Terrace Review, May, 28, 1986

Thrombosis and Hemostasi

Элементы природы в крымско–татарском народном искусстве

В статье рассматривается система образования элементов орнамента. Типы орнаментального искусства и принципы группировки элементов изобразительной формы. Цветовое решение в орнаменте.В статі розглядається система освіти елементів орнамента. Типи орнаментального мистецтва і принципи згрупування елементів образотворчої форми. Кольорове рішення в орнаменті.The system of ornament's elements is representative in this article. Same types of art's ornament and some principles of grouping art's elements are here. Color's design in ornament

Concurrent use of DOACs and pharmacodynamic interacting drugs is associated with an increased risk of major bleeding compared with patients using DOACs alone: Nested case-control study in UK CPRD

Background: Although many studies on bleeding risk associated with use of direct oral anticoagulants (DOACs) are conducted, the effect of concurrent use of potentially interacting drugs on this risk is not well studied. Objectives: To evaluate the association between concurrent use of DOACs with concurrent use of potential pharmacokinetic or pharmacodynamic interacting drugs on major bleeding. Methods: We used data from the UK Clinical Practice Research Datalink (period 2008-2015) to conduct a nested case-control study in a cohort of new users of DOACs (dabigatran, apixaban, and rivaroxaban). Cases were patients who were hospitalized with a primary discharge diagnosis of major bleeding while taking DOACs. Up to four controls were matched to each case on age, sex, and index date. Controls also had to be a current user of a DOAC on the index date. Conditional logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) to estimate the risk of major bleeding associated with concurrent use (30 days prior to the index date) of potential pharmacokinetic or pharmacodynamic interacting drugs. The analysis was adjusted for well-known risk factors for bleeding Results: We identified 393 cases from 29 120 new users of DOACs and 1494 controls. Most subjects were current users of rivaroxaban (58.8%). The concurrent use of DOACs and pharmacokinetic interacting drugs did not increase the risk of major bleeding vs use of DOACs alone (45.0% vs 51.2%, adjusted OR 0.90; 95% CI 0.60-1.36). However, concurrent use of pharmacodynamic interacting drugs was associated with an increased risk of major bleeding (21.6% vs 13.5%, adjusted OR, 1.91; 95% CI, 1.39-2.62). This effect was mainly driven by selective serotonin reuptake inhibitors (SSRIs, adjusted OR, 1.73; 95% CI, 1.12-2.65) and antiplatelet drugs (adjusted OR, 1.90; 95% CI, 1.23-2.93), respectively. Conclusions: Among patients taking a DOAC, concurrent use of an SSRIs or antiplatelet drug was associated with increased risk of major bleeding compared with DOAC use without these drugs

Pharmacogenomic testing in paediatrics: clinical implementation strategies

Pharmacogenomics (PGx) relates to the study of genetic factors determining variability in drug response. Implementing PGx testing in paediatric patients can enhance drug safety, helping to improve drug efficacy or reduce the risk of toxicity. Despite its clinical relevance, the implementation of PGx testing in paediatric practice to date has been variable and limited. As with most paediatric pharmacological studies, there are well-recognised barriers to obtaining high-quality PGx evidence, particularly when patient numbers may be small, and off-label or unlicensed prescribing remains widespread. Furthermore, trials enrolling small numbers of children can rarely, in isolation, provide sufficient PGx evidence to change clinical practice, so extrapolation from larger PGx studies in adult patients, where scientifically sound, is essential. This review paper discusses the relevance of PGx to paediatrics and considers implementation strategies from a child health perspective. Examples are provided from Canada, the Netherlands and the UK, with consideration of the different healthcare systems and their distinct approaches to implementation, followed by future recommendations based on these cumulative experiences. Improving the evidence base demonstrating the clinical utility and cost-effectiveness of paediatric PGx testing will be critical to drive implementation forwards. International, interdisciplinary collaborations will enhance paediatric data collation, interpretation and evidence curation, while also supporting dedicated paediatric PGx educational initiatives. PGx consortia and paediatric clinical research networks will continue to play a central role in the streamlined development of effective PGx implementation strategies to help optimise paediatric pharmacotherapy.Personalised Therapeutic

Noacs replace VKA as preferred oral anticoagulant among new patients

Background: In 2012, around 400,000 patients in the Netherlands were treated with vitamin K antagonists (VKA) for thromboembolic diseases. Since 2011, non-VKA oral anticoagulants (NOACs) have been available. NOACs do not require frequent INR monitoring and cause less bleeding, which benefits patients, but also imposes a risk of reduced therapy adherence. Objectives: The objective of this study is to describe uptake of and patient compliance with NOACs in The Netherlands between July 2011 and October 2016. Methods: We analysed prescription data for 247.927 NOAC and/or VKA patients across 560 pharmacies. All patients who received at least one prescription of either VKA or NOACs between 1 July 2011 and 30 September 2016 were included in the study. Our database contained (not exhaustive) the following information about the prescriptions: dispensed medication and quantity, dispensing date, prescribed dosage and prescriber type, patient age and gender. We used these data to describe patient profiles, uptake of NOACs among new naïve patients and switch of patients between VKA and NOACs. We developed an algorithm to classify patients as new naïve starters, switcher or repeat patients. We calculated therapy compliance as the percentage of days covered (PDC). To obtain reliable results, in our PDC calculations we included only patients with a time period of at least 12 months between their first and last prescription. Results: During the studied period the share of NOACs in oral anticoagulants has grown to 57% of prescriptions to new patients. More than 70% of new NOAC users were new naïve patients and around 26% switched from VKA. The overall share of NOACs among starters is largest in the group of patients of 50-80 years. Calculated percentages of days covered (PDC) for NOAC patients show that 87% of all users were compliant. Conclusions: NOACs have overtaken VKA as the major treatment prescribed to patients starting on oral anticoagulants, and the number of starters on VKA is at present decreasing. We expect that almost all oral anticoagulants prescribed to new patients will be NOACs. NOAC users are in general compliant with therapy. This may provide additional confidence to physicians in prescribing NOACs instead of VKAs

Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial

Background The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak.Methods This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged >= 18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10).Findings Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0.95 [95% CI 0.76-1.20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0.51 [0.27-0.95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0.52 (95% CI 0.26-1.05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1.07 (0.63-1.80; p=0.81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0.0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events.Interpretation The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. Copyright (C) 2021 Elsevier Ltd. All rights reserved.Pathogenesis and treatment of chronic pulmonary disease