CalScope: methodology and lessons learned for conducting a remote statewide SARS-CoV-2 seroprevalence study in California using an at-home dried blood spot collection kit and online survey.

BACKGROUND: To describe the methodology for conducting the CalScope study, a remote, population-based survey launched by the California Department of Public Health (CDPH) to estimate SARS-CoV-2 seroprevalence and understand COVID-19 disease burden in California. METHODS: Between April 2021 and August 2022, 666,857 randomly selected households were invited by mail to complete an online survey and at-home test kit for up to one adult and one child. A gift card was given for each completed survey and test kit. Multiple customized REDCap databases were used to create a data system which provided task automation and scalable data management through API integrations. Support infrastructure was developed to manage follow-up for participant questions and a communications plan was used for outreach through local partners. RESULTS: Across 3 waves, 32,671 out of 666,857 (4.9%) households registered, 6.3% by phone using an interactive voice response (IVR) system and 95.7% in English. Overall, 25,488 (78.0%) households completed surveys, while 23,396 (71.6%) households returned blood samples for testing. Support requests (n = 5,807) received through the web-based form (36.3%), by email (34.1%), and voicemail (29.7%) were mostly concerned with the test kit (31.6%), test result (26.8%), and gift card (21.3%). CONCLUSIONS: Ensuring a well-integrated and scalable data system, responsive support infrastructure for participant follow-up, and appropriate academic and local health department partnerships for study management and communication allowed for successful rollout of a large population-based survey. Remote data collection utilizing online surveys and at-home test kits can complement routine surveillance data for a state health department.

Trends in blood transfusion, hydroxyurea use, and iron overload among children with sickle cell disease enrolled in Medicaid, 2004-2019.

BACKGROUND: There have been significant changes in clinical guidelines for sickle cell disease (SCD) over the past two decades, including updated indications for hydroxyurea, transfusions, and iron overload management. In practice however, there are few studies that examine SCD care utilization over time. METHODS: We conducted a serial cross-sectional cohort study of pediatric SCD patients from 2004 to 2019 using Georgia Medicaid claims data. For each year, we reported receipt of any transfusion, chronic transfusion, or three or more filled hydroxyurea prescriptions. For children receiving chronic transfusion (six or more annual transfusions), we evaluated iron overload diagnosis, monitoring, and chelation use. Among children with sickle cell anemia (SCA), we examined rates of transfusions and hydroxyurea use. The Cochran-Armitage test was used to assess trend. RESULTS: There were 5316 unique children 2-18 years old with SCD enrolled in Georgia Medicaid from 2004 to 2019. Children receiving any transfusion increased from 2004 to 2010, then stabilized. In SCA patients, chronic transfusions initially increased from 2004 to 2010, then stabilized from 2010 to 2019. For chronically transfused children, monitoring of iron burden and filled chelator prescriptions both increased significantly. Hydroxyurea use in SCA patients increased from 12% to 37%, with increases noted within each age group, most notably from 21% to 60% in the 13-18-year-old cohort. CONCLUSION: We demonstrated changes in SCD care utilization over time, including increased hydroxyurea use, changes in transfusion rates, and increased attention to iron overload management. While trends in clinical management do follow updates in treatment guidelines, there is still delayed and suboptimal uptake of guideline recommendations in pediatric SCD patients.

Influenza Vaccination Receipt in Pediatric Patients With Cancer or Sickle Cell Disease.

BACKGROUND: Influenza causes greater morbidity in children with cancer or sickle cell disease (SCD). Literature on influenza vaccination receipt for these populations is limited in low-vaccination states. Outpatient interventions improve vaccine receipt but isolated inpatient interventions remain unstudied. PROCEDURE: We reviewed influenza vaccine receipt of children with cancer or SCD treated at Children's Healthcare of Atlanta during three influenza seasons. We implemented a clinical decision support intervention during an influenza season and compared influenza vaccine receipt preintervention and postintervention among admitted children. RESULTS: The oncology cohort (N=1548, 60% to 62%) and the SCD cohort (N=2549, 61% to 65%) had similar-to-higher vaccination receipt to the United States (58% to 64%, P =0.01 to 0.79) and Georgia (51% to 56%, P <0.01). The intervention did not significantly improve vaccination receipt for admitted children with cancer (40% vs. 56%, P =0.05 to 0.88) or SCD (44% vs. 56%, P =0.01). Regression modeling also found no significant increase in vaccine receipt (hematologic malignancy: 0.8 [0.73 to 0.98], solid tumor: 0.9 [0.80 to 1.90], central nervous system tumor: 0.9 [0.71 to 1.14], SCD: 0.9 [0.85 to 0.99]). CONCLUSIONS: Children with cancer and SCD have similar-to-greater influenza vaccination receipt compared with Georgia and the United States. An inpatient intervention did not significantly improve influenza vaccine receipt in these patient cohorts. Future studies are needed to identify alternative approaches to improving vaccine receipt in these cohorts.

Evaluating the association between in-person work and the risk of SARS-CoV-2 infection through June 2021.

OBJECTIVES: Recent studies have evaluated COVID-19 outbreaks and excess mortality by occupation sectors. Studies on SARS-CoV-2 infection across occupation and occupation-related factors remain lacking. In this study, we estimate the effect of in-person work on SARS-CoV-2 infection risk and describe SARS-CoV-2 seroprevalence among working adults. METHODS: We used Wave 1 data (May to June 2021) from CalScope, a population-based seroprevalence study in California. Occupation data were coded using the National Institute for Occupational Safety and Health Industry and Occupation Computerized Coding System. Dried blood spot specimens were tested for antibodies to establish evidence of prior infection. We estimated the causal effect of in-person work on SARS-CoV-2 infection risk using the g-formula and describe SARS-CoV-2 seroprevalence across occupation-related factors. RESULTS: Among 4335 working adults, 53% worked in person. In-person work was associated with increased risk of prior SARS-CoV-2 infection (risk difference: 0.03; [95% CI: 0.02-0.04]) compared with working remotely. Workers that reported job loss or who were without medical insurance had higher evidence of prior infection. Amongst in-person workers, evidence of prior infection was highest within farming, fishing, and forestry (55%; [95% CI: 26%-81%]); installation, maintenance, and repair (23%; [12%-39%]); building and grounds cleaning and maintenance (23%; [13%-36%]); food preparation and serving related (22% [13%-35%]); and healthcare support (22%; [13%-34%]) occupations. Workers who identified as Latino, reported a household income of <$25K, or who were without a bachelor's degree also had higher evidence of prior infection. CONCLUSIONS: SARS-CoV-2 infection risk varies by occupation. Future vaccination strategies may consider prioritizing in-person workers.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.

Sex and frequency of pain episodes are associated with acute pain trajectories in adolescents with sickle cell disease.

Introduction/Objective: Acute pain episodes are a major cause of health care utilization (HCU) in sickle cell disease (SCD), and adolescence is associated with increased pain frequency. We sought to determine whether there were differences in acute pain trajectories by sex and frequency of pain episodes among adolescents with SCD who presented to the emergency department (ED). Methods: Retrospective review of electronic health records from a large, multicampus, pediatric SCD program. Results: Of the 113 adolescents included, the mean age was 16.6 (SD 0.9), 41.6% (n = 47) were female, 77.9% (n = 88) had HbSS or a similarly severe genotype, and 43.4% (n = 49) had ≥3 episodes of HCU for pain, which we defined as having history of high HCU for pain. Those with a history of high HCU for pain had higher mean pain intensity scores at presentation, were more likely to receive either intravenous or intranasal opioids, and were more likely to be hospitalized. In a model considering the 3-way interaction between sex, history of high HCU for pain, and follow-up time from the initial pain intensity score, adjusted for opioid per kilogram body weight, and prescription of hydroxyurea, adolescent female patients with high HCU for pain had the slowest decline in pain intensity during treatment for acute pain in the ED. Conclusion: Sex and history of high HCU for pain are associated with acute pain trajectories in adolescents with SCD presenting to the ED. These novel findings should be confirmed in future prospective studies.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines.

Children with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Comparison of Anti-Mullerian Hormone Levels Pre- and Post-Hematopoietic Cell Transplantation in Pediatric and Adolescent Females with Sickle Cell Disease.

Allogeneic hematopoietic cell therapy (HCT) is an established cure for sickle cell disease (SCD); however, HCT conditioning regimens are known to be gonadotoxic. Anti-mullerian hormone (AMH) measures ovarian reserve, and follicle-stimulating hormone (FSH) defines premature ovarian insufficiency (POI) at values >40 mIU/mL in pubertal females. The present study was conducted to assess ovarian reserve and function before and after transplantation in pediatric and adolescent females with SCD treated with allogeneic HCT between January 2015 and June 2020 at Children's Healthcare of Atlanta. In this retrospective review of 17 females age <21 years with SCD who had AMH levels measured at baseline and at 2 years post-HCT, AMH levels were categorized as normal, low, or undetectable, and FSH levels were measured and used to identify pubertal females who had developed POI. Demographic and treatment data were abstracted from the institutional database and medical records, and a descriptive statistical analysis was conducted. Of the 17 patients in the study cohort, 14 had been treated with hydroxyurea and 3 had chronic transfusions but with no significant iron overload. AMH levels were normal in 15 patients (88%) and low in 2 patients (12%) at baseline. The median age at HCT was 7.5 years (range, 3.7 to 20.3 years), and 14 patients (82%) underwent matched related donor HCT. After HCT, 15 patients (88%) had undetectable AMH and 2 (12%) had low AMH, with no apparent differences by HCT conditioning regimen. No pubertal patients had POI at baseline, whereas 55% of pubertal patients had progressed to POI by 2 years post-HCT. In this cohort, the majority of females had normal AMH levels at baseline but undetectable levels after HCT. Females with SCD considering HCT should be counseled about the treatment-related risk of gonadal dysfunction. © 2022 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Bloodstream Infections in Children With Sickle Cell Disease: 2010-2019.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS: We conducted a retrospective cohort study of children aged <18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45-1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20-2.94) and chronic transfusions (OR 2.66; 95% CI 1.51-4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39-0.84). CONCLUSIONS: BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD.

CalScope: Monitoring Severe Acute Respiratory Syndrome Coronavirus 2 Seroprevalence From Vaccination and Prior Infection in Adults and Children in California May 2021-July 2021.

Background: Understanding the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies from vaccination and/or prior infection is critical to the public health response to the pandemic. CalScope is a population-based serosurvey in 7 counties in California. Methods: We invited 200 000 randomly sampled households to enroll up to 1 adult and 1 child between April 20, 2021 and June 16, 2021. We tested all specimens for antibodies against SARS-CoV-2 nucleocapsid and spike proteins, and each participant completed an online survey. We classified participants into categories: seronegative, antibodies from infection only, antibodies from infection and vaccination, and antibodies from vaccination only. Results: A total of 11 161 households enrolled (5.6%), with 7483 adults and 1375 children completing antibody testing. As of June 2021, 33% (95% confidence interval [CI], 28%-37%) of adults and 57% (95% CI, 48%-66%) of children were seronegative; 18% (95% CI, 14%-22%) of adults and 26% (95% CI, 19%-32%) of children had antibodies from infection alone; 9% (95% CI, 6%-11%) of adults and 5% (95% CI, 1%-8%) of children had antibodies from infection and vaccination; and 41% (95% CI, 37%-45%) of adults and 13% (95% CI, 7%-18%) of children had antibodies from vaccination alone. Conclusions: As of June 2021, one third of adults and most children in California were seronegative. Serostatus varied regionally and by demographic group.

Preliminary evaluation of the clinical implementation of cognitive-behavioral therapy for chronic pain management in pediatric sickle cell disease.

OBJECTIVES: Evaluate the implementation of cognitive-behavioral therapy (CBT) for chronic pain in a clinical setting by comparing youth with sickle cell disease (SCD) who initiated or did not initiate CBT. DESIGN: Youth with SCD (ages 6-18; n = 101) referred for CBT for chronic pain were compared based on therapy attendance: Established Care; Early Termination; or Comparison (i.e., did not initiate CBT). SETTING: Outpatient pediatric psychology and comprehensive SCD clinics in 3 locations at a southeastern children's hospital. INTERVENTIONS: CBT delivery was standardized. Treatment plans were tailored to meet individualized needs. MAIN OUTCOME MEASURES: Healthcare utilization included pain-related inpatient admissions, total inpatient days, and emergency department reliance (EDR) at 12-months pre-post CBT. Patient-reported outcomes (PROs) included typical pain intensity, functional disability, and coping efficacy pre-post treatment. RESULTS: Adjusting for age, genotype, and hydroxyurea, early terminators of CBT had increased rates of admissions and hospital days over time relative to comparisons; those who established care had faster reduction in admissions and hospital days over time relative to comparisons. EDR decreased by 0.08 over time for Established Care and reduced by 0.01 for every 1 completed session. Patients who completed pre- and post-treatment PROs reported decreases in typical pain intensity, functional disability, and improved coping efficacy. CONCLUSIONS: Establishing CBT care may support reductions in admissions for pain, length of stay, and EDR for youth with chronic SCD pain, which may be partially supported by patient-reported improvements in functioning, coping, and lower pain intensity following CBT. Enhancing clinical implementation of multidisciplinary treatments may optimize the health of these youth.