A Network of Sites and Upskilled Therapists to Deliver Best-Practice Stroke Rehabilitation of the Arm: Protocol for a Knowledge Translation Study.

Implementation of evidence-informed rehabilitation of the upper limb is variable, and outcomes for stroke survivors are often suboptimal. We established a national partnership of clinicians, survivors of stroke, researchers, healthcare organizations, and policy makers to facilitate change. The objectives of this study are to increase access to best-evidence rehabilitation of the upper limb and improve outcomes for stroke survivors. This prospective pragmatic, knowledge translation study involves four new specialist therapy centers to deliver best-evidence upper-limb sensory rehabilitation (known as SENSe therapy) for survivors of stroke in the community. A knowledge-transfer intervention will be used to upskill therapists and guide implementation. Specialist centers will deliver SENSe therapy, an effective and recommended therapy, to stroke survivors in the community. Outcomes include number of successful deliveries of SENSe therapy by credentialled therapists; improved somatosensory function for stroke survivors; improved performance in self-selected activities, arm use, and quality of life; treatment fidelity and confidence to deliver therapy; and for future implementation, expert therapist effect and cost-effectiveness. In summary, we will determine the effect of a national partnership to increase access to evidence-based upper-limb sensory rehabilitation following stroke. If effective, this knowledge-transfer intervention could be used to optimize the delivery of other complex, evidence-based rehabilitation interventions.

Prioritising and incentivising productivity within indicator-based approaches to Research Impact Assessment: a commentary.

Research Impact Assessment (RIA) represents one of a suite of policies intended to improve the impact generated from investment in health and medical research (HMR). Positivist indicator-based approaches to RIA are widely implemented but increasingly criticised as theoretically problematic, unfair, and burdensome. This commentary proposes there are useful outcomes that emerge from the process of applying an indicator-based RIA framework, separate from those encapsulated in the metrics themselves. The aim for this commentary is to demonstrate how the act of conducting an indicator-based approach to RIA can serve to optimise the productive gains from the investment in HMR. Prior research found that the issues regarding RIA are less about the choice of indicators/metrics, and more about the discussions prompted and activities incentivised by the process. This insight provides an opportunity to utilise indicator-based methods to purposely optimise the research impact. An indicator-based RIA framework specifically designed to optimise research impacts should: focus on researchers and the research process, rather than institution-level measures; utilise a project level unit of analysis that provides control to researchers and supports collaboration and accountability; provide for prospective implementation of RIA and the prospective orientation of research; establish a line of sight to the ultimate anticipated beneficiaries and impacts; Include process metrics/indicators to acknowledge interim steps on the pathway to final impacts; integrate 'next' users and prioritise the utilisation of research outputs as a critical measure; Integrate and align the incentives for researchers/research projects arising from RIA, with those existing within the prevailing research system; integrate with existing peer-review processes; and, adopt a system-wide approach where incremental improvements in the probability of translation from individual research projects, yields higher impact across the whole funding portfolio.Optimisation of the impacts from HMR investment represents the primary purpose of Research Impact policy. The process of conducting an indicator-based approach to RIA, which engages the researcher during the inception and planning phase, can directly contribute to this goal through improvements in the probability that an individual project will generate interim impacts. The research project funding process represents a promising forum to integrate this approach within the existing research system.

Leakage beyond the primary lesion: A temporal analysis of cerebrovascular dysregulation at sites of hippocampal secondary neurodegeneration following cortical photothrombotic stroke.

We have previously demonstrated that a cortical stroke causes persistent impairment of hippocampal-dependent cognitive tasks concomitant with secondary neurodegenerative processes such as amyloid-ß accumulation in the hippocampus, a region remote from the primary infarct. Interestingly, there is emerging evidence suggesting that deposition of amyloid-ß around cerebral vessels may lead to cerebrovascular structural changes, neurovascular dysfunction, and disruption of blood-brain barrier integrity. However, there is limited knowledge about the temporal changes of hippocampal cerebrovasculature after cortical stroke. In the current study, we aimed to characterise the spatiotemporal cerebrovascular changes after cortical stroke. This was done using the photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Cerebrovascular morphology as well as the co-localisation of amyloid-ß with vasculature and blood-brain barrier integrity were assessed in the cortex and hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed transient cerebrovascular remodelling in the peri-infarct area up to 28 days post-stroke. Importantly, the cerebrovascular changes were extended beyond the peri-infarct region to the ipsilateral hippocampus and were sustained out to 84 days post-stroke. When investigating vessel diameter, we showed a decrease at 84 days in the peri-infarct and CA1 regions that were exacerbated in vessels with amyloid-ß deposition. Lastly, we showed sustained vascular leakage in the peri-infarct and ipsilateral hippocampus, indicative of a compromised blood-brain-barrier. Our findings indicate that hippocampal vasculature may represent an important therapeutic target to mitigate the progression of post-stroke cognitive impairment.

Using Presurgical Biopsychosocial Features to Develop an Advanced Clinical Decision-Making Support Tool for Predicting Recovery Trajectories in Patients Undergoing Total Knee Arthroplasty: Protocol for a Prospective Observational Study.

BACKGROUND: Following total knee arthroplasty (TKA), 10% to 20% of patients report dissatisfaction with procedural outcomes. There is growing recognition that postsurgical satisfaction is shaped not only by the quality of surgery but also by psychological and social factors. Surprisingly, information on the psychological and social determinants of surgical outcomes is rarely collected before surgery. A comprehensive collection of biopsychosocial information could assist clinicians in making recommendations in relation to rehabilitation, particularly if there is robust evidence to support the ability of presurgical constructs to predict postsurgical outcomes. Clinical decision support tools can help identify factors influencing patient outcomes and support the provision of interventions or services that can be tailored to meet individuals' needs. However, despite their potential clinical benefit, the application of such tools remains limited. OBJECTIVE: This study aims to develop a clinical decision tool that will assist with patient stratification and more precisely targeted clinical decision-making regarding prehabilitation and rehabilitation for TKA, based on the identified individual biopsychosocial needs. METHODS: In this prospective observational study, all participants provided written or electronic consent before study commencement. Patient-completed questionnaires captured information related to a broad range of biopsychosocial parameters during the month preceding TKA. These included demographic factors (sex, age, and rurality), psychological factors (mood status, pain catastrophizing, resilience, and committed action), quality of life, social support, lifestyle factors, and knee symptoms. Physical measures assessing mobility, balance, and functional lower body strength were performed via video calls with patients in their home. Information related to preexisting health issues and concomitant medications was derived from hospital medical records. Patient recovery outcomes were assessed 3 months after the surgical procedure and included quality of life, patient-reported knee symptoms, satisfaction with the surgical procedure, and mood status. Machine learning data analysis techniques will be applied to determine which presurgery parameters have the strongest power for predicting patient recovery following total knee replacement. On the basis of these analyses, a predictive model will be developed. Predictive models will undergo internal validation, and Bayesian analysis will be applied to provide additional metrics regarding prediction accuracy. RESULTS: Patient recruitment and data collection commenced in November 2019 and was completed in June 2022. A total of 1050 patients who underwent TKA were enrolled in this study. CONCLUSIONS: Our findings will facilitate the development of the first comprehensive biopsychosocial prediction tool, which has the potential to objectively predict a patient's individual recovery outcomes following TKA once selected by an orthopedic surgeon to undergo TKA. If successful, the tool could also inform the evolution rehabilitation services, such that factors in addition to physical performance can be addressed and have the potential to further enhance patient recovery and satisfaction. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48801.

Clopidogrel Administration Impairs Post-Stroke Learning and Memory Recovery in Mice.

Clopidogrel, which is one of the most prescribed antiplatelet medications in the world, is given to stroke survivors for the prevention of secondary cardiovascular events. Clopidogrel exerts its antiplatelet activity via antagonism of the P2Y12 receptor (P2RY12). Although not widely known or considered during the initial clinical trials for clopidogrel, P2RY12 is also expressed on microglia, which are the brain's immune cells, where the receptor facilitates chemotactic migration toward sites of cellular damage. If microglial P2RY12 is blocked, microglia lose the ability to migrate to damaged sites and carry out essential repair processes. We aimed to investigate whether administering clopidogrel to mice post-stroke was associated with (i) impaired motor skills and cognitive recovery; (ii) physiological changes, such as survival rate and body weight; (iii) changes in the neurovascular unit, including blood vessels, microglia, and neurons; and (iv) changes in immune cells. Photothrombotic stroke (or sham surgery) was induced in adult male mice. From 24 h post-stroke, mice were treated daily for 14 days with either clopidogrel or a control. Cognitive performance (memory and learning) was assessed using a mouse touchscreen platform (paired associated learning task), while motor impairment was assessed using the cylinder task for paw asymmetry. On day 15, the mice were euthanized and their brains were collected for immunohistochemistry analysis. Clopidogrel administration significantly impaired learning and memory recovery, reduced mouse survival rates, and reduced body weight post-stroke. Furthermore, clopidogrel significantly increased vascular leakage, significantly increased the number and appearance of microglia, and significantly reduced the number of T cells within the peri-infarct region post-stroke. These data suggest that clopidogrel hampers cognitive performance post-stroke. This effect is potentially mediated by an increase in vascular permeability post-stroke, providing a pathway for clopidogrel to access the central nervous system, and thus, interfere in repair and recovery processes.

Impact assessment of the Centre for Research Excellence in Stroke Rehabilitation and Brain Recovery.

BACKGROUND: Research impact is an emerging measure of research achievement alongside traditional academic outputs such as publications. We present the results of applying the Framework to Assess the Impact from Translational health research (FAIT) to the Centre for Research Excellence (CRE) in Stroke Rehabilitation and Brain Recovery (CRE-Stroke, 2014-2019) and report on the feasibility and lessons from the application of FAIT to a CRE rather than a discrete research project. METHODS: Data were gathered via online surveys, in-depth interviews, document analysis and review of relevant websites/databases to report on the three major FAIT methods: the modified Payback Framework, an assessment of costs against monetized consequences, and a narrative account of the impact generated from CRE-Stroke activities. FAIT was applied during the last 4 years of CRE-Stroke operation. RESULTS: With an economic investment of AU$ 3.9 million over 5 years, CRE-Stroke delivered a return on investment that included AU$ 18.8 million in leveraged grants, fellowships and consultancies. Collectively, CRE-Stroke members produced 354 publications that were accessed 470,000 times and cited over 7220 times. CRE-Stroke supported 26 PhDs, 39 postdocs and seven novice clinician researchers. There were 59 capacity-building events benefiting 744 individuals including policy-makers and consumers. CRE-Stroke created research infrastructure (including a research register of stroke survivors and a brain biobank), and its global leadership produced international consensus recommendations to influence the stroke research landscape worldwide. Members contributed to the Australian Living Stroke Guidelines: four researchers' outputs were directly referenced. Based only on the consequences that could be monetized, CRE-Stroke returned AU$ 4.82 for every dollar invested in the CRE. CONCLUSION: This case example in the developing field of impact assessment illustrates how researchers can use evidence to demonstrate and report the impact of and returns on research investment. The prospective application of FAIT by a dedicated research impact team demonstrated impact in broad categories of knowledge-gain, capacity-building, new infrastructure, input to policy and economic benefits. The methods can be used by other research teams to provide comprehensive evidence to governments and other research funders about what has been generated from their research investment but requires dedicated resources to complete.

How little is enough? The feasibility of conducting a dose-escalation study for exercise training in people with stroke.

QUESTION: Is it feasible and safe to conduct an exercise dose-finding study in people with stroke? Is it possible to determine a minimal dose of exercise required to see clinically meaningful improvements in cardiorespiratory fitness? METHODS: Dose-escalation study. Twenty people with stroke (n=5 per cohort) who were able to walk independently participated in home-based, telehealth-supervised aerobic exercise sessions 3 d/week at moderate-vigorous intensity for 8 weeks. Dose parameters of frequency (3 d/week), intensity (55-85% of heart rate peak) and program length (8 weeks) were kept constant. The duration of exercise sessions was increased by 5 min per session from Dose 1 (10 min/session) to Dose 4 (25 min/session). Doses were escalated if safe and tolerable (< 33% of a cohort reaching a dose-limiting threshold). Doses were efficacious if ≥ 67% of a cohort increased peak oxygen consumption ≥ 2mL/kg/min. RESULTS: Target exercise doses were well adhered to, and the intervention was safe (480 exercise sessions delivered; one fall resulting in minor laceration) and tolerable (no participants met the dose-limiting threshold). None of the exercise doses met our criterion for efficacy. CONCLUSIONS: It is possible to conduct a dose-escalation trial for people with stroke. The small cohort sizes may have limited the ability to determine an efficacious minimum dose of exercise. Providing supervised exercise session at these prescribed doses via telehealth was safe. REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000460303).

Mobile health to promote physical activity in people post stroke or transient ischemic attack - study protocol for a feasibility randomised controlled trial.

BACKGROUND: Physical activity is essential to improve health and reduce the risk of recurrence of stroke or transient ischemic attack (TIA). Still, people post stroke or TIA are often physically inactive and the availability of physical activity promotion services are often limited. This study builds on an existing Australian telehealth-delivered programme (i-REBOUND- Let's get moving) which provides support for home-based physical activity for people post stroke or TIA. The aim of this study is to test the feasibility, acceptability, and preliminary effects of a mobile Health (mHealth) version of the i-REBOUND programme for the promotion of physical activity in people post stroke or TIA living in Sweden. METHODS: One hundred and twenty participants with stroke or TIA will be recruited via advertisement. A parallel-group feasibility randomised controlled trial design with a 1:1 allocation ratio to 1) i-REBOUND programme receiving physical exercise and support for sustained engagement in physical activity through behavioural change techniques, or 2) behavioural change techniques for physical activity. Both interventions will proceed for six months and be delivered digitally through a mobile app. The feasibility outcomes (i.e., reach, adherence, safety and fidelity) will be monitored throughout the study. Acceptability will be assessed using the Telehealth Usability Questionnaire and further explored through qualitative interviews with a subset of both study participants and the physiotherapists delivering the intervention. Clinical outcomes on preliminary effects of the intervention will include blood pressure, engagement in physical activity, self-perceived exercise self-efficacy, fatigue, depression, anxiety, stress and health-related quality of life and will be measured at baseline and at 3, 6 and 12 months after the baseline assessments. DISCUSSION: We hypothesise that the mHealth delivery of the i-REBOUND programme will be feasible and acceptable in people post stroke/TIA living in rural and urban regions of Sweden. The results of this feasibility trial will inform the development of full-scale and appropriately powered trial to test the effects and costs of mHealth delivered physical activity for people after stroke or TIA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05111951. Registered November 8, 2021.

Evaluation of an App-Delivered Psychological Flexibility Skill Training Intervention for Medical Student Burnout and Well-being: Randomized Controlled Trial.

BACKGROUND: Physician burnout is a common problem, with onset frequently occurring during undergraduate education. Early intervention strategies that train medical students in psychological flexibility skills could support well-being and mitigate burnout risks associated with unmodifiable career stressors. There is a need for randomized controlled trials to assess effectiveness. As psychological flexibility varies contextually and among individuals, tailoring interventions may improve outcomes. Smartphone apps can facilitate individualization and accessibility, and the evaluation of this approach is an identified research priority. OBJECTIVE: This study aimed to evaluate the effectiveness of a stand-alone app-delivered Acceptance and Commitment Training intervention for improving medical students' self-reported burnout, well-being, psychological flexibility, and psychological distress outcomes. We aimed to explore whether an individualized app would demonstrate benefits over a nonindividualized version. METHODS: This parallel randomized controlled trial was conducted with a sample of medical students from 2 Australian universities (N=143). Participants were randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waitlist) using a 1:1:1 allocation ratio. Individualized and nonindividualized participants were blinded to group allocation. The 5-week intervention included an introductory module (stage 1) and on-demand access to short skill training activities (stage 2), which students accessed at their own pace. Stage 2 was either nonindividualized or individualized to meet students' identified psychological flexibility training needs. RESULTS: The mean differences in change from baseline between the intervention groups and the waitlist group were not statistically significant for burnout outcomes: exhaustion (primary; individualized: -0.52, 95% CI -3.70 to 2.65, P=.75; nonindividualized: 1.60, 95% CI -1.84 to 5.03, P=.37), cynicism (individualized: -1.26, 95% CI -4.46 to 1.94, P=.44; nonindividualized: 1.00, 95% CI -2.45 to 4.46, P=.57), and academic efficacy (individualized: 0.94, 95% CI -0.90 to 2.79, P=.32; nonindividualized: 2.02, 95% CI 0.02-4.03, P=.05). Following the intervention, the individualized group demonstrated improved psychological flexibility (0.50, 95% CI 0.12-0.89; P=.01), reduced inflexibility (0.48, 95% CI -0.92 to -0.04; P=.04), and reduced stress (-6.89, 95% CI -12.01 to 5.99; P=.01), and the nonindividualized group demonstrated improved well-being (6.46, 95% CI 0.49-12.42; P=.04) and stress (-6.36, 95% CI -11.90 to -0.83; P=.03) compared with waitlist participants. Between-group differences for the individualized and nonindividualized arms were not statistically significant. High attrition (75/143, 52.4%) was observed. CONCLUSIONS: This trial provides early support for the potential benefits of Acceptance and Commitment Training for medical student well-being and psychological outcomes and demonstrates that psychological flexibility and inflexibility can be trained using a smartphone app. Although postintervention burnout outcomes were not statistically significant, improvements in secondary outcomes could indicate early risk mitigation. Replication studies with larger samples and longer-term follow-up are required, and future research should focus on improving implementation frameworks to increase engagement and optimize individualization methods. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry 12621000911897; https://tinyurl.com/2p92cwrw. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/32992.

Medical Student Experiences of Engaging in a Psychological Flexibility Skill Training App for Burnout and Well-being: Pilot Feasibility Study.

BACKGROUND: Medical students are at higher risk of burnout than the general population. Interventions that facilitate adaptive coping behaviors (eg, Psychological Flexibility) in the context of inherent stressors associated with medical training could mitigate burnout risk and improve well-being. Delivering these interventions using smartphone apps offers advantages such as accessibility, scalability, mitigation of time and stigma barriers, and facilitation of individual tailoring (individualization). There is a need for feasibility trials with medical students in this emerging field. Formal evaluations of user experiences of app-based psychological skill training are required to identify barriers to and facilitators of engagement and optimize intervention development before implementation in efficacy trials and real-world settings. OBJECTIVE: This study aimed to assess the feasibility of delivering an individualized Psychological Flexibility skill training intervention (Acceptance and Commitment Training [ACTraining]) to medical students using an app-based delivery format. We further aimed to explore how formal evaluation of user experiences might inform and guide the development of this app before implementation in an efficacy trial and future research involving app-delivered psychological skill training for medical students. METHODS: This single-arm study was an early-phase feasibility trial of a stand-alone ACTraining app conducted with a sample of Australian medical students (n=11). We collected app usability and user experience data across a broad range of domains (eg, perceived helpfulness and relevance, learning experiences, and self-efficacy) using self-report questionnaires (quantitative and qualitative) and behavioral engagement outcomes. RESULTS: Behavioral engagement data demonstrated that the app delivered the assessment procedures and individualized ACTraining intervention to medical students as intended. The subjective feedback provided by students who actively engaged with the app was generally positive across several indicators, including usability, perceived relevance and helpfulness, accessibility, maintenance of privacy, and opportunity for self-reflection. Disengagement from the app was an identified challenge throughout the trial. Participant feedback identified several factors that may have affected engagement, such as time, expectations regarding app interface functioning, and individual differences in confidence and self-efficacy when implementing skills. CONCLUSIONS: This study reports user experience data that have been largely absent from the literature on digital psychological interventions for medical students. Our findings demonstrate the preliminary feasibility of an app-delivered ACTraining intervention for medical student well-being and burnout and support the value of future assessment of the efficacy of this approach with larger samples. We consider subjective feedback from medical students in relation to observed engagement and propose how this information might be used to inform the development of this app and future research in this nascent field.

Psychological Stress Management and Stress Reduction Strategies for Stroke Survivors: A Scoping Review.

BACKGROUND: Stroke can be a life-changing event, with survivors frequently experiencing some level of disability, reduced independence, and an abrupt lifestyle change. Not surprisingly, many stroke survivors report elevated levels of stress during the recovery process, which has been associated with worse outcomes. PURPOSE: Given the multiple roles of stress in the etiology of stroke recovery outcomes, we aimed to scope the existing literature on stress management interventions that have been trialed in stroke survivors. METHODS: We performed a database search for intervention studies conducted in stroke survivors which reported the effects on stress, resilience, or coping outcome. Medline (OVID), Embase (OVID), CINAHL (EBSCO), Cochrane Library, and PsycInfo (OVID) were searched from database inception until March 11, 2019, and updated on September 1, 2020. RESULTS: Twenty-four studies met the inclusion criteria. There was significant variation in the range of trialed interventions, as well as the outcome measures used to assess stress. Overall, just over half (13/24) of the included studies reported a benefit in terms of stress reduction. Acceptability and feasibility were considered in 71% (17/24) and costs were considered in 17% (4/24) of studies. The management of stress was rarely linked to the prevention of symptoms of stress-related disorders. The overall evidence base of included studies is weak. However, an increase in the number of studies over time suggests a growing interest in this subject. CONCLUSIONS: Further research is required to identify optimum stress management interventions in stroke survivors, including whether the management of stress can ameliorate the negative impacts of stress on health.

Correction: Assessing the Efficacy of an Individualized Psychological Flexibility Skills Training Intervention App for Medical Student Burnout and Well-being: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: 10.2196/32992.].

Physical Activity After Transient Ischemic Attack or Mild Stroke Is Business as Usual.

BACKGROUND AND PURPOSE: Regular, sustained moderate-to-vigorous physical activity (MVPA) is a recommended strategy to reduce the risk of recurrent stroke for people who have had transient ischemic attack (TIA) or mild stroke. This study aimed to explore attitudes toward, and experience of engaging in physical activity by adults following a TIA or mild stroke. METHODS: Constructivist grounded theory methodology informed data collection and analysis. Interviews from 33 adults with TIA or mild stroke (mean age 65 [SD 10] years, 48% female, 40% TIA) were collected. RESULTS: Business as usual characterized physical activity engagement post-TIA or mild stroke. Most participants returned to prestroke habits, as either regular exerciser or nonexerciser, with only a small number making changes. Influencing factors for physical activity participation included information, challenges, strategies, and support. Business as usual was associated with a perceived lack of information to suggest a need to change behaviors. Nonexercisers and those who decreased physical activity emphasized challenges to physical activity, while regular exercisers and those who increased physical activity focused on strategies and support that enabled participation despite challenges. DISCUSSION AND CONCLUSION: Information about the necessity to engage in recommended physical activity levels requires tailoring to the needs of the people with TIA or mild stroke. Helpful information in combination with support and strategies may guide how to navigate factors preventing engagement and might influence the low level of physical activity prevalent in this population.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A376).

Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries.

INTRODUCTION: The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. METHODS AND ANALYSIS: This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.

Effect of high-intensity interval training on hippocampal metabolism in older adolescents.

Although well-evidenced in older adults, the effects of exercise on the hippocampus in youth are relatively unknown. This study examined the impact of a 6-month school-based physical activity intervention on hippocampal metabolism in adolescents using magnetic resonance spectroscopy. A subset of lower fit older adolescents [N = 56, 61% female, 16.1 ± 0.4 years] was included from four secondary schools (10 classes) in New South Wales, Australia, who were participating in a larger cluster randomized controlled trial. Participants were randomized to the Burn 2 Learn (B2L) intervention (five classes, 30 participants) or a control group (five classes, 26 participants). Changes in hippocampal metabolism were assessed using linear mixed models adjusted for clustering at the class level. We observed group-by-time effects for the B2L intervention on N-acetylaspartate (NAA) (+2.66 mmol/L, 95% CI 0.20 to 5.11, d = 0.66) and glutamate+glutamine (Glx) (+3.38 mmol/L, 95% CI 0.34 to 6.42, d = 0.67) in the left hippocampus. Increases in left hippocampal NAA and Glx concentrations were associated with improvements in cardiorespiratory fitness (NAA: rs  = 0.52, p = .016; Glx: rs  = 0.57, p = .007), lower body muscular fitness (NAA: rs  = 0.49, p = .018; Glx: rs  = 0.59, p = .003), and working memory (NAA: rs  = 0.42, p = .032; Glx: rs  = 0.43, p = .028) in the intervention group. Our findings suggest physical activity may improve hippocampal metabolism in lower fit older adolescents with implications for working memory. Further studies involving larger samples are needed to replicate our findings.

Growth Hormone Increases BDNF and mTOR Expression in Specific Brain Regions after Photothrombotic Stroke in Mice.

Aims: We have shown that growth hormone (GH) treatment poststroke increases neuroplasticity in peri-infarct areas and the hippocampus, improving motor and cognitive outcomes. We aimed to explore the mechanisms of GH treatment by investigating how GH modulates pathways known to induce neuroplasticity, focusing on association between brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) in the peri-infarct area, hippocampus, and thalamus. Methods: Recombinant human growth hormone (r-hGH) or saline was delivered (0.25 µl/hr, 0.04 mg/day) to mice for 28 days, commencing 48 hours after photothrombotic stroke. Protein levels of pro-BDNF, total-mTOR, phosphorylated-mTOR, total-p70S6K, and phosporylated-p70S6K within the peri-infarct area, hippocampus, and thalamus were evaluated by western blotting at 30 days poststroke. Results: r-hGH treatment significantly increased pro-BDNF in peri-infarct area, hippocampus, and thalamus (p < 0.01). r-hGH treatment significantly increased expression levels of total-mTOR in the peri-infarct area and thalamus (p < 0.05). r-hGH treatment significantly increased expression of total-p70S6K in the hippocampus (p < 0.05). Conclusion: r-hGH increases pro-BDNF within the peri-infarct area and regions that are known to experience secondary neurodegeneration after stroke. Upregulation of total-mTOR protein expression in the peri-infarct and thalamus suggests that this might be a pathway that is involved in the neurorestorative effects previously reported in these animals and warrants further investigation. These findings suggest region-specific mechanisms of action of GH treatment and provide further understanding for how GH treatment promotes neurorestorative effects after stroke.

Correction: Assessing the Efficacy of an Individualized Psychological Flexibility Skills Training Intervention App for Medical Student Burnout and Well-being: Protocol for a Randomized Controlled Trial.

[This corrects the article DOI: .].

Assessing the Efficacy of an Individualized Psychological Flexibility Skills Training Intervention App for Medical Student Burnout and Well-being: Protocol for a Randomized Controlled Trial.

BACKGROUND: Medical student burnout is a prevalent problem with adverse long-term outcomes. Incorporating psychological resource-building interventions into comprehensive burnout prevention approaches during medical training is an identified priority among educators. These interventions could reduce burnout risk by buffering students against nonmodifiable career stressors. However, there is a need for rigorous investigation into optimal intervention targets and methods. Psychological flexibility (PF) is an adaptive behavioral skill set that has demonstrated relationships with medical student burnout and well-being. More broadly, there is evidence that PF mediates burnout and well-being outcomes and may be a protective factor. Efficacy studies assessing the benefits of interventions targeting PF among medical students are needed. Research also supports the need to establish optimal methods for increasing intervention efficacy in the context of individual differences in burnout and PF by using individualized approaches. OBJECTIVE: This study aims to assess whether an app-delivered PF intervention (Acceptance and Commitment Training) reduces burnout and improves well-being among medical students. We will examine whether changes in burnout and well-being are mediated by changes in PF. The potential benefits of an individualized version of the app versus those of a nonindividualized version will also be evaluated. METHODS: In this 3-arm, parallel, randomized controlled study, a sample of medical students will be randomly allocated to 1 of 3 intervention arms (individualized, nonindividualized, and waiting list) by using a 1:1:1 allocation ratio. Participants in the individualized and nonindividualized intervention arms will have 5 weeks to access the app, which includes a PF concepts training session (stage 1) and access to short PF skill activities on demand (stage 2). Stage 2 will be either individualized to meet participants' identified PF training needs at each log-in or nonindividualized. RESULTS: Burnout, well-being, and PF will be assessed at baseline and after the intervention. Quantitative analyses will include descriptive and inferential statistics. We hypothesize that the Acceptance and Commitment Training intervention app will be effective in improving burnout and well-being and that changes in these outcomes will be mediated by changes in PF. We further hypothesize that participants in the individualized intervention group will demonstrate greater improvements in burnout and well-being outcomes than those in the nonindividualized group. CONCLUSIONS: The findings of this study could guide the development of burnout prevention and well-being initiatives for medical students. Identifying PF as a mediating process would provide support for the delivery of preventive intervention programs that train individuals to strengthen this psychological resource before burnout symptoms emerge. This would be an important step in addressing and potentially offsetting the significant costs of burnout among medical students and physicians. Demonstrating the superiority of an individualized version of the app over a nonindividualized version would have implications for enhancing intervention precision and efficacy by using scalable interventions. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTR 12621000911897; https://www.anzctr.org.au/ACTRN12621000911897.aspx. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/32992.

Increasing time spent engaging in moderate-to-vigorous physical activity by community-dwelling adults following a transient ischemic attack or non-disabling stroke: a systematic review.

PURPOSE: The risk of recurrent stroke following a transient ischaemic attack (TIA) or non-disabling stroke is high. Clinical guidelines recommend this patient population accumulate at least 150 minutes of moderate-to-vigorous physical activity each week to reduce the risk of recurrent stroke. We aimed to identify interventions that increase time adults spend in moderate-to-vigorous physical activity following TIA or non-disabling stroke. METHOD: We searched thirteen databases for articles of secondary prevention interventions reporting outcomes for duration in moderate-to-vigorous physical activity or exercise capacity. RESULTS: Eight trials were identified (n = 2653). Of these, three (n = 198) reported changes in time spent in moderate-to-vigorous physical activity. Only one trial (n = 70), reported significant change in time spent engaging in moderate-to-vigorous physical activity (between-group difference: 11.7 min/day [95% CI 4.07-19.33]) when comparing participation in a six-month exercise education intervention to usual care. No trial measured moderate-to-vigorous physical activity after intervention end. CONCLUSION: Despite recommendations to participate in regular physical activity at moderate-to-vigorous intensity for secondary stroke prevention, there is very little evidence for effective interventions for this patient population. There is need for clinically feasible interventions that result in long-term participation in physical activity in line with clinical guidelines. Trial registration: Protocol registration: PROSPERO CRD42018092840Implications for rehabilitationThere is limited evidence of the effectiveness of interventions that aim to increase time spent engaging in moderate-to-vigorous physical activity (MVPA) for people following a TIA or non-disabling stroke.A program comprising aerobic and resistance exercises ≥2 per week, supervised by a health professional (supplemented with a home program) over at least 24 weeks appears to be effective in assisting people adhere to recommended levels of moderate to vigorous physical activity after TIA or non-disabling stroke.Secondary prevention programs which include health professional supervised exercise sessions contribute to better adherence to physical activity guidelines; didactic sessions alone outlining frequency and intensity are unlikely to be sufficient.

Altering the rehabilitation environment to improve stroke survivor activity: A Phase II trial.

BACKGROUND: Environmental enrichment involves organization of the environment and provision of equipment to facilitate engagement in physical, cognitive, and social activities. In animals with stroke, it promotes brain plasticity and recovery. AIMS: To assess the feasibility and safety of a patient-driven model of environmental enrichment incorporating access to communal and individual environmental enrichment. METHODS: A nonrandomized cluster trial with blinded measurement involving people with stroke (n = 193) in four rehabilitation units was carried out. Feasibility was operationalized as activity 10 days after admission to rehabilitation and availability of environmental enrichment. Safety was measured as falls and serious adverse events. Benefit was measured as clinical outcomes at three months, by an assessor blinded to group. RESULTS: The experimental group (n = 91) spent 7% (95% CI -14 to 0) less time inactive, 9% (95% CI 0-19) more time physically, and 6% (95% CI 2-10) more time socially active than the control group (n = 102). Communal environmental enrichment was available 100% of the time, but individual environmental enrichment was rarely within reach (24%) or sight (39%). There were no between-group differences in serious adverse events or falls at discharge or three months or in clinical outcomes at three months. CONCLUSIONS: This patient-driven model of environmental enrichment was feasible and safe. However, the very modest increase in activity by people with stroke, and the lack of benefit in clinical outcomes three months after stroke do not provide justification for an efficacy trial.