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

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2987-2987
Author(s):  
Clarisse Lobo ◽  
Jane S Hankins ◽  
Nickhill Bhakta ◽  
Emilia Nascimento ◽  
Patricia Gomes Moura ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Cost Savings ◽  
Organ Damage ◽  
Cell Disease ◽  
Middle Income ◽  
Disease Modifying Therapies ◽  
Ed Visits ◽  
Disease Modifying ◽  
The Cost ◽  
Hydroxyurea Therapy

Abstract 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. Figure 1 Figure 1. Disclosures Lobo: Novartis: Consultancy. Hankins: Global Blood Therapeutics: Consultancy; UpToDate: Consultancy; Vindico Medical Education: Consultancy; Bluebird Bio: Consultancy.

scholarly journals Cost analysis of acute care resource utilization among individuals with sickle cell disease in a middle-income country

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Clarisse Lobo ◽  
Patricia Moura ◽  
Delaine Fidlarczyk ◽  
Jane Duran ◽  
Roberto Barbosa ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Medication Possession Ratio ◽  
Cost Savings ◽  
Organ Damage ◽  
Cell Disease ◽  
Potential Cost ◽  
Middle Income ◽  
Ed Visits ◽  
The Cost

Abstract Background The costs associated with the treatment of sickle cell disease (SCD) are understudied in low and middle-income countries (LMIC). We evaluated the cost of treating SCD-related acute complications and the potential cost-savings of hydroxyurea in a specialized 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. The reasons for acute hospital visits were grouped as: 1) vaso-occlusive (VOC) pain, 2) infection, 3) anemia exacerbation, and 4) chronic organ damage complications. Hydroxyurea adherence was estimated by medication possession ratio (MPR) during the study period. Results In total, 1144 patients, median age 17 years (range 0–70), 903 (78.9%) with HbSS/HbSβ0-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. Anemia exacerbation was the most expensive reason for ED visit ($321.87/visit), while chronic organ damage carried the highest admission cost ($2176.40/visit). Compared with other genotypes, individuals with HbSS/HbSβ0-thalassemia were admitted more often (79% versus 21%, p < 0.0001), and their admission costs were higher ($1677.18 versus $1224.47/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. Costs of ED visits not resulting in admissions were lower among HbSS/HbSβ0-thalassemia individuals with hydroxyurea MPR ≥65% compared with visits by patients with MPR <65% ($98.16/visit versus $182.46/visit, p = 0.0007). No difference in admission costs were observed relative to hydroxyurea use. Discussion 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. Hydroxyurea may reduce ED costs among individuals with HbSS/HbSβ0-thalassemia but is dependent on adherence level.

scholarly journals Identifying Potential Drug Targets for Sickle Cell Disease through Gene Expression and Pathway Analysis of GEO Data

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Sharjeel Syed ◽  
Jihad Aljabban ◽  
Jonathan Trujillo ◽  
Saad Syed ◽  
Robert Cameron ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Drug Targets ◽  
Meta Analysis ◽  
Cell Disease ◽  
Blood Samples ◽  
Disease Modifying Therapies ◽  
Disease Modifying

Background: The pathogenesis of sickle cell disease (SCD) and its complications have been well characterized down to the molecular level. However, there remains a relative dearth of disease modifying therapies that reduce the frequency and number of vas-occlusive crises, hospitalizations, and deaths. Recent advancements in utilizing hydroxyurea and L-glutamine, which both impact unique disease pathways, should pave way for the identification of other molecular pathways as ideal drug targets. In this regard, our meta-analysis serves to identify key genes and associated pathways that are differentially expressed in SC patients. Methods: We employed our STARGEO platform to tag samples from the NCBI Gene Expression Omnibus and performed meta-analysis to compare SC and healthy control transcriptomes. For the meta-analysis, we tagged 285 peripheral blood samples from SC patients and 86 samples from healthy subjects as a control. We then analyzed the signature in Ingenuity Pathway Analysis to elucidate top disease functions from our analysis. Results: From our meta-analysis, we identified iron homeostasis signaling, NRF2-mediated oxidative stress response, cell senescence, and pyrimidine interconversion/biosynthesis as top canonical pathways that were upregulated in the peripheral blood samples from SC patients. Top upstream regulators included membrane associated protein and transporter ABCB6, non-coding RNY3, and erythroid maturation transcription factors GATA1, KLF1, and HIPK2 (with predicted activation). The most upregulated genes included inflammatory modulators RNF182 and IFI27, the latter of which has been shown to inhibit vascular endothelial growth and repair. Several membrane-associated protein coding genes such as GYPA, RAP1GAP, and PAQR9 were also upregulated in the SC samples. RAP1GAP is known to modulate neutrophil cell adhesion and homing while PAQR9 has roles in regulating protein quality control: a role also seen in similarly upregulated YOD1, a deubiquitinating enzyme involved in trafficking of misfolded proteins. Expectedly, also upregulated were HBBP1 and SOX6, which regulate globin genes and have been shown to silence γ-globin expression. Lastly, SLC6A19, the neutral amino acid transporter mutated in Hartnup disease, was also upregulated. Of the downregulated genes, WASF3, a member of the Wiskott-Aldrich syndrome protein family, has been linked to poor survival in many malignancies, including AML and CMML, but has not previously been linked to SCD pathogenesis. ENKUR was also downregulated and has been annotated as a tethering protein to cation channels as well as linked to pathways involving vascular leakage. SIGLEC10, which binds to vascular adhesion proteins, is a key suppressor of inflammatory responses to damage; it's downregulation along with ELAPOR1, a transmembrane protein involved in cellular response to stress, was also observed. Finally, based off the focus genes in our analysis we identified several networks with most being involved in amino acid metabolism, cellular assembly, function, and maintenance, hematological disease, and organismal injury. The top pathway is illustrated in Figure 1. Conclusions: Our study illustrates differentially expressed gene activity in SCD consistent with known pathophysiology such as immune response, endothelial damage and adherence, heme metabolism, and globin regulation. We also showed evidence of genes not previously studied in SCD, which may have novel roles such as those part of the ubiquitin-proteasome system like YOD1 and RNF182. Additionally, while some genes in our analysis like EKLF and GAT1 have been shown to enhance δ-globin expression, paving way for possible drug therapies for B-hemoglobinopathies, others like IFI27, PAQR9, RAP1GAP, ENKUR, SIGLEC10, WASF3, and SOX9 have yet to be studied as mediators of disease pathogenesis in SCD. A target to SOX9, a known suppressor of γ-globin, or ABCB6, a known modulator of erythroid cell shape and hydration, have particularly promising potential as disease modifying therapies. Finally, HIPK2, HBBP1, and SLC6A19 have previously been shown to have intriguing effects on hydroxyurea dosing and responsivity in SC patients and may also be candidate target molecules to enhance existing therapies. These data identify potential candidate pathways for mechanistic studies seeking to confirm a causative role in the pathogenesis of sickle cell disease. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proponent or collaborative: Physician perspectives and approaches to disease modifying therapies in sickle cell disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0178413 ◽  
Author(s):  
Nitya Bakshi ◽  
Cynthia B. Sinha ◽  
Diana Ross ◽  
Kirshma Khemani ◽  
George Loewenstein ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Disease Modifying Therapies ◽  
Physician Perspectives ◽  
Disease Modifying

Reduction in the Frequency of Emergency Department Visits for Complications Related to Sickle Hemoglobinopathies: Effects of Aggressive Hydroxyurea Therapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2067-2067 ◽  
Author(s):  
Ashok Raj ◽  
Arun Ranjan Panigrahi ◽  
Scott N. Myers ◽  
Jennifer Mullinax ◽  
John A Myers ◽  
...  
Keyword(s):  
Emergency Department ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Expert Panel ◽  
Treatment Protocol ◽  
Emergency Department Visits ◽  
Cell Disease ◽  
Hb S ◽  
Ed Visits ◽  
Hydroxyurea Therapy

Abstract Context Early and aggressive use of hydroxyurea (HU) in sickle hemoglobinopathies has been in practice at our comprehensive sickle cell center since 2012 when standardized protocols were still evolving. The consensus treatment protocol for hydroxyurea therapy in sickle cell disease (SCD) documented in the "Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014" has authenticated our clinical practice. Objectives Although emergency departments play an important role in providing acute and urgent care for patients with SCD, the frequency of visits by patients can possibly be reduced by increased use of sickle-directed therapies in the outpatient setting. The objective of this study was to determine the impact of aggressive HU therapy, including shared decision making with parents for early use of HU and dose escalation up to the maximum tolerated dose, on the frequency of emergency department (ED) visits for patients with sickle hemoglobinopathies. Methods ED visits by patients with sickle hemoglobinopathies (HbSS disease, Hb S beta zero thalassemia, HbSC disease, Hb S beta plus thalassemia) were identified using ICD-9-CM diagnosis codes of 282.6, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, 282.69, 282.41, and 282.42. From visits having one or more of these diagnoses, cases that had indicated that the visit was related to an injury, poisoning, or adverse effect of medical treatment were excluded to form the study group of emergency department visits by patients. However, if the ED visit was for HU complications/side effects, they were included. Data from 2010-2015 was collected from the ED of Kosair Children's Hospital and affiliated hospitals in Louisville, which are the community-wide and primary locations where pediatric patients with sickle hemoglobinopathies are evaluated for disease-related complications requiring emergency management including pain crises, fever episodes, acute chest syndrome, etc. To determine if aggressive use of HU was associated with adecrease in the frequency of ED visits, segmented linear regression techniques were used to compare the mean monthly rates of ED visits before and after implementation of this treatment strategy. Results: The rate of sickle hemoglobinopathies seen in the ED significantly decreased after implementation of the aggressive HU treatment protocol (β=2.48 vs. β=-3.91, p=0.003). After implementation of the aggressive HU protocol, there has been a 55% decrease in the monthly rate of sickle hemoglobinopathies seen in the ED (21.0 vs. 9.5, p<0.001) from the peak monthly rate seen in 2012, which is a 40% reduction since the start of the study period [15.8 vs. 9.5, p=0.011]). Conclusion: Substantial reduction in the frequency of ED visits occurred in children with sickle hemoglobinopathies with the simple intervention of early and aggressive usage of HU and its dose escalation to the maximally tolerated dose. The findings of this study suggest that improving the process of prescribing HU as outlined in the "Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014" reduced the complications of sickle hemoglobinopathies requiring emergency care management and is an indicator of the enhanced quality of health care in sickle hemoglobinopathies. Figure 1. The average monthly rate of sickle hemoglobinopathies seen in the ED stratified by year. --- = reference point in which aggressive HU was implemented. Figure 1. The average monthly rate of sickle hemoglobinopathies seen in the ED stratified by year. --- = reference point in which aggressive HU was implemented. Disclosures No relevant conflicts of interest to declare.

scholarly journals Drug Therapies for the Management of Sickle Cell Disease

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 592
Author(s):  
Parul Rai ◽  
Kenneth I. Ataga
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Organ Damage ◽  
The United States ◽  
Cell Disease ◽  
Multiple Agents ◽  
Middle Income ◽  
Hematopoietic Stem ◽  
Rich Countries ◽  
Low And Middle Income

Sickle cell disease (SCD) afflicts millions of people worldwide but is referred to as an orphan disease in the United States. Over the past several decades, there has been an increasing understanding of the pathophysiology of SCD and its complications. While most individuals with SCD in resource-rich countries survive into adulthood, the life expectancy of patients with SCD remains substantially shorter than for the general African-American population. SCD can be cured using hematopoietic stem cell transplantation and possibly gene therapy, but these treatment approaches are not available to most patients, the majority of whom reside in low- and middle-income countries. Until relatively recently, only one drug, hydroxyurea, was approved by the US Food and Drug Administration to ameliorate disease severity. Multiple other drugs (L-glutamine, crizanlizumab, and voxelotor) have recently been approved for the treatment of SCD, with several others at various stages of clinical testing. The availability of multiple agents to treat SCD raises questions related to the choice of appropriate drug therapy, combination of multiple agents, and affordability of recently approved products. The enthusiasm for new drug development provides opportunities to involve patients in low- and middle-income nations in the testing of potentially disease-modifying therapies and has the potential to contribute to capacity building in these environments. Demonstration that these agents, alone or in combination, can prevent or decrease end-organ damage would provide additional evidence for the role of drug therapies in improving outcomes in SCD.

scholarly journals Evidence-based interventions implemented in low-and middle-income countries for sickle cell disease management: A systematic review of randomized controlled trials

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246700
Author(s):  
Joyce Gyamfi ◽  
Temitope Ojo ◽  
Sabrina Epou ◽  
Amy Diawara ◽  
Lotanna Dike ◽  
...  
Keyword(s):  
Systematic Review ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Nutritional Supplements ◽  
Evidence Based ◽  
Cell Disease ◽  
Middle Income ◽  
Middle Income Countries ◽  
Disease Modifying ◽  
Disease Modifying Agents

Background Despite ~90% of sickle cell disease (SCD) occurring in low-and middle-income countries (LMICs), the vast majority of people are not receiving evidence-based interventions (EBIs) to reduce SCD-related adverse outcomes and mortality, and data on implementation research outcomes (IROs) and SCD is limited. This study aims to synthesize available data on EBIs for SCD and assess IROs. Methods We conducted a systematic review of RCTs reporting on EBIs for SCD management implemented in LMICs. We identified articles from PubMed/Medline, Global Health, PubMed Central, Embase, Web of Science medical subject heading (MeSH and Emtree) and keywords, published from inception through February 23, 2020, and conducted an updated search through December 24, 2020. We provide intervention characteristics for each study, EBI impact on SCD, and evidence of reporting on IROs. Main results 29 RCTs were analyzed. EBIs identified included disease modifying agents, supportive care agents/analgesics, anti-malarials, systemic treatments, patient/ provider education, and nutritional supplements. Studies using disease modifying agents, nutritional supplements, and anti-malarials reported improvements in pain crisis, hospitalization, children’s growth and reduction in severity and prevalence of malaria. Two studies reported on the sustainability of supplementary arginine, citrulline, and daily chloroquine and hydroxyurea for SCD patients. Only 13 studies (44.8%) provided descriptions that captured at least three of the eight IROs. There was limited reporting of acceptability, feasibility, fidelity, cost and sustainability. Conclusion EBIs are effective for SCD management in LMICs; however, measurement of IROs is scarce. Future research should focus on penetration of EBIs to inform evidence-based practice and sustainability in the context of LMICs. Clinical trial registration This review is registered in PROSPERO #CRD42020167289.

scholarly journals Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 296
Author(s):  
Rosa Vona ◽  
Nadia Maria Sposi ◽  
Lorenza Mattia ◽  
Lucrezia Gambardella ◽  
Elisabetta Straface ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Globin Gene ◽  
Organ Damage ◽  
Cell Disease ◽  
Vessel Occlusion ◽  
Antioxidant Agents ◽  
Oxidant Status

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population.

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