Comparison of US Federal and Foundation Funding of Research for Sickle Cell Disease and Cystic Fibrosis and Factors Associated With Research Productivity.

Importance: Sickle cell disease (SCD) and cystic fibrosis (CF) are severe autosomal recessive disorders associated with intermittent disease exacerbations that require hospitalizations, progressive chronic organ injury, and substantial premature mortality. Research funding is a limited resource and may contribute to health care disparities, especially for rare diseases that disproportionally affect economically disadvantaged groups. Objective: To compare disease-specific funding between SCD and CF and the association between funding and research productivity. Design, Setting, and Participants: This cross-sectional study examined federal and foundation funding, publications indexed in PubMed, clinical trials registered in ClinicalTrials.gov, and new drug approvals from January 1, 2008, to December 31, 2018, in an estimated US population of approximately 90 000 individuals with SCD and approximately 30 000 individuals with CF. Main Outcomes and Measures: Federal and foundation funding, publications indexed in PubMed, clinical trial registrations, and new drug approvals. Results: From 2008 through 2018, federal funding was greater per person with CF compared with SCD (mean [SD], $2807 [$175] vs $812 [$147]; P < .001). Foundation expenditures were greater for CF than for SCD (mean [SD], $7690 [$3974] vs $102 [$13.7]; P < .001). Significantly more research articles (mean [SD], 1594 [225] vs 926 [157]; P < .001) and US Food and Drug Administration drug approvals (4 vs 1) were found for CF compared with SCD, but the total number of clinical trials was similar (mean [SD], 27.3 [6.9] vs 23.8 [6.3]; P = .22). Conclusions and Relevance: The findings show that disparities in funding between SCD and CF may be associated with decreased research productivity and novel drug development for SCD. Increased federal and foundation funding is needed for SCD and other diseases that disproportionately affect economically disadvantaged groups to address health care disparities.

Do Words Matter? Stigmatizing Language and the Transmission of Bias in the Medical Record.

BACKGROUND: Clinician bias contributes to healthcare disparities, and the language used to describe a patient may reflect that bias. Although medical records are an integral method of communicating about patients, no studies have evaluated patient records as a means of transmitting bias from one clinician to another. OBJECTIVE: To assess whether stigmatizing language written in a patient medical record is associated with a subsequent physician-in-training's attitudes towards the patient and clinical decision-making. DESIGN: Randomized vignette study of two chart notes employing stigmatizing versus neutral language to describe the same hypothetical patient, a 28-year-old man with sickle cell disease. PARTICIPANTS: A total of 413 physicians-in-training: medical students and residents in internal and emergency medicine programs at an urban academic medical center (54% response rate). MAIN MEASURES: Attitudes towards the hypothetical patient using the previously validated Positive Attitudes towards Sickle Cell Patients Scale (range 7-35) and pain management decisions (residents only) using two multiple-choice questions (composite range 2-7 representing intensity of pain treatment). KEY RESULTS: Exposure to the stigmatizing language note was associated with more negative attitudes towards the patient (20.6 stigmatizing vs. 25.6 neutral, p < 0.001). Furthermore, reading the stigmatizing language note was associated with less aggressive management of the patient's pain (5.56 stigmatizing vs. 6.22 neutral, p = 0.003). CONCLUSIONS: Stigmatizing language used in medical records to describe patients can influence subsequent physicians-in-training in terms of their attitudes towards the patient and their medication prescribing behavior. This is an important and overlooked pathway by which bias can be propagated from one clinician to another. Attention to the language used in medical records may help to promote patient-centered care and to reduce healthcare disparities for stigmatized populations.

Utility of the Montreal Cognitive Assessment as a Screening Test for Neurocognitive Dysfunction in Adults with Sickle Cell Disease.

OBJECTIVES: Neurocognitive dysfunction is an important complication of sickle cell disease (SCD), but little is published on the utility of screening tests for cognitive impairment in people with the disease. The purpose of this study was to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool and identify predictors of MoCA performance in adults with sickle cell disease. METHODS: We conducted a retrospective, cross-sectional study of the first 100 adult patients with SCD who completed the MoCA as part of routine clinical care at the Johns Hopkins Sickle Cell Center for Adults. We abstracted demographic, laboratory, and clinical data from each participant's electronic medical record up to the date that the MoCA was administered. The factorial validity of each MoCA domain was analyzed using standard psychometric statistics. We evaluated the abstracted data for associations with the composite MoCA score and looked for independent predictors of performance using multivariable regressions. RESULTS: Components of the MoCA performed well in psychometric analyses and identified deficits in executive function that were described in other studies. Forty-six percent of participants fell below the cutoff for mild cognitive impairment. Increased education was an independent predictor of increased MoCA score (3.1, 95% confidence interval [CI] 1.5-4.7), whereas cerebrovascular accidents and chronic kidney disease were independent predictors of decreased score (-3.3, 95% CI -5.7 to -0.97 and -3.2, 95% CI -6.2 to -0.11, respectively). When analysis was restricted to patients with SCA, increased education (3.7, 95% CI 2.2-5.2) and a history of hydroxyurea therapy (2.0, 95% CI -0.022 to 4.0) were independent predictors of a higher score, whereas chronic kidney disease (-3.3, 95% CI -6.4 to -0.24) and increased aspartate transaminase (-0.045, 95% CI -0.089 to -0.0010) were independent predictors of a decreased score. CONCLUSIONS: The MoCA showed promise by identifying important cognitive deficits and associations with chronic complications and therapy.

Effect of Free Dental Services on Individuals with Sickle Cell Disease.

OBJECTIVES: Poor oral health can have a negative impact on overall health. This is especially concerning for individuals with sickle cell disease (SCD), an inherited blood disorder that affects hemoglobin and can lead to an increased risk of infection and hyperalgesia. Because the majority of individuals with SCD have Medicaid insurance and no dental coverage, we provided free basic dental care to individuals with SCD to determine whether it decreased overall healthcare utilization. METHODS: Through a contract with a private dental office, we provided free basic dental care (eg, cleanings, fillings, x-rays) to individuals with SCD. We reviewed medical records for the 12 months before and after their initial dental visit to determine whether there were any changes in acute care visits (defined as a visit to the emergency department, sickle cell infusion center, or visits to both in the same day), hospitalizations, and total days hospitalized. We conducted a negative binomial regression to determine any differences in the pre-post periods. RESULTS: In our multivariable analysis, there was a statistically significant decrease in hospital admissions. In addition, there was a significant decrease in total days hospitalized if dental work was completed, but an increase in days hospitalized in men. CONCLUSIONS: Providing dental care to individuals with SCD who did not have dental insurance did not greatly alter acute care visits. A larger sample size may be necessary to observe an effect.

Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis.

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model.

Measuring and explaining racial and ethnic differences in willingness to donate live kidneys in the United States.

BACKGROUND: Reasons for US racial-ethnic minority ESRD patients' reported difficulties identifying live kidney donors are poorly understood. METHODS: We conducted a national study to develop scales measuring willingness to donate live kidneys among US adults (scores ranged from 0 [not willing] to 10 [extremely willing]), and we tested whether racial-ethnic differences exist in willingness to donate. We also examined whether clinical, sociodemographic, and attitudinal factors mediated potential racial-ethnic differences in willingness. RESULTS: Among 845 participants, the majority were extremely willing to donate to relatives (77%) while fewer than half were extremely willing to donate to non-relatives (18%). In multivariable linear regression analyses, willingness to donate varied by race-ethnicity and recipient relationship to the donor. African Americans were less willing to donate to relatives than whites (ß: -0.48; 95% CI [Confidence Interval]: -0.94 to -0.17; p = 0.04), but these differences were eliminated after accounting for socioeconomic factors, medical trust, and concerns about burial after death. There were no differences in willingness to donate between Hispanics and whites. CONCLUSIONS: African Americans' burial concerns, medical trust, and socioeconomic factors explained differences in their willingness to donate to relatives, suggesting efforts to address these barriers may enhance rates of live kidney donation in this group.

Patient reactions to personalized medicine vignettes: an experimental design.

PURPOSE: Translational investigation on personalized medicine is in its infancy. Exploratory studies reveal attitudinal barriers to "race-based medicine" and cautious optimism regarding genetically personalized medicine. This study describes patient responses to hypothetical conventional, race-based, or genetically personalized medicine prescriptions. METHODS: Three hundred eighty-seven participants (mean age = 47 years; 46% white) recruited from a Baltimore outpatient center were randomized to this vignette-based experimental study. They were asked to imagine a doctor diagnosing a condition and prescribing them one of three medications. The outcomes are emotional response to vignette, belief in vignette medication efficacy, experience of respect, trust in the vignette physician, and adherence intention. RESULTS: Race-based medicine vignettes were appraised more negatively than conventional vignettes across the board (Cohen's d = -0.51-0.57-0.64, P < 0.001). Participants rated genetically personalized comparably with conventional medicine (-0.14-0.15-0.17, P = 0.47), with the exception of reduced adherence intention to genetically personalized medicine (Cohen's d = -0.38-0.41-0.44, P = 0.009). This relative reluctance to take genetically personalized medicine was pronounced for racial minorities (Cohen's d = -0.38-0.31-0.25, P = 0.02) and was related to trust in the vignette physician (change in R = 0.23, P < 0.001). CONCLUSIONS: This study demonstrates a relative reluctance to embrace personalized medicine technology, especially among racial minorities, and highlights enhancement of adherence through improved doctor- patient relationships.

Problematic hospital experiences among adult patients with sickle cell disease.

BACKGROUND: Adults with sickle cell disease (SCD) have often reported difficulties obtaining care during vaso-occlusive crisis (VOC) in qualitative studies. METHODS: We measured the experiences of 45 SCD patients who received in-hospital care for VOC using the Picker Patient Experience Questionnaire (PPE-15), and used the one sample binomial test to compare with national norms. RESULTS: Most SCD patients reported that they were insufficiently involved in decisions (86%), staff gave conflicting information (64%), it wasn't easy to find someone to discuss concerns (61%), doctors' answers to questions were not clear (58%), nurses' answers to questions were not clear (56%), doctors did not always discuss fears and anxieties (53%), and nurses did not always discuss fears and anxieties (52%). A greater percentage of SCD patients than the U.S. sample in 9 of 12 areas reported problems. CONCLUSIONS: Further research is needed to determine the consequences of and potential interventions to improve these poor experiences.

The burden of emergency department use for sickle-cell disease: an analysis of the national emergency department sample database.

It is estimated that there are 100,000 people living with sickle-cell disease (SCD) in the United States [1]. The most common manifestation of SCD is vaso-occlusive crisis, which is characterized by intermittent, unexpected episodes of excruciating pain. As these episodes often come on suddenly, much of the care for these crises occurs within emergency departments (EDs). Several studies have examined ED use and costs for certain groups of patients with SCD [2-4]. For example, in 1997, Woods et al. [2] found that 85.7% of 7,202 hospital admissions for SCD in Illinois were for patients that came through the ED, and the total charges for sickle-cell admissions in Illinois were found to be $30 million a year. A recent study of healthcare use by children with SCD demonstrated that children insured by Medicaid had higher ED utilization than those with private insurance (57% vs.45%) [5]. The purpose of our study was to provide national level estimates of ED utilization by SCD patients, which have not previously been available.

Sickle cell disease in the United States: looking back and forward at 100 years of progress in management and survival.

The past 100 years since James Herrick's first description of sickle cell disease in the United States have been characterized by the gradual development of management strategies. We review the progress in sickle cell disease management in the United States over the past 100 years, with emphasis on the diverse forces surrounding advances in disease management. Mortality and survival data are presented chronologically, with an attempt to highlight improvements in survival associated with specific advancements for pediatric and adult care. Finally, the future course for sickle cell disease management is explored, given the continued work in advancing the field.

Examining the effectiveness of hydroxyurea in people with sickle cell disease.

This study investigated hydroxyurea use in people with sickle cell disease (SCD) outside of a research setting. Pharmacy data, outpatient visits, hospital admissions, and length of stay were assessed for all patients with SCD enrolled in a Medicaid managed care organization in Maryland. Three hundred and ninety (390) people with SCD were covered between the years 2001-2005. A large majority (85.9%) never had a claim for a hydroxyurea refill. Hydroxyurea users had higher admission rates than non-hydroxyurea users (5 vs. 1.5, p=.004). Patients who were in the highest tertile of refills of hydroxyurea had significantly fewer hospital admissions than patients in the lowest tertile (2.44 vs. 7.57, p=.043). Patients with the lowest hydroxyurea refill usage had significantly higher mean costs per month enrolled than those with the highest number ($4,553 vs. $2,017, p=.031). Hydroxyurea was underutilized in this patient population. Patients with more regular refills of hydroxyurea had fewer admissions to the hospital and markedly decreased costs.

A systematic review of barriers and interventions to improve appropriate use of therapies for sickle cell disease.

Clinical experts have expressed concern about underutilization of sickle cell disease (SCD) therapies, including hydroxyurea, prophylactic antibiotics, iron chelation, bone marrow transplantation, pain management during vaso-occlusive crisis, and receipt of routine ambulatory health care. We synthesized studies that identified barriers to and interventions to improve appropriate use of these therapies. Of the 48 studies included in our review, 35 identified therapeutic barriers or facilitators, and 13 evaluated interventions to improve use of therapies. Consistently identified barriers to appropriate pain management were negative provider attitudes and lack of provider knowledge. Four of 9 pain management interventions improved direct measures of pain management quality, while 5 improved indirect measures. One intervention improved receipt of routine ambulatory care. We concluded that interventions to improve pain management in SCD can be effective and should address providers' negative attitudes and knowledge and that more intervention studies are needed to improve receipt of recommended SCD therapies.

The course and correlates of high hospital utilization in sickle cell disease: Evidence from a large, urban Medicaid managed care organization.

Although most patients with sickle cell disease (SCD) are hospitalized infrequently and manage painful crises at home, a small subpopulation is frequently admitted to emergency departments and inpatient units. This small group accounts for the majority of health care expenses for patients with SCD. Using inpatient claims data from a large, urban Medicaid MCO for 5 consecutive years, this study sought to describe the course of high inpatient utilization (averaging four or more admissions enrolled per year for at least 1 year) in members with a diagnosis of SCD and a history of hospitalizations for vaso-occlusive crisis. High utilizers were compared with the other members with SCD on demographics, medical and psychiatric comorbidity, and use of other health care resources. Members who were high utilizers had more diagnostic mentions of sickle cell complications than low utilizers. However, the pattern of high inpatient utilization was likely to moderate over successive years, and return to the pattern after moderation was uncommon. Despite this, a small subpopulation engaged in exceptional levels of inpatient utilization over multiple years.

Provider barriers to hydroxyurea use in adults with sickle cell disease: a survey of the Sickle Cell Disease Adult Provider Network.

The FDA approved hydroxyurea for use in adults with sickle cell disease (SCD) in 1998. In 2002, the NHLBI published recommendations for the use of hydroxyurea in this patient population. The purpose of this study was to evaluate providers' awareness of the NHLBI recommendations regarding hydroxyurea prescribing, whether these recommendations have changed providers' practices and how these providers prescribed hydroxyurea. We chose to survey a select group of providers of care to adults with SCD, members of the Sickle Cell Adult Provider Network. The response rate was 47%. Eighty-one percent of respondents reported they had read the NHLBI recommendations on hydroxyurea use, and 76% of respondents agreed with the NHLBI recommendations. Only 45% of respondents to this survey reported that they prescribe hydroxyurea to every eligible patient. Black respondents reported a higher percentage of their eligible patients being on hydroxyurea than white respondents. Seventy-seven percent of respondents thought that hydroxyurea was effective or very effective in patients with SCD. Ninety-four percent of black versus 73% of white versus 40% of other race respondents thought that hydroxyurea was effective or very effective in SCD patients (p = 0.006). The results of this survey suggest that lack of awareness, agreement and belief in the benefits of hydroxyurea contributes to providers underprescribing hydroxyurea.

Hospitalization rates and costs of care of patients with sickle-cell anemia in the state of Maryland in the era of hydroxyurea.

The multicenter study of hydroxyurea (MSH) in sickle-cell anemia (SCA) demonstrated that patients treated with hydroxyurea (HU) had a 44% decrease in hospitalizations when compared with those taking placebo. A subsequent study looking at the cost-effectiveness of HU showed that decreased hospitalizations for painful crisis accounted for the majority of cost savings in those taking HU. The purpose of this study was to examine whether the expected decrease in hospital utilization occurred after the approval of HU in Maryland. We used data collected by the Maryland Health Services Cost Review Commission to obtain SCA discharge data for Maryland from FY1995 through FY2003. We also reviewed the inpatient and outpatient charts of all adults with SCA admitted to a large university hospital during 2003. Hospitalization rates for adults with SCA in Maryland have increased significantly since approval of HU. While the total costs of inpatient care in Maryland are estimated to have increased by 31% above inflation from 1995 to 2003, the costs of inpatient care for adult SCA patients has increased by almost 60% above inflation. By comparison, there has been no significant increase in the pediatric hospitalization rate. We found that 70% of patients in one hospital who were appropriate candidates for HU were not taking the medication. Hospital utilization among adults with SCA has increased significantly. There are likely many factors that have played a role in this increase. One factor that appears to be involved is the underutilization of HU.