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OBJECTIVES/GOALS: Diffusion basis spectrum imaging (DBSI) allows for detailed evaluation of white matter microstructural changes present in cervical spondylotic myelopathy (CSM). Our goal is to utilize multidimensional clinical and quantitative imaging data to characterize disease severity and predict long-term outcomes in CSM patients undergoing surgery. METHODS/STUDY POPULATION: A single-center prospective cohort study enrolled fifty CSM patients who underwent surgical decompression and twenty healthy controls from 2018-2021. All patients underwent diffusion tensor imaging (DTI), DBSI, and complete clinical evaluations at baseline and 2-years follow-up. Primary outcome measures were the modified Japanese Orthopedic Association score (mild [mJOA 15-17], moderate [mJOA 12-14], severe [mJOA 0-11]) and SF-36 Physical and Mental Component Summaries (PCS and MCS). At 2-years follow-up, improvement was assessed via established MCID thresholds. A supervised machine learning classification model was used to predict treatment outcomes. The highest-performing algorithm was a linear support vector machine. Leave-one-out cross-validation was utilized to test model performance. RESULTS/ANTICIPATED RESULTS: A total of 70 patients – 20 controls, 25 mild, and 25 moderate/severe CSM patients – were enrolled. Baseline clinical and DTI/DBSI measures were significantly different between groups. DBSI Axial and Radial Diffusivity were significantly correlated with baseline mJOA and mJOA recovery, respectively (r=-0.33, p<0.01; r=-0.36, p=0.02). When predicting baseline disease severity (mJOA classification), DTI metrics alone performed with 38.7% accuracy (AUC: 72.2), compared to 95.2% accuracy (AUC: 98.9) with DBSI metrics alone. When predicting improvement after surgery (change in mJOA), clinical variables alone performed with 33.3% accuracy (AUC: 0.40). When combining DTI or DBSI parameters with key clinical covariates, model accuracy improved to 66.7% (AUC: 0.65) and 88.1% (AUC: 0.95) accuracy, respectively. DISCUSSION/SIGNIFICANCE: DBSI metrics correlate with baseline disease severity and outcome measures at 2-years follow-up. Our results suggest that DBSI may serve as a valid non-invasive imaging biomarker for CSM disease severity and potential for postoperative improvement.
The COVID-19 pandemic prompted the development and implementation of hundreds of clinical trials across the USA. The Trial Innovation Network (TIN), funded by the National Center for Advancing Translational Sciences, was an established clinical research network that pivoted to respond to the pandemic.
The TIN’s three Trial Innovation Centers, Recruitment Innovation Center, and 66 Clinical and Translational Science Award Hub institutions, collaborated to adapt to the pandemic’s rapidly changing landscape, playing central roles in the planning and execution of pivotal studies addressing COVID-19. Our objective was to summarize the results of these collaborations and lessons learned.
The TIN provided 29 COVID-related consults between March 2020 and December 2020, including 6 trial participation expressions of interest and 8 community engagement studios from the Recruitment Innovation Center. Key lessons learned from these experiences include the benefits of leveraging an established infrastructure, innovations surrounding remote research activities, data harmonization and central safety reviews, and early community engagement and involvement.
Our experience highlighted the benefits and challenges of a multi-institutional approach to clinical research during a pandemic.
There is an urgent need to provide evidence-based well-being and mental health support for front-line clinical staff managing the COVID-19 pandemic who are at risk of moral injury and mental illness. We describe the evidence base for a tiered model of care, and practical steps on its implementation.
An improved understanding of diagnostic and treatment practices for patients with rare primary mitochondrial disorders can support benchmarking against guidelines and establish priorities for evaluative research. We aimed to describe physician care for patients with mitochondrial diseases in Canada, including variation in care.
We conducted a cross-sectional survey of Canadian physicians involved in the diagnosis and/or ongoing care of patients with mitochondrial diseases. We used snowball sampling to identify potentially eligible participants, who were contacted by mail up to five times and invited to complete a questionnaire by mail or internet. The questionnaire addressed: personal experience in providing care for mitochondrial disorders; diagnostic and treatment practices; challenges in accessing tests or treatments; and views regarding research priorities.
We received 58 survey responses (52% response rate). Most respondents (83%) reported spending 20% or less of their clinical practice time caring for patients with mitochondrial disorders. We identified important variation in diagnostic care, although assessments frequently reported as diagnostically helpful (e.g., brain magnetic resonance imaging, MRI/MR spectroscopy) were also recommended in published guidelines. Approximately half (49%) of participants would recommend “mitochondrial cocktails” for all or most patients, but we identified variation in responses regarding specific vitamins and cofactors. A majority of physicians recommended studies on the development of effective therapies as the top research priority.
While Canadian physicians’ views about diagnostic care and disease management are aligned with published recommendations, important variations in care reflect persistent areas of uncertainty and a need for empirical evidence to support and update standard protocols.
Dementia is currently incurable, irreversible and a major cause of disability for the world's older population. The association between mental health difficulties, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), and dementia has a long history within the civilian population. Despite the increased importance of this link within the military veteran population, who suffer a greater propensity of mental health difficulties and consist largely of over 65s, attention is only recently being paid to the salience of such an association for this group. This paper aims to explore the relationship between PTSD and MDD with dementia within the military veteran population.
A systematic review was conducted on articles from 1990 to July 2016 on MEDLINE, EMBASE, EBSCO and Web of Science electronic databases with an update conducted in February 2017.
Six empirical studies were identified from the review, the majority of which originated from the USA. Five of the studies asserted that veterans with a diagnosis of either PTSD or MDD are at a significantly greater risk of developing dementia than ‘healthy’ controls. The final study, conducted in Australia, found only a small, but non-significant, correlation between earlier MDD and future dementia, but no concurrent correlation.
While causality cannot be determined, it is likely that PTSD and depressive disorders are related to an increased risk of dementia in military veterans. Potential pathological explanations and risk factors are reviewed and the clinical and neuroscience implications of these findings are explored.
The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families.
OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed.
EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders).
Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.
Because individuals develop dementia as a manifestation of neurodegenerative or neurovascular disorder, there is a need to develop reliable approaches to their identification. We are undertaking an observational study (Ontario Neurodegenerative Disease Research Initiative [ONDRI]) that includes genomics, neuroimaging, and assessments of cognition as well as language, speech, gait, retinal imaging, and eye tracking. Disorders studied include Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, and vascular cognitive impairment. Data from ONDRI will be collected into the Brain-CODE database to facilitate correlative analysis. ONDRI will provide a repertoire of endophenotyped individuals that will be a unique, publicly available resource.
This study examined how native speakers of Spanish formulated sentences in English as a second language (L2) when randomly ordered words were orally presented. Participants included 206 adult literacy students (70 native Spanish speakers and 136 native English speakers) whose word reading equivalency was at third- through fifth-grade levels. The Word Ordering subtest of the Test of Language Development-3 was administered. Although they showed a similar pattern of performance in the sentence type (i.e., declarative, interrogative, or imperative sentence), the two groups showed a different pattern in the misuse of syntactic features. Pertaining to grammatical features, verbs were the most difficult item for the native speakers of Spanish. The findings of this study were explained through the intricate nature of English verbs as well as unique lexicalization patterns resulting from the typological difference between Spanish and English.
Accidental hypothermia can lead to untoward cardiac manifestations and arrest. This report presents a case series of severe accidental hypothermia with cardiac complications in three emergency patients who were treated with extracorporeal membrane oxygenation (ECMO) and survived after re-warming. The aim of this discussion was to encourage more clinicians to consider ECMO as a re-warming therapy for severe hypothermia with circulatory collapse and to prompt discussion about decreasing the barriers to its use.
NiehausMT, PechulisRM, WuJK, FreiS, HongJJ, SandhuRS, GreenbergMR. Extracorporeal Membrane Oxygenation (ECMO) for Hypothermic Cardiac Deterioration: A Case Series. Prehosp Disaster Med. 2016;31(5):570–571.
Research of military personnel who deployed to the conflicts in Iraq or
Afghanistan has suggested that there are differences in mental health
outcomes between UK and US military personnel.
To compare the prevalence of post-traumatic stress disorder (PTSD),
hazardous alcohol consumption, aggressive behaviour and multiple physical
symptoms in US and UK military personnel deployed to Iraq.
Data were from one US (n = 1560) and one UK
(n = 313) study of post-deployment military health of
army personnel who had deployed to Iraq during 2007–2008. Analyses were
stratified by high- and low-combat exposure.
Significant differences in combat exposure and sociodemographics were
observed between US and UK personnel; controlling for these variables
accounted for the difference in prevalence of PTSD, but not in the total
symptom level scores. Levels of hazardous alcohol consumption (low-combat
exposure: odds ratio (OR) = 0.13, 95% CI 0.07–0.21; high-combat exposure:
OR = 0.23, 95% CI 0.14–0.39) and aggression (low-combat exposure: OR =
0.36, 95% CI 0.19–0.68) were significantly lower in US compared with UK
personnel. There was no difference in multiple physical symptoms.
Differences in self-reported combat exposures explain most of the
differences in reported prevalence of PTSD. Adjusting for self-reported
combat exposures and sociodemographics did not explain differences in
hazardous alcohol consumption or aggression.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Early onset aggression precipitates a cascade of risk factors, increasing the probability of a range of externalizing and internalizing psychopathological outcomes. Unfortunately, decades of research on the etiological contributions to the manifestation of aggression have failed to yield identification of any risk factors determined to be either necessary or sufficient, likely attributable to etiological heterogeneity within the construct of aggression. Differential pathways of etiological risk are not easily discerned at the behavioral or self-report level, particularly in young children, requiring multilevel analysis of risk pathways. This study focuses on three domains of risk to examine the heterogeneity in 207 urban kindergarten children with high levels of aggression: cognitive processing, socioemotional competence and emotion processing, and family context. The results indicate that 90% of children in the high aggression group could be characterized as either low in verbal ability or high in physiological arousal (resting skin conductance). Children characterized as low verbal, high arousal, or both differed in social and emotional competence, physiological reactivity to emotion, and aspects of family-based contextual risk. The implications of this etiologic heterogeneity of aggression are discussed in terms of assessment and treatment.
Experts have proposed removing obsessive–compulsive disorder (OCD) from the anxiety disorders section and grouping it with putatively related conditions in DSM-5. The current study uses co-morbidity and familiality data to inform these issues.
Case family data from the OCD Collaborative Genetics Study (382 OCD-affected probands and 974 of their first-degree relatives) were compared with control family data from the Johns Hopkins OCD Family Study (73 non-OCD-affected probands and 233 of their first-degree relatives).
Anxiety disorders (especially agoraphobia and generalized anxiety disorder), cluster C personality disorders (especially obsessive–compulsive and avoidant), tic disorders, somatoform disorders (hypochondriasis and body dysmorphic disorder), grooming disorders (especially trichotillomania and pathological skin picking) and mood disorders (especially unipolar depressive disorders) were more common in case than control probands; however, the prevalences of eating disorders (anorexia and bulimia nervosa), other impulse-control disorders (pathological gambling, pyromania, kleptomania) and substance dependence (alcohol or drug) did not differ between the groups. The same general pattern was evident in relatives of case versus control probands. Results in relatives did not differ markedly when adjusted for demographic variables and proband diagnosis of the same disorder, though the strength of associations was lower when adjusted for OCD in relatives. Nevertheless, several anxiety, depressive and putative OCD-related conditions remained significantly more common in case than control relatives when adjusting for all of these variables simultaneously.
On the basis of co-morbidity and familiality, OCD appears related both to anxiety disorders and to some conditions currently classified in other sections of DSM-IV.
Employers such as the Armed Forces (AF) and emergency services, who predictably expose their staff to potentially traumatic events (PTEs), often provide psycho-educational briefings in an attempt to mitigate possible adverse psychological sequelae. Within the military, psycho-educational briefings are widely used, particularly following exposure to PTEs on operations. The aim of this review was to evaluate the efficacy of these interventions and make appropriate recommendations.
A search of Medline, PsycINFO and EMBASE was conducted, bibliographies of retrieved articles were searched and experts in the field were consulted.
Two surveys and seven intervention studies were identified for inclusion in the review. Only three studies were randomized controlled trials (RCTs). Overall, the review found some evidence of benefit of psycho-educational interventions but it was not consistent across studies or outcomes and effects were small. However, there was also little evidence to suggest that they caused harm. There was some evidence that the beneficial effects may be greater for those who have been exposed to a higher number of PTEs.
Given the high operational tempo currently faced by coalition forces personnel, there remains a pressing need to identify the most effective way of minimizing the impact of exposure to potentially traumatic deployment incidents. To date, few psycho-educational interventions designed to prevent deployment-related psychological ill-health have been evaluated systematically in methodologically robust studies. The review recommends that future interventions are theoretically based and evaluated in cluster RCTs that examine both process and outcome variables.