Heterogeneity in acute myeloid leukemia : basic and diagnostic studies

The heterogeneity of AML is subject of this thesis. The purpose of this study was to characterize the different subpopulations which can be found in the various types of AML at diagnosis and during follow-up. For this purpose we especially used extensive immunological marker analysis. In close collaboration with clinical scientists and laboratory scientists our results were correlated with other features of these patients, especially clinical characteristics and cytogenetics. Both the clinical significance and some basic aspects of specific immunophenotypes in AML patients were determine

Prospective evaluation of a computerized algorithm for Vitamin K antagonist drug dose calculation

Introduction: In an earlier study, we described and validated a VKA dose-finding algorithm (B2A), based on a novel bidirectional factor (BF). We designed a prospective study to evaluate the B2A in a daily care setting. Methods: In this open-label prospective study, we compared the outcomes of the B2A over the year 2020 with the outcomes of the previous year (2019), using regular algorithms. The outcomes were the duration of Time in the Therapeutic Range (TTR), the percentage of automated dose proposals (PAuP) and the percentage of accepted dose proposals (PAcP). The data were obtained from three anticoagulation centers in the Netherlands, in four locations. The outcomes of this study were based on a non-inferiority level.Results: The TTR over the year 2020 was at least non-inferior compared with the standard of care treatment. The percentage of automated proposals increased in all centers to approximately 96% of all dosages. Conclusion: The B2A performs non-inferior compared with the existing algorithms and in some aspects even better

Reaching intrinsic compute efficiency requires adaptable micro-architectures

Today’s embedded applications demand high compute performance at a tight energy budget, which requires a high compute efficiency. Compute efficiency is upper-bound by the technology node, however in practice programmable devices are orders of magnitude away from achieving this intrinsic compute efficiency. This work investigates the sources of inefficiency that cause this, and identifies four key design guidelines that can steer compute efficiency towards sub-picojoule per operation. Based on these guidelines a novel architecture with adaptive micro-architecture, and accompanying tool flow is proposed.\u3cbr/\u3

Screening for metabolic vitamin B-12 deficiency by holotranscobalamin in patients suspected of vitamin B-12 deficiency:a multicentre study

Background: Vitamin B-12 deficiency occurs frequently, especially among the elderly. However, screening for vitamin B-12 deficiency is hampered by poor sensitivity of the existing total vitamin B-12 assay. Methylmalonic acid (MMA) is considered as the most representative indicator of metabolic vitamin B-12 deficiency and is used as such in this study. The aim of this study was to validate the clinical usefulness of holotranscobalamin (holoTC) as an initial screening assay for metabolic vitamin B-12 deficiency in a mixed patient population. Methods: Three hundred and sixty blood samples were collected by five Dutch hospitals. Vitamin B-12 and holoTC in serum were measured (AxSYM; Abbott). MMA in serum was measured by tandem mass spectrometry (LC-MS/MS). Results: Receiver operating curve (ROC) analysis demonstrated a greater area under the curve (AUC) for holoTC than for vitamin B-12 in detecting vitamin B-12 deficiency characterized by three predefined cut-off levels of MMA. A cut-off value of 32 pmol/L of holoTC resulted in the highest sensitivity (83%) with acceptable specificity (60%) in detecting MMA concentrations above 0.45 mu mol/L. The combination of vitamin B-12 and holoTC did not improve diagnostic accuracy at this cut-off level. Conclusions: HoloTC has a better diagnostic accuracy than vitamin B-12 and can replace the existing vitamin B-12 assay as a primary screening test in patients suspected of vitamin B-12 deficiency. Critical evaluation of cut-off values of holoTC indicated that a cut-off value of 32 pmol/L can be considered in screening for metabolic vitamin B-12 deficiency (defined by MMA > 0.45 mu mol/L) in a mixed patient population

Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring:the ROBINSCA trial

Aim Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n= 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE = 20%). According to CAC screening, 76.0% were at low risk (Agatston = 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated