Showing papers by "Russell L. Gruen published in 2022"

Serum metabolome associated with severity of acute traumatic brain injury

Abstract: Abstract 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.

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

Abstract: Abstract 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. Trial registration The core study was registered with ClinicalTrials.gov, number NCT02210221 , registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

Health care utilization and outcomes in older adults after Traumatic Brain Injury: A CENTER-TBI study.

Abstract: The incidence of Traumatic Brain Injury (TBI) is increasingly common in older adults aged ≥65 years, forming a growing public health problem. However, older adults are underrepresented in TBI research. Therefore, we aimed to provide an overview of health-care utilization, and of six-month outcomes after TBI and their determinants in older adults who sustained a TBI.We used data from the prospective multi-center Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. In-hospital and post-hospital health care utilization and outcomes were described for patients aged ≥65 years. Ordinal and linear regression analyses were performed to identify determinants of the Glasgow Outcome Scale Extended (GOSE), health-related quality of life (HRQoL), and mental health symptoms six-months post-injury.Of 1254 older patients, 45% were admitted to an ICU with a mean length of stay of 9 days. Nearly 30% of the patients received inpatient rehabilitation. In total, 554/1254 older patients completed the six-month follow-up questionnaires. The mortality rate was 9% after mild and 60% after moderate/severe TBI, and full recovery based on GOSE was reported for 44% of patients after mild and 6% after moderate/severe TBI. Higher age and increased injury severity were primarily associated with functional impairment, while pre-injury systemic disease, psychiatric conditions and lower educational level were associated with functional impairment, lower generic and disease-specific HRQoL and mental health symptoms.The rate of impairment and disability following TBI in older adults is substantial, and poorer outcomes across domains are associated with worse preinjury health. Nonetheless, a considerable number of patients fully or partially returns to their preinjury functioning. There should not be pessimism about outcomes in older adults who survive.

Climate, housing, energy and Indigenous health: a call to action

Abstract: Most Australians take safe housing and uninterrupted electricity for granted. Yet in remote Indigenous communities, low quality poorly insulated housing and energy instability are common.1 Most houses require prepaid power cards, resources are meagre, financial literacy is low, and people often have to choose between power and food. New evidence reveals extreme rates of prepaid electricity meters’ disconnection in these communities,2 making people with chronic diseases who depend on cool storage and electrical equipment particularly vulnerable. The convergence of excessive heat, poor housing, energy insecurity and chronic disease has reached critical levels in many parts of northern Australia, and a multisectoral response is needed to avert catastrophe. Medical professionals have a key role to play. Over recent summers it’s been too hot. Particularly them hot days when the power do go off, we all get out of the house, we always sit outside. I normally just sit under the sprinkler or under the hose, over my head. Everything’s been dying out here around Tennant Creek. All the water in the rock holes went dry. The heat killed animals. Even the spinifex went black, it looked like it’d been burnt or poisoned. A lot of them trees around town, not them native trees but cedar trees and African mahogany, all them mango trees around Tennant Creek, all died, nothing left. That heat would just come too low, the heat wave killed the whole lot. (Norman Frank Jupurrurla, Warramungu Elder and dialysis patient from Tennant Creek) Source: Bureau of Meteorology; reproduced with authorisation from Pandora Hope. Some people on the outskirts of Tennant Creek still live in old tin houses and there’s no running water, there’s no power, there’s not even a toilet, not even an old drop toilet. Kids go to school from there and people go to work … “You’ll end up getting cooked in that tin house today,” that’s what we say … There’s a renal patient out there, living in a camp, he got renal at the same time as me and the renal bus go out there, pick him up in the camp, near his tin shed, take him to dialysis with me. Doctors should start asking the question, if you’ve got a fridge or not. I reckon that’s what these doctors think, every Wumpurrarni [Indigenous person] lives the same as a whitefella and they’ve got everything the same. But not all of us got a fridge. When doctors put people on insulin and educate them, when dieticians talk to them and tell them, “You need to be on insulin”, they don’t ask that question “Do you have a fridge? Where do you stay? What kind of condition you live in?” When the power disconnects because we run out of money [on a prepaid meter], you have to hurry up. If you catch it in a few hours, you’ll be lucky, but if I’m out somewhere on the weekend and it goes off, everything goes off in the fridge. When I come in late or at night and find that the power’s been off, everything’s off in the fridge, so I’ve had to throw everything out. I’m in a brick house. I’m in an old brick house still and it’s really hot in that house … It’s really hot in summertime. When you’ve got winter, that brick is really cold. In winter it’s the other way around, that house of mine. Health care practitioners need to be cognisant of the direct impacts of heat on their patients’ health and recognise comorbid conditions and risk factors that increase vulnerability to heat.7 It is equally important for clinicians to understand people’s access to thermal safety, capacity to appropriately store medications, and resources to power essential health infrastructure such as oxygen concentrators. Explicit inquiry about housing conditions, the availability of refrigeration and air conditioning, and how regularly the power turns off may be particularly revealing. Beyond individual patient care, the medical profession can engage with pharmaceutical and health care device industries to ensure that details of thermal stability of products are available to clinicians. For example, although almost all pharmaceuticals’ labelling mandate storage below 30°C, it is likely that many products can withstand higher temperatures. On the other hand, some antibiotics, antidiabetic medications, antiepileptics and warfarin, which are all medications regularly prescribed in Indigenous communities, are known to degrade in the heat.14 In the NT, clinicians need to understand the thermal stability of everything they prescribe. There are also many unknowns and misconceptions about how to protect human health from extreme heat, for instance, air conditioning and cooling technology may not be a panacea.15 Therefore, a high priority is to develop an evidence-based agenda of heat adaptation and health, including public health responses to extreme heat events, that provides a robust basis for advocacy and action as we all try to adapt to a rapidly heating world. In the context of heat, housing, energy, and chronic disease, there is much that health professionals can advocate for to reduce structural inequities that perpetuate Indigenous peoples’ health risks and relative disadvantage.16 This begins with health professions bearing witness to current housing disparities and their impact on health and safety of remote community residents. The profession can highlight the association of housing quality, heat stress and energy security in relation to demand on health services so it is given appropriate priority in government decision making. In relationship to housing and health, our profession needs to advocate for strengthening of building codes and housing standards for remote Indigenous dwellings (Box 3). Identifying and rectifying deteriorating infrastructure, reviewing maintenance standards to ensure dwellings are fit for purpose into the future, and ensuring appropriate design and quality construction of new buildings is all of urgent priority in a warming climate. This includes enhanced responsiveness of public utilities in the interest of the health and safety of remote community residents. You’ve got to stand strong. If you’re going to give up on them and stop holding them accountable, they’ll give up on you too and won’t do what they are supposed to, that’s how they are. If you stop making noise, they’ll just sit there quietly and do nothing, they wouldn’t worry and would leave things broken as they are. They don’t give a damn about you. The way I see it I’ve been in my house for nearly 5 years, and I’ve been trying to get help with housing and providers coming round, trying to ask them for help or support or fix plumbing. I’ve had to report it over and over and over before they do anything about it. If I give up, they’ll give up. But I am not ever going to give up. The community needs to be in charge of what they want done in their housing and how they want their lifestyle, and be allowed to make the solutions. Then they can bring that to the table, to the housing and to the providers. Then it’s not coming from some government from Canberra, it’s not coming from some politician. It’s coming from us, it’s coming straight from the horse’s mouth and straight from the ground, from the grassroots, that’s where you’ve got to listen, from their home. Acknowledgements: We thank Pandora Hope (Bureau of Meteorology) for her work on the climate maps. Open access: Open access publishing facilitated by Australian National University, as part of the Wiley - Australian National University agreement via the Council of Australian University Librarians. Competing interests: No relevant disclosures. Provenance: Not commissioned; externally peer reviewed.

Computational modeling of orthostatic intolerance for travel to Mars

Abstract: Abstract Astronauts in a microgravity environment will experience significant changes in their cardiopulmonary system. Up until now, there has always been the reassurance that they have real-time contact with experts on Earth. Mars crew however will have gaps in their communication of 20 min or more. In silico experiments are therefore needed to assess fitness to fly for those on future space flights to Mars. In this study, we present an open-source controlled lumped mathematical model of the cardiopulmonary system that is able simulate the short-term adaptations of key hemodynamic parameters to an active stand test after being exposed to microgravity. The presented model is capable of adequately simulating key cardiovascular hemodynamic changes—over a short time frame—during a stand test after prolonged spaceflight under different gravitational conditions and fluid loading conditions. This model can form the basis for further exploration of the ability of the human cardiovascular system to withstand long-duration space flight and life on Mars.

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

Abstract: 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.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.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.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.ClinicalTrials.gov NCT02210221.