An analysis of the use of historical control data in the assessment of regulatory pesticide toxicity studies.

The concurrent control group is the most important reference for the interpretation of toxicity studies. However, pooled information on control animals from independent studies, i.e., historical control data (HCD), is also used for the interpretation of results. Currently, an overview on actual HCD use in regulatory toxicology is lacking. Therefore, we evaluated the HCD use of the Joint FAO/WHO Meeting on Pesticide Residues from 2004 to 2021 and compared it with recommendations in regulatory guidelines and in the literature. We found that HCD was used routinely and exclusively to avoid potential false positive decisions regarding the treatment-relatedness of effects, mostly using the HCD range, i.e., the most extreme values, as a benchmark. HCD were not used to avoid potential false negative decisions or for quality control of the index study. The central assumption of the HCD use, namely that the HCD and control group of the index study follow the same underlying distribution because they are samples of the same data generation process, was not investigated, although numerous factors potentially contribute to effect variation between the different control groups pooled in the HCD. We recommend that the existing guidelines be revised to improve the robustness and transparency of toxicological assessments.

Low-Frequency Ventilation May Facilitate Weaning in Acute Respiratory Distress Syndrome Treated with Extracorporeal Membrane Oxygenation: A Randomized Controlled Trial.

Although extracorporeal membrane ventilation offers the possibility for low-frequency ventilation, protocols commonly used in patients with acute respiratory distress syndrome (ARDS) and treated with extracorporeal membrane oxygenation (ECMO) vary largely. Whether strict adherence to low-frequency ventilation offers benefit on important outcome measures is poorly understood. Background/Objectives: This pilot clinical study investigated the efficacy of low-frequency ventilation on ventilator-free days (VFDs) in patients suffering from ARDS who were treated with ECMO therapy. Methods: In this single-center randomized controlled trial, 44 (70% male) successive ARDS patients treated with ECMO (aged 56 ± 12 years, SAPS III 64 (SD ± 14)) were randomly assigned 1:1 to the control group (conventional ventilation) or the treatment group (low-frequency ventilation during first 72 h on ECMO: respiratory rate 4-5/min; PEEP 14-16 cm H2O; plateau pressure 23-25 cm H2O, tidal volume: <4 mL/kg). The primary endpoint was VFDs at day 28 after starting ECMO treatment. The major secondary endpoint was ICU mortality, 28-day mortality and 90-day mortality. Results: Twenty-three (52%) patients were successfully weaned from ECMO and were discharged from the intensive care unit (ICU). Twelve patients in the treatment group and five patients in the control group showed more than one VFD at day 28 of ECMO treatment. VFDs were 3.0 (SD ± 5.5) days in the control group and 5.4 (SD ± 6) days in the treatment group (p = 0.117). Until day 28 of ECMO initiation, patients in the treatment group could be successfully weaned off of the ventilator more often (OR of 0.164 of 0 VFDs at day 28 after ECMO start; 95% CI 0.036-0.758; p = 0.021). ICU mortality did not differ significantly (36% in treatment group and 59% in control group; p = 0.227). Conclusions: Low-frequency ventilation is comparable to conventional protective ventilation in patients with ARDS who have been treated with ECMO. However, low-frequency ventilation may support weaning from invasive mechanical ventilation in patients suffering from ARDS and treated with ECMO therapy.

Characteristics and outcome of hospitalized patients with heart failure stratified for chronic kidney disease.

AIMS: Heart failure (HF) and chronic kidney disease (CKD) place significant challenges on the healthcare system, and their co-existence is associated with shared adverse outcomes. The multinational CaReMe project was initiated to provide contemporary, real-world epidemiological data on cardiovascular and reno-metabolic diseases. Utilizing data from the German CaReMe cohort, we characterize a multicentric HF population and describe in-hospital outcomes stratified for co-morbid CKD. METHODS AND RESULTS: This retrospective, observational study analysed administrative data from inpatient cases hospitalized in 87 German Helios hospitals between 1 January 2016 and 31 August 2022. The first hospitalization of patients aged ≥18 years with a primary discharge diagnosis of HF, based on ICD-10 codes, were considered the index cases, and subsequent hospitalizations were considered as readmissions. Baseline characteristics and outcomes were stratified for co-morbid CKD using ICD-10-encoding from the index cases. Cox regression was utilized for readmission endpoints and in-hospital mortality. In total, 174 829 index cases (mean age 79 ± 15 years, 49.9% female) were included; of these, 55.0% had coexisting CKD. Patients with CKD were older, suffered from worse HF-related symptoms, had a higher co-morbidity burden, and in-hospital mortality was increased at index and during follow-up. Prevalent CKD was associated with higher rehospitalization rates and was an independent predictor for in-hospital death. CONCLUSIONS: Within this HF inpatient cohort from a multicentric German database, CKD was diagnosed in more than half of the patients and was associated with increased in-hospital mortality at baseline and during follow-up. Rehospitalizations were observed earlier and more frequently in patients with HF and co-morbid CKD.

Patient Characteristics and Outcomes of Hospitalized Chronic Kidney Disease Patients with and without Type 2 Diabetes Mellitus: Observations from the German Claims Data-Based Cohort of the CaReMe-CKD Multinational Study.

Introduction: Type 2 diabetes mellitus (T2DM) is a leading cause of chronic kidney disease (CKD) globally. Both conditions substantially worsen patients' prognosis. Current data on German in-hospital CKD cohorts are scarce. The multinational CaReMe study was initiated to evaluate the current epidemiology and healthcare burden of cardiovascular, renal and metabolic diseases. In this substudy, we share real-world data on CKD inpatients stratified for coexisting T2DM derived from a large German hospital network. Methods: This study used administrative data of inpatient cases from 89 Helios hospitals from 01/01/2016 to 28/02/2022. Data were extracted from ICD-10-encoded discharge diagnoses and OPS-encoded procedures. The first case meeting a previously developed CKD definition (defined by ICD-10- and OPS-codes) was considered the index case for a particular patient. Subsequent hospitalizations were analysed for readmission statistics. Patient characteristics and pre-defined endpoints were stratified for T2DM at index case. Results: In total, 48,011 patients with CKD were included in the present analysis (mean age ± standard deviation, 73.8 ± 13.1 years; female, 44%) of whom 47.9% had co-existing T2DM. Patients with T2DM were older (75 ± 10.6 vs 72.7 ± 14.9 years, p < 0.001), but gender distribution was similar to patients without T2DM. The burden of cardiovascular disease was increased in patients with T2DM, and index and follow-up in-hospital mortality rates were higher. Non-T2DM patients were characterised by more advanced CKD at baseline. Patients with T2DM had consistently higher readmission numbers for all events of interest, except for readmissions due to kidney failure/dialysis, which were more common in non-T2DM patients. Conclusion: In this study, we present recent data on hospitalized patients with CKD in Germany. In this CKD cohort, nearly half had T2DM, which substantially affected cardiovascular disease burden, rehospitalization frequency and mortality. Interestingly, non-diabetic patients had more advanced underlying renal disease, which affected renal outcomes.

Retrospective, Observational Analysis on the Impact of SARS-CoV-2 Variant Omicron in Hospitalized Immunocompromised Patients in a German Hospital Network-The VISAGE Study.

AIMS: Endemic SARS-CoV-2 infections still burden the healthcare system and represent a considerable threat to vulnerable patient cohorts, in particular immunocompromised (IC) patients. This study aimed to analyze the in-hospital outcome of IC patients with severe SARS-CoV-2 infection in Germany. METHODS: This retrospective, observational study, analyzed administrative data from inpatient cases (n = 146,324) in 84 German Helios hospitals between 1 January 2022 and 31 December 2022 with regard to in-hospital outcome and health care burden in IC patients during the first 12 months of Omicron dominance. As the primary objective, in-hospital outcomes of patients with COVID-19-related severe acute respiratory infection (SARI) were analyzed by comparing patients with (n = 2037) and without IC diagnoses (n = 14,772). Secondary analyses were conducted on IC patients with (n = 2037) and without COVID-19-related SARI (n = 129,515). A severe in-hospital outcome as a composite endpoint was defined per the WHO definition if one of the following criteria were met: intensive care unit (ICU) treatment, mechanical ventilation (MV), or in-hospital death. RESULTS: In total, 12% of COVID-related SARI cases were IC patients, accounting for 15% of ICU admissions, 15% of MV use, and 16% of deaths, resulting in a higher prevalence of severe in-hospital courses in IC patients developing COVID-19-related SARI compared to non-IC patients (Odds Ratio, OR = 1.4, p < 0.001), based on higher in-hospital mortality (OR = 1.4, p < 0.001), increased need for ICU treatment (OR = 1.3, p < 0.001) and mechanical ventilation (OR = 1.2, p < 0.001). Among IC patients, COVID-19-related SARI profoundly increased the risk for severe courses (OR = 4.0, p < 0.001). CONCLUSIONS: Our findings highlight the vulnerability of IC patients to severe COVID-19. The persistently high prevalence of severe outcomes in these patients in the Omicron era emphasizes the necessity for continuous in-hospital risk assessment and monitoring of IC patients.

Artificial intelligence-based identification of left ventricular systolic dysfunction from 12-lead electrocardiograms: external validation and advanced application of an existing model.

Aims: The diagnostic application of artificial intelligence (AI)-based models to detect cardiovascular diseases from electrocardiograms (ECGs) evolves, and promising results were reported. However, external validation is not available for all published algorithms. The aim of this study was to validate an existing algorithm for the detection of left ventricular systolic dysfunction (LVSD) from 12-lead ECGs. Methods and results: Patients with digitalized data pairs of 12-lead ECGs and echocardiography (at intervals of ≤7 days) were retrospectively selected from the Heart Center Leipzig ECG and electronic medical records databases. A previously developed AI-based model was applied to ECGs and calculated probabilities for LVSD. The area under the receiver operating characteristic curve (AUROC) was computed overall and in cohorts stratified for baseline and ECG characteristics. Repeated echocardiography studies recorded ≥3 months after index diagnostics were used for follow-up (FU) analysis. At baseline, 42 291 ECG-echocardiography pairs were analysed, and AUROC for LVSD detection was 0.88. Sensitivity and specificity were 82% and 77% for the optimal LVSD probability cut-off based on Youden's J. AUROCs were lower in ECG subgroups with tachycardia, atrial fibrillation, and wide QRS complexes. In patients without LVSD at baseline and available FU, model-generated high probability for LVSD was associated with a four-fold increased risk of developing LVSD during FU. Conclusion: We provide the external validation of an existing AI-based ECG-analysing model for the detection of LVSD with robust performance metrics. The association of false positive LVSD screenings at baseline with a deterioration of ventricular function during FU deserves a further evaluation in prospective trials.

Charged-Particle Bound States in Periodic Boxes.

We consider the binding energy of a two-body system with a repulsive Coulomb interaction in a finite periodic volume. We define the finite-volume Coulomb potential as the usual Coulomb potential, except that the distance is defined as the shortest separation between the two bodies in the periodic volume. We investigate this problem in one and three-dimensional periodic boxes and derive the asymptotic behavior of the volume dependence for bound states with zero angular momentum in terms of Whittaker functions. We benchmark our results against numerical calculations and show how the method can be used to extract asymptotic normalization coefficients for charged-particle bound states. The results we derive here have immediate applications for calculations of atomic nuclei in finite periodic volumes for the case where the leading finite-volume correction is associated with two charged clusters.

Patient perspectives on same-day discharge following catheter ablation for atrial fibrillation: results from a patient survey as part of the monocentric FAST AFA trial.

AIMS: Same-day discharge (SDD) following catheter ablation (CA) of atrial fibrillation (AF) was already introduced in selected facilities in Europe, but a widespread implementation has not yet succeeded. Data on patients' perspectives are lacking. Therefore, we conducted a survey to address patients' beliefs towards SDD and identify variables that are associated with their evaluation. METHODS AND RESULTS: As part of the prospective, monocentric FAST AFA trial, patients aged ≥20 years undergoing left atrial CA for AF were asked to participate in the survey consisting of a study-specific questionnaire, the AF knowledge scale, and pre-defined patient-reported outcome measures. The study cohort was stratified based on SDD willingness, and a logistic regression analysis was used to identify predictors for patients' valuation. Between 26 July 2021 and 01 July 2022, 256 of 376 screened patients consented to study participation of whom 248 (mean age 61.8 years, 33.9% female) completed the SDD survey. Of them, 50.0% were willing to have SDD concepts integrated into their clinical course with increased patient comfort (27.5%), shorter waiting times (14.6%), and a cost-efficient treatment (14.0%) being imaginable benefits. In contrast, expressed concerns included uncertainties with occurring complaints (50.6%), the insufficient recognition (47.8%), and treatment (48.9%) of complications. European Heart Rhythm Association class at baseline and inpatient treatments within the preceding year were predictors for SDD willingness whereas comorbidity burden or AF knowledge were not. CONCLUSION: We provide a detailed survey expressing patients' beliefs towards SDD following left atrial CA. Our findings may facilitate adequate patient selection to improve the future implementation of SDD programs in suitable cohorts.

COVID-19 and Severe Acute Respiratory Infections: Monitoring Trends in 421 German Hospitals During the First Four Pandemic Waves.

Introduction: Reliable surveillance systems to monitor trends of COVID-19 case numbers and the associated healthcare burden play a central role in efficient pandemic management. In Germany, the federal government agency Robert-Koch-Institute uses an ICD-code-based inpatient surveillance system, ICOSARI, to assess temporal trends of severe acute respiratory infection (SARI) and COVID-19 hospitalization numbers. In a similar approach, we present a large-scale analysis covering four pandemic waves derived from the Initiative of Quality Medicine (IQM), a German-wide network of acute care hospitals. Methods: Routine data from 421 hospitals for the years 2019-2021 with a "pre-pandemic" period (01-01-2019 to 03-03-2020) and a "pandemic" period (04-03-2020 to 31-12-2021) was analysed. SARI cases were defined by ICD-codes J09-J22 and COVID-19 by ICD-codes U07.1 and U07.2. The following outcomes were analysed: intensive care treatment, mechanical ventilation, in-hospital mortality. Results: Over 1.1 million cases of SARI and COVID-19 were identified. Patients with COVID-19 and additional codes for SARI were at higher risk for adverse outcomes when compared to non-COVID SARI and COVID-19 without any coding for SARI. During the pandemic period, non-COVID SARI cases were associated with 28%, 23% and 27% higher odds for intensive care treatment, mechanical ventilation and in-hospital mortality, respectively, compared to pre-pandemic SARI. Conclusion: The nationwide IQM network could serve as an excellent data source to enhance COVID-19 and SARI surveillance in view of the ongoing pandemic. Future developments of COVID-19/SARI case numbers and associated outcomes should be closely monitored to identify specific trends, especially considering novel virus variants.

Environmental, bystander and resident exposure from orchard applications using an agricultural unmanned aerial spraying system.

Unmanned aerial spraying systems (UASS), i.e., unmanned aerial vehicles designed for pesticide applications, are widely used in East Asia and increasingly prevalent in other regions of the world, including North America and Europe. However, according to a recent report of the Organization for Economic Co-operation and Development, spray drift and exposure caused by these systems are not yet fully understood. In particular, there are at present no peer-reviewed reports on direct exposure of residents and bystanders to spray drift following UASS applications. This lack of data results in regulatory concerns with respect to the environment and human safety. The objective of this study was to quantify environmental, resident and bystander exposure following the application of a plant protection product to an orchard using a commercial UASS under field conditions. Using a fluorescent tracer, horizontal and vertical downwind drift data were collected and direct exposure of residents and bystanders located downwind the sprayed area to spray drift was quantified using display mannequins equipped with personal air sampling pumps. Spray drift and exposure inversely correlated with sampling height and downwind distance. Furthermore, drift and exposure were strongly influenced by wind speed and direction, albeit hardly affected by the growth stage of the trees. In addition, substantially less tracer was extracted from the filters of the air sampling pumps than from the coveralls worn by mannequins, suggesting that direct resident/bystander exposure to spray drift may predominantly occur via the dermal route. This report provides essential data on UASS spray drift potential that are relevant for environmental and health risk assessments related to these systems. The results are compared to predicted values of current regulatory models and previously reported field data on drift and exposure caused by different spraying equipment.

Usefulness and limitations of the acute respiratory distress syndrome definitions in non-intubated patients. A narrative review.

According to the Berlin Definition of acute respiratory distress syndrome (ARDS), a positive end-expiratory pressure (PEEP) of at least 5 cmH2O is required to diagnose and grade ARDS. While the Berlin consensus statement specifically acknowledges the role of non-invasive ventilation (NIV) in mild ARDS, this stratification has traditionally presumed a mechanically ventilated patient in the context of moderate to severe ARDS. This may not accurately reflect today's reality of clinical respiratory care. NIV and high-flow nasal cannula oxygen therapy (HFNO) have been used for managing of severe forms of acute hypoxemic respiratory failure with growing frequency, including in patients showing pathophysiological signs of ARDS. This became especially relevant during the COVID-19 pandemic. The levels of PEEP achieved with HFNO have been particularly controversial, and the exact FiO2 it achieves is subject to variability. Pinpointing the presence of ARDS in patients receiving HNFO and the severity in those receiving NIV therefore remains methodically problematic. This narrative review highlights the evolution of the ARDS definition in the context of non-invasive ventilatory support and provides an overview of the parallel development of definitions and ventilatory management of ARDS. It summarizes the methodology applied in clinical trials to classify ARDS in non-intubated patients and the respective consequences on treatment. As ARDS severity has significant therapeutic and prognostic consequences, and earlier treatment in non-intubated patients may be beneficial, closing this knowledge gap may ultimately be a relevant step to improve comparability in clinical trial design and outcomes.

A Digital Infrastructure for Cardiovascular Patient Care Based on Mobile Health Data and Patient-Reported Outcomes: Concept Details of the Helios TeleWear Project Including Preliminary Experiences.

BACKGROUND: Mobile health (mHealth) approaches are already having a fundamental impact on clinical practice in cardiovascular medicine. A variety of different health apps and wearable devices for capturing health data such as electrocardiograms (ECGs) exist. However, most mHealth technologies focus on distinct variables without integrating patients' quality of life, and the impact on clinical outcome measures of implementing those digital solutions into cardiovascular health care is still to be determined. OBJECTIVE: Within this document, we describe the TeleWear project, which was recently initiated as an approach for contemporary patient management integrating mobile-collected health data and the standardized mHealth-guided measurement of patient-reported outcomes (PROs) in patients with cardiovascular disease. METHODS: The specifically designed mobile app and clinical frontend form the central elements of our TeleWear infrastructure. Because of its flexible framework, the platform allows far-reaching customization with the possibility to add different mHealth data sources and respective questionnaires (patient-reported outcome measures). RESULTS: With initial focus on patients with cardiac arrhythmias, a feasibility study is currently carried out to assess wearable-recorded ECG and PRO transmission and its evaluation by physicians using the TeleWear app and clinical frontend. First experiences made during the feasibility study yielded positive results and confirmed the platform's functionality and usability. CONCLUSIONS: TeleWear represents a unique mHealth approach comprising PRO and mHealth data capturing. With the currently running TeleWear feasibility study, we aim to test and further develop the platform in a real-world setting. A randomized controlled trial including patients with atrial fibrillation that investigates PRO- and ECG-based clinical management based on the established TeleWear infrastructure will evaluate its clinical benefits. Widening the spectrum of health data collection and interpretation beyond the ECG and use of the TeleWear infrastructure in different patient subcohorts with focus on cardiovascular diseases are further milestones of the project with the ultimate goal to establish a comprehensive telemedical center entrenched by mHealth.

Electroanatomical mapping-guided left bundle branch area pacing in patients with structural heart disease and advanced conduction abnormalities.

AIMS: Left bundle branch area pacing (LBBAP) can be technically challenging and fluoroscopy-intense. Three-dimensional electroanatomical mapping (EAM) facilitates non-fluoroscopic lead navigation and electrogram mapping. We sought to prospectively evaluate the feasibility, safety, and outcomes of routine EAM-guided LBBAP in patients with structural heart disease (SHD) and advanced conduction abnormalities. METHODS AND RESULTS: Consecutive patients with SHD and conduction abnormalities who underwent an attempt at EAM-guided LBBAP were included. The feasibility, safety, procedural, and mid-term outcomes were evaluated. Electrical, echocardiographic, and clinical parameters were assessed at implantation and last follow-up. Thirty-two patients (68 ± 18 years; 19% female) were included, of which 75% had intrinsic QRS > 150 ms, 53% left bundle branch block, and 25% right bundle branch block. Primary EAM-guided LBBAP was successful in 29 patients (91%). The procedural duration was 95 (70-110) min, total fluoroscopy time 0.93 (0.40-1.73) min, and total fluoroscopy dose 35.4 (20.5-77.2) cGy cm2. Paced QRS duration (QRSd) was significantly shorter than intrinsic QRSd (121.9 ± 10.7 vs. 159.2 ± 34.4 ms; P < 0.001) and remained stable during the mean follow-up of 7.0 ± 5.9 months. The LBBAP capture threshold was 0.57 ± 0.23 V/0.4 ms at implantation and remained low during follow-up (0.58 ± 0.18 V/0.5 ± 0.2 ms; P = 0.877). Overall left ventricular ejection fraction improved significantly from 44.2 ± 14.3% at baseline to 49.4 ± 13.1% at follow-up (P = 0.009), New York Heart Association class from 2.4 ± 0.6 to 1.8 ± 0.6 (P = 0.002), respectively. No complications occurred that required intervention. CONCLUSION: Routine near-zero fluoroscopy EAM-guided LBBAP can safely be performed in patients with SHD and advanced conduction abnormalities with high success rates and favourable mid-term outcomes. Further studies are needed to investigate whether the use of EAM improves the overall outcome of conduction system pacing and to identify specific patient populations who benefit the most from EAM-guided lead implantation.

Profiling endogenous adrenal function during veno-venous ECMO support in COVID-19 ARDS: a descriptive analysis.

Background: Prolonged critical illness is often accompanied by an impairment of adrenal function, which has been frequently related to conditions complicating patient management. The presumed connection between hypoxia and the pathogenesis of this critical- illness- related corticosteroid insufficiency (CIRCI) might play an important role in patients with severe acute respiratory distress syndrome (ARDS). Since extracorporeal membrane oxygenation (ECMO) is frequently used in ARDS, but data on CIRCI during this condition are scarce, this study reports the behaviour of adrenal function parameters during oxygenation support with veno-venous (vv)ECMO in coronavirus disease 2019 (COVID-19) ARDS. Methods: A total of 11 patients undergoing vvECMO due to COVID-19 ARDS at the Medical University of Vienna, who received no concurrent corticosteroid therapy, were retrospectively included in this study. We analysed the concentrations of cortisol, aldosterone, and angiotensin (Ang) metabolites (Ang I-IV, Ang 1-7, and Ang 1-5) in serum via liquid chromatography/tandem mass spectrometry before, after 1 day, 1 week, and 2 weeks during vvECMO support and conducted correlation analyses between cortisol and parameters of disease severity. Results: Cortisol concentrations appeared to be lowest after initiation of ECMO and progressively increased throughout the study period. Higher concentrations were related to disease severity and correlated markedly with interleukin-6, procalcitonin, pH, base excess, and albumin during the first day of ECMO. Fair correlations during the first day could be observed with calcium, duration of critical illness, and ECMO gas flow. Angiotensin metabolite concentrations were available in a subset of patients and indicated a more homogenous aldosterone response to plasma renin activity after 1 week of ECMO support. Conclusion: Oxygenation support through vvECMO may lead to a partial recovery of adrenal function over time. In homogenous patient collectives, this novel approach might help to further determine the importance of adrenal stress response in ECMO and the influence of oxygenation support on CIRCI.

Changing trends of patient characteristics and treatment pathways during the COVID-19 pandemic: A cross-sectional analysis of 72,459 inpatient cases from the German Helios database.

Background: This study compared patient profiles and clinical courses of SARS-CoV-2 infected inpatients over different pandemic periods. Methods: In a retrospective cross-sectional analysis, we examined administrative data of German Helios hospitals using ICD-10-codes at discharge. Inpatient cases with SARS-CoV-2 infection admitted between 03/04/2020 and 07/19/2022 were included irrespective of the reason for hospitalization. All endpoints were timely assigned to admission date for trend analysis. The first pandemic wave was defined by change points in time-series of incident daily infections and compared with different later pandemic phases according to virus type predominance. Results: We included 72,459 inpatient cases. Patients hospitalized during the first pandemic wave (03/04/2020-05/05/2020; n = 1,803) were older (68.5 ± 17.2 vs. 64.4 ± 22.6 years, p < 0.01) and severe acute respiratory infections were more prevalent (85.2 vs. 53.3%, p < 0.01). No differences were observed with respect to distribution of sex, but comorbidity burden was higher in the first pandemic wave. The risk of receiving intensive care therapy was reduced in all later pandemic phases as was in-hospital mortality when compared to the first pandemic wave. Trend analysis revealed declines of mean age and Elixhauser comorbidity index over time as well as a decline of the utilization of intensive care therapy, mechanical ventilation and in-hospital mortality. Conclusion: Characteristics and outcomes of inpatients with SARS-CoV-2 infection changed throughout the observational period. An ongoing evaluation of trends and care pathways will allow for the assessment of future demands.

Characteristics and outcomes of COVID-19 patients during B.1.1.529 (Omicron) dominance compared to B.1.617.2 (Delta) in 89 German hospitals.

BACKGROUND: The SARS-CoV-2 variant B.1.1.529 (Omicron) was first described in November 2021 and became the dominant variant worldwide. Existing data suggests a reduced disease severity with Omicron infections in comparison to B.1.617.2 (Delta). Differences in characteristics and in-hospital outcomes of COVID-19 patients in Germany during the Omicron period compared to Delta are not thoroughly studied. ICD-10-code-based severe acute respiratory infections (SARI) surveillance represents an integral part of infectious disease control in Germany. METHODS: Administrative data from 89 German Helios hospitals was retrospectively analysed. Laboratory-confirmed SARS-CoV-2 infections were identified by ICD-10-code U07.1 and SARI cases by ICD-10-codes J09-J22. COVID-19 cases were stratified by concomitant SARI. A nine-week observational period between December 6, 2021 and February 6, 2022 was defined and divided into three phases with respect to the dominating virus variant (Delta, Delta to Omicron transition, Omicron). Regression analyses adjusted for age, gender and Elixhauser comorbidities were applied to assess in-hospital patient outcomes. RESULTS: A total cohort of 4,494 inpatients was analysed. Patients in the Omicron dominance period were younger (mean age 47.8 vs. 61.6; p < 0.01), more likely to be female (54.7% vs. 47.5%; p < 0.01) and characterized by a lower comorbidity burden (mean Elixhauser comorbidity index 5.4 vs. 8.2; p < 0.01). Comparing Delta and Omicron periods, patients were at significantly lower risk for intensive care treatment (adjusted odds ratio 0.72 [0.57-0.91]; p = 0.005), mechanical ventilation (adjusted odds ratio 0.42 [0.31-0.57]; p < 0.001), and in-hospital mortality (adjusted odds ratio 0.42 [0.32-0.56]; p < 0.001). This also applied mostly to the separate COVID-SARI group. During the Delta to Omicron transition, case numbers of COVID-19 without SARI exceeded COVID-SARI for the first time in the pandemic's course. CONCLUSION: Patient characteristics and outcomes differ during the Omicron dominance period as compared to Delta suggesting a reduced disease severity with Omicron infections. SARI surveillance might play a crucial role in assessing disease severity of future SARS-CoV-2 variants.

Machine learning-derived prediction of in-hospital mortality in patients with severe acute respiratory infection: analysis of claims data from the German-wide Helios hospital network.

BACKGROUND: Severe acute respiratory infections (SARI) are the most common infectious causes of death. Previous work regarding mortality prediction models for SARI using machine learning (ML) algorithms that can be useful for both individual risk stratification and quality of care assessment is scarce. We aimed to develop reliable models for mortality prediction in SARI patients utilizing ML algorithms and compare its performances with a classic regression analysis approach. METHODS: Administrative data (dataset randomly split 75%/25% for model training/testing) from years 2016-2019 of 86 German Helios hospitals was retrospectively analyzed. Inpatient SARI cases were defined by ICD-codes J09-J22. Three ML algorithms were evaluated and its performance compared to generalized linear models (GLM) by computing receiver operating characteristic area under the curve (AUC) and area under the precision-recall curve (AUPRC). RESULTS: The dataset contained 241,988 inpatient SARI cases (75 years or older: 49%; male 56.2%). In-hospital mortality was 11.6%. AUC and AUPRC in the testing dataset were 0.83 and 0.372 for GLM, 0.831 and 0.384 for random forest (RF), 0.834 and 0.382 for single layer neural network (NNET) and 0.834 and 0.389 for extreme gradient boosting (XGBoost). Statistical comparison of ROC AUCs revealed a better performance of NNET and XGBoost as compared to GLM. CONCLUSION: ML algorithms for predicting in-hospital mortality were trained and tested on a large real-world administrative dataset of SARI patients and showed good discriminatory performances. Broad application of our models in clinical routine practice can contribute to patients' risk assessment and quality management.

Relevance of Chronic Total Occlusion for Outcome of Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy.

Background: Catheter ablation of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) is an effective tool to prevent VT recurrences. Chronic total occlusion (CTO) represents a clinically relevant entity in ICM patients and is an independent predictor of ventricular arrhythmia and mortality. The effects of CTO on the outcome of VT ablation are not well-studied. Objective: This analysis aimed to identify the impact of CTO, revascularized, or not revascularized, on the outcome of VT ablation. Methods and Results: Of 385 consecutive subjects with ICM-VT who underwent catheter VT ablation for monomorphic VT at Heart Center Leipzig between 2008 and 2017, 108 patients without CTO and 191 patients with CTO were included in the analysis. Within a median follow-up time of 557 days (IQR 149, 1095), VT recurred in 77 (40%) patients in the CTO and 40 (37.0%) in the non-CTO cohort (p = 0.62). In a multivariable model, a 10% stepwise change in LVEF as well as ICD on admission was associated with VT recurrence (HRadj 1.82, 95% CI 1.04-3.18 and HRadj 1.35, 95% CI 1.23-1.61, respectively). Of the CTO cohort before ablation, 45% had received revascularization, which was independently associated with a higher risk for VT recurrence (HR 2.12, 95% CI 1.35-3.34) as compared to nonrevascularized CTO. Conclusion: In ICM patients with and without CTO, VT ablation was associated with equal effectiveness with regard to VT recurrence. However, in revascularized CTO patients, the risk of recurrence of VT after ablation was significantly increased.