Pediatric Sickle Cell Disease Research Articles

Whole-blood transcriptome analysis reveals distinct gene expression signatures in paediatric patients with sickle cell anaemia before and after exercise.

Sickle cell anaemia (SCA) patients display elevated levels of circulating pro-inflammatory cytokines and endothelial activation markers compared to healthy peers. The impact of exercise on the pro-inflammatory state in SCA remains unclear. This study aimed to characterize the whole-blood transcriptome profile in response to an acute bout of exercise in paediatric SCA patients. Twenty-three SCA participants (13 ± 3 years, 52% girls) and 17 healthy controls (14 ± 3 years, 29% girls) performed eight 2-min bouts of cycle ergometry interspersed with 1-min rest intervals. Whole-blood transcriptome profile (RNA-seq) was performed before and after exercise. At baseline, gene pathways associated with gas transport in erythrocytes were up-regulated in SCA patients compared to controls. Following exercise, gene pathways associated with innate immunity were altered in both groups. Interaction analyses revealed 160 annotated genes (101 up- and 59 down-regulated) that differentially altered by exercise in SCA patients. Moreover, genes that exhibited a blunted response to exercise in SCA patients were enriched in the IL-17 signalling pathway, suggesting an impaired innate immune response to exercise. This data will contribute to the development of evidence-based exercise prescription guidelines for this patient population.

Attitudes, Beliefs, and Intention to Receive a COVID-19 Vaccine for Pediatric Patients With Sickle Cell Disease.

Sickle cell disease (SCD), which occurs primarily in individuals of African descent, has been identified as a preexisting health condition for COVID-19 with higher rates of hospitalization, intensive care unit admissions, and death. National data indicate Black individuals have higher rates of vaccine hesitancy and lower COVID-19 vaccination rates. Understanding the key predictors of intention to receive a COVID-19 vaccine is essential as intention is strongly associated with vaccination behavior. This multisite study examined attitudes, beliefs, intentions to receive COVID-19 vaccines, and educational preferences among adolescents, young adults, and caregivers of children living with SCD. Participants completed an online survey between July 2021 and March 2022. Multivariate logistic regression was used to examine the association between participant age and COVID-19 vaccine attitudes, beliefs, and vaccine intentions. Of the 200 participants, 65.1% of adolescents, 62.5% of young adults, and 48.4% of caregivers intended to receive a COVID-19 vaccine for themselves or their child. Perception that the vaccine was safe was statistically significant and associated with patient and caregiver intention to receive the COVID-19 vaccine for themselves or their child. Participant age was also statistically significant and associated with the intent to get a booster for patients. Study findings highlight key concerns and influencers identified by patients with SCD and their caregivers that are essential for framing COVID-19 vaccine education during clinical encounters. Study results can also inform the design of messaging campaigns for the broader pediatric SCD population and targeted interventions for SCD subpopulations (eg, adolescents, caregivers).

Body composition analysis using dual-energy x-ray absorptiometry in an Egyptian pediatric sickle cell disease cohort.

Growth failure is commonly encountered in sickle cell disease (SCD). Tissue compartment growth and development are subsequently likely to be altered in such patients. We aimed to analyze body composition in an Egyptian pediatric SCD cohort using dual-energy x-ray absorptiometry (DEXA), one of the most comprehensive and noninvasive assessment methods available. Forty children with SCD ≤18years and 40 healthy youngsters age- and gender-matched were enrolled. Patients' demographic, clinical, and laboratory parameters were obtained from their archived files. All patients and controls were subjected to body composition assessment using a MedixDR-Whole Body DEXA System. In SCD patients; weight and height relative to age Z scores were significantly lower (p<.001), total body lean was significantly higher (p=.006), and total body fat percentage was lower, yet the difference was not statistically significant (p=.09). There were no statistically significant variations in bone mineral density or content, basal metabolic rate, subcutaneous adipose tissue, android/gynoid fat ratio, and visceral adipose tissue. There were no significant gender disparities between SCD patients and controls. Faltering growth in children with SCD should be addressed with a multidisciplinary approach including nutritional support, correction of anemia, and proper medical care. Body composition parameters assessed using DEXA were comparable between cases and controls apart from total body lean. Further clinical studies are needed with multicenter cooperation and a larger sample size to assess the usefulness of DEXA as an assessment tool for body composition in children with SCD.

New Horizons in Emergency Department Management of Pediatric Sickle Cell Disease.

Sickle cell disease (SCD) is an important topic for emergency medicine audiences because complications of the disease account for a large proportion of hematologic emergencies that are seen in the emergency department each year. Early recognition and aggressive management of emergency complications of SCD can help to reduce the morbidity and mortality associated with this disease. Although the treatment recommendations for some complications of SCD are based on expert opinion, there has been advancement in the understanding of the pathogenesis of the disease and evidence regarding the treatment options available for managing acute complications. This continuing medical education article will provide a summary of the clinical manifestation and management of the most common acute complications of SCD: infection, vaso-occlusive episode, acute chest syndrome, splenic sequestration, stroke, and priapism.

Malaria infection reveals hemoglobinopathy: A pediatric sickle cell anemia case reports

Malaria infection reveals hemoglobinopathy: A pediatric sickle cell anemia case reports

Partial Splenic Embolization in Paediatric Sickle Cell Disease Patients with Hypersplenism.

To assess the safety and efficacy of partial splenic embolization (PSE) to reduce the need of transfusions and improve hematologic parameters in patients with hypersplenism and sickle cell disease (SCD). This prospective study includes 35 homozygous hemoglobin S patients with SCD and hypersplenism who underwent PSE from 2015 until 2021 in Kinshasa. Patients were evaluated, before and after PSE (1, 3 and 6months), using clinical, laboratory and ultrasonographic methods. PSE was performed with the administration of gelatin sponge particles embolizing 60-70% of the splenic parenchyma. The mean age was 10 (± 4) years and (21/35, 60%) were male. After PSE Leucocytes decreased at 3 months (16 692.94 vs 13 582.86, p = 0.02) and at six months Erythrocytes increased 2 004 000 vs. 2 804 142 (p < 0.001), Platelets increased (168 147 vs. 308 445, p < 0.001) and Hemoglobin increased (5.05g/dL vs. 6.31g/dL, p < 0.001) There was a significant dicrease in the need of transfusions from 6 (2-20) before PSE to 0.06 (0-1) after PSE (p < 0.001). The most frequent complication was splenic rupture (4/35, 11.4%), seen only and in all patients with hypoechogenic nodules at baseline. PSE is a safe procedure in patients with SCD and hypersplenism, that do not have hypoechogenic nodules in the spleen. PSE improves the hematological parameters and reduces the frequency of blood transfusions.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies. Antibodies to biotinylated RBC (B-RBC) occasionally are detected after exposure, which may impact B-RBC survival in subsequent RCS studies. Pediatric patients with SCD receiving monthly chronic transfusions underwent RCS studies, receiving aliquots of allogeneic RBC labeled at distinct densities of biotin (2-18 μg/mL). B-RBC survival was followed for 4 months post-transfusion, and B-RBC antibody screening for 6 months. Patients with warm autoantibodies (WAA) or B-RBC antibodies are reported here. RBC antibodies were detected during RCS in four patients: one with WAA, one with WAA followed by B-RBC-specific antibodies, and two with transient B-RBC antibodies within the first 5 weeks of exposure. B-RBC half-lives (T50) ranged 37.6-61.7 days (mean 47.8 days). There was no evidence of increased hemolysis or accelerated B-RBC clearance in the presence of WAA or B-RBC antibodies. Biotinylation of allogenic RBC can be used to assess the possible effects of RBC antibodies on transfusion survival in individual cases, particularly when it is uncertain if the detected antibodies may result in hemolysis. In the cases presented here, neither WAA nor B-RBC antibodies were associated with significant shortening of B-RBC survival in individuals with SCD.

Stroke without cerebral arteriopathy in sickle cell disease children: causes and treatment.

Cerebral arteriopathy (CA) in children with sickle cell disease (SCD) is classically described as chronic stenosis of arteries in the anterior brain circulation, leading to ischemic stroke. Some studies have however reported strokes in children with SCD but without CA. In order to better understand the etiology and risk factors of these strokes, we retrospectively analyzed ischemic strokes occurring in a large cohort of children over a 13 year-period. Between 2007 and 2020, 25/1500 children with SCD had an ischemic stroke in our center. Among them, 13 (52%) had CA, described as anatomical arterial stenosis, while 12 (48%) did not. Patients with stroke without CA were older than patients with stroke attributed to SCD-CA (9.0 years old vs 3.6 years old, p=0.008), and had more frequently a SC genotype (25% vs 0% respectively). Their stroke involved posterior circulation more frequently, with cerebellar involvement in 42%. Retained stroke etiologies in patients without typical SCD-related CA were reversible cerebral vasoconstriction syndrome, cerebral fat embolism, arterial thrombosis or thromboembolism, hyperviscosity, vasculitis in a context of infectious meningoencephalitis, and severe hemodynamic failure. No recurrence was observed in the 24 months following stroke, even though 67% of the patients were no longer receiving exchange transfusions in this group. In conclusion, in a cohort of pediatric SCD patients with efficient stroke screening strategy, half of occurring ischemic strokes were related to causes other than CA. They affected a different population of SCD children and systematic long-term transfusion programs may not be necessary in these cases.

National Quality Indicators in Pediatric Sickle Cell Anemia.

To assess nationally endorsed claims-based quality measures in pediatric sickle cell anemia (SCA). Using data from the Sickle Cell Data Collection programs in California and Georgia from 2010 to 2019, we evaluated 2 quality measures in individuals with hemoglobin S/S or S/β-zero thalassemia: (1) the proportion of patients aged 3 months to 5 years who were dispensed antibiotic prophylaxis for at least 300 days within each measurement year and (2) the proportion of patients aged 2 to 15 years who received at least 1 transcranial Doppler ultrasound (TCD) within each measurement year. We then evaluated differences by year and tested whether performance on quality measures differed according to demographic and clinical factors. Only 22.2% of those in California and 15.5% in Georgia met or exceeded the quality measure for antibiotic prophylaxis, with increased odds associated with rural residence in Georgia (odds ratio 1.61; 95% confidence interval 1.21-2.14) compared with urban residence and a trend toward increased odds associated with a pediatric hematologist prescriber (odds ratio 1.28; 95% confidence interval 0.97, 1.69) compared with a general pediatrician. Approximately one-half of the sample received an annual assessment of stroke risk using TCD (47.4% in California and 52.7% in Georgia), with increased odds each additional year in both states and among younger children. The rates of receipt of recommended antibiotic prophylaxis and annual TCD were low in this sample of children with SCA. These evidence-based quality measures can be tracked over time to help identify policies and practices that maximize survival in SCA.

Exploring Factors Associated with Quality of Life in Caregivers of Children and Adolescents with Sickle Cell Disease and HIV: A Comparative Analysis.

Paediatric HIV and sickle cell disease (SCD) are two stigmatising and potentially fatal illnesses that place a significant burden on families. HIV patients benefit from a longstanding free-service national programme in Cameroon, and this could considerably alleviate burden of care on HIV caregivers, possibly leading to better quality of life (QoL) in HIV caregivers compared to SCD caregivers. Our study aimed to compare the QoL between caregivers of children and adolescents with SCD and HIV and explore factors associated with this QoL in Cameroon. We conducted a hospital-based cross-sectional analytic study at Douala Laquintinie Hospital from February to May 2023. A questionnaire was administered to caregivers of paediatric patients (≤18 years) with SCD and HIV. The Pediatrics Quality of Life-Family Impact Module (PedsQL FIM), the 7-item Generalized Anxiety Disorder (GAD-7), and the 9-item Patient Health Question (PHQ-9) tools were used as measures of quality of life, anxiety, and depression, respectively. Multivariable linear regression was used to determine factors associated with quality of life. A significance level was set at p < 0.05. We included 199 caregivers: SCD = 104 and HIV = 95. The mean age of caregivers in our sample was 40.47 ± 10.18 years. Caregivers of paediatric patients with HIV had a better mean quality of life than SCD (93.01 ± 7.35SD versus 64.86 ± 9.20SD, p < 0.001). PHQ-9 score (B = -1.52, 95% CI = [-2.08; -0.96], p=<0.001), GAD-7 score (B = -1.46, 95% CI = [-2.09; -0.83], p=<0.001), spending less than 75 000 FCFA on medications monthly (B = 12.13, 95% CI = [5.73; 18.94], p=<0.001), and being a SCD caregiver (B = -11.62, 95% CI = [-18.46; -4.78], p=0.001) were factors independently associated with quality of life on multivariable analysis. Quality of life is lower in caregivers of children and adolescents with SCD than with HIV. Preventing depression and anxiety as well as advocating for the subsidization of medications through a national SCD program may improve quality of life in SCD caregivers.

Enhancing the Management of Pediatric Sickle Cell Disease by Integrating Functional Evaluation to Mitigate the Burden of Vaso-Occlusive Crises

Sickle cell disease (SCD) imposes a significant health burden, particularly in low- and middle-income countries where healthcare professionals and resources are scarce. This opinion paper delves into the management strategies employed for vaso-occlusive crises (VOCs) in pediatric patients with SCD, advocating for the adoption of a transformative strategy. We explore the integration of functional assessment approaches into existing procedures, highlighting the potential of technology-assisted rehabilitation, including wearable sensors and digital biomarkers, to enhance the effectiveness of managing and preventing VOCs. Rehabilomics, as a comprehensive framework, merges rehabilitation-related data with biomarkers, providing a basis for personalized therapeutic interventions. Despite the promising advantages of these approaches, persistent obstacles such as the limited availability of rehabilitation programs, especially in resource-limited settings, pose challenges. This paper underscores the importance of a collaborative strategy to effectively address the unique obstacles faced by patients with SCD. This collaborative approach involves improving accessibility to rehabilitation services, incorporating technology-supported therapy, and fostering focused research endeavors. The primary objective of this comprehensive approach is to enhance the overall care of SCD patients, with a specific focus on preventing VOCs, as well as providing tailored (neuro)rehabilitation services in resource-limited settings. By examining the current state of SCD management and proposing transformative strategies, this opinion paper seeks to inspire collective action and collaboration to improve outcomes for pediatric SCD patients globally.

Constitutive hypercoagulability in pediatric sickle cell disease patients with hemoglobin SS genotype

BackgroundConstitutive inflammation and hemostatic activation have been identified as key contributors to the pathophysiology of sickle cell disease (SCD), leading to clinical consequences such as vaso-occlusive crises and stroke. Patients with hemoglobin SS (HbSS) and hemoglobin SC (HbSC) genotypes are reported to have different symptoms, as do patients in steady-state and crisis situations. Differences among these groups remain unclear in pediatric patients. ObjectivesTo compare hemostatic activity in HbSS and HbSC pediatric patients during steady state, in crisis, and in clinical follow-up and compare HbSS and HbSC patients with normal healthy children. MethodsWhole-blood coagulation assay thromboelastography (TEG) was used to assess hemostatic activity. In parallel, flow cytometry was used to assess procoagulant surface expression of platelets and red blood cells. ResultsTEG results indicated no significant differences in clotting onset (R time), clot maximum amplitude, or maximum rate of thrombus generation among steady-state, crisis, and follow-up subgroups of HbSS and HbSC patients. TEG parameters did not differ significantly between HbSC patients and healthy children, while HbSS patients showed significantly shorter R time and greater maximum amplitude and maximum rate of thrombus generation, all indicative of a constitutive hypercoagulable state. Flow cytometry results did not detect increased platelet integrin αIIbβ3 activation or red blood cell procoagulant surface expression in SCD patients compared with unaffected children. ConclusionOur results indicate that pediatric SCD patients with the HbSS genotype have constitutively activated hemostasis relative to HbSC patients and healthy children. It remains to be determined how treatments that improve clinical outcomes in SCD patients affect this constitutively hypercoagulable state.

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease

AbstractVoxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin–labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI–measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

Pain screening in youth with sickle cell disease: A quality improvement study.

Youth with sickle cell disease (SCD) face several challenges as they age, including increased pain frequency, duration, and interference. The purpose of this study was to (i) determine the feasibility of routine pain screening; (ii) identify and describe various clinical pain presentations; and (iii) understand preferences/resources related to engaging in integrative health and medicine (IHM) modalities within an outpatient pediatric SCD clinic. During routine outpatient visits, patients aged 8-18 completed measures of pain frequency, duration, and chronic pain risk (Pediatric Pain Screening Tool [PPST]). Participants screening positive for (i) persistent or chronic pain or (ii) medium or high risk for persistent symptoms and disability on the PPST were asked to complete measures of pain interference, pain catastrophizing, and interest in/resources for engaging in IHM modalities. Between March 2022 and May 2023, 104/141 (73.8%) patients who attended at least one outpatient visit were screened. Of these 104 (mean age 12.46, 53.8% female, 63.5% HbSS), 34 (32.7%) reported persistent or chronic pain, and 48 (46.2%) reported medium or high risk for persistent symptoms and disability. Patients completing subsequent pain screening measures reported a mean pain interference T-score of 53.2±8.8 and a mean pain catastrophizing total score of 24.3±10.2. Patients expressed highest interest in music (55.6%) and art therapy (51.9%) and preferred in-person (81.5%) over virtual programming (22.2%). Comprehensive pain screening is feasible within pediatric SCD care. Classifying patients by PPST risk may provide a means of triaging patients to appropriate services to address pain-related psychosocial factors.

Unveiling mortality risk factors in paediatric sickle cell disease patients during acute crises in the Democratic Republic of the Congo

Sickle cell disease (SCD) is a significant health burden in the Democratic Republic of the Congo (DRC). This study aims to identify predictive factors of mortality in SCD children admitted to emergency care in Lubumbashi, DRC. We performed a non-interventional cohort follow-up on SCD patients aged 0 to 16 admitted for a “true emergency”. Demographic, clinical, and biological data were collected. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors associated with mortality. Among the 121 patients included, 24 died during the follow-up period. Univariate regression revealed age, Mikobi score, referral origin, stroke, and severe infection as significant risk factors. Multivariate analyses identified Hb, WBC, SR, and LDH as predictive factors of mortality. Notably, patients aged 12 to 16 years faced a higher risk, shifting the age of mortality from early to late childhood and adolescence. This study provides valuable insights into mortality risk factors for paediatric SCD patients during acute crises. Early diagnosis, regular follow-up, and therapeutic education are essential to improve patient outcomes and survival rates. These findings contribute to better disease management and targeted interventions, aiming to reduce mortality associated with SCD.

Neighborhood Disadvantage and Healthcare Utilization in Pediatric Sickle Cell Patients

Background: Sickle cell disease (SCD) is a complex heritable blood disorder associated with higher acute healthcare utilization further complicated by psychosocial and socioeconomic factors. Other studies have indicated a relationship between neighborhood disadvantage and increased healthcare utilization. We hypothesize that those with greater neighborhood disadvantage will have greater acute healthcare utilization.&#x0D; Methods: Data was collected retrospectively from the electronic medical record between 9/30/2021 and 7/11/2023 for patients followed at Riley Hospital for Children’s Pediatric SCD Clinic who completed a psychosocial needs assessment (PAT). Number of emergency department (ED) visits, hospitalizations, and missed clinic visits were collected from the time the PAT was completed up to 1 year after (or the end of the data collection period). Data regarding area deprivation index (ADI) and childhood opportunity index (COI) were collected utilizing patient home address. Descriptive statistics were performed on all data above, as well as t-tests and chi square tests for univariate analyses.&#x0D; Results: 142 patients completed a PAT during the study period. 88% had a primary care provider documented, and 73% had public insurance. The median state and national ADI (6, 76.5) and COI (2, 2) demonstrated greater neighborhood disadvantage and less childhood opportunity. There was no statistically significant difference between ADI or COI and number of ED encounters or hospitalizations. However, patients who missed 1 or more SCD visits had a higher median state ADI than those who did not miss a visit (7.5 vs 5, p=0.002). Median state COI was also lower in this group than those who did not miss a visit (1 vs 2, p=0.001).&#x0D; Conclusion: Those with higher ADI and lower COI could benefit from more directed support to improve access to preventative care visits. Further analysis accounting for comorbidities (seizures, asthma, depression) could disambiguate a relationship between ADI or COI and acute care utilization.

Clinical Features in Paediatric Sickle Cell Anaemia Cases from Rajasthan, India: A Case Series

Clinical Features in Paediatric Sickle Cell Anaemia Cases from Rajasthan, India: A Case Series

Initial outcomes in a sickle cell disease transition clinic

BackgroundTransition in sickle cell disease (SCD) is associated with an alarming increase in acute care utilization, cost, and risk of early mortality. Effective transition preparation is crucial to address these issues. We established a multidisciplinary transition clinic at our urban SCD center in the fall of 2021. At each visit patients were introduced to the transition process and met with a pediatric and adult SCD provider. MethodsWe reviewed charts of patients attending the clinic from September 2021 to May 2023. Data were collected on the number of visits in the transition and adult SCD clinics. Clinic notes were reviewed, identifying the main topics of discussion, and examining patient attitudes and feelings towards transition. ResultsTwenty-two patients aged 20–27 years with 35 total visits were included in the analysis. Eighteen (82%) patients had at least 1 visit to transition clinic. Out of 10 scheduled patients, 8 attended their first adult care visit within 2.4 months of their last transition visit. Medical topics brought up by patients included difficulty remembering to take hydroxyurea, questions about reproductive and menstrual health, and support pursing higher education with a chronic disease. Patients expressed a variety of feelings about transition from “no concerns” to “nervousness” and questioning “what to expect”. Concerns were alleviated by learning about the process. One patient reported feeling “much better" after being introduced to the adult provider. ConclusionWe demonstrated that a collaborative transition clinic prepares young adults with SCD for transition to adult care. Meeting with their adult SCD provider prior to transfer helped alleviate patients’ concerns. Future work will involve tracking patients as they integrate into adult clinic.

Novel Multidimensional Pain Assessment Tool Is a Feasible, Valid, and Enjoyable Approach to Communication of Pain Symptoms in Pediatric Sickle Cell Disease

Background: Pain is the most common symptom of sickle cell disease (SCD) and is especially difficult to assess in the pediatric population. Children have varied developmental stages and cognitive abilities making the communication of this subjective experience hard to operationalize. Both the assessment of pain and validation of these assessments is challenging. No pediatric pain assessment tool has been deemed valid and reliable across all ages and types of pain. Commonly used pediatric tools include the Wong-Baker Faces scale, the numeric rating scale, and the visual analog scale (VAS), which combines the visuals of faces and numeric rating. These are unidimensional - only assessing the severity of pain, and in the case of faces, can cause confusion between pain severity and patient affect. In children with SCD, accurate pain assessment is crucial to current and lifelong management. “Painimation” is a technology-based pain assessment tool that incorporates conceptual animations, rather than numbers or words, to characterize pain. These animations are intended to help clinicians better understand pain from the patient's perspective. They are dynamic and transcend language. For example, animations are designed to communicate dull pulsating pain, sharp electric pain, or anything in between. “Painimation” does not rely on verbal communication skills, making it ideal for use in the pediatric population. “Painimation” has been validated in adults with SCD and is currently in implementation trials. Our study aims to determine the feasibility and validity of “Painimation” in pediatric SCD. Methods: This is a single site non-randomized cross-sectional feasibility and validity study. Participants were 10 - 21 years old with SCD who presented to clinic in baseline health. Participants completed the Painimation application, which consists of a numeric pain rating scale (1-10), a front and back 2-dimensional body image that can be shaded to indicate areas affected by pain, and eight abstract animations intended to represent different pain qualities (tingling, shooting, stabbing, throbbing, pounding, cramping, electrifying, and burning). The patient chose up to three animations and the intensity of each chosen animation was adjusted using a sliding bar without numeric labels. The animations were presented to the patient without labeling the intended quality. The patients then completed a survey consisting of questions regarding the usability of Painimation, clinical questions regarding their disease, Lansky Play-Performance Scale, and validated patient reported outcomes questions (PedsQL, Ped-PRO-CTCAE, PROMIS). Results: We enrolled 30 participants between April 1 and July 31, 2023, with recruitment ongoing. Five records were incomplete and were not analyzed at this time. The mean ratings when asked whether 1) Painimation was easy to use, 2) the patient enjoyed using Painimation, and 3) the patient would use Painimation to communicate pain with their provider were respectively 3.28±.74 (SD), 3.08±.95, and 3.12±1.17 (scale 0-4), indicating a generally favorable result for feasibility. The median VAS score was 5.10 (IQR = 0.25, 8.25). Pain was most reported in the back lower chest (60%), front stomach (48%), and front chest (44%). The stabbing animation was the most chosen at 56% followed by the cramping animation at 20%. Electrifying and Cramping animations had the highest agreement with their intended McGill descriptors at 40%. VAS scores and Painimation severity scores demonstrated excellent positive correlation (Pearson r=.74). Conclusion: Painimation is a feasible pain assessment tool in pediatric SCD with high user satisfaction. Severity scores on Painimation correlate strongly with VAS scores. The pain characteristic conveyed by each animation adds unique dimensions to this measure and will be further analyzed. Painimation is a novel pediatric pain assessment that holds the promise of greatly improving the communication of pain and transforming care in Pediatric SCD.

Risk Factors for Pediatric Acute Chest Syndrome Utilizing Machine Learning Techniques

Introduction: Acute chest syndrome (ACS) causes significant morbidity and mortality in both adult and pediatric sickle cell disease (SCD). Fifty to thirty percent of all pediatric SCD admissions develop ACS, with each episode potentially causing irreversible lung damage. Although there are some known risk factors for developing ACS (e.g., history of asthma), often this complication occurs unexpectedly. Our hypothesis was that a machine learning model could be developed to predict progression to ACS. Methods: A retrospective cohort study was designed to develop this prediction model. Data was abstracted from the electronic health record (EHR) from a single institution for all pediatric SCD admissions from 0-21 years old between June 1, 2016, and December 31, 2022. Inputs into the model included demographics (e.g., age, genotype), vital signs (e.g., heart rate, oxygen saturation), laboratory values (e.g., hemoglobin, neutrophil count), medication orders (e.g., albuterol, oxycodone) and additional co-morbidities (e.g., asthma, obstructive sleep apnea). The inputs had maximum and minimum values based on normal ranges by age. The output was a diagnosis of ACS as a continuous dependent variable to develop a continuous likelihood estimation score from 0 to 1. A positive output of ACS was defined as 2 doses of the antibiotic azithromycin and a chest x-ray ordered in the same encounter. The negative output included all patients who did not meet criteria for a positive output as defined above. Both positive and negative cohorts for ACS were included in the model. The time of ACS diagnosis was when the first dose of azithromycin was ordered. All ACS encounters were verified by chart review. A random forest model was implemented using Sklearn Python library. Different depth of trees was experimented between 1 to 24. A prediction for ACS was calculated every 6 hours after admission to the inpatient setting. Eighty percent of the data was used for training and twenty percent for testing. Results: Two thousand two hundred and sixty encounters were included in the negative cohort and 512 encounters were included in the positive cohort. One thousand four hundred and fourteen (51%) were male patients and 1358 were female patients (49%). The maximum depth of the tree was determined to be 10. Sixty-five percent of the positive cohort developed ACS 24 hours after the admission time. The median time that the random forest model predicted ACS was 18 hours before the diagnosis was determined in the chart. The model had a sensitivity of 80% and specificity of 64% at the cutoff point of 0.17. The area under the receiver operating characteristic (ROC) curve was 71%. The model's negative predictive value was 92% and the positive predictive value was 36% of diagnosing ACS. The features that were important predictors in the model were age, height, weight, pulse, respiratory rate, presence of hypoxia, temperature, neutrophil count, hemoglobin, absolute reticulocyte count and reticulocyte percent. Conclusion: A machine learning model demonstrated markers of hemolysis and vital sign changes were important to predict ACS in pediatric patients. This is the first model utilizing machine learning techniques in pediatric SCD to predict ACS. Detecting patients who are a higher risk for ACS could impact treatment options and approach to inpatient management.