D HFE mutations were defined as genotype positive, or G+), elevated iron phenotype (individuals exceeding gender‐specific transferrin saturation and serum ferritin threshold levels were considered phenotype positive, or P+), and leukocyte telomere length, a marker of biological aging and cumulative oxidative stress. In unadjusted analyses in comparison to individuals who were G−P−, G+P− were not significantly different (OR 0.74; 95% CI 0.26–2.04), while the G+P+ (OR 2.03; 95% CI 1.15–3.56), and G−P+ (OR 2.24; 95% CI 1.5–3.29) had increased risk of short telomeres (<=25th percentile) rather than long telomeres (>=75th percentile). In analyses adjusting for age, gender, and race/ethnicity, the effect of individuals with elevated iron phenotypes having short telomeres persisted with G+P+ individuals (OR 1.94; 95% CI 1.02–3.72), and G−P+ individuals (OR 2.17; 95% CI 1.39–3.39) being significantly different from the G−P− group. In conclusion, elevated iron phenotype, but not HFE genotype, was associated with shortened telomeres. Further studies will be needed to determine whether telomere length provides a marker for morbidities specifically associated with iron overload. Am. J. Hematol. 88:492–496, 2013.

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.Genet Med 17 2, 125–130.

Defining Sickle Cell Disease Mortality Using a Population-Based Surveillance System, 2004 through 2008:

Objective. Population-based surveillance data from California and Georgia for years 2004 through 2008 were linked to state death record files to determine the all-cause death rate among 12,143 patients identified with sickle cell disease (SCD). Methods. All-cause death rates, by age, among these SCD patients were compared with all-cause death rates among both African Americans and the total population in the two states. All-cause death rates were also compared with death rates for SCD derived from publicly available death records: the compressed mortality files and multiple cause of death files. Results. Of 12,143 patients identified with SCD, 615 patients died. The all-cause mortality rate for the SCD population was lower than the all-cause mortality rate among African Americans and similar to the total population all-cause mortality rates from birth through age 4 years, but the rate was higher among those with SCD than both the African American and total population rates from ages 5 through 74 years. The count of deceased patients identified by using population-based surveillance data (n=5615) was more than twice as high as the count identified in compressed mortality files using SCD as the underlying cause of death alone (n=5297). Conclusion. Accurate assessment of all-cause mortality and age at death requires long-term surveillance via population-based registries of patients with accurately diagnosed SCD.

Transferrin Saturation and Hospital Length of Stay and Mortality in Medicare Beneficiaries

To evaluate in a large, nationally representative cohort the association between high serum transferrin saturation (TS) and hospital length of stay and mortality in older adults.

Attitudes toward Management of Sickle Cell Disease and Its Complications: A National Survey of Academic Family Physicians.

Objective. Sickle cell disease (SCD) is a disease that requires a significant degree of medical intervention, and family physicians are one potential provider of care for patients who do not have access to specialists. The extent to which family physicians are comfortable with the treatment of and concerned about potential complications of SCD among their patients is unclear. Our purpose was to examine family physicians attitudes toward SCD management. Methods. Data was collected as part of the Council of Academic Family Medicine Educational Research Alliance (CERA) survey in the United States and Canada that targeted family physicians who were members of CERA-affiliated organizations. We examined attitudes regarding management of SCD. Results. Overall, 20.4% of respondents felt comfortable with treatment of SCD. There were significant differences in comfort level for treatment of SCD patients depending on whether or not physicians had patients who had SCD, as well as physicians who had more than 10% African American patients. Physicians also felt that clinical decision support (CDS) tools would be useful for treatment (69.4%) and avoiding complications (72.6%) in managing SCD patients. Conclusions. Family physicians are generally uncomfortable with managing SCD patients and recognize the utility of CDS tools in managing patients.