Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Emergency department utilization before and during the COVID-19 pandemic among individuals with sickle cell disease.

BACKGROUND: The emergency department (ED) is a vital source of healthcare for individuals living with sickle cell disease (SCD). Prior research indicates that during the COVID-19 pandemic some individuals with SCD avoided the ED for fear of acquiring COVID-19 or delayed visiting the ED by self-management of symptoms or pain crisis at home. The purpose of the current study was to understand ED utilization rates before and during the pandemic among individuals living with SCD. METHODS: We conducted a retrospective cohort study using population-based SCD surveillance systems in California, Georgia, Michigan, and Tennessee to assess the impact of the pandemic on ED utilization among people with SCD by (1) analyzing trends in monthly ED utilization from January 2019 - December 2020, with specific attention given to immediate changes at the onset of the pandemic; and (2) calculating changes in the volume of utilization by comparing the total ED visits made from March - December 2020 to the same period in 2019, both overall and by demographic characteristics. RESULTS: Across all states, a decline in ED utilization during the onset of the pandemic was seen, with the largest decline seen in those under age 10. By December 2020, utilization rates were higher than their lowest observed month of April 2020, but had not fully returned to pre-COVID levels. During the pandemic, ED visits in each state decreased by as much as 25%, and the number of people with any ED utilization decreased by as much as 26%. CONCLUSIONS: This study confirms and extends the existing literature related to the impact of the pandemic on healthcare utilization patterns in the US, in a unique population with increased healthcare needs.

Impact of Medicaid expansion on access and healthcare among individuals with sickle cell disease.

PURPOSE: Sickle cell disease (SCD) is associated with high acute healthcare utilization. The purpose of this study was to examine whether Medicaid expansion in California increased Medicaid enrollment, increased hydroxyurea prescriptions filled, and decreased acute healthcare utilization in SCD. METHODS: Individuals with SCD (≤65 years and enrolled in Medicaid for ≥6 total calendar months any year between 2011 and 2016) were identified in a multisource database maintained by the California Sickle Cell Data Collection Program. We describe trends and changes in Medicaid enrollment, hydroxyurea prescriptions filled, and emergency department (ED) visits and hospital admissions before (2011-2013) and after (2014-2016) Medicaid expansion in California. RESULTS: The cohort included 3635 individuals. Enrollment was highest in 2014 and lowest in 2016 with a 2.8% annual decease postexpansion. Although <20% of the cohort had a hydroxyurea prescription filled, the percentage increased by 5.2% annually after 2014. The ED visit rate was highest in 2014 and decreased slightly in 2016, decreasing by 1.1% annually postexpansion. Hospital admission rates were similar during the pre- and postexpansion periods. Young adults and adults had higher ED and hospital admission rates than children and adolescents. CONCLUSIONS: Medicaid expansion does not appear to have improved enrollment or acute healthcare utilization among individuals with SCD in California. Future studies should explore whether individuals with SCD transitioned to other insurance plans or became uninsured postexpansion, the underlying reasons for low hydroxyurea utilization, and the lack of effect on hospital admissions despite a modest effect on ED visits.

Estimating the Proportion of Childhood Cancer Cases and Costs Attributable to the Environment in California.

OBJECTIVES: To estimate the proportion of cases and costs of the most common cancers among children aged 0 to 14 years (leukemia, lymphoma, and brain or central nervous system tumors) that were attributable to preventable environmental pollution in California in 2013. METHODS: We conducted a literature review to identify preventable environmental hazards associated with childhood cancer. We combined risk estimates with California-specific exposure prevalence estimates to calculate hazard-specific environmental attributable fractions (EAFs). We combined hazard-specific EAFs to estimate EAFs for each cancer and calculated an overall EAF. Estimated economic costs included annual (indirect and direct medical) and lifetime costs. RESULTS: Hazards associated with childhood cancer risks included tobacco smoke, residential exposures, and parental occupational exposures. Estimated EAFs for leukemia, lymphoma, and brain or central nervous system cancer were 21.3% (range = 11.7%-30.9%), 16.1% (range = 15.0%-17.2%), and 2.0% (range = 1.7%-2.2%), respectively. The combined EAF was 15.1% (range = 9.4%-20.7%), representing $18.6 million (range = $11.6 to $25.5 million) in annual costs and $31 million in lifetime costs. CONCLUSIONS: Reducing environmental hazards and exposures in California could substantially reduce the human burden of childhood cancer and result in significant annual and lifetime savings.

Prevalence, Mortality, and Access to Care for Chronic Kidney Disease in Medicaid-Enrolled Adults With Sickle Cell Disease in California: Retrospective Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is a significant complication in patients with sickle cell disease (SCD), leading to increased mortality. OBJECTIVE: This study aims to investigate the burden of CKD in Medicaid-enrolled adults with SCD in California, examine differences in disease burden between male and female individuals, and assess mortality rates and access to specialized care. METHODS: This retrospective cohort study used the California Sickle Cell Data Collection program to identify and monitor individuals with SCD. Medicaid claims, vital records, emergency department, and hospitalization data from 2011 to 2020 were analyzed. CKD prevalence was assessed based on ICD (International Classification of Diseases) codes, and mortality rates were calculated. Access to specialized care was examined through outpatient encounter rates with hematologists and nephrologists. RESULTS: Among the 2345 adults with SCD, 24.4% (n=572) met the case definition for CKD. The SCD-CKD group was older at the beginning of this study (average age 44, SD 14 vs 34, SD 12.6 years) than the group without CKD. CKD prevalence increased with age, revealing significant disparities by sex. While the youngest (18-29 years) and oldest (>65 years) groups showed similar CKD prevalences between sexes (female: 12/111, 10.8% and male: 12/101, 11.9%; female: 74/147, 50.3% and male: 34/66, 51.5%, respectively), male individuals in the aged 30-59 years bracket exhibited significantly higher rates than female individuals (30-39 years: 49/294, 16.7%, P=.01; 40-49 years: 52/182, 28.6%, P=.02; and 50-59 years: 76/157,48.4%, P<.001). During this study, of the 2345 adults, 435 (18.5%) deaths occurred, predominantly within the SCD-CKD cohort (226/435, 39.5%). The median age at death was 53 (IQR 61-44) years for the SCD-CKD group compared to 43 (IQR 33-56) years for the SCD group, with male individuals in the SCD-CKD group showing significantly higher mortality rates (111/242, 45.9%; P=.009) than female individuals (115/330, 34.9%). Access to specialist care was notably limited: approximately half (281/572, 49.1%) of the SCD-CKD cohort had no hematologist visits, and 61.9% (354/572) did not see a nephrologist during this study's period. CONCLUSIONS: This study provides robust estimates of CKD prevalence and mortality among Medicaid-enrolled adults with SCD in California. The findings highlight the need for improved access to specialized care for this population and increased awareness of the high mortality risk and progression associated with CKD.

Sickle cell disease among Latinx in California.

INTRODUCTION: After African Americans, Latinx are the second largest population affected by Sickle Cell Disease (SCD) in the U.S. However, research has largely ignored how this devastating rare blood disorder specifically affects Latinx nationwide. METHODS: This study compared demographics, genotypes, primary insurance, and health care utilization among Latinx and non-Latinx Californians living with SCD, using data from the California SCD Data Collection Program (2016-2018) and newborn screening cases 2000-2017. RESULTS: Stemming from 6,837 SCD patients, 501(7%) were Latinx. Latinx with SCD (Lx-SCD) were statistically significantly younger than non-Latinx (NLx-SCD) counterparts. Within both groups, females predominated, with 70% being insured by Medicaid. Mean Emergency Department encounters were statistically significantly lower among Lx-SCD adults. DISCUSSION: Lx-SCD differ in age, genotype, and Emergency Department utilization, when compared to NLx-SCD counterparts in California. Latinx are now the largest racial and/or ethnic group in the US, and their presence in SCD population is expected to grow. Therefore, their specific demographic, genotypic, and health care utilization characteristics merit attention to inform policies and programs that will improve their health.

Association between long-term exposure to particulate air pollution with SARS-CoV-2 infections and COVID-19 deaths in California, U.S.A.

Previous studies have reported associations between air pollution and COVID-19 morbidity and mortality, but most have limited their exposure assessment to a large area, have not used individual-level variables, nor studied infections. We examined 3.1 million SARS-CoV-2 infections and 49,691 COVID-19 deaths that occurred in California from February 2020 to February 2021 to evaluate risks associated with long-term neighborhood concentrations of particulate matter less than 2.5 µm in diameter (PM2.5). We obtained individual address data on SARS-CoV-2 infections and COVID-19 deaths and assigned 2000-2018 1km-1km gridded PM2.5 surfaces to census block groups. We included individual covariate data on age and sex, and census block data on race/ethnicity, air basin, Area Deprivation Index, and relevant comorbidities. Our analyses were based on generalized linear mixed models utilizing a Poisson distribution. Those living in the highest quintile of long-term PM2.5 exposure had risks of SARS-CoV-2 infections 20% higher and risks of COVID-19 mortality 51% higher, compared to those living in the lowest quintile of long-term PM2.5 exposure. Those living in the areas of highest long-term PM2.5 exposure were more likely to be Hispanic and more vulnerable, based on the Area Deprivation Index. The increased risks for SARS-CoV-2 Infections and COVID-19 mortality associated with highest long-term PM2.5 concentrations at the neighborhood-level in California were consistent with a growing body of literature from studies worldwide, and further highlight the importance of reducing levels of air pollution to protect public health.

Concurrent use of hydroxyurea and deferasirox in Californians with sickle cell disease.

BACKGROUND AND AIMS: When patients with sickle cell disease have appropriate indications, they can be prescribed hydroxyurea (HU) and deferasirox (DFX) concurrently despite little knowledge about how the two medications interact. We wished to analyze whether there was evidence of adverse interaction between HU and DFX when taken simultaneously and hypothesized that those who took both drugs together had similar clinical complications when compared to those who took only one or neither drug. METHODS: We conducted this retrospective cohort investigation between 2009 and 2016 of persons with SCD in the California Sickle Cell Data Collection Program, a validated database of Californians with SCD a statewide. People in the database who took HU and DFX simultaneously for at least 3 months as compared to those who took either HU or DFX alone or to matched persons who took neither drug were eligible. RESULTS: We identified 104 people who were prescribed both HU and DFX concurrently, 877 who were prescribed HU only, and 314 who were prescribed DFX only during the study period. We identified 416 matched controls who took neither HU nor DFX. People who took both HU and DFX concurrently had similar rates of ED and inpatient encounters and had similar rates and distribution of adverse effects compared to those who took either HU or DFX alone or took neither drug. CONCLUSION: Three months of concurrent use of DFX and HU appears safe, but further studies are required to better understand the safety and effectiveness of this medication combination. (Funded by CDC, CDC Foundation, and others).

Incidence of and Mortality From Amyotrophic Lateral Sclerosis in National Football League Athletes.

Importance: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; understanding ALS risk factors is a critical public health issue. Objectives: To evaluate the incidence of and mortality from ALS in National Football League (NFL) athletes and to describe characteristics associated with ALS within this cohort. Design, Setting, and Participants: This population-based cohort study included all 19 423 NFL athletes who debuted between 1960 and 2019 and played 1 or more professional game. It was conducted between October 3, 2020, and July 19, 2021. Exposure: Participation in the NFL, including playing 1 or more professional games. Main Outcomes and Measures: Cases of ALS and death information were identified based on public records from NFL statistics aggregators, news reports, obituaries, and National Death Index results. The standardized incidence ratio and the standardized mortality ratio were calculated based on data acquired from surveillance studies of ALS accounting for age, sex, and race. Secondary analyses examined the association of body mass index, NFL career duration, race, birth location, and markers of fame, using a nested case-control design, matching athletes with ALS to athletes without ALS, by NFL debut year. Results: A total of 19 423 male former and current NFL players (age range, 23-78 years) were included in this cohort study and were followed up for a cumulative 493 168 years (mean [SD] follow-up, 30.6 [13.7] years). Thirty-eight players received a diagnosis of ALS, and 28 died during the study time frame, representing a significantly higher incidence of ALS diagnosis (standardized incidence ratio, 3.59; 95% CI, 2.58-4.93) and mortality (standardized mortality ratio, 3.94; 95% CI, 2.62-5.69) among NFL players compared with the US male population, adjusting for age and race. Among NFL athletes, nested-case-control analyses found that those who received a diagnosis of ALS had significantly longer careers (mean [SD] duration, 7.0 [3.9] years) than athletes without ALS (mean [SD] duration, 4.5 [3.6] years; odds ratio, 1.2; 95% CI, 1.1-1.3). There were no differences in ALS status based on proxies of NFL fame, body mass index, position played, birth location, or race. Conclusions and Relevance: The age-, sex-, and race-adjusted incidence of and mortality from ALS among all NFL players who debuted between 1960 and 2019 were nearly 4 times as high as those of the general population. Athletes with a diagnosis of ALS had longer NFL careers than those without ALS, suggesting an association between NFL duration of play and ALS. The identification of these risk factors for ALS helps to inform the study of pathophysiological mechanisms responsible for this fatal neurodegenerative disease.

Is in utero exposure to maternal socioeconomic disadvantage related to offspring ovarian reserve in adulthood?

BACKGROUND: Because the ovarian follicle pool is established in utero, adverse exposures during this period may be especially impactful on the size and health of the initial follicle endowment, potentially shaping trajectories of ovarian follicle loss and the eventual onset of menopause. Building on a robust literature linking socioeconomic status (SES) and menopausal timing, the current study examined adverse prenatal exposures related to maternal SES, hypothesizing that greater maternal socioeconomic disadvantage would be associated with lower ovarian reserve in the adult offspring. METHODS: In a healthy, community-based sub-sample (n = 350) of reproductive age participants in the OVA Study (2006-2011), prenatal maternal SES was examined in relation to two biomarkers of ovarian reserve, antimullerian hormone (AMH) and antral follicle count (AFC). Prenatal maternal SES was assessed indirectly using maternal addresses abstracted from participant birth certificates, geocoded, and linked to US Census-derived variables, including neighborhood-level characteristics: education (% of individuals with a HS diploma); poverty (% of families below the poverty line); unemployment (% of individuals > 16 years who are unemployed); and income (median family income). RESULTS: In separate covariate-adjusted linear regression models (following the backward elimination of main effects with P > .10), greater maternal neighborhood education was related to higher ovarian reserve as marked by higher levels of offspring AMH (beta = .142, P < .001) and AFC (beta = .092, P < .10) with models accounting for 19.6% and 21.5% of the variance in AMH and AFC, respectively. In addition, greater maternal neighborhood poverty was related to lower ovarian reserve as marked by lower offspring AMH (beta = -.144, P < .01), with the model accounting for 19.5% of the variance in AMH. CONCLUSIONS: Maternal socioeconomic disadvantage measured indirectly at the neighborhood level was associated with lower ovarian reserve among the adult offspring, independently of offspring SES and other potential confounding factors. This suggests SES-related adversity exposures may have a detrimental impact on the size or health of the initial follicle endowment, leading to accelerated follicle loss over time.

Assessing Child Lead Poisoning Case Ascertainment in the US, 1999-2010.

OBJECTIVES: To compare prevalence estimates for blood lead level ≥10.0 µg/dL (elevated blood lead level [EBLL]) with numbers reported to the Centers for Disease Control and Prevention (CDC) for children 12 months to 5 years of age from 1999 to 2010 on a state-by-state basis. METHODS: State-specific prevalence estimates were generated based on the continuous NHANES according to newly available statistical protocols. Counts of case reports were based on the 39 states (including the District of Columbia) reporting to the CDC Childhood Lead Poisoning Prevention Program during the study period. Analyses were conducted both including and excluding states and years of nonreporting to the CDC. RESULTS: Approximately 1.2 million cases of EBLL are believed to have occurred in this period, but 607 000 (50%) were reported to the CDC. Including only states and years for which reporting was complete, the reporting rate was 64%. Pediatric care providers in 23 of 39 reporting states identified fewer than half of their children with EBLL. Although the greatest numbers of reported cases were from the Northeast and Midwest, the greatest numbers based on prevalence estimates occurred in the South. In southern and western states engaged in reporting, roughly 3 times as many children with EBLL were missed than were diagnosed. CONCLUSIONS: Based on the best available estimates, undertesting of blood lead levels by pediatric care providers appears to be endemic in many states.

Epidemiology and surveillance of amyotrophic lateral sclerosis in two large metropolitan areas in California.

Our objective was to provide demographic profiles and incidence estimates of amyotrophic lateral sclerosis (ALS) in two diverse California metropolitan areas: Los Angeles County (LA) and the San Francisco Bay Area (SFBA). Data were retrospectively collected from multiple sources. Case eligibility criteria included residency in SFBA or LA, and treatment for or diagnosis of ALS between 1 January 2009 and 31 December 2011. Overall incidence rates as well as age-, gender-, race- and ethnicity-specific rates were calculated. We identified 539 ALS cases in SFBA and 545 in LA; 618 were incident cases. Cases were more likely to be male and white. There were considerably more cases (p < 0.05) in LA who were foreign-born (LA, 22%; SFBA, 15%), black (LA, 10%; SFBA, 6%) or Hispanic (LA, 19%; SFBA, 10%). Conversely, the age adjusted incidence rates (per 100,000) were higher in SFBA for whites (LA, 1.40; SFBA, 2.49) and Hispanics (LA, 0.66; SFBA, 1.57) compared with LA. General case demographics and incidence rates in these two areas were similar to published studies. However, the differences between the two areas raise questions about how factors such as geography, access to care, and referral patterns may affect case ascertainment and diagnosis.

Survival and Cause of Death among a Cohort of Confirmed Amyotrophic Lateral Sclerosis Cases.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. Estimates of survival from disease onset range from 20 to 48 months and have been generated using clinical populations or death records alone. METHODS: Data on a cohort of ALS cases diagnosed between 2009-2011 were collected as part of the Los Angeles and San Francisco Bay Area Metropolitan ALS Surveillance projects; death records 2009-2013 were linked to these confirmed cases to determine survival post diagnosis and factors associated with survival time. RESULTS: There were 618 cases identified and 283 of these died during the follow up time period. Median age at death was 64.3 years, and median survival time post-diagnosis was 2.6 years. Age at diagnosis and year of diagnosis were predictors of survival time in adjusted models; those diagnosed at age 80 or older had shorter survival than those diagnosed at age 50 or younger. Most (92%) had ALS noted as a cause of death. DISCUSSION: Survival post-diagnosis may be improved compared with previous reports. Age at diagnosis continues to be the strongest predictor of prognosis; recall case reporting bias may play a role in estimates of survival time.