Francis Vekeman

Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study

IntroductionRecent data indicate that transfusion of packed red blood cells (pRBCs) may increase the risk for the development of acute respiratory distress syndrome (ARDS) in critically ill patients. Uncertainty remains regarding the strength of this relationship.MethodsTo quantify the association between transfusions and intensive care unit (ICU)-onset ARDS, we performed a cohort study within Crit, a multicenter, prospective, observational study of transfusion practice in the ICU which enrolled 4,892 critically ill patients in 284 ICUs in the United States. Diagnostic criteria for ARDS were prospectively defined, and we focused on subjects without ARDS at admission. The development of ARDS in the ICU served as the primary endpoint.ResultsAmong the 4,730 patients without ARDS at admission, 246 (5.2%) developed ARDS in the ICU. At baseline, ARDS cases were younger, more likely to be in a surgical ICU, and more likely to be admitted with pneumonia or sepsis than controls without ARDS. Cases also were more likely to have a serum creatinine of greater than 2.0 mg/dl (23% versus 18%) and a serum albumin of less than or equal to 2.3 g/dl (54% versus 30%) and were more severely ill upon ICU admission as measured by either the APACHE II (Acute Physiology and Chronic Health Evaluation II) or SOFA (Sequential Organ Failure Assessment) score (p < 0.05 for all). Sixty-seven percent and 42% of cases and controls, respectively, had exposure to pRBC transfusions (p < 0.05), and the unadjusted odds ratio (OR) of developing ARDS in transfused patients was 2.74 (95% confidence interval [CI], 2.09 to 3.59; p < 0.0001) compared to those never transfused. After age, baseline severity of illness, admitting diagnosis, and process-of-care factors were adjusted for, the independent relationship between pRBC transfusions and ICU-onset ARDS remained significant (adjusted OR, 2.80; 95% CI, 1.90 to 4.12; p < 0.0001).ConclusionDevelopment of ARDS after ICU admission is common, occurring in approximately 5% of critically ill patients. Transfusion of pRBCs is independently associated with the development of ARDS in the ICU.

An assessment of erythroid response to epoetin α as a single agent versus in combination with granulocyte– or granulocyte-macrophage–colony-stimulating factor in myelodysplastic syndromes using a meta-analysis approach†

Epoetin α (EPO) continues to be the initial treatment of choice for most anemic patients with myelodysplastic syndromes (MDS). Over the years, different therapeutic strategies have been adopted to optimize the clinical benefits of EPO in this setting.

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV‐based all‐oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy‐proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End‐Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child‐Turcotte‐Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV‐based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV‐based all‐oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status. Liver Transplantation 22 446‐458 2016 AASLD

Relationship between hemoglobin level and quality of life in anemic patients with chronic kidney disease receiving epoetin alfa

ABSTRACT Objectives: To evaluate the relationship between hemoglobin (Hb) level and quality of life (QOL) in anemic patients with non-dialysis chronic kidney disease receiving epoetin alfa. Patients and methods: A post-hoc analysis using data from a multicenter, open-label, prospective study of epoetin alfa for anemia in patients with chronic kidney disease not on dialysis was conducted. The relationship between Hb and QOL was analyzed using correlation and longitudinal analyses, the latter adjusting for sample selection bias. The Linear Analog Scale Assessment (LASA) and the Kidney Disease Questionnaire (KDQ) subscales were used to measure QOL. The impact of an incremental 1 g/dL increase in Hb level on LASA and KDQ scores was determined using an incremental analysis. Results: A total of 1183 and 1044 patients formed the study populations for the LASA and KDQ analyses, respectively. There was a positive and significant relationship between Hb levels and QOL ( p < 0.05). Using non-linear regression analysis, we characterized the sigmoid-shape of the relationship between Hb levels and QOL scores. Hemoglobin change was a statistically significant determinant of QOL improvement for both LASA and KDQ scales ( p < 0.05). The model predicted that, based on a 2 unit change in Hb, the greatest incremental QOL improvement per unit of Hb increase occurred when Hb was in the range of 11 to 12 g/dL. Conclusions: This study demonstrates that, beyond the well-known relationship between Hb increases and QOL improvements, the maximal incremental gain in QOL occurred when Hb reached 11 to 12 g/dL. This suggests that treating anemic patients with non-dialysis chronic kidney disease until their Hb level reaches 12 g/dL will result in the greatest QOL improvement per Hb unit increase. The analyses were conducted based on an open-label study of epoetin alfa and could be further validated using a randomized, controlled trial, comparing incremental gains in QOL associated with treatment initiation at varying levels of Hb across arms.

Age-related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs.

This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD.

Impact of adverse events, treatment modifications, and dose intensity on survival among patients with advanced renal cell carcinoma treated with first-line sunitinib: a medical chart review across ten centers in five European countries

Angiogenesis inhibitors have become standard of care for advanced and/or metastatic renal cell carcinoma (RCC), but data on the impact of adverse events (AEs) and treatment modifications associated with these agents are limited. Medical records were abstracted at 10 tertiary oncology centers in Europe for 291 patients ≥18 years old treated with sunitinib as first‐line treatment for advanced RCC (no prior systemic treatment for advanced disease). Logistic regression models were estimated to compare dose intensity among patients who did and did not experience AEs during the landmark periods (18, 24, and 30 weeks). Cox proportional hazard models were used to explore the possible relationship of low‐dose intensity (defined using thresholds of 0.7, 0.8, and 0.9) and treatment modifications during the landmark periods to survival. 64.4% to 67.9% of patients treated with sunitinib reported at least one AE of any grade, and approximately 10% of patients experienced at least one severe (grade 3 or 4) AE. Patients reporting severe AEs were statistically significantly more likely to have dose intensities below either 0.8 or 0.9. Dose intensity below 0.7 and dose discontinuation during all landmark periods were statistically significantly associated with shorter survival time. This study of advanced RCC patients treated with sunitinib in Europe found a significant relationship between AEs and dose intensity. It also found correlations between dose intensity and shorter survival, and between dose discontinuation and shorter survival. These results confirm the importance of tolerable treatment and maintaining dose intensity.

Impact of limiting erythropoiesis‐stimulating agent use for chemotherapy‐induced anemia on the United States blood supply margin

BACKGROUND: Recently, the Centers for Medicare and Medicaid Services issued a national coverage determination that limited erythropoiesis‐stimulating agents (ESAs) utilization in patients with chemotherapy‐induced anemia (CIA). This study evaluated the impact of limiting the use of ESAs for CIA on the US blood supply margin.

In-hospital risk of venous thromboembolism and bleeding and associated costs for patients undergoing total hip or knee arthroplasty

Abstract Objective: Benefits of anti-coagulation for venous thromboembolism (VTE) prevention in total hip and knee arthroplasty (THA/TKA) may be offset by increased risk of bleeding. The aim was to assess in-hospital risk of VTE and bleeding after THA/TKA and quantify any increased costs. Methods: Healthcare claims from the Premier PerspectiveTM Comparative Hospital Database (January 2000–September 2008) were selected for subjects ≥18 years with ≥1 diagnosis code for THA/TKA. VTE was defined as ≥1 code for deep vein thrombosis or pulmonary embolism. Bleeding was classified as major/non-major. Incremental in-hospital costs associated with VTE and bleeding were calculated as cost differences between inpatients with VTE or bleeding matched 1:1 with inpatients without VTE or bleeding. Results: A total of 820,197 inpatient stays were identified: 8042 had a VTE event and 7401 a bleeding event (2740 major bleeding). The risks of VTE, any bleeding, and major bleeding were 0.98, 0.90, and 0.33/100 inpatient stays, respectively. Mean incremental in-hospital costs per inpatient were

Risk of Hepatotoxicity‐Related Hospitalizations among Patients Treated with Opioid/Acetaminophen Combination Prescription Pain Medications

2663 for VTE,

Kidney involvement in tuberous sclerosis complex: the impact on healthcare resource use and costs

2028 for bleeding, and