Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts

Objectives In older patients, the the D-dimer test for pulmonary embolism has reduced specificity and is therefore less useful. In this study a new, age dependent cut-off value for the test was devised and its usefulness with older patients assessed

Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery  76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival

Biomarkers in pulmonary embolism

Purpose of review Controversy exists about the precise role of thrombolytic therapy in normotensive patients with pulmonary embolism. To resolve this controversy two major questions must be addressed. First, can a subgroup of normotensive pulmonary embolism patients with a high risk for adverse outcomes, such as in-hospital mortality or early recurrent venous thromboembolism, be identified? Second, is there convincing evidence that the benefits of more aggressive therapy counterbalance its risks? Troponin I and T as well as brain natriuretic peptide (BNP) have recently been introduced as promising tools in the risk assessment of patients with pulmonary embolism. Recent findings The studies in series of patients with pulmonary embolism showed prevalences of elevated cardiac biomarkers of 16 to 84%. Positive predictive values for in-hospital mortality varied from 6 to 44%, whereas negative predictive values for uneventful outcome were above 93% in all studies. Summary Although a correlation between elevated biomarkers and in-hospital mortality in pulmonary embolism patients is present in most of the studies, the positive predictive value appears to be insufficient to extend the indication for thrombolytic therapy to all patients with elevated biomarkers. Future research is necessary to show whether combining different biomarkers with echocardiography is more usefu

Prognostic value of echocardiographically assessed right ventricular dysfunction in patients with pulmonary embolism

Background: Echocardiographically assessed right ventricular dysfunction is increasingly used to guide more aggressive therapy in hemodynamically stable patients with acute pulmonary embolism (PE). However, the prognostic value of right ventricular dysfunction in these patients is still unclear. Methods: We systemically reviewed the literature to assess the prevalence of echocardiographic right ventricular dysfunction and the association with adverse outcomes in patients with PE who had this condition. The methodologic quality of each study was scored. Absolute risks of the outcome events were calculated for each study separately, and positive predictive values of PE-related mortality were determined for normotensive patients. Results: Seven studies were included. All had methodologic shortcomings, but they suggested an at least 2-fold increased risk of PE-related mortality in patients with right ventricular dysfunction, the prevalence of which varied from 40% to 70%. However, this seems to be less convincing in hemodynamically stable patients. The only 2 studies that allowed for an estimation of the accuracy in normotensive patients showed low positive predictive values of echo cardiographic right ventricular dysfunction for PE-related in-hospital mortality (positive predictive value, 4% and 5% in the 2 studies). Conclusion: It remains unclear whether echocardiographic right ventricular dysfunction is a prevalent and reliable predictor of adverse outcomes in hemodynamically stable patients with acute P

Quality of clinical Direct Oral Anticoagulants (DOACs) prescribing and identification of risk factors for inappropriate prescriptions

AIMS: Even though the use of Direct Oral Anticoagulants (DOACs) is safe based on clinical outcomes, drug safety also depends on appropriateness of drug prescription, which is challenging for DOACs since many patient factors need to be considered. The aim of this study was to assess the appropriateness of DOAC prescriptions and to identify risk factors of determinants for inappropriate DOAC prescriptions. METHOD: A retrospective study in a non-university teaching hospital was performed of hospitalized patients (≥18 years) who received an initial DOAC prescription between February and August 2018. Appropriateness of prescribing was evaluated on eight criteria by using a modified version of the Medication Appropriateness Index (MAI). RESULTS: A total of 770 initial DOAC prescriptions of inpatients were evaluated: 267 patients (34.6%) had at least met one inappropriate criterion for a DOAC prescription. The most frequent inappropriate criterion was 'dosage' (17.4%). Of all the four DOACs, dabigatran (21.6%) and apixaban (21.2%) were mostly inappropriate dosed. In a multivariable analysis, reduced renal function (eGFR < 50 mL/min) (OR=2.35; p<0.001), a diagnosis of atrial fibrillation (OR=1.87; p=0.004), and 'prescribed by surgeons' (OR=1.9; p=0.013) were independently associated with inappropriateness of prescribing. CONCLUSION: This study has highlighted a high degree of inappropriate prescribing of DOACs. These results underline the need for targeted interventions to improve DOAC prescribing

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Abstract Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery  76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival