Clustering identifies endotypes of traumatic brain injury in an intensive care cohort: a CENTER-TBI study

Background While the Glasgow coma scale (GCS) is one of the strongest outcome predictors, the current classification of traumatic brain injury (TBI) as ‘mild’, ‘moderate’ or ‘severe’ based on this fails to capture enormous heterogeneity in pathophysiology and treatment response. We hypothesized that data-driven characterization of TBI could identify distinct endotypes and give mechanistic insights. Methods We developed an unsupervised statistical clustering model based on a mixture of probabilistic graphs for presentation (< 24 h) demographic, clinical, physiological, laboratory and imaging data to identify subgroups of TBI patients admitted to the intensive care unit in the CENTER-TBI dataset (N = 1,728). A cluster similarity index was used for robust determination of optimal cluster number. Mutual information was used to quantify feature importance and for cluster interpretation. Results Six stable endotypes were identified with distinct GCS and composite systemic metabolic stress profiles, distinguished by GCS, blood lactate, oxygen saturation, serum creatinine, glucose, base excess, pH, arterial partial pressure of carbon dioxide, and body temperature. Notably, a cluster with ‘moderate’ TBI (by traditional classification) and deranged metabolic profile, had a worse outcome than a cluster with ‘severe’ GCS and a normal metabolic profile. Addition of cluster labels significantly improved the prognostic precision of the IMPACT (International Mission for Prognosis and Analysis of Clinical trials in TBI) extended model, for prediction of both unfavourable outcome and mortality (both p < 0.001). Conclusions Six stable and clinically distinct TBI endotypes were identified by probabilistic unsupervised clustering. In addition to presenting neurology, a profile of biochemical derangement was found to be an important distinguishing feature that was both biologically plausible and associated with outcome. Our work motivates refining current TBI classifications with factors describing metabolic stress. Such data-driven clusters suggest TBI endotypes that merit investigation to identify bespoke treatment strategies to improve care

Rehabilitation and outcomes after complicated vs uncomplicated mild TBI: results from the CENTER-TBI study

Background: Despite existing guidelines for managing mild traumatic brain injury (mTBI), evidence-based treatments are still scarce and large-scale studies on the provision and impact of specific rehabilitation services are needed. This study aimed to describe the provision of rehabilitation to patients after complicated and uncomplicated mTBI and investigate factors associated with functional outcome, symptom burden, and TBI-specific health-related quality of life (HRQOL) up to six months after injury. Methods: Patients (n = 1379) with mTBI from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study who reported whether they received rehabilitation services during the first six months post-injury and who participated in outcome assessments were included. Functional outcome was measured with the Glasgow Outcome Scale – Extended (GOSE), symptom burden with the Rivermead Post Concussion Symptoms Questionnaire (RPQ), and HRQOL with the Quality of Life after Brain Injury – Overall Scale (QOLIBRI-OS). We examined whether transition of care (TOC) pathways, receiving rehabilitation services, sociodemographic (incl. geographic), premorbid, and injury-related factors were associated with outcomes using regression models. For easy comparison, we estimated ordinal regression models for all outcomes where the scores were classified based on quantiles. Results: Overall, 43% of patients with complicated and 20% with uncomplicated mTBI reported receiving rehabilitation services, primarily in physical and cognitive domains. Patients with complicated mTBI had lower functional level, higher symptom burden, and lower HRQOL compared to uncomplicated mTBI. Rehabilitation services at three or six months and a higher number of TOC were associated with unfavorable outcomes in all models, in addition to pre-morbid psychiatric problems. Being male and having more than 13 years of education was associated with more favorable outcomes. Sustaining major trauma was associated with unfavorable GOSE outcome, whereas living in Southern and Eastern European regions was associated with lower HRQOL. Conclusions: Patients with complicated mTBI reported more unfavorable outcomes and received rehabilitation services more frequently. Receiving rehabilitation services and higher number of care transitions were indicators of injury severity and associated with unfavorable outcomes. The findings should be interpreted carefully and validated in future studies as we applied a novel analytic approach. Trial registration: ClinicalTrials.gov NCT02210221

Serum metabolome associated with severity of acute traumatic brain injury

Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain

Factors influencing continuing professional development: A Delphi study among nursing experts

Purpose The aim of this paper is to present an inventory of expert opinions on the factors that influence the participation of registered nurses in continuing professional development (CPD) activities. Design/methodology/approach A Delphi study was conducted among 38 Dutch experts (nursing employers, managers, education institutions, and professional associations). Data collection comprised three rounds: experts completed two consecutive rounds of questionnaires and participated in a discussion meeting. Findings Main influencing factors were: a CPD registration system, the attractiveness of the nursing profession, nurses ' identification with the nursing profession, opportunities for workplace learning, the line manager as role model, and attractive education programs. Research limitations/implications Being part of a larger study, for the present paper only nursing experts were asked their opinion about shaping CPD for nurses. Further research should bring in the views of nurses themselves and investigate how the wider environment influences CPD participation. Practical implications As all stakeholders were found to have their own roles in the CPD process, collaboration among employers, managers, education institutions, and professional associations will be crucial to create a conducive learning climate for nurses. HRD practitioners in healthcare can use the study findings to advise hospitals about implementing the right conditions to support CPD for nurses. Originality/value A qualitative study using the Delphi method to discover factors influencing CPD in nursing had not been conducted before. Unlike many studies looking essentially at formal education, the present paper takes into account workplace learning among nurses as well. Keywords: Continuing professional development, Delphi study, Nurses, The Netherland

The development and empirical validation of the Q-PDN: A questionnaire measuring continuing professional development of nurses

Background Although separate studies among nurses have been conducted into their continuing professional development (CPD) motives, importance attached to CPD, conditions deemed needed for CPD, and actual CPD activities undertaken, these variables have not yet been investigated at the same time, on the same sample. Objectives The aim of this study is to report on the development and initial psychometric testing of the Q-PDN, a questionnaire measuring several aspects of CPD among nurses. Method Based on a survey administered to 1329 nurses in hospitals in the Netherlands, a multi-dimensional instrument for CPD was validated. The constructs ‘CPD motives’, ‘CPD importance’, ‘CPD conditions’, and ‘CPD activities undertaken’ were established through factor analyses. Results Reliability analyses showed satisfactory to good Cronbach's alpha scores on all factors, ranging from .70 to .89. Conclusion Using this instrument can stimulate and support CPD of nurses, which has been shown to contribute to increasing the quality of care. Human resource development (HRD) professionals, educators in healthcare, and managers can use this questionnaire to gain insight in the extent to which nurses undertake CPD activities, in the importance they attribute to CPD activities, in the conditions they deem necessary to participate in CPD, and in the motives that they have to engage in CPD. Keywords: Continuing professional development, Nurses, Instrument development, Questionnaire, Psychometric validatio

Ultrastructural and immunocytochemical characterization of the rat non-preganglionic edinger-westphal nucleus

Contains fulltext : 75625.pdf (publisher's version ) (Closed access)8 p

Development and implementation of guidelines in allergic rhinitis - an ARIA-GA2LEN paper

The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients&apos; values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved. © 2010 John Wiley &amp; Sons A/S