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Objective: Neuropsychological assessment (NP) feedback helps patients and caregivers understand assessment results to maximise their utility and impact in everyday life. Yet feedback practices are inconsistent and there are no evidence-based guidelines for how feedback should be most effectively delivered. The aim of our study was to develop a psychometrically sound feedback competency checklist, the Psychology Competency Assessment Tool – Feedback (PsyCET-F), for use in research, training, and clinical settings. Method: The Delphi method of expert consensus was used to establish checklist items that clearly described competencies important for NP feedback. To examine the inter-rater reliability of the checklist, two experienced neuropsychologists rated the competencies demonstrated by trainee neuropsychologists across four feedback sessions. Results: After two Delphi rounds, consensus was reached on the 20-item checklist. Consensus was defined as at least 80% agreement amongst the panel of 20 experts. Four item categories resulted from the Delphi: (a) Opening the Session; (b) Applying Specific Feedback Techniques; (c) Engagement, Collaboration, and Alliance; and (d) Structuring and Ending the Session. Inter-rater reliability was moderate (κW = 0.79, p <.001, 80.52% agreement) when using a simple coding system, coded as Beginner, Intermediate, Competent, and Skilful; and strong (κW = 0.82, p <.001) when competency level was coded using an 8-point, detailed coding method. Conclusions: The PsyCET-F is psychometrically sound and fit-for-purpose for measuring competencies in giving NP feedback. It can be used in the training of clinicians to develop effective feedback skills. International benchmarking and usability testing will be conducted in a future study. [ABSTRACT FROM AUTHOR]

Agitation is common in the early recovery period following traumatic brain injury (TBI), known as post-traumatic amnesia (PTA). Non-pharmacological interventions are frequently used to manage agitation, yet their efficacy is largely unknown. This systematic review aims to synthesize current evidence on the effectiveness of non-pharmacological interventions for agitation during PTA in adults with TBI. Key databases searched included MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO and CENTRAL, with additional online reviewing of key journals and clinical trial registries to identify published or unpublished studies up to May 2020. Eligible studies included participants aged 16 years and older, showing agitated behaviours during PTA. Any non-pharmacological interventions for reducing agitation were considered, with any comparator accepted. Eligible studies were critically appraised for methodological quality using Joanna Briggs Institute Critical Appraisal Instruments and findings were reported in narrative form. Twelve studies were included in the review: two randomized cross-over trials, three quasi-experimental studies, four cases series and three case reports. Non-pharmacological interventions were music therapy, behavioural strategies and environmental modifications, physical restraints and electroconvulsive therapy. Key methodological concerns included absence of a control group, a lack of formalised agitation measurement and inconsistent concomitant use of pharmacology. Interventions involving music therapy had the highest level of evidence, although study quality was generally low to moderate. Further research is needed to evaluate non-pharmacological interventions for reducing agitation during PTA after TBI. Systematic review registration number: PROSPERO (CRD42020186802), registered May 2020. [ABSTRACT FROM AUTHOR]

Family expressed emotion (EE) is a strong predictor of outcome in a range of psychiatric and medical conditions. This study aimed to examine the relationship between family EE-criticism, patient perceived criticism and criticism sensitivity and psychiatric disorders following moderate to severe traumatic brain injury (TBI). Participants were 60 patients with TBI and their family members. Patients were assessed for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID-I) and completed the Perceived Criticism Measure (PCM) to determine levels of perceived criticism and criticism sensitivity. Family members completed the Family Questionnaire (FQ) to assess patient directed EE-criticism. Patients were reassessed approximately 12-months post-baseline. After controlling for diagnostic status at baseline, high criticism sensitivity at baseline was associated with greater probability of psychiatric diagnosis at follow-up (odds ratio=3.99, 95% CI=1.15–13.71). Family EE-criticism and perceived criticism were not predictive of patient diagnostic status at follow-up, but patients with high EE-family members were more likely to have a concurrent psychiatric diagnosis at baseline. Findings suggest that sensitivity to interpersonal criticism may have a role in the development and course of psychiatric disorders following TBI. [ABSTRACT FROM AUTHOR]

Abstract: The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T 1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. [Copyright &y& Elsevier]

The Austin Maze is a neuropsychological assessment tool used to measure cognitive function. A computerised version of the tool has recently been developed and shown to be equivalent to the conventional version in terms of performance. However, controversy remains regarding which specific cognitive constructs the conventional and computer versions of the Austin Maze purport to measure. The aim of this study was to investigate which cognitive constructs are associated with Austin Maze performance and whether these constructs remain equivalent across conventional and computer versions. Sixty-three healthy people completed both conventional and computerised versions of the Austin Maze in addition to a number of established measures of planning, error utilisation, working memory, visuospatial ability and visuospatial memory. Results from a series of regression analyses demonstrated that both versions of the Austin Maze were predominantly associated with visuospatial ability and visuospatial memory. No executive measures, including those of planning, error utilisation or working memory, significantly contributed to any Austin Maze performances. This study complements previous research and supports equivalency of the conventional and computer versions of the Austin Maze. [ABSTRACT FROM AUTHOR]

Agitation is a common behavioral problem following traumatic brain injury (TBI); however, the precise proportion of patients who experience agitation in the early stages of recovery is unknown. The aim of this systematic review and meta-analysis was to evaluate the prevalence of agitation in TBI patients undergoing inpatient care, and whether this prevalence differed by post-traumatic amnesia (PTA) status and setting (acute and rehabilitation). We also aimed to describe the prevalence of sub-types of agitated behavior (disinhibited, aggressive, and emotionally labile). We searched five databases and one clinical trials register, with additional review of websites and key journals to identify any relevant records up to July 2020. We included studies describing the proportion of hospitalized TBI patients age 16 years or older demonstrating agitated behavior. We included comparative studies with and without concurrent controls, randomized controlled trials, pseudo-randomized controlled trials, and case series. Methodological quality was critically appraised using a Joanna Briggs Institute checklist. Sixteen studies met eligibility criteria, with a total of 5592 participants. The pooled prevalence of agitation was 31.73% (95% confidence interval [CI], 25.25%-39.00%) during inpatient care (acute and rehabilitation), 32.23% (95% CI, 27.13%-37.80%) during rehabilitative care and 44.06% (95% CI, 36.15%-52.28%) for inpatients in PTA specifically. Disinhibited behaviors were the most common. There was substantial heterogeneity between studies. Additional high-quality research featuring large samples, frequent and long-term measurement of agitation, use of validated scales, and consideration of variables such as PTA status will further improve estimates of agitation prevalence following TBI. [ABSTRACT FROM AUTHOR]

Delivery of neuropsychological interventions addressing the cognitive, psychological, and behavioural consequences of brain conditions is increasingly recognised as an important, if not essential, skill set for clinical neuropsychologists. It has the potential to add substantial value and impact to our role across clinical settings. However, there are numerous approaches to neuropsychological intervention, requiring different sets of skills, and with varying levels of supporting evidence across different diagnostic groups. This clinical guidance paper provides an overview of considerations and recommendations to help guide selection, delivery, and implementation of neuropsychological interventions for adults and older adults. We aimed to provide a useful source of information and guidance for clinicians, health service managers, policy-makers, educators, and researchers regarding the value and impact of such interventions. Considerations and recommendations were developed by an expert working group of neuropsychologists in Australia, based on relevant evidence and consensus opinion in consultation with members of a national clinical neuropsychology body. While the considerations and recommendations sit within the Australian context, many have international relevance. We include (i) principles important for neuropsychological intervention delivery (e.g. being based on biopsychosocial case formulation and person-centred goals); (ii) a description of clinical competencies important for effective intervention delivery; (iii) a summary of relevant evidence in three key cohorts: acquired brain injury, psychiatric disorders, and older adults, focusing on interventions with sound evidence for improving activity and participation outcomes; (iv) an overview of considerations for sustainable implementation of neuropsychological interventions as ‘core business’; and finally, (v) a call to action. [ABSTRACT FROM AUTHOR]

Abstract: We obtained high-resolution (λ/Δλ ∼28,000) infrared spectra of Comet 103P/Hartley 2 on UT 2010 November 4.6 using the NIRSPEC spectrometer at the W.M. Keck Observatory. Here we present spectra of Hartley 2 between 2.832 and 3.639μm (3531–2748cm−1), representing the most complete high-resolution infrared survey of a Jupiter-family comet to date in this wavelength region. We have tabulated rest frequencies, line fluxes, line signal-to-noise ratios and line widths for all detected emissions. Fluorescence models, published line lists and laboratory spectra were used to obtain molecular assignments for detected emissions. Multiple lines of the following species were detected in Hartley 2: H2O, OH, CH3OH, C2H6, HCN, C2H2, H2CO, NH3 and NH2. All identified species seen in this survey have been previously detected in comets. There were 364 distinct emission features present in these spectra, of which 36 were unidentified. We compare the spectrum of Hartley 2 to chemically different Jupiter-family Comets 73P/Schwassmann–Wachmann 3-B and 17P/Holmes in order to obtain additional information on the characteristics of unknown lines through the comparison of relative line fluxes for corresponding emissions in these comets. For the strongest unidentified emissions, additional information was also obtained through a comparison of their spatial distributions in the coma to that of known emission features in Hartley 2. This spectral survey of Hartley 2 provides detailed information about its overall volatile chemistry, provides a comparison to past and future high-resolution infrared datasets, and further characterizes the most promising spectral regions for future molecular searches in comets. [Copyright &y& Elsevier]

Abstract: We conducted high-dispersion spectroscopic observations of Comet 103P/Hartley 2 in the near-infrared wavelength region using the Keck II telescope with NIRSPEC. We obtained observations on four dates, with the last observations performed during the EPOXI closest approach. For this work we focus on the observations performed on UT 2010 October 17 and 21, while observations carried out on UT 2010 September 16 and November 4 have been reported elsewhere. On all dates the spatial distributions in the coma of C2H6, HCN and C2H2 were similar to each other and consistent with the CN-jet morphology observed from optical observations. The spatial distributions in the coma of H2O and CH3OH were also similar to each other, but were generally different from C2H6, HCN and C2H2. There might be two distinct phases of ice in Comet Hartley 2; one is enriched in H2O and CH3OH, and another is enriched in more volatile species (C2H6, C2H2, and HCN). It is possible that highly volatile species like C2H6 were segregated from the H2O matrix when warmer conditions were prevalent. We summarize our spectroscopic observations and report absolute production rates and mixing ratios of parent volatiles. There was no evidence of any significant diversity in the mixing ratios of parent volatiles on different dates. Comet Hartley 2 was normal in CH3OH/H2O, C2H6/H2O, C2H2/H2O, NH3/H2O but depleted in H2CO/H2O and CH4/H2O. OPRs of H2O in Comet Hartley 2 measured in its 2010 apparition were consistent with those observed by the Infrared Satellite Observatory in 1997. [Copyright &y& Elsevier]

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets. [ABSTRACT FROM AUTHOR]

• A range of interventions are used worldwide to manage agitation after head injury. • Non-pharmacological strategies are favoured, although medication use remains high. • Clinicians with training and guidelines are more confident in managing agitation. • Only half of clinicians were satisfied with agitation management in their services. • Findings support the development of formal guidelines for managing agitation after head injury. Managing agitation is a significant challenge in the early stages of recovery after traumatic brain injury (TBI), and research investigating current practice during this period is lacking. This study examined how clinicians worldwide conceptualise, measure and manage agitation during early TBI recovery. A cross-sectional anonymous online survey was distributed via email, newsletters, conferences and social media to clinicians involved in early TBI care worldwide. Respondents were 331 clinicians (66% female) from 34 countries worldwide who worked in inpatient and outpatient settings in disciplines including medicine, nursing and allied health. Participants had an average of 13 years' clinical experience working specifically with an adult TBI population. Agitated behaviour was commonly defined as aggression and restlessness. Three quarters of clinicians reported that their services measure agitation, and clinicians in North America more frequently use standardised assessment tools. Common non-pharmacological approaches used across all regions surveyed included providing familiarising information (85%) and environmental cues (82%), managing patients in single rooms (81%) and reducing noise levels (80%). Most clinicians (90%) reported pharmacology use, particularly atypical antipsychotic agents. Clinicians' mean rating of confidence in managing agitation was 7 out of 10 (10 being excellent) and was higher for services that provided staff with written guidelines for agitation management. Only half of clinicians reported sufficient training for managing agitation and 52% were satisfied with current agitation management practices. Despite high rates of agitation measurement and management, many clinicians reported dissatisfaction with current agitation management and insufficient training. This study supports the development of international guidelines and training to ensure consistent and effective agitation management in early TBI care. [ABSTRACT FROM AUTHOR]

High-resolution infrared spectra of Jupiter-family comet 45P/Honda-Mrkos-Pajdušáková were obtained with NIRSPEC at the W. M. Keck Observatory on two post-perihelion dates (UT 2017 February 13 and 19), when the comet was at heliocentric distances of 1.01 and 1.10 AU, respectively. On UT February 13, H 2 O was measured simultaneously with six trace parent molecules: CH 3 OH, C 2 H 6 , HCN, NH 3 , C 2 H 2 , and H 2 CO. On UT February 19, CH 4 and CO were also targeted in addition to the species measured on UT February 13. Abundances of CO, CH 4 , and C 2 H 2 relative to H 2 O are consistent with values obtained from IRTF/iSHELL observations of 45P in early January 2017 just after perihelion when the heliocentric distance was 0.55–0.56 AU. Differences are seen in H 2 CO/H 2 O, C 2 H 6 /H 2 O, CH 3 OH/H 2 O, and HCN/H 2 O in February compared to January. Additionally, NH 3 abundances appear highly variable during the February measurements, suggesting possible fluctuations of a factor of ten; however, there is significant uncertainty in quantifying NH 3 owing to the marginal detections of only one or two lines on each of the two dates. Combining all infrared spectroscopic observations of 45P in January and February 2017, a post-perihelion relationship of Q(H 2 O) = (2.81 ± 0.25) × 1027 [R h (−3.83±0.18)] molecules s−1 is derived. However, all measurements suggest significant variability in H 2 O production on timescales of hours and days. Compared to other comets, volatile abundances relative to H 2 O in 45P are as follows: CO (depleted relative to all measured comets), CH 3 OH (enriched/all comets), CH 4 and C 2 H 6 (typical/all comets, enriched/Jupiter-family comets), C 2 H 2 (depleted/all comets, typical/Jupiter-family comets), H 2 CO (January: typical, February depleted/all comets), HCN (January: severely depleted, February: typical/Jupiter-family comets). The small geocentric distances of the comet in February 2017 provide high spatial resolution in the coma of 45P (~12 and 19 km/pixel on February 13 and 19, respectively). Overall, the spatial distributions of volatiles and dust suggest a relatively symmetric and uniform coma during the UT February 13 and 19 observations, with small spatial differences noted between some volatile species. Measured C 2 H 2 and HCN abundances are consistent with HCN as the primary parent of CN and C 2 H 2 as a significant but not primary parent for C 2 , based on C 2 and CN production rate measurements from the 2017 and previous apparitions. Extracted spectra show an increase in the dust-to-gas ratio in 45P from February 13 to 19 in agreement with contemporaneous narrowband optical measurements. • Reports production rates and relative abundances for parent volatiles in comet 45P. • Significant chemical differences measured in 45P near perihelion compared to six weeks later near closest Earth approach. • Dust-to-gas ratio in 45P increased significantly from February 13 to 19. • 45P chemistry is further evidence that comets retain a significant if not dominant natal signature. [ABSTRACT FROM AUTHOR]

During the early recovery period after traumatic brain injury (TBI), referred to as post-traumatic amnesia (PTA), approximately 44% of individuals may exhibit agitated behaviours. Agitation can impede recovery and poses a significant management challenge for healthcare services. As families provide significant support for their injured relatives during this time, this study aimed to explore the family's experience during PTA to better understand their role in agitation management. There were 20 qualitative semi-structured interviews conducted with 24 family members of patients exhibiting agitation during early TBI recovery (75% female, aged 30-71 years), predominantly parents ( n  = 12), spouses ( n  = 7) and children ( n  = 3). The interviews explored the family's experience of supporting their relative exhibiting agitation during PTA. The interviews were analyzed using reflexive thematic analysis, which revealed three key themes: family contributions to patient care, expectations of the health care service and supporting families to support patients. This study emphasized the significant role of families in managing agitation during early TBI recovery and highlighted that families who are well-informed and well-supported have the potential to minimize their relative's agitation during PTA, which may reduce the burden on healthcare staff and promote patient recovery.

Background Despite evidence of the efficacy of activities of daily living (ADL) retraining during post-traumatic amnesia (PTA) following traumatic brain injury (TBI), utilisation of this intervention in practice is unclear. Utilising an implementation science framework, the Consolidated Framework for Implementation Research, this study explored efforts to translate ADL retraining during PTA into the clinical practice of occupational therapists (OTs) working in TBI rehabilitation settings across Australia. Methods Participants were 44 OTs who attended a day-long training workshop that included knowledge and skill-based content regarding ADL retraining during PTA. Baseline and post-training ratings were completed including evaluation of workshop utility, and skill and knowledge-based competencies relevant to the intervention. Approximately 2 years later, nine trained OTs and two administrators were interviewed to explore the results of implementing the intervention. Results Overall, the training workshop was rated as being helpful and OT ratings of confidence (P  P   Conclusion Multiple barriers were identified in implementation of ADL retraining during PTA and require consideration to facilitate translation and promote best practice.

Purpose: Agitated behaviours pose a significant challenge during early recovery following traumatic brain injury (TBI). This study aimed to gain a deeper understanding of how clinicians worldwide manage post-TBI agitation. Understanding the factors that influence how clinicians manage agitation can help inform the use of consistent and effective management strategies for reducing agitation in TBI care., Methods: Using a qualitative design, semi-structured interviews were conducted with 33 clinicians (58% female, aged 23-71 years) from 16 countries who had experience working with agitated patients. The interviews explored the approaches used to manage agitation during early TBI recovery., Results: Interviews were analysed using thematic analysis. The central theme of the interviews was the effective management of agitation, consisting of three sub-themes: managing the safety of staff and patients, reducing triggers for agitation, and implementing behavioural principles for managing agitation. Two overarching themes influenced the effective management of agitation: clinician-related factors and systemic factors., Conclusions: This study highlighted key approaches for effective agitation management during early TBI recovery, as described by clinicians working with these patients worldwide. There were similarities in the strategies described, although there were many challenges that impeded the consistent implementation of such strategies in TBI care settings., IMPLICATIONS FOR REHABILITATIONEffective management of agitation during early traumatic brain injury (TBI) recovery continues to pose a significant challenge for clinicians worldwide.Healthcare services may improve the management of agitation by involving the patient's family in care delivery and implementing low-cost less-restrictive non-pharmacological interventions to reduce reliance on pharmacological interventions.Proactively addressing and removing potential sources of agitation (patient-related and environmental) may help reduce the risk of agitation occurring.The use of simple behaviour management strategies may be effective for reducing agitation, but strategies need to be implemented consistently and the approach should be flexible and tailored to the patient.Clinicians should develop an understanding of a patient's premorbid behaviours and interests to best inform the management approach.Management of agitation may be improved by increasing clinicians' agency in responding to agitated behaviours, through the provision of information and resources, ongoing training and skill development, supervision and support.

Background: Despite clinical guidelines recommending an interdisciplinary approach to persisting post-concussion symptom (PPCS) management, evaluations of interdisciplinary interventions remain scant., Objectives: This pilot study aimed to explore the feasibility and preliminary efficacy of an interdisciplinary intervention for PPCSs., Method: A single-case experimental design with randomisation to multiple baselines (2, 4, or 6 weeks) was repeated across 15 participants (53% female) with mild traumatic brain injury (mean age 38.3 years, SD 15.7). The 12-week treatment incorporated psychology, physiotherapy, and medical interventions. Feasibility outcomes included recruitment and retention rates, adverse events, treatment adherence and fidelity. Patient-centred secondary outcomes included the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), assessed 3 times per week during the baseline and treatment phases, and at the 1- and 3-month follow-ups. Other secondary outcomes included measures of mood, sleep and fatigue, physical functioning, health-related quality of life, illness perceptions, and goal attainment. Changes in PPCSs were evaluated using systematic visual analysis and Tau-U. Clinically significant changes in secondary outcomes were explored descriptively., Results: 16/26 individuals assessed for eligibility were enroled (61% recruitment rate); 15 completed the post-treatment follow-ups, and 13 completed the 1- and 3-month follow-up assessments (81% retention rate). High treatment adherence and competence in delivering treatments was observed. Moderate-large effect sizes for reducing PPCSs were observed in 12/15 cases, with 7/15 reaching statistical significance. Improvements were maintained at the 1- and 3-month follow-ups and were accompanied by reductions in fatigue, sleep difficulties, and mood symptoms, and changes in illness perceptions. All participants had clinically significant improvements in at least 1 outcome, with 81% of individual therapy goals achieved., Conclusions: This pilot study provided preliminary support for a subsequent randomised controlled trial (RCT), with satisfactory recruitment, retention, treatment compliance, and treatment fidelity. Improvement was evident on participant outcomes including symptom reduction and goal attainment, suggesting that progressing to a phase-II RCT is worthwhile. Findings highlight the potential benefit of individualized interdisciplinary treatments., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Agitation is common during post-traumatic amnesia (PTA) following traumatic brain injury (TBI) and is associated with risk of harm to patients and caregivers. Antipsychotics are frequently used to manage agitation in early TBI recovery despite limited evidence to support their efficacy, safety, and impact upon patient outcomes. The sedating and cognitive side effects of these agents are theorized to exacerbate confusion during PTA, leading to prolonged PTA duration and increased agitation. This study, conducted in a subacute inpatient rehabilitation setting, describes the results of a double-blind, randomized, placebo-controlled trial investigating the efficacy of olanzapine for agitation management during PTA, analyzed as an n-of-1 series. Group comparisons were additionally conducted, examining level of agitation; number of agitated days; agitation at discharge, duration, and depth of PTA; length of hospitalization; cognitive outcome; adverse events; and rescue medication use. Eleven agitated participants in PTA (mean [M] age = 39.82 years, standard deviation [SD] = 20.06; mean time post-injury = 46.09 days, SD = 32.75) received oral olanzapine ( n  = 5) or placebo ( n  = 6) for the duration of PTA, beginning at a dose of 5 mg/day and titrated every 3 to 4 days to a maximum dose of 20 mg/day. All participants received recommended environmental management for agitation. A significant decrease in agitation with moderate to very large effect (Tau-U effect size = 0.37-0.86) was observed for three of five participants receiving olanzapine, while no significant reduction in agitation over the PTA period was observed for any participant receiving placebo. Effective olanzapine dose ranged from 5-20 mg. Response to treatment was characterized by lower level of agitation and response to treatment within 3 days. In group analyses, participants receiving olanzapine demonstrated poorer orientation and memory during PTA with large effect size (olanzapine, mean = 9.32, SD = 0.69; placebo, M = 10.68, SD = 0.30; p  = .009, d  = -2.16), and a trend toward longer PTA duration with large effect size (olanzapine, M = 71.96 days, SD = 20.31; placebo, M = 47.50 days, SD = 11.27; p  = 0.072, d  = 1.26). No further group comparisons were statistically significant. These results suggest that olanzapine can be effective in reducing agitation during PTA, but not universally so. Importantly, administration of olanzapine during PTA may lead to increased patient confusion, possibly prolonging PTA. When utilizing olanzapine, physicians must therefore balance the possible advantages of agitation management with the possibility that the patient may never respond to the medication and may experience increased confusion, longer PTA and potentially poorer outcomes. Further high-quality research is required to support these findings and the efficacy and outcomes associated with the use of any pharmacological agent for the management of agitation during the PTA period.

Objective: To investigate the factor structure of the Agitated Behavior Scale (ABS) in patients with traumatic brain injury (TBI) in posttraumatic amnesia (PTA)., Setting: Inpatient TBI rehabilitation ward in Victoria, Australia., Participants: A total of 364 patients aged 16 to 92 years meeting diagnostic criteria for TBI and PTA admitted between September 2013 and October 2020., Design: Retrospective cohort study utilizing electronic medical record data., Main Measures: The ABS and the Westmead Post-Traumatic Amnesia Scale (WPTAS)., Results: Exploratory factor analysis uncovered 2 moderately correlated underlying factors (0.52), labeled Restlessness and Aggression/Lability. Two items failed to demonstrate sufficiently large loadings on either factor. Both factors demonstrated adequate reliability (Cronbach α = 0.87 and 0.81 for Restlessness and Aggression/Lability, respectively). Linear regression indicated that higher WPTAS scores were associated with lower levels of Restlessness (β = -.14, P < .001), supporting construct validity. Conversely, WPTAS scores were not significantly associated with Aggression/Lability (β = -.12, P = .08). Subgroup analysis indicated that a history of mood disorder was associated with greater severity of Aggression/Lability (P = .02). Confirmatory factor analysis indicated superior fit of the identified 2-factor solution when compared with previously explored 1-, 2-, 3-, and 4-factor structures., Conclusion: This study suggests that the latent structure of the ABS is best explained by a single construct of agitation with 2 discrete facets reflecting Restlessness and Aggression/Lability. These subscales may be used in clinical practice to evaluate the severity of different aspects of agitated behavior, inform treatment decisions, and judge the efficacy of interventions over time. Further research is required to explain low factor loadings demonstrated by 2 items., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Posttraumatic amnesia (PTA) is a common occurrence following moderate to severe traumatic brain injury (TBI) and emergence from coma. It is characterized by confusion, disorientation, retrograde and anterograde amnesia, poor attention and frequently, agitation. Clinicians and family need guidelines to support management practices during this phase., Methods: An international team of researchers and clinicians (known as INCOG) met to update the INCOG guidelines for assessment and management of PTA. Previous recommendations and audit criteria were updated on the basis of review of the literature from 2014., Results: Six management recommendations were made: 1 based on level A evidence, 2 on level B, and 3 on level C evidence. Since the first version of INCOG (2014), 3 recommendations were added: the remainder were modified. INCOG 2022 recommends that individuals should be assessed daily for PTA, using a validated tool (Westmead PTA Scale), until PTA resolution. To date, no cognitive or pharmacological treatments are known to reduce PTA duration. Agitation and confusion may be minimized by a variety of environmental adaptations including maintaining a quiet, safe, and consistent environment. The use of neuroleptic medications and benzodiazepines for agitation should be minimized and their impact on agitation and cognition monitored using standardized tools. Physical therapy and standardized activities of daily living training using procedural and errorless learning principles can be effective, but delivery should be tailored to concurrent levels of cognition, agitation, and fatigue., Conclusions: Stronger recommendations regarding assessment of PTA duration and effectiveness of activities of daily living training have been made. Evidence regarding optimal pharmacological and nonpharmacological management of confusion and agitation during PTA remains limited, with further research needed. These guidelines aim to enhance evidence-based care and maximize consistency of PTA management., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Up to 25% of concussed individuals experience persistent post-concussion symptoms (PPCSs) which may interfere with the return to pre-injury activities and cause significant stress. Given that multiple etiological factors are thought to contribute to PPCSs, an interdisciplinary approach is recommended. This pilot study aims to primarily investigate the feasibility of a novel interdisciplinary treatment for PPCSs. Given this intervention is novel, uncertainty exists in terms of potential recruitment and retention rates, adverse events, and treatment adherence and fidelity. These factors will be explored to inform the feasibility of a phase-2 randomised controlled trial. Preliminary efficacy of this intervention will also be explored., Methods: Fifteen individuals with mild traumatic brain injury and PPCSs will receive up to 12 weeks of interdisciplinary treatments including psychology, physiotherapy, and medical interventions. Primary feasibility outcomes including data on recruitment and retention rates and treatment adherence will be explored descriptively. The cognitive therapy rating scale will be used to assess treatment fidelity. A single-case series with multiple baseline design will be used to explore preliminary efficacy. Participants will be randomly assigned to baseline phases of 2, 4, or 6 weeks. Regarding patient-centred secondary outcomes, the Rivermead Post-Concussion Symptoms Questionnaire will be assessed three times a week during baseline and treatment phases. Secondary outcomes also include measures of mood, sleep and fatigue, physical functioning, return to activity, and health-related quality of life. Patient-centred outcomes will be assessed at baseline, pretreatment, post-treatment, and one- and three-month follow-up. Thematic analysis of participant experiences will be explored through qualitative interviews., Discussion: Results from this trial will inform the feasibility and preliminary efficacy of this interdisciplinary concussion intervention and whether proceeding to a future definitive phase-2 randomised controlled trial is worthwhile. Understanding the end-user perspective of the treatment will also enable modifications to the treatment protocol for future trials to best suit the needs of individuals with PPCSs after mTBI. Outcomes from this trial can be directly translated into community rehabilitation programmes., Trial Registration: ANZCTR, ACTRN12620001111965. Registered 27 October 2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=379118., (© 2022. The Author(s).)

Background: In psychological research, control conditions in the form of "treatment as usual" provide support for intervention efficacy, but do not allow the attribution of positive outcomes to the unique components of the treatment itself. Attentionally and structurally equivalent active control conditions, such as health education (HE), have been implemented in recent trials of cognitive behavioural therapy (CBT). However, descriptions and evaluations of these control conditions are limited. The aims of this paper were to (i) provide a detailed description and rationale for a novel HE active control condition and (ii) to evaluate the face validity, treatment integrity and feasibility of HE., Method: We developed a HE active control similar in structure and duration to a CBT intervention for reducing sleep disturbance and fatigue (CBT-SF) in a pilot randomised controlled trial (n = 51). Face validity was measured using post-treatment participant satisfaction and helpfulness ratings for fatigue and sleep symptoms, treatment fidelity was measured with integrity monitoring ratings from an independent expert and feasibility was measured with completion and attrition rates. HE and CBT-SF groups were compared using Wilcoxon rank-sum tests and chi-square tests of independence., Results: There were no significant differences in participant ratings of overall satisfaction between HE (n = 17) and CBT (n = 34) or in how helpful each intervention was for fatigue symptoms. Participants rated helpfulness for sleep symptoms higher in the CBT-SF group compared to HE. Integrity monitoring ratings were not significantly different for overall treatment delivery and therapist competency, but HE had greater module adherence than CBT-SF. There were no significant differences in completion or attrition rates between groups., Conclusion: Our findings suggest that the HE control had adequate face validity, was delivered with fidelity and was feasible and suitable for use as a comparator for CBT-SF. In providing a real-world example of practical and theoretical issues we considered when designing this control condition, we aim to provide a framework and guidance for future investigators., Trial Registration: ACTRN12617000879369 (registered 15/06/2017) and ACTRN12617000878370 (registered 15/06/2017)., (© 2022. The Author(s).)

Objective: To identify factors associated with treatment response to cognitive behavioral therapy for sleep disturbance and fatigue (CBT-SF) after acquired brain injury (ABI)., Setting: Community dwelling., Participants: Thirty participants with a traumatic brain injury or stroke randomized to receive CBT-SF in a parent randomized controlled trial., Design: Participants took part in a parallel-groups, parent randomized controlled trial with blinded outcome assessment, comparing an 8-week CBT-SF program with an attentionally equivalent health education control. They were assessed at baseline, post-treatment, 2 months post-treatment, and 4 months post-treatment. The study was completed either face-to-face or via telehealth (videoconferencing). Following this trial, a secondary analysis of variables associated with treatment response to CBT-SF was conducted, including: demographic variables; injury-related variables; neuropsychological characteristics; pretreatment sleep disturbance, fatigue, depression, anxiety and pain; and mode of treatment delivery (face-to-face or telehealth)., Main Measures: Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS)., Results: Greater treatment response to CBT-SF at 4-month follow-up was associated with higher baseline sleep and fatigue symptoms. Reductions in fatigue on the FSS were also related to injury mechanism, where those with a traumatic brain injury had a more rapid and short-lasting improvement in fatigue, compared with those with stroke, who had a delayed but longer-term reduction in fatigue. Mode of treatment delivery did not significantly impact CBT-SF outcomes., Conclusion: Our findings highlight potential differences between fatigue trajectories in traumatic brain injury and stroke, and also provide preliminary support for the equivalence of face-to-face and telehealth delivery of CBT-SF in individuals with ABI., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To synthesize current evidence on the effects and harms of non-pharmacological interventions for managing agitation during post-traumatic amnesia in adults who have sustained a traumatic brain injury., Introduction: Agitation is one of the most disruptive and clinically significant sequelae observed during post-traumatic amnesia. Patients who experience agitation during this period demonstrate reduced engagement in rehabilitation and poorer long-term functional outcomes. Agitation also poses a risk to staff and patient safety. Research for the effects of pharmacological intervention for managing agitation during this period is inconclusive. Thus, synthesis of the research for non-pharmacological interventions for reducing agitation during post-traumatic amnesia is essential for improving long-term outcomes for survivors of traumatic brain injury., Inclusion Criteria: Studies will be considered if they include participants aged 16 years and older who exhibit agitated behaviors during post-traumatic amnesia after sustaining a traumatic brain injury (irrespective of severity or mechanism). Studies will be considered if they evaluate any non-pharmacological intervention for reducing agitation, with all types of comparators accepted. Primary outcomes of interest include a change in agitation severity and any adverse effects., Methods: Key information sources include MEDLINE Ovid SP interface, PubMed, CINAHL, Excerpta Medica Database, PsycINFO, and Cochrane CENTRAL. Studies published in English will be included, irrespective of publication year. Two independent reviewers will be involved in study selection and data extraction. Eligible studies will be critically appraised for methodological quality. Studies will be pooled with statistical meta-analysis where possible; otherwise findings will be reported in narrative form., Systematic Review Registration Number: PROSPERO CRD42020186802., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Background: Agitation is common in the early stages of recovery from traumatic brain injury (TBI), when patients are in post-traumatic amnesia (PTA). Agitation is associated with risk of harm to patients and caregivers. Recent guidelines recommend that agitation during PTA is managed using environmental modifications. Agitation is also frequently treated pharmacologically, with the use of atypical antipsychotics such as olanzapine among the most common. This is despite a lack of well-designed studies to support the use of antipsychotics within this context. This study will be a double-blind, placebo-controlled randomised controlled trial. We will examine the efficacy, safety, cost-effectiveness and outcomes associated with the use of olanzapine for reducing agitation in patients in PTA following TBI over and above recommended environmental management., Methods: Fifty-eight TBI rehabilitation inpatients who are in PTA and are agitated will receive olanzapine or placebo for the duration of PTA. All participants will additionally receive optimal environmental management for agitation. Measures of agitation, PTA and health will be undertaken at baseline. Treatment administration will begin at a dose of 5 mg daily and may be escalated to a maximum dose of 20 mg per day. Throughout the treatment period, agitation and PTA will be measured daily, and adverse events monitored weekly. Efficacy will be assessed by treatment group comparison of average Agitated Behaviour Scale scores during PTA. Participants will cease treatment upon emergence from PTA. Agitation levels will continue to be monitored for a further 2 weeks, post-treatment measures of health will be undertaken and cognitive and functional status will be assessed. Level of agitation and functional health will be assessed at hospital discharge. At 3 months post-discharge, functional outcomes and health service utilisation will be measured., Discussion: This trial will provide crucial evidence to inform the management of agitation in patients in PTA following TBI. It will provide guidance as to whether olanzapine reduces agitation over and above recommended environmental management or conversely whether it increases or prolongs agitation and PTA, increases length of inpatient hospitalisation and impacts longer term cognitive and functional outcomes. It will also speak to the safety and cost-effectiveness of olanzapine use in this population., Trial Registration: ANZCTR ACTRN12619000284167 . Registered on 25 February 2019.

Background: Given the high frequency and significance of anxiety and depression following traumatic brain injury (TBI), there is a need to evaluate the efficacy of psychological interventions and to understand factors influencing response to such interventions. The present study investigated factors associated with positive response to cognitive behavioral therapy adapted for cognitive impairments (CBT-ABI) for individuals with anxiety and depression following TBI, including demographic and injury-related factors, pretreatment levels of anxiety and depression, working alliance, and change expectancy as predictors., Methods: Participants were 45 individuals enrolled in an active treatment condition within a randomized controlled trial, examining the efficacy of a 9-session CBT-ABI program for anxiety and depression following TBI. These participants completed all CBT sessions., Results: Mixed-effects regressions controlling for baseline anxiety and depression indicated that for anxiety, older age at injury, as well as higher level of baseline anxiety, was associated with greater symptom reduction. For depression, longer time since injury and higher expectancy for change, as well as higher baseline level of depression, were significantly associated with a greater reduction in depression symptoms., Conclusions: This study paves the way for more detailed studies of the therapeutic processes involved in alleviating anxiety and depression following TBI.

Background: Patients in posttraumatic amnesia (PTA) may receive limited rehabilitation due to the risk of overstimulation and agitation. This assumption has not been tested., Objective: To examine the relationship between agitated behavior and participation in therapy for retraining of activities of daily living (ADL) while in PTA., Setting: Inpatient rehabilitation center., Participants: A total of 104 participants with severe traumatic brain injury, admitted to rehabilitation, in PTA of more than 7 days., Intervention: ADL retraining during PTA followed errorless and procedural learning principles., Design: Group comparison and regression modeling of patient agitation data from a randomized controlled trial comparing ADL retraining in PTA (treatment) versus no ADL retraining in PTA (treatment as usual, TAU)., Outcome Measures: Agitation using the Agitated Behavior Scale. Therapy participation measured in minutes and missed sessions., Results: There were no group differences in agitated behavior (average scores, peak scores, or number of clinically agitated days) between the treatment and TAU groups. For treated patients, there was no significant relationship between agitation and therapy participation (therapy minutes or missed ADL treatment sessions)., Conclusions: This study demonstrated that agitation is not increased by delivery of structured ADL retraining during PTA and agitation did not limit therapy participation. This supports the consideration of active therapy during PTA.

Background: This study prospectively examined the relationship between preinjury, injury-related, and postinjury factors and posttraumatic stress disorder (PTSD) following moderate to severe traumatic brain injury (TBI)., Method: Two hundred and three participants were recruited during inpatient admission following moderate to severe TBI. Participants completed an initial assessment soon after injury and were reassessed at 3, 6, and 12 months, 2, 3, 4, and 5 years postinjury. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-fourth edition was used to diagnose pre- and postinjury PTSD and other psychiatric disorders. The Glasgow Outcome Scale-Extended (GOSE) and the Quality of Life Inventory (QOLI) were used to evaluate functional and psychosocial outcome from 6 months postinjury., Results: The frequency of PTSD ranged between 0.5 and 9.4% during the 5-year period, increasing throughout the first 12 months and declining thereafter. After controlling for other predictors, shorter posttraumatic amnesia duration (odds ratio = 0.96, 95% CI = 0.92-1.00), other concurrent psychiatric disorder (odds ratio = 14.22, 95% CI = 2.68-75.38), and lower GOSE (odds ratio = 0.38, 95% CI = 0.20-0.72) and QOLI scores (odds ratio = 0.97, 95% CI = 0.95-0.97) were associated with greater odds of having injury-related PTSD., Discussion: The results of this study indicate that while shorter posttraumatic amnesia duration is associated with PTSD, greater TBI severity does not prevent PTSD from evolving. Patients with PTSD experienced high rates of psychiatric comorbidity and poorer functional and quality of life outcomes after TBI., Conclusion: There is a need to direct clinical attention to early identification and treatment of PTSD following TBI to improve outcomes., (© 2015 Wiley Periodicals, Inc.)

Native, metastable serpins inherently tend to undergo stabilizing conformational transitions in mechanisms of health (e.g., enzyme inhibition) and disease (serpinopathies). This intrinsic tendency is modifiable by ligand binding, thus structure-based drug design is an attractive strategy in the serpinopathies. This can be viewed as a labor-intensive approach, and historically, its intellectual attractiveness has been tempered by relatively limited success in development of drugs reaching clinical practice. However, the increasing availability of a range of powerful experimental systems and higher-throughput techniques is causing academic and early-stage industrial pharmaceutical approaches to converge. In this review, we outline the different systems and techniques that are bridging the gap between what have traditionally been considered distinct disciplines. The individual methods are not serpin-specific. Indeed, many have only recently been applied to serpins, and thus investigators in other fields may have greater experience of their use to date. However, by presenting examples from our work and that of other investigators in the serpin field, we highlight how techniques with potential for automation and scaling can be combined to address a range of context-specific challenges in targeting the serpinopathies., (Copyright © 2011 Elsevier Inc. All rights reserved.)