Investigation on Dabigatran Etexilate and Worsening of Renal Function in Patients with Atrial fibrillation : the IDEA Study

BACKGROUND AND OBJECTIVES: Warfarin-related nephropathy is an unexplained acute kidney injury, and may occur in patients with supratherapeutic INR, in the absence of overt bleeding. Similar findings have been observed in rats treated with dabigatran etexilate. We conducted a prospective study in dabigatran etexilate-treated patients to assess the incidence of dabigatran-related nephropathy and to investigate the possible correlation between dabigatran plasma concentration (DPC) and worsening renal function. METHOD: One hundred and seven patients treated long term with dabigatran etexilate for non-valvular atrial fibrillation (NVAF) were followed up for 90 days. DPC, serum creatinine (SCr) and serum cystatin C were prospectively measured. Ninety five patients had complete follow-up data and were evaluable for primary endpoint. RESULTS: Eleven patients had supratherapeutic DPC, defined as DPC higher than 200 ng/ml at study enrolment, but at the end of follow-up no patient showed a persistent increase in SCr. No patients experienced acute kidney injury. CONCLUSIONS: Our study shows that no persistent renal detrimental effect is associated with dabigatran treatment. An increase in SCr during dabigatran treatment is reversible and it seems to be unrelated to dabigatran itself

Clinical experience with ipilimumab 3 mg/kg: real-world efficacy and safety data from an expanded access programme cohort.

Ipilimumab improves survival in patients with advanced melanoma. The activity and safety of ipilimumab outside of a clinical trial was assessed in an expanded access programme (EAP).Ipilimumab was available upon physician request for patients aged 16 or over with pretreated stage III (unresectable)/IV melanoma, for whom no other therapeutic option was available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Patients with stable disease or an objective response to ipilimumab were eligible for retreatment upon disease progression. Tumour assessments were conducted at baseline and week 12. Patients were monitored for adverse events (AEs) within 3 to 4 days of each scheduled visit.Of 855 patients participating in the EAP in Italy, 833 were evaluable for response. Of these, 13\% had an objective immune response, and the immune-related disease control rate was 34\%. Median progression-free survival and overall survival were 3.7 and 7.2 months, respectively. Efficacy was independent of BRAF and NRAS mutational status. Overall, 33\% of patients reported an immune-related AE (irAE). The frequency of irAEs was not associated with response to ipilimumab.Outside of a clinical trial setting, ipilimumab is a feasible treatment option in patients with pretreated metastatic melanoma, regardless of BRAF and NRAS mutational status. Data from this large cohort of patients support clinical trial evidence that ipilimumab can induce durable disease control and long-term survival in patients who have failed to respond to prior treatment

Effectiveness of a Hospital-Based Computerized Decision Support System on Clinician Recommendations and Patient Outcomes: A Randomized Clinical Trial.

IMPORTANCE: Sophisticated evidence-based information resources can filter medical evidence from the literature, integrate it into electronic health records, and generate recommendations tailored to individual patients. OBJECTIVE: To assess the effectiveness of a computerized clinical decision support system (CDSS) that preappraises evidence and provides health professionals with actionable, patient-specific recommendations at the point of care. DESIGN, SETTING, AND PARTICIPANTS: Open-label, parallel-group, randomized clinical trial among internal medicine wards of a large Italian general hospital. All analyses in this randomized clinical trial followed the intent-to-treat principle. Between November 1, 2015, and December 31, 2016, patients were randomly assigned to the intervention group, in which CDSS-generated reminders were displayed to physicians, or to the control group, in which reminders were generated but not shown. Data were analyzed between February 1 and July 31, 2018. INTERVENTIONS: Evidence-Based Medicine Electronic Decision Support (EBMEDS), a commercial CDSS covering a wide array of health conditions across specialties, was integrated into the hospital electronic health records to generate patient-specific recommendations. MAIN OUTCOMES AND MEASURES: The primary outcome was the resolution rate, the rate at which medical problems identified and alerted by the CDSS were addressed by a change in practice. Secondary outcomes included the length of hospital stay and in-hospital all-cause mortality. RESULTS: In this randomized clinical trial, 20 563 patients were admitted to the hospital. Of these, 6480 (31.5%) were admitted to the internal medicine wards (study population) and randomized (3242 to CDSS and 3238 to control). The mean (SD) age of patients was 70.5 (17.3) years, and 54.5% were men. In total, 28 394 reminders were generated throughout the course of the trial (median, 3 reminders per patient per hospital stay; interquartile range [IQR], 1-6). These messages led to a change in practice in approximately 4 of 100 patients. The resolution rate was 38.0% (95% CI, 37.2%-38.8%) in the intervention group and 33.7% (95% CI, 32.9%-34.4%) in the control group, corresponding to an odds ratio of 1.21 (95% CI, 1.11-1.32; P < .001). The length of hospital stay did not differ between the groups, with a median time of 8 days (IQR, 5-13 days) for the intervention group and a median time of 8 days (IQR, 5-14 days) for the control group (P = .36). In-hospital all-cause mortality also did not differ between groups (odds ratio, 0.95; 95% CI, 0.77-1.17; P = .59). Alert fatigue did not differ between early and late study periods. CONCLUSIONS AND RELEVANCE: An international commercial CDSS intervention marginally influenced routine practice in a general hospital, although the change did not statistically significantly affect patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02577198

Brentuximab vedotin consolidation after autologous stem cell transplantation for Hodgkin lymphoma: A Fondazione Italiana Linfomi real-life experience

The standard management for relapsed or refractory classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous stem cell transplantation (ASCT). This strategy allows almost 50% of patients to be cured. Post-ASCT maintenance treatment with brentuximab vedotin (BV) confers improved progression-free survival (PFS) to cHL patients at high risk of relapse. We investigated the outcome of 105 cHL patients receiving post-ASCT BV maintenance in the real-life setting of 23 Italian hematology centers. This population included naïve patients and those previously exposed to BV. Median follow-up was 20 months. Patients presented a median of two lines of treatment pre-ASCT, with 51% receiving BV. Twenty-nine percent of patients had at least two high-risk factors (refractory disease, complete response [CR] less than 12 months, extranodal disease at relapse), while 16% presented none. At PET-CT, a Deauville score (DS) of 1–3 was reported in 75% and 78% of pre- and post-ASCT evaluations, respectively. Grade 3–4 adverse events (AEs), mainly peripheral neuropathy, were observed in 16% of patients. Three-year PFS and overall survival (OS) were 62% and 86%, respectively. According to BV exposure, 3-year PFS and OS were 54% and 71%, respectively, for naïve and 77% and 96%, respectively, for previously exposed patients. Refractory disease (hazard ratio [HR] 4.46; p&nbsp;=&nbsp;0.003) and post-ASCT DS 4–5 (HR 3.14; p&nbsp;=&nbsp;0.005) were the only two factors significantly associated with PFS reduction in multivariable analysis. Post-ASCT BV maintenance is an effective, safe treatment option for cHL naïve patients and those previously exposed to BV

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial

Background: The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance. Methods: In 771 newly diagnosed advanced-stage Hodgkin Lymphoma (HL) patients we evaluated the baseline values of NLR and LMR as predictors of clinical outcome. According to the multicenter prospective phase II GITIL-HD0607 trial, all patients received two ABVD courses and if PET-2 negative received four additional ABVD cycles while if PET-2-positive patients were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4 + 4 courses) or Be + Bb (4 + 4) and Rituximab. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review. Results: Higher NLR and lower LMR were associated with a PET-2 positivity and failure to achieve long-term disease control, respectively. By univariate and multivariate analysis, large nodal mass (>7 cm), IPS ≥ 3, NLR > 6 were strong independent predictors of early PET-2 response after ABVD. Only NLR > 6 and IPS ≥ 3 were strong independent predictors of outcome at diagnosis; however, when PET-2 status was added, only PET-2-positive status and IPS ≥ 3 were independent predictors of PFS. Focusing on PET-2-negative patients, those with NLR > 6 had an inferior 3-year PFS compared to patients with NLR ≤ 6 (84% vs 89% months, P =.03). Conclusion: In advanced-stage HL patients treated with a PET-2-driven strategy, IPS ≥ 3 and NLR > 6 are independent predictors of outcome at diagnosis while the presence of large nodal mass, IPS ≥ 3, and NLR > 6 at diagnosis are independent predictors of early ABVD response

The neutrophil to lymphocyte ratio (NLR) and the presence of large nodal mass are independent predictors of early response: A subanalysis of the prospective phase II PET-2-adapted HD0607 trial

The neutrophil to lymphocyte ratio (NLR) and the lymphocyte to monocyte ratio (LMR) can reflect both the myeloid dysfunction and T-cell immune suppression and have prognostic significance

Predicting major bleeding in patients with noncardioembolic stroke on antiplatelets

Objective: To develop and externally validate a prediction model for major bleeding in patients with a TIA or ischemic stroke on antiplatelet agents. Methods: We combined individual patient data from 6 randomized clinical trials (CAPRIE, ESPS-2, MATCH, CHARISMA, ESPRIT, and PRoFESS) investigating antiplatelet therapy after TIA or ischemic stroke. Cox regression analyses stratified by trial were performed to study the association between predictors and major bleeding. A risk prediction model was derived and validated in the PERFORM trial. Performance was assessed with the c statistic and calibration plots. Results: Major bleeding occurred in 1,530 of the 43,112 patients during 94,833 person-years of follow-up. The observed 3-year risk of major bleeding was 4.6% (95% confidence interval [CI] 4.4%–4.9%). Predictors were male sex, smoking, type of antiplatelet agents (aspirin-clopidogrel), outcome on modified Rankin Scale ≥3, prior stroke, high blood pressure, lower body mass index, elderly, Asian ethnicity, and diabetes (S2TOP-BLEED). The S2TOP-BLEED score had a c statistic of 0.63 (95% CI 0.60–0.64) and showed good calibration in the development data. Major bleeding risk ranged from 2% in patients aged 45–54 years without additional risk factors to more than 10% in patients aged 75–84 years with multiple risk factors. In external validation, the model had a c statistic of 0.61 (95% CI 0.59–0.63) and slightly underestimated major bleeding risk. Conclusions: The S2TOP-BLEED score can be used to estimate 3-year major bleeding risk in patients with a TIA or ischemic stroke who use antiplatelet agents, based on readily available characteristics. The discriminatory performance may be improved by identifying stronger predictors of major bleeding

Antiplatelet therapy in the prevention of cardiovascular diseases

Antiplatelet agents have been studied in a number of clinical trials to evaluate their efficacy in the prevention of ischemic cardiovascular events related to platelet-rich thrombi. Acetylsalicylic acid (ASA) is definitely effective in the hospital phase of acute myocardial infarction; it also prevents cardiovascular events but not anginal attacks in patients with unstable angina and reduces the rate of occlusion of coronary artery bypass grafts. ASA is often used in the post-infarction period, even though anticoagulant therapy is probably more effective; it is also effective in patients with transient ischemic attacks in the brain. Ticlopidine is the treatment of choice in patients with major stroke and in those with peripheral vascular ischemia; it can also be considered a valid alternative to ASA in the management of transient ischemic attacks and unstable angina. There is at the moment little role for antiplatelet agents in the primary prevention of cardiovascular disease