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Zusammenfassung. Ein Patient stellt sich mit einer Allgemeinzustandsverschlechterung, Schüttelfrost und Belastungsdyspnoe vor. Bei St.n. Aortenklappenersatz in der Vorgeschichte besteht der Verdacht auf eine infektiöse Endokarditis, die jedoch aufgrund zunächst negativer Bildgebung mittels TEE und bei negativen Blutkulturen nicht bestätigt werden kann. Eine verlängerte Bebrütung der Blutkulturen, das Auftreten embolischer Komplikationen sowie ein typischer Befund im PET-CT ermöglicht schliesslich die Diagnose einer Kunstklappenendokarditis mit Cutibacterium acnes.

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.

Urinary tract infections are extremely common and often caused by Escherichia coli. Bacterial virulence factors and patient characteristics have been linked separately to progressive, invasive infection. The interaction of these factors has however rarely been considered. We whole genome sequenced 1076 E. coli isolates recovered from urine- or blood culture samples from 825 clinical cases. The majority of isolates belonged to the phylogroups B2 and D and encoded polysaccharide capsules. In line with previous studies, our bGWAS identified papGII to be associated with bacteraemia. In a generalised linear model correcting for patient characteristics, papGII was substantiated as a major contributor to invasive infection. Further, an independent cohort of 1,657 urine samples was PCR screened for papGII carrying E. coli, confirming the increased relative frequency of papGII+ strains to cause invasive infection. This study builds on previous work linking papGII with invasive infection by showing that it is a patient-independent risk factor that has diagnostic potential.

Few methicillin-resistantStaphylococcus 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.We accessed 451 ancient (1965-1987) Swiss MRSA isolates, stored in the Culture Collection of Switzerland. We determined phenotypic antimicrobial resistance (AMR) and performed 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 genomes from 1960 to 1992 and sequenced 1207 modern Swiss MRSA isolates from 2007 to 2022. We analyzed the core genome (cg)MLST and predicted SCCmeccassette types, AMR, and virulence genes.Among the 451 ancient 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-IIII. Early MRSA were predominantly from clonal complex (CC) 8. From 1980 to the end of the 20thcentury we observed that CC22 and CC5 as well as CC8 were present, both locally and internationally.The combined analysis of 1761 ancient and contemporary MRSA isolates across more than 50 years uncovered novel STs and allowed us a glimpse into the lineage flux between Swiss and international MRSA across time.

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.

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.

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.

Introduction: Since angiotensin converting enzyme-2 (ACE2) was discovered as an essential entry factor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2), there has been conflicting evidence regarding the role of renin-angiotensin-aldosterone system (RAAS) in COVID-19. This study elucidates pulmonary expression patterns SARS-CoV-2 entry factors (ACE2 and transmembrane protease serine subtype 2, TMPRSS2) and RAAS components in lethal COVID-19. Methods: Lung tissue from COVID-19 autopsies (n = 27) and controls (n = 23) underwent immunohistochemical staining for RAAS components (angiotensin receptors 1 and 2, ACE2 and Mas-receptor) and bradykinin receptors 1 and 2. Staining of individual cellular populations (alveolar pneumocytes [ALV], desquamated cells [DES] and endothelium [END]) was measured by a binary scale (positive/negative). SARS-CoV-2 was detected using immunohistochemistry against nucleocapsid protein, in-situ hybridization and quantitative reverse transcriptase polymerase chain reaction. Gene expression profiling for ACE2, ACE and TMPRSS2 was performed. Results: Subtle differences were observed when comparing COVID-19 patients and controls not reaching statistical significance, such as a higher incidence of ACE2-positivity in END (52% vs. 39%) but lower positivity in ALVs (63% vs. 70%) and an overall downregulation of ACE2 gene expression (0.25 vs. 0.55). However, COVID-19 patients with RAAS inhibitor (RAASi) intake had significantly shorter hospitalization times (5 vs. 12 days), higher viral loads (57,517 vs. 15,980/106 RNase P-gene copies) and decreased ACE/ACE2-expression ratios (4.58 vs. 11.07) than patients without. TMPRSS2 expression was significantly (1.76-fold) higher in COVID-19 patients than controls. Conclusion: Our study delineates the heterogeneous expression patterns of RAAS components in the lungs, which vary amongst cellular populations, and implies that COVID-19 patients with RAASi-intake present with a more rapid disease progression, although this requires further investigation.

Aim: Patients receiving oral anticoagulants with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have an increased risk of gastrointestinal bleeding (GIB). We compared cases of GIB associated with VKAs and DOACs in terms of risk factors, scores, timing, location, severity, and outcome.Methods: Data from patients treated at a university hospital in Switzerland for GIB under VKA and DOACs between 2012 and 2018 were analyzed in this investigator-driven, retrospective, single-center study. Results: A total of 248 patients (110 males; median age, 80 years; 134 VKA, 114 DOAC) were included. No significant differences in age, weight or sex were observed. The propensity of the VKA group for risk factors such as comorbidities, interacting medications, or a high risk for bleeding (HAS-BLED score) was higher than that of the DOAC group. 56% of the VKA-treated patients had a supratherapeutic INR, and 25% in the DOAC group received an unlicensed dose. Significantly more patients in the DOAC group were not formally overdosed with OAC whilst receiving amiodarone compared to the VKA group (57% vs. 18%, respectively, p = 0.03). Latency between the documented start of oral anticoagulation and GIB was shorter in the DOAC group (median 3 months) than in the VKA group (median 23.5 months, p

Better Late than Never - Fever of Unknown Origin in a Patient with a Prosthetic Valve

Background: In real-life settings, guidelines frequently cannot be followed since many patients are multimorbid and/or elderly or have other complicating conditions which carry an increased risk of drug-drug interactions. This document aimed to adapt recommendations from existing clinical practice guidelines (CPGs) to assist physicians' decision-making processes concerning specific and complex scenarios related to acute CAP.Methods: The process for the adaptation procedure started with the identification of unsolved clinical questions (PICOs) in patients with CAP and continued with critically appraising the updated existing CPGs and choosing the recommendations, which are most applicable to these specific scenarios.Results: Seventeen CPGs were appraised to address five PICOs. Twenty-seven recommendations were endorsed based on 7 high, 9 moderate, 10 low, and 1 very low-quality evidence. The most valid recommendations applicable to the clinical practice were the following ones: Respiratory virus testing is strongly recommended during periods of increased respiratory virus activity. Assessing the severity with a validated prediction rule to discriminate where to treat the patient is strongly recommended along with reassessing the patient periodically for improvement as expected. In adults with multiple comorbidities, polypharmacy, or advanced age, it is strongly recommended to check for possible drug interactions before starting treatment. Strong graded recom-mendations exist on antibiotic treatment and its duration. Recommendations on the use of biomarkers such as C -reactive protein or procalcitonin to improve severity assessment are reported.Conclusion: This document provides a simple and reliable updated guide for clinical decision-making in the management of complex patients with multimorbidity and CAP in the real-life setting.

BackgroundThromboinflammation may influence disease outcome in COVID-19. We aimed to evaluate complement and endothelial cell activation in patients with confirmed COVID-19 compared to controls with clinically suspected but excluded SARS-CoV-2 infection.MethodsIn a prospective, observational, single-center study, patients presenting with clinically suspected COVID-19 were recruited in the emergency department. Blood samples on presentation were obtained for analysis of C5a, sC5b-9, E-selectin, Galectin-3, ICAM-1 and VCAM-1.Results153 cases and 166 controls (suffering mainly from non-SARS-CoV-2 respiratory viral infections, non-infectious inflammatory conditions and bacterial pneumonia) were included. Hospital admission occurred in 62% and 45% of cases and controls, respectively. C5a and VCAM-1 concentrations were significantly elevated and E-selectin concentrations decreased in COVID-19 out- and inpatients compared to the respective controls. However, relative differences in outpatients vs. inpatients in most biomarkers were comparable between cases and controls. Elevated concentrations of C5a, Galectin-3, ICAM-1 and VCAM-1 on presentation were associated with the composite outcome of ICU- admission or 30-day mortality in COVID-19 and controls, yet more pronounced in COVID-19. C5a and sC5b-9 concentrations were significantly higher in COVID-19 males vs. females, which was not observed in the control group.ConclusionsOur data indicate an activation of the complement cascade and endothelium in COVID-19 beyond a nonspecific inflammatory trigger as observed in controls (i.e., “over”-activation).

Background: Elevated D-dimer levels have been observed in COVID-19 and are of prognostic value, but have not been compared to an appropriate control group. Methods: Observational cohort study including emergency patients with suspected or confirmed COVID-19. Logistic regression defined the association of D-dimer levels, COVID-19 positivity, age, and gender with 30-day-mortality. Results: 953 consecutive patients (median age 58, 43% women) presented with suspected COVID-19: 12 (7.4%) patients with confirmed SARS-CoV-2-infection died, compared with 28 (3.5%) patients without SARS-CoV-2-infection. Overall, most (56%) patients had elevated D-dimer levels (≥0.5mg/l). Age (OR 1.07, CI 1.05-1.10), D-dimer levels ≥0.5mg/l (OR 2.44, CI 0.98-7.39), and COVID-19 (OR 2.79, CI 1.28-5.80) were associated with 30-day-mortality. Conclusion: D-dimer levels are effective prognosticators in both patient groups.

Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics.In a single-center hypothesis-generating prospective case-control study with 1:2 matched dCCP recipients to controls according to disease severity at day 1, hospitalized adults with COVID-19 pneumonia received 2 × 200 ml pathogen-reduced treated dCCP from 2 different donors. We evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in COVID-19 convalescent plasma donors and recipients using multiple antibody assays including a Coronavirus antigen microarray (COVAM), and binding and neutralizing antibody assays. Outcomes were dCCP characteristics, antibody responses, 28-day mortality, and dCCP -related adverse events in recipients.Eleven of 13 dCCPs (85%) contained neutralizing antibodies (nAb). PRT did not affect dCCP antibody activity. Fifteen CCP recipients and 30 controls (median age 64 and 65 years, respectively) were enrolled. dCCP recipients received 2 dCCPs from 2 different donors after a median of one hospital day and 11 days after symptom onset. One dCCP recipient (6.7%) and 6 controls (20%) died (p = 0.233). We observed no dCCP-related adverse events. Transfusion of unselected dCCP led to heterogeneous SARS CoV-2 antibody responses. COVAM clustered dCCPs in 4 distinct groups and showed endogenous immune responses to SARS-CoV-2 antigens over 14-21 days post dCCP in all except 4 immunosuppressed recipients.PRT did not impact dCCP anti-virus neutralizing activity. Transfusion of unselected dCCP did not impact survival and had no adverse effects. Variable dCCP antibodies and post-transfusion antibody responses indicate the need for controlled trials using well-characterized dCCP with informative assays.

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.

Objectives SARS-CoV-2 may cause acute lung injury, and secondary infections are thus relevant complications in patients with COVID-19 pneumonia. However, detailed information on community- and hospital-acquired infections among patients with COVID-19 pneumonia is scarce. Methods We identified 220 SARS-CoV-2-positive patients hospitalized at the University Hospital Basel, Switzerland (between 25 February and 31 May 2020). We excluded patients who declined the general consent (n = 12), patients without clinical evidence of pneumonia (n = 29), and patients hospitalized for n = 17). We evaluated the frequency of community- and hospital-acquired infections using respiratory and blood culture materials with antigen, culture-based, and molecular diagnostics. For ICU patients, all clinical and microbial findings were re-evaluated interdisciplinary (intensive care, infectious disease, and clinical microbiology), and agreement reached to classify patients with infections. Results In the final cohort of 162 hospitalized patients (median age 64.4 years (IQR, 50.4–74.2); 61.1% male), 41 (25.3%) patients were admitted to the intensive care unit, 34/41 (82.9%) required mechanical ventilation, and 17 (10.5%) of all hospitalized patients died. In total, 31 infections were diagnosed including five viral co-infections, 24 bacterial infections, and three fungal infections (ventilator-associated pneumonia, n = 5; tracheobronchitis, n = 13; pneumonia, n = 1; and bloodstream infection, n = 6). Median time to respiratory tract infection was 12.5 days (IQR, 8–18) and time to bloodstream infection 14 days (IQR, 6–30). Hospital-acquired bacterial and fungal infections were more frequent among ICU patients than other patients (36.6% vs. 1.7%). Antibiotic or antifungal treatment was administered in 71 (43.8%) patients. Conclusions Community-acquired viral and bacterial infections were rare among COVID-19 pneumonia patients. By contrast, hospital-acquired bacterial or fungal infections were frequently complicating the course among ICU patients.

OBJECTIVES: Detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is key to the clinical and epidemiological assessment of CoVID-19. We cross-validated manual and automated high-throughput testing for SARS-CoV-2-RNA, evaluated SARS-CoV-2 loads in nasopharyngeal-oropharyngeal swabs (NOPS), lower respiratory fluids, and plasma, and analyzed detection rates after lockdown and relaxation measures. METHODS: Basel-S-gene, Roche-E-gene, and Roche-cobas®6800-Target1 and Target2 were prospectively validated in 1344 NOPS submitted during the first pandemic peak (Week 13). Follow-up cohort (FUP) 1, 2, and 3 comprised 10,999, 10,147, and 19,389 NOPS submitted during a 10-week period until Weeks 23, 33, and 43, respectively. RESULTS: Concordant results were obtained in 1308 cases (97%), including 97 (9%) SARS-CoV-2-positives showing high quantitative correlations (Spearman's r > .95; p < .001) for all assays and high precision by Bland-Altman analysis. Discordant samples (N = 36, 3%) had significantly lower SARS-CoV-2 loads (p < .001). Following lockdown, detection rates declined to

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).

(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: 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

Respiratory infections following status epilepticus (SE) are frequent, and associated with higher mortality, prolonged ICU stay, and higher rates of refractory SE. Lack of airway protection may contribute to respiratory infectious complications. This study investigates the order and frequency of physicians treating a simulated SE following a systematic Airways-Breathing-Circulation-Disability-Exposure (ABCDE) approach, identifies risk factors for non-adherence, and analyzes the compliance of an ABCDE guided approach to SE with current guidelines. We conducted a prospective single-blinded high-fidelity trial at a Swiss academic simulator training center. Physicians of different affiliations were confronted with a simulated SE. Physicians (n = 74) recognized SE and performed a median of four of the five ABCDE checks (interquartile range 3–4). Thereof, 5% performed a complete assessment. Airways were checked within the recommended timeframe in 46%, breathing in 66%, circulation in 92%, and disability in 96%. Head-to-toe (exposure) examination was performed in 15%. Airways were protected in a timely manner in 14%, oxygen supplied in 69%, and antiseizure drugs (ASDs) administered in 99%. Participants’ neurologic affiliation was associated with performance of fewer checks (regression coefficient −0.49; p = 0.015). We conclude that adherence to the ABCDE approach in a simulated SE was infrequent, but, if followed, resulted in adherence to treatment steps and more frequent protection of airways.

ImportanceWhether interprofessional collaboration is effective and safe in decreasing hospital length of stay remains controversial.ObjectiveTo 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 ParticipantsThis 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.InterventionAfter 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 MeasuresMixed-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.ResultsThere 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 RelevanceIn 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 Registrationisrctn.org Identifier: ISRCTN83274049

For some patients, survival with good neurologic function after cardiopulmonary resuscitation (CPR) is highly unlikely, thus CPR would be considered medically futile. Yet, in clinical practice, there are no well-established criteria, guidelines or measures to determine futility. We aimed to investigate how medical futility for CPR in adult patients is defined, measured, and associated with do-not-resuscitate (DNR) code status as well as to evaluate through meta-analysis the predictive value of clinical risk scores.; We searched Embase, PubMed, CINAHL, and PsycINFO from the inception of each database up to January 22, 2021. Data were pooled using a fixed-effects model. Data collection and reporting followed the PRISMA guidelines.; Thirty-one studies were included in the systematic review and 11 in the meta-analysis. Medical futility defined by risk scores was associated with a significantly higher risk of in-hospital mortality (5 studies, 3102 participants with Pre-Arrest Morbidity (PAM) and Prognosis After Resuscitation (PAR) score; overall RR 3.38 [95% CI 1.92-5.97]) and poor neurologic outcome/in-hospital mortality (6 studies, 115213 participants with Good Outcome Following Attempted Resuscitation (GO-FAR) and Prediction of Outcome for In-Hospital Cardiac Arrest (PIHCA) score; RR 6.93 [95% CI 6.43-7.47]). All showed high specificity (>90%) for identifying patients with poor outcome.; There is no international consensus and a lack of specific definitions of CPR futility in adult patients. Clinical risk scores might aid decision-making when CPR is assumed to be futile. Future studies are needed to assess their clinical value and reliability as a measure of futility regarding CPR.

Amina El Saghir,1,&ast; Georgios Dimitriou,2,&ast; Miriam Scholer,3 Ioanna Istampoulouoglou,1 Patrick Heinrich,3 Klaus Baumgartl,3 René Schwendimann,4 Stefano Bassetti,2 Anne Leuppi-Taegtmeyer1 1Department of Clinical Pharmacology & Toxicology, University Hospital and University of Basel, Basel, Switzerland; 2Division of Internal Medicine, University Hospital and University of Basel, Basel, Switzerland; 3Department of Information Technology, University Hospital Basel, Basel, Switzerland; 4Patient Safety Office, University Hospital Basel, Basel, Switzerland&ast;These authors contributed equally to this workCorrespondence: Anne Leuppi-TaegtmeyerDepartment of Clinical Pharmacology & Toxicology, University Hospital Basel, Schanzenstrasse 55, Basel, CH4031, SwitzerlandTel +41 61 328 68 48Fax +41 61 265 45 60Email anne.leuppi-taegtmeyer@usb.chPurpose: 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.Keywords: electronic health record, medication module, drug safety, patient safety, digital health

IntroductionCOVID-19 vaccines significantly reduce SARS-CoV-2 (SCoV2)-related hospitalization and mortality in randomized controlled clinical trials, as well as in real-world effectiveness against different circulating SCoV2-lineages. However, some vaccine recipients show breakthrough infection and it remains unknown, which host and viral factors contribute to this risk and how many resulted in severe outcomes. Our aim was to identify demographic and clinical risk factors for SCoV2 breakthrough infections and severe disease in fully vaccinated individuals and to compare patient characteristics in breakthrough infections caused by SCoV2 Alpha or Delta variant.MethodsWe conducted an exploratory retrospective case-control study from 28th of December to 25th of October 2021 dominated by the Delta SCoV2 variant. All cases of infection had to be reported by law to the local health authorities. Vaccine recipients’ data was anonymously available from the national Vaccination Monitoring Data Lake and the main local vaccine center. We compared anonymized patients’ characteristics of breakthrough infection (n=492) to two overlapping control groups including all vaccine recipients from the Canton of Basel-City (group 1 n=126’586 and group 2 n=109’382). We also compared patients with breakthrough infection caused by the Alpha to Delta variant. We used different multivariate generalized linear models (GLM).ResultsWe found only 492/126’586 (0.39%) vaccine recipients with a breakthrough infection after vaccination during the 10 months observational period. Most cases were asymptomatic or mild (478/492 97.2%) and only very few required hospitalization (14/492, 2.8%). The time to a positive SCoV2 test shows that most breakthrough infections occurred between a few days to about 170 days after full vaccination, with a median of 78 days (interquartile range, IQR 47-124 days). Factors associated with a lower odds for breakthrough infection were: age (OR 0.987, 95%CI 0.983-0.992), previous COVID-19 infection prior to vaccination (OR 0.296, 95%CI 0.117-0.606), and (self-declared) serious side-effects from previous vaccines (OR 0.289, 95%CI 0.033-1.035). Factors associated with a higher odds for breakthrough infection were: vaccination with the Pfizer/BioNTech vaccine (OR 1.459, 95%CI 1.238-1.612), chronic disease as vaccine indication (OR 2.109, 95%CI 1.692-2.620), and healthcare workers (OR 1.404, 95%CI 1.042-1.860). We did not observe a significantly increased risk for immunosuppressed patients (OR 1.248, 95% CI 0.806-1.849).ConclusionsOur study shows that breakthrough infections are rare and show mild illness, but that it occurs early after vaccination with more than 50% of cases within 70 to 80 days post-full vaccination. This clearly implies that boost vaccination should be much earlier initiated compared to the currently communicated 180-day threshold. This has important implications especially for risk groups associated with more frequent breakthrough infections such as healthcare workers, and people in high-risk care facilities. Due to changes in the epidemiological dynamic with new variants emerging, continuous monitoring of breakthrough infections is helpful to provide evidence on booster vaccines and patient groups at risk for potential complications.

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.

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.

AimsAlthough 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.MethodsIn 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.ResultsThe 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 ConclusionOur 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.

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.

Background Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort. Objective To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care. Design Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987). Setting 3 Swiss teaching hospitals. Patients Adult medical patients who were hospitalized. Intervention Patients were randomly assigned to bedside or outside the room case presentation. Measurements The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care. Results Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P Limitation Only Swiss hospitals and medical patients were included. Conclusion Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings. Primary funding source Swiss National Foundation (10531C_ 182422).

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 “time” 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.

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.

Most studies investigating early risk predictors in coronavirus disease 19 (COVID-19) lacked comparison with controls. We aimed to assess and directly compare outcomes and risk predictors at time of emergency department (ED) presentation in COVID-19 and controls. Consecutive patients presenting to the ED with suspected COVID-19 were prospectively enrolled. COVID-19-patients were compared with (i) patients tested negative (overall controls) and (ii) patients tested negative, who had a respiratory infection (respiratory controls). Primary outcome was the composite of intensive care unit (ICU) admission and death at 30 days. Among 1081 consecutive cases, 191 (18%) were tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 890 (82%) were tested negative (overall controls), of which 323 (30%) had a respiratory infection (respiratory controls). Incidence of the composite outcome was significantly higher in COVID-19 (23%) as compared with the overall control group (10%, adjusted-HR 2.45 (95%CI, 1.61–3.74), p &lt, 0.001) or the respiratory control group (10%, adjusted-HR 2.93 (95%CI, 1.66–5.17), p &lt, 0.001). Blood oxygen saturation, age, high-sensitivity troponin, c-reactive protein, and lactate dehydrogenase were identified as the strongest predictors of poor outcome available at time of ED presentation in COVID-19 with highly comparable prognostic utility in overall and respiratory controls. In conclusion, patients presenting to the ED with COVID-19 have a worse outcome than controls, even after adjustment for differences in baseline characteristics. Most predictors of poor outcome in COVID-19 were not restricted to COVID-19, but of comparable prognostic utility in controls and therefore generalizable to unselected patients with suspected COVID-19.

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

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 &lt, 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.

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.

BackgroundDue to the dramatic measures accompanying isolation and the general uncertainty and fear associated with COVID-19, patients and relatives may be at high risk for adverse psychological outcomes. Until now there has been limited research focusing on the prevalence of psychological distress and associated factors in COVID-19 patients and their relatives. The objective of our study was to assess psychological distress in COVID-19 patients and their relatives 30 days after hospital discharge.MethodsIn this prospective observational cohort study at two Swiss tertiary-care hospitals we included consecutive adult patients hospitalized between March and June 2020 for a proven COVID-19 and their relatives. Psychological distress was defined as symptoms of anxiety and/or depression measured with the Hospital Anxiety and Depression Scale (HADS), i.e., a score of ≥8 on the depression and/or anxiety subscale. We further evaluated symptoms of post-traumatic stress disorder (PTSD), defined as a score of ≥1.5 on the Impact of Event Scale-Revised (IES-R).ResultsAmong 126 included patients, 24 (19.1%) had psychological distress and 10 (8.7%) had symptoms of PTSD 30 days after hospital discharge. In multivariate logistic regression analyses three factors were independently associated with psychological distress in patients: resilience (OR 0.82; 95%CI 0.71 to 0.94; p = 0.005), high levels of perceived stress (OR 1.21; 95%CI 1.06 to 1.38; p = 0.006) and low frequency of contact with relatives (OR 7.67; 95%CI 1.42 to 41.58; p = 0.018). The model showed good discrimination, with an area under the receiver-operating characteristic curve (AUC) of 0.92. Among 153 relatives, 35 (22.9%) showed symptoms of psychological distress, and 3 (2%) of PTSD. For relatives, resilience was negatively associated (OR 0.85; 95%CI 0.75 to 0.96; p = 0.007), whereas perceived overall burden caused by COVID-19 was positively associated with psychological distress (OR 1.72; 95%CI 1.31 to 2.25; pConclusionA relevant number of COVID-19 patients as well as their relatives exhibited psychological distress 30 days after hospital discharge. These results might aid in development of strategies to prevent psychological distress in COVID-19 patients and their relatives.

Background and Aims Previous studies have indicated a coherency between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI), indicating poor outcomes. However, most studies only included patients with COVID-19 and lacked a control group. Therefore, the aim of this study was to investigate the prevalence and prognostic impact of AKI in patients with COVID-19 in comparison with other respiratory tract infections. Method The prospective single-center observational case-control COronaVIrus surviVAl (COVIVA, clinicaltrials.gov NCT04366765) study performed at the University Hospital Basel Switzerland consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March 23 and May 31, 2020. The final diagnosis that led to the inclusion in the study was adjudicated by physicians after reviewing all available medical data including laboratory test results 30 days after discharge. For this analysis, we compared patients tested positive for SARS-CoV-2 with patients tested negative but with an adjudicated diagnosis of upper or lower respiratory tract infection including pneumonia. Primary outcome measure was death at 30 days, secondary outcomes were AKI incidence, renal recovery and need for renal replacement therapy. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline. Results Of the 1086 patients included, 507 had a final adjudicated diagnosis of respiratory tract infection and were eligible for this analysis. Of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. Baseline characteristics were comparable between patients with and without COVID-19. AKI occurred in 95 patients (19%) with a higher incidence (30%, 95%CI 24-37 versus 12%, 95%CI 9-17, p Conclusion AKI occurs more frequently and more severely in patients with COVID-19 compared to other respiratory tract infections. It is associated with an increased risk for death, with the highest risk observed in COVID-19 patients. This underlines the augmented burden of AKI during the COVID-19 pandemic.

Background and Aims Acute kidney injury (AKI) is common and associated with increased mortality and morbidity. The impact of AKI on subsequent heart failure remains largely unknown. Method The Basics in Acute Shortness of Breath Evaluation Study (BaselV) prospectively enrolled patients presenting the emergency department with acute dyspnea. Two independent specialists adjudicated the final cause of dyspnea. Serum creatinine concentrations were prospectively assessed throughout the hospitalization. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline. AKI adjudication occurred blinded to the cause of dyspnea. Mortality and rehospitalizations were prospectively assessed during follow-up (median:768 days [IQR:290-950]. Renal recovery was defined as a discharge creatinine Results AKI occurred in 809 (40%) of 2021 patients and was associated with increased all-cause (adjusted Hazard Ratio [aHR] 1.33, 95%CI 1.13-1.55; p Conclusion AKI independently increases the risk of hHF by almost 50%. This association persists in patients with non-cardiac dyspnea, even after renal recovery by discharge. This suggests AKI to be a novel risk-factor for the development of clinically significant HF.

Rationale This study aimed to describe cardiopulmonary function during exercise 3 months after hospital discharge for COVID-19 and compare groups according to dyspnea and intensive care unit (ICU) stay. Methods Participants with COVID-19 discharged from five large Norwegian hospitals were consecutively invited to a multicentre, prospective cohort study. In total, 156 participants (mean age 56.2 years, 60 females) were examined with a cardiopulmonary exercise test (CPET) 3 months after discharge and compared to a reference population. Dyspnea was assessed using the modified Medical Research Council dyspnea scale (mMRC). Results Peak oxygen uptake (V̇O2), Oxygen uptake was reduced in one-third of the participants 3 months after hospitalisation for COVID-19. The most common exercise limitation was deconditioning. Circulatory limitations to exercise were more common than ventilatory limitations.