Changes in diagnostic patterns and resource utilisation in Swiss adult ICUs during the first two COVID-19 waves: an exploratory study.

BACKGROUND AND AIM: The coronavirus disease 2019 (COVID-19) outbreak deeply affected intensive care units (ICUs). We aimed to explore the main changes in the distribution and characteristics of Swiss ICU patients during the first two COVID-19 waves and to relate these figures with those of the preceding two years. METHODS: Using the national ICU registry, we conducted an exploratory study to assess the number of ICU admissions in Switzerland and their changes over time, characteristics of the admissions, the length of stay (LOS) and its trend over time, ICU mortality and changes in therapeutic nursing workload and hospital resources in 2020 and compare them with the average figures in 2018 and 2019. RESULTS: After analysing 242,935 patient records from all 84 certified Swiss ICUs, we found a significant decrease in admissions (-9.6%, corresponding to -8005 patients) in 2020 compared to 2018/2019, with an increase in the proportion of men admitted (61.3% vs 59.6%; p <0.001). This reduction occurred in all Swiss regions except Ticino. Planned admissions decreased from 25,020 to 22,021 in 2020 and mainly affected the neurological/neurosurgical (-14.9%), gastrointestinal (-13.9%) and cardiovascular (-9.3%) pathologies. Unplanned admissions due to respiratory diagnoses increased by 1971 (+25.2%), and those of patients with acute respiratory distress syndrome (ARDS) requiring isolation reached 9973 (+109.9%). The LOS increased by 20.8% from 2.55 ± 4.92 days (median 1.05) in 2018/2019 to 3.08 ± 5.87 days (median 1.11 days; p <0.001), resulting in an additional 19,753 inpatient days. The nine equivalents of nursing manpower use score (NEMS) of the first nursing shift (21.6 ± 9.0 vs 20.8 ± 9.4; p <0.001), the total NEMS per patient (251.0 ± 526.8 vs 198.9 ± 413.8; p <0.01) and mortality (5.7% vs 4.7%; p <0.001) increased in 2020. The number of ICU beds increased from 979 to 1012 (+3.4%), as did the number of beds equipped with mechanical ventilators (from 773 to 821; +6.2%). CONCLUSIONS: Based on a comprehensive national data set, our report describes the profound changes triggered by COVID-19 over one year in Swiss ICUs. We observed an overall decrease in admissions and a shift in admission types, with fewer planned hospitalisations, suggesting the loss of approximately 3000 elective interventions. We found a substantial increase in unplanned admissions due to respiratory diagnoses, a doubling of ARDS cases requiring isolation, an increase in ICU LOS associated with substantial nationwide growth in ICU days, an augmented need for life-sustaining therapies and specific therapeutic resources and worse outcomes.

Misconceptions and do-not-resuscitate preferences of healthcare professionals commonly involved in cardiopulmonary resuscitations: A national survey.

Aims: To assess the DNR preferences of critical care-, anesthesia- and emergency medicine practitioners, to identify factors influencing decision-making, and to raise awareness for misconceptions concerning CPR outcomes. Methods: A nationwide multicenter survey was conducted in Switzerland confronting healthcare professionals with a case vignette of an adult patient with an out-of-hospital cardiac arrest (OHCA). The primary outcome was the rate of DNR Code Status vs. CPR Code Status when taking the perspective from a clinical case vignette of a 70-year-old patient. Secondary outcomes were participants' personal preferences for DNR and estimates of survival with good neurological outcome after in- and out-of-hospital cardiac arrest. Results: Within 1803 healthcare professionals, DNR code status was preferred in 85% (n = 1532) in the personal perspective of the case vignette and 53.2% (n = 932) when making a decision for themselves. Main predictors for a DNR Code Status regarding the case vignette included preferences for DNR Code Status for themselves (n [%] 896 [58.5] vs. 87 [32.1]; adjusted odds ratio [OR] 2.97, 95% confidence interval [CI] 2.25-3.92; p < 0.001) and lower estimated OHCA survival (mean [±SD] 12.3% [±11.8] vs. 14.7%[±12.8]; adjusted OR 0.98, 95% CI 0.97-0.99; p = 0.001). Physicians chose a DNR order more often when compared to nurses and paramedics. Conclusions: The estimation of outcomes following cardiac arrest and personal living conditions are pivotal factors influencing code status preferences in healthcare professionals. Healthcare professionals should be aware of cardiac arrest prognosis and potential implications of personal preferences when engaging in code status- and end-of-life discussions with patients and their relatives.

Impact of sex and gender on post-COVID-19 syndrome, Switzerland, 2020.

BackgroundWomen are overrepresented among individuals with post-acute sequelae of SARS-CoV-2 infection (PASC). Biological (sex) as well as sociocultural (gender) differences between women and men might account for this imbalance, yet their impact on PASC is unknown.AimWe assessed the impact of sex and gender on PASC in a Swiss population.MethodOur multicentre prospective cohort study included 2,856 (46% women, mean age 44.2 ± 16.8 years) outpatients and hospitalised patients with PCR-confirmed SARS-CoV-2 infection.ResultsAmong those who remained outpatients during their first infection, women reported persisting symptoms more often than men (40.5% vs 25.5% of men; p < 0.001). This sex difference was absent in hospitalised patients. In a crude analysis, both female biological sex (RR = 1.59; 95% CI: 1.41-1.79; p < 0.001) and a score summarising gendered sociocultural variables (RR = 1.05; 95% CI: 1.03-1.07; p < 0.001) were significantly associated with PASC. Following multivariable adjustment, biological female sex (RR = 0.96; 95% CI: 0.74-1.25; p = 0.763) was outperformed by feminine gender-related factors such as a higher stress level (RR = 1.04; 95% CI: 1.01-1.06; p = 0.003), lower education (RR = 1.16; 95% CI: 1.03-1.30; p = 0.011), being female and living alone (RR = 1.91; 95% CI: 1.29-2.83; p = 0.001) or being male and earning the highest income in the household (RR = 0.76; 95% CI: 0.60-0.97; p = 0.030).ConclusionSpecific sociocultural parameters that differ in prevalence between women and men, or imply a unique risk for women, are predictors of PASC and may explain, at least in part, the higher incidence of PASC in women. Once patients are hospitalised during acute infection, sex differences in PASC are no longer evident.

Red blood cell distribution width for the prediction of outcomes after cardiac arrest.

The red blood cell distribution width (RDW) is a routinely available blood marker that measures the variation of the size/volume of red blood cells. The aim of our study was to investigate the prognostic value of RDW in cardiac arrest patients and to assess whether RDW improves the prognostic value of three cardiac arrest-specific risk scores. Consecutive adult cardiac arrest patients admitted to the ICU of a Swiss university hospital were included. The primary outcome was poor neurological outcome at hospital discharge assessed by Cerebral Performance Category. Of 702 patients admitted to the ICU after cardiac arrest, 400 patients (57.0%) survived, of which 323 (80.8%) had a good neurological outcome. Higher mean RDW values showed an independent association with poor neurological outcomes at hospital discharge (adjusted OR 1.27, 95% CI 1.14 to 1.41; p < 0.001). Adding the maximum RDW value to the OHCA- CAHP- and PROLOGUE cardiac arrest scores improved prognostic performance. Within this cohort of cardiac arrest patients, RDW was an independent outcome predictor and slightly improved three cardiac arrest-specific risk scores. RDW may therefore support clinical decision-making.

"Do-not-resuscitate" preferences of the general Swiss population: Results from a national survey.

AIMS: To assess the do-not-resuscitate preferences of the general Swiss population and to identify predictors influencing decision-making. Methods: A nationwide web-based survey was conducted in Switzerland on a representative sample of the adult population. The primary endpoint was the preference for a "Do Not Resuscitate" order (DNR Code Status) vs. cardiopulmonary resuscitation (CPR Code Status) in a clinical case vignette of an out-of-hospital cardiac arrest. Secondary endpoint were participants' own personal preferences for DNR. Results: 1138 subjects participated in the web-based survey, 1044 were included in the final analysis. Preference for DNR code status was found in 40.5% (n = 423) in the case vignette and in 20.3% (n = 209) when making a personal decision for themselves. Independent predictors for DNR Code Status for the case vignette were: Personal preferences for their own DNR Code Status (adjusted OR 2.44, 95%CI 1.67 to 3.55; p < 0.001), intubation following respiratory failure (adjusted OR 1.95, 95%CI 1.20 to 3.18; p = 0.007), time-period after which resuscitation should not be attempted (adjusted OR 0.91, 95%CI 0.89 to 0.93); p < 0.001), and estimated chance of survival in case of a cardiac arrest (adjusted OR per decile 0.91, 95%CI 0.84 to 0.99, p = 0.02; which was overestimated by all participants. Conclusions: Main predictors for a DNR Code Status were personal preferences and the overestimation of good neurological outcome after cardiac arrest. Overestimation of positive outcomes after cardiac arrest seems to influence patient opinion and should thus be addressed during code status discussions.

Subjective and objective survival prediction in mechanically ventilated critically ill patients: a prospective cohort study.

BACKGROUND: ICU risk assessment tools, routinely used for predicting population outcomes, are not recommended for evaluating individual risk. The state of health of single patients is mostly subjectively assessed to inform relatives and presumably to decide on treatment decisions. However, little is known how subjective and objective survival estimates compare. METHODS: We performed a prospective cohort study in mechanically ventilated critically ill patients across five European centres, assessed 62 objective markers and asked the clinical staff to subjectively estimate the probability of surviving 28 days. RESULTS: Within the 961 included patients, we identified 27 single objective predictors for 28-day survival (73.8%) and pooled them into predictive groups. While patient characteristics and treatment models performed poorly, the disease and biomarker models had a moderate discriminative performance for predicting 28-day survival, which improved for predicting 1-year survival. Subjective estimates of nurses (c-statistic [95% CI] 0.74 [0.70-0.78]), junior physicians (0.78 [0.74-0.81]) and attending physicians (0.75 [0.72-0.79]) discriminated survivors from non-survivors at least as good as the combination of all objective predictors (c-statistic: 0.67-0.72). Unexpectedly, subjective estimates were insufficiently calibrated, overestimating death in high-risk patients by about 20% in absolute terms. Combining subjective and objective measures refined discrimination and reduced the overestimation of death. CONCLUSIONS: Subjective survival estimates are simple, cheap and similarly discriminative as objective models; however, they overestimate death risking that live-saving therapies are withheld. Therefore, subjective survival estimates of individual patients should be compared with objective tools and interpreted with caution if not agreeing. Trial registration ISRCTN ISRCTN59376582 , retrospectively registered October 31st 2013.

External validation of the PROLOGUE score to predict neurological outcome in adult patients after cardiac arrest: a prospective cohort study.

BACKGROUND: The PROLOGUE score (PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages) is a novel prognostic model for the prediction of neurological outcome after cardiac arrest, which showed exceptional performance in the internal validation. The aim of this study is to validate the PROLOGUE score in an independent cohort of unselected adult cardiac arrest patients and to compare it to the thoroughly validated Out-of-Hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP) scores. METHODS: This study included consecutive adult cardiac arrest patients admitted to the intensive care unit (ICU) of a Swiss tertiary teaching hospital between October 2012 and July 2022. The primary endpoint was poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score of 3 to 5 including death. RESULTS: Of 687 patients included in the analysis, 321 (46.7%) survived to hospital discharge with good neurological outcome, 68 (9.9%) survived with poor neurological outcome and 298 (43.4%) died. The PROLOGUE score showed an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI 0.80 to 0.86) and good calibration for the prediction of the primary outcome. The OHCA and CAHP score showed similar performance (AUROC 0.83 and 0.84 respectively), the differences between the three scores were not significant (p = 0.495). In a subgroup analysis, the PROLOGUE score performed equally in out-of-hospital and in-hospital cardiac arrest patients whereas the OHCA and CAHP score performed significantly better in OHCA patients. CONCLUSION: The PROLOGUE score showed good prognostic accuracy for the early prediction of neurological outcome in adult cardiac arrest survivors in our cohort and might support early goals-of-care discussions in the ICU. Trial registration Not applicable.

Development and validation of a prognostic model for the early identification of COVID-19 patients at risk of developing common long COVID symptoms.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic demands reliable prognostic models for estimating the risk of long COVID. We developed and validated a prediction model to estimate the probability of known common long COVID symptoms at least 60 days after acute COVID-19. METHODS: The prognostic model was built based on data from a multicentre prospective Swiss cohort study. Included were adult patients diagnosed with COVID-19 between February and December 2020 and treated as outpatients, at ward or intensive/intermediate care unit. Perceived long-term health impairments, including reduced exercise tolerance/reduced resilience, shortness of breath and/or tiredness (REST), were assessed after a follow-up time between 60 and 425 days. The data set was split into a derivation and a geographical validation cohort. Predictors were selected out of twelve candidate predictors based on three methods, namely the augmented backward elimination (ABE) method, the adaptive best-subset selection (ABESS) method and model-based recursive partitioning (MBRP) approach. Model performance was assessed with the scaled Brier score, concordance c statistic and calibration plot. The final prognostic model was determined based on best model performance. RESULTS: In total, 2799 patients were included in the analysis, of which 1588 patients were in the derivation cohort and 1211 patients in the validation cohort. The REST prevalence was similar between the cohorts with 21.6% (n = 343) in the derivation cohort and 22.1% (n = 268) in the validation cohort. The same predictors were selected with the ABE and ABESS approach. The final prognostic model was based on the ABE and ABESS selected predictors. The corresponding scaled Brier score in the validation cohort was 18.74%, model discrimination was 0.78 (95% CI: 0.75 to 0.81), calibration slope was 0.92 (95% CI: 0.78 to 1.06) and calibration intercept was -0.06 (95% CI: -0.22 to 0.09). CONCLUSION: The proposed model was validated to identify COVID-19-infected patients at high risk for REST symptoms. Before implementing the prognostic model in daily clinical practice, the conduct of an impact study is recommended.

Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study.

Growing evidence links COVID-19 with acute and long-term neurological dysfunction. However, the pathophysiological mechanisms resulting in central nervous system involvement remain unclear, posing both diagnostic and therapeutic challenges. Here we show outcomes of a cross-sectional clinical study (NCT04472013) including clinical and imaging data and corresponding multidimensional characterization of immune mediators in the cerebrospinal fluid (CSF) and plasma of patients belonging to different Neuro-COVID severity classes. The most prominent signs of severe Neuro-COVID are blood-brain barrier (BBB) impairment, elevated microglia activation markers and a polyclonal B cell response targeting self-antigens and non-self-antigens. COVID-19 patients show decreased regional brain volumes associating with specific CSF parameters, however, COVID-19 patients characterized by plasma cytokine storm are presenting with a non-inflammatory CSF profile. Post-acute COVID-19 syndrome strongly associates with a distinctive set of CSF and plasma mediators. Collectively, we identify several potentially actionable targets to prevent or intervene with the neurological consequences of SARS-CoV-2 infection.

Characterization of pathogen-inactivated COVID-19 convalescent plasma and responses in transfused patients.

BACKGROUND: Efficacy of donated COVID-19 convalescent plasma (dCCP) is uncertain and may depend on antibody titers, neutralizing capacity, timing of administration, and patient characteristics. STUDY DESIGN AND METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Non-invasive evaluation of new-onset atrial fibrillation after cardiac surgery: a protocol for the BigMap study.

AIMS: New-onset atrial fibrillation (NOAF) is the most common complication after cardiac surgery, occurring in 25-50% of patients. It is associated with post-operative stroke, increased mortality, prolonged hospital length of stay, and higher treatment costs. Previous small observational studies have identified the left atrium as a source of the electrical rotors and foci maintaining NOAF, but confirmation by a large prospective clinical study is still missing. The aim of the proposed study is to investigate whether the source of NOAF lies in the left atrium. The correct identification of NOAF-maintaining structures in cardiac surgical patients might offer potential therapeutic targets for prophylactic perioperative ablation strategies. METHODS AND RESULTS: This is a prospective single-centre observational study of patients developing NOAF after cardiac surgery. The primary outcome is the description of NOAF-maintaining structures within the atria. Key secondary outcomes include overall mortality, intensive care unit length of stay, hospital-ventilator-free days, and proportion of persistent NOAF. In NOAF patients, the non-invasive electrophysiological mapping will be conducted using a 252-electrode electrocardiogram vest. After mapping, a low-dose computed tomography scan of the chest will be performed to integrate the electrophysiological mapping results into a 3D picture of the heart. The study will include approximately 570 patients, of whom 30% (n = 170) are expected to develop NOAF. Sample size calculation revealed that 157 NOAF patients are necessary to assess the primary outcome. Patients will be tracked for a total of 5 years. CONCLUSIONS: This is the largest prospective study to date describing the electrophysiological mechanisms of NOAF using non-invasive mapping.

Mortality 7 years after prolonged treatment on a surgical intensive care unit.

AIMS OF THE STUDY: Long-term intensive care treatment confers a substantial physical, psychological and social burden on patients, their relatives and the treatment team. It is essential to know the outcome of patients with long-term treatment and to establish factors that possibly can predict mortality. Only few Swiss studies have previously addressed this issue. METHODS: This retrospective observational study at a Swiss tertiary academic medical care centre included patients who were treated for ≥7 consecutive days at the surgical intensive care unit (ICU) between 1 January 2011 and 31 December 2012. Follow-up ended on 30 September 2018. RESULTS: Two-hundred and fifty patients were included, and three were lost to follow-up. Fifty-two patients (21.1%) died in the ICU, 25 (10.1%) after transfer to the normal ward. Thirty-one patients (12.5%) died within one year after the beginning of intensive care treatment. Altogether, the one-year mortality was 43.7% (108 patients). At the end of follow-up, 99 patients (40.1%) were still alive. Polytrauma patients represent a special group with a survival of more than 90%. Median patient age was 66 years (interquartile range 56-75); two thirds were men. Patients who died within one year of beginning treatment in the ICU were significantly older (median 71 vs 63 years, p <0.001), had a higher Charlson comorbidity index (mean 2.3 vs 1.2, p <0.001), a longer intensive care stay (median 13.9 vs 10.6 days, p = 0.001), a higher SAPS-II score (mean 52.7 vs 45.6, p = 0.001), a higher NEMS score (mean 1772.4 vs 1230.4, p <0.001) and more complications (mean 2.9 vs 2.0, p <0.001) than patients who survived at least 1 year. Those who died within 1 year more often developed pneumonia (50.9% vs 29.5%, p = 0.001), pleural empyema (13.0% vs 2.9%, p = 0.005), septic shock (51.9% vs 20.1%, p <0.001) or critical illness polyneuropathy (16.7% vs 2.9%, p <0.001). Moreover, they more frequently (30.6% vs 15.1%, p = 0.006) required a renal replacement therapy. CONCLUSIONS: Long-term mortality of patients with prolonged intensive-care treatment is high. Scores combined with factors shown to be associated with an increased short- and long-term mortality can help to identify patients at risk for death within one year after ICU treatment.

Determinants of SARS-CoV-2 transmission to guide vaccination strategy in an urban area.

Transmission chains within small urban areas (accommodating ∼30 per cent of the European population) greatly contribute to case burden and economic impact during the ongoing coronavirus pandemic and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in a European urban area, Basel-City (Switzerland). We combined detailed epidemiological, intra-city mobility and socio-economic data sets with whole-genome sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44 per cent of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60 per cent of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare system burden (intensive care unit (ICU) occupancy). Transmissions were driven by socio-economically weaker and highly mobile population groups with mostly cryptic transmissions which lacked genetic and identifiable epidemiological links. Amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90 per cent transmission reduction and 70-90 per cent reduction of severe cases showed that prioritising mobile, socio-economically weaker populations for vaccination would effectively reduce case numbers. However, long-term ICU occupation would also be effectively reduced if senior population groups were prioritised, provided there were no changes in testing and prevention strategies. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area.

Activation of the kynurenine pathway predicts mortality and neurological outcome in cardiac arrest patients: A validation study.

PURPOSE: Activation of the kynurenine pathway (KP) has been shown to predict outcome in cardiac arrest (CA) patients. We validated these findings in a Swiss cohort. METHODS: We measured admission tryptophan and kynurenine levels in 270 consecutive CA patients (38 in-hospital CA) and investigated associations with in-hospital mortality and neurological outcome at hospital discharge. RESULTS: 120 of 270 (44%) patients died in the hospital. Compared to survivors, non-survivors showed higher median initial kynurenine levels (5.28 µmol/l [IQR 2.91 to 7.40] vs 3.58 µmol/l [IQR 2.47 to 5.46]; p < 0.001) and a higher median kynurenine/tryptophan ratio (0.10 µmol/l [IQR 0.07 to 0.17] vs 0.07 µmol/l [IQR 0.05 to 0.1]; p < 0.001). In a model adjusted for age, gender and comorbidities, kynurenine (OR 1.16, 95% CI 1.05 to 1.27; p = 0.001) and kynurenine/tryptophan ratio (OR 1.19, 95% CI 1.08 to 1.31; p = 0.003) were significantly associated with mortality. Results were similar for neurological outcome. CONCLUSIONS: Our findings validate a previous study and show associations of the activation of the KP with unfavorable outcomes after CA. Future studies should evaluate whether therapeutic modulation of the KP may impact clinical outcomes after CA.

Neuron-Specific Enolase (NSE) Predicts Long-Term Mortality in Adult Patients after Cardiac Arrest: Results from a Prospective Trial.

BACKGROUND: We investigated whether Neuron-specific enolase (NSE) serum concentration predicts long-term mortality and poor neurological outcome in adult cardiac arrest patients. METHODS: Within this prospective observational study, we included consecutive adult patients admitted to the intensive care unit (ICU) after cardiac arrest. NSE was measured upon ICU admission and on days 1, 2, 3, 5 and 7. RESULTS: Of 403 patients, 176 (43.7%) survived. Median follow-up duration was 43.7 months (IQR 14.3 to 63.0 months). NSE levels on day 3 were increased more than threefold in non-survivors compared to survivors (median NSE (ng/mL) 19.8 (IQR 15.7 to 27.8) vs. 72.6 (IQR 26 to 194)) and showed the highest prognostic performance for mortality compared to other days of measurement, with an AUC of 0.81 and an adjusted hazard ratio of 1.55 (95% CI 1.41 to 1.71, p < 0.001). Subgroup analysis showed an excellent sensitivity and negative predictive value of 100% of NSE in patients <54 years of age. CONCLUSION: NSE measured three days after cardiac arrest is associated with long-term mortality and neurological outcome and may provide prognostic information that improves clinical decision making. Particularly in the subgroup of younger patients (<54 years), NSE showed excellent negative predictive value.

Comparing Immunoassays for SARS-CoV-2 Antibody Detection in Patients with and without Laboratory-Confirmed SARS-CoV-2 Infection.

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.

Variations in end-of-life practices in intensive care units worldwide (Ethicus-2): a prospective observational study.

BACKGROUND: End-of-life practices vary among intensive care units (ICUs) worldwide. Differences can result in variable use of disproportionate or non-beneficial life-sustaining interventions across diverse world regions. This study investigated global disparities in end-of-life practices. METHODS: In this prospective, multinational, observational study, consecutive adult ICU patients who died or had a limitation of life-sustaining treatment (withholding or withdrawing life-sustaining therapy and active shortening of the dying process) during a 6-month period between Sept 1, 2015, and Sept 30, 2016, were recruited from 199 ICUs in 36 countries. The primary outcome was the end-of-life practice as defined by the end-of-life categories: withholding or withdrawing life-sustaining therapy, active shortening of the dying process, or failed cardiopulmonary resuscitation (CPR). Patients with brain death were included in a separate predefined end-of-life category. Data collection included patient characteristics, diagnoses, end-of-life decisions and their timing related to admission and discharge, or death, with comparisons across different regions. Patients were studied until death or 2 months from the first limitation decision. FINDINGS: Of 87 951 patients admitted to ICU, 12 850 (14·6%) were included in the study population. The number of patients categorised into each of the different end-of-life categories were significantly different for each region (p<0·001). Limitation of life-sustaining treatment occurred in 10 401 patients (11·8% of 87 951 ICU admissions and 80·9% of 12 850 in the study population). The most common limitation was withholding life-sustaining treatment (5661 [44·1%]), followed by withdrawing life-sustaining treatment (4680 [36·4%]). More treatment withdrawing was observed in Northern Europe (1217 [52·8%] of 2305) and Australia/New Zealand (247 [45·7%] of 541) than in Latin America (33 [5·8%] of 571) and Africa (21 [13·0%] of 162). Shortening of the dying process was uncommon across all regions (60 [0·5%]). One in five patients with treatment limitations survived hospitalisation. Death due to failed CPR occurred in 1799 (14%) of the study population, and brain death occurred in 650 (5·1%). Failure of CPR occurred less frequently in Northern Europe (85 [3·7%] of 2305), Australia/New Zealand (23 [4·3%] of 541), and North America (78 [8·5%] of 918) than in Africa (106 [65·4%] of 162), Latin America (160 [28·0%] of 571), and Southern Europe (590 [22·5%] of 2622). Factors associated with treatment limitations were region, age, and diagnoses (acute and chronic), and country end-of-life legislation. INTERPRETATION: Limitation of life-sustaining therapies is common worldwide with regional variability. Withholding treatment is more common than withdrawing treatment. Variations in type, frequency, and timing of end-of-life decisions were observed. Recognising regional differences and the reasons behind these differences might help improve end-of-life care worldwide. FUNDING: None.

Ninety-day outcome of patients with severe COVID-19 treated with tocilizumab - a single centre cohort study.

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 <93%, respiratory rate >30/min, C-reactive protein levels >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] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) 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.

Adverse Events of Percutaneous Microaxial Left Ventricular Assist Devices-A Retrospective, Single-Centre Cohort Study.

Worldwide, the left ventricular assist device Impella® (Abiomed, Danvers, MA, USA) is increasingly implanted in patients with acute cardiogenic shock or undergoing high-risk cardiac interventions. Despite its long history of use, few studies have assessed its safety and possible complications associated with its use. All patients treated with a left-sided Impella® device at the University Hospital of Basel from 1 January 2011 to 31 December 2019 were enrolled. The primary endpoint was the composite rate of mortality and adverse events (bleeding, acute kidney injury, and limb ischemia). Out of 281 included patients, at least one adverse event was present in 262 patients (93%). Rates of in-hospital, 90-day, and one-year mortality were 48%, 47%, and 50%, respectively. BARC type 3 bleeding (62%) and hemolysis (41.6%) were the most common complications. AKI was observed in 50% of all patients. Renal replacement therapy was required in 97 (35%) of all patients. Limb ischemia occurred in 13% of cases. Bleeding and hemolysis are common Impella®-associated complications. Additionally, we found a high rate of AKI. A careful selection of patients receiving microaxial LV support and defining the indication for its use are essential measures to be taken for the benefits to outweigh potential complications.

Temporal trends of COVID-19 related in-hospital mortality and demographics in Switzerland - a retrospective single centre cohort study.

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’ 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] 53–76) 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] 1.45–2.26; p <0.001), male sex (aOR 1.68, 95% CI 1.00–2.82; p = 0.048), immunocompromising condition (aOR 2.09, 95% CI 1.01–4.33; p = 0.048) and chronic kidney disease (aOR 2.25, 95% CI 1.35–3.76; 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.