Reach, Adoption, and Implementation Strategies of a Telehealth Fall Prevention Program: Perspectives From Francophone Communities Across Canada.

Introduction. A fall may impact a person's physical, emotional, and psychological well-being. Fall prevention programs are being implemented to reduce these negative outcomes. However, linguistic barriers in health services may reduce access to such prevention programs. A telehealth fall prevention program was designed to increase access to such programs in French for Francophone minority communities in Canada. This capacity-building project aimed to support community partners to deliver this telehealth program and document strategies used to reach, adopt, and implement the program within various Francophone and Acadian Minority Communities. Methods. A sequential explanatory mixed methodology was used to document reach, adoption, and implementation strategies and describe the lived experiences of program facilitators and organization representatives. Reach, adoption, and implementation were documented and analyzed descriptively, while lived experiences were analyzed using content analysis following the Consortium Framework for Implementation Research. Results. Twelve organization representatives or program facilitators from eight organizations operating in four different provinces participated in the study. Three themes emerged from the qualitative data on reach and adoption: external context, internal context, and capacity building. Four themes were identified as barriers and facilitators to implementation: level of preparation and time management, interpersonal relations and telepresence, exercise facilitation and safety, and technological problem-solving. Conclusion. Using tailored reach and adoption strategies such as prioritizing provinces with higher proportions of needs and training local community program facilitators may lead to the successful implementation of a new telehealth fall prevention program. Results from this study could potentially inform other primary prevention programs or telehealth program implementation.

Telerehabilitation in Physical Therapist Practice: A Clinical Practice Guideline From the American Physical Therapy Association.

A clinical practice guideline on telerehabilitation was developed by an American Physical Therapy Association volunteer guideline development group consisting of international physical therapists and physiotherapists, a physician, and a consumer. The guideline was based on systematic reviews of current scientific literature, clinical information, and accepted approaches to telerehabilitation in physical therapist practice. Seven recommendations address the impact of, preparation for, and implementation of telerehabilitation in physical therapist practice. Research recommendations identify current gaps in knowledge. Overall, with shared decision-making between clinicians and patients to inform patients of service delivery options, direct and indirect costs, barriers, and facilitators of telerehabilitation, the evidence supports the use of telerehabilitation by physical therapists for both examination and intervention. The Spanish and Chinese versions of this clinical practice guideline, as well as the French version of the recommendations, are available as supplementary material (Suppl. Materials).

XTX301, a Tumor-Activated Interleukin-12 Has the Potential to Widen the Therapeutic Index of IL12 Treatment for Solid Tumors as Evidenced by Preclinical Studies.

IL12 is a proinflammatory cytokine, that has shown promising antitumor activity in humans by promoting the recruitment and activation of immune cells in tumors. However, the systemic administration of IL12 has been accompanied by considerable toxicity, prompting interest in researching alternatives to drive preferential IL12 bioactivity in the tumor. Here, we have generated XTX301, a tumor-activated IL12 linked to the human Fc protein via a protease cleavable linker that is pharmacologically inactivated by an IL12 receptor subunit beta 2 masking domain. In vitro characterization demonstrates multiple matrix metalloproteases, as well as human primary tumors cultured as cell suspensions, can effectively activate XTX301. Intravenous administration of a mouse surrogate mXTX301 demonstrated significant tumor growth inhibition (TGI) in inflamed and non-inflamed mouse models without causing systemic toxicities. The superiority of mXTX301 in mediating TGI compared with non-activatable control molecules and the greater percentage of active mXTX301 in tumors versus other organs further confirms activation by the tumor microenvironment-associated proteases in vivo. Pharmacodynamic characterization shows tumor selective increases in inflammation and upregulation of immune-related genes involved in IFNγ cell signaling, antigen processing, presentation, and adaptive immune response. XTX301 was tolerated following four repeat doses up to 2.0 mg/kg in a nonhuman primate study; XTX301 exposures were substantially higher than those at the minimally efficacious dose in mice. Thus, XTX301 has the potential to achieve potent antitumor activity while widening the therapeutic index of IL12 treatment and is currently being evaluated in a phase I clinical trial.

The Impact of Two Telerehabilitation Supervision Schedules on Physical Activity, Mobility, and Balance Among People with Moderate to Severe Traumatic Brain Injury: A Mixed-Method Single-Subject Design.

Background: Many individuals who experience a moderate or severe traumatic brain injury (TBI) have long-term deficits in physical activity, balance, and mobility requiring specialized care. New delivery models are being investigated for interventions to address challenges caused by living in remote communities, difficulties with transportation, and/or physical distancing requirements. Determining the effectiveness of telerehabilitation is critical given the current movement toward remote health care delivery. Objective: We investigated the effectiveness of two teletherapy supervision schedules used to deliver a home-based, intensive exercise programme on 1) physical activity, mobility, balance, participation, and 2) concerns with falling, and satisfaction with life. Methods: A mixed methods approach with alternating single subject design (SSD) and interviews was used. Five individuals who experienced a moderate or severe TBI completed two intensive home-based telerehabilitation programmes. Programmes differed only by supervision schedule - daily or weekly. Impacts on objective and patient-reported outcomes were measured. Results: Four individuals demonstrated clinically significant improvements in physical activity level, balance, and mobility. One individual experienced less concerns with falling after both schedules, while two other individuals showed a trend in that direction after the weekly remote supervision. Important functional gains (i.e., improved balance and decreased fatigue) were also perceived and reported by family partners regardless of supervision schedule. Conclusion: Although the study has limitations, the findings indicate that exercise programmes delivered via telerehabilitation can improve balance and mobility as well as positively affect concerns with falling and physical activity levels for this population. No clear differences were seen between the two telerehabilitation supervision schedules.

Historique : de nombreuses personnes qui sont victimes d'un traumatisme crânien (TC) modéré ou grave ont des déficits à long terme en matière d'activité physique, d'équilibre et de mobilité et doivent recevoir des soins spécialisés. De nouveaux modèles de prestation sont en cours d'étude afin que les interventions relèvent les problèmes liés à la vie en région éloignée, au transport ou à la distanciation physique. Il est essentiel de déterminer l'efficacité de la téléréadaptation en raison du mouvement actuel vers la prestation des soins à distance. Objectif : examiner l'efficacité de deux horaires de supervision de la téléthérapie utilisés pour fournir un programme d'exercice intensif à domicile sur 1) l'activité physique, la mobilité, l'équilibre et la participation et 2) les craintes de chutes et la satisfaction de vivre. Méthodologie : méthodologie mixte faisant appel à une alternance entre la méthodologie individuelle et les entrevues. Cinq personnes qui avaient été victimes d'un TC modéré ou grave ont suivi deux programmes intensifs de téléréadaptation à domicile. Les programmes différaient seulement en fonction de l'horaire de supervision, qui était quotidien ou hebdomadaire. Les chercheurs ont mesuré les répercussions sur les résultats cliniques objectifs et déclarés par les patients. Résultats : quatre personnes ont démontré des améliorations cliniquement significatives au taux d'activité physique, à l'équilibre et à la mobilité. Une personne craignait moins les chutes après les deux programmes tandis que les deux autres ressentaient une tendance dans cette direction après la supervision hebdomadaire à distance. Des gains fonctionnels importants (amélioration de l'équilibre et diminution de la fatigue) étaient également perçus et déclarés par les partenaires familiaux, quel que soit l'horaire de supervision. Conclusion : même si l'étude comporte des limites, les observations indiquent que les programmes d'exercices donnés en téléréadaptation peuvent améliorer l'équilibre et la mobilité et avoir des effets positifs sur les craintes de tomber et les taux d'activité physique dans cette population. Il n'y avait pas de différences évidentes entre les deux horaires de supervision de la téléréadaptation.

Remotely Supervised Exercise Programmes to Improve Balance, Mobility, and Activity Among People with Moderate to Severe Traumatic Brain Injury: Description and Feasibility.

Purpose: Further investigation into the feasibility of using videoconferencing and activity tracking devices to provide high-intensity home-based exercise programmes for people with a moderate or severe traumatic brain injury (TBI) is needed to inform clinical implementation and patient adoption. This study aimed to (1) determine if home-based telerehabilitation exercise programmes were feasible for people with a moderate or severe TBI and (2) better understand the lived experience of people with a TBI and their family partners with this programme. Methods: A mixed-methods approach consisting of measures of feasibility and semi-structured interviews was used. Five participants with moderate to severe TBI and their family partners completed two high-intensity home-based exercise programmes delivered remotely by a physiotherapist (i.e., daily and weekly). Results: Telerehabilitation services in home-based settings were feasible for this population. Adherence and engagement were high. Dyads were satisfied with the use of technology to deliver physiotherapy sessions. Conclusion: Telerehabilitation provides a delivery option that allows people with TBI to spend energy on therapy rather than on travelling. A pre-programme training on key components, such as the use of technology, safety precautions, and communication methods, likely improved the overall feasibility. Further research is needed to better understand the effectiveness of such a programme on balance, mobility, and physical activity levels.

Objectif : des recherches plus approfondies s'imposent sur la faisabilité d'utiliser les visioconférences et les dispositifs de suivi des activités pour fournir des programmes d'exercices à domicile à haute intensité aux personnes atteintes d'un traumatisme crânien (TC) modéré à grave qui éclaireront la mise en œuvre clinique et l'adoption par le patient. Cette étude visait à 1) déterminer s'il était faisable d'offrir des programmes d'exercices en téléréadaptation à domicile pour les personnes atteintes d'un TC modéré à grave et 2) mieux comprendre l'expérience vécue des personnes atteintes d'un TC et de leurs partenaires familiaux au sein de ce programme. Méthodologie : les chercheurs ont utilisé une approche mixte composée de mesures de faisabilité et d'entrevues semi-structurées. Cinq participants atteints d'un TC modéré à grave et leurs partenaires familiaux ont effectué deux programmes d'exercices à domicile à haute intensité donnés à distance par un physiothérapeute (quotidiennement et hebdomadairement). Résultats : les services de téléréadaptation à domicile étaient faisables pour cette population. L'adhésion et la participation étaient élevées. Les dyades étaient satisfaites par l'utilisation de la technologie pour la prestation des séances de physiothérapie. Conclusion : la téléréadaptation fournit un mode de prestation qui permet aux personnes atteintes d'un TC à consacrer leur énergie au traitement plutôt qu'aux déplacements. Une formation avant le programme portant sur les principaux éléments, tels que le recours à la technologie, les mesures de précaution et les modes de communication, améliorait probablement la faisabilité globale. D'autres recherches seront réalisées pour mieux comprendre l'efficacité de ce programme sur l'équilibre, la mobilité et les taux d'activité physique.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review.

PURPOSE: To examine the reporting completeness of randomized controlled trials (RCTs) of non-pharmacological interventions following concussion. METHODS: We searched MEDLINE, Embase, PsycInfo, CINAHL, and Web of Science up to May 2022. Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication (TIDieR), Consensus on Exercise Reporting Template (CERT), and international Consensus on Therapeutic Exercise aNd Training (i-CONTENT) checklists. Additional information was sought my study authors where reporting was incomplete. Risk of bias (ROB) was assessed with the Cochrane ROB-2 Tool. RCTs examining non-pharmacological interventions following concussion. RESULTS: We included 89 RCTs (n = 53 high ROB) examining 11 different interventions for concussion: sub-symptom threshold aerobic exercise, cervicovestibular therapy, physical/cognitive rest, vision therapy, education, psychotherapy, hyperbaric oxygen therapy, transcranial magnetic stimulation, blue light therapy, osteopathic manipulation, and head/neck cooling. Median scores were: TIDieR 9/12 (75%; interquartile range (IQR) = 5; range: 5-12), CERT 17/19 (89%; IQR = 2; range: 10-19), and i-CONTENT 6/7 (86%; IQR = 1; range: 5-7). Percentage of studies completely reporting all items was TIDieR 35% (31/89), CERT 24% (5/21), and i-CONTENT 10% (2/21). Studies were more completely reported after publication of TIDieR (t87 = 2.08; p = 0.04) and CERT (t19 = 2.72; p = 0.01). Reporting completeness was not strongly associated with journal impact factor (TIDieR: rs = 0.27; p = 0.01; CERT: rs = -0.44; p = 0.06; i-CONTENT: rs = -0.17; p = 0.48) or ROB (TIDieR: rs = 0.11; p = 0.31; CERT: rs = 0.04; p = 0.86; i-CONTENT: rs = 0.12; p = 0.60). CONCLUSION: RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness, but are often missing key components, particularly modifications, motivational strategies, and qualified supervisor. Reporting completeness improved after TIDieR and CERT publication, but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Identification and description of telerehabilitation assessments for individuals with neurological conditions: A scoping review.

Background: The clinical adoption of telerehabilitation accelerated rapidly over the last few years, creating opportunities for clinicians and researchers to explore the use of digital technologies and telerehabilitation in the assessment of deficits related to neurological conditions. The objectives of this scoping review were to identify outcome measures used to remotely assess the motor function and participation in people with neurological conditions and report, when available, the psychometric data of these remote outcome measures. Methods: MEDLINE (Ovid), CINAHL, PubMed, PsychINFO, EMBASE, and Cochrane databases were searched between December 13, 2020, and January 4, 2021, for studies investigating the use of remote assessments to evaluate motor function and participation in people with neurological conditions. An updated search was completed on May 9, 2022, using the same databases and search terms. Two reviewers independently screened each title and abstract, followed by full-text screening. Data extraction was completed using a pre-piloted data extraction sheet where outcome measures were reported as per the International Classification of Functioning, Disability and Health. Results: Fifty studies were included in this review. Eighteen studies targeted outcomes related to body structures and 32 targeted those related to activity limitation and participation restriction. Seventeen studies reported psychometric data; of these, most included reliability and validity data. Conclusion: Clinical assessments of motor function of people living with neurological conditions can be completed in a telerehabilitation or remote context using validated and reliable remote assessment measures.

A path forward in the development of new aerosol drug delivery devices for pediatrics.

Inhaled medications are widely accepted as being the optimal route for treating pediatric respiratory diseases, a leading cause of hospitalization and death. Despite jet nebulizers being the preferred inhalation device for neonates and infants, current devices face performance issues with most of the drug never reaching the target lung location. Previous work has aimed to improve pulmonary drug deposition, yet nebulizer efficiency remains low. The development of an inhalant therapy that is efficacious and safe for pediatrics depends on a well-designed delivery system and formulation. To accomplish this, the field needs to rethink the current practice of basing pediatric treatments on adult studies. The rapidly evolving pediatric patient (i.e. neonates to eighteen) needs to be considered because they are different from adults with respect to airway anatomy, breathing patterns, and adherence. Previous research approaches to improve deposition efficiency have been limited due to the complexity of combining physics, which drives aerosol transport and deposition, and biology, especially within the area of pediatrics. To address these critical knowledge gaps, we need a better understanding of how patient age and disease state affect deposition of aerosolized drugs. The complexity of the multiscale respiratory system makes scientific investigation very challenging. The authors have simplified the complex problem into five components with these three areas as ones to address first: how the aerosol is (i) generated in a medical device, (ii) delivered to the patient, and (iii) deposited inside the lung. In this review, we discuss the technological advances and innovations made from experiments, simulations, and predictive models in each of these areas. In addition, we discuss the impact on patient treatment efficacy and recommend a clinical direction, with a focus on pediatrics. In each area, a series of research questions are posed and steps for future research to improve efficacy in aerosol drug delivery are outlined.

Clinician Perspectives on Providing Concussion Assessment and Management via Telehealth: A Mixed-Methods Study.

OBJECTIVE: To examine clinician perspectives regarding the use of telehealth for concussion assessment and management. SETTING: A Pan-Canadian survey. PARTICIPANTS: Twenty-five purposively sampled multidisciplinary clinician-researchers with concussion expertise (female, n = 21; physician, n = 11; and other health professional, n = 14). DESIGN: Sequential mixed-method design: (1) electronic survey and (2) semistructured interviews with focus groups via videoconference. Qualitative descriptive design. MAIN OUTCOME MEASURES: Survey : A 59-item questionnaire regarding the suitability of telehealth to perform recommended best practice components of concussion assessment and management. Focus groups : 10 open-ended questions explored survey results in more detail. RESULTS: Clinicians strongly agreed that telehealth could be utilized to obtain a clinical history (96%), assess mental status (88%), and convey a diagnosis (83%) on initial assessment; to take a focused clinical history (80%); to monitor functional status (80%) on follow-up; and to manage symptoms using education on rest (92%), planning and pacing (92%), and sleep recommendations (91%); and to refer to a specialist (80%). Conversely, many clinicians believed telehealth was unsuitable to perform a complete neurologic examination (48%), cervical spine (38%) or vestibular assessment (61%), or to provide vestibular therapy (21%) or vision therapy (13%). Key benefits included convenience, provision of care, and patient-centered approach. General and concussion-specific challenges included technology, quality of care, patient and clinician characteristics, and logistics. Strategies to overcome identified challenges are presented. CONCLUSIONS: From the perspective of experienced clinicians, telehealth is suited to manage symptomatic concussion patients presenting without red flags or following an initial in-person assessment, but may have limitations in ruling out serious pathology or providing return-to-sport clearance without an in-person physical examination.

A physiotherapist's perception of their own behavior compared to the perception of their behavior by persons with TBI within the context of telerehabilitation: A self-determination theory perspective.

BACKGROUND: According to Self-Determination Theory, the fulfillment of basic psychological needs of autonomy, competence, and relatedness plays an important role in one's motivation, engagement, and well-being. How a therapist is perceived to support or thwart these needs can impact adherence to treatment, thus influencing the effectiveness of therapeutic interventions. OBJECTIVES: This alternating single-subject design explores how the physiotherapist self-reports interpersonal behaviors, how the person living with a disability (PwD) perceives the physiotherapist's supportive/thwarting interpersonal behaviors, and how the two align in the context of telerehabilitation. METHODS: Five PwD and their physiotherapist completed two telerehabilitation exercise programs. The PwD completed the Interpersonal Behavior Questionnaire (IBQ) to examine how they perceived the physiotherapist interpersonal behaviors. The physiotherapist completed the Interpersonal Behavior Questionnaire-Self (IBQ-Self) to document how they self-reported these same behaviors. Descriptive statistics were used to document self-reports and perceptions of behaviors. RESULTS: Each PwD perceived the physiotherapist as being more supportive than thwarting. The supportive/thwarting behaviors varied across relationships. Greater alignment of the perceptions of therapist and the PwD was observed at the end of the programme when compared to baseline. CONCLUSION: Assessing how therapist support/thwart psychological needs and how these behaviors are perceived by PwD is recommended as it may influence the therapist's behavior and the PwD's adherence to future telerehabilitation exercise programs.

XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 monoclonal antibody, demonstrates tumor-growth inhibition and tumor-selective pharmacodynamics in mouse models of cancer.

INTRODUCTION: The clinical benefit of the anti-CTLA-4 monoclonal antibody (mAb) ipilimumab has been well established but limited by immune-related adverse events, especially when ipilimumab is used in combination with anti-PD-(L)1 mAb therapy. To overcome these limitations, we have developed XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4 mAb. METHODS: XTX101 consists of an anti-human CTLA-4 mAb covalently linked to masking peptides that block the complementarity-determining regions, thereby minimizing the mAb binding to CTLA-4. The masking peptides are designed to be released by proteases that are typically dysregulated within the tumor microenvironment (TME), resulting in activation of XTX101 intratumorally. Mutations within the Fc region of XTX101 were included to enhance affinity for FcγRIII, which is expected to enhance potency through antibody-dependent cellular cytotoxicity. RESULTS: Biophysical, biochemical, and cell-based assays demonstrate that the function of XTX101 depends on proteolytic activation. In human CTLA-4 transgenic mice, XTX101 monotherapy demonstrated significant tumor growth inhibition (TGI) including complete responses, increased intratumoral CD8+T cells, and regulatory T cell depletion within the TME while maintaining minimal pharmacodynamic effects in the periphery. XTX101 in combination with anti-PD-1 mAb treatment resulted in significant TGI and was well tolerated in mice. XTX101 was activated in primary human tumors across a range of tumor types including melanoma, renal cell carcinoma, colon cancer and lung cancer in an ex vivo assay system. CONCLUSIONS: These data demonstrate that XTX101 retains the full potency of an Fc-enhanced CTLA-4 antagonist within the TME while minimizing the activity in non-tumor tissue, supporting the further evaluation of XTX101 in clinical studies.

Traduction franco-canadienne de l'Assessment of Systematic Reviews Revised (AMSTAR 2) : validation transculturelle et fidélité interjuges.

Objective: Produce a French-Canadian translation of AMSTAR 2, affirm its content validity, and examine interrater reliability. Methods: Based on Vallerand's methodological approach, we conducted forward and parallel inverse-translations. Subsequently, an expert panel evaluated the translations to create a preliminary experimental French-Canadian version. A second expert panel examined this version and proposed additional modifications. Twenty future health professionals then rated the second experimental version for ambiguity on a scale (from 1 to 7). The principal co-investigators then reviewed the problematic elements and proposed a pre-official version. To ascertain content validity, a final back-translation was conducted resulting in the official version. Four judges evaluated 13 systematic reviews using the official French-Canadian version of AMSTAR 2. The Kappa coefficient was used to evaluate interrater reliability. Results: This rigorous adaptation enabled the development of a Franco-Canadian version of AMSTAR 2. Its application demonstrated low ambiguity (mean 1.15; SD 0.26) as well as good overall interrater reliability (total κ > 0.64) across all items. Conclusion: The French-Canadian version of AMSTAR 2 can now support francophone clinicians, educators, and managers in Canada as they undertake evidence-based practice.

The management of lower back pain using pilates method: assessment of content exercise reporting in RCTs.

PURPOSE: To evaluate the quality of the reporting of exercise interventions with Pilates method for the treatment of lower back pain (LBP) in adults. MATERIALS AND METHODS: Two independent evaluators selected randomized controlled trials (RCTs) of moderate and high methodological quality included in a Cochrane Systematic Review (SR) and from an additional updated search in the following databases: CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro and SPORTDiscus. Three assessment tools (Consensus on Therapeutic Exercise Training (CONTENT) scale, Template for Intervention Description and Replication (TIDieR) checklist and Consensus on Exercise Reporting Template (CERT) checklist) were utilized by three pairs of two independent researchers trained. The scales' concordance was measured using the Kappa coefficient. RESULTS: Ten RCTs were included. The CONTENT scale score was 5.3 (± 1.33) out of 9 points; the TIDieR checklist was 8.5 (± 1.71) out of 12 points and the CERT checklist was 9.5 (± 3.62) out of 19 points. The CONTENT and CERT had moderate concordance, while there was fair concordance between the other tools. CONCLUSIONS: The overall reporting quality for the Pilates exercises in ten moderate-to-high quality RTCs for the management of LBP was low according to CONTENT scale and CERT checklist and high according to TIDieR checklist.Implications for RehabilitationReporting of Pilates exercise program in moderate-to-high quality RCTs for the management of lower back pain remains incomplete.Pilates exercise program should be personalized and contextualized to individual participants.There may be a need to consider adding to or combining the information available from various trials.

The impact of socioeconomic status and race on the outcomes of congenital heart disease.

PURPOSE OF REVIEW: Studying the outcomes of congenital heart disease and their associations allows paediatric cardiologists and intensivists to improve the care and health equity of their patients. This review presents the most recent literature discussing the socioeconomic and racial disparities that pervade the outcomes of patients with congenital heart disease in every facet of treatment. The outcomes of congenital heart disease discussed are prenatal detection, maintenance of care, quality of life, neurodevelopment and mortality. RECENT FINDINGS: Historically, it has been documented that patients with congenital heart disease who are of racial and ethnic minorities disproportionately experience poor outcomes. Recently, the association between racial minorities and mortality has been traced to underlying socioeconomic disparities emphasizing that race and ethnicity are not independent determinants of health. SUMMARY: The effect of socioeconomic status on the outcomes of congenital heart disease is profound and reaches beyond the association with racial and ethnic minorities. Changes to address these disparities in outcomes must be made at the individual, institutional, community and system levels.

Dosage of resistance exercises in fibromyalgia: evidence synthesis for a systematic literature review up-date and meta-analysis.

Several studies have examined the effect of different types of exercise on people with fibromyalgia. The aim of this study was to identify which dosage of resistance training is effective to reduce pain in women with fibromyalgia. Two authors independently selected studies included in a Cochrane Systematic Review and from an updated search up to May 2021 using the following databases: Embase, Central, Lilacs, PEDro, Current Controlled Trials, and WHO International Clinical Trials Registry Platform, Scopus and ISI Web of Science. Inclusion criteria were randomized clinical trials (RCTs) with female patients (18 years of age or older) diagnosed with fibromyalgia according to the American College of Rheumatology (ACR) criteria and the intervention, resistance exercises for pain reduction. The pain outcome value was extracted from studies for meta-analysis. Nine RCTs were included. Compared to the control groups, resistance exercise groups demonstrated a clinically and statistically significant effect on pain reduction when each exercise was performed in 1-2 sets or 3-5 sets of 4-12 or 5-20 repetitions twice a week, for 8-12 weeks, at intensities of 40-80% with one repetition maximum or perceived exertion. Resistance training exercises are effective to reduce pain in women with fibromyalgia when performed at moderate-to-high intensity in 1-2 sets of 4-20 repetitions twice a week, for 8-12 weeks. The protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) platform, CRD42018095205.

Identification and Description of Balance, Mobility, and Gait Assessments Conducted via Telerehabilitation for Individuals With Neurological Conditions: Protocol for a Scoping Review.

BACKGROUND: The COVID-19 global pandemic pushed many rehabilitation practitioners to pivot their in-person practice to adopt telerehabilitation as their main method of delivery. In addition to documenting information on interventions used with clients, it is best practice for therapists to use reliable and validated outcome measures to inform their interventions. OBJECTIVE: Through this scoping review, we aim to identify (1) which outcomes are being used remotely to assess balance, mobility, and gait in patients with neurological conditions, and (2) what psychometric data (validity, reliability, etc.) for remotely administered outcomes are available. METHODS: Three main concepts will be included in our search: (1) neurological conditions; (2) administration by telerehabilitation; and (3) outcome measures for balance, mobility, and gait. Studies reporting remote assessment of neurological conditions published since 1990 will be included. The database search will be completed in MEDLINE (Ovid), CINAHL, PubMed, PsycINFO, EMBASE, and Cochrane. Gray literature including dissertations, conference papers, and protocol papers will also be sourced. Two reviewers will independently screen each title and abstract using pre-established inclusion and exclusion criteria. Manuscripts that appear to meet the criteria will be subject to further review, and full-text extraction using a pre-piloted extraction sheet if all criteria are met. The data will be categorized by assessment types describing impairments (such as balance, strength, and mobility) or activity limitations or participation restriction (such as functional mobility, ambulatory functions, and activities of daily living). RESULTS: This scoping review will document outcome measures currently used in the remote assessment of neurological conditions. To date, 235 titles and abstracts were screened. We are in the process of finalizing the full text screening for the inclusion of articles. We expect the full screening to be completed in November 2021 and data analysis in January 2022. Our results are expected to be published in early 2022. CONCLUSIONS: The optimal use of telerehabilitation as a mode to deliver rehabilitation intervention should be coupled with the completion of validated outcome measures. Therefore, it is crucial to further our knowledge on remote outcome measures and therapeutic assessments. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/27186.

Structure-Based Discovery of Proline-Derived Arginase Inhibitors with Improved Oral Bioavailability for Immuno-Oncology.

Recent data suggest that the inhibition of arginase (ARG) has therapeutic potential for the treatment of a number of indications ranging from pulmonary and vascular disease to cancer. Thus, high demand exists for selective small molecule ARG inhibitors with favorable druglike properties and good oral bioavailability. In light of the significant challenges associated with the unique physicochemical properties of previously disclosed ARG inhibitors, we use structure-based drug design combined with a focused optimization strategy to discover a class of boronic acids featuring a privileged proline scaffold with superior potency and oral bioavailability. These compounds, exemplified by inhibitors 4a, 18, and 27, demonstrated a favorable overall profile, and 4a was well tolerated following multiple days of dosing at concentrations that exceed those required for serum arginase inhibition and concomitant arginine elevation in a syngeneic mouse carcinoma model.

Cryo-EM structures of inhibitory antibodies complexed with arginase 1 provide insight into mechanism of action.

Human Arginase 1 (hArg1) is a metalloenzyme that catalyzes the hydrolysis of L-arginine to L-ornithine and urea, and modulates T-cell-mediated immune response. Arginase-targeted therapies have been pursued across several disease areas including immunology, oncology, nervous system dysfunction, and cardiovascular dysfunction and diseases. Currently, all published hArg1 inhibitors are small molecules usually less than 350 Da in size. Here we report the cryo-electron microscopy structures of potent and inhibitory anti-hArg antibodies bound to hArg1 which form distinct macromolecular complexes that are greater than 650 kDa. With local resolutions of 3.5 Å or better we unambiguously mapped epitopes and paratopes for all five antibodies and determined that the antibodies act through orthosteric and allosteric mechanisms. These hArg1:antibody complexes present an alternative mechanism to inhibit hArg1 activity and highlight the ability to utilize antibodies as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

A qualitative study of persons with persistent postconcussion symptoms and clinicians with concussion expertise to inform the development of a concussion-specific questionnaire.

PURPOSE: To explore the experiences of adults with persistent postconcussion symptoms and clinicians to inform the development of a concussion-specific questionnaire. METHODS: Using a qualitative descriptive design, we conducted 10 focus groups with persons with persistent post-concussion symptoms (n = 35; female 66%; age range 19.0-65.1 years) and semi-structured interviews with clinicians with concussion expertise (n = 16; female 81%). Thematic analysis was used to identify themes within their narratives. The International Classification of Functioning, Disability and Health (ICF) provided a standardized language for coding. RESULTS: Three overarching themes emerged from the data: Functioning, Environmental and Personal Factors, and Capacity. Functioning mapped closely onto Activities and Participation within the ICF. Contextual factors, both Environmental and Personal, had a significant influence on functioning following concussion. Capacity was a unique finding that described how long a person is able to engage in a task before the onset or worsening of symptoms. CONCLUSIONS: Capacity is fundamental to measuring limitations in functioning based on symptom threshold and time to recovery. The impact of contextual factors on functioning needs to be considered on a continuum from barrier to facilitator. These findings provide the basis for the development of a concussion-specific questionnaire.Implications for RehabilitationClinicians should explore with their patients limitations across all areas of functioning.Clinicians should explore and address support and relationships, attitudes of others, access to affordable and high-quality healthcare, coping strategies, and a patient's own knowledge of concussion as these influence functioning.Current guidelines recommend a symptom-based approach to concussion management, whereas persons with concussion emphasize the importance of measuring functional capacity.Capacity is defined as the length of time one can perform a task before symptom onset, primarily fatigue.Currently, no concussion-specific measure of functioning exists.