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Older age and frailty are predictors of adverse outcomes in patients with COVID-19. In emergency medicine, patients do not present with the diagnosis, but with suspicion of COVID-19. The aim of this study was to assess the association of frailty and age with death or admission to intensive care in patients with suspected COVID-19. This single-centre prospective cohort study was performed in the Emergency Department of a tertiary care hospital. Patients, 65 years and older, with suspected COVID-19 presenting to the Emergency Department during the first wave of the pandemic were consecutively enrolled. All patients underwent nasopharyngeal SARS-CoV-2 PCR swab tests. Patients with a Clinical Frailty Scale (CFS) > 4, were considered to be frail. Associations between age, gender, frailty, and COVID-19 status with the composite adverse outcome of 30-day-intensive-care-admission and/or 30-day-mortality were tested. In the 372 patients analysed, the median age was 77 years, 154 (41.4%) were women, 44 (11.8%) were COVID-19-positive, and 125 (33.6%) were frail. The worst outcome was seen in frail COVID-19-patients with six (66.7%) adverse outcomes. Frailty (CFS > 4) and COVID-19-positivity were associated with an adverse outcome after adjustment for age and gender (frailty: OR 5.01, CI 2.56–10.17, p < 0.001; COVID-19: OR 3.47, CI 1.48–7.89, p = 0.003). Frailty was strongly associated with adverse outcomes and outperformed age as a predictor in emergency patients with suspected COVID-19. [ABSTRACT FROM AUTHOR]

Previous studies have indicated an association between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI) but lacked a control group. The prospective observational COronaVIrus-surviVAl (COVIVA) study performed at the University Hospital, Basel, Switzerland consecutively enrolled patients with symptoms suggestive of COVID-19. We compared patients who tested positive for SARS-CoV-2 with patients who tested negative but with an adjudicated diagnosis of a respiratory tract infection, including pneumonia. The primary outcome measure was death at 30 days, and the secondary outcomes were AKI incidence and a composite endpoint of death, intensive care treatment or rehospitalization at 30 days. Five hundred and seven patients were diagnosed with respiratory tract infections, and of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. The incidence of AKI was higher in patients with COVID-19 (30% versus 12%, p < 0.001), more severe (KDIGO stage 3, 22% versus 13%, p = 0.009) and more often required renal replacement therapy (4.4% versus 0.93%; p = 0.03). The risk of 30-day mortality and a composite endpoint was higher in patients with COVID-19-associated AKI (adjusted hazard ratio (aHR) mortality 3.98, 95% confidence interval (CI) 1.10–14.46, p = 0.036; composite endpoint aHR 1.84, 95% CI 1.02–3.31, p = 0.042). The mortality risk was attenuated when adjusting for disease severity (aHR 3.60, 95% CI 0.93–13.96, p = 0.062). AKI occurs more frequently and with a higher severity in patients with COVID-19 and is associated with worse outcomes. [ABSTRACT FROM AUTHOR]

We investigated the clinical relevance of Dermabacter hominis isolated from samples of 108 patients. Polymicrobial growth was evident in 88% of specimens. Isolation of D. hominis was of definitive or possible significance in only 14% of patients. Vancomycin remains the drug of choice given a penicillin resistance rate of 84%. [ABSTRACT FROM AUTHOR]

Background: Infective endocarditis (IE) caused by gram-negative bacilli is rare. However, the incidence of this severe infection is rising because of the increasing number of persons at risk, such as patients with immunosuppression or with cardiac implantable devices and prosthetic valves. The diagnosis of IE is often difficult, particularly when microorganisms such as Pseudomonas aeruginosa, which rarely cause this infection, are involved. One of the mainstays for the diagnosis of IE are persistently positive blood cultures with the same bacteria, while polymicrobial bacteremia usually points to another cause, e.g. an abscess. The antimicrobial resistance profile of some P. aeruginosa strains may change, falsely suggesting an infection with several strains, thus further increasing the diagnostic difficulties.Case Presentation: A 66-year old male patient who had a transcatheter aortic valve implantation (TAVI) one year previously developed fever seven days after an elective inguinal hernia repair. During the following four weeks, P. aeruginosa with different antibiotic resistance profiles was repeatedly isolated from blood cultures. Repeated trans-esophageal echocardiograms (TEE) were negative and an infection by different P. aeruginosa strains was suspected. Extensive diagnostic workup for an infectious focus was performed with no results. Finally, an oscillating mass on the aortic valve was detected by TEE five weeks after the initial positive blood cultures. P. aeruginosa endocarditis was confirmed by culture of the surgically removed valve. Whole genome sequencing of the last two P. aeruginosa isolates (valve and blood culture) revealed identical strains, with genome mutations for AmpR, AmpD and OprD.Conclusions: The diagnosis of prosthetic valve endocarditis is particularly difficult for several reasons. The modified Duke criteria have a lower sensitivity for patients with prosthetic valve endocarditis and the infection may be caused by "unusual" pathogens such as P. aeruginosa. Patients with repeatedly positive blood cultures should make clinicians suspicious for endocarditis even if imaging studies are negative and if isolated pathogens are "unusual". Repeatedly positive blood cultures for P. aeruginosa should be considered as "persistent bacteremia" (suspicious for IE) even in the presence of different antibiotic susceptibility patterns, since P. aeruginosa might rapidly activate or deactivate resistance mechanisms depending on antibiotic exposition. [ABSTRACT FROM AUTHOR]

Background: A comprehensive in-hospital patient management with reasonable and economic resource allocation is arguably the major challenge of health-care systems worldwide, especially in elderly, frail, and polymorbid patients. The need for patient management tools to improve the transition process and allocation of health care resources in routine clinical care particularly for the inpatient setting is obvious. To address these issues, a large prospective trial is warranted.Methods: The "Integrative Hospital Treatment in Older patients to benchmark and improve Outcome and Length of stay" (In-HospiTOOL) study is an investigator-initiated, multicenter effectiveness trial to compare the effects of a novel in-hospital management tool on length of hospital stay, readmission rate, quality of care, and other clinical outcomes using a time-series model. The study aims to include approximately 35`000 polymorbid medical patients over an 18-month period, divided in an observation, implementation, and intervention phase. Detailed data on treatment and outcome of polymorbid medical patients during the in-hospital stay and after 30 days will be gathered to investigate differences in resource use, inter-professional collaborations and to establish representative benchmarking data to promote measurement and display of quality of care data across seven Swiss hospitals. The trial will inform whether the "In-HospiTOOL" optimizes inter-professional collaboration and thereby reduces length of hospital stay without harming subjective and objective patient-oriented outcome markers.Discussion: Many of the current quality-mirroring tools do not reflect the real need and use of resources, especially in polymorbid and elderly patients. In addition, a validated tool for optimization of patient transition and discharge processes is still missing. The proposed multicenter effectiveness trial has potential to improve interprofessional collaboration and optimizes resource allocation from hospital admission to discharge. The results will enable inter-hospital comparison of transition processes and accomplish a benchmarking for inpatient care quality. [ABSTRACT FROM AUTHOR]

Background: The clinical course of Campylobacter infection varies in symptoms and severity depending on host factors, virulence of the pathogen and initiated therapy. The type VI secretion system (T6SS) has been identified as a novel virulence factor, which mediates contact-dependent injection of enzymes and toxins into competing bacteria or host cells and facilitates the colonisation of a host organism. We aimed to compare the clinical course of Campylobacter infection caused by strains with and without the T6SS and identify possible associations between this putative virulence factor and the clinical manifestations of disease.Methods: From April 2015 to January 2017, patients with detection of Campylobacter spp. were identified at the University Hospital of Basel and the University Children's Hospital of Basel and included in this case-control study. Presence of the T6SS gene cluster was assayed by PCR targeting the hcp gene, confirmed with whole genome sequencing. Pertinent clinical data was collected by medical record review. Differences in disease- and host-characteristics between T6SS-positive (case) and -negative (control) were compared in a uni- and multi-variable analysis. Hospital admission, antibiotic therapy, admission to intensive care unit, development of bacteraemia and in-hospital mortality were considered as clinical endpoints.Results: We identified 138 cases of Campylobacter jejuni infections and 18 cases of Campylobacter coli infections from a paediatric and adult population. Analyses were focused on adult patients with C. jejuni (n = 119) of which 16.8% were T6SS-positive. Comparisons between T6SS-positive and -negative C. jejuni isolates did not reveal significant differences regarding clinical manifestations or course of disease. All clinical endpoints showed a similar distribution in both groups. A higher score in the Charlson Comorbidity Index was associated with T6SS-positive C. jejuni isolates (p < 0.001) and patients were more likely to have a solid organ transplant and to be under immunosuppressive therapy.Conclusions: Our study does not provide evidence that T6SS is associated with a more severe clinical course. Interestingly, T6SS-positive isolates are more commonly found in immunocompromised patients: an observation which merits further investigation. [ABSTRACT FROM AUTHOR]

Objective We aimed to prospectively derive and validate a novel 1h-algorithm using high-sensitivity cardiac troponin I (hs-cTnI) for early rule-out and rule-in of acute myocardial infarction. Methods We performed a prospective multicenter diagnostic study enrolling 1811 patients with suspected acute myocardial infarction. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including coronary angiography, echocardiography, follow-up data, and serial measurements of hs-cTnT (but not hs-cTnI). The hs-cTnI 1h-algorithm, incorporating measurements performed at baseline and absolute changes within 1 hour, was derived in a randomly selected sample of 906 patients (derivation cohort), and then validated in the remaining 905 patients (validation cohort). Results Acute myocardial infarction was the final diagnosis in 18% of patients. After applying the hs-cTnI 1h-algorithm developed in the derivation cohort to the validation cohort, 50.5% of patients could be classified as “rule-out,” 19% as “rule-in,” 30.5% as “observe.” In the validation cohort, the negative predictive value for acute myocardial infarction in the “rule-out” zone was 99.6% (95% confidence interval, 98.4%-100%), and the positive predictive value for acute myocardial infarction in the “rule-in” zone was 73.9% (95% confidence interval, 66.7%-80.2%). Negative predictive value of the 1h-algorithm was higher compared with the classical dichotomous interpretation of hs-cTnI and to the standard of care combining hs-cTnI with the electrocardiogram (both P < .001). Positive predictive value also was higher compared with the standard of care ( P < .001). Conclusion Using a simple algorithm incorporating baseline hs-cTnI values and the absolute change within the first hour allows safe rule-out as well as accurate rule-in of acute myocardial infarction in 70% of patients presenting with suspected acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Abstract: Background: Absolute changes in high-sensitivity cardiac troponin T (hs-cTnT) seem to have higher diagnostic accuracy in the early diagnosis of acute myocardial infarction compared with relative changes. It is unknown whether the same applies to high-sensitivity cardiac troponin I (hs-cTnI) assays and whether the combination of absolute and relative change might further increase accuracy. Methods: In a prospective, international multicenter study, high-sensitivity cardiac troponin (hs-cTn) was measured with 3 novel assays (hs-cTnT, Roche Diagnostics Corp, Indianapolis, Ind; hs-cTnI, Beckman Coulter Inc, Brea, Calif; hs-cTnI, Siemens, Munich, Germany) in a blinded fashion at presentation and after 1 and 2 hours in a blinded fashion in 830 unselected patients with suspected acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Results: The area under the receiver operating characteristic curve for diagnosing acute myocardial infarction was significantly higher for 1- and 2-hour absolute versus relative hs-cTn changes for all 3 assays (P < .001). The area under the receiver operating characteristic curve of the combination of 2-hour absolute and relative change (hs-cTnT 0.98 [95% confidence interval {CI}, 0.97-0.99]; hs-cTnI, Beckman Coulter Inc, 0.97 [95% CI, 0.96-0.99]; hs-cTnI, Siemens, 0.96 [95% CI, 0.93-0.99]) were high and provided some benefit compared with the use of absolute change alone for hs-cTnT, but not for the hs-cTnI assays. Reclassification analysis confirmed the superiority of absolute changes versus relative changes. Conclusions: Absolute changes seem to be the preferred metrics for both hs-cTnT and hs-cTnI in the early diagnosis of acute myocardial infarction. The combination of absolute and relative changes provides a small added value for hs-cTnT, but not for hs-cTnI. [Copyright &y& Elsevier]

Abstract: Objective: The study objective was to compare the incidence and prognosis of acute myocardial infarction when using high-sensitivity cardiac troponin assays instead of a standard cardiac troponin assay for the diagnosis of acute myocardial infarction. Methods: In a prospective international multicenter study, we enrolled 1124 consecutive patients presenting with suspected acute myocardial infarction. Final diagnoses were adjudicated by 2 independent cardiologists 2 times using all available clinical information: first using standard cardiac troponin levels and second using high-sensitivity cardiac troponin T levels for adjudication. Patients were followed up for a mean of 19±9 months. Results: The use of high-sensitivity cardiac troponin T instead of standard cardiac troponin resulted in an increase in the incidence of acute myocardial infarction from 18% to 22% (242 vs 198 patients), a relative increase of 22%. Of the 44 additional acute myocardial infarctions, 35 were type 1 acute myocardial infarctions and 9 were type 2 acute myocardial infarctions. This was accompanied by a reciprocal decrease in the incidence of unstable angina (unstable angina, 11% vs 13%). The most pronounced increase was observed in patients adjudicated with cardiac symptoms of origin other than coronary artery disease with cardiomyocyte damage (83 vs 31 patients, relative increase of 268%). Cumulative 30-month mortality rates were 4.8% in patients without acute myocardial infarction, 16.4% in patients with a small acute myocardial infarction detected only by high-sensitivity cardiac troponin T but not standard cardiac troponin, and 23.9% in patients with a moderate/large acute myocardial infarction according to standard cardiac troponin assays and high-sensitivity cardiac troponin T (P <.001). Conclusions: The introduction of high-sensitivity cardiac troponin assays leads to only a modest increase in the incidence of acute myocardial infarction. The novel sensitive assays identify an additional high-risk group of patients with increased mortality, therefore appropriately classified with acute myocardial infarction (Advantageous Predictors of Acute Coronary Syndromes Evaluation; NCT00470587). [Copyright &y& Elsevier]

Abstract: Background: It is unknown to what extent noncardiac causes, including renal dysfunction, may contribute to high-sensitivity cardiac troponin T levels. Methods: In an observational international multicenter study, we enrolled consecutive patients presenting with acute chest pain to the emergency department. Of 1181 patients enrolled, 572 were adjudicated by 2 independent cardiologists to have a noncardiac cause of chest pain. Multiple linear regression analyses were used to determine the important predictors of log-transformed high-sensitivity cardiac troponin T. Kaplan-Meier curve was used to assess the prognostic significance of high-sensitivity cardiac troponin T>0.014 μg/L (99th percentile). Results: A total of 88 patients (15%) had high-sensitivity cardiac troponin T>0.014 μg/L. Less than 50% of cardiac troponins could be explained by known cardiac or noncardiac diseases. In decreasing order of importance, age, estimated glomerular filtration rate, hypertension, previous myocardial infarction, and chronic kidney disease (adjusted r 2 0.44) emerged as significant factors in linear regression analysis to predict high-sensitivity cardiac troponin T. High-sensitivity cardiac troponin T was best explained by a linear curve with age as≤0.014 μg/L. Patients with high-sensitivity cardiac troponin T levels>0.014 μg/L were at increased risk for all-cause mortality (hazard ratio 3.0; 95% confidence interval, 0.8-10.6; P=.02) during follow-up. Conclusion: Among the known covariates, age and not renal dysfunction is the most important determinant of high-sensitivity cardiac troponin T. Because known cardiac and noncardiac factors, including renal dysfunction, explain less than 50% of high-sensitivity cardiac troponin T levels among patients with a noncardiac cause of chest pain, unknown or underestimated cardiac involvement during the acute presenting condition seems to be the major cause of elevated high-sensitivity cardiac troponin T. [Copyright &y& Elsevier]

"Clinical reasoning" refers to all the thought processes that physicians use to make a diagnosis and determine a treatment and care plan. Artificial intelligence (AI) will enhance, improve, and accelerate human clinical diagnostic thinking, but it is unlikely to replace it. Its application in medicine has the potential to drastically reduce medical diagnostic errors and give doctors more time to care for their patients. Here, we provide an overview of some of the key elements of clinical diagnostic reasoning and the potential impacts of AI on clinical reasoning., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

An outbreak of OXA-23-producing carbapenem-resistant Acinetobacter baumannii amongst ICU-patients with COVID-19 likely occurred by transmission through inanimate surfaces, potentially facilitated by a contaminated positioning pillow shared between patients. Subsequent rapid spread may have been caused by exposure to respiratory secretions contaminating healthcare worker's gloves and gowns during prone positioning., (© 2024. The Author(s).)

This study aimed to determine cefazolin target attainment in patients with invasive Staphylococcus aureus ( S. aureus ) infections and to develop a population pharmacokinetic (PK) model. Adult patients with invasive S. aureus infections treated with cefazolin bolus infusions were included. Unbound and total trough and mid-dose cefazolin concentrations were measured, and strain-specific MICs were determined. The primary outcome was the proportion of patients attaining 100% f T >MIC at all time points evaluated. A population PK model was developed, using non-linear mixed-effects modelling. Overall, 51 patients were included, with a total of 226 unbound and total cefazolin concentrations measured (mean: 4.4 per patient). The median daily dosage in patients with an estimated glomerular filtration rate of >60 mL/min/m 2 was 8 g. The median age was 74 years (interquartile range (IQR) 57-82) and 26% were female. A history of chronic kidney disease and acute kidney injury were present in 10/51 (19.6%) and 6/51 (11.7%), respectively. Achievement of 100% f T >MIC occurred in 86% of the patients and decreased to 45% when a target of 100% f T >4xMIC was evaluated. The mean unbound cefazolin fraction was 27.0% (standard deviation (SD) 13.4). Measured and estimated mean cefazolin trough concentrations differed significantly [13.1 mg/L (SD 23.5) vs. 7.4 mg/L (SD 7.9), p < 0.001]. In the population PK model, elevated estimated creatinine clearance and bolus instead of continuous application were covariates for target non-attainment. In conclusion, cefazolin target achievement was high, and the measurement of the unbound cefazolin concentration may be favored. The Monte Carlo simulations indicated that target attainment was significantly improved with continuous infusion.

The implementation of isolation precautions for patients with suspected Coronavirus Disease 2019 (COVID-19) and pending test results is resource intensive. Due to the limited availability of single-bed rooms at our institution, we isolated patients with suspected COVID-19 together with patients without suspected COVID-19 on-site in multiple-bed rooms until SARS-CoV-2-test results were available. We evaluated the likelihood of SARS-CoV-2 transmission to individuals sharing the room with patients isolated on-site. This observational study was performed at the University Hospital Basel, Switzerland, from 03/20 - 11/20. Secondary attack rates were compared between patients hospitalized in multiple-bed rooms and exposed to individuals subjected to on-site isolation precautions (on-site isolation group), and patients exposed to individuals initially not identified as having COVID-19, and not placed under isolation precautions until the diagnosis was suspected (control group). Transmission events were confirmed by whole-genome sequencing. Among 1,218 patients with suspected COVID-19, 67 (5.5%) tested positive for SARS-CoV-2. Of these, 21 were isolated on-site potentially exposing 27 patients sharing the same room. Median contact time was 12 h (interquartile range 7-18 h). SARS-CoV-2 transmission was identified in none of the patients in the on-site isolation group vs. 10/63 (15.9%) in the control group (p = 0.03). Isolation on-site of suspected COVID-19-patients in multiple-bed rooms avoided single-room occupancy and subsequent in-hospital relocation for many patients without confirmed SARS-CoV-2-infection. The absence of secondary transmission among the exposed patients in the on-site isolation group allows for assessment of the risk/benefit ratio of this strategy given the limitation of a small sample size., (© 2024. The Author(s).)

Study Aims: During the COVID-19 pandemic, there was increasing pressure to be vaccinated to prevent further spread of the virus and improve outcomes. At the same time, part of the population expressed reluctance to vaccination, for various reasons. Only a few studies have compared the perceptions of vaccinated and non-vaccinated patients being treated in hospitals for COVID-19. Our aim was to investigate the association between vaccination status and perceived healthcare-associated discrimination in patients with COVID-19 receiving hospital treatment., Methods: Adult patients presenting to the emergency department or hospitalised for inpatient care due to or with COVID-19 from 1 June to 31 December 2021 in two Swiss hospitals were eligible. The primary endpoint was patients' perceived healthcare-associated discrimination, measured with the Discrimination in Medical Settings (DMS) scale. Secondary endpoints included different aspects of perceived quality of care and symptoms of psychological distress measured with the Hospital Anxiety and Depression Scale., Results: Non-vaccinated patients (n = 113) had significantly higher DMS scores compared to vaccinated patients (n = 80) (mean: 9.54 points [SD: 4.84] vs 7.79 points [SD: 1.85]; adjusted difference: 1.18 [95% CI: 0.04-2.33 points]) and 21 of 80 vaccinated patients felt discriminated against vs 54 of 113 non-vaccinated patients (adjusted OR: 2.09 [95% CI: 1.10-3.99 ]). Non-vaccinated patients reported lower scores regarding respectful treatment by the nursing team (mean: 8.39 points [SD: 2.39] vs 9.30 points [SD: 1.09]; adjusted difference: -0.6 [95% CI: -1.18 - -0.02 points])., Conclusion: We found an association between vaccination status and perceived healthcare-associated discrimination. Healthcare workers should act in a professional manner regardless of a patient's vaccination status; in doing so, they might prevent the creation of negative perceptions in patients.

Infections with carbapenemase-producing Gram-negative bacteria are related to increased morbidity and mortality, yet little is known regarding infections caused by non-beta-lactamase mediated carbapenem-resistant bacteria. Our objective was to identify risk factors for, and the clinical impact of infections caused by carbapenem-resistant carbapenemase-negative Enterobacterales and Pseudomonas aeruginosa. This retrospective matched case-control study was performed at the University Hospital of Basel, Switzerland, in 2016. We focused on other resistance mechanisms by excluding laboratory-confirmed carbapenemase-positive cases. Carbapenem resistance was set as the primary endpoint, and important risk factors were investigated by conditional logistic regression. The clinical impact of carbapenem resistance was estimated using regression models containing the resistance indicator as explanatory factor and adjusting for potential confounders. Seventy-five cases of infections with carbapenem-resistant, carbapenemase-negative bacteria were identified and matched with 75 controls with carbapenem-susceptible infections. The matched data set was well-balanced regarding age, gender, and comorbidity. Duration of prior carbapenem treatment (OR 1.15, [1.01, 1.31]) correlated with resistance to carbapenems. Our study showed that patients with carbapenem-resistant bacteria stayed 1.59 times (CI [0.81, 3.14]) longer in an ICU. The analyzed dataset did not provide evidence for strong clinical implications of resistance to carbapenems or increased mortality. The duration of prior carbapenem treatment seems to be a strong risk factor for the development of carbapenem resistance. The higher risk for a longer ICU stay could be a consequence of a carbapenem resistance. In contrast to carbapenemase-producers, the clinical impact of carbapenamase-negative, carbapenem-resistant strains may be limited. Trial registration: The study design was prospectively approved by the local Ethics Commission on 10.08.2017 (EKNZ BASEC 2017-00222)., (© 2023. The Author(s).)

Background: Few methicillin-resistant Staphylococcus aureus (MRSA) from the early years of its global emergence have been sequenced. Knowledge about evolutionary factors promoting the success of specific MRSA multi-locus sequence types (MLSTs) remains scarce. We aimed to characterize a legacy MRSA collection isolated from 1965 to 1987 and compare it against publicly available international and local genomes., Methods: We accessed 451 historic (1965-1987) MRSA isolates stored in the Culture Collection of Switzerland, mostly collected from the Zurich region. We determined phenotypic antimicrobial resistance (AMR) and performed whole genome sequencing (WGS) using Illumina short-read sequencing on all isolates and long-read sequencing on a selection with Oxford Nanopore Technology. For context, we included 103 publicly available international assemblies from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmec cassette types, AMR, and virulence genes., Results: Among the 451 historic Swiss MRSA isolates, we found 17 sequence types (STs) of which 11 have been previously described. Two STs were novel combinations of known loci and six isolates carried previously unsubmitted MLST alleles, representing five new STs (ST7843, ST7844, ST7837, ST7839, and ST7842). Most isolates (83% 376/451) represented ST247-MRSA-I isolated in the 1960s, followed by ST7844 (6% 25/451), a novel single locus variant (SLV) of ST239. Analysis by cgMLST indicated that isolates belonging to ST7844-MRSA-III cluster within the diversity of ST239-MRSA-III. Early MRSA were predominantly from clonal complex (CC)8. From 1980 to the end of the twentieth century, we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally., Conclusions: The combined analysis of 1761 historic and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss-German and international MRSA across time., (© 2024. The Author(s).)

Background: Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether the severity of the initial PE has an impact on QoL is unknown., Objectives: To evaluate the association between severity of PE and QoL over time., Methods: We prospectively assessed PE-specific QoL using the Pulmonary Embolism Quality of Life (lower scores indicate better QoL) questionnaire and generic QoL using the Short Form 36 (higher scores indicate better QoL) questionnaire at baseline and 3 and 12 months in older patients with acute PE. We examined whether QoL differed by PE severity based on hemodynamic status, simplified Pulmonary Embolism Severity Index (sPESI), right ventricular function, and high-sensitivity troponin T in mixed-effects models, adjusting for known QoL predictors after PE., Results: Among 546 patients with PE (median age, 74 years), severe vs nonsevere PE based on the sPESI was associated with a worse PE-specific (adjusted mean Pulmonary Embolism Quality of Life score difference of 6.1 [95% CI, 2.4-9.8] at baseline, 7.6 [95% CI, 4.0-11.3] at 3 months, and 6.7 [95% CI, 2.9-10.4] at 12 months) and physical generic QoL (adjusted mean Short Form 36 Physical Component Summary score difference of -3.8 [95% CI, -5.5 to -2.1] at baseline, -4.8 [95% CI, -6.4 to -3.1] at 3 months, and -4.1 [95% CI, -5.8 to -2.3] at 12 months). Elevated troponin levels were also associated with lower PE-specific QoL at 3 months and lower physical generic QoL at 3 and 12 months. QoL did not differ by hemodynamic status or right ventricular function., Conclusion: Severe PE based on the sPESI was consistently associated with worse PE-specific and physical generic QoL over time as compared to nonsevere PE., Competing Interests: Declaration of Competing Interests There are no competing interests to disclose.

Purpose: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire © FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples., Methods: Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance., Results: We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7-1.6) for PN-panel-positive only; 2.6 (95% CI 1.3-5.3) for culture-positive only, and 1.6 (95% CI 1.0-2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia., Conclusion: While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia-thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials., (© 2023. The Author(s).)

Background: Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, often caused by uropathogenic Escherichia coli. Multiple bacterial virulence factors or patient characteristics have been linked separately to progressive, more invasive infections. In this study, we aim to identify pathogen- and patient-specific factors that drive the progression to urosepsis by jointly analysing bacterial and host characteristics., Methods: We analysed 1076 E. coli strains isolated from 825 clinical cases with UTI and/or bacteraemia by whole-genome sequencing (Illumina). Sequence types (STs) were determined via srst2 and capsule loci via fastKaptive. We compared the isolates from urine and blood to confirm clonality. Furthermore, we performed a bacterial genome-wide association study (bGWAS) (pyseer) using bacteraemia as the primary clinical outcome. Clinical data were collected by an electronic patient chart review. We concurrently analysed the association of the most significant bGWAS hit and important patient characteristics with the clinical endpoint bacteraemia using a generalised linear model (GLM). Finally, we designed qPCR primers and probes to detect papGII-positive E. coli strains and prospectively screened E. coli from urine samples (n = 1657) at two healthcare centres., Results: Our patient cohort had a median age of 75.3 years (range: 18.00-103.1) and was predominantly female (574/825, 69.6%). The bacterial phylogroups B2 (60.6%; 500/825) and D (16.6%; 137/825), which are associated with extraintestinal infections, represent the majority of the strains in our collection, many of which encode a polysaccharide capsule (63.4%; 525/825). The most frequently observed STs were ST131 (12.7%; 105/825), ST69 (11.0%; 91/825), and ST73 (10.2%; 84/825). Of interest, in 12.3% (13/106) of cases, the E. coli pairs in urine and blood were only distantly related. In line with previous bGWAS studies, we identified the gene papGII (p-value < 0.001), which encodes the adhesin subunit of the E. coli P-pilus, to be associated with 'bacteraemia' in our bGWAS. In our GLM, correcting for patient characteristics, papGII remained highly significant (odds ratio = 5.27, 95% confidence interval = [3.48, 7.97], p-value < 0.001). An independent cohort of cases which we screened for papGII-carrying E. coli at two healthcare centres further confirmed the increased relative frequency of papGII-positive strains causing invasive infection, compared to papGII-negative strains (p-value = 0.033, chi-squared test)., Conclusions: This study builds on previous work linking papGII with invasive infection by showing that it is a major risk factor for progression from UTI to bacteraemia that has diagnostic potential., (© 2023. The Author(s).)

Background: Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether severity of the initial PE has an impact on QoL is unknown., Objective: To evaluate the association between severity of PE and QoL over time., Methods: We prospectively assessed PE-specific QoL using the Pulmonary Embolism Quality of Life (PEmb-QoL; lower scores indicate better QoL) and generic QoL using the Short Form 36 (SF-36; higher scores indicate better QoL) questionnaire at baseline, 3, and 12 months in older patients with acute PE. We examined whether QoL differed by PE severity based on hemodynamic status, simplified Pulmonary Embolism Severity Index (sPESI), right-ventricular function, and high-sensitivity (hs)-troponin T in mixed-effects models, adjusting for known QoL predictors after PE., Results: Among 546 patients with PE (median age 74 years), severe vs. non-severe PE based on the sPESI was associated with a worse PE-specific (adjusted mean PEmb-QoL score difference of 6.1 [95%CI 2.4;9.8] at baseline, 7.6 [95%CI 4.0;11.3] at 3 months, and 6.7 [95%CI 2.9;10.4] at 12 months) and physical generic QoL (adjusted mean SF-36 Physical Component Summary score difference -3.8 [95%CI -5.5;-2.1] at baseline; -4.8 [95%CI -6.4;-3.1] at 3 months; -4.1 [95%CI -5.8;-2.3] at 12 months). Elevated troponin was also associated with lower PE-specific QoL at 3 and physical generic QoL at 3 and 12 months. QoL did not differ by hemodynamic status or right-ventricular function., Conclusion: Severe PE based on the sPESI was consistently associated with worse PE-specific and physical generic QoL over time as compared to non-severe PE., (Copyright © 2023. Published by Elsevier Inc.)

Background: The BioFire® FilmArray® Blood Culture Identification Panel 1 (BF-FA-BCIP) detects microorganisms with high accuracy in positive blood cultures (BC) - a key step in the management of patients with suspected bacteraemia. We aimed to compare the time to optimal antimicrobial therapy (OAT) for the BF-FA-BCIP vs. standard culture-based identification., Methods: In this retrospective single-centre study with a before-after design, 386 positive BC cases with identification by BF-FA-BCIP were compared to 414 controls with culture-based identification. The primary endpoint was the time from BC sampling to OAT. Secondary endpoints were time to effective therapy, length of stay, (re-)admission to ICU, in-hospital and 30-day mortality. Outcomes were assessed using Cox proportional hazard models and logistic regressions., Results: Baseline characteristics of included adult inpatients were comparable. Main sources of bacteraemia were urinary tract and intra-abdominal infection (19.2% vs. 22.0% and 16.8% vs. 15.7%, for cases and controls, respectively). Median (95%CI) time to OAT was 25.5 (21.0-31.2) hours with BF-FA-BCIP compared to 45.7 (37.7-51.4) hours with culture-based identification. We observed no significant difference for secondary outcomes., Conclusions: Rapid microorganism identification by BF-FA-BCIP was associated with a median 20-h earlier initiation of OAT in patients with positive BC. No impact on length of stay and mortality was noted., Trial Registration: Clinicaltrials.gov, NCT04156633, registered on November 5, 2019., (© 2023. The Author(s).)

Aims: There is a lack of national and international publicly available long-term survival outcome data from individual healthcare providers in medical oncology. In this study, the overall survival at a medium-sized medical oncology service at Olten Cantonal Hospital was evaluated and compared as a local benchmark report with national data from the Swiss Cancer Registries. Furthermore, adherence to treatment guidelines was investigated as an additional quality indicator., Methods: The 1- and 5-year overall survival of all patients with breast cancer, testicular cancer, colon cancer, non-small-cell lung cancer, Hodgkin lymphoma, and diffuse large B-cell lymphoma in Switzerland from 2008 to 2017 with at least one outpatient visit at the in-house medical oncology service at Olten Cantonal Hospital was analysed and compared with the specific overall population-based outcome data provided by the National Agency for Cancer Registration (NACR), which were set as a national benchmark. Until 2020, no data from the Canton of Solothurn, to which Olten belongs, were reported to the NACR. Further, adherence to internationally recognized clinical guidelines for stage-specific treatment was assessed., Results: Until September 8, 2020, data on 842 patients with a median follow-up period of 70 months were collected and analysed. The 1- and 5-year overall survival for colon and non-small cell cancer, Hodgkin lymphoma, and diffuse large B-cell lymphoma and the 5-year overall survival for testicular cancer in the Olten cohort did not significantly differ from the NACR data. The 1-year overall survival for testicular cancer was not comparable statistically. The 5-year overall survival for breast cancer (unadjusted for stage) was significantly higher in the NACR collective (84.5%) than in the Olten collective (79.7%) but not for the individual breast cancer stages. The Olten collective included approximately 2.5 times as many patients with stage 4 breast cancer (17.5%) as the NACR collective (6.9%). Approximately 92.4% of the patients in the curative setting and 85.8% of the patients in the palliative setting received first-line treatment according to guidelines., Conclusions: The statistically comparable local 1- and 5-year overall survival of the analysed malignancies, with adjustment for stage for the 5-year overall survival for breast cancer, is in line with the national benchmark. Adherence to treatment guidelines is high.

Background: We sought to decipher transmission pathways in healthcare-associated infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within our hospital by epidemiological work-up and complementary whole genome sequencing (WGS). We report the findings of the four largest epidemiologic clusters of SARS-CoV-2 transmission occurring during the second wave of the pandemic from 11/2020 to 12/2020., Methods: At the University Hospital Basel, Switzerland, systematic outbreak investigation is initiated at detection of any nosocomial case of SARS-CoV-2 infection, as confirmed by polymerase chain reaction, occurring more than five days after admission. Clusters of nosocomial infections, defined as the detection of at least two positive patients and/or healthcare workers (HCWs) within one week with an epidemiological link, were further investigated by WGS on respective strains., Results: The four epidemiologic clusters included 40 patients and 60 HCWs. Sequencing data was available for 70% of all involved cases (28 patients and 42 HCWs), confirmed epidemiologically suspected in house transmission in 33 cases (47.1% of sequenced cases) and excluded transmission in the remaining 37 cases (52.9%). Among cases with identical strains, epidemiologic work-up suggested transmission mainly through a ward-based exposure (24/33, 72.7%), more commonly affecting HCWs (16/24, 66.7%) than patients (8/24, 33.3%), followed by transmission between patients (6/33, 18.2%), and among HCWs and patients (3/33, 9.1%, respectively two HCWs and one patient)., Conclusions: Phylogenetic analyses revealed important insights into transmission pathways supporting less than 50% of epidemiologically suspected SARS-CoV-2 transmissions. The remainder of cases most likely reflect community-acquired infection randomly detected by outbreak investigation. Notably, most transmissions occurred between HCWs, possibly indicating lower perception of the risk of infection during contacts among HCWs., (© 2023. The Author(s).)

Background: Patients may prefer different levels of involvement in decision-making regarding their medical care which may influence their medical knowledge., Objective: We investigated associations of patients' decisional control preference (DCP) with their medical knowledge, ward round performance measures (e.g., duration, occurrence of sensitive topics), and perceived quality of care measures (e.g., trust in the healthcare team, satisfaction with hospital stay)., Design: This is a secondary analysis of a randomized controlled multicenter trial conducted between 2017 and 2019 at 3 Swiss teaching hospitals., Participants: Adult patients that were hospitalized for inpatient care., Main Measures: The primary outcome was patients' subjective average knowledge of their medical care (rated on a visual analog scale from 0 to 100). We classified patients as active, collaborative, and passive according to the Control Preference Scale. Data collection was performed before, during, and after the ward round., Key Results: Among the 761 included patients, those with a passive DCP had a similar subjective average (mean ± SD) knowledge (81.3 ± 19.4 points) compared to patients with a collaborative DCP (78.7 ± 20.3 points) and active DCP (81.3 ± 21.5 points), p = 0.25. Regarding patients' trust in physicians and nurses, we found that patients with an active vs. passive DCP reported significantly less trust in physicians (adjusted difference, - 5.08 [95% CI, - 8.69 to - 1.48 points], p = 0.006) and in nurses (adjusted difference, - 3.41 [95% CI, - 6.51 to - 0.31 points], p = 0.031). Also, patients with an active vs. passive DCP were significantly less satisfied with their hospital stay (adjusted difference, - 7.17 [95% CI, - 11.01 to - 3.34 points], p < 0.001)., Conclusion: Patients with active DCP have lower trust in the healthcare team and lower overall satisfaction despite similar perceived medical knowledge. The knowledge of a patient's DCP may help to individualize patient-centered care. A personalized approach may improve the patient-physician relationship and increase patients' satisfaction with medical care., Trial Registration: ClinicalTrials.gov (NCT03210987)., (© 2022. The Author(s).)

Background: Blood cultures (BC) are critical for the diagnosis of bloodstream infections, pathogen identification, and resistance testing. Guidelines recommend a blood volume of 8-10 mL per bottle as lower volumes result in decreased sensitivity. We aimed to evaluate factors for non-adherence to recommended volumes and assess the effects on diagnostic performance., Methods: From February to April 2020, we measured collected blood volumes by weighing all BC containers from inpatient samples at the University Hospital Basel. Information on BC volumes was merged with clinical and microbiological data, as well as nursing staff schedules. We analyzed factors associated with (i) BC sampling volume, (ii) reaching recommended volumes (≥8 mL), (iii) BC positivity, and (iv) time to positivity using linear and generalized linear mixed effect models., Results: We evaluated a total of 4'118 BC bottles collected from 686 patients. A total of 1'495 (36.3%) of all bottles contained the recommended filling volume of ≥8 mL. Using a central venous and arterial catheter for drawing blood resulted in an increase of filling volume by 0.26 mL (95% CI 0.10, 0.41) and 0.50 mL (95% CI 0.31, 0.69) compared to peripheral venipuncture, respectively. Each additional nursing staff working at the time of blood drawing was associated with 6% higher odds of achieving the recommended filling volume. We found no significant correlation between the filling volume and the positivity rate., Conclusion: Our results indicate critical pre-analytical quality markers linked to BC collection procedures to reach recommended collection volumes. No significant impact on the positivity rate was found., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Romann et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Core body temperature (CBT) is a key vital sign and fever is an important indicator of disease. In the past decade, there has been growing interest for vital sign monitoring technology that may be embedded in wearable devices, and the COVID-19 pandemic has highlighted the need for remote patient monitoring systems. While wrist-worn sensors allow continuous assessment of heart rate and oxygen saturation, reliable measurement of CBT at the wrist remains challenging. In this study, CBT was measured continuously in a free-living setting using a novel technology worn at the wrist and compared to reference core body temperature measurements, i.e., CBT values acquired with an ingestible temperature-sensing pill. Fifty individuals who received the COVID-19 booster vaccination were included. The datasets of 33 individuals were used to develop the CBT prediction algorithm, and the algorithm was then validated on the datasets of 17 participants. Mean observation time was 26.4 h and CBT > 38.0 °C occurred in 66% of the participants. CBT predicted by the wrist-worn sensor showed good correlation to the reference CBT (r = 0.72). Bland-Altman statistics showed an average bias of 0.11 °C of CBT predicted by the wrist-worn device compared to reference CBT, and limits of agreement were - 0.67 to + 0.93 °C, which is comparable to the bias and limits of agreement of commonly used tympanic membrane thermometers. The small size of the components needed for this technology would allow its integration into a variety of wearable monitoring systems assessing other vital signs and at the same time allowing maximal freedom of movement to the user., (© 2023. The Author(s).)

The increasing integration of genomics into routine clinical diagnostics requires reliable computational tools to identify determinants of antimicrobial resistance (AMR) from whole-genome sequencing data. Here, we developed PorinPredict, a bioinformatic tool that predicts defects of the Pseudomonas aeruginosa outer membrane porin OprD, which are strongly associated with reduced carbapenem susceptibility. PorinPredict relies on a database of intact OprD variants and reports inactivating mutations in the coding or promoter region. PorinPredict was validated against 987 carbapenemase-negative P. aeruginosa genomes, of which OprD loss was predicted for 454 out of 522 (87.0%) meropenem-nonsusceptible and 46 out of 465 (9.9%) meropenem-susceptible isolates. OprD loss was also found to be common among carbapenemase-producing isolates, resulting in even further increased MICs. Chromosomal mutations in quinolone resistance-determining regions and OprD loss commonly co-occurred, likely reflecting the restricted use of carbapenems for multidrug-resistant infections as recommended in antimicrobial stewardship programs. In combination with available AMR gene detection tools, PorinPredict provides a robust and standardized approach to link P. aeruginosa phenotypes to genotypes. IMPORTANCE Pseudomonas aeruginosa is a major cause of multidrug-resistant nosocomial infections. The emergence and spread of clones exhibiting resistance to carbapenems, a class of critical last-line antibiotics, is therefore closely monitored. Carbapenem resistance is frequently mediated by chromosomal mutations that lead to a defective outer membrane porin OprD. Here, we determined the genetic diversity of OprD variants across the P. aeruginosa population and developed PorinPredict, a bioinformatic tool that enables the prediction of OprD loss from whole-genome sequencing data. We show a high correlation between predicted OprD loss and meropenem nonsusceptibility irrespective of the presence of carbapenemases, which are a second widespread determinant of carbapenem resistance. Isolates with resistance determinants to other antibiotics were disproportionally affected by OprD loss, possibly due to an increased exposure to carbapenems. Integration of PorinPredict into genomic surveillance platforms will facilitate a better understanding of the clinical impact of OprD modifications and transmission dynamics of resistant clones.

The current data on climate change and environmental degradation are dramatic. The consequences of these changes are already having a significant impact on people's health. Physicians - as advocates of the patients, but also as citizens - have an ethical obligation to be involved in efforts to stop these changes. The European Federation of Internal Medicine (EFIM) strongly encourages the Internal Medicine societies and internists across Europe to play an active role in matters related to climate change and environmental degradation. At a national level, this includes advocating the adoption of measures that reduce greenhouse gas (GHG) emissions and environmental degradation and contributing to policy decisions related to these issues. At a hospital level and in clinical practice, supporting actions by the health sector to reduce its ecological footprint is vital. At the level of EFIM and its associated internal societies, promoting educational activities and developing a toolkit to prepare internists to better care for citizens who suffer from the consequences of climate change. In addition to advocating and implementing effective actions to reduce the ecological footprint of the health industry, recommending the introduction of these themes in scientific programs of Internal Medicine meetings and congresses and the pre- and postgraduate medical training. At a personal level, internists must be active agents in advocating sustainable practices for the environment, increasing the awareness of the community about the health risks of climate change and environmental degradation, and being role models in the adoption of environmentally friendly behaviour., Competing Interests: Declaration of Competing Interest The authors declare they have no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Importance: Whether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial., Objective: To evaluate the outcomes and safety associated with an electronic interprofessional-led discharge planning tool vs standard discharge planning to safely reduce length of stay among medical inpatients with multimorbidity., Design, Setting, and Participants: This multicenter prospective nonrandomized controlled trial used interrupted time series analysis to examine medical acute hospitalizations at 82 hospitals in Switzerland. It was conducted from February 2017 through January 2019. Data analysis was conducted from March 2021 to July 2022., Intervention: After a 12-month preintervention phase (February 2017 through January 2018), an electronic interprofessional-led discharge planning tool was implemented in February 2018 in 7 intervention hospitals in addition to standard discharge planning., Main Outcomes and Measures: Mixed-effects segmented regression analyses were used to compare monthly changes in trends of length of stay, hospital readmission, in-hospital mortality, and facility discharge after the implementation of the tool with changes in trends among control hospitals., Results: There were 54 695 hospitalizations at intervention hospitals, with 27 219 in the preintervention period (median [IQR] age, 72 [59-82] years; 14 400 [52.9%] men) and 27 476 in the intervention phase (median [IQR] age, 72 [59-82] years; 14 448 [52.6%] men) and 438 791 at control hospitals, with 216 261 in the preintervention period (median [IQR] age, 74 [60-83] years; 109 770 [50.8%] men) and 222 530 in the intervention phase (median [IQR] age, 74 [60-83] years; 113 053 [50.8%] men). The mean (SD) length of stay in the preintervention phase was 7.6 (7.1) days for intervention hospitals and 7.5 (7.4) days for control hospitals. During the preintervention phase, population-averaged length of stay decreased by -0.344 hr/mo (95% CI, -0.599 to -0.090 hr/mo) in control hospitals; however, no change in trend was observed among intervention hospitals (-0.034 hr/mo; 95% CI, -0.646 to 0.714 hr/mo; difference in slopes, P = .09). Over the intervention phase (February 2018 through January 2019), length of stay remained unchanged in control hospitals (slope, -0.011 hr/mo; 95% CI, -0.281 to 0.260 hr/mo; change in slope, P = .03), but decreased steadily among intervention hospitals by -0.879 hr/mo (95% CI, -1.607 to -0.150 hr/mo; change in slope, P = .04, difference in slopes, P = .03). Safety analyses showed no change in trends of hospital readmission, in-hospital mortality, or facility discharge over the whole study time., Conclusions and Relevance: In this nonrandomized controlled trial, the implementation of an electronic interprofessional-led discharge planning tool was associated with a decline in length of stay without an increase in hospital readmission, in-hospital mortality, or facility discharge., Trial Registration: isrctn.org Identifier: ISRCTN83274049.

Background: PCR-based testing has transformed the management of suspected respiratory viral infections. We aimed to determine whether multiplex bacterial PCR of bronchoalveolar lavage fluid aids antibiotic stewardship in patients with pneumonia., Methods: This investigator-initiated, multicentre, randomised controlled trial was conducted at two tertiary care centres in Switzerland (University Hospital of Basel and Kantonsspital St Gallen). Patients aged 18 years or older who were admitted to hospital with suspected pneumonia, had a clinical indication for bronchoscopy with bronchoalveolar lavage, and were at risk of Gram-negative bacterial infection were included. Patients were randomly assigned (1:1) to either the multiplex bacterial PCR group or the conventional microbiology control group using a random allocation sequence. Treating physicians were not masked, but the committee panel was masked to patient randomisation. All patients underwent bronchoscopy with bronchoalveolar lavage and samples were assessed by conventional microbiological culture (and additionally, in the PCR group, by multiplex bacterial PCR for Gram-negative rods using the Unyvero Hospitalized Pneumonia [HPN] Cartridge; Curetis, Holzgerlingen, Germany). Patients received empirical antibiotic therapy as clinically indicated by the treating physician. In the PCR group, a recommendation regarding antibiotic therapy was made approximately 5 h after taking the sample. The primary outcome was the time in hours on inappropriate antibiotic therapy from bronchoscopy to discharge or to 30 days after bronchoscopy. This trial was registered with the International Clinical Trials Registry Platform, ISRCTN95828556., Findings: Between May 31, 2017, and Sept 25, 2019, 740 patients with pneumonia were screened for eligibility and 208 were included and randomly assigned to the PCR group (n=100) or conventional microbiology control group (n=108). The mean age of patients was 65·9 years (SD 14·0) and 135 (65%) were male. After daily follow-up until hospital discharge or for a maximum of 30 days, the duration of inappropriate antibiotic treatment was significantly shorter by 38·6 h (95% CI 19·5-57·7) in the PCR group than in the control group (adjusted mean 47·1 h [34·7-59·5] vs 85·7 h [78·8-95·6]; p<0·0001), which translates as a decrease in the duration of inappropriate antibiotic therapy of 45·0% (37·9-52·1). Adverse events due to antimicrobial therapy occurred in nine patients (five [5%] in the PCR group vs four [4%] in the control group) and due to bronchoscopy occurred in four patients (two [1%] vs two [1%]). There were eight (8%) deaths in the PCR group and 11 (10%) in the control group. All in-hospital deaths were attributed to a respiratory cause., Interpretation: Multiplex bacterial PCR examination of bronchoalveolar lavage decreases the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and at risk of Gram-negative rod infection. This approach warrants further consideration in future antibiotic stewardship strategies., Funding: Curetis and the Clinic of Respiratory Medicine and Pulmonary Cell Research, University Hospital Basel, Switzerland., Competing Interests: Declaration of interests DS reports an unrestricted grant from Curetis; grants from AstraZeneca, Weinmann, ResMed, and Boston Scientifics; and honoraria from and participation on data safety monitoring or advisory boards for CSL Behring, Berlin-Chemie Menarini, Novartis, GlaxoSmithKline, AstraZeneca, Vifor, Merck, Chiesi, and Sanofi. MT reports participation on data safety monitoring or advisory boards for Indorsia and GlaxoSmithKline. WCA reports grants from Gottfried and Julia Bangerter-Rhyner Stiftung, Fungal Infection Network of Switzerland, Swiss National Science Foundation, and Kantonsspital St Gallen; honoraria from Pfizer and Medscape; and participation on advisory boards for Merck, Pfizer, and Sanofi. KJ reports honoraria from Schwabe, Curetis, Vertex, and Actelion; support for attending meetings from Vifor and Actelion; and participation on data safety monitoring or advisory boards for Vifor and OM Pharma. HH reports consulting fees from Roche Diagnostics and Molecular Partners; and honoraria from Gilead and Biotest. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Inflammatory biomarkers are associated with severity of coronavirus disease 2019 (COVID-19). However, direct comparisons of their utility in COVID-19 versus other respiratory infections are largely missing., Objective: We aimed to investigate the prognostic utility of various inflammatory biomarkers in COVID-19 compared to patients with other respiratory infections., Materials and Methods: Patients presenting to the emergency department with symptoms suggestive of COVID-19 were prospectively enrolled. Levels of Interleukin-6 (IL-6), c-reactive protein (CRP), procalcitonin, ferritin, and leukocytes were compared between COVID-19, other viral respiratory infections, and bacterial pneumonia. Primary outcome was the need for hospitalisation, secondary outcome was the composite of intensive care unit (ICU) admission or death at 30 days., Results: Among 514 patients with confirmed respiratory infections, 191 (37%) were diagnosed with COVID-19, 227 (44%) with another viral respiratory infection (viral controls), and 96 (19%) with bacterial pneumonia (bacterial controls). All inflammatory biomarkers differed significantly between diagnoses and were numerically higher in hospitalized patients, regardless of diagnoses. Discriminative accuracy for hospitalisation was highest for IL-6 and CRP in all three diagnoses (in COVID-19, area under the curve (AUC) for IL-6 0.899 [95%CI 0.850-0.948]; AUC for CRP 0.922 [95%CI 0.879-0.964]). Similarly, IL-6 and CRP ranged among the strongest predictors for ICU admission or death at 30 days in COVID-19 (AUC for IL-6 0.794 [95%CI 0.694-0.894]; AUC for CRP 0.807 [95%CI 0.721-0.893]) and both controls. Predictive values of inflammatory biomarkers were generally higher in COVID-19 than in controls., Conclusion: In patients with COVID-19 and other respiratory infections, inflammatory biomarkers harbour strong prognostic information, particularly IL-6 and CRP. Their routine use may support early management decisions., Competing Interests: RT has received speaker honoraria/consulting honoraria from Abbott, Amgen, Astra Zeneca, Roche, Siemens, Singulex, and Thermo Scientific BRAHMS, outside the submitted work. GK has received consultant fees from Janssen, outside the submitted work. Authors not named here have disclosed no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims of the Study: In the global COVID-19 pandemic, female sex is associated with comparable infection rates but better outcome. However, most studies lacked appropriate controls. We investigated whether these sex disparity findings are specific to patients with COVID-19 or generalizable to patients presenting to the emergency room (ER) with similar symptoms but no COVID-19., Methods: In this prospective cohort study, consecutive patients presenting with symptoms suggestive of COVID-19 were recruited at the ER of the University Hospital Basel, Switzerland from March to June 2020. Patients were categorized as SARS-CoV-2 positive (cases) or negative (controls) based on nasopharyngeal PCR swab tests. The final clinical diagnosis was determined for all patients. The primary outcome was a composite of intensive care admission, rehospitalization for respiratory distress and all-cause death within 30 days. We used Kaplan-Meier curves and Cox proportional hazards models to explore associations between sex and outcomes., Results: Among 1,081 consecutive ER patients, 191 (18%) tested positive for SARS-CoV-2, with an even sex distribution (17.9% female vs. 17.5% male, p = 0.855). In COVID-19 patients, female sex was associated with lower risk of hospitalization (51% vs. 66%, p = 0.034), lower necessity of haemodynamic support (8% vs. 20%, p = 0.029), lower rates of intubation (10% vs. 21%, p = 0.037) and the primary outcome (18% vs. 31%, p = 0.045; age-adjusted HR 0.536, 95%CI 0.290-0.989, p = 0.046) compared with male sex. Sex disparities were most prominent in patients ≥55 years (HR for composite primary outcome in women 0.415, 95%CI 0.201-0.855, p = 0.017). In contrast to the COVID-19 patients, no sex-specific differences in outcomes were observed in the unselected overall control group (age-adjusted HR 0.844, 95%CI 0.560-1.273, p = 0.419) or in a subgroup of controls with upper respiratory tract infections or pneumonia (age-adjusted HR 0.840, 95%CI 0.418-1.688, p = 0.624)., Conclusion: In this unselected, consecutive cohort study at a tertiary hospital in Switzerland, female sex is associated with better outcome in patients presenting to the ER with COVID-19. These sex disparities seem to be at least partly specific to COVID-19, as they were not observed in comparable controls.

The incidence of infections caused by bacteria that are resistant to antibiotics is constantly increasing. In Europe alone, it has been estimated that each year about 33'000 deaths are attributable to such infections. One important driver of antimicrobial resistance is the use and abuse of antibiotics in human medicine. Inappropriate prescribing of antibiotics is still very frequent: up to 50% of all antimicrobials prescribed in humans might be unnecessary and several studies show that at least 50% of antibiotic treatments are inadequate, depending on the setting. Possible strategies to optimize antibiotic use in everyday clinical practice and to reduce the risk of inducing bacterial resistance include: the implementation of rapid microbiological diagnostics for identification and antimicrobial susceptibility testing, the use of inflammation markers to guide initiation and duration of therapies, the reduction of standard durations of antibiotic courses, the individualization of antibiotic therapies and dosing considering pharmacokinetics/pharmacodynamics targets, and avoiding antibiotic classes carrying a higher risk for induction of bacterial resistance. Importantly, measures to improve antibiotic prescribing and antibiotic stewardship programs should focus on facilitating clinical reasoning and improving prescribing environment in order to remove any barriers to good prescribing., (Copyright © 2022. Published by Elsevier B.V.)

Sleep disordered breathing may be a risk factor or a sequela of COVID-19. https://bit.ly/37v5Gyz., Competing Interests: Conflict of interest: E. Cardoso has nothing to disclose. Conflict of interest: M.J. Herrmann has nothing to disclose. Conflict of interest: L. Grize has nothing to disclose. Conflict of interest: K.E. Hostettler has nothing to disclose. Conflict of interest: S. Bassetti has nothing to disclose. Conflict of interest: M. Siegemund has nothing to disclose. Conflict of interest: N. Khanna has nothing to disclose. Conflict of interest: M. Sava has nothing to disclose. Conflict of interest: G. Sommer has nothing to disclose. Conflict of interest: M. Tamm has nothing to disclose. Conflict of interest: D. Stolz has nothing to disclose., (Copyright ©The authors 2022.)

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.

Background: Arterial stiffness as assessed by Pulse Wave Velocity (PWV) represents an independent predictor of cardiovascular disease. Several dietary compounds and lifestyle factors could influence arterial stiffness. The debate on the significance of the correlation between alcohol consumption and arterial stiffness is still open, given that the relationship is complex and potentially affected by several factors such as alcohol type, consumption levels, gender and age differences., Objective: This systematic literature review aims to examine the evidence supporting an association between alcohol use and PWV, in electronic databases including PubMed/MEDLINE and the Cochrane Library, from January 2010 to November 2020. Screening and full-text reviews were performed by three investigators and data extraction by two. Considering the significant heterogeneity of data only a qualitative analysis (systematic review) was performed., Results: A total of 13 studies met the inclusion criteria. Alcohol consumption was independently associated with arterial stiffness in a J-shaped way in most of the studies included. A benefit of alcohol consumption on arterial stiffness was found in four experimental studies, whilst an unfavorable increasing linear association was found in four others. Associations were confirmed with both oscillometric and tonometric PWV assessment methods. In some studies, a gender and age correlation was found with a more pronounced association in older males. In all studies elevated levels of alcohol consumption were associated with a worsening of arterial stiffness., Conclusions: Despite the variable findings across studies, the current review provides preliminary evidence that light-to-moderate alcohol consumption is associated with arterial stiffness values lower than expected, and evidence that high doses accelerate arterial ageing. These findings could be useful for clinicians who provide recommendations for patients at cardiovascular (CV) risk. Nevertheless, given the heterogeneity of study designs, interventions, measurement methods and statistical evaluations, the protective role of moderate alcohol consumption on arterial stiffness is likely but not certain, warranting additional trials and evidence.

Background: We recently compared the effects of bedside and outside the room ward rounds on patients' knowledge about their medical care. Here, we report preferences of medical and nursing staff members regarding outside versus bedside ward rounds., Methods: Within this ancillary project of a large multicentre randomised controlled trial, we prospectively conducted a survey of medical and nursing staff members participating in the weekly consultant ward rounds in the internal medicine division of three Swiss teaching hospitals between July 2017 and October 2019. Participants were asked about their preferences on outside versus bedside ward rounds. The primary endpoint was satisfaction of healthcare workers with the ward round measured with a visual analogue scale from 0 to 100., Results: Between July 2017 and October 2019, 919 patients were included in the trial, and we received 891 survey responses (nurses 15.6%, residents 26.8%, attending physicians 29.6%, consultants 7.8% and chief physicians 20.2%. In the overall analysis, mean (± standard deviation) satisfaction of healthcare workers was higher with outside the room than bedside ward rounds (78.03 ± 16.96 versus 68.25 ± 21.10 respectively; age-, gender- and centre-adjusted difference of -10.46, 95% confidence interval [CI] -12.73 to -8.19; p <0.001). Healthcare workers reported better time management, more discussion of sensitive topics and less discomfort when case presentations were conducted outside the room. A stratified subgroup analysis considering the profession, however, showed strong differences, with nurses being more satisfied with bedside rounds (69.20 ± 20.32 versus 65.32 ± 20.92, respectively; adjusted difference 4.35, 95% CI -1.79 to 10.51; p <0.001), whereas attending physicians showed higher satisfaction with outside the room rounds (82.63 ± 13.87 versus 66.59 ± 21.82; adjusted difference -16.51, 95% CI -20.29 to -12.72; p = 0.002)., Conclusions: While bedside ward rounds are considered more patient centred and are preferred by the nursing staff, physicians prefer outside the room presentation of patients during ward rounds because of the perceived better discussion of sensitive topics, better time management and less staff discomfort. Continuous training including medical communication techniques may help to increase satisfaction of physicians with bedside ward rounds. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03210987.

Purpose: The purpose of the study was to develop and implement an institution-specific trigger tool based on the Institute for Healthcare Improvement medication module trigger tool (IHI MMTT) in order to detect and monitor ADEs., Methods: We performed an investigator-driven, single-center study using retrospective and prospective patient data to develop ("development phase") and implement ("implementation phase") an efficient, institution-specific trigger tool based on the IHI MMTT. Complete medical data from 1008 patients hospitalized in 2018 were used in the development phase. ADEs were identified by chart review. The performance of two versions of the tool was assessed by comparing their sensitivities and specificities. Tool A employed only digitally extracted triggers ("e-trigger-tool") while Tool B employed an additional manually extracted trigger. The superior tool - taking efficiency into account - was applied prospectively to 19-22 randomly chosen charts per month for 26 months during the implementation phase., Results: In the development phase, 189 (19%) patients had ≥1 ADE (total 277 ADEs). The time needed to identify these ADEs was 15 minutes/chart. A total of 203 patients had ≥1 trigger (total 273 triggers - Tool B). The sensitivities and specificities of Tools A and B were 0.41 and 0.86, and 0.43 and 0.86, respectively. Tool A was more time-efficient than Tool B (4 vs 9 minutes/chart) and was therefore used in the implementation phase. During the 26-month implementation phase, 22 patients experienced trigger-identified ADEs and 529 did not. The median number of ADEs per 1000 patient days was 6 (range 0-13). Patients with at least one ADE had a mean hospital stay of 22.3 ± 19.7 days, compared to 8.0 ± 7.6 days for those without an ADE (p = 2.7×10 -14 )., Conclusion: We developed and implemented an e-trigger tool that was specific and moderately sensitive, gave consistent results and required minimal resources., Competing Interests: Amina El Saghir and Georgios Dimitriou are co-first authors for this study. The authors have no competing interests to declare., (© 2021 El Saghir et al.)

Although initial immunophenotypical studies on peripheral blood and bronchoalveolar lavage samples have provided a glimpse into the immunopathology of COVID-19, analyses of pulmonary draining lymph nodes are currently scarce. 22 lethal COVID-19 cases and 28 controls were enrolled in this study. Pulmonary draining lymph nodes (mediastinal, tracheal, peribronchial) were collected at autopsy. Control lymph nodes were selected from a range of histomorphological sequelae [unremarkable histology, infectious mononucleosis, follicular hyperplasia, non-SARS related HLH, extrafollicular plasmablast activation, non-SARS related diffuse alveolar damage (DAD), pneumonia]. Samples were mounted on a tissue microarray and underwent immunohistochemical staining for a selection of immunological markers and in-situ hybridization for Epstein Barr Virus (EBV) and SARS-CoV-2. Gene expression profiling was performed using the HTG EdgeSeq Immune Response Panel. Characteristic patterns of a dysregulated immune response were detected in COVID-19: 1. An accumulation of extrafollicular plasmablasts with a relative paucity or depletion of germinal centers. 2. Evidence of T-cell dysregulation demonstrated by immunohistochemical paucity of FOXP3+, Tbet+ and LEF1+ positive T-cells and a downregulation of key genes responsible for T-cell crosstalk, maturation and migration as well as a reactivation of herpes viruses in 6 COVID-19 lymph nodes (EBV, HSV). 3. Macrophage activation by a M2-polarized, CD163+ phenotype and increased incidence of hemophagocytic activity. 4. Microvascular dysfunction, evidenced by an upregulation of hemostatic (CD36, PROCR, VWF) and proangiogenic (FLT1, TEK) genes and an increase of fibrin microthrombi and CD105+ microvessels. Taken together, these findings imply widespread dysregulation of both innate and adoptive pathways with concordant microvascular dysfunction in severe COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Haslbauer, Zinner, Stalder, Schneeberger, Menter, Bassetti, Mertz, Went, Matter and Tzankov.)

Commercially available SARS-CoV-2-directed antibody assays may assist in diagnosing past exposure to SARS-CoV-2 antigens. We cross-compared the following eight immunoassays detecting antibodies against SARS-CoV-2 nucleocapsid (N) or spike (S) antigens in three cohorts consisting of 859 samples from 622 patients: (#1) EDI novel coronavirus COVID-19 (Epitope), (#2) RecomWell SARS-CoV-2 (Mikrogen), (#3) COVID-19 ELISA (VirCell), (#4) Elecsys anti-SARS-CoV-2 N (Roche), (#5) Liaison SARS-CoV-2 S1/S2 (DiaSorin), (#6) anti-SARS-CoV-2 ELISA (EuroImmun), (#7) Elecsys anti-SARS-CoV-2 S (Roche), and (#8) Liaison SARS-CoV-2 TrimericS (DiaSorin). In cross-sectional cohort 1 (68 sera from 38 patients with documented SARS-CoV-2 infection), agreement between assays #1 to #6 ranged from 75% to 93%, whereby discordance mostly resulted from N-based assays #1 to #4. In cross-sectional cohort 2 (510 sera from 510 patients; 56 documented, 454 unknown SARS-CoV-2 infection), assays #4 to #6 were analyzed further together with assays #7 and #8, revealing 94% concordance (44 [9%] positives and 485 [85%] negatives). Discordance was highest within 2 weeks after SARS-CoV-2/COVID-19 diagnosis and confirmed in the longitudinal cohort 3 (281 sera from 74 COVID-19 patients), using assays #4, #6, #7, and #8. Subanalysis of 20 (27%) initially seronegative cohort 3 patients revealed assay-dependent 50% and 90% seroconversion rates after 8 to 11 days and 14 to 18 days, respectively. Increasing SARS-CoV-2 antibodies were significantly associated with declining levels of viral loads, lactate dehydrogenase, interleukin-6, and C-reactive protein and preceded clearance of SARS-CoV-2 detection in the upper respiratory tract by approximately 1 week. SARS-CoV-2-specific antibody assays show substantial agreement, but interpretation of qualitative and semiquantitative results depends on the time elapsed postdiagnosis and the choice of viral antigen. Mounting of systemic SARS-CoV-2-specific antibodies may predict recovery from viral injury and clearance of mucosal replication.

Aims: Although the exact factors promoting disease progression in COVID-19 are not fully elucidated, unregulated activation of the complement system (CS) seems to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by SARS-CoV-2. In particular, the lectin pathway (LP) has been implicated in previous autopsy studies. The primary purpose of our study is to investigate the role of the CS in hospitalized COVID-19 patients with varying degrees of disease severity., Methods: In a single-center prospective observational study, 154 hospitalized patients with PCR-confirmed SARS-CoV-2 infection were included. Serum samples on admission to the COVID-19 ward were collected for analysis of CS pathway activities and concentrations of LP proteins [mannose-binding lectin (MBL) and ficolin-3 (FCN-3)] & C1 esterase inhibitor (C1IHN). The primary outcome was mechanical ventilation or in-hospital death., Results: The patients were predominately male and had multiple comorbidities. ICU admission was required in 16% of the patients and death (3%) or mechanical ventilation occurred in 23 patients (15%). There was no significant difference in LP activity, MBL and FCN-3 concentrations according to different peak disease severities. The median alternative pathway (AP) activity was significantly lower (65%, IQR 50-94) in patients with death/invasive ventilation compared to patients without (87%, IQR 68-102, p=0.026). An optimal threshold of <65.5% for AP activity was derived from a ROC curve resulting in increased odds for death or mechanical ventilation (OR 4,93; 95% CI 1.70-14.33, p=0.003) even after adjustment for confounding factors. Classical pathway (CP) activity was slightly lower in patients with more severe disease (median 101% for death/mechanical ventilation vs 109%, p=0.014). C1INH concentration correlated positively with length of stay, inflammatory markers and disease severity on admission but not during follow-up., Conclusion: Our results point to an overactivated AP in critically ill COVID-19 patients in vivo leading to complement consumption and consequently to a significantly reduced AP activity in vitro. The LP does not seem to play a role in the progression to severe COVID-19. Apart from its acute phase reaction the significance of C1INH in COVID-19 requires further studies., Competing Interests: MT reports receiving a grant from the Swiss National Science Foundation, and having research collaborations with Roche, Novartis, and Idorsia (all outside of the submitted work). MO reports receiving grants from the Swiss National Science foundation outside of the submitted work, and consulting fees from Pharming Technologies B.V. during the conduct of the study and grants from Pharming Biotechnologies B.V. outside the submitted work. AE reports receiving grants from the Swiss National Science foundation outside of the submitted work. No conflict of interest for this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Charitos, Heijnen, Egli, Bassetti, Trendelenburg and Osthoff.)

AIMS OF THE STUDY: There is increasing interest in better understanding of long COVID, a condition characterised by long-term sequelae — appearing or persisting after the typical convalescence period — of coronavirus disease 2019 (COVID-19). Herein, we describe long-term outcomes regarding residual symptoms and psychological distress in hospitalised patients 1 year after COVID-19. METHODS: This prospective cohort study included consecutive adult patients hospitalised for confirmed COVID-19 in two Swiss tertiary-care hospitals between March and June 2020. The primary endpoint was evidence of long COVID 1 year after discharge, defined as ≥1 persisting or new symptom related to COVID-19, from a predefined list of symptoms. Secondary endpoints included psychological distress and symptoms of post-traumatic stress disorder (PTSD). RESULTS: Among 90 patients included in the study, 63 (70%) had symptoms of long COVID 1 year after hospitalisation, particularly fatigue (46%), concentration difficulties (31%), shortness of breath (21%) and post-exertion malaise (20%). Three predictors, namely duration of hospitalisation (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.00–1.22; p = 0.041), severity of illness (OR 1.19, 95% CI 1.04–1.37; p = 0.013), and self-perceived overall health status 30 days after hospitalisation (OR 0.97, 95% CI 0.94–1.00; p = 0.027) were associated with long COVID. Regarding secondary endpoints, 16 (18%) experienced psychological distress and 3 (3.3%) patients had symptoms of PTSD. CONCLUSION: A high proportion of COVID-19 patients report symptoms of long COVID 1 year after hospitalisation, which negatively affects their quality of life. The most important risk factors were severe initial presentation of COVID-19 with long hospital stays.

Objectives: Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking., Methods: In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation &lt;93%, respiratory rate &gt;30/min, C-reactive protein levels &gt;75 mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16., Results: Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10&ndash;24) with 24 days (IQR 14&ndash;32) in ICU patients and 10 days (IQR 7&ndash;15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients., Conclusions: In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function., Trial Registration: ClinicalTrials.gov NCT04351503.

Aims: The aim of this study was to analyse the demographics, risk factors and in-hospital mortality rates of patients admitted with coronavirus disease 2019 (COVID-19) to a tertiary care hospital in Switzerland., Methods: In this single-centre retrospective cohort study at the University Hospital Basel, we included all patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection hospitalised from 27 February 2020 to 10 May 2021. Patients&rsquo; characteristics were extracted from the electronic medical record system. The primary outcome of this study was temporal trends of COVID-19-related in-hospital mortality. Secondary outcomes were COVID-19-related mortality in patients hospitalised on the intensive care unit (ICU), admission to ICU, renal replacement therapy and length of hospital stay, as well as a descriptive analysis of risk factors for in-hospital mortality., Results: During the study period we included 943 hospitalisations of 930 patients. The median age was 65 years (interquartile range [IQR] 53&ndash;76) and 63% were men. The numbers of elderly patients, patients with multiple comorbidities and need for renal replacement therapy decreased from the first and second to the third wave. The median length of stay and need for ICU admission were similar in all waves. Throughout the study period 88 patients (9.3%) died during the hospital stay. Crude in-hospital mortality was similar over the course of the first two waves (9.5% and 10.2%, respectively), whereas it decreased in the third wave (5.4%). Overall mortality in patients without comorbidities was low at 1.6%, but it increased in patients with any comorbidity to 12.6%. Predictors of all-cause mortality over the whole period were age (adjusted odds ratio [aOR] per 10-year increase 1.81, 95% confidence interval [CI] 1.45&ndash;2.26; p &lt;0.001), male sex (aOR 1.68, 95% CI 1.00&ndash;2.82; p = 0.048), immunocompromising condition (aOR 2.09, 95% CI 1.01&ndash;4.33; p = 0.048) and chronic kidney disease (aOR 2.25, 95% CI 1.35&ndash;3.76; p = 0.002)., Conclusion: In our study in-hospital mortality was 9.5%, 10.2% and 5.4% in the first, second and third waves, respectively. Age, immunocompromising condition, male sex and chronic kidney disease were factors associated with in-hospital mortality. Importantly, patients without any comorbidity had a very low in-hospital mortality regardless of age.

Aim of the Study: Teaching is one of the three pillars of medical-academic activity, alongside patient care and research. The aim of our study was to assess current teaching practice in the medical departments of the University Hospital Basel, Switzerland, in order to organise a faculty development programme tailored to local needs., Methods: We performed a cross-sectional online survey among the teaching faculty and the residents. For both groups, we assessed their estimation of the general importance and perceived frequency of various teaching formats in everyday practice. Additionally, we asked the senior physicians to evaluate their teaching competencies and the residents to state their opinion on factors promoting a positive learning experience., Results: Twenty-eight of 34 senior physicians (82%) and 48 of 90 residents (53%) participated in the study. Both groups broadly agreed on the importance of various teaching formats for the professional development of physicians, placing particular importance on bedside teaching, providing feedback, teaching during case discussions, and observation and modeling. However, the residents perceived that they obtained less teaching, feedback and support than the senior physicians perceived they were giving. Overall, teaching during case discussions represented the format most often applied, and it was also the one in which the senior physicians felt most competent. Residents claimed &ldquo;time&rdquo; to be the most important factor promoting a positive learning experience, followed by a positive attitude und the personal characteristics of the supervisor., Conclusion: Our study shows that, despite being an integral part of everyday work at a university clinic, many aspects of current teaching practice allow discussion on possibilities of adaptations and improvement. Evaluation of current teaching practice provides the basis for designing a faculty development programme tailored to specific needs.

A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8 ) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima's D = -2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.

Objective: The pandemic of coronavirus disease (COVID-19) has rapidly spread globally and infected millions of people. The prevalence and prognostic impact of dysnatremia in COVID-19 is inconclusive. Therefore, we investigated the prevalence and outcome of dysnatremia in COVID-19., Design: The prospective, observational, cohort study included consecutive patients with clinical suspicion of COVID-19 triaged to a Swiss Emergency Department between March and July 2020., Methods: Collected data included clinical, laboratory and disease severity scoring parameters on admission. COVID-19 cases were identified based on a positive nasopharyngeal swab test for SARS-CoV-2, patients with a negative swab test served as controls. The primary analysis was to assess the prognostic impact of dysnatremia on 30-day mortality using a cox proportional hazard model., Results: 172 (17%) cases with COVID-19 and 849 (83%) controls were included. Patients with COVID-19 showed a higher prevalence of hyponatremia compared to controls (28.1% vs 17.5%, P < 0.001); while comparable for hypernatremia (2.9% vs 2.1%, P = 0.34). In COVID-19 but not in controls, hyponatremia was associated with a higher 30-day mortality (HR: 1.4, 95% CI: 1.10-16.62, P = 0.05). In both groups, hypernatremia on admission was associated with higher 30-day mortality (COVID-19 - HR: 11.5, 95% CI: 5.00-26.43, P < 0.001; controls - HR: 5.3, 95% CI: 1.60-17.64, P = 0.006). In both groups, hyponatremia and hypernatremia were significantly associated with adverse outcome, for example, intensive care unit admission, longer hospitalization and mechanical ventilation., Conclusion: Our results underline the importance of dysnatremia as predictive marker in COVID-19. Treating physicians should be aware of appropriate treatment measures to be taken for patients with COVID-19 and dysnatremia.