Publications by authors named "Hanno Heuzeroth"

3 Publications

  • Page 1 of 1

Pre-medication with oral anticoagulants is associated with better outcomes in a large multinational COVID-19 cohort with cardiovascular comorbidities.

Clin Res Cardiol 2021 Sep 21. Epub 2021 Sep 21.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Aims: Coagulopathy and venous thromboembolism are common findings in coronavirus disease 2019 (COVID-19) and are associated with poor outcome. Timely initiation of anticoagulation after hospital admission was shown to be beneficial. In this study we aim to examine the association of pre-existing oral anticoagulation (OAC) with outcome among a cohort of SARS-CoV-2 infected patients.

Methods And Results: We analysed the data from the large multi-national Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS) from March to August 2020. Patients with SARS-CoV-2 infection were eligible for inclusion. We retrospectively analysed the association of pre-existing OAC with all-cause mortality. Secondary outcome measures included COVID-19-related mortality, recovery and composite endpoints combining death and/or thrombotic event and death and/or bleeding event. We restricted bleeding events to intracerebral bleeding in this analysis to ensure clinical relevance and to limit reporting errors. A total of 1 433 SARS-CoV-2 infected patients were analysed, while 334 patients (23.3%) had an existing premedication with OAC and 1 099 patients (79.7%) had no OAC. After risk adjustment for comorbidities, pre-existing OAC showed a protective influence on the endpoint death (OR 0.62, P = 0.013) as well as the secondary endpoints COVID-19-related death (OR 0.64, P = 0.023) and non-recovery (OR 0.66, P = 0.014). The combined endpoint death or thrombotic event tended to be less frequent in patients on OAC (OR 0.71, P = 0.056).

Conclusions: Pre-existing OAC is protective in COVID-19, irrespective of anticoagulation regime during hospital stay and independent of the stage and course of disease.
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September 2021

Development and validation of a simplified risk score for the prediction of critical COVID-19 illness in newly diagnosed patients.

J Med Virol 2021 Jul 31. Epub 2021 Jul 31.

Department of Nephrology, School of Medicine, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany.

Scores to identify patients at high risk of progression of coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may become instrumental for clinical decision-making and patient management. We used patient data from the multicentre Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) and applied variable selection to develop a simplified scoring system to identify patients at increased risk of critical illness or death. A total of 1946 patients who tested positive for SARS-CoV-2 were included in the initial analysis and assigned to derivation and validation cohorts (n = 1297 and n = 649, respectively). Stability selection from over 100 baseline predictors for the combined endpoint of progression to the critical phase or COVID-19-related death enabled the development of a simplified score consisting of five predictors: C-reactive protein (CRP), age, clinical disease phase (uncomplicated vs. complicated), serum urea, and D-dimer (abbreviated as CAPS-D score). This score yielded an area under the curve (AUC) of 0.81 (95% confidence interval [CI]: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (95% CI: 0.77-0.85) during full follow-up. We used an additional prospective cohort of 682 patients, diagnosed largely after the "first wave" of the pandemic to validate the predictive accuracy of the score and observed similar results (AUC for the event within 7 days: 0.83 [95% CI: 0.78-0.87]; for full follow-up: 0.82 [95% CI: 0.78-0.86]). An easily applicable score to calculate the risk of COVID-19 progression to critical illness or death was thus established and validated.
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July 2021

The 4-Aminopyridine Model of Acute Seizures Elucidates Efficacy of New Antiepileptic Drugs.

Front Neurosci 2019 27;13:677. Epub 2019 Jun 27.

Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Up to date, preclinical screening for new antiepileptic substances is performed by a combination of different models of acute seizures, for which large numbers of animals are necessary. So far, little attention has been paid to models, which are also able to detect antiepileptic efficacy and in principle could likewise serve for exploratory preclinical screening. One of the established models of acute seizures is the 4-aminopyridine (4-AP) model. Previous studies have shown that the 4-AP model is capable to recapitulate the antiepileptic efficacy of standard antiepileptic drugs (AEDs) such as valproate or carbamazepine. Here, we employed a dual methodological approach using electrophysiology and optical imaging to systematically test the antiepileptic efficacy of three new-generation AEDs with distinct mechanisms of action (lacosamide, zonisamide, and levetiracetam). We found that frequency of 4-AP induced seizure like events (SLE) was the most sensitive parameter to detect dose-dependent antiepileptic effects in these compounds. Specifically, levetiracetam reduced SLE frequency while lacosamide and zonisamide at higher doses completely blocked SLE incidence. Analysis of the intrinsic optical signal additionally revealed a subiculum-specific reduction of the area involved in the propagation of ictal activity when lacosamide or zonisamide were administered. Taken together, our data adds some evidence that acute seizure models are in principle capable to detect antiepileptic effects across different mechanisms of action with efficacy similar to acute models . Further studies with negative controls, e.g., penicillin as a proconvulsant, and other clinically relevant AEDs are needed to determine if this acute model might be useful as exploratory screening tool. In view of the increasing sensitivity toward animal welfare, an affective model may help to reduce the number of laboratory animals deployed in burdening experiments and to preselect substances for subsequent testing in time- and cost-laborious models of chronic epilepsy.
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June 2019