Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.
Aims A clinically important interaction between the cardiac glycoside digoxin and the antibiotic clarithromycin has been suggested in earlier reports. The aim of this study was to investigate the extent of the interaction and the relative contribution of different mechanisms. Methods In a randomized, placebo-controlled, double-blind cross-over design single oral doses of 0.75 mg digoxin with oral coadministration of placebo or 250 mg clarithromycin twice daily for 3 days were administered to 12 healthy men. Additionally, three of the subjects received single intravenous doses of 0.01 mg kg -1 digoxin with oral placebo or clarithromycin. Digoxin plasma and urine concentrations were determined by a highly sensitive radioimmunoassay. Results Oral coadministration of clarithromycin resulted in a 1.7-fold increase of the area under the digoxin plasma concentration-time curve [mean AUC(0,24) ± SD 23 ± 5.2 vs. 14 ± 2.9 m g L -1 h; 95% confidence interval (CI) on the difference 7.0, 12; P = 0.002] and in a reduction of the nonglomerular renal clearance of digoxin [mean Cl Rng (0, 24) ± SD 34 ± 39 vs. 57 ± 41 mL min -1 ; 95% CI on the difference 7.2, 45; P = 0.03]. The ratios of mean digoxin plasma concentrations with and without clarithromycin were highest during the absorption period of clarithromycin. After intravenous administration digoxin AUC(0,24) increased only 1.2-fold during coadministration of clarithromycin. Conclusions Increased oral bioavailability and reduced nonglomerular renal clearance of digoxin both contribute to the interaction between digoxin and clarithromycin, probably due to inhibition of intestinal and renal P-glycoprotein.
Background: Cardiac manifestation of COVID-19 has been reported during the COVID pandemic. The role of cardiac arrhythmias in COVID-19 is insufficiently understood. This study assesses the incidence of cardiac arrhythmias and their prognostic implications in hospitalized COVID-19-patients. Methods: A total of 166 patients from eight centers who were hospitalized for COVID-19 from 03/2020–06/2020 were included. Medical records were systematically analyzed for baseline characteristics, biomarkers, cardiac arrhythmias and clinical outcome parameters related to the index hospitalization. Predisposing risk factors for arrhythmias were identified. Furthermore, the influence of arrhythmia on the course of disease and related outcomes was assessed using univariate and multiple regression analyses. Results: Arrhythmias were detected in 20.5% of patients. Atrial fibrillation was the most common arrhythmia. Age and cardiovascular disease were predictors for new-onset arrhythmia. Arrhythmia was associated with a pronounced increase in cardiac biomarkers, prolonged hospitalization, and admission to intensive- or intermediate-care-units, mechanical ventilation and in-hospital mortality. In multiple regression analyses, incident arrhythmia was strongly associated with duration of hospitalization and mechanical ventilation. Cardiovascular disease was associated with increased mortality. Conclusions: Arrhythmia was the most common cardiac event in association with hospitalization for COVID-19. Older age and cardiovascular disease predisposed for arrhythmia during hospitalization. Whereas in-hospital mortality is affected by underlying cardiovascular conditions, arrhythmia during hospitalization for COVID-19 is independently associated with prolonged hospitalization and mechanical ventilation. Thus, incident arrhythmia may indicate a patient subgroup at risk for a severe course of disease.
Introduction
Traumatic and non-traumatic spinal cord injury bears a high risk for thromboembolism in the first few months after injury. So far, there is no consented guideline regarding diagnostic and prophylactic measures to prevent thromboembolic events in spinal cord injury. Based on a Pubmed research of related original papers and review articles, international guidelines and a survey conducted in German-speaking spinal cord injury centers about best practice prophylactic procedures at each site, a consensus process was initiated, which included spinal cord medicine experts and representatives from medical societies involved in the comprehensive care of spinal cord injury patients. The recommendations comply with the German S3 practice guidelines on prevention of venous thromboembolism.
Recommendations
Specific clinical or instrument-based screening methods are not recommended in asymptomatic SCI patients. Based on the severity of neurological dysfunction (motor completeness, ambulatory function) low dose low molecular weight heparins are recommended to be administered up to 24 weeks after injury. Besides, mechanical methods (compression stockings, intermittent pneumatic compression) can be applied. In chronic SCI patients admitted to the hospital, thromboembolism prophylactic measures need to be based on the reason for admission and the necessity for immobilization.
Conclusions
Recommendations for thromboembolism diagnostic and prophylactic measures follow best practice in most spinal cord injury centers. More research evidence needs to be generated to administer more individually tailored risk-adapted prophylactic strategies in the future, which may help to further prevent thromboembolic events without causing major side effects. The present article is a translation of the guideline recently published online (https://www.awmf.org/uploads/tx_szleitlinien/179-015l_S1_Thromboembolieprophylaxe-bei-Querschnittlaehmung_2020-09.pdf).
Acute hypoxia corresponding to hypoxia at altitudes of 4,500 m does not impair the metabolism mediated by CYP1A2 or CYP3A4. At rapid ascent to and short-term stay at altitudes up to 4,500 m, the doses of drugs metabolized by these CYPs do therefore not require dose modification, and major changes in the disposition of already administered drugs are not to be expected.
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