Diagnosis Of Sickle Cell Disease Research Articles

Maternal malnutrition during pregnancy among women with sickle cell disease.

The objective of this study was to compare the nutritional status and dietary intake of pregnant women with sickle cell disease (SS hemoglobinopathy and SC hemoglobinopathy) to healthy controls and report the maternal and perinatal outcomes. This is a prospective, longitudinal cohort study. Pregnant women with a diagnosis of sickle cell disease and control group were recruited in an outpatient clinic of a tertiary care hospital in São Paulo, Brazil. Maternal anthropometric data and dietary intake data were collected at the second and third trimesters. A total of 49 pregnancies complicated by sickle cell disease were included. Prepregnancy body mass index was significantly lower in the SS hemoglobinopathy group (n=26, median 20.3 kg/m2) than the SC hemoglobinopathy group (n=23, 22.7 kg/m2) or control group (n=33, 23.2 kg/m2, p<0.05). The prepregnancy nutritional status revealed significantly more women classified as underweight in the SS hemoglobinopathy group (15.4%) than in the SC hemoglobinopathy group (4.4%) and control group (1.6%, p=0.009). In the second trimester, maternal protein intake was significantly lower in SS hemoglobinopathy (73.2 g/day) and SC hemoglobinopathy (68.8 g/day) than in the control group (95.7 g/day, p=0.004). In the third trimester, only SS hemoglobinopathy mothers showed dietary intake of protein significantly lower than that of the controls (67.5 g/day vs. 92.8 g/day, p=0.02). Vitamin A and E consumption was also reduced in the third trimester in the SS hemoglobinopathy group (p<0.05). The nutritional status of pregnant women with SS hemoglobinopathy is characterized by a state of undernutrition. The lower protein intake in the second and third trimesters of pregnant women with SS hemoglobinopathy may contribute to this condition. Undernourishment is a serious complication of sickle cell disease, primarily during pregnancy, and it should be addressed during the prenatal period.

Association between Vaso-occlusive Crises and Opioid Prescriptions among Patients with Sickle Cell Disease: A Retrospective Claims-based Study.

Background/ObjectivesAmong sickle cell disease (SCD) patients, vaso-occlusive crises (VOCs) are recurrent and unpredictable attacks of acute pain. These pain crises are often treated with analgesics, including opioids, which have been associated with misuse and overdose. The aim of this study was to examine the association between VOC events and opioid use and assess the association between opioid prescriptions and health care resource utilization among SCD patients.MethodsThis was a retrospective cohort study using Texas Medicaid medical and prescription claims between September 2011 and August 2016. The index date was the first SCD diagnosis. Patients (2–63 years) with at least one inpatient or two outpatient SCD diagnoses, who were continuously enrolled during 12 months postindex, were included in the study. The primary outcome was number of opioid prescriptions, while the independent variable was number of VOC events. Covariates included age, gender, nonopioid medication use, nonstudy SCD-related medication (penicillin and folic acid) use, evidence of blood transfusions, number of SCD-related complications, number of SCD-related comorbid conditions, and Charlson Comorbidity Index score. Negative binomial regression analysis was used to address study objectives.ResultsOf 3368 included patients, 1978 (58.7%) had at least one opioid prescription with a mean of 4.2 (SD=7.2). Overall, 2071 (61.5%) had at least one VOC event with an average of 2.9 (SD=4.4). The results from the negative binomial regression showed that for every increase in VOC events, the number of opioid prescriptions increased by 9.5% (Incidence rate ratio=1.095, 95% CI: 1.078–1.111; P ≤ 0.0001). Other significant covariates associated with higher opioid use included age (13 and older compared to 2–12) and increase in the number of nonopioid pain medications, nonstudy SCD-related medications, and SCD-related complications.ConclusionsThe majority of SCD patients had at least one VOC event and were prescribed opioids during the 12-month study period. We found that each VOC event was associated with a 9.5% increase in the use of opioids. SCD guidelines recommend opioids for the treatment of VOC-related pain. Payers and providers should be aware of opioid use in this population, consider appropriate VOC prevention measures, and provide SCD patients with access to appropriate pain management.

Patient and Caregiver Perspectives on Care-Seeking During a Vaso-Occlusive Crisis in Sickle Cell Disease: Results from Qualitative Interviews in Canada

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. 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. 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). 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.

Real-World Evidence on Disease Burden and Economic Impact of Sickle Cell Disease in Italy.

A real-world analysis was conducted in Italy among sickle cell disease (SCD) patients to evaluate the epidemiology of SCD, describe patients' characteristics and the therapeutic and economic burden. A retrospective analysis of administrative databases of various Italian entities was carried out. All patients with ≥1 hospitalization with SCD diagnosis were included from 01/2010-12/2017 (up to 12/2018 for epidemiologic analysis). The index date corresponded to the first SCD diagnosis. In 2018, SCD incidence rate was 0.93/100,000, the prevalence was estimated at 13.1/100,000. Overall, 1816 patients were included. During the 1st year of follow-up, 50.7% of patients had one all-cause hospitalization, 27.8% had 2, 10.4% had 3, and 11.1% had ≥4. Over follow-up, 6.1-7.2% of patients were treated with SCD-specific, 58.4-69.4% with SCD-related, 60.7-71.3% with SCD-complications-related drugs. Mean annual number per patient of overall treatments was 14.9 ± 13.9, hospitalizations 1.1 ± 1.1, and out-patient services 5.3 ± 7.6. The total mean direct cost per patient was EUR 7918/year (EUR 2201 drugs, EUR 3320 hospitalizations, and EUR 2397 out-patient services). The results from this real-world analysis showed a high disease burden for SCD patients with multiple hospitalizations during the follow-up. High healthcare resource utilization and costs were associated with patient' management and were most likely underestimated since indirect costs and Emergency Room admissions were not included.

Prenatal diagnosis and preimplantation genetic diagnosis for sickle cell disease in Africa

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide, and it is a major public health concern, especially in Sub-Saharan Africa. Prenatal diagnosis (PD) and preimplantation genetic diagnosis (PGD) are important reproductive options for the prevention of SCD. Despite the high prevalence of SCD in Nigeria and Sub-Saharan Africa, current trends in PD and PGD for the prevention of SCD are still slow compared to that in developed countries. Attitudes towards PD and PGD for the prevention of SCD in African are influenced by level of awareness, knowledge and educational status, and the main barriers to the uptake of PD and PGD for SCD in Africa are cost, religion, sociocultural, ethical and moral considerations. We reviewed available data on PD and PGD for SCD in Africa, using the PubMed, PubMed Central, Google Scholar and African Index Medicus search engines, through a combination of words and phrases relevant to the subject. This article reviewed the current trends in PD and PGD for the prevention of SCD and discussed the attitudes towards and the barriers to the uptake of PD and PGD for SCD in Africa.

AN INTERESTING CASE OF LOBAR PNEUMONIA

Sickle cell disease (SCD) is an inherited haemoglobinopathy that may present acutely as stroke, vaso-occlusive crisis or acute chest syndrome. Acute conditions require prompt diagnosis and intensive management to prevent morbidity and mortality. Here, we present a case of sickle cell anemia treated with therapeutic red cell exchange that manifested as acute chest syndrome. A 26 year old male who had history of high-grade intermittent fever and cough with expectoration was diagnosed as pneumonia and put on antibiotics. Peripheral smear showed sickle cells and HPLC showed HbS of 67%. we made a diagnosis of sickle cell anemia with acute chest syndrome. We treated the patient with therapeutic red cell exchange following which HbS reduced to 24% from the initial 67%. We observed significant clinical improvement suggesting red cell exchange as a useful therapeutic option for acute sickle cell anaemia.

Association of Sickle Cell Disease With Severe Maternal Morbidity.

To evaluate the association between sickle cell disease (SCD) and severe maternal morbidity (SMM) in a contemporary cohort of deliveries by non-Hispanic Black people. We retrospectively examined SMM by using electronic health record data on deliveries by non-Hispanic Black patients between 2011 and 2020 at a single tertiary, public institution. Sickle cell disease was identified during the delivery admission by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. The primary outcome, SMM at delivery hospitalization, was ascertained using ICD-9-CM and ICD-10-CM codes and excluded sickle cell crisis as an indicator of SMM. We also constructed a secondary measure of SMM that excluded deliveries in which blood transfusion was the only indication of SMM. Poisson regression models were used to estimate risk ratios (RRs) and 95% CIs for the associations between SCD and SMM (overall and for individual indicators). Multivariable models adjusted for age, parity, insurance type, chronic conditions (chronic hypertension, diabetes mellitus, obesity), and multiple gestation. Among 17,493 deliveries by non-Hispanic Black patients during the study period, 132 (0.8%) had a diagnosis of SCD. Of those patients, 87 (65.9%, 95% CI 57.2-73.9) with SCD and 2,035 (11.7%), 95% CI 11.2-12.2) without SCD had SMM. Sickle cell disease was associated with increased risk of SMM (87 vs 2,035, adjusted risk ratio [aRR] 5.4, 95% CI 4.6-6.3) and nontransfusion SMM (51 vs 1,057, aRR 6.0, 95% CI 4.6-8.0). Effect estimates were highest for cardiac arrest (3 vs 14, RR 28.2, 95% CI 3.8-209.3), air and thrombotic embolism (14 vs 72, RR 25.6, 95% CI 12.0-54.6), and puerperal cerebrovascular disorders (10 vs 53, RR 24.8, 95% CI 10.2-60.5). Sickle cell disease was associated with a more than fivefold increased risk of SMM during the delivery hospitalization. Our data suggest cardiovascular morbidity as the driving major risk. The identification and monitoring of cardiovascular pathology in patients with SCD before and during pregnancy may reduce SMM.

Multispectral imaging for MicroChip electrophoresis enables point-of-care newborn hemoglobin variant screening

Hemoglobin (Hb) disorders affect nearly 7% of the world’s population. Globally, around 400,000 babies are born annually with sickle cell disease (SCD), primarily in sub-Saharan Africa where morbidity and mortality rates are high. Screening, early diagnosis, and monitoring are not widely accessible due to technical challenges and cost. We hypothesized that multispectral imaging will allow sensitive hemoglobin variant identification in existing affordable paper-based Hb electrophoresis. To test this hypothesis, we developed the first integrated point-of-care multispectral Hb variant test: Gazelle-Multispectral. Here, we evaluated the accuracy of Gazelle-Multispectral for Hb variant newborn screening in 265 newborns with known hemoglobin variants including hemoglobin A (Hb A), hemoglobin F (Hb F), hemoglobin S (Hb S) and hemoglobin C (Hb C). Gazelle-Multispectral detected levels of Hb A, Hb F, Hb S, and Hb C/E/A2, demonstrated high correlations with the results reported by laboratory gold standard high performance liquid chromatography (HPLC) at Pearson Correlation Coefficient = 0.97, 0.97, 0.93, and 0.95. Gazelle-Multispectral demonstrated accuracy of 96.8% in subjects of 0–3 days, and 96.9% in newborns. The ability to obtain accurate results on newborn samples suggest that Gazelle-Multispectral can be suitable for large-scale newborn screening and for diagnosis of SCD in low resource settings.

Impact of adherence to hydroxyurea on health outcomes among patients with sickle cell disease.

Although new pharmaceutical therapy options have recently become available, hydroxyurea is still the most commonly used and affordable treatment option for sickle cell disease (SCD). This study aimed to update the evidence on hydroxyurea adherence and its association with clinical and economic outcomes among individuals with SCD. This retrospective study used Texas Medicaid claims data from 09/2011-08/2016. Individuals were included if they had ≥1 inpatient or ≥2 outpatient SCD diagnoses, had ≥1 hydroxyurea prescription, were 2-63 years of age, and were continuously enrolled in Texas Medicaid between 6 months before and 1 year after the first hydroxyurea prescription fill date (index date). Hydroxyurea adherence (Medication Possession Ratio; MPR), vaso-occlusive crisis (VOC)-related outcomes, healthcare utilization and expenditures (SCD-related and all-cause) during the 1 year following the index date were measured. Bivariate and multivariable analyses were used to address the study objectives. Among 1035 included individuals (age: 18.8 ± 12.5 years, female: 52.1%), 20.9% were adherent to hydroxyurea (defined as MPR≥0.8). After adjustment for demographic and clinical characteristics, compared to being non-adherent, adhering to hydroxyurea was significantly associated with: a lower risk (Odds Ratio [OR]=0.480, p= .0007) and hazard rate (Hazard Ratio [HR]=0.748, p= .0005) of a VOC event, fewer VOC events (Incidence Rate Ratio [IRR]=0.767, p= .0009), fewer VOC-related hospital days (IRR=0.593, p= .0003), fewer all-cause and SCD-related hospitalizations (IRR=0.712, p= .0008; IRR=0.707, p= .0008, respectively) and emergency department visits (IRR=0.768, p= .0037; IRR=0.746, p= .0041, respectively), and lower SCD-related total healthcare expenditures (IRR=0.796, p= .0266). Efforts to increase adherence to hydroxyurea could improve clinical and economic outcomes among individuals with SCD.

Perception of Marijuana Use, Risk/Benefits in Sickle Cell Disease

Background: Pain in Sickle Cell Disease (SCD) is responsible for frequent hospitalizations and significant morbidity and mortality. Patients SCD need effective, long-term pain management in the outpatient setting to reduce hospital length of stays, readmissions and ultimately decrease the healthcare system economic burden. Treatment of chronic SCD pain has primarily relied on opiates. Safer and more effective alternative treatments are needed. Anxiety, depression and sleep disturbances are well known moderators of pain. Few studies have evaluated the use of marijuana in SCD. One showed that SCD patients had used cannabis in the previous 12 months to relieve symptoms associated with SCD. Currently, only four USA states, included SCD as a qualifying condition for the use of medical marijuana. A large number of our SCD patients report using recreational and medical marijuana to treat SCD related symptoms. This study seeks to learn how adults with SCD use and/or are interested in using different forms of marijuana to help manage SCD-related pain and behavioral complications affecting them such as depression, anxiety, mood changes, etc. The results will be used to educate providers and patients about their preference for non-medication options to manage SCD-related complications and further studies on marijuana use risks / benefits for SCD. Methods: Adults (18 years old ) with diagnosis of SCD were asked to complete an IRB approved anonymous and confidential online Qualtrics-based survey. The survey consisted of 35 questions including demographics data age, gender, and socioeconomic status, pain characteristics and its management as well as reasons, frequency and type of the two different marijuana types, i.e. Non prescribed Marijuana (NPM), defined as any marijuana compound obtained and used without medical certification or prescription. Prescribe Medical Marijuana(MM) defined as any marijuana compound obtained after certification by a provider and used based on recommended specific doses and frequency. Descriptive statistics were used to report the data. Results: Of the 55 participants that initiated the survey, 44 were completed and that data was included in this analysis. One third, 16 of the 44 patients were between the ages of 26-35 years old (yrs.) and 56% were between the ages of 18 and 35 yrs. Twenty seven (61% ) of the responders were females. As, shown on the table, thirty-two (72%) participants reported regularly experiencing more than one combination of mood swing (31), fatigue(31), restless sleep (27), depression (24) or anxiety (23). Five (11%) did not reported any symptoms. The average pain score was 5 and did not differ between those using Marijuana independently of the type or not. Most of the participants reported having chronic pain and most of those used a form of Marijuana regularly. Two third of the participants reported using opioids pain treatment on a daily basis, with most of them also using either NPM, MM or both at the same time. Contrary than excepted, those using NPM preferred ingestible methods over inhalation or topicals, while those using MM preferred inhaled methods, specially blunt and vaporizers over ingestible or topics methods. Most of the participants that have not used any form of Marijuana in the past two years, have considered using them. The most common reason for considering using marijuana was to relieve pain. Conclusion: This data shows a high use of both NPM and MM in adults with SCD, for management of pain and pain modifiers such as depression, anxiety, sleep and mood disorders. The predominance of NPM over the MM on a state with MM is approved for management of Sickle Cell Disease presentations, may be related to some barriers of obtaining medical marijuana, including certification process, cost, lack of insurance coverage and overall availability. Further studies are needed to evaluate role of medical marijuana as a non-medication intervention in SCD, appropriate dosing, methods of use, and combined effect with other medications prescribed for Sickle Cell Disease patients.

Movement Behavior in Adults with Sickle Cell Disease Compared to Healthy Adults: Preliminary Results

Background Sickle cell disease (SCD) is one of the most common monogenic disorders in the world. People with SCD experience pain due to blood flow obstruction and have musculoskeletal and cardiopulmonary complications, which correspond to different chronic conditions. In other chronic diseases, this leads to a reduction in movement behavior. Movement behavior during the day consists of sedentary behavior (sitting and lying), and physical activity (PA) (walking, biking, and running). It has recently been shown that low-to-moderate physical exercises are safe to perform and yield benefits by increasing exercise tolerance and decreasing inflammation in individuals with sickle cell anemia1. Movement behavior of adults with SCD has not been analyzed so far, although patients with SCD have demonstrated to have a reduced 6 minutes walking test previously2. It is hypothesized that adults with SCD are less active and have a more sedentary lifestyle compared to healthy adults. The aim of this study is to identify differences in movement behavior between patients with SCD and healthy adults. Methods Movement behavior of patients with a diagnosis of SCD (>16 years) was evaluated prospectively during their regular outpatient check-ups in two tertiary teaching hospitals in the Netherlands. To compare movement behavior of patients with SCD with a healthy population, data of healthy adults with migration background from a former movement behavior study was used. Demographic characteristics of the healthy adults were compared to statistics of the Dutch population with a migration background to check whether the sample was representative. Movement behavior was measured for seven consecutive days with an accelerometer (Activ8), distinguishing between lying/non-wear, sitting, walking, running, and biking. Absolute time spent on activities and PA (combining walking, running, and biking) were compared between patients with SCD and healthy adults with the Mann-Whitney U test. To adjust for multiple testing, season, sex, and age, a linear regression for each activity was performed using a Bonferroni correction, with activity as dependent variable and group as independent variable. To account for differences in wear time (spending 90 minutes or more lying down/non-wear during the day was classified as non-wear), a sensitivity analysis was performed with absolute time spent on activities expressed as percentage of wear time. Results Twenty-five patients with SCD (median age (IQR) 30 years (21.5) were analyzed and compared with 57 healthy adults (37 years (20)). Patients with SCD were less physically active per day than healthy adults (SCD median (IQR) 117 (70.8) vs healthy 154 (85.8) minutes respectively). With respect to the type of activity, patients with SCD walked 42 minutes per day (-0,7 hours 99.2% CI [-1.27 to -0.13]) less than healthy adults. Sensitivity analysis showed similar results. After adjusting for actual wear time, patients with SCD walked -4.24% less 99.2%CI [-7.51 to -0.97]) than healthy adults and lied down more (5.74% 99.2%CI [0.65 - 10.82]). No significant differences in other activities were identified (sitting, running, and biking). Conclusion and key findings Patients with SCD appear to be less physically active compared to healthy adults, which is mainly reflected by less walking during the day. Less PA during the day in patients with SCD can possibly be explained by SCD-related complications such as poor physical functioning, pain, anemia, and fatigue. These factors can disincentive PA and restrict activity levels during the day. Guidance in changing movement behavior is helpful for patients with SCD. Given the heterogeneity of symptoms in SCD, an individual approach will be necessary. Therefore, a physical therapist could be a key health professional in the multidisciplinary team to help patients with SCD to positively change their movement behavior without significantly increasing the risk of triggering a vaso-occlusive crisis.

Red blood cell alloimmunisation in sickle cell disease patients in the Democratic Republic of the Congo.

To determine the prevalence of red blood cell (RBC) alloimmunisation and alloantibody specificity in sickle cell disease (SCD) patients in Kisangani, Democratic Republic of Congo (DRC) in comparison with those followed at the Centre Hospitalier Régional (CHR) de la Citadelle of Liège (Belgium). Data regarding RBC alloimmunisation (immune response of the organism to foreign erythrocyte antigens, antigens that lack on its own RBC) in SCD patients are scarce in sub-Saharan Africa. We conducted a multi-site-based cross-sectional study among 125 SCD patients at Kisangani and 136 at the CHR de la Citadelle of Liège. The diagnosis of SCD was confirmed by high-performance liquid chromatography. Alloantibodies were screened using the agglutination technique on gel cards and their specificity determined using 11 and/or 16 cell panels. Statistical analyses were carried out using SPSS. The prevalence of RBC alloimmunisation was 9.6% among SCD patients in Kisangani versus 22.8% in those of Liège. At Kisangani as well as at Liège, the median age of alloimmunised patients was higher than that of non-alloimmunised patients, 15.5 years (IQR:4.8-19.8) and 24 years (IQR:14-31) versus 10 years (IQR: 6.5-17) and 17 years (IQR:12-24), respectively. The median number of blood units was higher in both Kisangani and Liège immunised patients compared to non-immunised patients, 8 (IQR:5-11) versus 5 (IQR:3-13) and 41(IQR:6-93) versus 6.5(3-37) respectively. At Kisangani (N=14), the most frequent antibodies were anti-D (28.6%) and anti-C versus anti-E (13.6%), anti-S (13.6%) and anti-Lea (11.4%) at Liège (N=44). These findings stated that alloimmunisation is a common complication in SCD patients in the DRC. In the resource-limited setting of this country, blood transfusion with minimal ABO, D, C and E antigen matching in addition to the use of compatibility test could significantly reduce the incidence of this complication.

Trends of Disease Modifying Treatment Use in Sickle Cell Disease: Retrospective Analysis of Claims Data, 2014-2020

Introduction Over the last few years, several disease modifying treatments (DMTs) have received approval for the treatment of sickle cell disease (SCD). DMTs target key aspects of the pathophysiological processes of SCD and can reduce disease progression and morbidity. Prior to 2017, hydroxyurea was the only FDA-approved pharmacological DMT. After decades of limited pharmacologic options, three novel therapeutics have become available: L-glutamine, voxelotor, and crizanlizumab-tmca. However, data on real-world use of contemporary DMTs are limited to single centers, small sample sizes, and usually focus on single DMTs. Investigating the uptake of new DMTs in SCD is important as patients with SCD continue to experience high morbidity and mortality and, therefore, aggressive adoption of new treatments is paramount to improve patient outcomes. This study uses claims data from a large national insurer to provide information on treatment patterns for all four DMTs from 2014-2020. Methods We conducted a retrospective cohort study using de-identified prescription and medical claims data from the Optum's Clinformatics Data Mart Database (Eden Prairie, MN) from January 2014 - September 2020. Optum contains information on commercial and Medicare insurance beneficiaries. We identified SCD individuals as those with a qualifying ICD-9/10 diagnosis code for SCD in the inpatient or outpatient setting within the study timeframe (index date).We required 6 months of continuous enrollment prior to the index date to collect patient characteristics. Outcomes evaluated were rates of DMT use per year for all DMTs and by each individual DMT. Rates of DMT use were calculated as the number of SCD individuals with at least one prescription fill for the respective DMT divided by total number of SCD individuals in the given year. We also evaluated sociodemographic and clinical characteristics . Results A total of 5,688 individuals had a diagnosis of SCD between 2014-2020. In our cohort, 21.8% of individuals were less than 18 years of age, while 43.1% were between 18-45 years old. During the study period, we identified 1,933 individuals who had at least one prescription fill for any DMT and 3,755 individuals who had no fill for any DMT. Descriptive analyses of patient characteristics revealed that compared to non-DMT users, DMT users were more likely to be male (45.9% vs 40.5%), to be aged 18-45 (50.1% vs 39.5% ), have a higher number of pain episodes (4.1 vs 2.3), and a greater number of SCD complications such as acute chest syndrome (9.1% vs. 3.3%) and avascular necrosis (9.7% vs. 3.0%). For healthcare utilization, DMT users were more likely to have emergency department (ED) visits and inpatient hospitalizations compared to non-DMT users (7.0% vs. 3.7%; 12.1% vs. 8.1% respectively). However, non-DMT users were more likely to have outpatient visits (13.4% vs. 12.5%). When evaluating trends in treatment use, the overall use of DMTs has remained stable with a modest increase over the last 6 years. Analysis of individual DMT use patterns revealed that hydroxyurea use followed the same pattern. Newer DMTs were used in less than 5% of the population with a slight increase in rate of use over the years after approval. Conclusion DMT users had a higher prevalence of SCD complications, pain crises, inpatient hospitalizations and ED visits, which likely reflects indication bias, and were more likely to be young adults, possibly because of concerns over poorer tolerability in older patients. Overall, in spite of the availability of newer DMTs since 2017, the overall rate of DMT use has remained largely stable with only modest increases. As expected, the most commonly used DMT was hydroxyurea, however, <30% of SCD individuals used hydroxyurea over the last 6 years, which confirms prior data showing that hydroxyurea is under prescribed and underutilized in SCD. Lack of guidelines with respect to the newer DMTs may have hampered more widespread adoption of these drugs, alongside knowledge gaps regarding their mechanism of action and place in therapy. In addition, the high cost of the new DMTs and lack of payer approval may have also been a factor in their poor uptake. These data point to the importance of educating health care providers and patients about the importance of pharmacologic DMTs in SCD, and of addressing all potential barriers to their utilization. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Vaccination Status and Disease Burden in Patients with Sickle Cell Disease

Background: Patients with sickle cell disease (SCD) are immunocompromised due to impaired splenic function, dysfunctional antibody production and opsonization, and defects in complement activation leading to increased susceptibility to infections (PMID: 19497774). Therefore, severe acute respiratory syndrome coronavirus 2, also known as COVID-19, may potentially cause severe complications in patients with SCD. The clinical course of COVID-19 infection in SCD has been described in larger cohorts with disease severity varying widely among patients (PMID: 34882837, 33570644). The COVID-19 vaccines have been used since becoming available in late 2020 but data regarding COVID-19 vaccination status, efficacy, and safety in patients with SCD is lacking. The purpose of this study is to investigate COVID-19 vaccination acceptance rates and its efficacy and safety in SCD. Methods: A total of 535 adults (age ≥ 18 years old) with the diagnosis of SCD who had encounters at the University of Illinois Hospital and Health Sciences System (UIHealth) between January 1st, 2021 and December 31st, 2021 were included in this retrospective study. Demographic information, COVID-19 vaccination status, COVID-19 infection and other relevant clinical information were collected. The COVID-19 vaccination status for residents in Chicago was collected from the official website of the city of Chicago. Univariate analyses of patient characteristics were conducted using the Kruskal-Wallis test for continuous variables and the Chi-square test for categorical variables. Stepwise logistic regression analysis was used to identify clinical correlates of COVID-19 vaccination status and infection. Results: In this retrospective cohort, 52.3% received at least one dose and 48.6% completed the primary series of COVID-19 vaccination by December 31, 2021 (Figure 1). This vaccination rate is lower than that of the general African American population (64.7% and 59.1%, respectively). Older age, being employed or a student, and previous influenza immunization history were significant predictors of COVID-19 vaccination completion (Table 1). Approximately 23% of the patients contracted COVID-19 infection with the highest incidence in patients with a higher number of acute healthcare encounters. COVID-19 vaccination decreased the infection risk by 70% (OR 0.311, 95%CI: 0.127-0.766, p = 0.01), but no significant difference in COVID-19 infection severity was found in patients with versus without COVID-19 vaccination. The incidence of side effects associated with COVID-19 vaccination was evaluated by comparing the number of ACC/ED/hospitalization after receiving the vaccine to the same time period in the previous year. No significant difference was found for each dose received (for the 1st door dose: p = 0.105; for the 2nd dose: p = 0.143; and for the 3rd dose: p = 0.397). Summary: We conclude that COVID-19 vaccination did not cause significant side effects and was effective in patients with SCD, but the completion rate is not ideal considering the greater need for vaccination in this patient population. Our findings further emphasize the importance of developing strategies to address vaccination hesitance in patients with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Association of Elevated Tricuspid Regurgitation Velocity with Kidney and Cerebrovascular Disease in Children with Sickle Cell Disease

Introduction: Adult patients with sickle cell disease (SCD) develop progressive end-organ injury leading to multi-organ disease and increased mortality. It is plausible that this multi-organ damage begins in pediatric patients. Tricuspid regurgitation velocity (TRV), measured by echocardiography is a surrogate marker for pulmonary hypertension that is a poor prognostic factor in adults with SCD. The utility of screening echocardiograms as a marker of disease severity is being studied in pediatrics. In this study, we assessed associations between elevated TRV with early development of chronic kidney disease (albuminuria), and cerebrovascular disease (CVD). Methods: We performed an IRB approved cross-sectional study to evaluate the prevalence of elevated TRV ≥ 2.5 m/s and its associations with albuminuria and CVD in patients with SCD ages 1-21 years. We included children with a diagnosis of SCD who had at least one echocardiogram performed during an outpatient clinic visit at steady-state for screening for pulmonary hypertension. We categorized patients as receiving either transfusion therapy (chronic transfusion for >12 months), SCD modifying therapy (hydroxyurea, voxelotor, crizanlizumab, or L-glutamine), or no therapy. Patients on both transfusion and a SCD modifying therapy were defined as being on transfusion therapy. We defined albuminuria as patients with two of three consecutive albumin creatinine ratios ≥30mg/g measured during standard clinic visits. Cerebrovascular disease was defined as having either 1) an overt stroke, 2) silent cerebral stroke defined by MRI, 3) vasculopathy by abnormal magnetic resonance angiography (MRA), 4) transient ischemic event defined by stroke symptoms that resolved within 24 hours, or 5) abnormal TCD (>200 cm/second). We performed bivariate analysis utilizing t-test (or Kruskal-Wallis test) and Cochran-Mantel-Haenszel test for continuous and categorical variables respectively. To determine the association between elevated TRV and albuminuria, and elevated TRV and CVD, logistic regression was fit and adjusted for variables that were significant in the bivariate analysis. Using the TRV <2.5m/sec as the reference group, adjusted odds ratios with their accompanying confidence intervals were calculated for those with albuminuria and those with CVD in separate models. All reported P values were 2-sided. Statistical significance was defined as p<0.05. All analyses were performed using Statistical Analysis Software 9.4, (SAS Institute, Cary, NC). Results: Among 166 children with echocardiography, the prevalence of an elevated TRV was 21%. On bivariate analysis, elevated TRV was significantly associated with persistent albuminuria (OR 2.85 (95% CI: 1.27-6.43) and cerebrovascular disease (OR: 2.46 (95% CI: 1.09-5.53) (Table 1). An elevated TRV was also significantly associated with increased age (15.6 vs 12.9 yrs, p=0.005), lower hemoglobin F% (2.5 vs 4.6%, p=0.01), higher absolute reticulocyte count (0.5 vs 0.4 x 106/ µL p=0.005) and chronic transfusion therapy (p=0.04). After adjusting for age, absolute reticulocyte count, HbF and treatment in a multivariable logistic regression, the associations between elevated TRV with either persistent albuminuria (OR: 1.82 (0.71 - 4.67)) and cerebrovascular disease (OR: 1.15 (0.43-3.10)) were no longer statistically significant (Table 1). Our data suggests that with an odds ratio of 2.9 and a prevalence of elevated TRV of 20%, a prospective study of 166 adolescent patients with SCD would be needed to detect the association between elevated TRV and persistent albuminuria with 80% power and 233 children would be needed to detect this difference with 90% power. Conclusion: This data provides additional evidence that around 20% of pediatric patients have an elevated TRV and those patients may also have an increased risk for developing chronic kidney disease and cerebrovascular disease. A larger, prospective cohort study should be conducted to confirm these findings and determine the role of screening echocardiography in pediatric SCD. At minimum, our data suggests that pediatric patients with known chronic kidney disease or cerebrovascular disease should be screened for cardiac complications. Furthermore, longitudinal studies are needed to evaluate the association between elevated TRV in children with early end-organ complications in adults. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Economic Disparities in the Outcomes of Sickle Cell Disease-Related Admissions over a Decade

Background: According to the CDC, Sickle Cell Disease (SCD) occurs in 1 out of every 365 African American births and 1 out of every 16,300 Hispanic American births. It is an inherited disorder caused secondary to a mutation in the hemoglobin beta subunit and has complex phenotypes. The disease is characterized by recurrent hemolysis, vaso-occlusion leading to pain episodes, and chronic organ damage due to ischemia. A comprehensive care management team is not well established for this disease. There is sparse information regarding the trends in outcomes of SCD admissions in the past decade where rapid advances have been made in treatment including the evolving hematopoietic stem cell transplant. In this study, we sought to analyze the trends and outcomes of SCD admissions in the United States from 2011- 2019 and the influence of socioeconomic status. Methods: The National Inpatient Sample (NIS) database was queried to identify adult patients admitted with a principal diagnosis of Sickle Cell Disease using the International Classification of Disease (ICD-9) and ICD-10 codes. Trends for primary in-hospital outcomes including mortality, length of stay (LOS), and total hospitalization charges (THC) were assessed. The impact of economic status on these outcomes was also studied. Statistics were performed using STATA and multivariate linear and logistic regression analysis was used to adjust for confounders. Results: The rate of hospitalizations for SCD remained stable from 2010 to 2019. Women constituted 53.99% and the majority of patients were young adults (86.62%) and Black (90.36%) as expected. Many patients belonged to the low-income quartile group and were admitted to hospitals with a large bed size and urban teaching hospitals. The overall mortality rate among adult SCD hospitalizations from 2010 to 2019 decreased by an odds ratio of 0.96 (p=0.008) after adjusting for age, sex, and race and is reassuring. However, on subgroup analysis, this trend was replicated for those belonging to a higher income quartile group whereas there was no statistically significant decrease in the mortality rate trend for those belonging to the lower income quartile group. After adjusting for confounders there was an increase in the total charges in all subgroups (p<0.001). The mean LOS decreased for the total population and most subgroups (p<0.001). Conclusion: Despite the advances in the understanding of SCD and its treatment, its benefits have not reached all the people affected. Access to healthcare and the treatment costs associated could be one among the possible reasons why the lower income quartile group have not yet benefited. Meaningful progress in healthcare is not achievable unless these economic disparities are addressed. It is imperative to develop economic policies to address these inequities. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Implementation of Transcranial Doppler Ultrasound Stroke Risk Screening in Urban and Rural Sickle Cell Disease Clinics in Zambia

Introduction Transcranial Doppler Ultrasound (TCD) has a long-established role in the diagnosis of sickle cell disease (SCD) related vasculopathy, paving the way for therapeutic interventions that reduce stroke risk by 92% in high-risk children. In sub-Saharan Africa (SSA), where 75% of the global burden of SCD resides and an estimated 1.03 million children are afflicted, SCD-associated stroke risk evaluation with TCD remains an urgent unmet need. Methods Through a collaborative network with Nationwide Children's Hospital in the USA, 6 health facilities including two in Zambia, had personnel and infrastructure set up to introduce Transcranial Doppler Ultrasonography clinical and research centres of excellence (TCD-COE). The SSA TCD Academy course, designed to advance the technical expertise and capability of participants to perform TCD was created. Learners completed virtually delivered didactic lectures focused on neuroanatomy, scan techniques, doppler waveform characteristics, diagnostic criteria, and clinical application in children. Thereafter, they underwent a week-long, hands-on, practical, introduction to TCD, to increase understanding of the key concepts and to develop basic TCD scanning proficiency. An electronic registry, collecting demographic, clinical and laboratory data was also set up. Ongoing mentorship occurred through real-time consultation and evaluation with feedback given directly from a TCD expert to trainees as they performed the screening. Following completion of the course, participants trained began TCD screening in existing sickle cell out-patient clinics at their institutions, namely, the University Teaching Hospitals-Children's Hospital in Lusaka, and at Chipata Central Hospital in Chipata, in Zambia. Results Trainees selected included a pediatric neurologist, a pediatrician in training, 2 nurses and 2 radiographers. They completed the TCD academy course content over 6 months’ time. To date, over a period of an additional six months, 171 children in Lusaka and 71 children in Chipata with SCD have undergone their first ever, successful TCD stroke risk screening, using a standardized protocol focused on terminal internal carotid artery and middle cerebral artery evaluation. Plans to incorporate TCD screening into routine clinical care are underway. This will require rolling out the screening from the current outpatient clinic day to additional days, to the in-lay ward, as well as to train more staff. Several factors may have facilitated the successful implementation of TCD services into the SCD clinics. The participating institutions had already established SCD clinics, with dedicated staff, therapeutic interventions, and monitoring facilities in place. A referral system was in place to allow the trained staff to interact with the physicians in charge of each SCD clinic. Additionally, the trainees had prior experience with other kinds of ultrasound performance, allowing for more rapid acquisition of the technical skill. Lastly, TCD screening for stroke risk was considered standard of care, according to the Zambian guidelines, catalyzing a notable pre-existing high awareness among the staff and affected families and a high acceptance of the service. Several challenges were also encountered. The physical space available is relatively limited, with insufficient room to set up TCD equipment and examination tables for children to rest comfortably during examinations. Additional space was provided, and the teams were able to expand to locations adjacent to clinics to overcome this obstacle. Staff often had multiples tasks, oftentimes only a single provider could be present to perform TCD examinations. Providing dedicated time and staff may offset this setback. Additionally, other days when staff were available, screening was limited based on the availability of the single machine. This obstacle was overcome with the provision of an additional TCD unit. Lastly, some families did not have financial means to return for the recommended follow up visits. Conclusions TCD screening, to determine stroke risk in children with SCD in SSA is feasible with a modest degree of investment in equipment, staff, and training.

Breaking Down Barriers and Addressing Mental Wellness in Pediatric Sickle Cell Patients

Sickle cell disease is an inherited hemoglobinopathy that is characterized with multi-organ involvement and frequent pain crises. Over the last two decades, a growing body of clinical evidence has pointed out that these somatic complaints can give rise to neuropsychiatric disorders, among which anxiety and depression are the most common, that worsen the health-related quality of life of these patients. Mood disorders can in turn increase fatigue and pain through a psychosomatic component. Although mental health is deemed to play an important role in their health outcomes, at this time, we don't have standardized approach to screening sickle cell patients for depression at most sickle cell centers across the country and at Texas Children's Hospital(TCH). The objective of this Quality Improvement (QI) study is to increase the annual depression screening rate from 0 to 50% in English/Spanish speaking patients who are 12 years and older with an established diagnosis of Sickle Cell Disease (SCD) who present for follow-up care to the Texas Children's Hospital - West Campus (TCH-WC). Our QI project consisted of three distinct PDSA cycles. Prior to the start of the first PDSA cycle, we did not have a streamlined approach for depression screening. The physician team would verbally screen for depression and Social Work was consulted as needed. During our first PDSA cycle, a clinical psychologist was integrated into our monthly Hematology-Pulmonary Joint Clinic and all patients with SCD who presented to Joint Clinic were assessed for depression by the psychologist as part of the psychological evaluation. During the second PDSA cycle, all patients with SCD over the age of 12 who presented to Joint Clinic (with psychologist present) were given the Patient Health Questionnaire-9 modified for Adolescents (PHQ-A) by the Medical Assistant prior to the start of the medical appointment. After the physician team completed their visit, the psychologist addressed concerns raised on the PHQ-A, completed the psychological evaluation and provided appropriate intervention. During the third and final PDSA cycle, the PHQ-A was given to all patients with SCD above the age of 12 who presented to hematology clinic (including those outside of Joint Clinic during which the psychologist was not present). During this cycle, the MA gave the patient the PHQ-A at the start of the visit. The MA then followed an outlined and detailed algorithm. If patient scored 0-6 on the PHQ-A, no intervention was performed. If patient scored 7-9 on the PHQ-A, psychological resources were provided via handout. If patient scored > 10 on the PHQ-A, Social Work referral was placed and patient was preferably seen same day. If patient screened positive for suicide, an urgent Social Work referral was made and patient was seen same day prior to leaving clinic for further evaluation. During our first PDSA cycle, 19 patients above the age of 12 presented to Joint Clinic. Seventeen patients were seen by the psychologist. Twenty-four percent (4/17) of patients were given the PHQ-A; 50% of patients screened positive. Twenty-four percent (4/17) of patients were referred for outpatient follow-up with psychology. During our second PDSA cycle, 14 patients above the age of 12 presented to Joint Clinic. Ninety-three percent (13/14) of patients were given the PHQ-A; 7% (1/14) of patients screened positive for depression. Twenty-one percent (3/14) of patients were referred for outpatient follow-up with psychology. During our third PDSA cycle, 54 patients above the age of 12 presented to Hematology Clinic. Eighty percent (43/54) of eligible patients were given the PHQ-A. Fourteen percent of patients endorsed mild symptoms of depression; 23% of patients endorsed moderate to severe symptoms of depression; 23% of patients endorsed suicidal ideation. Eighty percent of patients with moderate to severe depression received same day Social Work Assessment. One hundred percent of patients with suicidal ideation received same day Social Work assessment. During the first three PDSA's cycle of our project, we achieved our goal of screening greater than 50% of eligible patients with SCD and providing same day intervention. In the future, we will need to examine if there are any downstream effects that negatively impact the clinic flow while administering the questionnaire. We also hope to expand screening for all patients with SCD over the age of 12 across Texas Children's Hospital campuses.

Assessment of Emergency Department Care for Patients with Acute Pain Crisis after the Formation of a Multidisciplinary Team

Introduction:American Society of Hematology (ASH) guidelines recommend the rapid evaluation and treatment of patients presenting to the Emergency Department (ED) with pain from an acute vaso-occlusive episode (VOE) related to sickle cell disease (SCD). The treatment of severe pain from VOE in SCD is time dependent and time sensitive. Guidelines recommend that treatment for acute VOE with parental opioid analgesia occurs within 60 minutes of ED registration. With respect to the five-level Emergency Severity Index (ESI) triage tool, in which lower numbers indicate higher acuity, patients with SCD are to be assigned an Emergency Severity Index (ESI) of 2 indicating (a) greater disease burden, and (b) the need for high priority bed assignment. Objectives: We aimed to create a multidisciplinary team of providers to assess and address the existing barriers and facilitators to improving guideline adherence for the management of acute crises in our large academic health system. The primary outcome of this initiative was to improve guideline adherence by ensuring 90% or greater adherence to ESI 2 assignment to acknowledge illness severity as well as timely, within 60-minute opioid analgesia. Methods: In March 2020, we convened a multidisciplinary team of stakeholders to discuss the ED care of patients with SCD presenting with an acute VOE. The group comprises ED and infusion center nurse champions, nurse educators, nurse leaders, hematologists, palliative care specialists, primary care physicians, psychologists, advanced practice providers and other allied health professionals including social work and spiritual care. Initial monthly meetings established recommendations based on national guidelines and discussed interventions to improve guideline adherence including 1. a nursing driven pain management orderset with subcutaneous and intranasal opioids, 2. a best practice alert with the recommended guidelines. We conducted a retrospective review of ED visit data including all patients with a known diagnosis of sickle cell disease presenting to the ED with a chief complaint of acute pain related to VOE from January 2018-February 2020 and March 2020 to March 2022. We compared the before and after intervention using descriptive statistics. Results: Of the 760 unique encounters for acute pain related to sickle cell disease from 2018-2022, 406 visits occurred before the group formation and 354 visits occurred after the group formed. Mean age was 30.5 years (+/- 19.5) in the pre-intervention period compared to the 29.5 years (+/- 18.9) in the post intervention period. The time to the first opioid order placed pre-intervention averaged 53.3 mins (+/- 64.9) was not significantly different compared to the post period 75.2 mins (+/- 125.8; p =0.17). The proportion of patients assigned an ESI 2 changed from 49.3% to 50.5%. Conclusion: While there was a marginal increase in the ESI 2 assignment among SCD patients presenting in acute VOE, there was no significant change in the ED time to first opioid after the formation of a multidisciplinary team.

Long-Term Efficacy and Safety of L-Glutamine in Preventing Sickle Cell Disease-Related Acute Complications and Hemolysis in Pediatric and Adult Patients: A Real-World Observational Study

Introduction: L-glutamine plays an important role in regulating oxidative stress, one of the key contributors to sickle cell disease pathophysiology. An earlier 48-week Phase 3 study conducted in the United States demonstrated significant reductions in acute complications associated with sickle cell disease, such as vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) in patients on L-glutamine therapy compared to those on placebo (Niihara et al., 2018). This study also showed a significantly fewer number of hospitalizations and hospitalization days for those treated with L-glutamine. Our current real-world observational study is the first to report long term evaluation (120 weeks) of efficacy and safety of L-glutamine (Endari®) therapy in patients living with sickle cell disease in Qatar and French Guiana. Methods: Nineteen patients (10 pediatric and 9 adults), 63% on hydroxyurea, with confirmed diagnosis of sickle cell disease (HbSS genotype) were treated with L-glutamine oral powder (~0.3 g/kg body weight) twice daily for 120 weeks. Of the enrolled patients, 4 patients were from Qatar with the Arab-Indian haplotype and 15 patients were from French Guiana with the African haplotype. The median age was 17 years (range 8 to 54 years) where 53% were <18 years of age. The median body weight of patients was 50 kilograms (range of 25 to 75 kilograms); 53% were males. Clinical events and laboratory parameters (hemoglobin, hematocrit, reticulocytes, and LDH) were collected or measured at baseline, 24, 48, 72, 96, and at 120 weeks. Baseline measures for VOCs, number of hospitalizations, hospitalization days, ACS events, and blood transfusions were collected for the 12 months prior to L-glutamine initiation. Changes from baseline to 120 weeks (annualized) were analysed using MedCalc statistical software Version 20.015. Results: Eighteen patients completed 120 weeks of the real-world L-glutamine treatment observation period. There were significantly fewer VOCs; median of 3 VOCs at baseline and median of 0 at 120 weeks. There were significantly fewer hospitalizations (median of 3 hospitalizations at baseline and 0 at 120 weeks), shorter hospitalization days (median of 15 days at baseline and 0 at end of the observation period), and fewer blood transfusions (median of 3 at baseline and 0 at 120 weeks). The change from baseline values to 120 weeks were significant (p < .00001) for VOCs, hospitalizations, days hospitalized, and the number of units transfused. The number of ACS events were also reduced from 11 at baseline to 0 at 120 weeks. Consistent with these findings, the mean increase in hemoglobin concentrations from baseline was 1.36 g/dL ± 0.17 SE and the mean percent increase in hematocrit from baseline was 5.85% ± 1.10 SE, both significantly improved at 120 weeks (p < .001) Figure 1A. Furthermore, mean reticulocyte counts decreased from baseline (-52.39 x 109/L ± 25.68 SE) and LDH levels decreased from baseline (-311.11 U/L ± 56.02 SE) both significantly changed at 120 weeks (p < .001) Figure 1B. Fewer number of patients were taking hydroxyurea at 120 weeks (8 patients) compared to baseline (12 patients). One patient died during the study (after the 72-week follow up visit) due to multiple deep vein thromboses resulting in a pulmonary embolism; this event was not related to L-glutamine treatment. Conclusion: In this long-term observational study, oral L-glutamine therapy in pediatric and adults living with sickle cell disease resulted in sustained clinical efficacy with improvements in hematologic parameters. L-glutamine therapy was well-tolerated by all patients and there were no safety concerns. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal