Oxygen Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODS: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days. RESULTS: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 µg per liter in the restrictive-target group and 18 µg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

The risk of diabetes and HbA1c deterioration during antipsychotic drug treatment: A Danish two-cohort study among patients with first-episode schizophrenia.

BACKGROUND: Antipsychotics increase the risk of developing diabetes, but clinical trials are not generalizable with short follow-up, while observational studies often lack important information, particularly hemoglobin A1c (HbA1c). METHODS: We followed two Danish cohorts with schizophrenia. First, using Danish nationwide registers, we identified all individuals diagnosed with first-episode schizophrenia (FES) between 1999 and 2019 (n = 31,856). Exposure was a redeemed prescription for an antipsychotic, and the outcome was diabetes, defined via hospital-based diagnosis and redeemed prescriptions for glucose-lowering drugs. Adjusted Cox regression calculated hazard rate ratios (HRR). Second, using data from the Central Denmark Region, we identified all individuals diagnosed with FES from October 2016 to September 2022 (n = 2671). Using a within-subject design, we analyzed the change in HbA1c during the 2 years after initiation of specific antipsychotics compared to the 2 years before. RESULTS: In the nationwide cohort, 2543 (8.0%) individuals developed diabetes (incidence rate = 9.39 [95% CI = 9.03-9.76] per 1000 person-years). Antipsychotics, compared to periods without, were associated with an increased risk of developing diabetes (HRR = 2.04, 95% CI = 1.75-2.38). We found a dose-response association, particularly for second-generation antipsychotics, and different risk rates for specific antipsychotics. In the Central Denmark Region cohort, a total of 9.2% developed diabetes but mean HbA1c levels remained stable at 37 mmol/mol during the 2 years after initiation of antipsychotic medication. CONCLUSION: This comprehensive real-world two-cohort study emphasizes that diabetes affects almost 10% of patients with FES. Antipsychotics increase this risk, while HbA1c deterioration requires longer treatment. These findings are important for clinicians and young patients with FES.

The use of prone position ventilation in Danish patients with COVID-19-induced severe acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation: A nationwide cohort study with focus on pulmonary effects.

BACKGROUND: Prone position ventilation (PPV) is recommended for patients with COVID-19 induced severe Adult Respiratory Distress Syndrome (ARDS) and is used for patients supported with V-V ECMO as well. The purpose of this study was to describe the use of PPV in these patients focusing on physiological effects with the hypothesis that PPV could reduce oxygen need and improve dynamic compliance. METHODS: This study was a nationwide retrospective analysis of all COVID-19 patients in Denmark from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. Data on the number of patients treated with PPV, number of PPV sessions, timing, the time spent in prone position, pulmonary physiological response types with analysis of variables affecting the response are reported. RESULTS: Out of 68 patients 44 were treated with 220 PPV sessions and a positive clinical response was observed in 80% of patients but only in 45% of sessions. On a single session level, increased compliance was observed in 38% and increased oxygenation in only 15% of 220 sessions, with within-patient heterogeneity. Higher dynamic compliance at the beginning of a PPV session was associated with a lower delta change in dynamic compliance during PPV. The response to a PPV session could not be predicted by the response in the prior session. Dynamic compliance did not change during the ECMO course. CONCLUSION: Eighty percent of patients responded positively during a PPV session, but this was not associated with overall pulmonary improvement. On a single patient level, responses were heterogenous and only 45% of sessions resulted in clinical improvement. Response in dynamic compliance was associated with starting values of compliance.

Precision Measurement of Trident Production in Strong Electromagnetic Fields.

We demonstrate experimentally that the trident process e^{-}→e^{-}e^{+}e^{-} in a strong external field, with a spatial extension comparable to the effective radiation length, is well understood theoretically. The experiment, conducted at CERN, probes values for the strong field parameter χ up to 2.4. Experimental data and theoretical expectations using the local constant field approximation show remarkable agreement over almost 3 orders of magnitude in yield.

Within-patient horizontal transfer of pOXA-48 from a hypervirulent Klebsiella pneumoniae SL218 to Serratia marcescens following spread of the K. pneumoniae isolate among hospitalised patients, Denmark, 2021.

A hypervirulent Klebsiella pneumoniae SL218 (ST23-KL57), phylogenetically distinct from the classical hypervirulent SL23 (ST23-KL1) lineage, was transmitted between hospitalised patients in Denmark in 2021. The isolate carried a hybrid resistance and virulence plasmid containing bla NDM-1 and a plasmid containing bla OXA-48 (pOXA-48); the latter plasmid was horizontally transferred within-patient to Serratia marcescens. The convergence of drug resistance and virulence factors in single plasmids and in different lineages of K. pneumoniae is concerning and requires surveillance.

Use of prone position ventilation in patients with COVID-19 induced severe ARDS supported with V-V ECMO: A danish cohort study with focus on adverse events.

INTRODUCTION: Prone position ventilation (PPV) of patients with adult respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO) may improve oxygenation and alveolar recruitment and is recommended when extensive dorsal consolidations are present, but only few data regarding adverse events (AE) related to PPV in this group of patients have been published. METHODS: Nationwide retrospective analysis of 68 COVID-19 patients admitted from March 2020 - December 2021 with severe ARDS and need of V-V ECMO support. The number of patients treated with PPV, number of PPV-events, timing, the time spent in prone position, number and causes of AE are reported. Causes to stop the PPV regimen and risk factors for AE were explored. RESULTS: 44 out of 68 patients were treated with PPV, and 220 PPV events are evaluated. AE were identified in 99 out of 220 (45%) PPV events and occurred among 31 patients (71%). 1 fatal PPV related AE was registered. Acute supination occurred in 19 events (9%). Causes to stop the PPV regimen were almost equally distributed between effect (weaned from ECMO), no effect, death (of other reasons) and AE. Frequent causes of AE were pressures sores and ulcers, hypoxia, airway related and ECMO circuit related. Most AE occurred during patients first or second PPV event. CONCLUSIONS: PPV treatment was found to carry a high incidence of PPV related AE in these patients. Causes and preventive measures to reduce occurrence of PPV related AE during V-V ECMO support need further exploration.

Ethics in extracorporeal life support: a narrative review.

During 50 years of extracorporeal life support (ECLS), this highly invasive technology has left a considerable imprint on modern medicine, and it still confronts researchers, clinicians and policymakers with multifarious ethical challenges. After half a century of academic discussion about the ethics of ECLS, it seems appropriate to review the state of the argument and the trends in it. Through a comprehensive literature search on PubMed, we identified three ethical discourses: (1) trials and evidence accompanying the use of ECLS, (2) ECLS allocation, decision-making and limiting care, and (3) death on ECLS and ECLS in organ donation. All included articles were carefully reviewed, arguments extracted and grouped into the three discourses. This article provides a narrative synthesis of these arguments, evaluates the opportunities for mediation and substantiates the necessity of a shared decision-making approach at the limits of medical care.

Accepting the avoidable death: The philosophy of limiting intensive care.

Limiting intensive care is paid increasing attention. In the echoing call for physicians' ethical self-restriction, it is easily overlooked, however, that ethics needs a critical epistemological analysis before it can suffice as an emergency brake to futile treatment. This analysis is provided by the present essay. The authors suggest that the difficulties of resolving moral dilemmas related to limiting intensive care may just be due to the unclarified epistemological status of moral claims. Even if normative ethics cannot prescribe right decisions, but only draw conclusions from defined premises, the premises may or may not be true. Their intertwined descriptive and normative evidence is endorsed in an academic and political discourse. There will necessarily be various demands for rationality in prudent decisions between physicians, their patients and society. These demands are formulated dialogically through critical questions and justified answers. A good argument is the convincing one that, finally and ideally, leads to the absence of open objections. Thus, in the end the rightness of a given decision does not depend on axiomatic moral principles, but is comparative and conditional, as it is given in an omnilateral argument. Neither is it the democratic process of shared decision making that we should evaluate, but rather the argumentative state itself, when we judge the morality of health politics and clinical practice.

Standard operating procedures as a tool to improve medical documentation in preclinical emergency medicine.

AIM: To evaluate the effect of standard operating procedures (SOPs) to improve the completion of patient care documentation items on patient care reports (PCRs) in a physician-staffed, 4500-calls-per-year preclinical ground emergency medical service (EMS) base. METHODS: Two series of PCRs were analysed before (n=505) and after (n=520) the introduction of SOPs. PCR forms were analysed for the rate of completion of documentation comparing prompted data in check boxes and non-prompted data written in blank spaces at the discretion of the emergency physician. The chi2 test for independence was used to assess the effect of SOPs and prompting on data completion rate. RESULTS: SOPs improved the documentation rate of numerous prompted and non-prompted items, independent of whether these items had a high (eg, Glasgow Coma Score: 91.5% vs 95.7%) or a low documentation rate during the pre-SOP period (eg, allergies: 6.2% vs 18.7%). Prompted items were more frequently documented than non-prompted items, both before and after the introduction of SOPs. Lowest rates were found among non-prompted items (eg, 'last meal' 3.6%). CONCLUSIONS: In this EMS base, developing SOPs is an effective tool to improve the quality of PCRs and the rate of completion of documentation items. Check boxes on PCR forms seem to have an important impact as they prompt the initial assessment, treatment and documentation of the actions taken during an EMS call. Consequently, SOPs and check boxes may serve to improve the transition of important information to emergency department staff, and thus contribute to improved patient care.

Effects of a standard operating procedure on prehospital emergency care of patients presenting with symptoms of the acute coronary syndrome.

To determine whether a standard operating procedure (SOP) for prehospital management of patients with the acute coronary syndrome (ACS) improves the quality of patient care in terms of adherence to treatment guidelines of the European Society of Cardiology. Among a total of 1025 patient medical records collected from a period before and after the introduction of the SOP, 269 records included the working diagnosis of ACS and were then reviewed for guideline adherence. Most aspects of patient evaluation, monitoring, treatment, and hospital allocation were fairly guideline adherent (>70%) before the SOP was introduced and were not affected by the SOP. The percentage of cases in whom sublingual nitrate (55.2 vs. 66.7%) or intravenous morphine (26.9 vs. 43.0%) was administered without contraindications was higher after the SOP had been introduced. Therefore, the use of an SOP in prehospital emergency medicine can partly improve the adherence to guideline recommendations for the treatment of patients with ACS.