Acute Pain Crisis Research Articles

Cost Analysis of ACUTE Care Resource Utilization Among Individuals with Sickle Cell Disease in a Middle-Income Country

Background: The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC), where resources are scarcer and policy decisions about resource allocation rely on detailed cost data. Few studies have investigated the cost-savings of disease-modifying therapies in SCD in real-world setting. We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea therapy at HEMORIO, a specialized tertiary hematology center in Brazil.Methods: The costs (US dollars) of emergency department (ED) and hospitalizations from SCD-related complications between 01.01.2018 and 06.30.2018 were ascertained using absorption and micro-costing approaches. ED costs are presented as cost per each ED event and hospital admission costs are presented as cost per each admission event. ED and admission costs (separated and combined) were determined and compartmentalized into several inputs by fixed and variable categories for all patients over the period of the study [Falk JA et al, Atlas 2001]. The cause of ED or hospital admission visit was verified by a physician and abstracted via medical record review. All hospital admissions were evaluated in the ED. If an ED encounter resulted in an admission, the encounter was counted as an admission event only. The causes related to SCD were grouped and classified according to the discharge diagnosis: 1) VOC (acute pain crisis, priapism or dactylitis); 2) Infection (fever, sepsis, or acute chest syndrome); 3) Anemia exacerbation (acute hemolytic crisis, transient aplastic crisis, or acute splenic sequestration); 4) Chronic organ damage (overt stroke, chronic kidney disease, chronic liver disease or organ failure. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period [Shah N, et al. Health and quality of life outcomes. 2019]. The one-sample proportions test with continuity correction compared the differences in frequency of ED or admissions across discharge diagnoses and the Wilcoxon rank sum test with continuity correction was used to compare cost differences across the groups.Results: In total, 1144 patients, median age 17 years (range 0-70), 903 (78.9%) with HbSS/HbSβ 0-thalassemia, 441 (38.5%) prescribed hydroxyurea, visited the ED, of whom 381 (33%) were admitted. VOC accounted for 64% of all ED visits and 60% of all admissions (Table 1). Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2,176.40/visit) (Figure 1). Compared with other genotypes, individuals with HbSS/HbSβ 0-thalassemia were admitted more often (79% versus 21%, p<0.0001), and their admission costs were higher ($1,677.18 versus $1,224.47/visit, p=0.0001). Antibiotics and analgesics accounted for 43% and 42% of the total ED costs, respectively, while housing accounted for 46% of the total admission costs (Figure 2). In a regression tree analysis, costs of ED visits were lower among HbSS/HbSβ 0-thalassemia individuals with hydroxyurea MPR ≥65% compared with those with MPR<65% or untreated ($182.46 versus $98.16/visit, p=0.0007). No difference in admission costs were observed relative to hydroxyurea use.Discussion: It is estimated that between 60,000 to 100,000 individuals live with SCD in Brazil today [Lobo CL, et al. Pediatric blood & cancer. 2014]. In a LMIC hematology-specialized center, VOCs accounted for most acute visits from patients with SCD, but costs were highest due to anemia exacerbation. Analgesics, antibiotics, and housing drove most expenses. Our results confirm the lower acute health care resource utilization with hydroxyurea therapy (fewer ED visits and admissions among those prescribed this medication). Hydroxyurea therapy reduced ED costs among individuals with HbSS/HbSβ 0-thalassemia, however, was dependent on adherence level. A cost analysis of individuals with SCD has never been performed in Brazil previously. Our study will facilitate appropriate planning of allocation of funds and development of health policies for individuals with SCD and may serve as the benchmark against which new SCD disease-modifying therapies may be compared for cost-effectiveness and cost-savings estimation in LMIC, such as Brazil. [Display omitted] DisclosuresLobo: Novartis: Consultancy. Hankins: Global Blood Therapeutics: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Bluebird Bio: Consultancy.

Successful Use of Plasma Exchange Preceding RBC Exchange in Sickle Cell Disease Hyperhemolytic Crisis with Hepatic Sequestration: A Case Report

IntroductionHyperhemolytic crisis is an uncommon complication of SCD that may cause multiorgan failure and lead to significant mortality. There are no current national or international guidelines for management of hyperhemolytic crisis and associated complications. There have been limited number of case reports and series that demonstrated utility of plasma exchange in the patients with multiorgan failure resulting from hemolysis complications (Zaidi GZ et al.,2020). We are presenting the case where hyperhemolytic crisis was complicated by hepatic sequestration and acute liver failure, that was dramatically reversed by 2 plasma exchange treatments followed by RBC exchange.Case reportWe present a case of a 35-year-old African American male with SCD and beta thalassemia trait with frequent hospitalizations for sickle cell pain crisis. He presented with pain typical for his acute pain crises and was admitted for intravenous hydration and pain control. The next morning, lab work showed bicytopenia with a drop in hemoglobin from 10.5 to 5.8 g/dL and platelets (PLT) from 100 to 22 X10E3/uL. Lactate dehydrogenase (LDH) increased from 434 to 2848 U/L, haptoglobin was 36 mg/dL, but disseminated intravascular coagulation (DIC) and Heparin-induced Thrombocytopenia (HIT) antibody panel were negative. The blood urea nitrogen (BUN) creatinine (Cr) ratio was also elevated (30.6) suggesting renal damage as well. He was transferred to the intensive care unit and started on Intravenous Immunoglobulin (IVIG) 0.4 grams/kilogram daily for 5 days and methylprednisolone 500 mg daily for 2 days followed by a prednisone taper. Liver enzymes continued to trend upward with AST of 19,866 U/L and ALT of 3,675 U/L on day 3 of hospitalization. Ultrasound of abdomen demonstrated mild splenomegaly with a spleen measuring 13.3 cm. The clinical presentation and hepatocellular pattern of injury was consistent with hepatic sequestration crisis. Despite receiving 1 unit of platelet 3 units of pRBC, there was little improvement and apheresis service was consulted. Plasma exchange was initiated for 2 procedures on consecutive days followed by RBC exchange with rapid improvement in clinical status and laboratory findings with a reduction of LDH (1304), AST (129), ALT (204), Hgb (8.0), PLT (41), BUN/Cr (20.0). He was discharged on day 7 at baseline status.DiscussionAlthough the mechanism of development of hyperhemolysis in SCD is not fully understood, the hemolysis leads to release of free hemoglobin (Hb) and free heme that activate neutrophils, and vascular endothelial cells via TLR-4. This ultimately leads to inflammatory, coagulative, and cytotoxic damages and decreased nitric oxide (NO) bioavailability which further contributes to SCD complications such as pulmonary and systemic vasculopathy, pain crisis and acute chest syndrome and multi organ failure (Louie JE et al., 2018). This provides a rationale for plasma exchange - removal of free heme from the patient plasma and replenishing exhausted haptoglobin and hemopexin reserves from donor plasma.Hemolytic crisis causing visceral organ damage is relatively rare. There are no current guidelines for management of such patients. In 1996 Betrosian et al. discussed the first case of liver failure in a SCD with vasa-occlusive crisis treated with RBC and plasma transfusions (Betrosian A et al., 1996). Since then, there have been case reports/series of plasma exchange/plasma transfusions in SCD with multi organ failure (Geigel EJ et al., 1997, Louie JE et al., 2018) but reports about use of plasma exchange in SCD patients with hepatic sequestration have not been identified by our literature review.Our case demonstrates that plasma exchange in hyperhemolysis and hepatic sequestration is: •Safe•Leads to quick and significant improvement in hemolysis laboratory values.•Results in quick and durable reversal of hepatic sequestration and associated liver failure.•Adds plasma exchange as therapeutic apheresis modality in addition to previously accepted RBC exchange.•Provides data about priority of plasma exchange over RBC exchange in this clinical situation. DisclosuresNo relevant conflicts of interest to declare.

L-Glutamine and Crizanlizumab for Adults with Sickle Cell Disease (SCD) in Qatar: A Cost Effectiveness Analysis

Background :Sickle cell disease (SCD) is a hereditary disease that is caused by autosomal recessive gene fault in the beta (β) allele of the hemoglobin (Hb) gene. As a result, sickled cells are characterized by easy and abnormal hemolysis with resultant varying degrees of anemia. Globally, the incidence of SCD is estimated to reach 400,000 persons per year, and in the United States alone, for example, the prevalence estimation is approximately 100,000 patients. Possible clinical presentations of SCD may come from different pathophysiologic mechanisms: the disfiguration of the RBC with subsequent loss of function can lead to vascular occlusion and a short lifetime of these RBCs that leads to hemolysis. The most severe and serious manifestation of SCD is the recurrent acute pain, or better known as vaso-occlusive crisis (VOC). Additionally, other clinical manifestations that SCD patients may show are acute complications such as acute chest syndrome (ACS), recurrent infections, kidney necrosis, and stroke. Such complications may affect multiple organs and can result in early death. Acute pain crisis is another common complication of SCD and is usually managed with pain medications, especially opioids,This is the first study to address two of novel therapies in patients with SCD in the Middle East. Our study was comprehensive in terms of outcome mostly encountered by SCD patients which is VOC and inclusivity of interventions mostly used for its management and was focused on the target population of in one of areas of high prevalence of SCD in the world. Our analysis tracked the CHEERS guidelines and checklist for reporting. To be also complete, we used only RCT evidence in our analysis. Additionally, in considering VOC, we ensured only studies with a definition compatible with that of the principal Crizanlizumab study were analyzed.Objectives:Treatment options for preventing vaso-occlusive crises (VOC) among sickle cell disease (SCD) patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety and acquisition cost of L-glutamine and Crizanlizumab for older adolescent and adults (≥16 years old) SCD in Qatar, with an emphasis on treatment costs and acute pain crises.Methods:We conduct a decision tree model, where we compare the clinical and economic outcomes of two novel FDA-approved medications which are available in Qatar; L-glutamine and Crizanlizumab over a time horizon of one year in a hypothetical cohort of adult SCD patients from a Qatar healthcare perspective. The main outcome is incremental cost per SCD-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system. A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars.Results:Study results showed that both treatment modalities' costs were the main driver of this analysis, with average annual cost of the treatments per patient being $189,014 for Crizanlizumab (5mg/Kg), $143,798 Crizanlizumab (2.5mg/Kg) and $74,323 for L-glutamine. The probability of no first time SCD-related VOC averted were 0.001/year for Glutamine, 0.26/year for Crizanlizumab (5mg/Kg) and 0.34/year for Crizanlizumab (2.5mg/Kg). Lower dose Crizanlizumab (2.5mg/Kg) dominated the higher one (5mg/Kg). The ICER of Crizanlizumab (2.5mg/Kg), when compared to L-Glutamine was $81,265 per SCD-related VOC averted. When comparing Crizanlizumab (5mg/Kg) and L-Glutamine, Crizanlizumab (5mg/Kg) showed higher efficacy, yet the Crizanlizumab ICER was at $459,620 than L-glutamine.Conclusions:Crizanlizumab (2.5mg/Kg) may be cost-effective interventions yet it is not the approved dose for preventing VOC in adolescents and adults with sickle cell disease. Crizanlizumab (5mg/Kg) was more cost effective than the approved L-glutamine per SCD vaso-occlusive crisis prevented. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Effects of Quercetin on Neutrophil Extracellular Trap Formation in Sickle Cell Disease

Introduction: Sickle Cell Disease (SCD) is characterized by chronic inflammation with innate immune cell activation, especially observed in neutrophils. Emerging evidence implicates the imbalance between neutrophil extracellular trap (NET) formation and degradation as having a central role in the pathophysiology of thromboinflammation and venous thrombosis. Although NETosis and NET formation influences venous thromboembolism (VTE) pathophysiology, little is known about baseline and agonist-induced NETosis in SCD. We hypothesized that systemic neutrophil activation would lead to higher baseline and agonist induced NETosis in SCD and would influence phenotypic variability. To test this hypothesis, we assessed baseline and agonist induced NETosis in patients with SCD and ethnic matched controls. We also investigated the anti-inflammatory effects of flavonoid Quercetin on neutrophil activation.Methods: Neutrophils negatively selected from citrate anticoagulated blood using an immunomagnetic bead based kit (MACSxpress® Miltenyi Biotec) were either fixed immediately to assess baseline NETosis or stimulated with fMLP (1 µM) for 1 hour to assess agonist-induced NETosis. To study flavonoid anti-inflammatory effects, neutrophils were pretreated with Quercetin (100 µM) for 30 min prior to fixation and fMLP stimulation. NETosis was assessed by flow cytometry. Extracellular DNA extrusion on neutrophils was detected by gating the neutrophil population staining with Sytox green. Sytox green positive neutrophils that were positive for both myeloperoxidase (MPO) and tri-Citrullinated Histones (H3Cit) were defined as undergoing NETosis. In some experiments, NET formation was independently confirmed by image flow cytometry (AMNIS).Results: Subjects included SCD patients (genotype SS n=11) and ethnic matched controls (genotype AA, n=11) with a median age of 49 years (p=0.58) and a predominance of males (70%). All SCD patients were at least 60 days remote from an acute painful vaso-occlusive crisis or blood transfusion and were receiving hydroxyurea. The white cell and absolute neutrophil counts were higher in SCD patients (mean ± SD 8.77 ± 1.52 and 5.07 ± 1.78 x 10 9/L) when compared with controls (mean ± SD 5.33 ± 1.05 and 2.8 ± 0.95 x 10 9/L). Subsequent data are presented as median percentages with interquartile ranges (IQR).A subgroup of the study population demonstrated spontaneous NETosis (27%; SS = 4; AA = 4) and were therefore excluded from our analysis. Contrary to expectations, SCD patients exhibited a lower percentage of NETosis at baseline compared to controls (20 % (11, 36) vs. 33 % (15, 58); p=0.22). Similarly, neutrophils from SCD patients exhibited lower agonist-induced NETosis compared to controls (42% (19, 47) vs. 51% (37, 70); p=0.15) (Fig 1 A and B)Pretreatment of neutrophils from SCD patients with Quercetin appeared to inhibit basal levels of NETosis (6%, (2, 26) vs. 20% (11, 36) p=0.08) although this effect was not appreciable in controls (33% (11, 58) vs. 33% (15, 58) p=0.41) (Fig 1 C and D). Neutrophils from SCD patients that were pretreated with Quercetin and then stimulated with fMLP demonstrated significantly reduced NETosis compared to untreated neutrophils (17.1% (10, 38) vs 41.7% (19, 47) p=0.007) although this effect was not significant in controls (35% (17, 72) vs 50.7% (37, 70) p=0.11) Fig 1 E and F.Our ongoing experiments will demonstrate the effects of more specific inhibitors of neutrophil activation (e.g. R406) in human and mouse models of SCD.Conclusion: These preliminary data suggest lowered NETosis in SCD patients despite neutrophil activation in the systemic inflammatory environment that are partially explained by hydroxyurea treatment. The results also support further evaluation of anti-inflammatory therapies to reduce neutrophil activation in SCD and ameliorate thrombo-inflammatory disease pathology. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Pilot Implementation of Remote Patient Monitoring Program for Outpatient Management of CAR-T Cell Therapy

Pilot Implementation of Remote Patient Monitoring Program for Outpatient Management of CAR-T Cell Therapy

Visualizing Sickle Cell Disease Whole Blood Flow and Viscosity through Modifications to Hemoglobin Levels from a Simple Blood Transfusion

Red cell transfusions are an effective part of a clinical care regiment in the treatment of chronic sickle cell disease; however, the understanding of the target hemoglobin levels has not been investigated past the standard hematocrit/hemoglobin (HgB) of 10 g/dL. A simple transfusion of packed red cells can be a beneficial clinical treatment of acute pain crisis or even stroke. Along with other transfusion-based complications, when performing a simple transfusion, the changes in blood velocity as a result of increased blood viscosity from the additional red cells can lead to complications of their own. Because of this, clinical treatment has hesitated to transfuse sickle patients above a HgB of 10 g/dL.The complications of sickle cell disease tend to be more pronounced on the microvascular scale than then macrovascular. Along with this, the overall slower blood flow caused by the increase in viscosity from a simple blood transfusion is more probable to lead to complications on the microvascular level. Our device allows us to target the changes in whole blood on multiple scales including down to arteriole sizes. Here, we have begun to investigate how transfusion could be more patient-specific by identifying the velocity profile of whole blood flowing through a “microvasculature-on-a-chip” device that mimics the microvascular geometry (Figure 1A). The devices were microfabricated using polydimethylsiloxane (PDMS) and then coated with 0.1% bovine serum albumin (BSA) to help prevent red cell adhesion to channel walls. To simulate various HgB levels, healthy whole blood samples were centrifuged to separate red cells. To simulate a simple clinical transfusion of a sickle patient, isolated red cells were added to sickle whole blood samples. Similar to a clinical setting, sickle samples were only transfused up to higher HgB levels. HgB levels were then confirmed on a differential hematology analyzer (Sysmex XN 330). 3.2mm CA+ was added to various HgB samples to defeat the citrate anticoagulant. Samples were loaded into syringes then perfused into the BSA coated devices (Figure 1B).During perfusion, a 450 frame video of flow was captured at 40x resolution and 163 fps. Following capture, videos parameters such as frame rate and pixel distance were defined in a custom MATLAB (Mathworks, Natick, MA) script. The script segmented videos into cropped frames of the desired regions of interest then a Kanade-Lucas-Tomasi (KLT) tracking algorithm detected red cell features in each frame across 4 frames (Figure 1 B&C). 12 equal spaced bins were created across the width of the channel in the direction of flow; Tracked velocities were assigned to their corresponding bin and averaged to create a velocity profile of function as the distance from the center of the channel (Figure 1 D&E).To create a case study, two patient samples were received with the same starting HgB of 6.8 g/dL and were transfused upwards incrementally to a HgB of 12 g/dL. One patient is currently on a hydroxyurea regiment and the other patient is not. At each HgB level, the perfused whole blood was tracked through several different arteriole-sized vessels (30, 40 & 60 um) at two appropriate flow rates. To quantify the differences in the flow, the average cell velocity (um/s) through the channel and the peak velocity (um/s) through channels were charted against the various HgB levels (Figure 2).Continuing this series of experiments, 2 additional sickle whole blood on hydroxyurea samples were transfused upwards from their respective starting hemoglobin (9.7 & 10 g/dL). The flow was tracked and averages were quantified across the channel through its distance from the center of the channel. As transfused sickle HgB levels were increased, the bluntness of the velocity profile, or the difference between the average flow velocity in the center of the channel and at the walls of the channel, became less dramatic. This could be primarily attributed to the increase in the viscosity from the addition of the red cells (Figure 3).Our data shows that viscosity plays an important factor in whole blood flow. HgB of 10 g/dL is an important target for sickle transfusions; however, this target HgB may be more patient-specific than previously stated. Understanding patient viscosity may prove to be more important than hemoglobin levels. As patient blood increases in viscosity, blood slows down on the microvascular level the most. This may be critical in understanding the appropriate transfusion. [Display omitted] DisclosuresLam: Sanguina, Inc.: Current holder of individual stocks in a privately-held company. Kemp: Parthenon Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Nicotinamide Improves Anemia and Decreases Reactive Oxygen Species in Sickle Cell Disease Mice

The polymerization of deoxygenated HbS molecules in the red blood cells (RBCs) of patients with sickle cell disease (SCD) causes RBC destruction resulting in chronic pain, debilitating acute pain crises, strokes, multi-organ damage and a reduced life span. Therapeutic options remain limited. Bone marrow transplantation can be curative but is not an option for the majority of patients. Gene therapy interventions that also offer the promise of a cure are under investigation but are not likely to be available to the vast majority of patients in the near future. Hydroxyurea, the first drug approved for treatment of SCD, increases levels of Fetal Hemoglobin (HbF) that inhibit polymerization of HbS molecules but is not effective in all patients while a more powerful HbF-inducing drug, the DNA methyltransferase inhibitor decitabine has yet to be approved. L-glutamine, another approved therapeutic option, increases NAD redox potential and decreases reactive oxygen species (ROS) in the sickle RBCs to reduce symptoms. In our laboratory we have observed that increased ROS is associated with the retention of mitochondria in the SCD RBCs and have hypothesized that the abnormal presence of mitochondria in these cells is a major source of ROS (Jagadeeswaran et al Exp Hematol 50:46-52, 2017). In this investigation we have tested the hypothesis that chronic oral supplementation with nicotinamide, a direct precursor of NAD synthesis, would improve NAD redox potential, decrease mitochondrial retention and ROS in SCD RBCs, and reduce anemia in the SCD mouse model. The effect of nicotinamide was tested in SCD mice whose drinking water was supplemented for three months with 1% nicotinamide. The percentage of RBCs retaining mitochondria and the levels of ROS were determined by flow cytometric assays using the mitochondrial-specific dye TMRM and the ROS probe CM-H2DCFDA, respectively. In SCD mice receiving nicotinamide the fraction of RBCs retaining mitochondria was reduced 22.1% (p<0.05) and the level of ROS in RBCs was reduced 41% (p<0.01) compared to control SCD mice. The reticulocyte percentage was reduced 28% in nicotinamide-treated SCD mice compared to control SCD mice (p<0.01). The total RBC count was 30% higher (p<0.05) in nicotinamide-treated mice (6.61±0.76 X 10 6/μl) compared to control SCD mice (5.08±0.70 X 10 6/μl). Similar differences in hematocrit and total hemoglobin were also observed but failed to reach statistical significance. Total NAD levels were not significantly different in SCD mice receiving nicotinamide compared to control SCD mice (p<0.05), but the NADH/NAD total ratio was increased 2 fold (p<0.05). These results show that oral administration of high doses of nicotinamide decreases mitochondrial retention and ROS in SCD RBCs and improves NAD redox potential and anemia in SCD mice. These effects strongly suggest that additional studies be performed to investigate nicotinamide as a therapeutic option in SCD. [Display omitted] DisclosuresSaunthararajah: EpiDestiny: Consultancy, Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.

BACTERIAL MYOCARDITIS IN SICKLE CELL PATIENT WITH ACUTE CHEST SYNDROME

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Sickle cell anemia is an autosomal recessive disorder leading to chronic hemolytic anemia secondary to abnormal hemoglobin. Sickle cell anemia has numerous clinical consequences such as acute pain crisis, acute chest syndrome, osteomyelitis, and renal failure. The most common cause of death for sickle cell patients is infection. A rare cause of death for sickle cell patients is infection secondary to viral myocarditis; and even rarer is bacterial myocarditis. In this case, our sickle cell patient passed away from a staphylococcal bacterial myocarditis. CASE PRESENTATION: A 44-year-old female with a significant past medical history of Sickle Cell Disease (Hemoglobin SS) presented to the emergency department with complaints of shortness of breath, 5 days of fever with abdominal pain and dysuria. Initial pertinent investigations showed a hemoglobin of 5.3, WBC 23.5, and mild hypokalemia with an acute kidney injury with elevated BUN/Creatinine (71/2.31). The urine analysis was positive, although the culture was negative. Blood cultures were drawn. Ceftriaxone and IV fluids were started. A CT abdomen and chest was obtained and showed mixed alveolar and interstitial opacities in bilateral lower lobes consistent with acute chest syndrome, hepatomegaly, and an enlarged heart. She was transferred to a tertiary center due to acute sickle cell pain crisis complicated by AKI, and acute chest syndrome. Patient was given a PCA pump with hydromorphone. Hematology recommended starting hydroxyurea and transfusing 2 units packed red blood cells. Troponin levels became elevated. Echocardiogram showed no wall motion abnormalities and a normal ejection fraction (50-55%). Patient continued to clinically deteriorate, so an exchange transfusion was started. During the exchange transfusion the patient coded and passed away. An autopsy was performed and showed interstitial neutrophilic infiltrates within the myocardium with micro abscesses with gram positive cocci identified. Blood cultures were positive for Staphylococcus aureus. The cause of death was identified as staphylococcal bacterial myocarditis. DISCUSSION: Sickle cell patients are susceptible to serious adverse outcomes from infections; notably infections are the leading cause of death in sickle cell patients. Death is often sudden and unexpected. Our patient was an example of an extremely rare cause of staphylococcal bacterial myocarditis with a concomitant acute chest syndrome that may have contributed to masking the underlying myocarditis and thus ultimately leading to death. CONCLUSIONS: Bacterial myocarditis is a very rare but potential cause of death in patients with sickle cell disease and the symptoms could be concealed from the clinician due to and overlapping acute chest syndrome. REFERENCE #1: Manci EA, Culberson DE, Yang YM, et al; Investigators of the Cooperative Study of Sickle Cell Disease. Causes of death in sickle cell disease: an autopsy study. Br J Haematol. 2003 Oct;123(2):359-65. REFERENCE #2: Cooper LT Jr. Myocarditis. N Engl J Med. 2009 Apr 9;360(15):1526-38. REFERENCE #3: McGee M, Shiel E, Brienesse S, et al; Staphylococcus aureus Myocarditis with Associated Left Ventricular Apical Thrombus. Case Rep Cardiol. 2018 May 23;2018:7017286. DISCLOSURES: No relevant relationships by Chad DeMott, source=Web Response No relevant relationships by Badri Giri, source=Web Response No relevant relationships by Elspeth Springsted, source=Web Response

PEDIATRIC PLASTIC BRONCHITIS IN THE SETTING OF SICKLE CELL DISEASE TREATED WITH INHALED TISSUE PLASMINOGEN ACTIVATOR

TOPIC: Pediatrics TYPE: Medical Student/Resident Case Reports INTRODUCTION: Plastic bronchitis is seen in congenital heart disease, cystic fibrosis, asthma, and less commonly sickle cell disease. It has high morbidity and can be difficult to treat. CASE PRESENTATION: We present an 11-year-old African American boy with past medical history of hemoglobin SS disease, acute chest syndrome, pain crises, and obstructive sleep apnea status post tonsillectomy and adenoidectomy who presented with vaso-occlusive pain crisis consisting of chest pain. CXR was clear without consolidation. He was placed on a pain regimen of morphine and ketorolac. Acute chest prophylaxis was initiated with albuterol plus PEP every 4 hours, incentive spirometry, and oxygen saturation maintenance ≥95%. Over the next two days he developed fevers, increased oxygen requirement, and crackles. CXR progressed to consolidation of left lung. He was transferred to the Pediatric ICU for BiPAP and given 2 units pRBCs, 7 days ceftriaxone, and 5 days azithromycin for acute chest treatment. Despite intense respiratory treatments while on BiPAP with albuterol every 4 hours, dornase alfa every 12 hours, CPT every 4 hours, and home mometasone/formoterol every 12 hours, his CXR demonstrated persistent opacification of left lung. Pulmonology was consulted for bronchoscopy which demonstrated large white mucoid material in the left mainstem consistent with plastic bronchitis. The cast was unable to be removed on initial bronchoscopy. He was initiated on inhaled tissue plasminogen activator 4 times daily in addition to above respiratory treatments. Bronchoscopy was repeated two days later and cast was successfully removed. BiPAP and oxygen were weaned as tolerated and he was discharged home on mometasone/formoterol twice daily. DISCUSSION: Plastic bronchitis describes endobronchial plugs of rubber-like casts in the bronchial trees. It is more commonly seen in patients with congenital heart disease after single-ventricle palliation. There have been various treatments trialed including bronchoscopy, chest physiotherapy, inhaled steroids, hypertonic saline, dornase alfa, nebulized heparin, lymphatic embolization, and inhaled tissue plasminogen activator. Studies performed on casts have demonstrated a substantial fibrin component supporting inhaled tissue plasminogen activator as a potentially effective treatment option. CONCLUSIONS: We present a case of pediatric plastic bronchitis in the setting of a patient with sickle cell disease. This case emphasizes that plastic bronchitis must be considered in patients diagnosed with acute chest. Additionally, inhaled tissue plasminogen activator may be considered as a treatment modality in pediatric patients with plastic bronchitis, particularly in patients who are unable to undergo bronchoscopy or when it has been unsuccessful for removal. REFERENCE #1: Feray S, Mora P, Decavele M, Pham T, Hafiani EM, Fartoukh M. Plastic bronchitis: An unusual complication of acute chest syndrome in adult. Respir Med Case Rep. 2017 Apr 7;21:93–5. REFERENCE #2: Li Y, Williams RJ, Dombrowski ND, Watters K, Daly KP, Irace AL, et al. Current evaluation and management of plastic bronchitis in the pediatric population. Int J Pediatr Otorhinolaryngol. 2020 Mar 1;130:109799. REFERENCE #3: Heath L, Ling S, Racz J, Mane G, Schmidt L, Myers JL, et al. Prospective, Longitudinal Study of Plastic Bronchitis Cast Pathology and Responsiveness to Tissue Plasminogen Activator (tPA). Pediatr Cardiol. 2011 Dec;32(8):1182–9. DISCLOSURES: No relevant relationships by Megan Lilley, source=Web Response No relevant relationships by Carla Roberts, source=Web Response No relevant relationships by Heather Staples, source=Web Response

Ketamine administration for acute painful sickle cell crisis: Arandomized controlled trial.

ObjectiveThe objective was to evaluate the efficacy and safety of single‐dose ketamine infusion in adults with sickle cell disease (SCD) who presented with acute sickle vasoocclusive crisis (VOC).MethodsThis study was a parallel‐group, prospective, randomized, double‐blind, pragmatic trial. Participants were randomized to receive a single dose of either ketamine or morphine, infused over 30 min. Primary outcome was mean difference in the numerical pain rating scale (NPRS) score over 2 h. NPRS was recorded every 30 min for a maximum of 180 min and secondary outcomes were cumulative dose of opioids, emergency department (ED) length of stay, hospital admission, change in vital signs, and drug‐related side effects. Authors performed the analysis using intention‐to‐treat principle.ResultA total of 278 adults with SCD and who presented with acute sickle VOC participated in this trial. A total of 138 were allocated to the ketamine group. Mean (±standard deviation [SD]) NPRS scores over 2 h were 5.7 (±2.13) and 5.6 (±1.90) in the ketamine and morphine groups. The ketamine group received significantly lower cumulative doses of morphine during their ED stay (mean ± SD = 4.5 ± 4.6 mg) than of the morphine group (mean ± SD = 8.5 ± 7.55 mg). Both groups had similar rates of hospital admission: 6.3% in the ketamine group had drug‐related side effects compared to 2.2% in the morphine group.ConclusionEarly use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2‐h period and reduced the cumulative morphine dose in the ED with no significant drug‐related side effects in the ketamine‐treated group.

Timed Average Mean Maximum Velocity (TAMMV) of Cerebral Blood Flow of Children and Adolescents with Sickle cell Disease: correlation with clinical and hematological profiles in country.

Detection of abnormal TAMMV with transcranial Doppler is fundamental in primary stroke prevention in children with sickle cell disease (SCD). The study aimed at evaluating TAMMV and correlating it with clinical and hematological profiles of children and adolescent with SCD. Transcranial Doppler was performed on subjects aged 2-16 years, using a 2 MHz probe placed over the transtemporal windows. Pulse oximetry was used to determine the peripheral oxygen saturation while clinical and hematological profiles were retrieved from their medical records. One hundred and thirty five patients were recruited. The mean TAMMV was 125cm/s. Patients with HbSS had a significantly higher TAMMV (131cm/s) than those with HbSC (107cm/s). Only one (0.74%) patient had abnormal TAMMV. TAMMV correlated inversely with oxygen saturation, Hct and patient's age, and positively with white cell and platelet counts. Previous history of acute chest syndrome (ACS) and recurrent painful crises increased the risk of development of abnormal and conditional velocity. Frequency of abnormal TAMMV in this study was low. Younger children and those with HbSS had higher TAMMV. Age, oxygen saturation and haematocrit correlated negatively while white cell and platelet counts correlated positively with TAMMV. Previous history of ACS and recurrent bone pain were associated with increased risk of having abnormal and conditional TAMMV.

Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.

A Randomized Clinical Hypnosis Pilot Study: Improvements in Self-Reported Pain Impact in Adults with Sickle Cell Disease.

Sickle cell disease (SCD) is characterized by recurrent painful vasoocclusive crises. Current evidence focuses on the frequency of acute pain crises resulting in emergency department use and nonplanned inpatient hospital admissions; yet few studies focus on pain sequelae outside the healthcare system or how individuals self-manage their chronic SCD-related pain. This study investigated the feasibility of a biobehavioral intervention as an adjunct nonpharmacological therapy to assist in the self-management of chronic pain. A randomized, controlled clinical trial of hypnosis was conducted in outpatients with SCD (n = 31). Patient-reported outcomes (PROs) administered at baseline, five, and twelve weeks from both groups included pain frequency, intensity, and quality (Pain Impact Scale (PIQ) and Numerical Rating Scales); anxiety (State-Trait Anxiety Inventory), coping strategies (Coping Strategies Scale), sleep (Pittsburgh Sleep Quality Index (PSQI)), and depression (Beck Depression Inventory (BDI)). The same PROs were collected at weeks seventeen and twenty-four from the control group after the crossover. No significant group by time interaction effects were found in any of the PROs based on the repeated-measures mixed models. The PIQ and PSQI scores decreased over time in both groups. Post hoc pairwise comparisons with the Bonferroni adjustment indicated that the mean PIQ score at baseline decreased significantly by week 12 (p = 0.01) in the hypnosis group. There were no significant changes across time before and after the crossover in any of the PROs in the control group. As suggested by these findings, pain impact and sleep in individuals with SCD may be improved through guided mind-body and self-care approaches such as hypnosis.

A non-injected opioid analgesia protocol for acute pain crisis in adolescents and adults with sickle cell disease.

Initial management of the acute pain crisis (APC) of sickle cell disease (SCD) is often unsatisfactory, and might be improved by developing a standardised analgesia protocol. Here, we report the first stages in developing a standard oral protocol for adolescents and adults. Initially, we performed a dose finding study to determine the maximal tolerated dose of sublingual fentanyl (MTD SLF) given on arrival in the acute care facility, when combined with repeated doses of oral oxycodone. We used a dose escalation algorithm with two dosing ranges based on patient’s weight (<50 kg or >50 kg). We also made a preliminary evaluation of the safety and efficacy of the protocol. The study took place in a large tertiary centre in London, UK. Ninety patients in the age range 14–60 years were pre-consented and 31 treatment episodes were evaluated. The first 21 episodes constituted the dose escalation study, establishing the MTD SLF at 600 mcg (>50 kg) or 400 mcg (<50 kg). Further evaluation of the protocol indicated no evidence of severe opioid toxicity, nor increased incidence of acute chest syndrome (ACS). Between 0 and 6 hours, the overall gradient of reduction of visual analogue pain score (visual analogue scale (VAS)) was 0.32 centimetres (cm) per hour (95% confidence interval (CI) = 0.20 to 0.44, p < 0.001). For episodes on MTD SLF, there was median (interquartile range (IQR)) reduction in VAS score of 2.8 cm (0–4.2) and 59% had at least a 2.6-cm reduction. These results are supportive of further evaluation of this protocol for acute analgesia of APC in a hospital setting and potentially for supervised home management.

Platelet Aggregation Dysfunction in Sickle Cell Disease

Acute systemic painful vaso-occlusive crisis (VOC) is the predominant clinical event requiring sickle cell disease (SCD) patients to seek emergency medical care. VOC often serves as an antecedent to acute chest syndrome (ACS), which is a type of acute lung injury and the leading cause of mortality in SCD. Current treatments for ACS are primarily supportive, and there is a critical need for rescue strategies to prevent the progression of VOC to ACS. ACS involves thrombosis across pulmonary artery branches, but the pathophysiology of thrombosis in SCD is largely unknown. Adenosine diphosphate (ADP) released from lysed erythrocytes can activate platelets by stimulating the purinergic receptors P2Y1 and P2Y12, suggesting that blocking these receptors may prevent VOC. Surprisingly, P2Y12 receptor blockade was unsuccessful in preventing VOC in a recent DOVE trial, justifying the need for better understanding of purinergic signaling in SCD.We used a novel intravital microscopy enabled experimental model of vaso-occlusive pulmonary thrombosis in transgenic SCD mice triggered by an intravenous (IV) administration of ADP. This method allows real time in vivo visualization of platelet aggregation in the lung of live SCD mice using multi-photon-excitation based quantitative fluorescence intravital lung microscopy (qFILM). We discovered that vaso-occlusive thrombosis involves entrapment of large circulating platelet aggregates in the bottle-necks located between the pulmonary arterioles and capillaries. Surprisingly, the dose of ADP that led to the pulmonary vaso-occlusive thrombosis in control mice, failed to induce vaso-occlusive thrombosis in SCD mice. Remarkably, further in vivo and in vitro platelet aggregation studies confirmed that SCD mouse platelets were indeed refractory to ADP but not collagen.Our preliminary findings suggest that therapeutic inhibition of P2Y1 and P2Y12 platelet receptors will not be a successful therapy in SCD. Our findings also warrant the need for further studies to understand the role of purinergic signaling in SCD DisclosuresNo relevant conflicts of interest to declare.

Neutrophil Extracellular Traps Promote Lung Arteriole Occlusion in Sickle Cell Disease

Introduction:Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder, which leads to red blood cell sickling and hemolysis. Acute systemic painful vaso-occlusive crisis (VOC) is the predominant pathophysiology requiring emergency medical care by SCD patients. 10-20% of SCD patients hospitalized with VOC tend to develop acute chest syndrome (ACS), a type of lung injury within next few days, suggesting a role for pulmonary vaso-occlusion in ACS. The cellular, molecular and biophysical mechanism of pulmonary vaso-occlusion has just started to unfold and a profound understanding is needed for the development of rescue therapies to halt the progression of VOC to ACS. Our recent findings using quantitative fluorescence intravital lung microscopy (qFILM) revealed that lung vaso-occlusion is enabled by the entrapment of embolic neutrophil-platelet aggregates in the pulmonary arterioles of transgenic humanized SCD mice. Neutrophil extracellular traps (NETs) are web-like structures of decondensed nuclear DNA decorated with citrunilated-histones and neutrophil granule proteins. NETs are released by activated neutrophils under inflammatory conditions and are known to possess pro-inflammatory and pro-thrombotic properties. Recently, hemolysis driven release of cell free hemoglobin or hemin has been shown to promote NETs formation in the pulmonary microcirculation of SCD mice. Nevertheless, how these NETs can serve to facilitate pulmonary vaso-occlusion and promote ACS is still unclear.Materials and Methods:Townes knock-in humanized SS (hα/hα:βS/βS) and AS (hα/hα:βA/βS) mice were used as SCD and control mice, respectively. SS and AS mice were intravascularly (IV) challenged with Oxy-hemoglobin (Oxy-Hb) and hemin to model VOC. Fluorescently-conjugated anti-mouse CD49b and Ly6G mAbs, Sytox Orange, and FITC dextran were administered IV to visualize platelets, neutrophils, extracellular DNA and lung vasculature in the mouse, respectively. Lung microcirculation was visualized in real time in vivo using qFILM and analyzed as described elsewhere. Also, SCD or control human blood with or without treatment with Oxy-Hb or hemin was perfused through in vitro microfluidic microchannels presenting a combination of P-selectin, ICAM-1 and IL-8, and neutrophil-platelet interactions as well as NET formation was visualized using Quantitative Microfluidic Fluorescence Microscopy (qMFM). Fluorescent anti-human mAbs against CD49b, CD16, citrullinated histones (H3-Cit) and neutrophil elastase were added to human blood to visualize platelets, neutrophils, histones, and neutrophil elastase, respectively.Results and Discussion:Our initial findings using qFILMreveal that non-lethal dose of 20 µmole/kg IV hemin or 10 µmole/kg IV Oxy-Hb led to entrapment of neutrophil-platelet embolic aggregates in the lung arteriolar bottlenecks of SCD but not control mice. These aggregates resulted loss of blood perfusion in the lung, followed by shedding of NETs from neutrophils into the blood circulation.Conclusion: Erythroid DAMPs, hemin and Oxy-Hb promote occlusion of lung arterioles by neutrophil-platelet aggregates in SCD mice. These aggregates promote loss of blood flow and release of NETs from neutrophils in the lung arterioles. DisclosuresKato:Bayer: Research Funding; Global Blood Therapeutics: Consultancy; Novartis: Consultancy; MAST Therapeutics: Research Funding.

Characteristics of a Chronic Pain Phenotype in Adults with Sickle Cell Disease

▪Background: Sickle cell disease (SCD) is characterized by pain, typically, acute in onset with a subset of events which require hospitalization for treatment with opioid analgesics. A proportion of adults also experience nearly daily pain that appears to share features with chronic pain in other diseases. However, the prevalence of chronic SCD pain in adults is largely undefined. Furthermore, the relationship between chronic pain in SCD and mortality has not been evaluated despite the known association between frequent acute pain crises and increased risk of death. The American Pain Society Pain Taxonomy working group on SCD has recently proposed core diagnostic criteria for chronic pain, although these criteria were not based upon population based data.Methods: Two hundred thirty five adults were questioned about the presence of chronic pain defined as pain present on more than 50% of days for more than 6 months. This was performed as part of an outpatient evaluation at 2 different clinical sites that included a history, exam and lab studies while patients were in steady state. Subjects enrolled on this study were then followed for up to 5.7 years to evaluate survival by Kaplan Meier analysis.Results: Forty-nine (21%) met the chronic pain definition. Mean age was 31.1 versus 32.1 years, respectively, and there was no sex difference between groups. Characteristics distinguishing the chronic pain group from all others were a higher body mass index (BMI; P=0.007), more hospitalizations for SCD pain over the past year (mean 6.6 hospitalizations for the chronic pain group; P< 0.0001), a higher number of moderate pain days (i.e. missing work; mean of 66.3 days; P< 0.0001), avascular necrosis in 49% of chronic pain patients (odds ratio 2.53 compared to all others; 95% confidence interval 1.33 to 4.85; P=0.006) and a higher prevalence of any current opioid use (90% versus 69%, P=0.003). In men, priapism was more prevalent for those with chronic pain (71% versus 46% respectively; odds ratio 2.80; 95% confidence interval 1.07 to 7.34; P=0.04). Systolic and diastolic blood pressure were also higher with chronic pain, but these were not quite statistically significant (P=0.06 for both). Overall, the proportion of subjects with both chronic pain and any contributory disease complications defined by the Pain Taxonomy working group (like leg ulcers or avascular necrosis) was 57% (28 out of 49), even though leg ulcers by themselves were not associated with chronic pain (P=0.52). Direct bilirubin was also higher and approached significance (P=0.053), but no other lab studies were associated with chronic pain. Multivariable logistic regressions showed that the number of hospitalizations for pain during the 12 months prior to evaluation (P=2.14 x 10-6), current opioid use (P=0.02) and higher systolic blood pressure (P=0.007) were independent markers associated with chronic pain. Finally, the chronic pain group was not at increased risk of death (Hazard Ratio 1.26; 95% CI 0.24 - 6.63; P=0.79) in a Kaplan Meier survival analysis with a median follow-up of 1.4 years for 174 subjects.Conclusion: Our definition for chronic pain is consistent with the Pain Taxonomy working group criteria for SCD chronic pain, which was proposed after the initiation of this study. Chronic pain in SCD is characterized by clinical features like frequent hospitalizations, opioid use and vascular manifestations including relative systolic hypertension. Importantly, chronic pain by itself does not appear to be associated with mortality. Larger patient cohorts are needed to confirm these findings and define appropriate chronic pain management for these high risk patients. DisclosuresNo relevant conflicts of interest to declare.

Critical Role of Hemopexin Mediated Cytoprotection in the Pathophysiology of Sickle Cell Disease.

Circulating hemopexin is the primary protein responsible for the clearance of heme; therefore, it is a systemic combatant against deleterious inflammation and oxidative stress induced by the presence of free heme. This role of hemopexin is critical in hemolytic pathophysiology. In this review, we outline the current research regarding how the dynamic activity of hemopexin is implicated in sickle cell disease, which is characterized by a pathological aggregation of red blood cells and excessive hemolysis. This pathophysiology leads to symptoms such as acute kidney injury, vaso-occlusion, ischemic stroke, pain crises, and pulmonary hypertension exacerbated by the presence of free heme and hemoglobin. This review includes in vivo studies in mouse, rat, and guinea pig models of sickle cell disease, as well as studies in human samples. In summary, the current research indicates that hemopexin is likely protective against these symptoms and that rectifying depleted hemopexin in patients with sickle cell disease could improve or prevent the symptoms. The data compiled in this review suggest that further preclinical and clinical research should be conducted to uncover pathways of hemopexin in pathological states to evaluate its potential clinical function as both a biomarker and therapy for sickle cell disease and related hemoglobinopathies.

MO218ALTERNATING EPISODES OF TRUE HYPERKALEMIA AND PSEUDOHYPERKALEMIA IN ADULT SICKLE CELL DISEASE - A NEPHROLOGIST'S DILEMA

Abstract Background and Aims To illustrate the phenomenon of alternating true hyperkalemia and pseudohyperkalemia in adult sickle cell disease. Method Case Report Results Sickle cell disease (SCD) predisposes the patient to recurrent episodes of acute painful hemolytic crisis. Sickle cell nephropathy (SCN) is not uncommon in adult patients. The presence of sickled erythrocytes in the renal medullary vessels is the hallmark of the disease and renal manifestations include renal ischemia, microinfarcts, renal papillary necrosis and renal tubular abnormalities with variable clinical presentations. Furthermore, acute hemolytic crisis can be complicated by sepsis. Hemolysis, specifically, intravascular hemolysis, can produce hyperkalemia. Additionally, reduced glomerular filtration rate from SCN predisposes to hyperkalemia. Pseudo-hyperkalemia was first reported by Hartmann and Mellinkoff in 1955 as a marked elevation of serum potassium levels in the absence of clinical evidence of electrolyte imbalance. In pseudohyperkalmia, simultaneously estimated serum potassium exceeds plasma potassium by &amp;gt;0.4 mmol/L. This is often associated with moderate to severe thrombocytosis or leukocytosis. Clearly, hyperkalemia is a potentially lethal condition. At the same time, the institution of inappropriate treatment of pseudo-hyperkalemia leading to hypokalemia is also equally potentially lethal. We describe a 40-yo African American male patient with sickle cell anemia who exhibited alternating episodes of hyperkalemia and pseudo-hyperkalemia, during consecutive hospital admissions. Pseudohyperkalemia was associated with severe thrombocytosis complicating sepsis. EKG was normal despite measured serum potassium of 6.7 mmol/L (Figure). Conclusion We believe that this is the first report of adult SCD demonstrating alternating cycles of true hyperkalemia and pseudo-hyperkalemia at different times. We must draw attention to the new availability of the new potassium binders, Patiromer and sodium zirconium cyclosilicate. We would advocate for caution in the use of these potent potassium binders and to always give consideration to the presence of pseudo-hyperkalemia under appropriate clinical scenarios. We posit that providers managing adult patients with sickle cell disease must be aware of such a phenomenon to avoid the dangers of overtreatment of episodes of pseudo-hyperkalemia in such patients.

Rapid Evidence and Gap Map of virtual care solutions across a stepped care continuum for youth with chronic pain and their families in response to the COVID-19 pandemic.

Poor access to pediatric chronic pain care is a longstanding concern. The COVID-19 pandemic has necessitated virtual care delivery at an unprecedented pace and scale. We conducted a scoping review to create an interactive Evidence and Gap Map of virtual care solutions across a stepped care continuum (ie, from self-directed to specialist care) for youth with chronic pain and their families. Review methodology was codesigned with 8 youth with chronic pain and 7 parents/caregivers. Data sources included peer-reviewed scientific literature, gray literature (app stores and web sites), and a call for innovations. Records were independently coded and assessed for quality. Overall, 185 records were included (105 scientific records, 56 apps, 16 web sites, and 8 innovations). Most virtual care solutions were applicable across pediatric chronic pain diagnoses, with the greatest proportion at lower levels of stepped care (ie, >100 self-guided apps and web sites). Virtual delivery of psychological strategies was common. Evidence gaps were noted at higher levels of stepped care (ie, requiring more resource and health professional involvement), integration with health records, communication with health professionals, web accessibility, and content addressing social/family support, medications, school, substance use, sleep, diet, and acute pain flares or crises. Evidence and Gap Maps are a novel visual knowledge synthesis tool, which enable rapid evidence-informed decision-making by patients and families, health professionals, and policymakers. This evidence and gap map identified high-quality virtual care solutions for immediate scale and spread and areas with no evidence in need of prioritization. Virtual care should address priorities identified by youth with chronic pain and their families.