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). 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/HbSß0-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/HbSß0-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/HbSß0-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/HbSß0-thalassemia but is dependent on adherence level.

Impact of the Use of Benznidazole Followed by Antioxidant Supplementation in the Prevalence of Ventricular Arrhythmias in Patients With Chronic Chagas Disease: Pilot Study.

Patients with chronic Chagas disease have a higher prevalence of premature ventricular contraction (PVC) because of immunoinflammatory response magnified by the increased oxidative stress. Thus, the sequential treatment with benznidazole (BZN) and antioxidants can reduce the prevalence of PVC. We wish to establish whether the etiological treatment of Chagas disease followed by supplementation with the antioxidant vitamins E and C decreases the prevalence of PVC in these patients. A sample of 41 patients with chronic Chagas disease at different stages of the heart disease was selected for the treatment against the causative agent using BZN (5 mg·kg·d, minimum dose 300 mg daily) for 2 months followed by supplementation with antioxidants such as vitamins E (800 UI/d) and C (500 mg/d) for 6 months. The prevalence of PVC was observed by conducting 24-hour Holter. To evaluate the oxidative status of the patients, serum markers of oxidative stress like glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase were measured, and also reduced glutathione, vitamin E, and markers of tissue damage like thiobarbituric acid reactive substances and protein carbonyl. A decrease in the prevalence of PVC in patients with advanced Chagas heart disease was observed (5391 vs. 1185, P = 0.0068). This reduction was followed by decrease of serum markers of oxidative stress. In patients with a lower degree of cardiac damage, the reduction on prevalence of PVC was not significant. The etiological treatment with BZN followed by supplementation with antioxidant vitamins E and C reduces episodes of PVC in patients with severe Chagas heart disease.

Deep venous thrombosis in children with sickle cell disease.

BACKGROUND: Deep venous thrombosis (DVT) is rare in children compared to adults. Its incidence and risk factors in children are not well known. This study determined these aspects of DVT in children with sickle cell disease (SCD). PROCEDURE: A retrospective, observational and descriptive study was performed. Patients born between October 2000 and October 2012 with SCD and registered in HEMORIO, including those who died in HEMORIO, were included in this study. Patients whose medical records were inaccessible, who died in institutions other than HEMORIO, who died with implanted deep venous catheters, and those who were not monitored in HEMORIO for a period of 1 year or more were excluded from the study. Of a total of 1,519 patients, 456 were excluded and 1,063 patients were included in the study. Data were obtained from the computer system and the medical records at HEMORIO. RESULTS: Of the 1,063 patients, 2 (0.2%) developed DVT with both cases being related to central venous catheters (CVCs) (P-value <0.001). Of the patients who required CVCs, the prevalence of DVT was 10%. No other variable was clinically or statistically significant with respect to DVT. CONCLUSION: The establishment of CVCs in children with SCD poses a high risk for DVT. If this procedure is necessary, the internal jugular vein should be utilized instead of the subclavian and femoral veins. The identification of associated risk factors may justify antithrombotic prophylaxis.

Treatment of the acute sickle cell vaso-occlusive crisis in the Emergency Department: a Brazilian method of switching from intravenous to oral morphine.

OBJECTIVES: Describe the treatment of patients with vaso-occlusive crises (VOC) in a Brazilian emergency department (ED) and the successful switch from intravenous to oral morphine. PATIENTS AND METHODS: We analyzed records of 315 patients with sickle cell disease using two different protocols for pain: one in March 2010 prescribing intravenous morphine every 4 h throughout their stay, and another in March 2011 and 2012 prescribing one initial dose of intravenous morphine followed by equianalgesic doses of oral morphine every 4 h. Patients were triaged into three groups: mild, moderate, and severe VOC. The mild group was treated within 1 h after triage, the moderate within 30 min and the severe was treated immediately. Patients whose pain was not relieved within 6 h after the first dose of morphine were transferred into a different holding area of the ED where they continued to receive the same treatment for 48 h after which they were hospitalized if still in pain. RESULTS: The number of patients who stayed <24 h in the ED increased significantly from 63 in 2010 to 87 in 2012, and the number of admissions decreased from 26 in 2010 to 10 in 2012. The incidence of acute chest syndrome decreased from 8.5% in 2010 to 1.9% in 2012. CONCLUSION: Patients treated with oral morphine stayed a shorter time in the ED, had more pain relief, were admitted less frequently, and had less acute chest syndrome. These differences may be due to environmental, cultural, psychological, and pharmacogenetic factors.

Newborn screening program for hemoglobinopathies in Rio de Janeiro, Brazil.

BACKGROUND: Newborn screening for hemoglobinopathy in Brazil has been decentralized until 2001 when the Health Ministry of Brazil established the National Newborn Hemoglobinopathy Screening Program. The State of Rio de Janeiro started a program in collaboration with the State Health Department and the Institute of Hematology in Rio (HEMORIO). The goal of this study was to evaluate the effectiveness of the first 10 years of the Newborn Hemoglobinopathy Screening Program in identifying and managing infants with Sickle cell disease (SCD) in the State of Rio de Janeiro. PROCEDURE: Blood samples from 1,217,833 neonates were analyzed by High Performance Liquid Chromatography. Infants with SCD were enrolled in comprehensive treatment programs. RESULTS: Data showed that 4.87% of the newborns were heterozygous for a hemoglobin variant, 0.08% were homozygous or doubly heterozygous for abnormal hemoglobins and 95.02% had normal hemoglobin. All the 912 newborns with SCD were referred for treatment at HEMORIO, 34 (3.7%) of these died due to acute chest syndrome, sepsis or splenic sequestration. Four more children died of unknown causes. The implementation of the Rio de Janeiro Newborn Screening Program gradually increased the area of the State covered by the program. CONCLUSION: Data collected during the 10 years of the program showed reduction in mortality of patients with SCD in comparison to available historical statistical data before the implementation of the national screening program. This 10-year study showed that early diagnosis and treatment of newborns was associated with improved survival and quality of life of Brazilian children with SCD.

In-hospital Outcomes of Infective Endocarditis from 1978 to 2015: Analysis Through Machine-Learning Techniques.

BACKGROUND: Early identification of patients with infective endocarditis (IE) at higher risk for in-hospital mortality is essential to guide management and improve prognosis. METHODS: A retrospective analysis was conducted of a cohort of patients followed up from 1978 to 2015, classified according to the modified Duke criteria. Clinical parameters, echocardiographic data, and blood cultures were assessed. Techniques of machine learning, such as the classification tree, were used to explain the association between clinical characteristics and in-hospital mortality. Additionally, the log-linear model and graphical random forests (GRaFo) representation were used to assess the degree of dependence among in-hospital outcomes of IE. RESULTS: This study analyzed 653 patients: 449 (69.0%) with definite IE; 204 (31.0%) with possible IE; mean age, 41.3 ± 19.2 years; 420 (64%) men. Mode of IE acquisition: community-acquired (67.6%), nosocomial (17.0%), undetermined (15.4%). Complications occurred in 547 patients (83.7%), the most frequent being heart failure (47.0%), neurologic complications (30.7%), and dialysis-dependent renal failure (6.5%). In-hospital mortality was 36.0%. The classification tree analysis identified subgroups with higher in-hospital mortality: patients with community-acquired IE and peripheral stigmata on admission; and patients with nosocomial IE. The log-linear model showed that surgical treatment was related to higher in-hospital mortality in patients with neurologic complications. CONCLUSIONS: The use of a machine-learning model allowed identification of subgroups of patients at higher risk for in-hospital mortality. Peripheral stigmata, nosocomial IE, absence of vegetation, and surgery in the presence of neurologic complications are predictors of fatal outcomes in machine learning-based analysis.

CONTEXTE: Le dépistage précoce des patients atteints d'endocardite infectieuse (EI) présentant un risque élevé de mortalité à l'hôpital est essentiel pour orienter la prise en charge et améliorer le pronostic. MÉTHODOLOGIE: Une analyse rétrospective a été réalisée sur une cohorte de patients suivis de 1978 à 2015 et classés selon les critères de Duke modifiés. Les paramètres cliniques, les données des échocardiographies et les hémocultures ont été évalués. Des techniques d'apprentissage automatique, comme l'arbre de classification, ont été utilisées pour expliquer l'association entre les caractéristiques cliniques et la mortalité hospitalière. De plus, le modèle log-linéaire et la représentation graphique en forêts aléatoires ont été utilisés pour évaluer le degré de dépendance entre les résultats hospitaliers et l'EI. RÉSULTATS: Cette étude a permis d'analyser 653 patients : 449 (69,0 %) avec une EI avérée; 204 (31,0 %) avec une EI possible; âge moyen de 41,3 ± 19,2 ans; 420 (64 %) étaient des hommes. Mode d'acquisition de l'EI : communautaire (67,6 %), nosocomial (17,0 %), indéterminé (15,4 %). Des complications sont survenues chez 547 patients (83,7 %), les plus fréquentes étant l'insuffisance cardiaque (47,0 %), les complications neurologiques (30,7 %) et l'insuffisance rénale dépendante de la dialyse (6,5 %). La mortalité hospitalière était de 36,0 %. L'analyse de l'arbre de classification a permis d'identifier des sous-groupes présentant une mortalité hospitalière plus élevée : les patients présentant une EI communautaire et des stigmates périphériques à l'admission; et les patients présentant une EI nosocomiale. Le modèle log-linéaire a montré que le traitement chirurgical était lié à une mortalité hospitalière plus élevée chez les patients présentant des complications neurologiques. CONCLUSIONS: L'utilisation d'un modèle d'apprentissage automatique a permis d'identifier des sous-groupes de patients présentant un risque plus élevé de mortalité à l'hôpital. Les stigmates périphériques, l'EI nosocomiale, l'absence de végétation et la chirurgie en présence de complications neurologiques sont des prédicteurs d'issue fatale dans l'analyse basée sur l'apprentissage automatique.

Risk Factors for Hepatocellular Carcinoma Recurrence and Survival after Liver Transplantation in Patients with HCV-Related Cirrhosis.

PURPOSE: We aimed to identify prognostic factors for survival and recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for patients with HCC and hepatitis C virus-related cirrhosis (HCV-cirrhosis). METHODS: This retrospective cohort study followed all adult patients with HCV-cirrhosis who underwent LT because of HCC or had incidental HCC identified through pathologic examination of the explanted liver at a university hospital in Rio de Janeiro, Brazil, over 11 years (1998-2008). We used Cox regression models to assess the following risk factors regarding HCC recurrence or death after LT: age, Model for End-stage Liver Disease score, Child-Pugh classification, alpha-fetoprotein (AFP), whether patients had undergone locoregional treatment before transplantation, the number of packed red blood cell units (PRBCU) transfused during surgery, the number and size of HCC lesions in the explanted liver, and the presence of microvascular invasion and necrotic areas within HCC lesions. RESULTS: Seventy-six patients were followed up for a median (interquartile range (IQR)) of 4.4 (0.7-6.6) years. Thirteen (17%) patients had HCC recurrence during the follow-up period, and 26 (34%) died. The median survival time was 6.6 years (95% CI: 2.4-12.0), and the 5-year survival was 52.5% (95% CI: 42.3-65.0%). The final regression model for overall survival included four variables: age (hazard ratio (HR): 1.02, 95% CI: 0.96-1.08, P = 0.603), transplantation waiting time (HR: 1.00, 95% CI: 1.00-1.00, P = 0.190), preoperative AFP serum levels (HR: 1.01, 95% CI: 1.00-1.02, P = 0.006), and whether >4 PRBCU were transfused during surgery (HR: 1.15, 95% CI: 1.05-1.25, P = 0.001). The final cause-specific Cox regression model for HCC recurrence included only microvascular invasion (HR: 14.86, 95% CI: 4.47-49.39, P < 0.001). CONCLUSION: In this study of LT for HCV-cirrhosis, preoperative AFP levels and the number of PRBCU transfused during surgery were associated with overall survival, whereas microvascular invasion with HCC recurrence.

Survival Probability in Patients with Sickle Cell Anemia Using the Competitive Risk Statistical Model.

The clinical picture of patients with sickle cell anemia (SCA) is associated with several complications some of which could be fatal. The objective of this study is to analyze the causes of death and the effect of sex and age on survival of Brazilian patients with SCA. Data of patients with SCA who were seen and followed at HEMORIO for 15 years were retrospectively collected and analyzed. Statistical modeling was performed using survival analysis in the presence of competing risks estimating the covariate effects on a sub-distribution hazard function. Eight models were implemented, one for each cause of death. The cause-specific cumulative incidence function was also estimated. Males were most vulnerable for death from chronic organ damage (p = 0.0005) while females were most vulnerable for infection (p=0.03). Age was significantly associated (p ≤ 0.05) with death due to acute chest syndrome (ACS), infection, and death during crisis. The lower survival was related to death from infection, followed by death due to ACS. The independent variables age and sex were significantly associated with ACS, infection, chronic organ damage and death during crisis. These data could help Brazilian authorities strengthen public policies to protect this vulnerable population.

Risk Factors of Pulmonary Hypertension in Brazilian Patients with Sickle Cell Anemia.

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was the covariate that influenced the outcome of normal or abnormal TRJV with a cutoff age of thirty-two years. The survival rate for the group of patients with creatinine (Cr) > 1.0 mg/dL was lower than the group with Cr ≤ 1 and normal TRJV. A coefficient matrix showed that the LDH values were weakly correlated with the reticulocyte count but strongly correlated with hemoglobin suggesting that the TRJV values were not correlated with the hemolytic rate but with anemia. Ten patients died during the follow-up of whom 7 had TRJV > 2.5 m/sec. Acute chest syndrome was the most common cause of death followed by sepsis. In conclusion, this study shows that patients with SS older than thirty-two years with high LDH, elevated TRJV, severe anemia and Cr > 1 have poor prognosis and may be at risk of having pulmonary hypertension and should undergo RHC.

Survival tree and MELD to predict long term survival in liver transplantation waiting list.

MELD score is a formula based on laboratory variables used as a predictor of short-term mortality index in cirrhotic patients. It is applied to allocate patients in liver transplantation waiting list in many countries. However, MELD score cutoff point accuracy to predict long term mortality has not been statistically evaluated. The aim of this study was to analyze the MELD score and other variables related to long-term mortality using a new model: the Survival Tree analysis. The variables considered in this study were obtained at the time of liver transplantation list enrollment. The graphical representation of the survival trees showed that MELD 16 was the most statistically significant mortality cutoff point. The results were compatible with the MELD cutoff point reported in the clinical literature. This methodology can be extended to identify significant cutoff points related to other diseases whose severity is not necessarily expressed by MELD.