Post Stroke Exercise Training: Intensity, Dosage, and Timing of Therapy.

More intense, earlier exercise in rehabilitation results in improved motor outcomes following stroke. Timing and intensity of therapy delivery vary from study to study. For more intensive therapies, there are practical challenges in implementation. However, there are also opportunities for high intensity treatment through innovative approaches and new technologies. Timing of rehabilitation is important. As time post stroke increases, the dosage of therapy required to improve motor recovery outcomes increases. Very early rehabilitation may improve motor outcomes but should be delayed for at least 24 hours post stroke.

Female Enrollment in Rehabilitation Trials: A Systematic Review of Reporting Sex and Female Participation in Randomized Controlled Trials of Poststroke Upper Extremity Rehabilitation Over 50 Years.

OBJECTIVE: To systematically assess the reporting of sex and the percentage of female participants in randomized controlled trials (RCTs) examining interventions for the post-stroke rehabilitation of upper extremity (UE) motor disorders. DATA SOURCES: CINAHL, Embase, PubMed, Scopus and Web of Science were searched from 1960 to April 1, 2021. Additional articles were identified using the Evidence-Based Review of Stroke Rehabilitation. STUDY SELECTION: Studies were eligible for inclusion if they (1) were RCTs or crossovers published in English, (2) ≥50% of participants were diagnosed and affected by stroke, (3) included adults ≥18 years old, and (4) applied an intervention to the hemiparetic UE as the primary objective of the study. DATA EXTRACTION: Two investigators independently screened the title and abstracts, and duplicates were removed. A full-text review was done for studies that met all inclusion criteria. Data were extracted using a custom data extraction template in Covidence and were transferred to online Excel (V16) for data management. Study characteristics and extracted variables were summarized using standard descriptive statistics. Data analyses were performed using SPSS (V29.0). DATA SYNTHESIS: A total of 1276 RCTs met inclusion criteria, and of these, 5.2% did not report results on sex, accounting for 5.6% of participants. Women have been underrepresented in stroke RCTs, accounting for 38.8% of participants. Female participation was greater in the acute poststroke phase than in the chronic and subacute phases. Over almost 5 decades, there has been a small decrease in the proportion of female participants in these trials. CONCLUSIONS: Evidence-based medicine for the treatment and prevention of stroke is guided by results from RCTs. Generalizability depends on sufficient representation in clinical trials. Stakeholders, such as funders and journal editors, play a key role in encouraging researchers to enroll enough of both sexes and to report the presence or absence of sex differences in RCTs.

A national survey of evidence-based stroke rehabilitation intervention use in clinical practice among Canadian occupational therapists.

BACKGROUND: More than 1,000 randomized controlled trials have been published examining the effectiveness of stroke rehabilitation interventions. OBJECTIVE: The objective of this study was to explore the use and non-use of evidence-based stroke rehabilitation interventions in clinical practice among Occupational Therapists across various stroke rehabilitation settings in Canada. METHODS: Participants were recruited from medical centres providing rehabilitation to stroke patients in each of the ten provinces across Canada (January-July 2021). Adult (18 + years) Occupational Therapists who provide direct rehabilitative care to individuals after a stroke completed a survey in either English or French. Therapists rated their awareness, use, and reasons for non-use of stroke rehabilitation interventions. RESULTS: 127 therapists (female = 89.8%), largely from Ontario or Quebec (62.2%) were included; most worked full-time (80.3%) in moderate-large (86.1%) cities. The greatest use of interventions were those applied to the body peripherally, without a technological component. Few individuals were aware of interventions applied to the brain (priming or stimulating) with a technological component, and they were rarely, if ever, used. CONCLUSION: Significant efforts should be made to increase the awareness of interventions which are supported by strong evidence through knowledge translation and implementation initiatives, particularly for those with a technological component.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury: Methods, Overview, and Principles.

INTRODUCTION: Moderate to severe traumatic brain injury (TBI) results in complex cognitive sequelae. Despite hundreds of clinical trials in cognitive rehabilitation, the translation of these findings into clinical practice remains a challenge. Clinical practice guidelines are one solution. The objective of this initiative was to reconvene the international group of cognitive researchers and clinicians (known as INCOG) to develop INCOG 2.0: Guidelines for Cognitive Rehabilitation Following TBI. METHODS: The guidelines adaptation and development cycle was used to update the recommendations and derive new ones. The team met virtually and reviewed the literature published since the original INCOG (2014) to update the recommendations and decision algorithms. The team then prioritized the recommendations for implementation and modified the audit tool accordingly to allow for the evaluation of adherence to best practices. RESULTS: In total, the INCOG update contains 80 recommendations (25 level A, 15 level B, and 40 level C) of which 27 are new. Recommendations developed for posttraumatic amnesia, attention, memory, executive function and cognitive-communication are outlined in other articles, whereas this article focuses on the overarching principles of care for which there are 38 recommendations pertaining to: assessment (10 recommendations), principles of cognitive rehabilitation (6 recommendations), medications to enhance cognition (10 recommendations), teleassessment (5 recommendations), and telerehabilitation intervention (7 recommendations). One recommendation was supported by level A evidence, 7 by level B evidence, and all remaining recommendations were level C evidence. New to INCOG are recommendations for telehealth-delivered cognitive assessment and rehabilitation. Evidence-based clinical algorithms and audit tools for evaluating the state of current practice are also provided. CONCLUSIONS: Evidence-based cognitive rehabilitation guided by these recommendations should be offered to individuals with TBI. Despite the advancements in TBI rehabilitation research, further high-quality studies are needed to better understand the role of cognitive rehabilitation in improving patient outcomes after TBI.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part IV: Cognitive-Communication and Social Cognition Disorders.

INTRODUCTION: Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others' emotions, and infer others' thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person's ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition. METHODS: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for interventions for cognitive-communication and social cognition disorders, a decision-making algorithm tool, and an audit tool for review of clinical practice. RESULTS: Since INCOG 2014, there has been significant growth in cognitive-communication interventions and emergence of social cognition rehabilitation research. INCOG 2.0 has 9 recommendations, including 5 updated INCOG 2014 recommendations, and 4 new recommendations addressing cultural competence training, group interventions, telerehabilitation, and management of social cognition disorders. Cognitive-communication disorders should be individualized, goal- and outcome-oriented, and appropriate to the context in which the person lives and incorporate social communication and communication partner training. Group therapy and telerehabilitation are recommended to improve social communication. Augmentative and alternative communication (AAC) should be offered to the person with severe communication disability and their communication partners should also be trained to interact using AAC. Social cognition should be assessed and treated, with a focus on personally relevant contexts and outcomes. CONCLUSIONS: The INCOG 2.0 recommendations reflect new evidence for treatment of cognitive-communication disorders, particularly social interactions, communication partner training, group treatments to improve social communication, and telehealth delivery. Evidence is emerging for the rehabilitation of social cognition; however, the impact on participation outcomes needs further research.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part III: Executive Functions.

INTRODUCTION: Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments. METHODS: An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice. RESULTS: A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 new recommendations were made and 4 were modified and updated from previous recommendations. Six recommendations are based on level A evidence, and 2 are based on level C. Recommendations retained from the previous guidelines and updated, where new evidence was available, focus on enhancement of self-awareness (eg, feedback to increase self-monitoring; training with video-feedback), meta-cognitive strategy instruction (eg, goal management training), enhancement of reasoning skills, and group-based treatments. New recommendations addressing music therapy, virtual therapy, telerehabilitation-delivered metacognitive strategies, and caution regarding other group-based telerehabilitation (due to a lack of evidence) have been made. CONCLUSIONS: Effective management of impairments in executive functioning can increase the success and well-being of individuals with MS-TBI in their day-to-day lives. These guidelines provide management recommendations based on the latest evidence, with support for their implementation, and encourage researchers to explore and validate additional factors such as predictors of treatment response.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part II: Attention and Information Processing Speed.

INTRODUCTION: Moderate to severe traumatic brain injury (MS-TBI) commonly causes disruption in aspects of attention due to its diffuse nature and injury to frontotemporal and midbrain reticular activating systems. Attentional impairments are a common focus of cognitive rehabilitation, and increased awareness of evidence is needed to facilitate informed clinical practice. METHODS: An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated guidelines for the management of attention in adults, as well as a decision-making algorithm, and an audit tool for review of clinical practice. RESULTS: This update incorporated 27 studies and made 11 recommendations. Two new recommendations regarding transcranial stimulation and an herbal supplement were made. Five were updated from INCOG 2014 and 4 were unchanged. The team recommends screening for and addressing factors contributing to attentional problems, including hearing, vision, fatigue, sleep-wake disturbance, anxiety, depression, pain, substance use, and medication. Metacognitive strategy training focused on everyday activities is recommended for individuals with mild-moderate attentional impairments. Practice on de-contextualized computer-based attentional tasks is not recommended because of lack of evidence of generalization, but direct training on everyday tasks, including dual tasks or dealing with background noise, may lead to gains for performance of those tasks. Potential usefulness of environmental modifications is also discussed. There is insufficient evidence to support mindfulness-based meditation, periodic alerting, or noninvasive brain stimulation for alleviating attentional impairments. Of pharmacological interventions, methylphenidate is recommended to improve information processing speed. Amantadine may facilitate arousal in comatose or vegetative patients but does not enhance performance on attentional measures over the longer term. The antioxidant Chinese herbal supplement MLC901 (NeuroAiD IITM) may enhance selective attention in individuals with mild-moderate TBI. CONCLUSION: Evidence for interventions to improve attention after TBI is slowly growing. However, more controlled trials are needed, especially evaluating behavioral or nonpharmacological interventions for attention.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part I: Posttraumatic Amnesia.

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.

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory.

INTRODUCTION: Memory impairments affecting encoding, acquisition, and retrieval of information after moderate-to-severe traumatic brain injury (TBI) have debilitating and enduring functional consequences. The interventional research reviewed primarily focused on mild to severe memory impairments in episodic and prospective memory. As memory is a common focus of cognitive rehabilitation, clinicians should understand and use the latest evidence. Therefore, the INCOG ("International Cognitive") 2014 clinical practice guidelines were updated. METHODS: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for intervention for memory impairments post-TBI, a decision-making algorithm, and an audit tool for review of clinical practice. RESULTS: The interventional research approaches for episodic and prospective memory from 2014 are synthesized into 8 recommendations (6 updated and 2 new). Six recommendations are based on level A evidence and 2 on level B. In summary, they include the efficacy of choosing individual or multiple internal compensatory strategies, which can be delivered in a structured or individualized program. Of the external compensatory strategies, which should be the primary strategy for severe memory impairment, electronic reminder systems such as smartphone technology are preferred, with technological advances increasing their viability over traditional systems. Furthermore, microprompting personal digital assistant technology is recommended to cue completion of complex tasks. Memory strategies should be taught using instruction that considers the individual's functional and contextual needs while constraining errors. Memory rehabilitation programs can be delivered in an individualized or mixed format using group instruction. Computer cognitive training should be conducted with therapist guidance. Limited evidence exists to suggest that acetylcholinesterase inhibitors improve memory, so trials should include measures to assess impact. The use of transcranial direct current stimulation (tDCS) is not recommended for memory rehabilitation. CONCLUSION: These recommendations for memory rehabilitation post-TBI reflect the current evidence and highlight the limitations of group instruction with heterogeneous populations of TBI. Further research is needed on the role of medications and tDCS to enhance memory.

Anxiety, depression, and quality of life among subgroups of individuals with acquired brain injury: The role of anxiety sensitivity and experiential avoidance.

OBJECTIVES: The objectives of this observational cohort study were to 1) cluster individuals with acquired brain injury (ABI) into subgroups according to their level of anxiety sensitivity (AS) and experiential avoidance (EA), and 2) compare subgroups with respect to anxiety, depression, and quality of life (QoL). METHODS: Individuals were recruited from an ABI outpatient clinic in Ontario, Canada and completed comprehensive psychosocial questionnaires. A two-step cluster analysis was performed to identify unique subgroups based on the clustering variables Anxiety Sensitivity Index (ASI) and Acceptance and Action Questionnaire (AAQ) which measure AS and EA, respectively. Clinical outcome measures were compared between clusters using multivariate analysis of variance: Generalized Anxiety Disorder 7 item (anxiety); Patient Health Questionnaire-9 (depression), and EQ-5D overall health item (QoL). RESULTS: Among 86 participants included for analysis (mean age 47.1±14.2 years, 54.7% female), three unique clusters were produced. ASI and AAQ were significantly different among all groups (p < 0.001). Cluster 1 (n = 26) had the lowest levels of AS and EA whereas Cluster 3 (n = 24) had the highest levels of AS and EA; Cluster 2 (n = 36) had moderate levels of AS and EA. There was no significant difference between groups in age, gender, time since injury, or Glasgow Coma Scale scores. Cluster 3 had significantly higher anxiety and depression scores than Cluster 1 and 2 (p < 0.001 for all). Further, Cluster 2 had significantly higher anxiety and depression scores than Cluster 1 (p < 0.001 for all). There was no significant difference in EQ-5D scores between Clusters 1 and 2 or Cluster 2 and 3; however, Cluster 3 scored significantly lower on EQ-5D than Cluster 1 (p = 0.032). CONCLUSIONS: There exists a subgroup of individuals with ABI that have high levels of AS and EA; this was associated with greater symptoms of anxiety and depression, and poorer QoL. Interventions to address AS and EA may improve mood and QoL in this population.

Coping strategies and personality traits among individuals with brain injury and depressive symptoms.

OBJECTIVE: The objective of this observational cohort study was to compare coping strategies and personality traits among individuals with acquired brain injury (ABI), based on their level of depression symptoms. METHODS: Participants were recruited from an ABI outpatient clinic in Ontario, Canada. Participants were selected using the following inclusion criteria: 1) diagnosed with an ABI, 2) 18 years of age, and 3) able to read and write in English. Individuals completed the Patient Health Questionnaire 9-item (PHQ-9), Acceptance and Action Questionnaire, Anxiety Sensitivity Index, Adult Dispositional Hope Scale, Big Five Inventory, Brief Coping Orientation of Problems Experienced, and Rosenberg Self-Esteem Scale. A descriptive analysis was performed for the overall sample, as well as for each subclassification of depression: none (PHQ-9 = 0-4), mild (PHQ-9 = 5-9), moderate (PHQ-9 = 10-14), and severe (PHQ-9 = 15-27). A one-way multivariate analysis of variance, with post hoc Bonferroni-corrected tests, was conducted to assess the impact of depression symptoms on coping strategies and personality traits. RESULTS: A total of 89 individuals (56.2% females) were included with a mean age of 46.6±15.1 years and a mean Glasgow Coma Scale score of 13.2±3.4. Overall, individuals were 3.5±4.3 years post injury. There was a statistically significant interaction effect between depression groups and the combined coping strategy and personality trait variables (F(36,128)=2.959, p < .001; Wilks' Λ= .167). Individuals with mild (p = .045), moderate (p = .004) and severe (p < .001) depression symptoms had greater experiential avoidance (EA) than those without depression. Those with severe depression symptoms had significantly greater anxiety sensitivity than those with no (p < 0.001), mild, (p = .004) or moderate (p = .025) depression symptoms. Overall, individuals in the no, mild, and moderate depression groups used emotion-focused strategies primarily, followed by dysfunctional strategies for coping. Conversely, those with severe depression symptoms primarily used dysfunctional strategies, followed by emotion-focused strategies to cope. All depression groups applied problem-based coping strategies infrequently. CONCLUSIONS: The use of passive coping strategies combined with increased EA behaviours among severely depressed individuals with ABI may lead to long-term negative outcomes. Programs that promote problem-based coping and reduce EA behaviours may be beneficial in reducing disability and impaired quality of life associated with depression symptoms in individuals with ABI.

Role of the ERp57 protein (1,25D3-MARRS receptor) in murine mammary gland growth and development.

The protein disulfide isomerase ERp57 (GRp58/PDIA3/1,25D3-MARRS) has been implicated in a multitude of signaling pathways throughout the entire body. Most thoroughly studied for its protein-folding role, ERp57 has also been found to have multiple binding partners, and have significant effects on cellular growth. ERp57 has been studied n the context of several neurodegenerative disorders, metabolic conditions, and can be used as a prognosis marker in certain cancers. One role, as an alternate vitamin D binding receptor, has prompted research in tissues with known vitamin D activity, such as the intestine and bone. Vitamin D has been studied in relation to mammary gland growth and development, but it is not yet known if ERp57 plays an independent role in this tissue. In this study, ERp57 was knocked out in murine mammary gland epithelial cells of 30 4-week old mice. Several markers of mammary gland growth were measured, including number of terminal end buds (TEB), ductal coverage of the fat pad, and ductal extension. It was found the knockout animals had decreased numbers of TEBs (p = 0.019), and decreased ductal extension (p = 0.018) compared to wildtype animals, with no differences in gross body weight. Immunohistochemistry analysis of mammary glands showed ERp57 localized to the apical side of alveolar branches, and on leading edges of TEBs. These results provide further evidence for ERp57 functioning separately to the VDR, and further insights into the roles of ERp57.

Evaluating Changes in Omega-3 Fatty Acid Intake after Receiving Personal FADS1 Genetic Information: A Randomized Nutrigenetic Intervention.

Nutrigenetics research is anticipated to lay the foundation for personalized dietary recommendations; however, it remains unclear if providing individuals with their personal genetic information changes dietary behaviors. Our objective was to evaluate if providing information for a common variant in the fatty acid desaturase 1 (FADS1) gene changed omega-3 fatty acid (FA) intake and blood levels in young female adults (18-25 years). Participants were randomized into Genetic (intervention) and Non-Genetic (control) groups, with measurements taken at Baseline and Final (12 weeks). Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was assessed using an omega-3 food frequency questionnaire. Red blood cell (RBC) FA content was quantified by gas chromatography. Implications of participation in a nutrigenetics study and awareness of omega-3 FAs were assessed with online questionnaires. Upon completion of the study, EPA and DHA intake increased significantly (p = 1.0 × 10-4) in all participants. This change was reflected by small increases in RBC %EPA. Participants in the Genetic group showed increased awareness of omega-3 terminology by the end of the study, reported that the dietary recommendations were more useful, and rated cost as a barrier to omega-3 consumption less often than those in the Non-Genetic group. Providing participants FADS1 genetic information did not appear to influence omega-3 intake during the 12 weeks, but did change perceptions and behaviors related to omega-3 FAs in this timeframe.