Post-intensive care syndrome and health-related quality of life in long-term survivors of cardiac arrest: a prospective cohort study.

Patients discharged from intensive care are at risk for post-intensive care syndrome (PICS), which consists of physical, psychological, and/or neurological impairments. This study aimed to analyze PICS at 24 months follow-up, to identify potential risk factors for PICS, and to assess health-related quality of life in a long-term cohort of adult cardiac arrest survivors. This prospective cohort study included adult cardiac arrest survivors admitted to the intensive care unit of a Swiss tertiary academic medical center. The primary endpoint was the prevalence of PICS at 24 months follow-up, defined as impairments in physical (measured through the European Quality of Life 5-Dimensions-3-Levels instrument [EQ-5D-3L]), neurological (defined as Cerebral Performance Category Score > 2 or Modified Rankin Score > 3), and psychological (based on the Hospital Anxiety and Depression Scale and the Impact of Event Scale-Revised) domains. Among 107 cardiac arrest survivors that completed the 2-year follow-up, 46 patients (43.0%) had symptoms of PICS, with 41 patients (38.7%) experiencing symptoms in the physical domain, 16 patients (15.4%) in the psychological domain, and 3 patients (2.8%) in the neurological domain. Key predictors for PICS in multivariate analyses were female sex (adjusted odds ratio [aOR] 3.17, 95% CI 1.08 to 9.3), duration of no-flow interval during cardiac arrest (minutes) (aOR 1.17, 95% CI 1.02 to 1.33), post-discharge job-loss (aOR 31.25, 95% CI 3.63 to 268.83), need for ongoing psychological support (aOR 3.64, 95% CI 1.29 to 10.29) or psychopharmacologic treatment (aOR 9.49, 95% CI 1.9 to 47.3), and EQ-visual analogue scale (points) (aOR 0.88, 95% CI 0.84 to 0.93). More than one-third of cardiac arrest survivors experience symptoms of PICS 2 years after resuscitation, with the highest impairment observed in the physical and psychological domains. However, long-term survivors of cardiac arrest report intact health-related quality of life when compared to the general population. Future research should focus on appropriate prevention, screening, and treatment strategies for PICS in cardiac arrest patients.

Prediction of outcomes after cardiac arrest by a generative artificial intelligence model.

Aims: To investigate the prognostic accuracy of a non-medical generative artificial intelligence model (Chat Generative Pre-Trained Transformer 4 - ChatGPT-4) as a novel aspect in predicting death and poor neurological outcome at hospital discharge based on real-life data from cardiac arrest patients. Methods: This prospective cohort study investigates the prognostic performance of ChatGPT-4 to predict outcomes at hospital discharge of adult cardiac arrest patients admitted to intensive care at a large Swiss tertiary academic medical center (COMMUNICATE/PROPHETIC cohort study). We prompted ChatGPT-4 with sixteen prognostic parameters derived from established post-cardiac arrest scores for each patient. We compared the prognostic performance of ChatGPT-4 regarding the area under the curve (AUC), sensitivity, specificity, positive and negative predictive values, and likelihood ratios of three cardiac arrest scores (Out-of-Hospital Cardiac Arrest [OHCA], Cardiac Arrest Hospital Prognosis [CAHP], and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages [PROLOGUE score]) for in-hospital mortality and poor neurological outcome. Results: Mortality at hospital discharge was 43% (n = 309/713), 54% of patients (n = 387/713) had a poor neurological outcome. ChatGPT-4 showed good discrimination regarding in-hospital mortality with an AUC of 0.85, similar to the OHCA, CAHP, and PROLOGUE (AUCs of 0.82, 0.83, and 0.84, respectively) scores. For poor neurological outcome, ChatGPT-4 showed a similar prediction to the post-cardiac arrest scores (AUC 0.83). Conclusions: ChatGPT-4 showed a similar performance in predicting mortality and poor neurological outcome compared to validated post-cardiac arrest scores. However, more research is needed regarding illogical answers for potential incorporation of an LLM in the multimodal outcome prognostication after cardiac arrest.

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.

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.

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.

"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.

Procedures of brain death diagnosis and organ explantation in a tertiary medical centre - a retrospective eight-year cohort study.

AIM OF THE STUDY: To assess the frequency and variables associated with the need for ancillary tests to confirm suspected brain death in adult patients, and to assess the time from brain death to organ explantation in donors. We further sought to identify modifiable factors influencing the time between brain death and start of surgery. METHODS: Medical records and the Swiss organ allocation system registry were screened for all consecutive adult patients diagnosed with brain death at an intensive care unit of a Swiss tertiary medical centre from 2013 to 2020. The frequency and variables associated with the performance of ancillary tests (i.e., transcranial doppler, digital subtraction angiography, and computed tomography angiography) to confirm brain death were primary outcomes; the time from death to organ explantation as well as modifying factors were defined as secondary outcomes. RESULTS: Among 91 patients with a diagnosis of brain death, 15 were not explanted and did not undergo further ancillary tests. Of the remaining 76 patients, who became organ donors after brain death, ancillary tests were performed in 24%, most frequently in patients with hypoxic-ischaemic encephalopathy. The leading presumed causes of death (not mutually exclusive) were haemorrhagic strokes (49%), hypoxic-ischaemic encephalopathies (33%) and severe traumatic brain injuries (22%). Surgery for organ explantation was started within a median of 16 hours (interquartile range [IQR] 13-18) after death with delay increasing over time (nonparametric test for trend p = 0.05), mainly due to organ allocation procedures. Patients with brain death confirmed during night shifts were explanted earlier (during night shifts 14.3 hours, IQR 11.8-16.8 vs 16.3 hours, IQR 13.5-18.5 during day shifts; p = 0.05). CONCLUSIONS: Ancillary tests to confirm brain death are frequently performed, mainly in resuscitated patients. The delay to surgery for organ explantation after confirmed brain death was longer during day shifts, increased over time and was mainly determined by organ allocation procedures.

Predicting neurological outcome in adult patients with cardiac arrest: systematic review and meta-analysis of prediction model performance.

This work aims to assess the performance of two post-arrest (out-of-hospital cardiac arrest, OHCA, and cardiac arrest hospital prognosis, CAHP) and one pre-arrest (good outcome following attempted resuscitation, GO-FAR) prediction model for the prognostication of neurological outcome after cardiac arrest in a systematic review and meta-analysis. A systematic search was conducted in Embase, Medline, and Web of Science Core Collection from November 2006 to December 2021, and by forward citation tracking of key score publications. The search identified 1'021 records, of which 25 studies with a total of 124'168 patients were included in the review. A random-effects meta-analysis of C-statistics and overall calibration (total observed vs. expected [O:E] ratio) was conducted. Discriminatory performance was good for the OHCA (summary C-statistic: 0.83 [95% CI 0.81-0.85], 16 cohorts) and CAHP score (summary C-statistic: 0.84 [95% CI 0.82-0.87], 14 cohorts) and acceptable for the GO-FAR score (summary C-statistic: 0.78 [95% CI 0.72-0.84], five cohorts). Overall calibration was good for the OHCA (total O:E ratio: 0.78 [95% CI 0.67-0.92], nine cohorts) and the CAHP score (total O:E ratio: 0.78 [95% CI 0.72-0.84], nine cohorts) with an overestimation of poor outcome. Overall calibration of the GO-FAR score was poor with an underestimation of good outcome (total O:E ratio: 1.62 [95% CI 1.28-2.04], five cohorts). Two post-arrest scores showed good prognostic accuracy for predicting neurological outcome after cardiac arrest and may support early discussions about goals-of-care and therapeutic planning on the intensive care unit. A pre-arrest score showed acceptable prognostic accuracy and may support code status discussions.

Post-intensive care syndrome in out-of-hospital cardiac arrest patients: A prospective observational cohort study.

INTRODUCTION: Intensive care unit patients are at risk for post-intensive care syndrome (PICS), which includes psychological, physical and/or cognitive sequelae after their hospital stay. Our aim was to investigate PICS in adult patients with out-of-hospital cardiac arrest (OHCA). METHODS: In this prospective observational cohort study, we assessed risks for PICS at 3 and 12-month follow-up within the following domains: a) physical impairment (EuroQol [EQ-5D-3L]), b) cognitive functioning (Cerebral Performance Category [CPC] score >1, modified Rankin Scale [mRS] >2) and c) psychological burden (Hospital Anxiety and Depression Scale [HADS], Impact of Event Scale-Revised [IES-R]). RESULTS: At 3 months, 69/139 patients (50%) met the definition of PICS including 37% in the physical domain, 25% in the cognitive domain and 13% in the psychological domain. Intubation (OR 2.3, 95%CI 1.1 to 5,0 p = 0.03), sedatives (OR 3.4, 95%CI 1 to 11, p = 0.045), mRS at discharge (OR 4.3, 95%CI 1.70 to 11.01, p = 0.002), CPC at discharge (OR 3.3, 95%CI 1.4 to 7.6, p = 0.005) and post-discharge work loss (OR 13.4, 95%CI 1.7 to 107.5, p = 0.014) were significantly associated with PICS. At 12 months, 52/110 (47%) patients had PICS, which was associated with prolonged duration of rehabilitation, higher APACHE scores, and higher mRS and CPC scores at hospital discharge. CONCLUSIONS: Nearly half of long-term OHCA survivors show PICS after 3 and 12 months. These high numbers call for more emphasis on appropriate screening and treatment in this patient population. Future studies should evaluate whether early identification of these patients enables preventive strategies and treatment options.

Comparison of different clinical risk scores to predict long-term survival and neurological outcome in adults after cardiac arrest: results from a prospective cohort study.

BACKGROUND: Several scoring systems have been used to predict short-term outcome in patients with out-of-hospital cardiac arrest (OHCA), including the disease-specific OHCA and CAHP (Cardiac Arrest Hospital Prognosis) scores, as well as the general severity-of-illness scores Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II). This study aimed to assess the prognostic performance of these four scores to predict long-term outcomes (≥ 2 years) in adult cardiac arrest patients. METHODS: This is a prospective single-centre cohort study including consecutive cardiac arrest patients admitted to intensive care in a Swiss tertiary academic medical centre. The primary endpoint was 2-year mortality. Secondary endpoints were neurological outcome at 2 years post-arrest assessed by Cerebral Performance Category with CPC 1-2 defined as good and CPC 3-5 as poor neurological outcome, and 6-year mortality. RESULTS: In 415 patients admitted to intensive care, the 2-year mortality was 58.1%, with 96.7% of survivors showing good neurological outcome. The 6-year mortality was 82.5%. All four scores showed good discriminatory performance for 2-year mortality, with areas under the receiver operating characteristics curve (AUROC) of 0.82, 0.87, 0.83 and 0.81 for the OHCA, CAHP, APACHE II and SAPS II scores. The results were similar for poor neurological outcome at 2 years and 6-year mortality. CONCLUSION: This study suggests that two established cardiac arrest-specific scores and two severity-of-illness scores provide good prognostic value to predict long-term outcome after cardiac arrest and thus may help in early goals-of-care discussions.

Long-term Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-analysis.

Importance: Data on long-term survival beyond 12 months after out-of-hospital cardiac arrest (OHCA) of a presumed cardiac cause are scarce. Objective: To investigate the long-term survival of adult patients after surviving the initial hospital stay for an OHCA. Data Sources: A systematic search of the EMBASE and MEDLINE databases was performed from database inception to March 25, 2021. Study Selection: Clinical studies reporting long-term survival after OHCA were selected based on predefined inclusion and exclusion criteria according to a preregistered study protocol. Data Extraction and Synthesis: Patient data were reconstructed from Kaplan-Meier curves using an iterative algorithm and then pooled to generate survival curves. As a separate analysis, an aggregate data meta-analysis was performed. Main Outcomes and Measures: The primary outcome was long-term survival (>12 months) after OHCA for patients surviving to hospital discharge or 30 days after OHCA. Results: The search identified 15 347 reports, of which 21 studies (11 800 patients) were included in the Kaplan-Meier-based meta-analysis and 33 studies (16 933 patients) in an aggregate data meta-analysis. In the Kaplan-Meier-based analysis, the median survival time for patients surviving to hospital discharge was 5.0 years (IQR, 2.3-7.9 years). The estimated survival rates were 82.8% (95% CI, 81.9%-83.7%) at 3 years, 77.0% (95% CI, 75.9%-78.0%) at 5 years, 63.9% (95% CI, 62.3%-65.4%) at 10 years, and 57.5% (95% CI, 54.8%-60.1%) at 15 years. Compared with patients with a nonshockable initial rhythm, patients with a shockable rhythm had a lower risk of long-term mortality (hazard ratio, 0.30; 95% CI, 0.23-0.39; P < .001). Different analyses, including an aggregate data meta-analysis, confirmed these results. Conclusions and Relevance: In this comprehensive systematic review and meta-analysis, long-term survival after 10 years in patients surviving the initial hospital stay after OHCA was between 62% and 64%. Additional research is needed to understand and improve the long-term survival in this vulnerable patient population.

First-Response ABCDE Management of Status Epilepticus: A Prospective High-Fidelity Simulation Study.

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.

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.

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.

Prevalence and factors associated with psychological burden in COVID-19 patients and their relatives: A prospective observational cohort study.

BACKGROUND: Due 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. METHODS: In 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). RESULTS: Among 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; p<0.001). The overall model also had good discrimination, with an AUC of 0.87. CONCLUSION: A 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.

Diagnostic Errors Induced by a Wrong a Priori Diagnosis: A Prospective Randomized Simulator-Based Trial.

Preventive strategies against diagnostic errors require the knowledge of underlying mechanisms. We examined the effects of a wrong a priori diagnosis on diagnostic accuracy of a focussed assessment in an acute myocardial infarction scenario. One-hundred-and-fifty-six medical students (cohort 1) were randomized to three study arms differing in the a priori diagnosis revealed: no diagnosis (control group), myocardial infarction (correct diagnosis group), and pulmonary embolism (wrong diagnosis group). Forty-four physicians (cohort 2) were randomized to the control group and the wrong diagnosis group. Primary endpoint was the participants' final presumptive diagnosis. Among students, the correct diagnosis of an acute myocardial infarction was made by 48/52 (92%) in the control group, 49/52 (94%) in the correct diagnosis group, and 14/52 (27%) in the wrong diagnosis group (p < 0.001 vs. both other groups). Among physicians, the correct diagnosis was made by 20/21 (95%) in the control group and 15/23 (65%) in the wrong diagnosis group (p = 0.023). In the wrong diagnosis group, 31/52 (60%) students and 6/23 (19%) physicians indicated their initially given wrong a priori diagnosis pulmonary embolism as final diagnosis. A wrong a priori diagnosis significantly increases the likelihood of a diagnostic error during a subsequent patient encounter.

Serum neurofilament measurement improves clinical risk scores for outcome prediction after cardiac arrest: results of a prospective study.

BACKGROUND: A recent study found serum neurofilament light chain (NfL) levels to be strongly associated with poor neurological outcome in patients after cardiac arrest. Our aim was to confirm these findings in an independent validation study and to investigate whether NfL improves the prognostic value of two cardiac arrest-specific risk scores. METHODS: This prospective, single-center study included 164 consecutive adult after out-of-hospital cardiac arrest (OHCA) patients upon intensive care unit admission. We calculated two clinical risk scores (OHCA, CAHP) and measured NfL on admission within the first 24 h using the single molecule array NF-light® assay. The primary endpoint was neurological outcome at hospital discharge assessed with the cerebral performance category (CPC) score. RESULTS: Poor neurological outcome (CPC > 3) was found in 60% (98/164) of patients, with 55% (91/164) dying within 30 days of hospitalization. Compared to patients with favorable outcome, NfL was 14-times higher in patients with poor neurological outcome (685 ± 1787 vs. 49 ± 111 pg/mL), with an adjusted odds ratio of 3.4 (95% CI 2.1 to 5.6, p < 0.001) and an area under the curve (AUC) of 0.82. Adding NfL to the clinical risk scores significantly improved discrimination of both the OHCA score (from AUC 0.82 to 0.89, p < 0.001) and CAHP score (from AUC 0.89 to 0.92, p < 0.05). Adding NfL to both scores also resulted in significant improvement in reclassification statistics with a Net Reclassification Index (NRI) of 0.58 (p < 0.001) for OHCA and 0.83 (p < 0.001) for CAHP. CONCLUSIONS: Admission NfL was a strong outcome predictor and significantly improved two clinical risk scores regarding prognostication of neurological outcome in patients after cardiac arrest. When confirmed in future outcome studies, admission NfL should be considered as a standard laboratory measures in the evaluation of OHCA patients.

Association of medical futility with do-not-resuscitate (DNR) code status in hospitalised patients.

Guidelines recommend a 'do-not-resuscitate' (DNR) code status for inpatients in which cardiopulmonary resuscitation (CPR) attempts are considered futile because of low probability of survival with good neurological outcome. We retrospectively assessed the prevalence of DNR code status and its association with presumed CPR futility defined by the Good Outcome Following Attempted Resuscitation score and the Clinical Frailty Scale in patients hospitalised in the Divisions of Internal Medicine and Traumatology/Orthopedics at the University Hospital of Basel between September 2018 and June 2019. The definition of presumed CPR futility was met in 467 (16.2%) of 2889 patients. 866 (30.0%) patients had a DNR code status. In a regression model adjusted for age, gender, main diagnosis, nationality, language and religion, presumed CPR futility was associated with a higher likelihood of a DNR code status (37.3% vs 7.1%, adjusted OR 2.99, 95% CI 2.31 to 3.88, p<0.001). In the subgroup of patients with presumed futile CPR, 144 of 467 (30.8%) had a full code status, which was independently associated with younger age, male gender, non-Christian religion and non-Swiss citizenship. We found a significant proportion of hospitalised patients to have a full code status despite the fact that CPR had to be considered futile according to an established definition. Whether these decisions were based on patient preferences or whether there was a lack of patient involvement in decision-making needs further investigation.

Arginine and Arginine/ADMA Ratio Predict 90-Day Mortality in Patients with Out-of-Hospital Cardiac Arrest-Results from the Prospective, Observational COMMUNICATE Trial.

(1) Background: In patients with shock, the L-arginine nitric oxide pathway is activated, causing an elevation of nitric oxide, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels. Whether these metabolites provide prognostic information in patients after out-of-hospital cardiac arrest (OHCA) remains unclear. (2) Methods: We prospectively included OHCA patients, recorded clinical parameters and measured plasma ADMA, SDMA and Arginine levels by liquid chromatography tandem mass spectrometry (LC-MS). The primary endpoint was 90-day mortality. (3) Results: Of 263 patients, 130 (49.4%) died within 90 days after OHCA. Compared to survivors, non-survivors had significantly higher levels of ADMA and lower Arginine and Arginine/ADMA ratios in univariable regression analyses. Arginine levels and Arginine/ADMA ratio were significantly associated with 90-day mortality (OR 0.51 (95%CI 0.34 to 0.76), p < 0.01 and OR 0.40 (95%CI 0.26 to 0.61), p < 0.001, respectively). These associations remained significant in several multivariable models. Arginine/ADMA ratio had the highest predictive value with an area under the curve (AUC) of 0.67 for 90-day mortality. Results for secondary outcomes were similar with significant associations with in-hospital mortality and neurological outcome. (4) Conclusion: Arginine and Arginine/ADMA ratio were independently associated with 90-day mortality and other adverse outcomes in patients after OHCA. Whether therapeutic modification of the L-arginine-nitric oxide pathway has the potential to improve outcome should be evaluated.