Stepped collaborative care for pain and posttraumatic stress disorder after major trauma: a randomized controlled feasibility trial.

PURPOSE: To examine feasibility and acceptability of providing stepped collaborative care case management targeting posttraumatic stress disorder (PTSD) and pain symptoms after major traumatic injury. MATERIALS AND METHODS: Participants were major trauma survivors in Victoria, Australia, at risk of persistent pain or PTSD with high baseline symptoms. Participants were block-randomized, stratified by compensation-status, to the usual care (n = 15) or intervention (n = 17) group (46% of eligible patients). The intervention was adapted from existing stepped collaborative care interventions with input from interdisciplinary experts and people with lived experience in trauma and disability. The proactive case management intervention targeted PTSD and pain management for 6-months using motivational interviewing, cognitive behavioral therapy strategies, and collaborative care. Qualitative interviews explored intervention acceptability. RESULTS: Intervention participants received a median of 7 h case manager contact and reported that they valued the supportive and non-judgmental listening, and timely access to effective strategies, resources, and treatments post-injury from the case manager. Participants reported few disadvantages from participation, and positive impacts on symptoms and recovery outcomes consistent with the reduction in PTSD and pain symptoms measured at 1-, 3- and 6-months. CONCLUSIONS: Stepped collaborative care was low-cost, feasible, and acceptable to people at risk of PTSD or pain after major trauma.IMPLICATIONS FOR REHABILITATIONAfter hospitalization for injury, people can experience difficulty accessing timely support to manage posttraumatic stress, pain and other concerns.Stepped case management-based interventions that provide individualized support and collaborative care have reduced posttraumatic stress symptom severity for patients admitted to American trauma centers.We showed that this model of care could be adapted to target pain and mental health in the trauma system in Victoria, Australia.The intervention was low cost, acceptable and highly valued by most participants who perceived that it helped them use strategies to better manage post-traumatic symptoms, and to access clinicians and treatments relevant to their needs.

Major traumatic pedestrian injury in Australia: Characteristics and in-hospital outcomes from the Australia New Zealand Trauma Registry.

BACKGROUND: The leading global cause of death for people aged 5-29 years is road traffic injury, a quarter of which is borne by pedestrians. The epidemiology of major hospitalised pedestrian injury across Australia is not reported. This study aims to address this gap using data from the Australia New Zealand Trauma Registry. METHODS: The registry hosts information on patients admitted to 25 major trauma centres across Australia who sustain a major injury (ISS > 12) or die following injury. Patients were included if they were injured due to pedestrian injury from 1st July 2015-30 th June 2019. Analysis included patient and injury characteristics, injury patterns and in-hospital outcomes. Primary endpoints included risk-adjusted mortality and length of stay. RESULTS: There were 2159 injured pedestrians; of these, 327 died. Young adults (20-25 years) were the largest group, especially on weekends. Older adults (70 + years) were the largest cohort in pedestrian deaths. The most common injuries were head (42.2 %). One-third of patients were intubated prior to or on ED arrival (n = 731, 34.3 %). CONCLUSION: Emergency clinicians should have a high index for severe pedestrian injury. Further reduction in road speed in residential areas could reduce all-age pedestrian injury in Australia.

Rural and urban patterns of severe injuries and hospital mortality in Australia: An analysis of the Australia New Zealand Trauma Registry: 2015-2019.

INTRODUCTION: In Australia, people living in rural areas, compared to major cities are at greater risk of poor health. There is much evidence of preventable disparities in trauma outcomes, however research quantifying geographic variations in injuries, pathways to specialised care and patient outcomes is scarce. AIMS: (i) To analyse the Australia New Zealand Trauma Registry (ATR) data and report patterns of serious injuries according to rurality of the injury location ii) to examine the relationship between rurality and hospital mortality and iii) to compare ATR death rates with all deaths from similar causes, Australia-wide. METHOD: A retrospective cohort study of patients in the ATR from 1st July 2015 to 30th June 2019 was conducted. Descriptive analyses of trauma variables according to rurality was performed. Logistic regression quantified the moderating effect of rurality on trauma variables and hospital mortality. Australian death data on similar injuries were sourced to quantify the additional mortality attributable to severe injury occurring outside Major Trauma Centres (MTCs). RESULTS: Compared to major cities, rural patients were younger, more likely to have spinal cord injuries, and sustain traffic-related injuries that are 'off road'. Injuries occurring outside people's homes are more likely. Mortality risk was greater for patients sustaining severe traumatic brain injury (TBI) spinal cord injury (SCI) and head trauma in addition to intentional injuries. Compared to the ATR data, Australian population-wide trauma mortality rates showed diverging trends according to rurality. The ATR only captures 14.1% of all injury deaths occurring in major cities and, respectively, 6.3% and 3.2% of deaths in regional and remote areas. CONCLUSION: Compared to major cities, injuries occurring in rural areas of Australia often involve different mechanisms and result in different types of severe injuries. Patients with neurotrauma and intentional injuries who survived to receive definitive care at a MTC were at higher risk of hospital death. To inform prevention strategies and reduce morbidity and mortality associated with rural trauma, improvements to data systems are required that involve data linkage and include information about patient care from pre-hospital providers, regional hospitals and major trauma centres.

Association of fear-avoidance and self-efficacy on pain disability in individuals with co-morbid post-traumatic stress and chronic pain.

This study investigated relationships between post-traumatic stress symptoms (PTSS) and pain disability. Fifty people with chronic pain (probable PTSD, n = 22) completed measures assessing pain interference, PTSS, fear avoidance, and pain self-efficacy. We hypothesized that people with probable PTSD would have higher fear avoidance and lower pain self-efficacy; and that PTSS would be indirectly associated with pain disability via fear avoidance and self-efficacy. People with probable PTSD had higher fear avoidance, but there were no differences in self-efficacy, pain severity or disability. There was an indirect association between PTSS and pain disability via fear avoidance, but not via self-efficacy.

Human sensorimotor organoids derived from healthy and amyotrophic lateral sclerosis stem cells form neuromuscular junctions.

Human induced pluripotent stem cells (iPSC) hold promise for modeling diseases in individual human genetic backgrounds and thus for developing precision medicine. Here, we generate sensorimotor organoids containing physiologically functional neuromuscular junctions (NMJs) and apply the model to different subgroups of amyotrophic lateral sclerosis (ALS). Using a range of molecular, genomic, and physiological techniques, we identify and characterize motor neurons and skeletal muscle, along with sensory neurons, astrocytes, microglia, and vasculature. Organoid cultures derived from multiple human iPSC lines generated from individuals with ALS and isogenic lines edited to harbor familial ALS mutations show impairment at the level of the NMJ, as detected by both contraction and immunocytochemical measurements. The physiological resolution of the human NMJ synapse, combined with the generation of major cellular cohorts exerting autonomous and non-cell autonomous effects in motor and sensory diseases, may prove valuable to understand the pathophysiological mechanisms of ALS.

Non-typeable Haemophilus influenzae chronic colonization in chronic obstructive pulmonary disease (COPD).

Haemophilus influenzae is the most common cause of bacterial infection in the lungs of chronic obstructive pulmonary disease (COPD) patients and contributes to episodes of acute exacerbation which are associated with increased hospitalization and mortality. Due to the ability of H. influenzae to adhere to host epithelial cells, initial colonization of the lower airways can progress to a persistent infection and biofilm formation. This is characterized by changes in bacterial behaviour such as reduced cellular metabolism and the production of an obstructive extracellular matrix (ECM). Herein we discuss the multiple mechanisms by which H. influenzae contributes to the pathogenesis of COPD. In particular, mechanisms that facilitate bacterial adherence to host airway epithelial cells, biofilm formation, and microbial persistence through immune system evasion and antibiotic tolerance will be discussed.

Perspectives on neuroinflammation contributing to chronic cough.

Chronic cough can be a troublesome clinical problem. Current thinking is that increased activity and/or enhanced sensitivity of the peripheral and central neural pathways mediates chronic cough via processes similar to those associated with the development of chronic pain. While inflammation is widely thought to be involved in the development of chronic cough, the true mechanisms causing altered neural activity and sensitisation remain largely unknown. In this back-to-basics perspective article we explore evidence that inflammation in chronic cough may, at least in part, involve neuroinflammation orchestrated by glial cells of the nervous system. We summarise the extensive evidence for the role of both peripheral and central glial cells in chronic pain, and hypothesise that the commonalities between pain and cough pathogenesis and clinical presentation warrant investigations into the neuroinflammatory mechanisms that contribute to chronic cough. We open the debate that glial cells may represent an underappreciated therapeutic target for controlling troublesome cough in disease.

Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology.

Mutations in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS). Accumulating evidence implicates astrocytes as important non-cell autonomous contributors to ALS pathogenesis, although the potential deleterious effects of astrocytes on the function of motor neurons remains to be determined in a completely humanized model of C9orf72-mediated ALS. Here, we use a human iPSC-based model to study the cell autonomous and non-autonomous consequences of mutant C9orf72 expression by astrocytes. We show that mutant astrocytes both recapitulate key aspects of C9orf72-related ALS pathology and, upon co-culture, cause motor neurons to undergo a progressive loss of action potential output due to decreases in the magnitude of voltage-activated Na+ and K+ currents. Importantly, CRISPR/Cas-9 mediated excision of the C9orf72 repeat expansion reverses these phenotypes, confirming that the C9orf72 mutation is responsible for both cell-autonomous astrocyte pathology and non-cell autonomous motor neuron pathophysiology.

The road to recovery for vulnerable road users hospitalised for orthopaedic injury following an on-road crash.

BACKGROUND: Pedestrians, cyclists and motorcyclists are vulnerable to serious injury due to limited external protective devices. Understanding the level of recovery, and differences between these road user groups, is an important step towards improved understanding of the burden of road trauma, and prioritisation of prevention efforts. This study aimed to characterise and describe patient-reported outcomes of vulnerable road users at 6 and 12 months following orthopaedic trauma. METHODS: A registry-based cohort study was conducted using data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) and included pedestrians, cyclists and motorcyclists who were hospitalised for an orthopaedic injury following an on-road collision that occurred between January 2009 and December 2016. Outcomes were measured using the 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3 L), Glasgow Outcome Scale - Extended (GOS-E) and return to work questions. Outcomes were collected at 6 and 12 months post-injury. Multivariable generalized estimating equations (GEE), adjusted for confounders, were used to compare outcomes between the road user groups over time. RESULTS: 6186 orthopaedic trauma patients met the inclusion criteria during the 8-year period. Most patients were motorcyclists (42.8%) followed by cyclists (32.6%) and pedestrians (24.6%). Problems were most prevalent on the usual activities item of the EQ-5D-3 L at 6-months post-injury, and the pain/discomfort item of the EQ-5D-3 L at 12 months. The adjusted odds of reporting problems on all EQ-5D-3 L items were lower for cyclists when compared to pedestrians. Moreover, an average cyclist had a greater odds of a good recovery on the GOS-E, (AOR 2.75, 95% CI 2.33, 3.25) and a greater odds of returning to work (AOR = 3.13, 95% CI 2.46, 3.99) compared to an average pedestrian. CONCLUSION: Pedestrians and motorcyclists involved in on-road collisions experienced poorer patient-reported outcomes at 6 and 12 months post-injury when compared to cyclists. A focus on both primary injury prevention strategies, and investment in ongoing support and treatment to maximise recovery, is necessary to reduce the burden of road trauma for vulnerable road users.

Pharmacological Profiling of Purified Human Stem Cell-Derived and Primary Mouse Motor Neurons.

Directed differentiation of human pluripotent stem cells (hPSCs) has enabled the generation of specific neuronal subtypes that approximate the intended primary mammalian cells on both the RNA and protein levels. These cells offer unique opportunities, including insights into mechanistic understanding of the early driving events in neurodegenerative disease, replacement of degenerating cell populations, and compound identification and evaluation in the context of precision medicine. However, whether the derived neurons indeed recapitulate the physiological features of the desired bona fide neuronal subgroups remains an unanswered question and one important for validating stem cell models as accurate functional representations of the primary cell types. Here, we purified both hPSC-derived and primary mouse spinal motor neurons in parallel and used extracellular multi-electrode array (MEA) recording to compare the pharmacological sensitivity of neuronal excitability and network function. We observed similar effects for most receptor and channel agonists and antagonists, supporting the consistency between human PSC-derived and mouse primary spinal motor neuron models from a physiological perspective.

Co-occurrence of posttraumatic stress symptoms, pain, and disability 12 months after traumatic injury.

INTRODUCTION: Chronic pain is common after traumatic injury and frequently co-occurs with posttraumatic stress disorder (PTSD) and PTSD symptoms (PTSS). OBJECTIVES: This study sought to understand the association between probable PTSD, PTSS, and pain. METHODS: Four hundred thirty-three participants were recruited from the Victorian Orthopaedic Trauma Outcomes Registry and Victorian State Trauma Registry and completed outcome measures. Participants were predominantly male (n = 324, 74.8%) and aged 17-75 years at the time of their injury (M = 44.83 years, SD = 14.16). Participants completed the Posttraumatic Stress Disorder Checklist, Brief Pain Inventory, Pain Catastrophizing Scale, Pain Self-Efficacy Questionnaire, Tampa Scale of Kinesiophobia, EQ-5D-3L and Roland-Morris Disability Questionnaire 12 months after hospitalization for traumatic injury. Data were linked with injury and hospital admission data from the trauma registries. RESULTS: Those who reported having current problems with pain were 3 times more likely to have probable PTSD than those without pain. Canonical correlation showed that pain outcomes (pain severity, interference, catastrophizing, kinesiophobia, self-efficacy, and disability) were associated with all PTSSs, but especially symptoms of cognition and affect, hyperarousal, and avoidance. Posttraumatic stress disorder symptoms, on the contrary, were predominantly associated with high catastrophizing and low self-efficacy. When controlling for demographics, pain and injury severity, depression, and self-efficacy explained the greatest proportion of the total relationship between PTSS and pain-related disability. CONCLUSION: Persons with both PTSS and chronic pain after injury may need tailored interventions to overcome fear-related beliefs and to increase their perception that they can engage in everyday activities, despite their pain.

Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which a greater understanding of early disease mechanisms is needed to reveal novel therapeutic targets. We report the use of human induced pluripotent stem cell (iPSC)-derived motoneurons (MNs) to study the pathophysiology of ALS. We demonstrate that MNs derived from iPSCs obtained from healthy individuals or patients harbouring TARDBP or C9ORF72 ALS-causing mutations are able to develop appropriate physiological properties. However, patient iPSC-derived MNs, independent of genotype, display an initial hyperexcitability followed by progressive loss of action potential output and synaptic activity. This loss of functional output reflects a progressive decrease in voltage-activated Na(+) and K(+) currents, which occurs in the absence of overt changes in cell viability. These data implicate early dysfunction or loss of ion channels as a convergent point that may contribute to the initiation of downstream degenerative pathways that ultimately lead to MN loss in ALS.

Self-regulation of older drivers with cognitive impairment: a systematic review.

BACKGROUND: Cognitive decline contributes significantly to the safety risk of older drivers. Some drivers may be able to compensate for the increased crash risk by avoiding complex driving situations or restricting their driving. OBJECTIVE AND METHOD: A comprehensive English-language systematic review was conducted to determine the level of evidence for older adult drivers with cognitive impairment engaging in self-regulation. RESULTS: Twelve studies were included in the review. The majority of studies investigated driver avoidance, followed by driver restriction. Few studies ascertained the reasons for changing driving behaviour. CONCLUSIONS: The evidence supports the view that drivers with cognitive impairment do restrict their driving and avoid complex driving situations. However, it remains to be determined whether the drivers who engage in self-regulation have insight into their own driving abilities or whether external factors result in self-regulation of driving behaviour.

Exploring the distribution and determinants of a change in recovery expectations following traumatic injury to Victorian workers.

PURPOSE: To examine the frequency, distribution and determinants of a change in recovery expectations following non-life threatening acute orthopaedic trauma to Victorian workers. It is proposed that interventions to modify recovery expectations may reduce the burden associated with injury. However, it is not known whether recovery expectations change over time or the factors that are associated with change. METHODS: A prospective inception cohort study was carried out in which participants were recruited following presentation to hospital for treatment of their injury and followed for 6 months post-injury. Baseline data was obtained by survey and medical record review. Binary logistic regression was used to examine factors associated with a change in recovery expectations between week 2 and week 12 post-injury. RESULTS: The cohort comprised injured workers (n = 145) who had sustained nonlife threatening acute orthopaedic trauma. Factors associated with an improvement in recovery expectations or recovery timeframe included more years of education and higher social functioning. Participants whose injury involved a perception of responsibility by a third party were 7.18 (95 % CI 1.86-27.68) times more likely to change their recovery expectations to more negative expectations and less likely to change to an earlier recovery timeframe. Participants with more severe injuries were more likely to change their recovery timeframe to a longer timeframe. CONCLUSION: Change in recovery expectations provide some information on injured workers who may benefit from targeted interventions to improve or maintain recovery expectations. The post-injury time-point at which recovery expectations are measured is important if recovery expectations are to inform long-term outcomes.

Parents' attitudes, knowledge and behaviours relating to safe child occupant travel.

This study investigated parents' attitudes, knowledge and behaviours relating to safe child occupant travel following new Australian legislation regarding child restraint system (CRS) and motor vehicle restraint use for children aged 7 years and under. A questionnaire exploring attitudes, knowledge and behaviours regarding general road safety, as well as safe child occupant travel, was completed by 272 participants with at least one child aged between 3 and 10 years residing in the Australian state of Victoria. Responses to the questionnaire revealed that participants' attitudes, knowledge and behaviours towards road safety in general were fairly positive, with most participants reporting that they restrict their alcohol consumption or do not drink at all while driving (87%), drive at or below the speed limit (85%) and 'always' wear their seatbelts (98%). However, more than half of the participants reported engaging in distracting behaviours 'sometimes' or 'often' (54%) and a small proportion of participants indicated that they 'sometimes' engaged in aggressive driving (14%). Regarding their attitudes, knowledge and behaviours relating to safe child occupant travel, most participants reported that they 'always' restrain their children (99%). However, there was a surprisingly high proportion of participants who did not know the appropriate age thresholds' to transition their child from a booster seat to an adult seatbelt (53%) or the age for which it is appropriate for their child to sit in the front passenger seat of the vehicle (20%). Logistic regression analyses revealed that parents' knowledge regarding safe child occupant travel was significantly related to their attitudes, knowledge and behaviours towards road safety in general, such as drinking habits while driving and CRS safety knowledge. Based on the findings of this study, a number of recommendations are made for strategies to enhance parents' attitudes, knowledge and behaviours relating to safe child occupant travel, as well as for future research.

Investigating driving behaviour of older drivers with mild cognitive impairment using a portable driving simulator.

While there is a large body of research indicating that individuals with moderate to severe dementia are unfit to drive, relatively little is known about the driving performance of older drivers with mild cognitive impairment (MCI). The aim of the current study was to examine the driving performance of older drivers with MCI on approach to intersections, and to investigate how their healthy counterparts perform on the same driving tasks using a portable driving simulator. Fourteen drivers with MCI and 14 age-matched healthy older drivers (aged 65-87 years) completed a 10-min simulator drive in an urban environment. The simulator drive consisted of stop-sign controlled and signal-controlled intersections. Drivers were required to stop at the stop-sign controlled intersections and to decide whether or not to proceed through a critical light change at the signal-controlled intersections. The specific performance measures included; approach speed, number of brake applications on approach to the intersection (either excessive or minimal), failure to comply with stop signs, and slower braking response times on approach to a critical light change. MCI patients in our sample performed more poorly than controls across a number of variables. However, because the trends failed to reach statistical significance it will be important to replicate the study using a larger sample to qualify whether the results can be generalised to the broader population.

Epilepsy and driving: current status of research.

In many parts of the world, licensing guidelines state that drivers with medical conditions such as epilepsy are restricted or prohibited from driving. These guidelines are sometimes subjective and not strongly evidence-based, rendering the task of assessing fitness to drive a complex one. Determining fitness to drive is not only essential for maintaining the safety of individual drivers but has implications for the community at large. It is therefore important to review the current state of knowledge regarding epilepsy and driving in order to aid health professionals required to assess fitness to drive and to guide future research directions. This review outlines the functional impairments related to epilepsy and driving, treatment and management issues, motor vehicle crash risk for drivers with epilepsy, estimates of predicted seizure occurrence and concludes with a discussion of the international licensing guidelines and relevant legal issues. More comprehensive research, including investigation into the effects of antiepileptic medication on driving, could aid in the development of policies and guidelines for assessing fitness to drive.

Adult age differences in the ability to mentally transform object and body stimuli.

Cognitive neuroscience literature suggests a strong dissociation between the ability to mentally transform object and body stimuli (Hegarty & Waller, 2004). However, little is known about how this ability changes with age. This dissociation was explored in 20 younger (19-24 years) and 20 older (65-87 years) adults. Mental rotation of object stimuli was demonstrated for both age groups, suggesting that the neuro-cognitive network involved with performing (object-based) mental transformations is relatively preserved in older age. Compared to young adults, older adults displayed the greatest decline in performance efficiency for the whole-body task. The authors propose that an age-related decline in the integrity of body-schema information may account for this change.