Predicting neurological outcome after out-of-hospital cardiac arrest with cumulative information; development and internal validation of an artificial neural network algorithm

BACKGROUND: Prognostication of neurological outcome in patients who remain comatose after cardiac arrest resuscitation is complex. Clinical variables, as well as biomarkers of brain injury, cardiac injury, and systemic inflammation, all yield some prognostic value. We hypothesised that cumulative information obtained during the first three days of intensive care could produce a reliable model for predicting neurological outcome following out-of-hospital cardiac arrest (OHCA) using artificial neural network (ANN) with and without biomarkers. METHODS: We performed a post hoc analysis of 932 patients from the Target Temperature Management trial. We focused on comatose patients at 24, 48, and 72 h post-cardiac arrest and excluded patients who were awake or deceased at these time points. 80% of the patients were allocated for model development (training set) and 20% for internal validation (test set). To investigate the prognostic potential of different levels of biomarkers (clinically available and research-grade), patients' background information, and intensive care observation and treatment, we created three models for each time point: (1) clinical variables, (2) adding clinically accessible biomarkers, e.g., neuron-specific enolase (NSE) and (3) adding research-grade biomarkers, e.g., neurofilament light (NFL). Patient outcome was the dichotomised Cerebral Performance Category (CPC) at six months; a good outcome was defined as CPC 1-2 whilst a poor outcome was defined as CPC 3-5. The area under the receiver operating characteristic curve (AUROC) was calculated for all test sets. RESULTS: AUROC remained below 90% when using only clinical variables throughout the first three days in the ICU. Adding clinically accessible biomarkers such as NSE, AUROC increased from 82 to 94% (p < 0.01). The prognostic accuracy remained excellent from day 1 to day 3 with an AUROC at approximately 95% when adding research-grade biomarkers. The models which included NSE after 72 h and NFL on any of the three days had a low risk of false-positive predictions while retaining a low number of false-negative predictions. CONCLUSIONS: In this exploratory study, ANNs provided good to excellent prognostic accuracy in predicting neurological outcome in comatose patients post OHCA. The models which included NSE after 72 h and NFL on all days showed promising prognostic performance

Advanced engineering environment collaboration project.

The Advanced Engineering Environment (AEE) is a model for an engineering design and communications system that will enhance project collaboration throughout the nuclear weapons complex (NWC). Sandia National Laboratories and Parametric Technology Corporation (PTC) worked together on a prototype project to evaluate the suitability of a portion of PTC's Windchill 9.0 suite of data management, design and collaboration tools as the basis for an AEE. The AEE project team implemented Windchill 9.0 development servers in both classified and unclassified domains and used them to test and evaluate the Windchill tool suite relative to the needs of the NWC using weapons project use cases. A primary deliverable was the development of a new real time collaborative desktop design and engineering process using PDMLink (data management tool), Pro/Engineer (mechanical computer aided design tool) and ProductView Lite (visualization tool). Additional project activities included evaluations of PTC's electrical computer aided design, visualization, and engineering calculations applications. This report documents the AEE project work to share information and lessons learned with other NWC sites. It also provides PTC with recommendations for improving their products for NWC applications

Social safety and behavioral aspects of populations financial inclusion: A multicountry analysis

This article aims to investigate the connection between behavioral aspects of populations financial inclusion and the level of social safety. The study was conducted in several stages: collecting the necessary input, determining The Index of socio-safety, selecting the most relevant factors that characterize the behavioral aspects of financial inclusion, determining the functional relationships between The Index of socio-safety and indicators describing critical behavioral issues of financial inclusion. The study involved 26 countries with different levels of economic development, and 18 indicators (10 characterized the behavioral aspects of financial involvement of the population, 8 - the world vectors of social safety). The Index of socio-safety was obtained with the help of PCA. Russian Federation and South Africa have the highest level of The Index among the studied countries. The lowest level of the calculated indicator is in Mozambique and Burkina Faso. Correlation and regression analysis revealed a statistically significant relationship between The Index of socio-safety and an increasing number of ATMs per 100,000 adults, usage of the internet to pay bills or to buy something online and increase the percentage of respondents who report having a credit card

Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial

Background: Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. Methods: In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4-6 on modified Rankin scale). Results: A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84-1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80-1.26). Conclusions: Using a hospital's average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever. Keywords: Hypothermia; Out of hospital cardiac arrest; Temperature management; Time to target temperature

Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease

BACKGROUND: Interstitial lung disease (ILD) is a common manifestation of systemic sclerosis and a leading cause of systemic sclerosis-related death. Nintedanib, a tyrosine kinase inhibitor, has been shown to have antifibrotic and antiinflammatory effects in preclinical models of systemic sclerosis and ILD. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to investigate the efficacy and safety of nintedanib in patients with ILD associated with systemic sclerosis. Patients who had systemic sclerosis with an onset of the first non-Raynaud's symptom within the past 7 years and a high-resolution computed tomographic scan that showed fibrosis affecting at least 10% of the lungs were randomly assigned, in a 1:1 ratio, to receive 150 mg of nintedanib, administered orally twice daily, or placebo. The primary end point was the annual rate of decline in forced vital capacity (FVC), assessed over a 52-week period. Key secondary end points were absolute changes from baseline in the modified Rodnan skin score and in the total score on the St. George's Respiratory Questionnaire (SGRQ) at week 52. RESULTS: A total of 576 patients received at least one dose of nintedanib or placebo; 51.9% had diffuse cutaneous systemic sclerosis, and 48.4% were receiving mycophenolate at baseline. In the primary end-point analysis, the adjusted annual rate of change in FVC was 1252.4 ml per year in the nintedanib group and 1293.3 ml per year in the placebo group (difference, 41.0 ml per year; 95% confidence interval [CI], 2.9 to 79.0; P=0.04). Sensitivity analyses based on multiple imputation for missing data yielded P values for the primary end point ranging from 0.06 to 0.10. The change from baseline in the modified Rodnan skin score and the total score on the SGRQ at week 52 did not differ significantly between the trial groups, with differences of 120.21 (95% CI, 120.94 to 0.53; P=0.58) and 1.69 (95% CI, 120.73 to 4.12 [not adjusted for multiple comparisons]), respectively. Diarrhea, the most common adverse event, was reported in 75.7% of the patients in the nintedanib group and in 31.6% of those in the placebo group. CONCLUSIONS: Among patients with ILD associated with systemic sclerosis, the annual rate of decline in FVC was lower with nintedanib than with placebo; no clinical benefit of nintedanib was observed for other manifestations of systemic sclerosis. The adverse-event profile of nintedanib observed in this trial was similar to that observed in patients with idiopathic pulmonary fibrosis; gastrointestinal adverse events, including diarrhea, were more common with nintedanib than with placebo

Survival in patients without acute ST elevation after cardiac arrest and association with early coronary angiography:a post hoc analysis from the TTM trial

To investigate whether early coronary angiography (CAG) after out-of-hospital cardiac arrest of a presumed cardiac cause is associated with improved outcomes in patients without acute ST elevation

Microbiological profile of nosocomial infections following cardiac arrest: Insights from the targeted temperature management (TTM) trial

Aims: Infectious complications frequently occur in intensive care unit patients admitted after out-of-hospital cardiac arrest. There is debate on the effects of temperature management on the incidence of infections, as well as on the efficacy and choice of antibiotic prophylaxis. In this substudy of the targeted temperature management (TTM) trial, we describe the microbiological profile of infectious complications in patients with cardiac arrest and examined the impact of TTM at 33 °C compared to TTM at 36 °C. Furthermore we aimed to determine the association between antibiotic prophylaxis and the incidence of infections. Methods: This is a posthoc analysis of the TTM cohort. Microbiological data was retrospectively collected for the first 14-days of ICU-admission. Logistic regression was used to determine the relationship between antibiotic prophylaxis and pneumonia adjusted for mortality. Results: Of 696 patients included in this analysis, 158 (23%) developed pneumonia and 28 (4%) had bacteremia with a clinically relevant pathogen. Staphylococcus aureus was the most common pathogen isolated in patients with pneumonia (23%) and in patients with bacteremia (24%). Gram-negative pathogens were most common overall. TTM did not have an impact on the microbiological profile. The use of antibiotic prophylaxis was significantly associated with a reduced risk of infection (OR 0.59, 95%CI 0.43-0.79, p = 0.0005). This association remained significant after correcting for confounders (OR 0.64, 95%CI 0.46-0.90; p = 0.01). The association is not present in a model after correction for clustering within centers (aOR 0.55, 95%CI 0.20–1.47, p = 0.22). Adjustment for mortality did not influence the outcome. Conclusion: Gram-negative pathogens are the most common causes of nosocomial infections following cardiac arrest. TTM does not impact the microbiological profile. It remains unclear whether patients in ICUs using antibiotic prophylaxis have a reduced risk of pneumonia and bacteremia that is unrelated to center effects