Providers' Perspectives on Treating Patients With Thalassemia.

In recent years, California has experienced a steady rise in Asian immigration which has led to a corresponding increased prevalence of clinically significant thalassemia in this state. As part of the Public Health Research, Education and Surveillance for Hemoglobinopathies emoglobinopathies project, a survey was developed to collect information from California providers who care for thalassemia patients in an effort to better understand their practice patterns, barriers to providing care, and educational needs. When asked about educational needs, providers most frequently expressed a desire for care and management guidelines (65.3%), health educational materials for patients (47.2%), and information on complications and clinical outcomes (32.1%). Only one quarter of providers (24.0%) reported that all of their thalassemia patients have a coordinated care plan. The increase in California thalassemia cases highlights the importance of provider knowledge to effectively serve the patients in their communities. Provider education and dissemination of treatment standards can not only improve knowledge about the disease but also increase awareness about the importance of coordinating care among a multidisciplinary team of specialists. Improvement in these areas will help achieve the overarching goal of better outcomes and quality of life for patients with thalassemia.

Emergency department utilization by Californians with sickle cell disease, 2005-2014.

BACKGROUND: Clinical care for children and adults living with sickle cell disease (SCD) is often provided in the emergency department (ED). Population-based surveillance data can be used to describe the ED utilization patterns of this patient population. PROCEDURE: A cohort of pediatric and adult California patients with SCD was identified from multiple data sources, and 10 years (2005-2014) of their treat-and-release ED utilization data were analyzed. RESULTS: Among a cohort of 4,636 patients with SCD, 4,100 (88%) had one or more treat-and-release ED visits. There were 2.1 mean annual visits per person for the cohort (median 0.7; range 0-185). In a single year (2005), 53% had 0 treat-and-release ED visits, 35% had 1-3 visits, 9% had 4-10 visits, and 3% had 11 or more visits; this highest utilization group accounted for 45% of all patients' ED visits. ED utilization in this cohort was highest among young adults and also higher among older adults than pediatric patients. CONCLUSION: The majority of identified patients in each of the 10 years did not go to the ED, but nearly all had one or more such visits over the full span of time. This study highlights the power and utility of a multisource longitudinal data collection effort for SCD. Further study of the segment of the population with highest ED utilization may highlight areas where changes in healthcare and health policy could improve and extend the lives of patients with SCD.

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.

Translation initiator EIF4G1 mutations in familial Parkinson disease.

Genome-wide analysis of a multi-incident family with autosomal-dominant parkinsonism has implicated a locus on chromosomal region 3q26-q28. Linkage and disease segregation is explained by a missense mutation c.3614G>A (p.Arg1205His) in eukaryotic translation initiation factor 4-gamma (EIF4G1). Subsequent sequence and genotype analysis identified EIF4G1 c.1505C>T (p.Ala502Val), c.2056G>T (p.Gly686Cys), c.3490A>C (p.Ser1164Arg), c.3589C>T (p.Arg1197Trp) and c.3614G>A (p.Arg1205His) substitutions in affected subjects with familial parkinsonism and idiopathic Lewy body disease but not in control subjects. Despite different countries of origin, persons with EIF4G1 c.1505C>T (p.Ala502Val) or c.3614G>A (p.Arg1205His) mutations appear to share haplotypes consistent with ancestral founders. eIF4G1 p.Ala502Val and p.Arg1205His disrupt eIF4E or eIF3e binding, although the wild-type protein does not, and render mutant cells more vulnerable to reactive oxidative species. EIF4G1 mutations implicate mRNA translation initiation in familial parkinsonism and highlight a convergent pathway for monogenic, toxin and perhaps virally-induced Parkinson disease.

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.

Incidence of sickle cell trait--United States, 2010.

Persons with sickle cell trait (SCT) are heterozygous carriers of an abnormal ß-globin gene that results in the production of an abnormal hemoglobin, Hb S, which can distort red blood cells (http://www.cdc.gov/ncbddd/sicklecell/facts.html). All state newborn screening (NBS) programs have provided universal sickle cell disease (SCD) screening for newborns since 2006. Screening for SCD detects both SCD and SCT. To obtain up-to-date measures of the occurrence of SCT among newborns by race/ethnicity and state of birth, data collected by state NBS programs in 2010 were examined. In 2010, the incidence of SCT in participating states was 15.5 per 1,000 newborns overall; 73.1 among black newborns and 6.9 among Hispanic newborns. Incidence by state ranged from 0.8 per 1,000 screened newborns in Montana to 34.1 per 1,000 in Mississippi. Although the occurrence of SCT varies greatly from state-to-state and among different races and ethnicities, every state and racial/ethnic population includes persons living with the condition. The period immediately following NBS is ideal for primary care providers and genetic counselors to begin educating the families of identified persons with SCT about potential health complications and reproductive considerations.

Elevated transferrin saturation, health-related quality of life and telomere length.

We sought to examine the relationship between elevated transferrin saturation (TS) and measures of health status (telomere length and patient-reported health-related quality of life) to assess whether elevated TS is associated with negative patient outcomes beyond increased risk for morbidity and mortality, using a cross-sectional analysis of the Hemochromatosis and Iron Overload Screening Study supplemented with assays for leukocyte telomere length in adults ≥25 years old (n = 669). Among individuals with elevated TS (≥45 % for women and ≥50 % for men), who also had a usual source of care, only 5.2 % reported ever being told by a doctor that they had an elevated iron condition. In a fully adjusted general linear regression model controlling for demographic characteristics as well as health conditions associated with iron overload, elevated TS versus non-elevated TS was associated with worse general health status (60.4 vs. 63.8, P < 0.05), mental health status (76.5 vs. 82.2, P < 0.0001) and shorter telomere length (241.4 vs. 261.3, P < 0.05). Increased surveillance of elevated TS may be in order as elevated TS is associated with decreased health status and very few patients with elevated TS are aware of their condition.

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.

Calcium channel blocker use and serum ferritin in adults with hypertension.

Iron overload cardiomyopathy is becoming more prevalent, and early recognition and intervention may alter outcomes. Calcium channels are key transporters of iron under iron-overloaded conditions, and potentially represent a new therapeutic target for iron overload. The purpose of this study was to examine the relationship between Calcium channel blocker (CCB) use and serum ferritin among adults with diagnosed hypertension. We analyzed the nationally representative NHANES (National Health and Nutrition Examination Survey) 1999-2002 for adults ≥40 years with diagnosed hypertension. The association between CCBs and serum ferritin was assessed using a t-test and adjusted multiple regressions.The study population included 2143 individuals (representing 37.4 million individuals, 42.0 % males). 12.6 % of the population reported taking CCBs in the last month. Individuals taking CCBs had lower mean serum ferritin (129.3 ng/mL versus 154.5 ng/mL, p = 0.02). After adjusting for age, sex, menopause and hysterectomy status for women, race/ethnicity, and C-reactive protein, mean serum ferritin for individuals taking CCBs was 26.3 ng/mL lower than for those not taking CCBs (p = 0.01). In an adjusted regression, individuals who took CCBs and had a daily vitamin C intake of ≥500 mg had a mean serum ferritin that was 60.1 ng/mL lower than people not taking CCBs and with daily vitamin C < 500 mg (p < 0.001). In conclusion, this study found an association between use of CCBs and lower serum ferritin levels in individuals with hypertension. Further studies are needed to assess the possible use of CCBs as non-traditional chelating agents for treatment of iron overload cardiomyopathy.

Surveillance for Sickle Cell Disease - Sickle Cell Data Collection Program, Two States, 2004-2018.

PROBLEM/CONDITION: Sickle cell disease (SCD), an inherited blood disorder affecting an estimated 100,000 persons in the United States, is associated with multiple complications and reduced life expectancy. Complications of SCD can include anemia, debilitating acute and chronic pain, infection, acute chest syndrome, stroke, and progressive organ damage, including decreased cognitive function and renal failure. Early diagnosis, screenings and preventive interventions, and access to specialist health care can decrease illness and death. Population-based public health surveillance is critical to understanding the course and outcomes of SCD as well as the health care use, unmet health care needs, and gaps in essential services of the population affected by SCD. PERIOD COVERED: 2004-2018. DESCRIPTION OF THE PROGRAM: In 2015, CDC established the Sickle Cell Data Collection (SCDC) program to characterize the epidemiology of SCD in two states (California and Georgia). Previously, surveillance for SCD was conducted by two short-term projects: Registry and Surveillance System for Hemoglobinopathies (RuSH), which was conducted during 2010-2012 and included 2004-2008 data, and Public Health Research, Epidemiology, and Surveillance for Hemoglobinopathies (PHRESH), which was conducted during 2012-2014 and included 2004-2008 data. Both California and Georgia participated in RuSH and PHRESH, which guided the development of the SCDC methods and case definitions. SCDC is a population-based tracking system that uses comprehensive data linkages in state health systems. These linkages serve to synthesize and disseminate population-based, longitudinal data for persons identified with SCD from multiple sources using selected International Classification of Diseases, Ninth Revision, Clinical Modification, and Tenth Revision codes and laboratory results confirmed through state newborn screening (NBS) programs or clinic case reporting. Administrative and clinical data sources include state Medicaid and Children's Health Insurance Program databases, death certificates, NBS programs, hospital discharge and emergency department records, and clinical records or case reports. Data from multiple sources and years are linked and deduplicated so that states can analyze and report on SCD population prevalence, demographic characteristics, health care access and use, and health outcomes. The SCD case definition is based on an algorithm that classifies cases with laboratory confirmation as confirmed cases and those with a reported clinical diagnosis or three or more diagnostic codes over a 5-year period from an administrative data source as probable cases. In 2019, nine states (Alabama, California, Georgia, Indiana, Michigan, Minnesota, North Carolina, Tennessee, and Virginia) were funded as part of an SCDC capacity-building initiative. The newly funded states developed strategies for SCD case identification and data linkage similar to those used by California and Georgia. As of 2021, the SCDC program had expanded to 11 states with the addition of Colorado and Wisconsin. RESULTS: During 2004-2018, the cumulative prevalence of confirmed and probable SCD cases identified in California and Georgia was 9,875 and 14,777 cases, respectively. The 2018 annual prevalence count was 6,027 cases for California and 9,141 for Georgia. Examination of prevalence counts by contributing data source during 2014-2018 revealed that each data source captured 16%-71% of cases in California and 17%-87% in Georgia; therefore, no individual source is sufficient to estimate statewide population prevalence. The proportion of pediatric SCD patients (children aged 0-18 years) was 27% in California and 40% in Georgia. The percentage of females with SCD in California and Georgia was 58% and 57%, respectively. Of the cases with SCD genotyping data available (n = 5,856), 63% of patients had sickle cell anemia. SCDC data have been used to directly apprise health care providers and policymakers about health care needs and gaps for patients with SCD. For example, an SCDC Georgia assessment indicated that 10% of babies born during 2004-2016 with SCD lived more than a 1-hour drive from any SCD specialty care option, and another 14% lived within a 1-hour drive of a periodic SCD specialty clinic only. Likewise, an SCDC California assessment indicated that during 2016-2018, most patients with SCD in Los Angeles County lived approximately 15-60 miles from hematologists experienced in SCD care. A surveillance capacity and performance assessment of all 11 SCDC states during 2020-2021 indicated that states differed in the availability of data sources used for SCD surveillance and the time frames for accessing each state data source. Nonetheless, methods for standardizing reporting were developed across all participating states. INTERPRETATION: This report is the first comprehensive description of CDC's efforts in collaboration with participating states to establish, maintain, and expand SCD surveillance through the SCDC program to improve health outcomes for persons living with SCD. Findings from California and Georgia analyses highlighted a need for additional SCD specialty clinics. Despite different approaches, expansion of SCDC to multiple states was possible using standardized, rigorous methods developed across all participating states for reporting on disease prevalence, health care needs and use, and deaths. PUBLIC HEALTH ACTION: Findings from surveillance can be used to improve and monitor care and outcomes for persons with SCD. These and other SCDC analyses have had a role in opening new SCD clinics, educating health care providers, developing state health care policies, and guiding new research initiatives. Public health officials can use this report as a guiding framework to plan or implement surveillance programs for persons with SCD. Both data-related activities (data sources; patient identifiers; and obtaining, transferring, and linking data) and the administrative considerations (stakeholder engagement, costs and resources, and long-term sustainability) are crucial to the success of these programs.

IRon Overload screeNing tool (IRON): development of a tool to guide screening in primary care.

Iron overload is associated with significant morbidity and mortality yet is easily treated. The objective of this study was to create a tool that could be easily adapted to clinical practice that indicates the likelihood of a patient having undetected iron overload. We used the National Health and Nutrition Examination Survey (NHANES) 1999-2002 for US adults aged 20 years and older to build a model (unweighted n=8,779). We chose potential variables for inclusion that could be gathered by self-report or measured without laboratory data and were suggested by past literature on hemochromatosis and iron overload. We computed logistic regressions to create the scores by initially evaluating the variables' relationship with elevated ferritin and elevated transferrin saturation and then using odds ratios to correspond to scores. The resulting score on the IRon Overload ScreeNing Tool (IRON) was then validated with data on 13,844 adults in the NHANES III, 1988-94. Predictors in the final tool were age, gender, previous diagnoses of liver condition, osteoporosis or thyroid disease. The IRON score yielded an area under the curve (AUC) in the NHANES 1999-02 of 0.720 and an AUC of 0.685 in the NHANES III validation sample. The IRON score is a tool to assist in identification of patients with iron overload that has several qualities that make it attractive for use in clinical practice with an undifferentiated patient population including brevity, easily collected information and predictive ability comparable to other tools that help in directing screening.

ATP13A2 variability in Parkinson disease.

Recessively inherited mutations in ATP13A2 result in Kufor-Rakeb syndrome (KRS), whereas genetic variability and elevated ATP13A2 expression have been implicated in Parkinson disease (PD). Given this background, ATP13A2 was comprehensively assessed to support or refute its contribution to PD. Sequencing of ATP13A2 exons and intron-exon boundaries was performed in 89 probands with familial parkinsonism from Tunisia. The segregation of mutations with parkinsonism was subsequently assessed within pedigrees. The frequency of genetic variants and evidence for association was also examined in 240 patients with nonfamilial PD and 372 healthy controls. ATP13A2 mRNA expression was also quantified in brain tissues from 38 patients with nonfamilial PD and 38 healthy subjects from the United States. Sequencing analysis revealed 37 new variants; seven missense, six silent, and 24 that were noncoding. However, no single ATP13A2 mutation segregated with familial parkinsonism in either a dominant or recessive manner. Four markers showed marginal association with nonfamilial PD, prior to correction for multiple testing. ATP13A2 mRNA expression was marginally decreased in PD brains compared with tissue from control subjects. In conclusion, neither ATP13A2 genetic variability nor quantitative gene expression in brain appears to contribute to familial parkinsonism or nonfamilial PD.

Genomic investigation of alpha-synuclein multiplication and parkinsonism.

OBJECTIVE: Copy number variation is a common polymorphic phenomenon within the human genome. Although the majority of these events are non-deleterious they can also be highly pathogenic. Herein we characterize five families with parkinsonism that have been identified to harbor multiplication of the chromosomal 4q21 locus containing the alpha-synuclein gene (SNCA). METHODS: A methodological approach using fluorescent in situ hybridization and Affymetrix (Santa Clara, CA) 250K SNP microarrays was used to characterize the multiplication in each family and to identify the genes encoded within the region. The telomeric and centromeric breakpoints of each family were further narrowed using semiquantitative polymerase chain reaction with microsatellite markers and then screened for transposable repeat elements. RESULTS: The severity of clinical presentation is correlated with SNCA dosage and does not appear to be overtly affected by the presence of other genes in the multiplicated region. With the exception of the Lister kindred, in each family the multiplication event appears de novo. The type and position of Alu/LINE repeats are also different at each breakpoint. Microsatellite analysis demonstrates two genomic mechanisms are responsible for chromosome 4q21 multiplications, including both SNCA duplication and recombination. INTERPRETATION: SNCA dosage is responsible for parkinsonism, autonomic dysfunction, and dementia observed within each family. We hypothesize dysregulated expression of wild-type alpha-synuclein results in parkinsonism and may explain the recent association of common SNCA variants in sporadic Parkinson's disease. SNCA genomic duplication results from intraallelic (segmental duplication) or interallelic recombination with unequal crossing over, whereas both mechanisms appear to be required for genomic SNCA triplication.

Genotype-phenotype correlates in Taiwanese patients with early-onset recessive Parkinsonism.

We screened for mutations in the PARKIN, DJ-1, and PINK1 genes in a Taiwanese cohort (68 probands; 58 sporadic and 10 familial) with early-onset parkinsonism (EOP, onset <50 years of age). We identified 9 patients harboring mutations in PARKIN (three compound heterozygous and six single heterozygous carriers), 3 patients with heterozygous PINK1 mutations (including two novel substitutions M341I and P209A), and no DJ-1 mutations. Our frequencies of PARKIN (two allele mutation, 4.4%; single allele, 8.8%) and PINK1 (single heterozygous, 4.4%) mutations in Taiwanese-Chinese are similar to those in Caucasian and other Asian EOP patients. Although the role of heterozygosity of recessive genes in EOP remains to be resolved, molecular analysis and functional imaging will play a decisive role in differential diagnosis and determined therapeutic strategy.

LRRK2 Gly2019Ser penetrance in Arab-Berber patients from Tunisia: a case-control genetic study.

BACKGROUND: Several genes have been implicated in the pathogenesis of Parkinson's disease (PD). The aim of this study was to define the clinical symptoms and age-associated cumulative incidence of the most frequent mutation associated with PD, LRRK2 Gly2019Ser. METHODS: 238 patients with sporadic PD and 371 unrelated control participants from the Arab-Berber population were screened at the Institut National de Neurologie, Tunis. Symptoms of PD were assessed using the Hoehn and Yahr scale, the unified Parkinson's disease rating scale, and the Epworth scale. Genotyping for LRRK2 6055G-->A, which causes the Gly2019Ser mutation, was done in all participants, and the age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. FINDINGS: 30% of patients with PD in this case-control sample were carriers of LRRK2 Gly2019Ser. The age of onset of symptoms and the clinical presentation of patients with LRRK2 Gly2019Ser were similar to those of patients with idiopathic PD. Carriers of LRRK2 Gly2019Ser were 22.6 times (95% CI 10.2-50.1) more likely to be affected by PD than non-carriers. Tremor was the predominant symptom in LRRK2 Gly2019Ser carriers (92% [homozygotes] vs 75% [heterozygotes] vs 69% [non-carriers]; Cochran-Armitage trend test p=0.0587). Disease severity, response to treatment, and disease duration were similar among LRRK2 Gly2019Ser homozygotes, heterozygotes, and non-carriers (p=0.85). Disease penetrance in LRRK2 Gly2019Ser carriers ranged from less than 20% in those younger than 50 years to greater than 80% at 70 years. INTERPRETATION: The LRRK2 Gly2019Ser mutation in patients with PD is a useful aid to diagnosis. LRRK2 Gly2019Ser penetrance can vary but in most carriers PD seems an inevitable consequence of ageing. LRRK2 Gly2019Ser considerably increases susceptibility to neuronal degeneration, although the process might be mediated by many triggers. By contrast, idiopathic PD is rare before 50 years and the prevalence only increases to 4% in the oldest members of the population. FUNDING: GlaxoSmithKline; National Institutes of Health; and Mayo Foundation.

Genetic variation of Omi/HtrA2 and Parkinson's disease.

Variants in the Omi/HtrA2 gene have been nominated as a cause of Parkinson's disease. This sequencing study of Omi/HtrA2 in 95 probands with apparent autosomal dominant inheritance of Parkinson's disease did not identify any pathogenic mutations. In addition, there was no association between common variations in the Omi/HtrA2 gene and susceptibility to Parkinson's disease in any of our four patient-control series (n=2373). Taken together our results do not support a role for Omi/HtrA2 variants in the pathogenesis of Parkinson's disease.

Effectiveness of Clinical Decision Support Based Intervention in the Improvement of Care for Adult Sickle Cell Disease Patients in Primary Care.

INTRODUCTION: Although most patients with rare diseases like sickle cell disease (SCD) are treated in the primary care setting, primary care physicians may find it challenging to keep abreast of medication improvements and complications associated with treatment for rare and complex diseases. The purpose of this study was to evaluate the effectiveness of a clinical decision support (CDS) -based intervention system for transfusional iron overload in adults with SCD to improve management in primary care. METHODS: An electronic medical record based clinical decision support system for potential transfusional iron overload in SCD patients in primary care was evaluated. The intervention was implemented in 3 family medicine clinics with a control group of 3 general internal medicine clinics. Data were collected in the 6 months before the intervention and 6 months after the intervention. There were 47 patients in the family medicine group and 24 in the general internal medicine group. RESULTS: There was no management change in the control group while the intervention group improved primary care management from 0% to 44% (P < .001). CONCLUSION: A CDS tool can improve management of SCD patients in primary care.