Sepsis awareness and knowledge amongst nurses, physicians and paramedics of a tertiary care center in Switzerland: A survey-based cross-sectional study.

BACKGROUND: Sepsis is a leading cause of morbidity and mortality. Prompt recognition and management are critical to improve outcomes. METHODS: We conducted a survey among nurses and physicians of all adult departments of the Lausanne University Hospital (LUH) and paramedics transporting patients to our hospital. Measured outcomes included professionals' demographics (age, profession, seniority, unit of activity), quantification of prior sepsis education, self-evaluation, and knowledge of sepsis epidemiology, definition, recognition, and management. Correlation between surveyed personnel and sepsis perceptions and knowledge were assessed with univariable and multivariable logistic regression models. RESULTS: Between January and October 2020, we contacted 1'216 of the 4'417 professionals (27.5%) of the LUH, of whom 1'116 (91.8%) completed the survey, including 619 of 2'463 (25.1%) nurses, 348 of 1'664 (20.9%) physicians and 149 of 290 (51.4%) paramedics. While 98.5% of the participants were familiar with the word "sepsis" (97.4% of nurses, 100% of physicians and 99.3% of paramedics), only 13% of them (physicians: 28.4%, nurses: 5.9%, paramedics: 6.8%) correctly identified the Sepsis-3 consensus definition. Similarly, only 48% and 49.3% of the physicians and 10.1% an 11.9% of the nurses knew that SOFA was a sepsis defining score and that the qSOFA score was a predictor of increased mortality, respectively. Furthermore, 15.8% of the physicians and 1.0% of the nurses knew the three components of the qSOFA score. For patients with suspected sepsis, 96.1%, 91.6% and 75.8% of physicians respectively chose blood cultures, broad-spectrum antibiotics and fluid resuscitation as therapeutic interventions to be initiated within 1 (76.4%) to 3 (18.2%) hours. For nurses and physicians, recent training correlated with knowledge of SOFA score (ORs [95%CI]: 3.956 [2.018-7.752] and 2.617 [1.527-4.485]) and qSOFA (ORs [95%CI]: 5.804 [2.653-9.742] and 2.291 [1.342-3.910]) scores purposes. Furthermore, recent training also correlated with adequate sepsis definition (ORs [95%CI]: 1.839 [1.026-3.295]) and the components of qSOFA (ORs [95%CI]: 2.388 [1.110-5.136]) in physicians. CONCLUSIONS: This sepsis survey conducted among physicians, nurses and paramedics of a tertiary Swiss medical center identified a deficit of sepsis awareness and knowledge reflecting a lack of sepsis-specific continuing education requiring immediate corrective measures.

Swiss Sepsis National Action Plan: A coordinated national action plan to stop sepsis-related preventable deaths and to improve the support of people affected by sepsis in Switzerland.

Background: Sepsis is a devastating disease which causes yearly over 10 million deaths worldwide. In 2017, the World Health Organization (WHO) issued a resolution prompting member states to improve the prevention, recognition, and management of sepsis. The 2021 European Sepsis Report revealed that-contrary to other European countries-Switzerland had not yet actioned the sepsis resolution. Methods: A panel of experts convened at a policy workshop to address how to improve awareness, prevention, and treatment of sepsis in Switzerland. Goal of the workshop was to formulate a set of consensus recommendations toward creating a Swiss Sepsis National Action Plan (SSNAP). In a first part, stakeholders presented existing international sepsis quality improvement programs and national health programs relevant for sepsis. Thereafter, the participants were allocated into three working groups to identify opportunities, barriers, and solutions on (i) prevention and awareness, (ii) early detection and treatment, and (iii) support for sepsis survivors. Finally, the entire panel summarized the findings from the working groups and identified priorities and strategies for the SSNAP. All discussions during the workshop were transcribed into the present document. All workshop participants and key experts reviewed the document. Results: The panel formulated 14 recommendations to address sepsis in Switzerland. These focused on four domains, including (i) raising awareness in the community, (ii) improving healthcare workforce training on sepsis recognition and sepsis management; (iii) establishing standards for rapid detection, treatment and follow-up in sepsis patients across all age groups; and (iv) promoting sepsis research with particular focus on diagnostic and interventional trials. Conclusion: There is urgency to tackle sepsis. Switzerland has a unique opportunity to leverage from lessons learnt during the COVID-19 pandemic to address sepsis as the major infection-related threat to society. This report details consensus recommendations, the rationale thereof, and key discussion points made by the stakeholders on the workshop day. The report presents a coordinated national action plan to prevent, measure, and sustainably reduce the personal, financial and societal burden, death and disability arising from sepsis in Switzerland.

Prediction of DNA rejoining kinetics and cell survival after proton irradiation for V79 cells using Geant4-DNA.

PURPOSE: Track structure Monte Carlo (MC) codes have achieved successful outcomes in the quantitative investigation of radiation-induced initial DNA damage. The aim of the present study is to extend a Geant4-DNA radiobiological application by incorporating a feature allowing for the prediction of DNA rejoining kinetics and corresponding cell surviving fraction along time after irradiation, for a Chinese hamster V79 cell line, which is one of the most popular and widely investigated cell lines in radiobiology. METHODS: We implemented the Two-Lesion Kinetics (TLK) model, originally proposed by Stewart, which allows for simulations to calculate residual DNA damage and surviving fraction along time via the number of initial DNA damage and its complexity as inputs. RESULTS: By optimizing the model parameters of the TLK model in accordance to the experimental data on V79, we were able to predict both DNA rejoining kinetics at low linear energy transfers (LET) and cell surviving fraction. CONCLUSION: This is the first study to demonstrate the implementation of both the cell surviving fraction and the DNA rejoining kinetics with the estimated initial DNA damage, in a realistic cell geometrical model simulated by full track structure MC simulations at DNA level and for various LET. These simulation and model make the link between mechanistic physical/chemical damage processes and these two specific biological endpoints.

A narrative review of the intermediate category of the antimicrobial susceptibility test: relation with dosing and possible impact on antimicrobial stewardship.

The interpretation of 'susceptible (S)' or 'resistant (R)' results of antimicrobial susceptibility testing is easily understood, but the interpretation of the 'intermediate (I)' category can be confusing. This review critically discusses how this categorization (clinical breakpoints) comes into being with the emphasis on the use of pharmacokinetics and pharmacodynamic data. It discusses the differences between the 'I' according to the CLSI and the EUCAST. This review also discusses the recent EUCAST change of the 'I' definition, and the impact of this change from laboratory and clinical points of view.

Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

OBJECTIVE: To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. DESIGN: Case description. STUDY SAMPLE: We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech®) and mRNA-1273 (Moderna®) vaccines. RESULTS: Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. CONCLUSIONS: The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2.

National Early Warning Score (NEWS) Outperforms Quick Sepsis-Related Organ Failure (qSOFA) Score for Early Detection of Sepsis in the Emergency Department.

Background: Prompt recognition of sepsis is critical to improving patients' outcomes. We compared the performance of NEWS and qSOFA scores as sepsis detection tools in patients admitted to the emergency department (ED) with suspicion of sepsis. Methodology: A single-center 12-month retrospective study comparing NEWS using the recommended cut-off of ≥5 and qSOFA as sepsis screening tools in a cohort of patients transported by emergency medical services (EMS) to the Lausanne University Hospital (LUH). We used the Sepsis-3 consensus definition. The primary study endpoint was the detection of sepsis. Secondary endpoints were ICU admission and 28-day all-cause mortality. Results: Among 886 patients admitted to ED by EMS for suspected infection, 556 (63%) had a complete set of vital parameters panel enabling the calculation of NEWS and qSOFA scores, of whom 300 (54%) had sepsis. For the detection of sepsis, the sensitivity of NEWS > 5 was 86% and that of qSOFA ≥ 2 was 34%. Likewise, the sensitivities of NEWS ≥ 5 for predicting ICU admission and 28-day mortality were higher than those of qSOFA ≥ 2 (82% versus 33% and 88% versus 37%). Conversely, the specificity of qSOFA ≥ 2 for sepsis detection was higher than that of NEWS ≥ 5 (90% versus 55%). The negative predictive value of NEWS > 5 was higher than that of qSOFA ≥ 2 (77% versus 54%), while the positive predictive value of qSOFA ≥ 2 was higher than that of NEWS ≥ 5 (80% versus 69%). Finally, the accuracy of NEWS ≥ 5 was higher than that of qSOFA ≥ 2 (72% versus 60%). Conclusions: The sensitivity of NEWS ≥ 5 was superior to that of qSOFA ≥ 2 to identify patients with sepsis in the ED and predict ICU admission and 28-day mortality. In contrast, qSOFA ≥ 2 had higher specificity and positive predictive values than NEWS ≥ 5 for these three endpoints.

Intradermal Testing With COVID-19 mRNA Vaccines Predicts Tolerance.

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy or with a suspected allergic reaction after the first dose remains to be defined. Methods: In this real-life study, we defined two cohorts of individuals: one pre-vaccination including 187 individuals with high-risk profiles for developing anaphylaxis and a second post-vaccination including 87 individuals with suspected allergic reactions after the COVID-19 mRNA vaccine. Upon negative skin test with an mRNA vaccine, a two-step (10-90%) vaccination protocol was performed. Positive skin tests were confirmed with the basophil activation test (BAT). Results: Among 604,267 doses of vaccine, 87 suspected allergic reactions (5 after the booster) were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% of the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced isolated asthmatic reactions during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Conclusion: Sensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10-90%-vaccination protocol can be safely administered upon negative skin testing.

Recommendations for the management of COVID-19 in patients with haematological malignancies or haematopoietic cell transplantation, from the 2021 European Conference on Infections in Leukaemia (ECIL 9).

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel virus that spread worldwide from 2019 causing the Coronavirus disease 19 (COVID-19) pandemic. SARS-CoV-2 infection is characterised by an initial viral phase followed in some patients by a severe inflammatory phase. Importantly, immunocompromised patients may have a prolonged viral phase, shedding infectious viral particles for months, and absent or dysfunctional inflammatory phase. Among haematological patients, COVID-19 has been associated with high mortality rate in acute leukaemia, high risk-myelodysplastic syndromes, and after haematopoietic cell transplant and chimeric-antigen-receptor-T therapies. The clinical symptoms and signs were similar to that reported for the overall population, but the severity and outcome were worse. The deferral of immunodepleting cellular therapy treatments is recommended for SARS-CoV-2 positive patient, while in the other at-risk cases, the haematological treatment decisions must be weighed between individual risks and benefits. The gold standard for the diagnosis is the detection of viral RNA by nucleic acid testing on nasopharyngeal-swabbed sample, which provides high sensitivity and specificity; while rapid antigen tests have a lower sensitivity, especially in asymptomatic patients. The prevention of SARS-CoV-2 infection is based on strict infection control measures recommended for aerosol-droplet-and-contact transmission. Vaccinations against SARS-CoV-2 has shown high efficacy in reducing community transmission, hospitalisation and deaths due to severe COVID-19 disease in the general population, but immunosuppressed/haematology patients may have lower sero-responsiveness to vaccinations. Moreover, the recent emergence of new variants may require vaccine modifications and strategies to improve efficacy in these vulnerable patients. Beyond supportive care, the specific treatment is directed at viral replication control (antivirals, anti-spike monoclonal antibodies) and, in patients who need it, to the control of inflammation (dexamethasone, anti-Il-6 agents, and others). However, the benefit of all these various prophylactic and therapeutic treatments in haematology patients deserves further studies.

ImmunoSep (Personalised Immunotherapy in Sepsis) international double-blind, double-dummy, placebo-controlled randomised clinical trial: study protocol.

INTRODUCTION: Sepsis is a major cause of death among hospitalised patients. Accumulating evidence suggests that immune response during sepsis cascade lies within a spectrum of dysregulated host responses. On the one side of the spectrum there are patients whose response is characterised by fulminant hyperinflammation or macrophage activation-like syndrome (MALS), and on the other side patients whose immune response is characterised by immunoparalysis. A sizeable group of patients are situated between the two extremes. Recognising immune endotype is very important in order to choose the appropriate immunotherapeutic approach for each patient resulting in the best chance to improve the outcome. METHODS AND ANALYSIS: ImmunoSep is a randomised placebo-controlled phase 2 clinical trial with a double-dummy design in which the effect of precision immunotherapy on sepsis phenotypes with MALS and immunoparalysis is studied. Patients are stratified using biomarkers. Specifically, 280 patients will be 1:1 randomly assigned to placebo or active immunotherapy as adjunct to standard-of-care treatment. In the active immunotherapy arm, patients with MALS will receive anakinra (recombinant interleukin-1 receptor antagonist) intravenously, and patients with immunoparalysis will receive subcutaneous recombinant human interferon-gamma. Τhe primary endpoint is the comparative decrease of the mean total Sequential Organ Failure Assessment score by at least 1.4 points by day 9 from randomisation. ETHICS AND DISSEMINATION: The protocol is approved by the German Federal Institute for Drugs and Medical Devices; the National Ethics Committee of Greece and by the National Organization for Medicines of Greece; the Central Committee on Research Involving Human Subjects and METC Oost Netherland for the Netherlands; the National Agency for Medicine and Medical Products of Romania; and the Commission Cantonale d'éthique de la recherche sur l'être human of Switzerland. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04990232.

SARS-CoV-2 seroprevalence in healthcare workers of a Swiss tertiary care centre at the end of the first wave: a cross-sectional study.

OBJECTIVE: To assess the SARS-CoV-2 transmission in healthcare workers (HCWs) using seroprevalence as a surrogate marker of infection in our tertiary care centre according to exposure. DESIGN: Seroprevalence cross-sectional study. SETTING: Single centre at the end of the first COVID-19 wave in Lausanne, Switzerland. PARTICIPANTS: 1874 of 4074 responders randomly selected (46% response rate), stratified by work category among the 13 474 (13.9%) HCWs. MAIN OUTCOME MEASURES: Evaluation of SARS-CoV-2 serostatus paired with a questionnaire of SARS-CoV-2 acquisition risk factors internal and external to the workplace. RESULTS: The overall SARS-CoV-2 seroprevalence rate among HCWs was 10.0% (95% CI 8.7% to 11.5%). HCWs with daily patient contact did not experience increased rates of seropositivity relative to those without (10.3% vs 9.6%, respectively, p=0.64). HCWs with direct contact with patients with COVID-19 or working in COVID-19 units did not experience increased seropositivity rates relative to their counterparts (10.4% vs 9.8%, p=0.69 and 10.6% vs 9.9%, p=0.69, respectively). However, specific locations of contact with patients irrespective of COVID-19 status-in patient rooms or reception areas-did correlate with increased rates of seropositivity (11.9% vs 7.5%, p=0.019 and 14.3% vs 9.2%, p=0.025, respectively). In contrast, HCWs with a suspected or proven SARS-CoV-2-infected household contact had significantly higher seropositivity rates than those without such contacts (19.0% vs 8.7%, p<0.001 and 42.1% vs 9.4%, p<0.001, respectively). Finally, consistent use of a mask on public transportation correlated with decreased seroprevalence (5.3% for mask users vs 11.2% for intermittent or no mask use, p=0.030). CONCLUSIONS: The overall seroprevalence was 10% without significant differences in seroprevalence between HCWs exposed to patients with COVID-19 and HCWs not exposed. This suggests that, once fully in place, protective measures limited SARS-CoV-2 occupational acquisition within the hospital environment. SARS-CoV-2 seroconversion among HCWs was associated primarily with community risk factors, particularly household transmission.

[New antibiotics for the clinical setting, an overview]. / Nouveaux antibiotiques pour la clinique†: un tour d'horizon.

Antibiotic resistance has become a major medical problem of our time. In 2015, the World Health Organisation (WHO) endorsed a global action plan in response. One of the main axes of this plan has been the sustained development of new antimicrobials. Despite its challenges, over half a dozen new substances have become clinically available in the last decade. Here, we review a selection of these novel antimicrobial and their applications and discuss their possible use in the clinical setting.

La problématique de la résistance aux antibiotiques a poussé l'Organisation mondiale de la santé (OMS) à élaborer en mai 2015 un plan d'action. Parmi les points centraux de ce plan, l'OMS insiste sur la nécessité de développer de nouveaux antibiotiques. Malgré la difficulté de cette entreprise, près d'une dizaine de nouvelles substances ont fait leur entrée en clinique pendant ces dernières années. Dans ce contexte, nous passons en revue les avancées principales de cette dernière décennie avec un regard critique sur la possibilité que ces nouvelles substances s'établissent dans notre quotidien clinique.