No evidence for association between late pregnancy maternal cortisol and gray matter volume in a healthy community sample of young adolescents.

A compelling amount of animal and human research has shown that perceived maternal stress during pregnancy can affect the neurodevelopment of the offspring. Prenatal maternal cortisol is frequently proposed as the biological key mechanism underlying this link; however, literature that investigates the effects of prenatal cortisol on subsequent neurodevelopment in humans is scarce. By using longitudinal data from a relatively large community sample of mother-child dyads (N = 73), this pre-registered study prospectively examined the role of maternal prenatal cortisol concentrations on subsequent individual differences in gray matter volume (GMV) and hippocampal subfield volumes at the onset of puberty of the offspring (12 years of age). Two markers of cortisol, that is, evening cortisol and circadian decline over the day, were used as indicators of maternal physiological stress during the last trimester of pregnancy. The results indicate that prenatal maternal cortisol levels were not associated with GMV or hippocampal subfield volumes of the children. These findings suggest that late pregnancy maternal cortisol may not be related to the structural development of the offspring's brain, at least not in healthy community samples and at the onset of puberty. When examining the influence of prenatal stress on offspring neurodevelopment, future investigations should delineate gestational timing effects of the cortisol exposure, cortisol assessment method, and impact of additional biomarkers, as these were not investigated in this study.

Pathway to a land-neutral expansion of Brazilian renewable fuel production.

Biofuels are currently the only available bulk renewable fuel. They have, however, limited expansion potential due to high land requirements and associated risks for biodiversity, food security, and land conflicts. We therefore propose to increase output from ethanol refineries in a land-neutral methanol pathway: surplus CO2-streams from fermentation are combined with H2 from renewably powered electrolysis to synthesize methanol. We illustrate this pathway with the Brazilian sugarcane ethanol industry using a spatio-temporal model. The fuel output of existing ethanol generation facilities can be increased by 43%-49% or ~100 TWh without using additional land. This amount is sufficient to cover projected growth in Brazilian biofuel demand in 2030. We identify a trade-off between renewable energy generation technologies: wind power requires the least amount of land whereas a mix of wind and solar costs the least. In the cheapest scenario, green methanol is competitive to fossil methanol at an average carbon price of 95€ tCO2-1.

Simulation-based training improves process times in acute stroke care (STREAM).

BACKGROUND: The objective of the STREAM Trial was to evaluate the effect of simulation training on process times in acute stroke care. METHODS: The multicenter prospective interventional STREAM Trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving intravenous thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the pre-existing treatment algorithm. RESULTS: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre-intervention (interquartile range [IQR] 25-43 min) to 33 min (IQR 23-39 min, p = 0.03) post-intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post-interventional phase (-21 min, simulation-naive: 95 min, IQR 69-111 vs. simulation-experienced: 74 min, IQR 51-92, p = 0.04). CONCLUSION: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.

Measuring Patient Safety Climate in Acute Stroke Therapy.

Background: Treatment of acute stroke is highly time-dependent and performed by a multiprofessional, interdisciplinary team. Interface problems are expectable and issues relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety climate. The objective of this study was to evaluate the SAQ for the first time in the context of acute stroke care. Methods: A survey was carried out during the STREAM trial (NCT00032282) at seven university hospitals in Germany from October 2017 to October 2018. The anonymous survey included 33 questions (5-point Likert scale, 1 = disagree to 5 = agree) and addressed the entire multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. Results: 164 questionnaires were completed yielding a response rate of 66.4%. 67.7% of respondents were physicians and 25.0% were nurses. Confirmatory Factor Analysis revealed that the original 6-factor structure fits the data adequately. The SAQ for acute stroke care showed strong internal consistency (α = 0.88). Exploratory analysis revealed differences in scores on the SAQ dimensions when comparing physicians to nurses and when comparing physicians according to their duration of professional experience. Conclusion: The SAQ is a helpful and well-applicable tool to measure patient safety in acute stroke care. In comparison to other high-risk fields in medicine, patient safety climate in acute stroke care seems to be on a similar level with the potential for further improvements. Trial registration: www.ClinicalTrials.gov Identifier: NCT032282.

Simulation-based training improves patient safety climate in acute stroke care (STREAM).

BACKGROUND: Treatment of acute stroke performed by a multiprofessional, interdisciplinary team is highly time dependent. Interface problems are preprogrammed and pitfalls relevant to patient safety are omnipresent. The Safety Attitudes Questionnaire (SAQ) is a validated and widely used instrument to measure patient safety. The objective of this study was to evaluate the influence of Simulation-based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM) on patient safety measured by SAQ in the context of acute stroke care. METHODS: During the STREAM trial at seven university hospitals in Germany from October 2017 to October 2018, an anonymous survey was conducted before and after the STREAM intervention centering around interdisciplinary simulation training. The questionnaire, based on the SAQ, included 33 items (5-point Likert scale, 1 = disagree to 5 = agree) and was addressed at the whole multiprofessional stroke team. Statistical analyses were used to examine psychometric properties as well as descriptive findings. RESULTS: In total 167 questionnaires were completed representing an overall response rate of 55.2%, including especially physicians (65.2%) and nurses (26.3%). Safety climate was significantly improved (pre-interventional: 3.34 ± .63 vs. post-interventional: 3.56 ± .69, p = .028). The same applies for teamwork climate among stroke teams (pre-interventional: 3.76 ± .59 vs. post-interventional: 3.84 ± .57, p = .001). The perceived benefit was most relevant among nurses. CONCLUSIONS: The STREAM intervention centering around interdisciplinary simulation training increases perceived patient safety climate assessed by the SAQ in acute stroke therapy. These results have the potential to be a basis for future quality improvement programs.

Evaluation of Endovascular Treatment for Acute Basilar Occlusion in a State-Wide Prospective Stroke Registry.

Context: Despite overwhelming evidence for endovascular therapy in anterior circulation ischemic stroke due to large-vessel occlusion, data regarding the treatment of acute basilar artery occlusion (BAO) are still equivocal. The BASICS trial failed to show an advantage of endovascular therapy (EVT) over best medical treatment (BMT). In contrast, data from the recently published BASILAR registry showed a better outcome in patients receiving EVT. Objective: The aim of the study was to investigate the safety and efficacy of EVT plus BMT vs. BMT alone in acute BAO. Methods: We analyzed the clinical course and short-term outcomes of patients with radiologically confirmed BAO dichotomized by BMT plus EVT or BMT only as documented in a state-wide prospective registry of consecutive patients hospitalized due to acute stroke. The primary endpoint was a favorable functional outcome (mRS 0-3) at hospital discharge assessed as common odds ratio using binary logistic regression. Secondary subgroup analyses and propensity score matching were added. Safety outcomes included mortality, the rate of intracerebral hemorrhages, and complications during hospitalization. Results: We included 403 patients with acute BAO (2017-2019). A total of 270 patients (67%) were treated with BMT plus EVT and 133 patients (33%) were treated with BMT only. A favorable outcome (mRS 0-3) was observed in 33.8% of the BMT and 26.7% of the BMT plus EVT group [OR.770, CI (0.50-1.2)]. Subgroup analyses for patients with a NIHSS score > 10 at admission to the hospital revealed a benefit from EVT [OR 3.05, CI (1.03-9.01)]. Conclusions: In this prospective, quasi population-based registry of patients hospitalized with acute BAO, BMT plus EVT was not superior to BMT alone. Nevertheless, our results suggest that severely affected BAO patients are more likely to benefit from EVT.

Neurological symptom burden impacts survival prognosis in patients with newly diagnosed non-small cell lung cancer brain metastases.

BACKGROUND: Brain metastases (BM) are a frequent complication of advanced cancer and are characterized by a variety of neurological symptoms. Although the presence of neurological symptoms is included in the response assessment in patients with primary brain tumors, to the authors' knowledge little is known regarding the prognostic impact of neurological symptoms in patients with BM. METHODS: Patients with newly diagnosed BM from non-small cell lung cancer were identified from the Vienna Brain Metastasis Registry and were evaluated according to the incidence, distribution, and prognostic impact of neurological symptoms at the time of diagnosis of BM. RESULTS: A total of 1608 patients (57.3% male and 42.7% female; median age, 62 years) were available for further analyses. Neurological symptoms including focal deficits (985 patients; 61.3%), signs of increased intracranial pressure (483 patients; 30.0%), epileptic seizures (224 patients; 13.9%), and neuropsychological symptoms (233 patients; 14.5%) were documented in 1186 of the 1608 patients (73.8%). Patients with asymptomatic BM presented with a longer median overall survival after the diagnosis of BM compared with patients with symptomatic BM (11 months vs 7 months; P < .001). In multivariate analysis with a diagnosis-specific graded prognostic assessment (hazard ratio, 1.41; 95% CI, 1.33-1.50 [P < .001]), the presence of neurological symptoms (hazard ratio, 1.39; 95% CI, 1.23-1.57 [P < .001]) was found to be independently associated with survival prognosis from the time of diagnosis of BM. CONCLUSIONS: Neurological symptoms at the time of BM diagnosis demonstrated a strong and independent association with survival prognosis. The results of the current study have highlighted the need for the integration of the presence of neurological symptoms into the prognostic assessment of patients with BM from non-small cell lung cancer. LAY SUMMARY: Neurological symptom evaluation is included regularly in the assessment of patients with primary brain tumors. However, to the authors' knowledge, little is known regarding the prognostic impact in patients with newly diagnosed brain metastases (BM). The current study has provided a detailed clinical characterization of the incidence, distribution, and prognostic impact of neurological symptoms in a large, real-life cohort of patients with BM from non-small cell lung cancer. In this cohort, neurological symptoms at the time of diagnosis of BM demonstrated a strong, independent prognostic impact on the survival prognosis. The results of the current study have highlighted the need for the integration of neurological symptom burden into the prognostic assessment of patients with BM from non-small cell lung cancer.

Simulation-Based Training of the Rapid Evaluation and Management of Acute Stroke (STREAM)-A Prospective Single-Arm Multicenter Trial.

Introduction: Acute stroke care delivered by interdisciplinary teams is time-sensitive. Simulation-based team training is a promising tool to improve team performance in medical operations. It has the potential to improve process times, team communication, patient safety, and staff satisfaction. We aim to assess whether a multi-level approach consisting of a stringent workflow revision based on peer-to-peer review and 2-3 one-day in situ simulation trainings can improve acute stroke care processing times in high volume neurocenters within a 6 months period. Methods and Analysis: The trial is being carried out in a pre-test-post-test design at 7 tertiary care university hospital neurocenters in Germany. The intervention is directed at the interdisciplinary multiprofessional stroke teams. Before and after the intervention, process times of all direct-to-center stroke patients receiving IV thrombolysis (IVT) and/or endovascular therapy (EVT) will be recorded. The primary outcome measure will be the "door-to-needle" time of all consecutive stroke patients directly admitted to the neurocenters who receive IVT. Secondary outcome measures will be intervention-related process times of the fraction of patients undergoing EVT and effects on team communication, perceived patient safety, and staff satisfaction via a staff questionnaire. Interventions: We are applying a multi-level intervention in cooperation with three "STREAM multipliers" from each center. First step is a central meeting of the multipliers at the sponsor's institution with the purposes of algorithm review in a peer-to-peer process that is recorded in a protocol and an introduction to the principles of simulation training and debriefing as well as crew resource management and team communication. Thereafter, the multipliers cooperate with the stroke team trainers from the sponsor's institution to plan and execute 2-3 one-day simulation courses in situ in the emergency department and CT room of the trial centers whereupon they receive teaching materials to perpetuate the trainings. Clinical Trial Registration: STREAM is a registered trial at https://clinicaltrials.gov/ct2/show/NCT03228251.

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses - A First-In-Man Trial.

BACKGROUND: Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. METHODS: In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protein 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellular stress responses, complemented by metabolomics and functional immunocompetence assays. RESULTS: AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shock protein expression (effect 1.51-fold, CI 1.07-2.14; p = 0.022), without changes in peritoneal ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation. Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulated cytokine release from healthy donor peripheral blood monocytes. In patients with a history of peritonitis (5 of 20), AlaGln supplementation decreased dialysate interleukin-8 levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokine release in a mouse model of PD-associated peritonitis. CONCLUSION: We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellular stress responses with attenuation of sterile inflammation, and may improve peritoneal host-defense in the setting of PD.

Development of text mining based classification of written communication within a telemedical collaborative network.

Chronic diseases like Heart Failure are widespread in the ageing population. Affected patients can be treated with the aid of a disease management program, including a telemedical collaborative network. Evaluation of a currently used system has shown that the information of the textual communication is of pivotal importance for the collaboration in the network. Thus, the challenge is to make this unstructured information useable, potentially leading to a better understanding of the collaboration so as to optimize the processes. This paper presents the setup of an analysis pipeline for processing textual information automatically, and, how this pipeline can be utilized to train a model that is able to automatically classify the written messages into a set of meaningful task and status categories.

Textual analysis of collaboration notes of the telemedical heart failure network HerzMobil Tirol.

UNLABELLED: Management of heart failure is usually multidisciplinary and collaboration between stakeholders in a dedicated HI network like the HerzMobil Tirol can be supported by a mHealth-based telemedicine approach. The aim is to gain insights through textual analysis of collaboration notes that might trigger further developments and improvements of the HI network. A reusable pipeline for textual analysis of unstructured textual notes was implemented using the open source analytics software KNIME. After preprocessing, a keyword analysis was performed resulting in a classification of all notes in predefined categories. RESULTS: Medical and organizational issues dominate the communication with health status and therapy aspects as well as clinical treatment, discharge letter and home visits. Beside aspects of data transmission and mobile phone, technological issues are minor topics during the collaboration. It is possible to gain new insights with respect to technology like additional control Apps for mobile phone settings and to the HI network like clinical experts and technical help desk involvement.

Evaluation of a clinical decision support rule-set for medication adjustments in mHealth-based heart failure management.

Decision-support based medication adjustment in heart failure management. Prospective analysis of clinical decision support in fifteen patients that collected vital parameters and medication intake up to one year within a clinical trial. Correlation of event episodes and medication adjustments with respect to applied rule-sets and medication classes. 713 events were grouped to 195 event episodes. Physicians performed 86 medication adjustments. 30 of them were triggered by event episodes. 35% of all performed medication adjustments occurred between event episodes. 20% of all episodes triggered a medication adjustment. 15% of all episodes triggered the expected medication adjustment. Correlation between episodes and medication adjustment was low. Further analysis needs to be done, to evaluate reasons for low correlation and how the rule-set should be adapted to increase reliability.