Search

Andrew Campbell,1 Avery A Rizio,2 Kristen L McCausland,2 Serban Iorga,3 Glorian P Yen,3 Jincy Paulose,3 Soyon Lee3 1Children’s National Hospital, Washington, DC, USA; 2QualityMetric Incorporated LLC, Johnston, RI, USA; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USACorrespondence: Avery A Rizio, QualityMetric Incorporated, LLC, 1301 Atwood Avenue, Suite 216E, Johnston, RI, 02919, USA, Tel +1 401-903-4631, Email arizio@qualitymetric.comBackground: Children with sickle cell disease (SCD) experience a multiplex of disease-related symptoms and complications, including vaso-occlusive crises (VOCs), episodes characterized by extreme pain.Methods: A cross-sectional observational survey examined the health-related quality of life (HRQoL) and school experiences of children with SCD 2 months– 11 years, burden experienced by their caregivers, and associations between these outcomes and VOC frequency. Caregivers (N=167) of children with SCD in the US completed the Infant-Toddler Quality of Life-Short Form 47 (ITQoL-SF47) for children 2 months– 4 years, the Child Health Questionnaire–Parent Form 50 (CHQ-PF50) and PROMIS Pain Interference and Sleep Disturbance Parent Proxy short forms for children 5– 11 years, and a study-specific survey of school experiences.Results: Children with SCD 2 months– 4 years had lower ITQoL-SF47 scores (ie, worse HRQoL, p< 0.001) than a normative sample of children; across domains, differences ranged from 18.73– 45.03 points and exceeded minimal important difference (MID) thresholds. Except for the behavior domain, children with SCD 5– 11 years had lower scores on all CHQ-PF50 domains than the normative sample (p< 0.001); differences ranged from 6.78– 36.37 points and exceeded MID thresholds. Children with more frequent VOCs had lower HRQoL and worse school experiences than children with less frequent VOCs (p< 0.05, except for behavior domains). The largest differences based on VOC frequency were observed for overall health and bodily pain/discomfort among children 2 months– 4 years (differences=40.88 and 32.50 points, respectively), and bodily pain and role/social limitations due to physical health among children 5– 11 years (differences=38.99 and 37.80, respectively). Caregivers of children with more frequent VOCs experienced greater burden than caregivers of children with less frequent VOCs, though specific areas of impact (eg, caregiver emotions, time) differed across child age groups.Conclusion: VOC frequency is negatively associated with HRQoL, highlighting the burden experienced by children with SCD and their caregivers.Keywords: pediatric, child, toddler, well-being, pain crisis, vaso-occlusion

Neha Durgam,1 Triza Brion,1 Hannah B Lewis,1 Biba Tinga,2 Wilson Sanon,3 Mark Lundie,4 Chantal Cadieux4 1ICON Plc, Raleigh, NC, USA; 2Sickle Cell Disease Association of Canada (SCDAC), Toronto, ON, Canada; 3Association d’Anémie Falciforme du Québec, Montreal, Quebec, Canada; 4Pfizer Canada ULC, Kirkland, Quebec, CanadaCorrespondence: Neha Durgam, 4130 Parklake Ave, Suite 400, Raleigh, NC, 27612, USA, Tel +1 267 827 7447, Email Neha.Durgam@iconplc.com; nehadurgam@gmail.comPurpose: There is little research on care-seeking preferences during active pain crises for sickle cell disease (SCD) patients and their caregivers. The objective of this study was to identify relevant, patient or caregiver narratives of the pain crisis experience, to understand the factors that contribute to care-seeking during a pain crisis, and to identify preferences when making care-seeking decisions during a pain crisis.Patients and Methods: Qualitative semi-structured interviews were conducted with Canadian residents with a self-reported SCD diagnosis, who were either ≥ 18 years of age or an adolescent between the ages of 12– 18. Interviews were hosted virtually, audio-recorded, and transcribed verbatim.Results: A total of 23 individuals participated (74% female; 26% male), including six adolescents with parent dyads and 11 adults. Almost all (N = 21, 91.3%) participants were Black/African American. Participants mentioned many factors that influenced care-seeking decisions, mainly the symptom and pain experience; institutional factors (waiting time, the presence of and adherence to treatment guidelines, and the empathy or racial bias felt from medical staff); and subject-level factors (age and a flexibility in daily responsibilities).Conclusion: This study identified important institutional and subject-level considerations involved in care-seeking decisions. Most importantly, this study highlights the racial stigma faced by many patients when care-seeking in the ER and the lack of care protocol implemented, which hinders care-seeking in a dedicated medical facility. From the patient perspective, these are clear gaps to fill to encourage patients to seek and receive the care they deserve.Keywords: vaso-occlusive crisis, sickle cell disease, pain crisis, care-seeking, standard of care

Abstract Background and purpose Sickle cell disease (SCD) is a collection of rare inherited blood disorders affecting approximately 100,000 people in the U.S. and 20–25 million people globally. Individuals with SCD experience recurrent episodes of severe and unpredictable pain that are caused by vaso-occlusive crises (VOCs), a hallmark of the disease. VOCs are the primary cause of hospitalization in SCD, result in missed workdays and school days, and decrease quality of life (QoL). Although VOCs cause significant burden in the lives of individuals with SCD, there is no synthesis on the frequency of VOCs in the real world. This systematic literature review sought to identify literature describing the frequency of VOCs experienced by individuals with SCD in real-world settings. Methods MEDLINE and 6 congresses were searched (date range: January 1, 2000 to June 30, 2020). Studies were reviewed independently by two researchers. Studies assessing frequency or prevalence of VOCs or VOC-related outcomes were included. Results Of 1438 studies identified in the search, 52 met pre-specified inclusion and exclusion criteria. Reported frequency of VOCs varied widely ranging from a mean or median of 0 VOCs/year to 18.2 VOCs/year. The proportion of patients experiencing ≥ 3 VOCs/year ranged from 4 to 67% and the proportion of patients experiencing ≥ 5 VOCs/year ranged from 18 to 59%. Measures of VOC severity were limited, with 13 studies considering frequency of complicated VOCs and only 1 study reporting duration of VOC episodes. Conclusions This is the first study to systematically assess published evidence pertaining to VOCs in real-world settings. Reported VOC frequency in real-world settings varied widely, with a majority of studies only considering VOCs managed in an inpatient or outpatient setting. Studies that considered VOCs managed at home reported a higher frequency of VOCs, suggesting that many studies may underestimate the frequency of VOCs. This systematic literature review (SLR) highlights the need for consistent reporting of (1) self-reported VOCs, including those managed at home, (2) definitions of VOCs, (3) complicated VOCs, and (4) duration of VOC episodes in literature.

Background: Sicklecell disorders (SCD) are the commonest inherited haemoglobin (Hb) disorders. Globally, about 300,000 babies are born annually with these conditions. The clinical profiles of SCD have been described in many parts of the world. These however have not been adequately investigated in some parts of Nigeria. This study evaluated the clinical features, Hb phenotype and complications of children with SCD being managed at a Paediatric aematology clinic in Northern Nigeria. Methods: A prospective observational study of steady state SCD patients aged 2 –16 years, was conducted from January, 2019 - October, 2020. Historical and examination findings were documented. Analysis of data was done with the Statistical Package for Social Sciences (SPSS) version 20.0. Results: One hundred children were studied. Mean age was 6.97 ± 3.63 years. Male: female ratio was 1.6:1. Mean weight and mean height were lower than reference standards (t= 1.20, p= 0.14), (t= 0.66, p= 0.27) respectively. Mean age at diagnosis was 13.24 ±14.83 months, and at first presentation was 13.86 ±17.51 months, 58.5% of subjects were adequately vaccinated for age, while 92% had a Hb phenotype of SS. Acute chest syndrome occurred more frequently in children aged 9 -12 years ( χ2= 11.59, P ˂ 0.001), and in those with severe bacterial infections (χ2 = 7.41, p= 0.006). Conclusion: The complications of Paediatric SCD in this part of North Eastern Nigeria mirrors those in other parts of the country. Socio- economic class, Hb phenotype and vaccination status had no influence on the development of complications.

Nabin Raj Karki, Abdullah Kutlar Division of Hematology/Oncology, Augusta University, Augusta, GA, USACorrespondence: Nabin Raj KarkiDivision of Hematology Oncology, Georgia Cancer Center at Augusta University, 1410, Laney Walker Blvd, CN 5347, Augusta, GA, 30912, USATel +1-706-721-2505Fax +1-706-721-5566Email nkarki@augusta.eduAbstract: Microvascular vaso-occlusion driven pain crisis is the hallmark of sickle cell disease with profound morbidity and increased mortality. Selectins, most notably P-selectins have an integral role in this phenomenon. P-selection was first identified in 1989. In 2019, after 3 decades of basic, translational, and clinical work with this pathway, the US Food and Drug Administration approved a P-selectin antibody, crizanlizumab to reduce frequency of pain crisis in patients more than 16 years with sickle cell disease. We review the fundamentals of P-selectin pathobiology, P-selectin blocking agents, clinical data with the use of crizanlizumab and prospects of this novel class of drugs in the context of other treatments for painful vaso-occlusive episodes.Keywords: P-selectin, sickle cell disease, pain crisis, crizanlizumab

Pain crisis in children with sickle cell disease (SCD) is typically managed with intravenous fluids and parenteral opioids in the pediatric emergency department. Electrical cardiometry (EC) can be utilized to measure cardiac output (CO) and cardiac index (CI) non-invasively. Near-infrared spectroscopy (NIRS) measuring cerebral (rCO2) and splanchnic regional (rSO2) mixed venous oxygenation non-invasively has been utilized for monitoring children with SCD. We studied the value and correlation of NIRS and EC in monitoring hemodynamic status in children with SCD during pain crisis. We monitored EC and NIRS continuously for 2 h after presentation and during management. Forty-five children participated in the study. CO (D = 1.72), CI (D = 1.31), rSO2 (D = 11.6), and rCO2 (D = 9.3), all increased over time. CO max and CI max were achieved 1 h after starting resuscitation. rCO2 max attainment was quicker than rSO2, as monitored by NIRS. CI max correlated with rCO2 max (r = −0.350) and rSO2 max (r = −0.359). In adjustment models, initial CI significantly impacted initial rCO2 (p = 0.045) and rCO2 max (p = 0.043), while initial CO impacted rCO2 max (p = 0.030). Cardiac output monitoring and NIRS monitoring for cerebral and splanchnic oxygenation were feasible and improved the monitoring of therapeutic interventions for children with SCD during pain crisis.