Side effects following COVID-19 vaccination in pediatric patients with sickle cell disease.

Vulnerable patient populations have seen decreased rates of vaccination against SARS-CoV2-19 (COVID-19) due to hesitancies and distrust, magnified by a paucity of data for certain populations. The rate of COVID-19 vaccination in children with sickle cell disease (SCD) remains low despite the risk for severe complications, resulting in continued infections and hospitalizations from COVID-19. We sought to describe vaccine reactions, including vaso-occlusive crises, emergency department visits, and hospitalizations, in children with SCD. Our findings will start to provide the necessary vaccine side effect data to inform patients, caregivers, and clinicians considering the COVID-19 primary vaccination series.

Side Effects With a Focus on Lymphadenopathy Following COVID-19 Vaccination in Pediatric and AYA Oncology Patients.

The Coronavirus Disease 2019 (COVID-19) pandemic led to the swift development of multiple vaccinations. Vaccine side effects were well-documented in the healthy adult cohort and included fever and lymphadenopathy, however, side effects in the pediatric immunocompromised population have not been reported. This retrospective study investigated vaccine-eligible children and adolescent young adult oncology patients 12 to 35 years old. We found uncommon, mild, and self-limiting side effects among pediatric cancer patients and survivors. This data will help guide pediatric and AYA oncologists in providing anticipatory guidance and serve as a guide to managing lymphadenopathy as a potential confounder of malignancy.

Identifying Barriers to HPV Vaccination for Patients With Sickle Cell Disease and Childhood Cancer Survivors.

Human papillomavirus (HPV) vaccination prevents the development of HPV-associated malignancies. Adolescent and young adult survivors of childhood cancers and patients with sickle cell disease (SCD) are vulnerable patient populations who would significantly benefit from HPV vaccination. In this multimethod study, a retrospective chart review found a notable difference between the rate of HPV vaccinations and other age-appropriate vaccinations in 177 childhood cancer survivors and in 70 patients with SCD. We then sought to describe patient and caregiver beliefs regarding HPV vaccination, through semistructured interviews with 21 patients and 48 caregivers. Interviews were analyzed with a thematic content approach to understand attitudes regarding the HPV vaccination. Qualitative interviews noted that many caregivers and adolescents had baseline misconceptions regarding the HPV vaccination in general and in context with their chronic illness. It was found that a strong recommendation from a trusted subspecialty provider would create reassurance about vaccination and reduce misconceptions and concerns about side effects in the context of a chronic illness. Counseling from subspecialists could have a strong impact on understanding the HPV vaccine in the context of chronic illness. This would likely help overcome many of the barriers to vaccination that are encountered by patients with SCD or oncology survivors.

Understanding caregiver burden with accessing sickle cell care in the Midwest and their perspective on telemedicine.

BACKGROUND: Survival for children with sickle cell disease (SCD) has improved significantly. However, patients with SCD still encounter several impediments to accessing adequate healthcare. Rural and medically underserved areas, such as parts of the Midwest, can exacerbate these barriers, separating children with SCD from subspecialists even further. Telemedicine has been a means to close these gaps in care for children with other special healthcare needs, but few studies have discussed how caregivers of children with SCD perceive its use. METHODS: The objective of this study is to understand the experiences of caregivers of pediatric SCD patients in a geographically diverse area in the Midwest in accessing care, and their perspectives of telemedicine. Caregivers of children with SCD completed an 88-item survey via a secured REDCap link either in-person or via secure text. Descriptive statistics (means, medians, ranges, frequencies) were performed for all responses. Univariate chi square tests were performed to analyze associations, particularly with telemedicine responses. RESULTS: The survey was completed by 101 caregivers. Nearly 20% of families traveled more than 1 hour to reach the comprehensive SCD center. Other than their SCD provider, caregivers reported their child having at least 2 other healthcare providers. Most barriers caregivers identified were financial or resource based. Almost a quarter of caregivers expressed feeling as though these barriers impacted their and/or their child's mental health. Ease of access to team members, as well as scheduling, were common facilitators of care cited by caregivers. The majority were willing to participate in telemedicine visits, regardless of how far they lived from the SCD center, though many noted aspects requiring adaptation. CONCLUSION: This cross-sectional study describes barriers to care experienced by caregivers of children with SCD, regardless of proximity to an SCD center, as well as caregiver perceptions of the usefulness and acceptability of telemedicine for SCD care.

Maintenance of an Immunogenic Response to Pneumococcal Vaccination in Children With Sickle Cell Disease.

Patients with sickle cell disease (SCD) are at increased risk for invasive pneumococcal disease because of splenic dysfunction. To mitigate this risk, patients are protected with prophylactic penicillin until completion of pneumococcal vaccination series. The objective of this study was to assess the maintenance of a protective immune response to pneumococcal vaccination in children with SCD. A retrospective review was conducted between June 2019 and June 2020 of all patients with SCD patients for whom it had been 5±1 year since completion of PPSV23 vaccination series. A total of 41 patients were analyzed. The majority of children (68%) were able to maintain an adequate immune response. There was no identifiable disease characteristic associated with maintenance of an appropriate immunogenic response. This study finds that patients with SCD are able to maintain an adequate immune response at the 5±1 year time point from completion of PPSV23 vaccination series. Similarly, patients were not found to have an increased rate of invasive pneumococcal disease even if not meeting criteria for adequate pneumococcal serum titer levels. Maintenance of pneumococcal titers suggests that there may not be a need for revaccination at the 5-year time point in this patient population.

Caregiver experiences with accessing sickle cell care and the use of telemedicine.

BACKGROUND: Sickle cell disease (SCD) is associated with a wide range of complications. However, a multitude of barriers prevent SCD patients from receiving adequate healthcare, including difficulties with transportation and lack of provider knowledge about disease sequelae. Importantly, studies have demonstrated the benefits of telemedicine in addressing barriers to healthcare. While previous studies have identified barriers to care through quantitative methods, few studies have explored barriers which affect the pediatric SCD patient population in the Midwest, wherein the geographical landscape can prohibit healthcare access. Furthermore, few studies have established acceptability of telemedicine among caregivers and patients with SCD. METHODS: This study aims to increase understanding of barriers to care and perceptions of telemedicine by caregivers of pediatric SCD patients in a medically under-resourced area in the Midwest. Researchers conducted semi-structured interviews with caregivers of children with SCD. The interviews were audio-recorded and transcribed. Thematic analyses were performed. RESULTS: Researchers interviewed 16 caregivers of 15 children with SCD. Thematic analyses of the interview transcripts revealed four broad themes regarding caregiver burden/stress, both facilitators and barriers to SCD healthcare, and general thoughts on the acceptability/usefulness of telemedicine. CONCLUSION: This qualitative study describes common burdens faced by caregivers of SCD, barriers to and facilitators of SCD care in the Midwest, and caregiver perceptions of the usefulness and efficacy of telemedicine for SCD care.

Variation in hospital admission from the emergency department for children with cancer: A Pediatric Health Information System study.

BACKGROUND: Children with cancer experience a wide range of conditions that require urgent evaluation in the emergency department (ED), yet variation in admission rates is poorly documented. PROCEDURE: We performed a retrospective cohort study using the Pediatric Health Information System of ED encounters by children with cancer between July 2012 and June 2015. We compared demographics for admitted versus discharged using univariate statistics, and calculated admission rates by hospital, diagnosis, day of the week, and weekend versus weekday. We assessed the degree of interhospital admission rates using the index of dispersion (ID). RESULTS: Children with cancer had 60 054 ED encounters at 37 hospitals. Overall, 62.5% were admitted (range 43.2%-92.1%, ID 2.6) indicating overdispersed admission rates with high variability. Children with cancer that visited the ED for a primary diagnosis of fever experienced the largest amount of variability in admission with rates ranging from 10.4% to 74.1% (ID 8.1). Less variability existed among hospital admission rates for both neutropenia (range 60%-100%, ID 1.0) and febrile neutropenia (FN) (range 66.7%-100%, ID 0.83). Admission rates by day of the week did not demonstrate significant variability for any of the scenarios examined (overall P = 0.91). There were no differences by weekend versus weekday either (overall P = 0.52). CONCLUSION: The percentage of children with cancer admitted through the ED varies widely by institution and diagnosis. Standardization of best practices for children with cancer admitted through the ED should be an area of continued improvement.

Variation in hospital admission of sickle cell patients from the emergency department using the Pediatric Health Information System.

BACKGROUND: Universal newborn screening and improved treatment options have led to increased survival in sickle cell disease (SCD). However, patients with SCD still rely heavily on acute care services. OBJECTIVE: To determine the variation seen in hospitalizations for the top complaints for ED visits for children with SCD nationally. METHODS: We performed a retrospective review of the Pediatric Health Information Systems (PHIS) Database between October 2011 and September 2015. Emergency department (ED) encounters were selected by using International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes for SCD with and without crisis, fever, and pain. Univariate analyses were performed, as well as index of dispersion (ID) to assess variation by day of the week and region. ANOVA and t-test were used to determine statistical significance. RESULTS: A total of 68 661 ED encounters at 36 hospitals met the criteria for inclusion. Of those encounters, 50.1% were admitted to the hospital. Pain and fever were the most common primary diagnoses among this population. Although variation in hospitalization was seen overall, as well as for a primary diagnosis of pain or fever, this variation was not explained by weekday/weekend designation. CONCLUSION: The results of our study confirm pain and fever as the most common primary diagnoses for children with SCD who seek acute care, as well as demonstrate that while significant variation in hospitalization exists, it is not associated with day of the week. Further studies to elucidate patient- and hospital-level factors that influence admission variation are necessary.

Emergency Department Provider Survey Regarding Acute Sickle Cell Pain Management.

Sickle cell disease (SCD) can lead to potentially devastating complications that occur secondary to vaso-occlusion. Current national clinical guidelines are largely based on expert opinion, resulting in significant variation of management. Provider awareness regarding emergency department (ED) management of vaso-occlusive crises (VOC) remains unknown. A 23-question assessment of VOC management was administered to all eligible ED providers at Riley Hospital for Children between September and November 2018. Univariate analyses were performed to evaluate responses between groups. Of 52 respondents comprised of ED staff attendings (27%), resident trainees (58%), and ED nurses (15%), the majority were not aware of SCD management guidelines being available. Approximately 54% of providers endorsed a high comfort level in managing VOC, with staff and nurses more likely to report this than trainees (P=0.02). Less than 10% of all providers knew the recommended timeframe from triage to initial medication administration. Prolonged time between pain assessments was reported by 25% of providers with a high comfort level in managing VOC, which was similar to providers with a lower comfort level (13%, P=0.217). Only one fourth of all respondents appropriately did not use vital signs as an indication of a patient's pain level, and >10% reported not utilizing patient-reported pain scores. This was not significantly different between provider comfort levels (P=0.285 and 0.412, relatively). Our results suggest education regarding recommended practices was inadequate regardless of reported provider comfort. Further provider education and/or standardized ED VOC management guidelines may serve as areas for improvement in SCD care.

Emergency Department Chief Complaints Among Children With Cancer.

Children with cancer have high emergency department (ED) utilization, but little is known about their chief complaints. A retrospective chart review of ED chief complaints for children with cancer (actively receiving therapy) at Riley Hospital for Children from January 2014 to December 2015 was performed. Proportions of visits and disposition for top 5 chief complaints were determined. Multivariate logistic regression analyzed factors associated with admission. There were 598 encounters by 231 children with cancer. About half (49%) had >1 complaint. The 5 most common primary chief complaints were: fever (60.2%), pain (6.5%), nausea/vomiting (5.0%), bleeding (3.9%), and abnormal laboratory values (3.3%). Admission rates varied, with the highest rates being for nausea/vomiting (66.7%). Risk factors for admission were: hospitalization in prior 4 weeks (odds ratio [OR], 2.67; confidence interval [CI], 1.77-4.02), chief complaint of fever (OR, 1.90; CI, 1.16-3.09). For each increase in number of chief complaints, odds increased by 1.45 (CI, 1.14-1.83). Black, non-Hispanic (OR, 0.44; CI, 0.22-0.88) as compared with white, non-Hispanic, younger age (OR, 0.53; CI, 0.29-0.99) or complaint of abnormal laboratory values (OR, 0.20; CI, 0.06-0.68) had lower odds of admission. Children with cancer present to the ED with multiple and varied complaints. Future interventions could aim to improve caregiver anticipatory guidance and ED visit preparedness.

No improvement in clinical trial enrollment for adolescents and young adults with cancer at a children's hospital.

BACKGROUND: We have previously published data from 2001 to 2006 showing that adolescent and young adult (AYA) oncology patients have significantly lower therapeutic clinical trial enrollment rates than younger patients. Our objective was to determine if the enrollment of AYA patients on therapeutic studies at the same institution has improved in recent years with the greater focus on this population locally and nationally. METHODS: We retrospectively analyzed cancer registry data at the Children's Hospital of Pittsburgh (CHP) for all new oncologic diagnoses between January 2010 and December 2014. These data included age, gender, diagnosis, race and whether the patient was enrolled on an open treatment study. Univariate analyses were carried out to compare demographic data between AYA patients (aged 15-22) who enrolled on study and those who did not. RESULTS: Eight hundred sixty-five new oncology patients were seen at CHP during this time, 23% of whom were 15 years or older; 33% of all patients were treated on a clinical trial, including 34% of younger patients and 24% of older patients (P = 0.0017). The differences between these rates and those from prior years in both age groups (38% and 27%, respectively) were not statistically significant (P = 0.15, 0.53). The most common reason for the low enrollment rates was again the lack of an open therapeutic trial. CONCLUSION: Despite initiatives at CHP and on the national level to enroll more AYA patients on clinical trials, our most recent data show no improvement. This is a potentially remediable factor that needs to continue to be prioritized nationally.

Increasing Visibility of Sickle Cell Disease in Indiana: Establishing Baseline Prevalence Using Integrated Data From Multiple Sources.

OBJECTIVE: The Indiana Sickle Cell Data Collection (IN-SCDC) program aims to provide timely, reliable, and locally relevant information on the sickle cell disease (SCD) population in Indiana to inform public health interventions, research, and policy development. We describe the development of the IN-SCDC program and report the prevalence and geographic distribution of people with SCD in Indiana using an integrated data collection approach. METHODS: Using multiple integrated data sources and case definitions established by the Centers for Disease Control and Prevention, we classified cases of SCD in Indiana during 2015-2019. We calculated the prevalence and incidence of SCD and described characteristics of people with SCD. RESULTS: We identified 1695 people living with SCD in Indiana during the study period. The median age of people living with SCD was 21 years, and 1474 (87.0%) were Black or African American. Most (n = 1596, 91%) resided in metropolitan counties. The age-adjusted prevalence of SCD was 24.7 cases per 100 000 people. The prevalence of SCD among Black or African American people was 209.3 per 100 000 people. The incidence was 1 in 2608 live births overall and 1 in 446 live births among Black or African American people. Eighty-six deaths were confirmed in this population during 2015-2019. CONCLUSIONS: Our results establish a baseline for the IN-SCDC program. Baseline and future surveillance program efforts will help accurately inform standards of care for treatments, identify gaps in coverage and access to care, and provide guidance for legislators and community-based organizations.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 35 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT05045820.

The evolving treatment landscape for children with sickle cell disease.

Sickle cell disease is the most common inherited pathological haemoglobinopathy. Over the past 30 years, disease-related morbidity and mortality have improved in high-income countries due to advances in preventive care and treatments. Established disease-modifying therapies, such as hydroxyurea (hydrocarbamide), are continuing to have an important role in the treatment of sickle cell disease, and newer agents also show promise. In the past 5 years, the US Food and Drug Administration approved three additional sickle cell disease-modifying medications, and new gene therapies have been developed as an alternative curative treatment to haematopoietic stem-cell transplantation. In this Review, we discuss the current treatment landscape for paediatric sickle cell disease and emerging innovations in care. We also review the need for close, long-term management for children receiving newer therapies and the importance of ongoing investment in people with sickle cell disease in low-income and middle-income countries.

Pediatric hematology and oncology physician and nurse practitioner views of the HPV vaccine and barriers to administration.

Rates of Human papilloma virus (HPV) vaccination among pediatric survivors of cancer and patients with sickle cell disease are lower than the national average. While recent attention has focused on patient HPV vaccine hesitancy and refusal, less is known about provider-level and system-level barriers to vaccinations in pediatric hematology/oncology (PHO) populations. Applying thematic analysis to qualitative interviews with 20 pediatric hematology/oncology physicians and nurse practitioners, we examine their views regarding HPV vaccination, with a focus on access and barriers to providing HPV vaccination in PHO practices. Results demonstrated that despite 90% of interviewees supporting HPV vaccination in their population, the number of pediatric hematology/oncology providers who reported that they counsel about HPV or provide HPV vaccination was 45%, even in stem cell and sickle cell clinics, where other childhood vaccines are commonly provided. Clinicians identified provider-level, clinic-level, and system-level barriers to giving the HPV vaccination, including but not limited to time/flow constraints, lack of resources, and continued education regarding the HPV vaccine. These barriers impede the ability for pediatric hematology/oncology providers to counsel and provide HPV vaccination to this specialized population.

Protocol and biomarker strategy for a multi-site randomized controlled trial examining biological mechanisms and dosing of active music engagement in children with acute lymphoblastic leukemia and lymphoma and parents.

BACKGROUND: Music therapy is a standard palliative care service in many pediatric and adult hospitals; however, most research has focused on the use of music to improve psychosocial dimensions of health, without considering biological dimensions. This study builds on prior work examining psychosocial mechanisms of action underlying an Active Music Engagement (AME) intervention, designed to help manage emotional distress and improve positive health outcomes in young children with cancer and parents (caregivers), by examining its effects on biomarkers of stress and immune function. METHODS: This two-group randomized controlled trial (R01NR019190) is designed to examine biological mechanisms of effect and dose-response relationships of AME on child/parent stress during the consolidation phase of Acute B- or T-cell Lymphoblastic Leukemia (ALL) and T-cell Lymphoblastic Lymphoma (TLyLy) treatment. Child/parent dyads (n = 228) are stratified (by age, site, risk level) and randomized in blocks of four to the AME or attention control condition. Each group receives one session (30-minutes AME; 20-minutes control) during weekly clinic visits (4 weeks standard risk B-cell ALL; 8 weeks high risk B-cell ALL/T-cell ALL/TLyLy). Parents complete questionnaires at baseline and post-intervention. Child/parent salivary cortisol samples are taken pre- and post-session (sessions 1-4). Child blood samples are reserved from routine draws before sessions 1 and 4 (all participants) and session 8 (high risk participants). We will use linear mixed models to estimate AME's effect on child/parent cortisol. Examining child/parent cortisol as mediators of AME effects on child and parent outcomes will be performed in an ANCOVA setting, fitting the appropriate mediation models using MPlus and then testing indirect effects using the percentile bootstrap approach. Graphical plots and non-linear repeated measures models will be used to examine dose-response relationship of AME on child/parent cortisol. DISCUSSION: During pediatric cancer treatment there are special challenges that must be considered when measuring cortisol and immune function. In this manuscript we discuss how we addressed three specific challenges through our trial design. Findings from this trial will increase mechanistic understanding of the effects of active music interventions on multiple biomarkers and understanding of dose-response effects, with direct implications for clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04400071.

Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.

This study aimed to comprehensively analyze inflammatory and autoimmune characteristics of patients with sickle cell disease (SCD) at a steady-state condition (StSt) compared to healthy controls (HCs) to explore the pathogenesis of StSt and its impact on patients' well-being. The study cohort consisted of 40 StSt participants and 23 HCs enrolled between July 2021 and April 2023. StSt participants showed elevated white blood cell (WBC) counts and altered hematological measurements when compared to HCs. A multiplex immunoassay was used to profile 80 inflammatory cytokines/chemokines/growth factors in plasma samples from these SCD participants and HCs. Significantly higher plasma levels of 37 analytes were observed in SCD participants, with HGF, IL-18, IP-10, and MCP-2 being among the most significantly affected analytes. Additionally, autoantibody profiles were also altered, with elevated levels of anti-SSA/Ro60, anti-Ribosomal P, anti-Myeloperoxidase (MPO), and anti-PM/Scl-100 observed in SCD participants. Flow cytometric analysis revealed higher rates of red blood cell (RBC)/reticulocyte-leukocyte aggregation in SCD participants, predominantly involving monocytes. Notably, correlation analysis identified associations between inflammatory mediator levels, autoantibodies, RBC/reticulocyte-leukocyte aggregation, clinical lab test results, and pain crisis/sensitivity, shedding light on the intricate interactions between these factors. The findings underscore the potential significance of specific biomarkers and therapeutic targets that may hold promise for future investigations and clinical interventions tailored to the unique challenges posed by SCD. In addition, the correlations between vaso-occlusive crisis (VOC)/pain/sensory sensitivity and inflammation/immune dysregulation offer valuable insights into the pathogenesis of SCD and may lead to more targeted and effective therapeutic strategies.