Showing papers by "Frank Hanses published in 2022"
TL;DR: An extended GWAS meta-analysis of a well-characterized cohort of COVID-19 patients with respiratory failure and population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen (HLA) region and the SARS-CoV-2 peptidome is described.
Abstract: Abstract Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended genome-wide association meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from Italy, Spain, Norway and Germany/Austria, including stratified analyses based on age, sex and disease severity, as well as targeted analyses of chromosome Y haplotypes, the human leukocyte antigen region and the SARS-CoV-2 peptidome. By inversion imputation, we traced a reported association at 17q21.31 to a ~0.9-Mb inversion polymorphism that creates two highly differentiated haplotypes and characterized the potential effects of the inversion in detail. Our data, together with the 5th release of summary statistics from the COVID-19 Host Genetics Initiative including non-Caucasian individuals, also identified a new locus at 19q13.33, including NAPSA, a gene which is expressed primarily in alveolar cells responsible for gas exchange in the lung.
23 citations
TL;DR: The modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age, specifically in the absence of obesity and impaired metabolic health.
Abstract: Advanced age, followed by male sex, by far poses the greatest risk for severe COVID-19. An unresolved question is the extent to which modifiable comorbidities increase the risk of COVID-19-related mortality among younger patients, in whom COVID-19-related hospitalization strongly increased in 2021. A total of 3,163 patients with SARS-COV-2 diagnosis in the Lean European Open Survey on SARS-CoV-2-Infected Patients (LEOSS) cohort were studied. LEOSS is a European non-interventional multi-center cohort study established in March 2020 to investigate the epidemiology and clinical course of SARS-CoV-2 infection. Data from hospitalized patients and those who received ambulatory care, with a positive SARS-CoV-2 test, were included in the study. An additive effect of obesity, diabetes and hypertension on the risk of mortality was observed, which was particularly strong in young and middle-aged patients. Compared to young and middle-aged (18–55 years) patients without obesity, diabetes and hypertension (non-obese and metabolically healthy; n = 593), young and middle-aged adult patients with all three risk parameters (obese and metabolically unhealthy; n = 31) had a similar adjusted increased risk of mortality [OR 7.42 (95% CI 1.55–27.3)] as older (56–75 years) non-obese and metabolically healthy patients [n = 339; OR 8.21 (95% CI 4.10–18.3)]. Furthermore, increased CRP levels explained part of the elevated risk of COVID-19-related mortality with age, specifically in the absence of obesity and impaired metabolic health. In conclusion, the modifiable risk factors obesity, diabetes and hypertension increase the risk of COVID-19-related mortality in young and middle-aged patients to the level of risk observed in advanced age.
15 citations
TL;DR: The National Pandemic Cohort Network (NAPKON) as discussed by the authors created the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany, where adult and pediatric patients were observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up.
Abstract: The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.
12 citations
TL;DR: In immunologically naïve patients with Cirrhosis, mortality from wild‐type SARS‐CoV‐2 and the alpha variant is high and is largely determined by cirrhosis‐associated comorbidities and extrahepatic organ failure.
Abstract: Abstract Background and Objective International registries have reported high mortality rates in patients with liver disease and COVID‐19. However, the extent to which comorbidities contribute to excess COVID‐19 mortality in cirrhosis is controversial. Methods We used the multinational Lean European Open Survey on SARS‐CoV‐2‐infected patients (LEOSS) to identify patients with cirrhosis documented between March 2020 and March 2021, when the wild‐type and alpha variant were predominant. We compared symptoms, disease progression and mortality after propensity score matching (PSM) for age, sex, obesity, smoking status, and concomitant diseases. Mortality was also compared with that of patients with spontaneous bacterial peritonitis (SBP) without SARS‐CoV‐2 infection, a common bacterial infection and well‐described precipitator of acute‐on‐chronic liver failure. Results Among 7096 patients with SARS‐CoV‐2 infection eligible for analysis, 70 (0.99%) had cirrhosis, and all were hospitalized. Risk factors for severe COVID‐19, such as diabetes, renal disease, and cardiovascular disease were more frequent in patients with cirrhosis. Case fatality rate in patients with cirrhosis was 31.4% with the highest odds of death in patients older than 65 years (43.6% mortality; odds ratio [OR] 4.02; p = 0.018), Child‐Pugh class C (57.1%; OR 4.00; p = 0.026), and failure of two or more organs (81.8%; OR 19.93; p = 0.001). After PSM for demographics and comorbidity, the COVID‐19 case fatality of patients with cirrhosis did not significantly differ from that of matched patients without cirrhosis (28.8% vs. 26.1%; p = 0.644) and was similar to the 28‐day mortality in a comparison group of patients with cirrhosis and SBP (33.3% vs. 31.5%; p = 1.000). Conclusions In immunologically naïve patients with cirrhosis, mortality from wild‐type SARS‐CoV‐2 and the alpha variant is high and is largely determined by cirrhosis‐associated comorbidities and extrahepatic organ failure.
6 citations
14 Sep 2022
TL;DR: Early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS.
5 citations
03 Jan 2022
TL;DR: In this article , a seroepidemiological study was conducted to evaluate the risk of infection for employees at a tertiary care hospital, where seroprevalence of antibodies against SARS-CoV-2 was 5.1% at the end of the study in February 2021.
Abstract: Healthcare workers caring for coronavirus disease 2019 (COVID‑19) patients are at an increased risk for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this seroepidemiological study was to evaluate the risk of infection for employees at a tertiary care hospital.Serological tests for antibodies against SARS-CoV‑2 were carried out in a prospective cohort of employees directly involved in the care of COVID‑19 patients every 2 weeks from March to July 2020 (1st wave). Antibody status was examined again between December 2020 and February 2021 (2nd wave).The seroprevalence of antibodies against SARS-CoV‑2 was 5.1% at the end of the study in February 2021. The cumulative incidence was 3.9% after a median observation period of 261 days.We observed a low risk of SARS-CoV‑2 infection comparable to that of the general population in the examined cohort of healthcare workers involved in the acute care of COVID‑19 patients under the applied hygiene and protective measures.HINTERGRUND: Mitarbeiter im Gesundheitswesen mit Kontakt zu COVID‑19-Patienten sind einem erhöhten Risiko einer Infektion mit SARS-CoV‑2 ausgesetzt. Ziel dieser seroepidemiologischen Studie war es, das Infektionsrisiko für Klinikmitarbeiter eines Maximalversorgers zu evaluieren.Im Rahmen einer prospektiven Kohortenstudie wurden von März bis Juli 2020 (1. Welle) bei unmittelbar in der Versorgung von COVID‑19-Patienten eingesetzten Mitarbeitern im Abstand von jeweils 2 Wochen serologische Untersuchungen auf Antikörper gegen SARS-CoV‑2 durchgeführt. Von Dezember 2020 bis Februar 2021 (2. Welle) fand eine erneute Untersuchung des Antikörperstatus statt.Die Seroprävalenz von Antikörpern gegen SARS-CoV‑2 betrug am Studienende im Februar 2021 5,1 %. Die kumulative Inzidenz betrug nach einer medianen Beobachtungsdauer von 261 Tagen 3,9 %.In der untersuchten Kohorte von Klinikmitarbeitern, die in der Akutversorgung von COVID‑19-Patienten eingesetzt werden, fand sich unter den angewandten Hygiene- und Schutzmaßnahmen ein niedriges und mit der Gesamtbevölkerung vergleichbares Risiko einer SARS-CoV-2-Infektion.
3 citations
TL;DR: In this article , the authors performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis.
Abstract: Abstract Establishing the optimal treatment for COVID-19 patients remains challenging. Specifically, immunocompromised and pre-diseased patients are at high risk for severe disease course and face limited therapeutic options. Convalescent plasma (CP) has been considered as therapeutic approach, but reliable data are lacking, especially for high-risk patients. We performed a retrospective analysis of 55 hospitalized COVID-19 patients from University Hospital Duesseldorf (UKD) at high risk for disease progression, in a substantial proportion due to immunosuppression from cancer, solid organ transplantation, autoimmune disease, dialysis. A matched-pairs analysis (1:4) was performed with 220 patients from the Lean European Open Survey on SARS-CoV-2-infected Patients (LEOSS) who were treated or not treated with CP. Both cohorts had high mortality (UKD 41.8%, LEOSS 34.1%). A matched-pairs analysis showed no significant effect on mortality. CP administration before the formation of pulmonary infiltrates showed the lowest mortality in both cohorts (10%), whereas mortality in the complicated phase was 27.8%. CP administration during the critical phase revealed the highest mortality: UKD 60.9%, LEOSS 48.3%. In our cohort of COVID-19 patients with severe comorbidities CP did not significantly reduce mortality in a retrospective matched-pairs analysis. However, our data supports the concept that a reduction in mortality is achievable by early CP administration.
3 citations
03 Jan 2022
TL;DR: In this article , a seroepidemiological study was conducted to evaluate the risk of infection for employees at a tertiary care hospital, where seroprevalence of antibodies against SARS-CoV-2 was 5.1% at the end of the study in February 2021.
Abstract: Healthcare workers caring for coronavirus disease 2019 (COVID‑19) patients are at an increased risk for a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of this seroepidemiological study was to evaluate the risk of infection for employees at a tertiary care hospital.Serological tests for antibodies against SARS-CoV‑2 were carried out in a prospective cohort of employees directly involved in the care of COVID‑19 patients every 2 weeks from March to July 2020 (1st wave). Antibody status was examined again between December 2020 and February 2021 (2nd wave).The seroprevalence of antibodies against SARS-CoV‑2 was 5.1% at the end of the study in February 2021. The cumulative incidence was 3.9% after a median observation period of 261 days.We observed a low risk of SARS-CoV‑2 infection comparable to that of the general population in the examined cohort of healthcare workers involved in the acute care of COVID‑19 patients under the applied hygiene and protective measures.HINTERGRUND: Mitarbeiter im Gesundheitswesen mit Kontakt zu COVID‑19-Patienten sind einem erhöhten Risiko einer Infektion mit SARS-CoV‑2 ausgesetzt. Ziel dieser seroepidemiologischen Studie war es, das Infektionsrisiko für Klinikmitarbeiter eines Maximalversorgers zu evaluieren.Im Rahmen einer prospektiven Kohortenstudie wurden von März bis Juli 2020 (1. Welle) bei unmittelbar in der Versorgung von COVID‑19-Patienten eingesetzten Mitarbeitern im Abstand von jeweils 2 Wochen serologische Untersuchungen auf Antikörper gegen SARS-CoV‑2 durchgeführt. Von Dezember 2020 bis Februar 2021 (2. Welle) fand eine erneute Untersuchung des Antikörperstatus statt.Die Seroprävalenz von Antikörpern gegen SARS-CoV‑2 betrug am Studienende im Februar 2021 5,1 %. Die kumulative Inzidenz betrug nach einer medianen Beobachtungsdauer von 261 Tagen 3,9 %.In der untersuchten Kohorte von Klinikmitarbeitern, die in der Akutversorgung von COVID‑19-Patienten eingesetzt werden, fand sich unter den angewandten Hygiene- und Schutzmaßnahmen ein niedriges und mit der Gesamtbevölkerung vergleichbares Risiko einer SARS-CoV-2-Infektion.
3 citations
TL;DR: Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development, and the great importance of combination antibiotic therapies.
Abstract: Aims Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151.
2 citations
TL;DR: In this paper , the authors proposed the COVIDAL classifier for AI-based diagnosis of symptomatic COVID-19 subjects in hospitals based on laboratory parameters, and evaluated the algorithm's performance by unique multicenter data with approximately 4,000 patients and an extraordinary high ratio of SARS-CoV-2-positive patients.
Abstract: For the fight against the COVID-19 pandemic, it is particularly important to map the course of infection, in terms of patients who have currently tested SARS-CoV-2 positive, as accurately as possible. In hospitals, this is even more important because resources have become scarce. Although polymerase chain reaction (PCR) and point of care (POC) antigen testing capacities have been massively expanded, they are often very time-consuming and cost-intensive and, in some cases, lack appropriate performance. To meet these challenges, we propose the COVIDAL classifier for AI-based diagnosis of symptomatic COVID-19 subjects in hospitals based on laboratory parameters. We evaluate the algorithm's performance by unique multicenter data with approximately 4,000 patients and an extraordinary high ratio of SARS-CoV-2-positive patients. We analyze the influence of data preparation, flexibility in optimization targets, as well as the selection of the test set on the COVIDAL outcome. The algorithm is compared with standard AI, PCR, POC antigen testing and manual classifications of seven physicians by a decision theoretic scoring model including performance metrics, turnaround times and cost. Thereby, we define health care settings in which a certain classifier for COVID-19 diagnosis is to be applied. We find sensitivities, specificities, and accuracies of the COVIDAL algorithm of up to 90 percent. Our scoring model suggests using PCR testing for a focus on performance metrics. For turnaround times, POC antigen testing should be used. If balancing performance, turnaround times, and cost is of interest, as, for example, in the emergency department, COVIDAL is superior based on the scoring model.
2 citations
TL;DR: Of Detection Seroconversion Severe Acute Respiratory Syndrome and how this affects the prognosis for patients with severe acute respiratory illness is under investigation.
Abstract: of Detection Seroconversion Severe Acute Respiratory Syndrome
TL;DR: It is indicated that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response, and disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age.
Abstract: Although there is strong evidence that SARS-CoV-2 infection is associated with adverse outcomes in certain ethnic groups, the association of disease severity and risk factors such as comorbidities and biomarkers with racial disparities remains undefined. This retrospective study between March 2020 and February 2021 explores COVID-19 risk factors as predictors for patients’ disease progression through country comparison. Disease severity predictors in Germany and Japan were cardiovascular-associated comorbidities, dementia, and age. We adjusted age, sex, body mass index, and history of cardiovascular disease comorbidity in the country cohorts using a propensity score matching (PSM) technique to reduce the influence of differences in sample size and the surprisingly young, lean Japanese cohort. Analysis of the 170 PSM pairs confirmed that 65.29% of German and 85.29% of Japanese patients were in the uncomplicated phase. More German than Japanese patients were admitted in the complicated and critical phase. Ethnic differences were identified in patients without cardiovascular comorbidities. Japanese patients in the uncomplicated phase presented a suppressed inflammatory response and coagulopathy with hypocoagulation. In contrast, German patients exhibited a hyperactive inflammatory response and coagulopathy with hypercoagulation. These differences were less pronounced in patients in the complicated phase or with cardiovascular diseases. Coagulation/fibrinolysis-associated biomarkers rather than inflammatory-related biomarkers predicted disease severity in patients with cardiovascular comorbidities: platelet counts were associated with severe illness in German patients. In contrast, high D-dimer and fibrinogen levels predicted disease severity in Japanese patients. Our comparative study indicates that ethnicity influences COVID-19-associated biomarker expression linked to the inflammatory and coagulation (thrombo-inflammatory) response. Future studies will be necessary to determine whether these differences contributed to the less severe disease progression observed in Japanese COVID-19 patients compared with those in Germany.
TL;DR: In this paper , the authors compared short-course and long-course antibiotic treatments in hospitalized adult patients with uncomplicated vancomycin-resistant enterococcal (VRE) bacteraemia.
TL;DR: In this article , a multicentre cohort study was conducted to evaluate pre-existing dialysis dependency as a potential risk factor for mortality in SARS-CoV-2-infected CKD patients.
Abstract: Patients suffering from chronic kidney disease (CKD) are in general at high risk for severe coronavirus disease (COVID-19) but dialysis-dependency (CKD5D) is poorly understood. We aimed to describe CKD5D patients in the different intervals of the pandemic and to evaluate pre-existing dialysis dependency as a potential risk factor for mortality.In this multicentre cohort study, data from German study sites of the Lean European Open Survey on SARS-CoV-2-infected patients (LEOSS) were used. We multiply imputed missing data, performed subsequent analyses in each of the imputed data sets and pooled the results. Cases (CKD5D) and controls (CKD not requiring dialysis) were matched 1:1 by propensity-scoring. Effects on fatal outcome were calculated by multivariable logistic regression.The cohort consisted of 207 patients suffering from CKD5D and 964 potential controls. Multivariable regression of the whole cohort identified age (> 85 years adjusted odds ratio (aOR) 7.34, 95% CI 2.45-21.99), chronic heart failure (aOR 1.67, 95% CI 1.25-2.23), coronary artery disease (aOR 1.41, 95% CI 1.05-1.89) and active oncological disease (aOR 1.73, 95% CI 1.07-2.80) as risk factors for fatal outcome. Dialysis-dependency was not associated with a fatal outcome-neither in this analysis (aOR 1.08, 95% CI 0.75-1.54) nor in the conditional multivariable regression after matching (aOR 1.34, 95% CI 0.70-2.59).In the present multicentre German cohort, dialysis dependency is not linked to fatal outcome in SARS-CoV-2-infected CKD patients. However, the mortality rate of 26% demonstrates that CKD patients are an extreme vulnerable population, irrespective of pre-existing dialysis-dependency.
TL;DR: A demand for palliative care expertise with early involvement seems to exist in patients dying with SARS-CoV-2 infection, which suffers from high symptom burden and often deteriorate early with a demand for ICU treatment.
Abstract: Background COVID-19 is a severe disease with a high need for intensive care treatment and a high mortality rate in hospitalized patients. The objective of this study was to describe and compare the clinical characteristics and the management of patients dying with SARS-CoV-2 infection in the acute medical and intensive care setting. Methods Descriptive analysis of dying patients enrolled in the Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS), a non-interventional cohort study, between March 18 and November 18, 2020. Symptoms, comorbidities and management of patients, including palliative care involvement, were compared between general ward and intensive care unit (ICU) by univariate analysis. Results 580/4310 (13%) SARS-CoV-2 infected patients died. Among 580 patients 67% were treated on ICU and 33% on a general ward. The spectrum of comorbidities and symptoms was broad with more comorbidities (≥ four comorbidities: 52% versus 25%) and a higher age distribution (>65 years: 98% versus 70%) in patients on the general ward. 69% of patients were in an at least complicated phase at diagnosis of the SARS-CoV-2 infection with a higher proportion of patients in a critical phase or dying the day of diagnosis treated on ICU (36% versus 11%). While most patients admitted to ICU came from home (71%), patients treated on the general ward came likewise from home and nursing home (44% respectively) and were more frequently on palliative care before admission (29% versus 7%). A palliative care team was involved in dying patients in 15%. Personal contacts were limited but more often documented in patients treated on ICU (68% versus 47%). Conclusion Patients dying with SARS-CoV-2 infection suffer from high symptom burden and often deteriorate early with a demand for ICU treatment. Therefor a demand for palliative care expertise with early involvement seems to exist.
TL;DR: In this paper , the authors found that COVID-19 patients are at increased risk for thromboembolic events, and that the risk for gastrointestinal bleeding is also increased.
Abstract: Aims COVID-19 patients are at increased risk for thromboembolic events. It is unclear whether the risk for gastrointestinal (GI) bleeding is also increased.
TL;DR: Although the success rate of dalbavancin was lower than reported previously, this may be due to the severity of underlying infections and patients’ high Charlson Comorbidity Index, suggesting frequent off-label use in German routine practice.
Abstract: The antibiotic dalbavancin is approved for intravenous treatment of adults with acute bacterial skin and skin structure infections. This study aimed to observe the use, effectiveness, and safety of dalbavancin in clinical practice in Germany. It was a multicentre, prospective, and retrospective registry and consecutively enrolled patients treated with dalbavancin. Each patient was observed from the first to the last dose of dalbavancin, with a 30-day follow-up. Patient inclusion was planned for 2 years, but was terminated early due to low recruitment. All analyses were descriptive. Between November 2018 and December 2019, nine patients were enrolled. Only three patients were treated for the approved indication. Outcome was assessed by the physicians as ‘success’ in five (55.6%) patients, ‘failure’ in one (11.1%) patient, and non-evaluable in three (33.3%) patients. Although the success rate of dalbavancin was lower than reported previously, this may be due to the severity of underlying infections and patients’ high Charlson Comorbidity Index. None of the two reported adverse events were considered related to dalbavancin. These findings were in line with real-world data for dalbavancin from other countries, supporting the drug’s positive benefit–risk profile and suggesting frequent off-label use in German routine practice.
TL;DR: In this article , the authors studied the statistical validity of an open medical dataset based on the German National Pandemic Cohort Network (NAPKON), which was prepared for publication using a strong anonymization procedure.
Abstract: Abstract Anonymization has the potential to foster the sharing of medical data. State-of-the-art methods use mathematical models to modify data to reduce privacy risks. However, the degree of protection must be balanced against the impact on statistical properties. We studied an extreme case of this trade-off: the statistical validity of an open medical dataset based on the German National Pandemic Cohort Network (NAPKON), which was prepared for publication using a strong anonymization procedure. Descriptive statistics and results of regression analyses were compared before and after anonymization of multiple variants of the original dataset. Despite significant differences in value distributions, the statistical bias was found to be small in all cases. In the regression analyses, the median absolute deviations of the estimated adjusted odds ratios for different sample sizes ranged from 0.01 [minimum = 0, maximum = 0.58] to 0.52 [minimum = 0.25, maximum = 0.91]. Disproportionate impact on the statistical properties of data is a common argument against the use of anonymization. Our analysis demonstrates that anonymization can actually preserve validity of statistical results in relatively low-dimensional data.
TL;DR: Pape et al. as discussed by the authors evaluated the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA).
Abstract: Abstract Background Numerous predictive clinical scores with varying discriminatory performance have been developed in the context of the current coronavirus disease 2019 (COVID-19) pandemic. To support clinical application, we test the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA). Our project aims to externally validate these two scores, stratified for the most prevalent variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in Germany. Methods A total of 685 adults with polymerase chain reaction (PCR)-detected SARS-CoV-2 infection were included from NAPKON-SUEP. Patients were recruited from 11/2020 to 03/2022 at 34 university and non-university hospitals across Germany. Missing values were complemented using multiple imputation. Predictive performance for in-hospital mortality at day of baseline visit was determined by area under the curve (AUC) with 95%-confidence interval (CI) stratified by VOCs of SARS-CoV-2 (alpha, delta, omicron) (Figure 1). Figure 1: Study flow chart with inclusion criteria and methodological workflow. Results Preliminary results suggest a high predictive performance of the 4C score for in-hospital mortality (Table 1). This applies for the overall cohort (AUC 0.813 (95%CI 0.738-0.888)) as well as the VOC-strata (alpha: AUC 0.859 (95%CI 0.748-0.970); delta: AUC 0.769 (95%CI 0.657-0.882); omicron: AUC 0.866 (95%CI 0.724-1.000)). The overall mortality rates across the defined 4C score risk groups are 0.3% (low), 3.2% (intermediate), 11.6% (high), and 49.5% (very high). The 4C score performs significantly better than the qSOFA (Chi2-test: p=0.001) and the qSOFA does not seem to be a suitable tool in this context. Table 1: Discriminatory performance of the 4C Mortality Score and the qSOFA score within the validation cohort NAPKON-SUEP stratified by the Variant of Concerns of SARS-CoV-2. Conclusion Despite its development in the early phase of the pandemic and improved treatment, external validation of the 4C score in NAPKON-SUEP indicates a high predictive performance for in-hospital mortality across all VOCs. However, since the qSOFA was not specifically designed for this predictive issue, it shows low discriminatory performance, as in other validation studies. Any interpretations regarding the omicron stratum are limited due to the sample size. Disclosures Daniel Pape, Dr., Advanz Pharma Germany: Support for attending meetings and/or travel for ECCMID 2021 Martin Hower, n/a, MSD: Advisor/Consultant|Trogarzo: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant Björn-Erik O. Jensen, Dr. med., GILEAD: Advisor/Consultant|GILEAD: Lectures, Travel|GSK: Lectures, Travel Jörg J. Vehreschild, Univ.-Prof. Dr. med., Ärztekammer Nordrhein: Honoraria|Academy for Infectious Medicine, University Manchester: Honoraria|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Back Bay Strategies: Honoraria|Basilea: Grant/Research Support|Basilea: Honoraria|Deutsches Zetrum für Luft- und Raumfahrt (DLR): Grant/Research Support|German Centre for Infection Research (DZIF): Grant/Research Support|German Centre for Infection Research (DZIF): Honoraria|German Federal Ministry of Education and Research (BMBF): Grant/Research Support|German Society for Infectious Diseases (DGI): Honoraria|German Society for Internal Medicine (DGIM): Honoraria|GILEAD: Advisor/Consultant|GILEAD: Grant/Research Support|GILEAD: Honoraria|Janssen: Honoraria|Merck / MSD: Grant/Research Support|Merck / MSD: Honoraria|Molecular Health: Honoraria|Netzwerk Universitätsmedizin: Honoraria|NordForsk: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Rigshospitalet Copenhagen: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria|University Hospital Aachen: Honoraria|University Hospital Freiburg/ Congress and Communication: Honoraria|University of Bristol: Grant/Research Support.
TL;DR: In this article , the authors correct the article DOI: 10.1016/jailsci.2010.2021.100020] and present a new version of the article.
Abstract: [This corrects the article DOI: 10.1016/j.ailsci.2021.100020.].
TL;DR: Wu et al. as discussed by the authors have documented COVID-19-associated pulmonary aspergillosis (CAPA), invasive candidiasis (10), coccidioidomycosis (11), fusariosis (12), histoplasmosis (13), mucormycosis(14), pneumocystosis (15), and saccharomyciosis (16).
Abstract: 1077 C of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were fi rst described in Wuhan, China, at the end of December 2019 (1). The infection rapidly spread, causing the coronavirus disease (COVID-19) pandemic (2). Because SARS-CoV-2 and treatments such as dexamethasone or tocilizumab can impair the immune system, some researchers anticipated the possibility of fungal superinfection among COVID-19 patients (3–6). As of August 2020, researchers have documented COVID-19–associated pulmonary aspergillosis (CAPA) (7–9), invasive candidiasis (10), coccidioidomycosis (11), fusariosis (12), histoplasmosis (13), mucormycosis (14), pneumocystosis (15), and saccharomycosis (16). Varying cumulative rates of CAPA have been described, including rates of 0.7%– 7.7% among COVID-19 patients (17,18), 2.5%–39.1% among ICU patients with COVID-19 (19,20), and 3.2%–29.6% among COVID-19 patients on mechanical COVID-19–Associated Pulmonary Aspergillosis, March–August 2020