A Pilot Randomized Controlled Trial of Goal Management Training in Canadian Military Members, Veterans, and Public Safety Personnel Experiencing Post-Traumatic Stress Symptoms

Post-traumatic stress disorder (PTSD) is a severe psychiatric illness that disproportionately affects military personnel, veterans, and public safety personnel (PSP). Evidence demonstrates that PTSD is significantly associated with difficulties with emotion regulation (ER) and difficulties with cognitive functioning, including difficulties with attention, working memory, and executive functioning. A wide body of evidence suggests a dynamic interplay among cognitive dysfunction, difficulties with ER, and symptoms of PTSD, where numerous studies have identified overlapping patterns of alterations in activation among neuroanatomical regions and neural circuitry. Little work has examined interventions that may target these symptoms collectively. The primary objective of this pilot randomized controlled trial (RCT) with a parallel experimental design was to assess the effectiveness of goal management training (GMT), a cognitive remediation intervention, in reducing difficulties with cognitive functioning, and to determine its effects on PTSD symptoms and symptoms associated with PTSD, including difficulties with ER, dissociation, and functioning among military personnel, veterans, and PSP. Forty-two military personnel, veterans, and PSP between the ages of 18 and 70 with symptoms of PTSD were recruited across Ontario, Canada between October 2017 and August 2019. Participants were randomized to either the waitlist (WL) (n = 18) or the GMT (n = 22) condition. Participants in both conditions received self-report measures and a comprehensive neuropsychological assessment at baseline, post-intervention, and 3-month follow-up. Following their completion of the 3-month follow-up, participants in the WL condition were given the opportunity to participate in GMT. Assessors and participants were blind to intervention allocation during the initial assessment. A series of 2 (time) × 2 (group) ANOVAs were conducted to assess the differences between the WL and GMT conditions from pre-to post-intervention for the self-report and neuropsychological measures. The results demonstrated significant improvements in measures of executive functioning (e.g., verbal fluency, planning, impulsivity, cognitive shifting, and discrimination of targets) and trending improvements in short-term declarative memory for participants in the GMT condition. Participants in the GMT condition also demonstrated significant improvements from pre-to post-testing in measures of subjective cognition, functioning, PTSD symptom severity, difficulties with ER, dissociative symptom severity, and depression and anxiety symptoms. No adverse effects were reported as a result of participating in GMT. The results of this pilot RCT show promise that GMT may be a useful intervention to improve symptoms of cognitive dysfunction, symptoms of PTSD, and symptoms associated with PTSD within military personnel, veterans, and PSP. Future work is needed to address the small sample size and the durability of these findings

A Review of the Relation Between Dissociation, Memory, Executive Functioning and Social Cognition in Military Members and Civilians with Neuropsychiatric Conditions

Dissociative experiences, involving altered states of consciousness, have long been understood as a consequence or response to traumatic experiences, where a reduced level of consciousness may aid in survival during and after a traumatic event. Indeed, the dissociative subtype of post-traumatic stress disorder (PTSD-DS) was added recently to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). Dissociative symptoms are present across a host of neuropsychiatric conditions, including PTSD, psychotic spectrum illnesses, anxiety and mood disorders. Transdiagnostically, the presence of dissociative symptoms is associated with a greater illness burden and reduced treatment outcomes. Critically, dissociative symptoms are related to impaired performance on measures of attention, executive functioning, memory, and social cognition and may contribute to the widespread cognitive dysfunction observed across psychiatric illnesses. Despite this knowledge, the relation between dissociative symptoms and reduced cognitive function remains poorly understood. Here, we review the evidence linking dissociative symptoms to cognitive dysfunction across neuropsychiatric disorders. In addition, we explore two potential neurobiological mechanisms that may underlie the relation between dissociative symptoms and cognitive dysfunction in trauma-related neuropsychiatric conditions. Specifically, we hypothesize that: 1) functional sensory deafferentation at the level of the thalamus, as observed in the defence cascade model of dissociation, may underlie reduced attention and arousal leading to progressive cognitive dysfunction and; 2) altered functional connectivity between key brain networks implicated in cognitive functioning may represent a critical neurobiological mechanism linking dissociative symptoms and cognitive dysfunction in patients with PTSD-DS and transdiagnostically

A Pilot Study Assessing the Effects of Goal Management Training on Cognitive Functions among Individuals with Major Depressive Disorder and the Effect of Post-Traumatic Symptoms on Response to Intervention

Recent meta-analyses highlight alterations in cognitive functioning among individuals with major depressive disorder (MDD), with performance deficits observed across multiple cognitive domains including executive functioning, memory, and attention. Moreover, impaired concentration is a formal diagnostic criterion for a major depressive episode. Notably, cognitive impairment is reported frequently in MDD and is associated with poor treatment response. Despite this knowledge, research examining the effectiveness of top-down, adjunctive treatments for cognitive dysfunction in MDD remains in its infancy. The primary aim of the present study was to perform a pilot investigation of the implementation of a standardized cognitive remediation program, Goal Management Training (GMT), among individuals with a primary diagnosis of MDD. A secondary aim was to explore how comorbid symptoms of post-traumatic stress disorder (PTSD) among those MDD patients exposed to trauma may affect treatment response. A final sample of thirty individuals were randomized to either participate in the nine-week GMT program (active group; n = 16) or to complete a nine-week waiting period (waitlist control; n = 14). One participant was excluded from the GMT group analysis following study completion due to meeting an exclusion criteria. In total, 60% of the individuals allocated to the GMT program were trauma exposed (n = 9). Groups were assessed at baseline, post-treatment, and at three-month follow-up. The assessment comprised neuropsychological tasks assessing a variety of cognitive domains, subjective measures of functioning and symptom severity, as well as a clinical interview to establish a primary diagnosis of MDD. Significant gains in processing speed, attention/concentration, and response inhibition were observed for the participants in the GMT condition relative to participants in the waitlist control condition. Individuals in the GMT condition also reported improvements in subjective cognitive functioning from baseline to post-treatment. Heightened PTSD symptom severity was associated with reduced response to treatment with respect to the domain of processing speed. The results of this pilot investigation highlight not only the potential utility of GMT as an augmentative treatment in MDD, but also highlight the contribution of comorbid symptoms of PTSD to diminished treatment response among trauma-exposed individuals with MDD. The study is limited primarily by its small pilot sample and the absence of a program evaluation component to gauge participant opinions and feedback of the treatment protocol

The Relationship Between Adverse Childhood Experiences and Moral Injury in the Canadian Armed Forces

Background: There is increasing evidence that moral injuries (MIs) may affect the mental health of Canadian Armed Forces (CAF) members and veterans. Despite knowledge suggesting that MIs are related to multiple negative mental health outcomes, including the onset of post-traumatic stress disorder (PTSD), it is unknown whether pre-traumatic variables, including the presence of childhood abuse, are related to MIs. Objective: This study seeks to investigate the potential relationship between adverse childhood experiences and later onset MI in military members. Methods: Thirty-three patients newly admitted to an inpatient unit for treatment of trauma-related disorders received a standardized self-assessment package, including the PTSD Checklist for DSM-5 (PCL-5), the Moral Injury Events Scale (MIES; adapted for the Canadian context), and the Adverse Childhood Experiences Questionnaire (ACE-Q), which is a retrospective measure of childhood abuse. Results: Analyses revealed a significant relation between childhood emotional abuse and the presence of MI in adulthood. Specifically, emotional abuse during childhood was correlated with total score on the MIES (p = 0.006) and with its two subscales, perceived betrayals (p = 0.022) and perceived transgressions (p = 0.016). These correlations remained significant when controlling for age and gender. Conclusions: Among CAF members and veterans, childhood events are related to the presence of MI during adulthood. These preliminary data are provocative in suggesting that emotional abuse during childhood may increase the likelihood of endorsing MI during adult military service. Further work is needed to identify pre-traumatic variables that may serve to increase risk or enhance resilience to the development of MI in military members

Diagnosing delirium in critically ill children: Validity and reliability of the Pediatric Confusion Assessment Method for the Intensive Care Unit*

To validate a diagnostic instrument for pediatric delirium in critically ill children, both ventilated and nonventilated, that uses standardized, developmentally appropriate measurements

Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society