Codruta Chiuzan

Research Participants’ Preferences for Hypothetical Secondary Results from Genomic Research

Secondary or incidental results can be identified in genomic research that increasingly uses whole exome/genome sequencing. Understanding research participants’ preferences for secondary results and what influences these decisions is important for patient education, counseling, and consent, and for the development of policies regarding return of secondary results. Two hundred nineteen research participants enrolled in genomic studies were surveyed regarding hypothetical preferences for specific types of secondary results, and these preferences were correlated with demographic information and psychosocial data. The majority of research participants (73%) indicated a preference to learn about all results offered, with no clear pattern regarding which results were not desired by the remaining participants. Participants who reported greater interest in genetic privacy were less likely to indicate a preference to learn all results, as were individuals who self-identified as Jewish. Although most research participants preferred to receive all secondary results offered, a significant subset preferred to exclude some results, suggesting that an all-or-none policy would not be ideal for all participants. The correlations between preferences to receive secondary results, religious identification, and privacy concerns demonstrate the need for culturally sensitive counseling and educational materials accessible to all education levels to allow participants to make the best choices for themselves.

Considering Whether Medicaid Is Worth the Cost: Revisiting the Oregon Health Study

The Oregon Health Study was a groundbreaking experiment in which uninsured participants were randomized to either apply for Medicaid or stay with their current care. The study showed that Medicaid produced numerous important socioeconomic and health benefits but had no statistically significant impact on hypertension, hypercholesterolemia, or diabetes. Medicaid opponents interpreted the findings to mean that Medicaid is not a worthwhile investment. Medicaid proponents viewed the experiment as statistically underpowered and, irrespective of the laboratory values, suggestive that Medicaid is a good investment. We tested these competing claims and, using a sensitive joint test and statistical power analysis, confirmed that the Oregon Health Study did not improve laboratory values. However, we also found that Medicaid is a good value, with a cost of just

Concomitant aortic valve repair with continuous-flow left ventricular assist devices: Results and implications

62 000 per quality-adjusted life-years gained.

Importance of stratifying acute kidney injury in cardiogenic shock resuscitated with mechanical circulatory support therapy

OBJECTIVES Aortic insufficiency (AI) after continuous-flow left ventricular assist device implantation can affect patient outcomes. Central aortic valve closure (CAVC) is a strategy commonly practiced; however, its efficacy has not been extensively investigated. METHODS From March 2004 to May 2014, a total of 340 patients received a continuous-flow left ventricular assist device (89; 26.2%) as destination therapy (DT). Outcomes were compared between patients with CAVC (n = 57 [16.8%]; group A) versus without repair (n = 283 [83.2%]; group B). RESULTS Patients in group A were older, were more likely to be having DT, had a greater cardiopulmonary bypass and aortic crossclamp time, and more often received intraoperative transfusions than did patients in group B. Twenty-three (40.4%) patients in group A had significant pre-existing AI, defined as >mild AI, whereas none did in group B. Kaplan-Meier analysis revealed that freedom from significant AI was 66.7% and 59.9% at 2 years (P = .77) in groups A and B, respectively. In the DT cohort, freedom from significant AI was 78.1% and 41.8% at 2 years (P = .077). A generalized mixed-effects model demonstrated a 57% and 69% decrease in the odds of significant AI progression among repaired patients in the entire and DT cohort, respectively, after adjusting for time effect and degree of baseline pre-existing AI. CONCLUSIONS Despite pre-existing AI, the prevalence of significant AI in patients with CAVC was comparable to the AI in those without pre-existing AI/CAVC. The efficacy of this technique was more evident in DT patients. Thus, CAVC may be an effective and durable strategy, especially in patients who require lengthy device support.

A phase I study of romidepsin and pralatrexate reveals marked activity in relapsed and refractory T-cell lymphoma

Objective: Although the outcomes of patients with cardiogenic shock remain poor, short‐term mechanical circulatory support has become an increasingly popular modality for hemodynamic assistance and organ preservation. Because the kidney is exquisitely sensitive to poor perfusion, acute kidney injury is a common sequela of cardiogenic shock. This study examines the incidence and clinical impact of acute kidney injury in patients with short‐term mechanical circulatory support for cardiogenic shock. Methods: Retrospective review was performed of 293 consecutive patients with cardiogenic shock who were treated with short‐term mechanical circulatory support. The well‐validated 2014 Kidney Disease Improving Global Outcomes criteria were used to stage acute kidney injury. Outcomes of interest were long‐term mortality and renal recovery. Results: Acute kidney injury developed in 177 of 293 patients (60.4%), of whom 113 (38.6%) were classified with stage 3 (severe). Kaplan–Meier survival estimates indicated a 1‐year survival of 49.2% in the nonsevere (stages 0‐2) acute kidney injury cohort versus 27.3% in the severe acute kidney injury cohort (P < .001). Multivariable Cox regression demonstrated that severe acute kidney injury was a predictor of long‐term mortality (hazard ratio, 1.54; confidence interval, 1.10‐2.14; P = .011). Among hospital survivors, renal recovery occurred more frequently (82.4% vs 63.2%, P = .069) and more quickly (5.6 vs 24.5 days, P < .0001) in the nonsevere than in the severe acute kidney injury group. Conclusions: Acute kidney injury is common and frequently severe in patients in cardiogenic shock treated with short‐term mechanical circulatory support. Milder acute kidney injury resolves with survival comparable to patients without acute kidney injury. Severe acute kidney injury is an independent predictor of long‐term mortality. Nonetheless, many surviving patients with acute kidney injury do experience gradual renal recovery.

Concomitant mitral repair and continuous-flow left ventricular assist devices: Is it warranted?

Peripheral T-cell lymphomas (PTCL) are a group of rare malignancies characterized by chemotherapy resistance and poor prognosis. Romidepsin and pralatrexate were approved by the US Food and Drug Administration for patients with relapsed/refractory PTCL, exhibiting response rates of 25% and 29% respectively. Based on synergy in preclinical models of PTCL, we initiated a phase 1 study of pralatrexate plus romidepsin in patients with relapsed/refractory lymphoma. This was a single institution dose-escalation study of pralatrexate plus romidepsin designed to determine the dose-limiting toxicities (DLTs), maximum tolerated dose, pharmacokinetic profile, and response rates. Patients were treated with pralatrexate (10 to 25 mg/m2) and romidepsin (12 to 14 mg/m2) on 1 of 3 schedules: every week × 3 every 28 days, every week × 2 every 21 days, and every other week every 28 days. Treatment continued until progression, withdrawal of consent, or medical necessity. Twenty-nine patients were enrolled and evaluable for toxicity. Coadministration of pralatrexate and romidepsin was safe, well tolerated, with 3 DLTs across all schedules (grade 3 oral mucositis × 2; grade 4 sepsis × 1). The recommended phase 2 dose was defined as pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every other week. Twenty-three patients were evaluable for response. The overall response rate was 57% (13/23) across all patients and 71% (10/14) in PTCL. The phase 1 study of pralatrexate plus romidepsin resulted in a high response rate in patients with previously treated PTCL. A phase 2 study in PTCL will determine the efficacy of the combination. This trial was registered at www.clinicaltrials.gov as #NCT01947140.

Impact of small prosthesis size on transcatheter or surgical aortic valve replacement outcomes

Background: Pre‐existing mitral pathology is common in patients undergoing continuous‐flow left ventricular assist device implantation. We sought to investigate whether concurrent mitral repair confers any advantage. Methods: From March 2004 to October 2014, 374 patients received a continuous‐flow left ventricular assist device. Of these, a total of 115 patients with pre‐existing mitral regurgitation (MR) greater than moderate were identified and included in the analysis. Outcomes were compared between patients with concurrent mitral repair (n = 52 [45.2%]; Group A) and without repair (n = 63 [54.8%]; Group B). Results: The mean age was 56.8 years and 25 (21.5%) were women. Patients in Group A were more likely to have undergone destination therapy (48.1% vs 11.1%; P < .001) and had a greater cardiopulmonary bypass time (125 vs 89 minutes; P < .001) than did patients in Group B. Longitudinal analysis using a generalized mixed‐effects model demonstrated the odds of developing moderate or severe MR during device support were 86% lower for Group A patients (P < .001). Among those who were discharged alive, 9 (8.6%)—consisting of 1 (2.2%) in Group A and 8 (13.6%) in Group B (P = .039)—developed late right heart failure requiring a total of 13 readmissions (0.03 vs 0.15 readmissions per patient‐year; P = .011). Multivariable competing risks regression revealed mitral repair to be a protective factor (hazard ratio, 0.16; 95% confidence interval, 0.03‐0.94; P = .042) for late right heart failure occurrence. Conclusions: Concurrent mitral repair appears to be efficacious in controlling MR after device implant. The fact that repaired patients developed late right heart failure less frequently than did patients without repair challenges the notion that concurrent mitral repair is unwarranted.

Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis.

Determine the comparative impact of small prosthesis size on transcatheter and surgical aortic valve replacement (SAVR) outcomes.