Studies on COVID-19 lethality: Causes and dynamics at German University Hospitals

ABIDE_MI is a complementary funded 18 months project within the German Medical Informatics Initiative (MII), which aims to align IT infrastructures and regulatory/governance structures between biobanks/biobanking IT and the MII data integration centres (DIC) at German university hospitals. A major task in 2021 was the systematic collection of all documents describing rules, as well as proposal/contract templates for data and biosample use and access at each of the participating 24 university hospitals and their comparison with MII-wide consented data sharing principles, documents and governance structures. This comparison revealed large heterogeneity across the ABIDE_MI sites and further, redundant structures/regulations currently established at the German university hospitals. A second task was the design and stepwise development of an IT network infrastructure with central components (data and biosample query portal) and decentralized standardized FHIR servers to capture the standardized FHIR-based core data set modules (resources) defined within the MII working group "Interoperability". Subsequent steps in the project are the harmonization of the data and biosample sharing governance/regulation frameworks at each ABIDE_MI site, creating synergies for the research infrastructures at the German university hospitals and to link those resources to the German Portal for Medical Research Data and with the BBMRI-ERIC Directory and Negotiator tools.

Barotrauma, invasive ventilation, and timing of tocilizumab as predictors of mortality along with inflammatory markers and comorbidities in critically ill COVID-19 patients: A retrospective study.

Background Anti-inflammatory agents like dexamethasone (DEX) have become a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX. Methods This was a multi-site, retrospective, observational study of ventilated COVID-19-positive patients who received at least three days of DEX between June 1, 2020 and January 31, 2022. Sample size was calculated based on a 3:1 high:standard-dose prescribing pattern ratio. The primary outcome of this study was the association between mortality and SD (<6mg daily) versus HD ( >10mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS) and ICU LOS. Results Of 322 patients screened, 110 were excluded primarily for average daily DEX dose of > 6 to ≤ 10mg. Of the 212 included patients, 53 (25%) received SD DEX and 159 (75%) received HD DEX. Data demonstrate no significant effect of DEX dose on mortality, number of BG readings > 200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors no difference in mortality persisted (OR 1.45 95% CI 0.66- 3.20). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019 respectively). Conclusion There is no association between HD DEX and mortality among ventilated COVID-19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients. Disclosures All Authors: No reported disclosures.

Early vs. late tracheostomy in ventilated COVID-19 patients – A retrospective study

Anti-inflammatory agents like dexamethasone (DEX) are a mainstay of treatment for COVID-19. Despite randomized trials demonstrating that a 6 mg daily dose of DEX improved patient outcomes in hospitalized COVID-19 patients receiving oxygen, clinicians often prescribe higher doses of corticosteroids without evidence to support this practice. The purpose of this study was to compare outcomes of ventilated COVID-19 patients who received standard dose (SD) versus high dose (HD) DEX. This was a multi-site, retrospective, observational study on ventilated COVID-19- positive patients who received DEX for at least three days between June 1, 2020, and January 31, 2022. The primary outcome of this study was the association between mortality and SD (<6 mg daily) versus HD (>10 mg daily) DEX in ventilated COVID-19 patients. Secondary outcomes included average blood glucose (BG), number of BG readings above 200, incidence of bacterial nosocomial infection, ventilator-free days, length of stay (LOS), and ICU LOS. Of the 212 included patients, 53 (25%) received SD DEX, and 159 (75%) received HD DEX. There was no significant effect of DEX dose on mortality, number of BG readings >200, incidence of nosocomial infections, LOS, or ventilator-free days (p >0.05). After controlling for confounding factors, no difference in mortality persisted (OR 1.34 95% CI 0.62- 2.90). Average daily BG and ICU LOS were significantly greater in the HD group compared to the SD group (p = 0.003, p = 0.019, respectively). There was no association between HD DEX and mortality among ventilated COVID- 19 patients compared to SD DEX. Moreover, HD DEX is associated with detrimental effects such as prolonged ICU LOS and higher average daily BG. This study supports the use of SD DEX in ventilated COVID-19 patients.

In the last decade numerous real-world data networks have been established in order to leverage the value of data from electronic health records for medical research. In Germany, a nation-wide network based on electronic health record data from all German university hospitals has been established within the Medical Informatics Initiative (MII) and recently opened for researcherst' access through the German Portal for Medical Research Data (FDPG). In Bavaria, the six university hospitals have joined forces within the Bavarian Cancer Research Center (BZKF). The oncology departments aim at establishing a federated observational research network based on the framework of the MII/FDPG and extending it with a clear focus on oncological clinical data, imaging data and molecular high throughput analysis data. We describe necessary adaptions and extensions of existing MII components with the goal of establishing a Bavarian oncology real world data research platform with its first use case of performing federated feasibility queries on clinical oncology data. We share insights from developing a feasibility platform prototype and presenting it to end users. Our main discovery was that oncological data is characterized by a higher degree of interdependence and complexity compared to the MII core dataset that is already integrated into the FDPG. The significance of our work lies in the requirements we formulated for extending already existing MII components to match oncology specific data and to meet oncology researchers needs while simultaneously transferring back our results and experiences into further developments within the MII.

Effect of therapeutic anticoagulation on gas exchange in mechanically ventilated COVID-19 patients: A secondary analysis of the COVID-HEP trial

IntroductionThe number of patients on intensive care units (ICU) increased manifold during the initial COVID-19 surge and medical staff were relocated to help compensate. The need for central venous catheters (CVCs) increased accordingly and comprised a significant workload under challenging circumstances. Several models were proposed to manage the lines. We assigned a vascular team of vascular surgeons and interventional radiologists for CVCs in ICU. We report on the workload, outcomes and lessons learned.Method50 consecutive ventilated COVID-19 patients in ICU (median age 63 years, 80% male) who had a CVC inserted by the vascular team from March to May 2020 were assessed. Median follow up was 18 days (range 14– 29 days) after ICU admission.Result166 CVCs (80 VasCaths) were inserted. Femoral access was preferred. Each patient required a median of 3 lines (IQR 2–4). CVCs were exchanged after median 7 days (IQR 4–9) for thrombosis (35%), infection (24%) or prophylactically (41%). Our learning curve included the establishment of an online referral pathway, CVC teams of two operators, extended disposable CVC kits and ICU based ultrasound scanners. Additional staffing and retraining were avoided. There were no technical complications.ConclusionVentilated COVID-19 patients require multiple CVCs which is a challenging workload during a pandemic. Vascular surgeons and interventional radiologists with endovascular skills are well positioned to perform central venous cannulation to alleviate the burden on critical care teams. Our lessons learned can help to provide a safe and efficient model amidst the ongoing national outbreaks.Take-home MessageWith the postponement of many elective vascular procedures during the pandemic crisis, the involvement of vascular surgeons in a dedicated Lines team is an important way that they can contribute given their proficiency with wires and cannulation equipment, as well as familiarity in femoral triangle and jugular anatomy. The retraining of staff and additional on-call rotas can then be avoided.

Tracheotomy in Ventilated Patients With COVID-19.

Introduction: Mechanical ventilation is frequently utilised in critically ill COVID-19 patients, yet outcomes remain unclear. This study evaluated characteristics, outcomes and associations between mechanical ventilation and prognosis in COVID-19 patients admitted to the intensive care unit (ICU). Methods: A retrospective review was conducted of medical records from 1389 COVID-19 patients admitted to a single ICU between dates. Demographic, clinical, treatment data and outcomes including length of stay (LOS), microbiological cure and discharge status were collected. Comparisons were made between ventilated and non-ventilated patients. Results: The mean age was 56 years, 74% were male. Mechanical ventilation was utilised in 73.9% for a mean duration of 9.89 days. Ventilated patients had significantly longer ICU (15 days vs. 10 days) and hospital stays (22 days vs. 18 days). Microbiological cure was achieved in 16.1%, with higher rates in ventilated patients. Factors including older age, male gender, diabetes and higher body mass index correlated with worse outcomes. Ventilated patients more often experienced ICU (96% vs. 4%) and hospital mortality (60% vs. 40%). Mechanical ventilation duration positively correlated with ICU and hospital LOS. Longer ventilation durations correlated with cure and remaining in ICU. Conclusion: In this large cohort, mechanical ventilation was commonly utilised yet correlated with worse outcomes, although outcomes may be confounded by indication. Modifying risk profiles through glycaemic and weight control along with standardised evidence-based protocols may help optimise outcomes. Further prospective analyses accounting for the severity of illness are needed to determine causal relationships between ventilation and prognosis in COVID-19.

Electronic documentation of medication data is one of the biggest challenges associated with digital clinical documentation. Despite its importance, it has not been consistently implemented in German university hospitals. In this paper we describe the approach of the German Medical Informatics Initiative (MII) towards the modelling of a medication core dataset using FHIR® profiles and standard-compliant terminologies. The FHIR profiles for Medication and MedicationStatement were adapted to the core dataset of the MIl. The terminologies to be used were selected based on the criteria of the ISO-standard for the Identification of Medicinal Products (IDMP). For a first use case with a minimal medication dataset, the entries in the medication chapter of the German Procedure Classification (OPS codes) were analyzed and mapped to IDMP-compliant medication terminology. OPS data are available at all German hospitals as they are mandatory for reimbursement purposes. Reimbursement-relevant encounter data containing OPS medication procedures were used to create a FHIR representation based on the FHIR profiles MedicationStatement and Medication. This minimal solution includes - besides the details on patient and start-/end-dates - the active ingredients identified by the IDMP-compliant codes and - if specified in the OPS code - the route of administration and the range of the amount of substance administered to the patient, using the appropriate unit of measurement code. With FHIR, the medication data can be represented in the data integration centers of the MII to provide a standardized format for data analysis across the MII sites.

PurposeThe COVID-19 pandemic has caused intensive care units (ICUs) to reach capacities requiring triage. A tool to predict mortality risk in ventilated patients with COVID-19 could inform decision-making and resource allocation, and allow population-level comparisons across institutions.MethodsThis retrospective cohort study included all mechanically ventilated adults with COVID-19 admitted to three tertiary care ICUs in Toronto, Ontario, between 1 March 2020 and 15 December 2020. Generalized estimating equations were used to identify variables predictive of mortality. The primary outcome was the probability of death at three-day intervals from the time of ICU admission (day 0), with risk re-calculation every three days to day 15; the final risk calculation estimated the probability of death at day 15 and beyond. A numerical algorithm was developed from the final model coefficients.ResultsOne hundred twenty-seven patients were eligible for inclusion. Median ICU length of stay was 26.9 (interquartile range, 15.4–52.0) days. Overall mortality was 42%. From day 0 to 15, the variables age, temperature, lactate level, ventilation tidal volume, and vasopressor use significantly predicted mortality. Our final clinical risk score had an area under the receiver-operating characteristics curve of 0.9 (95% confidence interval [CI], 0.8 to 0.9). For every ten-point increase in risk score, the relative increase in the odds of death was approximately 4, with an odds ratio of 4.1 (95% CI, 2.9 to 5.9).ConclusionOur dynamic prediction tool for mortality in ventilated patients with COVID-19 has excellent diagnostic properties. Notwithstanding, external validation is required before widespread implementation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12630-021-02163-3.

Introduction: The inflammatory mechanisms of COVID-19 suggest that corticosteroids may be beneficial, but their benefits must outweigh their potential risks. The RECOVERY trial results suggest that dexamethasone 6 mg/day (but not other steroids) may confer mortality benefits on ventilated COVID-19 patients. Methods: This is a narrative review of the literature about the use of ciclesonide and dexamethasone for COVID-19 patients. Literature is being created rapidly and this review is offered as a state-of-the-science narration. Results: The SARS-CoV-2 virus is an RNA virus whose RNA is transcribed via open reading frames, making its elimination difficult. Coronaviruses have evolved multiple strategies for proteolytic activation of the spike; viral replication occurs entirely in the cytoplasm. In this connection, the RNA-cleaving endoribonuclease (NSP-15 also known as EndoU) may play a key role by facilitating viral double-stranded RNA recognition by the host’s macrophages. Furthermore, the virus is able to undergo RNA recombination rapidly, enabling it to evade host immunity and develop drug resistance. Ciclesonide is an inhaled corticosteroid that reduces lung inflammation and blocks the activity of specific kinases which may explain its anti-inflammatory effect. Dexamethasone is known to reduce mortality in ventilated COVID-19 patients. Discussion: Systemic corticosteroids were used in previous coronavirus epidemics (SARS and MERS) and pulmonary histology of these patients is similar to those in COVID-19 patients. Acute respiratory distress syndrome is the main cause of death in most COVID-19 infections and steroids may be effective in addressing that condition, brought on by cytokine storm. However, it should be noted that inhaled steroids likely have a narrower window for effect than systemic regimens. Conclusion: Dexamethasone has been proven to confer mortality benefits on ventilated COVID-19 patients and may be used with inhaled ciclesonide, which has few side effects and can be locally metabolized. Further study is needed.

ObjectiveTo estimate continuous positive airway pressure (CPAP) length of treatment effect on survival of hospitalised COVID-19 patients in a medium-sized UK Hospital, and how this effect changes according to the...

Utilization of peritoneal dialysis for ventilated COVID-19 patients with acute kidney injury