Coronary Heart Disease in Familial Hypercholesterolemia

Familial hypercholesterolemia (FH) (OMIM #143890) is an autosomal dominant disorder present in 1:500 Caucasians. FH is caused by defective low-density lipoprotein (LDL) receptors, leading to a diminished uptake of LDL cholesterol by the liver. As a result, FH patients have high LDL cholesterol levels and a high risk of contracting cardiovascular disease (CVD), mainly coronary heart disease (CHD). FH can be diagnosed on the basis of clinical criteria (Table 1) or by detection of the causal mutation in the LDL-receptor gene. Despite the homogenous background of hypercholesterolemia, the onset and severity of CHD among FH patients varies considerably. This introduction provides a short update of the classic and genetic factors influencing CHD risk in heterozygous FH patients. Besides the importance of CHD risk prediction for FH patients, FH being the most common monogenetic disorder, FH can also be considered a high-risk model population in which CHD risk factors can more easily be detected. Risk factors identified in FH patients might consequently be translated to the general population

Lessons learned from conducting a randomized controlled trial to improve non-adherence to antihypertensive drug treatment

Purpose: Hypertension significantly contributes to cardiovascular diseases and premature deaths. Effective treatment is crucial to reduce cardiovascular risks, but poor adherence to antihypertensive drugs is a major issue. Numerous studies attempted to investigate interventions for identifying non-adherence, but often failed to address the issue effectively. The RHYME-RCT trial sought to bridge this gap by measuring non-adherence by determining antihypertensive drug concentrations in blood through a dried blood spot (DBS) method in patients with resistant hypertension. This measurement was followed by personalized feedback to improve adherence. During the course of this trial several challenges emerged, including selection bias, the gatekeeper role of physicians, the Hawthorne effect and the role of randomization.Aim: This communication aims to inform fellow researchers and clinicians of challenges that can arise when conducting clinical trials to improve adherence and offer insights for refining study designs to avoid these issues in forthcoming adherence studies

High blood pressure in the hospital:intensify medication or ignore?

Regelmatig worden bij patiënten die in het ziekenhuis zijn opgenomen te hoge bloeddrukwaarden gemeten. Moeten we tijdens opname met een bloeddrukverlagende behandeling beginnen of die intensiveren? Of kunnen we de bloeddrukwaarden beter negeren

High blood pressure in the hospital:intensify medication or ignore?

Item does not contain fulltextHigh blood pressure is a common finding in hospitalized patients. Anxiety, pain and fever can all increase blood pressure to various degrees. The question is whether this adaptive response is harmful and should lead to initiation or intensification of treatment or can be ignored. A recent retrospective study has shown that intensification of blood pressure lowering medication in patients who are hospitalized with non-cardiac conditions is associated with a higher incidence of in-hospital complications, in particular myocardial infarction and renal insufficiency, while another study demonstrated that patients who are discharged from hospital with intensified antihypertensive treatment have an increased risk of readmission without a reduction in cardiac events after one year. Although retrospective in nature, these data show that we should be careful with anti-hypertensive medication in patients hospitalized for non-cardiac conditions and that blood pressure monitoring should be focused on the identification of low rather than high blood pressure values

A clinically relevant pharmacokinetic interaction between cyclosporine and imatinib

Purpose: Cyclosporine A (CsA) and imatinib are both CYP3A4 and P-glycoprotein substrates. Concomitant use after hematopoietic stem cell transplantation (HSCT) for chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (ALL) may therefore result in a pharmacokinetic interaction. Although case reports and a recent small study in children indeed suggested there is a relevant pharmacokinetic interaction, a larger study in adults is lacking. In this study, we assessed the presence and extent of this interaction in patients with CML or Ph+ ALL undergoing HSCT. Methods: From a large database containing data of all patients receiving HSCT in our center between 2005 and 2015, we selected 16 patients using this drug combination. The average dose-corrected CsA concentration was calculated before and after initiation of imatinib. Results: The average dose-corrected CsA concentration increased during imatinib use in all patients, on average by 94 % (p < 0.001). Based on measured drug con

COvid MEdicaTion (COMET) study: protocol for a cohort study

Various theories about drugs such as ACE inhibitors or angiotensin II receptor blockers (ARBs) in relation to severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) and clinical outcomes of COVID-19 are circulating in both mainstream media and medical literature. These are based on the fact that ACE2 facilitates SARSCoV-2 cell invasion via binding of a viral spike protein to ACE2. However, the effect of ACE inhibitors, ARBs and other drugs on ACE2 is unclear and all theories are based on conflicting evidence mainly from animal studies. Therefore, clinical evidence is urgently needed. The aim of this study is to investigate the relationship between use of these drugs on clinical outcome of patients with COVID-19. Patients will be included from several hospitals in Europe. Data will be collected in a user-friendly database (Digitalis) on an external server. Analyses will be adjusted for sex, age and presence of cardiovascular disease, hypertension and diabetes. These results will enable more rational choices for randomised controlled trials for preventive and therapeutic strategies in COVID-19

FPGA-based Bit-Error-Rate Tester for SEU-hardened Optical Links

The next generation of optical links for future High-Energy Physics experiments will require components qualified for use in radiation-hard environments. To cope with radiation induced single-event upsets, the physical layer protocol will include Forward Error Correction (FEC). Bit-Error-Rate (BER) testing is a widely used method to characterize digital transmission systems. In order to measure the BER with and without the proposed FEC, simultaneously on several devices, a multi-channel BER tester has been developed. This paper describes the architecture of the tester, its implementation in a Xilinx Virtex-5 FPGA device and discusses the experimental results