Identifying Relevant Content to Inform a Comprehensive Indigenous Health Curriculum: A Scoping Review.

Purpose: To identify the entry-level curricular content related to Indigenous health recommended for entry-level physiotherapy (PT) programs in Canada and other similar countries. Methods: Design: Scoping review. Procedures: Four electronic databases were searched using the terms physiotherapy, Indigenous health, entry-level curriculum, and their derivatives. Grey literature sources were hand searched and included Canadian PT professional documents, PT Program websites, Truth and Reconciliation Commission (TRC) sources, and a Google search. Data related to curriculum characteristics, methods of delivery, and barriers and facilitators to implementation were extracted from relevant references. Stakeholders reviewed study findings. Results: Forty-five documents were included. Documents focused on Indigenous peoples in Canada, Aboriginal and Torres Strait Islanders in Australia, and Maori in New Zealand. Canadian PT programs appeared to rely on passive teaching methods while programs in Australia and New Zealand emphasized the importance of partnering and engaging with Indigenous people. Barriers to incorporating indigenous health curriculum included an overcrowded curriculum and difficulty establishing relevance of Indigenous content (i.e., meaning). Conclusions: Similarities and differences were found between curricula content and approaches to teaching IH in Canada and the other countries reviewed. Strategies to promote greater engagement of Indigenous people in the development and teaching of IH is recommended.

Objectif: déterminer le contenu du cursus en santé autochtone recommandé pour les programmes d'entrée en pratique en physiothérapie au Canada et dans des pays semblables. Méthodologie: étude exploratoire. Méthode : les chercheurs ont fouillé quatre bases de données électroniques à l'aide des termes physiotherapy, Indigenous health, entry-level curriculum et leurs dérivés. Ils ont fouillé manuellement les sources de documentation parallèle et y ont inclus des documents professionnels canadiens sur la physiothérapie, les sites Web des programmes de physiothérapie, les sources de la Commission de vérité et réconciliation (CVR) et une recherche dans Google. Les données liées aux caractéristiques du cursus, aux modes de prestation et aux obstacles et incitatifs à la mise en œuvre provenaient de références pertinentes. Les intervenants ont examiné les résultats des études. Résultats: au total, 45 documents ont été retenus. Ils portaient sur les Autochtones du Canada, les Aborigènes et les insulaires du détroit de Torres en Australie et les Maori de la Nouvelle-Zélande. Les programmes de physiothérapie canadiens semblaient reposer sur des méthodes d'enseignement passives, tandis que ceux de l'Australie et de la Nouvelle-Zélande faisaient ressortir l'importance des partenariats et des relations avec les peuples autochtones. Les obstacles à l'intégration du cursus sur la santé autochtone incluaient un cursus surchargé et la difficulté à déterminer la pertinence du contenu sur les Autochtones (c'est-à-dire le sens). Conclusions: les chercheurs ont constaté des similarités et des différences de contenu entre les cursus et les approches d'enseignement de la santé autochtone au Canada et les autres pays analysés. Il est recommandé de trouver des stratégies pour favoriser une plus grande participation des peuples autochtones à la création et à l'enseignement de la santé autochtone.

Portfolios with Evidence of Reflective Practice Required by Regulatory Bodies: An Integrative Review.

Purpose: Regulatory bodies impose continuing professional development (CPD) requirements on health care professionals (HCPs) as a condition for license revalidation. Many regulatory bodies require annual evidence of CPD activities that are informed by reflective practices, guided by learning plans, and compiled into a portfolio. The purpose of this integrative review is to summarize the literature discussing how regulatory bodies use portfolios with evidence of reflection for licensure renewal. Method: We reviewed English-language articles published until May 2020 discussing evidence of CPD and reflective practice in portfolios in the context of licensure renewal. Results: We located 17 articles for the review. None reported or measured outcomes beyond submission of reflective evidence. Sixteen articles (93%) included information about passive learning resources that regulatory bodies provided to help guide HCPs' reflective learning activities. HCPs' feedback about using reflective learning activities indicated mixed opinions about their utility. Conclusions: Few publications reported how jurisdictions expected HCPs to provide evidence of reflective practices for licensure renewal. None of the regulatory bodies required evidence regarding the impact of reflective practice on patient or organizational outcomes. HCPs reported both benefits and challenges of a mandated reflective process.

Objectif : les organismes de réglementation imposent des exigences de perfectionnement professionnel continu (PPC) aux professionnels de la santé (PdS) afin qu'ils puissent renouveler leur permis. Bon nombre exigent des preuves annuelles d'activités de PPC éclairées par des pratiques réflexives, orientées par des plans d'apprentissage et compilées dans un portfolio. La présente analyse intégrative vise à résumer les publications qui expliquent l'utilisation que font les organismes de réglementation des portfolios contenant des preuves de pratiques réflexives dans le processus de renouvellement des permis. Méthodologie : articles de langue anglaise publiés jusqu'en mai 2020 sur des portfolios contenant des preuves de PPC et de pratiques réflexives pour renouveler le permis. Résultats : les chercheurs ont extrait 17 articles. Aucun ne portait sur les résultats mesurés après la soumission des preuves réflexives. Au total, 16 articles (93 %) contenaient de l'information sur les ressources d'apprentissage passif que les organismes de réglementation fournissaient pour contribuer à orienter les activités d'apprentissage réflexif des PdS. Les commentaires des PdS sur les activités de pratique réflexive faisaient foi d'avis mitigés quant à leur utilité. Conclusions : Peu de publications indiquaient la manière dont les régions sociosanitaires voulaient recevoir les preuves de pratiques réflexives des PdS en vue du renouvellement du permis. Aucun organisme de réglementation n'avait besoin de données probantes sur les répercussions de la pratique réflexive pour le patient ou sur les résultats organisationnels. Selon les PdS, le processus réflexif obligatoire comportait à la fois des avantages et des inconvénients.

Remediation Programs for Regulated Health Care Professionals: A Scoping Review.

PURPOSE: Clinical competence is essential for providing safe, competent care and is regularly assessed to ensure health care practitioners maintain competence. When deficiencies in competence are identified, practitioners may undergo remediation. However, there is limited evidence regarding the effectiveness of remediation programs. The purpose of this review is to examine the purpose, format, and outcomes of remediation programs for regulated health care practitioners. METHODS: All six stages of the scoping review process as recommended by Levac et al were undertaken. A search was conducted within MEDLINE, Embase, CINAHL, ERIC, gray literature databases, and websites of Canadian provincial regulatory bodies. Emails were sent to Registrars of Canadian regulatory bodies to supplement data gathered from their websites. RESULTS: A total of 14 programs were identified, primarily for physicians (n = 8). Reasons for remediation varied widely, with some programs identifying multiple reasons for referral such as deficiencies in recordkeeping (n = 7) and clinical skills (n = 6). Most programs (n = 9) were individualized to address specific deficiencies in competence. The process of remediation followed three stages: (1) assessment, (2) active remediation, and (3) reassessment. Most programs (n = 12) reported that remediation was effective in improving competence. CONCLUSIONS: Regulatory bodies should consider implementing individualized remediation programs to ensure that clinicians' deficiencies in competence are addressed effectively. Further research is indicated, using reliable and valid outcome measures to assess competence immediately after remediation programs and beyond.

Conjugation of Aztreonam, a Synthetic Monocyclic ß-Lactam Antibiotic, to a Siderophore Mimetic Significantly Expands Activity Against Gram-Negative Bacteria.

Monocyclic ß-lactams with antibiotic activity were first synthesized more than 40 years ago. Extensive early structure-activity relationship (SAR) studies, especially in the 1980s, emphasized the need for heteroatom activation of monocyclic ß-lactams and led to studies of oxamazins, monobactams, monosulfactams, and monocarbams with various side chains and peripheral substitution that revealed potent activity against select strains of Gram-negative bacteria. Aztreonam, still the only clinically used monobactam, has notable activity against many Gram-negative bacteria but limited activity against some of the most problematic multidrug resistant (MDR) strains of Pseudomonas aeruginosa and Acinetobacter baumannii. Herein, we report that extension of the side chain of aztreonam is tolerated and especially that coupling of the side chain free acid with a bis-catechol siderophore mimetic significantly improves activity against the MDR strains of Gram-negative bacteria that are of most significant concern.

Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds.

The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol N-oxide (BTO) analogs. Herein we report that nitro cyano phenoxybenzenes (MDL860 and analogs) reacted slowly and incompletely which reflected their moderate anti-TB activity, in contrast to the instantaneous reaction of BTO derivatives to quantitatively generate Meisenheimer complexes which corresponded to their enhanced anti-TB activity. These results were corroborated by mycobacterial and radiolabelling studies that confirmed inhibition of the DprE1 enzyme by BTO derivatives but not MDL860 analogs.

Baby STRENGTH: Eat, Sleep, Console for Infants With Neonatal Abstinence Syndrome.

BACKGROUND: Traditional medication-based management of neonatal abstinence syndrome (NAS) results in long hospitalizations. Nonpharmacologic treatment and using the Eat, Sleep, Console (ESC) model of care have been shown to decrease lengths of stay (LOSs). PURPOSE: To determine whether using the ESC model of care to treat infants with opioid withdrawal resulted in decreased LOSs and number of infants receiving morphine when compared with traditional medication management. METHODS: Retrospective medical review for all patients admitted for NAS 12 months before and 12 months after implementing the ESC model of care. Data collected from electronic health records included demographic data, maternal history, infant LOS, infants receiving morphine, and birth weight/weight on day of life (DOL) 5. Univariate analysis was used to control for demographic data/risk factors. A 2-samples t test was used to compare average LOSs. Chi-square test was used to detect differences in the number of infants receiving morphine. Data were analyzed using SAS 9.4 software. RESULTS: LOS decreased from mean of 17.7 days to a mean of 5.9 days (P < .0001). The number of infants receiving morphine decreased from 20 (58.9%) to 1 (2.7%) (P < .0001). No statistically significant difference was noted in the percentage of weight loss on DOL 5. Data showed an increase in breastfeeding rates from 41.18% to 64.86% (P = .0456). IMPLICATIONS FOR PRACTICE: The ESC model of care decreased infant LOS and the number of morphine doses administered for opioid withdrawal symptoms. Maternal breastfeeding rates increased. IMPLICATIONS FOR RESEARCH: More research is needed to determine long-term neurodevelopmental outcomes of infants managed using ESC principles.

Understanding health professional role integration in complex adaptive systems: a multiple-case study of physician assistants in Ontario, Canada.

BACKGROUND: To meet the complex needs of healthcare delivery, the Ministry of Health and Long Term Care (MOHLTC) introduced Physician Assistants (PAs) into the Ontario health care system in 2006 with the goal of helping to increase access to care, decrease wait times, improve continuity of care and provide a flexible addition to the healthcare workforce. The characterization of healthcare organizations as complex adaptive systems (CAS) may offer insight into the relationships and interactions that optimize and restrict successful PA integration. The aim of this study is to explore the integration of PAs across multiple case settings and to understand the role of PAs within complex adaptive systems. METHODS: An exploratory, multiple-case study was used to examine PA role integration in four settings: family medicine, emergency medicine, general surgery, and inpatient medicine. Interviews were conducted with 46 healthcare providers and administrators across 13 hospitals and 6 family medicine clinics in Ontario, Canada. Analysis was conducted in three phases including an inductive thematic analysis within each of the four cases, a cross-case thematic analysis, and a broader, deductive exploration of cross-case patterns pertaining to specific complexity theory principles of interest. RESULTS: Forty-six health care providers were interviewed across 19 different healthcare sites. Support for PA contributions across various health care settings, the importance of role awareness, supervisory relationship attributes, and role vulnerability are interconnected and dynamic. Findings represent the experiences of PAs and other healthcare providers, and demonstrate how the PAs willingness to work and ability to build relationships allows for the establishment of interprofessional, collaborative, and person-centered care. As a self-organizing agent in complex adaptive systems (i.e., health organizations), PA role exploration revealed patterns of team behavior, non-linear interconnections, open relationships, dynamic systems, and the legacy of role implementation as defined by complexity theory. CONCLUSIONS: By exploring the role of PAs across multiple sites, the complexity theory lens concurrently fosters an awareness of emerging patterns, relationships and non-linear interactions within the defined context of the Ontario healthcare system. By establishing collaborative, interprofessional care models in hospital and community settings, PAs are making a significant contribution to Ontario healthcare settings.

Antibiotic repurposing: bis-catechol- and mixed ligand (bis-catechol-mono-hydroxamate)-teicoplanin conjugates are active against multidrug resistant Acinetobacter baumannii.

Antibiotics that are normally used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they can circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein we report syntheses of bis-catechol-teicoplanin and mixed ligand catechol-hydroxamate-teicoplanin conjugates. Antibacterial activity assays revealed that conjugation of teicoplanin, which is only known to be active against Gram-positive bacteria, to the siderophore mimics induced potent activity against multidrug resistant strains of select Gram-negative bacteria (Acinetobacter baumannii) while retaining moderate activity against Gram-positive bacteria (Staphylococcus aureus).

Estimating the Threshold Value for Change for the Six Dimensions of the Impairment Inventory of the Chedoke-McMaster Stroke Assessment.

Purpose: Our purpose was to estimate a threshold value for change for the six dimensions of the Impairment Inventory of the Chedoke-McMaster Stroke Assessment and the confidence in labelling a person as having improved or not. Method: Secondary analysis of two data sets, previously reported by two research teams, consisted of two statistical analyses. The first analysis used a multiple of the standard error of measurement to calculate the threshold value for change for the six dimensions. The second analysis used the diagnostic test method to calculate a threshold improvement value and the confidence a clinician had in labelling a person as having improved or not on the leg, foot, and postural control dimensions. Results: The threshold value for change was determined to be 1 impairment point (i.e., stage) for the arm, hand, leg, foot, and postural control dimensions and 2 impairment points for the shoulder pain dimension. The positive predictive values associated with the leg, foot, and postural control dimensions were 74%, 59%, and 65%, respectively. Conclusions: Clinicians can use a change of 1 impairment point for the arm, hand, leg, foot, and postural control dimensions and a change of 2 impairment points for the shoulder pain dimension to identify true change in a patient's motor recovery.

Objectif : parvenir à une valeur seuil de changement aux six dimensions de l'inventaire des déficiences de l'évaluation Chedoke-McMaster de l'AVC ainsi que de la confiance à déclarer que l'état d'une personne s'est amélioré ou non. Méthodologie : l'analyse secondaire de deux ensembles de données, dont deux équipes de recherche avaient déjà rendu compte, s'est déclinée en deux analyses statistiques. La première faisait appel à un multiple de l'écart-type de mesure pour calculer la valeur seuil de changement aux six dimensions. La seconde puisait dans la méthode de test diagnostique pour calculer une valeur d'amélioration du seuil et la confiance du clinicien à déclarer que l'état d'une personne s'est amélioré ou non dans les dimensions du contrôle de la jambe, du pied et de la posture. Résultats : les chercheurs ont établi que la valeur seuil de changement correspondait à 1 point de déficience (phase) pour les dimensions du contrôle du bras, de la main, de la jambe, du pied et de la posture et de 2 points de déficience pour la dimension de la douleur de l'épaule. Les valeurs prédictives positives associées aux dimensions de contrôle de la jambe, du pied et de la posture s'élevaient à 74 %, 59 % et 65 %, respectivement. Conclusions : les cliniciens peuvent utiliser un changement d'1 point de déficience des dimensions de contrôle du bras, de la main, de la jambe, du pied et de la posture, et un changement de 2 points de déficience pour la dimension de la douleur de l'épaule pour déclarer un véritable changement dans le rétablissement moteur du patient.

Professional Values: Results of a Scoping Review and Preliminary Canadian Survey.

Purpose : Physiotherapists in Canada do not have an agreed-on list of core professional values. The purpose of this study was to identify physiotherapy values using a scoping review and to preliminarily identify the core professional values important to Canadian physiotherapists. Method: We undertook (1) a comprehensive scoping review of the primary and grey literature and (2) a cross-sectional survey of Canadian physiotherapists attending the 2016 Canadian Physiotherapy Association Congress. We conducted Ovid MEDLINE, Ovid EMBASE, and CINAHL database and Internet searches to identify peer-reviewed and grey literature. Survey participants were asked to list two professional values that guided their practice. Thematic and content analyses were used to analyze the results of both activities. We combined the results of the scoping review and the survey. Results : A total of 23 Web sites and 11 primary articles were retained from the search; 88 physiotherapists participated in the survey. A final list of 10 professional values (accountability, advocacy, altruism, compassion and caring, equity, excellence, integrity, patient and client centred, respect, and social responsibility) was drawn up after analyzing the scoping review and survey. Conclusions: This study describes the first steps in the process of identifying a set of core professional values for Canadian physiotherapists. Although many of values identified in this survey aligned with values published in the literature, some were unique, and further investigation is required.

Objectif : les physiothérapeutes du Canada ne disposent pas d'une liste commune de valeurs professionnelles fondamentales. La présente étude visait à circonscrire les valeurs en physiothérapie au moyen d'une analyse exploratoire et à procéder à une sélection préliminaire des valeurs professionnelles fondamentales importantes pour les physiothérapeutes canadiens. Méthodologie : les chercheurs ont procédé à 1) une analyse exploratoire complète des publications primaires et non officielles et 2) une analyse transversale des physiothérapeutes canadiens qui ont assisté au congrès 2016 de l'Association canadienne de physiothérapie. Ils ont fait des recherches dans les bases de données Ovid MEDLINE, Ovid EMBASE et CINAHL, ainsi que dans Internet pour extraire les publications parallèles. Ils ont invité les participants au sondage à fournir deux valeurs professionnelles qui orientaient leur pratique. Ils ont recouru à des analyses thématiques et de contenu pour examiner les résultats des deux activités, qu'ils ont combinés. Résultats : au total, les chercheurs ont extrait 23 sites Web et 11 articles primaires de leur recherche, et 88 physiothérapeutes ont participé au sondage. Ils ont retenu une liste finale de dix valeurs professionnelles (redevabilité, prise de position, altruisme, compassion, équité, excellence, intégrité, axe sur les patients et les clients, respect et responsabilité sociale) après avoir examiné l'analyse exploratoire et le sondage. Conclusion : la présente étude décrit les premières étapes du processus pour circonscrire les valeurs professionnelles fondamentales des physiothérapeutes canadiens. De nombreuses valeurs du sondage correspondaient à celles contenues dans les publications scientifiques, mais certaines étaient uniques. Des recherches plus approfondies s'imposent.

Synthetic sideromycins (skepticism and optimism): selective generation of either broad or narrow spectrum Gram-negative antibiotics.

New or repurposed antibiotics are desperately needed since bacterial resistance has risen to essentially all of our current antibiotics, and few new antibiotics have been developed over the last several decades. A primary cause of drug resistance is the overuse of antibiotics that can result in alteration of microbial permeability, alteration of drug target binding sites, induction of enzymes that destroy antibiotics (i.e., ß-lactamases) and even induction of efflux mechanisms. Research efforts are described that are designed to determine if the known critical dependence of iron assimilation by microbes for growth and virulence can be exploited for the development of new approaches to antibiotic therapy. Iron recognition and active transport relies on the biosyntheses and use of microbe-selective iron chelating compounds called siderophores. Several natural siderophore-antibiotic conjugates (sideromycins) have been discovered and studied. The natural sideromycins consist of an iron binding siderophore linked to a warhead that exerts antibiotic activity once assimilated by targeted bacteria. Inspired these natural conjugates, a combination of chemical syntheses, microbiological and biochemical studies have been used to generate semi-synthetic and totally synthetic sideromycin analogs. The results demonstrate that siderophores and analogs can be used for iron transport-mediated drug delivery ("Trojan Horse" antibiotics or sideromycins) and induction of iron limitation/starvation (development of new agents to block iron assimilation). While several examples illustrate that this approach can generate microbe selective antibiotics that are active in vitro, the scope and limitations of this approach, especially related to development of resistance, siderophore based molecular recognition requirements, appropriate linker and drug choices, will be described.

Siderophore Conjugates of Daptomycin are Potent Inhibitors of Carbapenem Resistant Strains of Acinetobacter baumannii.

Development of resistance to antibiotics is a major medical problem. One approach to extending the utility of our limited antibiotic arsenal is to repurpose antibiotics by altering their bacterial selectivity. Many antibiotics that are used to treat infections caused by Gram-positive bacteria might be made effective against Gram-negative bacterial infections, if they could circumvent permeability barriers and antibiotic deactivation processes associated with Gram-negative bacteria. Herein, we report that covalent attachment of the normally Gram-positive-only antibiotic, daptomycin, with iron sequestering siderophore mimetics that are recognized by Gram-negative bacteria, provides conjugates that are active against virulent strains of Acinetobacter baumannii, including carbapenemase and cephalosporinase producers. The result is the generation of a new set of antibiotics designed to target bacterial infections that have been designated as being of dire concern.

A Synthetic Dual Drug Sideromycin Induces Gram-Negative Bacteria To Commit Suicide with a Gram-Positive Antibiotic.

Many antibiotics lack activity against Gram-negative bacteria because they cannot permeate the outer membrane or suffer from efflux and, in the case of ß-lactams, are degraded by ß-lactamases. Herein, we describe the synthesis and studies of a dual drug conjugate (1) of a siderophore linked to a cephalosporin with an attached oxazolidinone. The cephalosporin component of 1 is rapidly hydrolyzed by purified ADC-1 ß-lactamase to release the oxazolidinone. Conjugate 1 is active against clinical isolates of Acinetobacter baumannii as well as strains producing large amounts of ADC-1 ß-lactamase. Overall, the results are consistent with siderophore-mediated active uptake, inherent activity of the delivered dual drug, and in the presence of ß-lactamases, intracellular release of the oxazolidinone upon cleavage of the cephalosporin to allow the freed oxazolidinone to inactivate its target. The ultimate result demonstrates that Gram-positive oxazolidinone antibiotics can be made to be effective against Gram-negative bacteria by ß-lactamase triggered release.

Methodology for Monobactam Diversification: Syntheses and Studies of 4-Thiomethyl Substituted ß-Lactams with Activity against Gram-Negative Bacteria, Including Carbapenemase Producing Acinetobacter baumannii.

Bromine induced lactamization of vinyl acetohydroxamates facilitated syntheses of monocyclic ß-lactams suitable for incorporation of a thiomethyl and extended functionality at the C(4) position. Elaboration of the resulting substituted N-hydroxy-2-azetidinones allowed incorporation of functionalized α-amino substituents appropriate for enhancement of antibiotic activity. Evaluation of antibacterial activity against a panel of Gram-positive and Gram-negative bacteria revealed structure-activity relationships (SAR) and identification of potent new monobactam antibiotics. The corresponding bis-catechol conjugate, 42, has excellent activity against Gram-negative bacteria including carbapenemase and carbacephalosporinase producing strains of Acinetobacter baumannii, which have been listed by the WHO as being of critical concern worldwide.

Targeted Antibiotic Delivery: Selective Siderophore Conjugation with Daptomycin Confers Potent Activity against Multidrug Resistant Acinetobacter baumannii Both in Vitro and in Vivo.

In order to address the dire need for new antibiotics to treat specific strains of drug resistant Gram-negative bacterial infections, a mixed ligand analog of the natural Acinetobacter baumannii selective siderophore, fimsbactin, was coupled to daptomycin, a Gram-positive only antibiotic. The resulting conjugate 11 has potent activity against multidrug resistant strains of A. baumannii both in vitro and in vivo. The study also indicates that conjugation of siderophores to "drugs" that are much larger than the siderophore (iron transport agent) itself facilitates active uptake that circumvents the normal permeability problems in Gram-negative bacteria. The results demonstrate the ability to extend activity of a normally Gram-positive only antibiotic to create a potent and targeted Gram-negative antibiotic using a bacterial iron transport based sideromycin Trojan horse strategy.

Studies at the ionizable position of cephalosporins and penicillins: hydroxamates as substitutes for the traditional carboxylate group.

Classically, ß-lactams need an ionizable group to potentiate antibacterial activity. Sets of cephalosporins and penicillins featuring different substituted hydroxamates in place of the traditional carboxylate group have been synthesized and tested for antibiotic activity. Many of the compounds exhibited anti-bacterial activities with notable MIC values in the range of 6-0.2 µM.

Alternate "Drug" Delivery Utilizing ß-Lactam Cores: Syntheses and Biological Evaluation of ß-Lactams Bearing Isocyanate Precursors.

The synthesis of a small set of ß-lactams containing isocyanate precursors is described. The release of the isocyanate precursor in model hydrolysis experiments was substantiated by trapping experiments, thus confirming that ß-lactams can be designed that are capable of releasing alternatively reactive species. Preliminary biological assessments are also briefly discussed.

PATIENT-REPORTED OUTCOMES IN RARE LYSOSOMAL STORAGE DISEASES: KEY INFORMANT INTERVIEWS AND A SYSTEMATIC REVIEW PROTOCOL.

OBJECTIVES: To investigate the use, challenges and opportunities associated with using patient-reported outcomes (PROs) in studies with patients with rare lysosomal storage diseases (LSDs), we conducted interviews with researchers and health technology assessment (HTA) experts, and developed the methods for a systematic review of the literature. The purpose of the review is to identify the psychometrically sound generic and disease-specific PROs used in studies with patients with five LSDs of interest: Fabry, Gaucher (Type I), Niemann-Pick (Type B) and Pompe diseases, and mucopolysaccharidosis (Types I and II). METHODS: Researchers and HTA experts who responded to an email invitation participated in a telephone interview. We used qualitative content analysis to analyze the anonymized transcripts. We conducted a comprehensive literature search for studies that used PROs to investigate burden of disease or to assess the impact of interventions across the five LSDs of interest. RESULTS: Interviews with seven researchers and six HTA experts representing eight countries revealed five themes. These were: (i) the importance of using psychometrically sound PROs in studies with rare diseases, (ii) the paucity of disease-specific PROs, (iii) the importance of having PRO data for economic analyses, (iv) practical and psychometric limitations of existing PROs, and (v) suggestions for new PROs. The systematic review has been completed. CONCLUSIONS: The interviews highlight current challenges and opportunities experienced by researchers and HTA experts involved in work with rare LSDs. The ongoing systematic review will highlight the experience, opportunities, and limitations of PROs in LSDs and provide suggestions for future research.

Development of a Telephone Interview Version of the Chedoke-McMaster Stroke Assessment Activity Inventory.

Purpose: To develop a telephone version of the Chedoke-McMaster Stroke Assessment Activity Inventory (CMSA-AI) and estimate the test-retest reliability, interrater reliability (between participant and proxy), and construct validity of the scores for individuals with stroke. Methods: Adults with stroke and their caregivers or proxies were included. Participants were assessed with the CMSA-AI at discharge from a stroke rehabilitation unit and interviewed using the telephone version (TCMSA-AI). Two months after discharge, participants were evaluated with the CMSA-AI and interviewed over the phone using the TCMSA-AI on two occasions 2-3 days apart. Proxies were interviewed with the TCMSA-AI within another 2-3 days. Results: The mean age of the 53 participants with stroke was 62 years; 59% were male; 43% had right-side hemiparesis; 42 completed follow-up interviews; and 18 had proxies who also participated. Test-retest reliability showed an intra-class correlation coefficient of 0.98 (95% CI: 0.96, 0.99) for the total score, 0.96 (95% CI: 0.91, 0.98) for the Gross Motor Function Index, and 0.96 (95% CI: 0.91, 0.98) for the Walking Index, and an interrater reliability (between participant and proxy) of 0.75 (95% CI: 0.28, 0.90) for total score. Spearman's rho correlation between CMSA-AI and TCMSA-AI total scores was 0.62 (lower-sided 95% CI: 0.42) at discharge and 0.90 (lower-sided 95% CI: 0.82) at 2 months after discharge. Correlations between the change scores of the CMSA-AI and TCMSA-AI were 0.50 or lower. Conclusion: There is potential for remote evaluation of the functional mobility of individuals with stroke in research and clinical settings.

Objectif : élaborer une version téléphonique de l'inventaire des activités post-AVC Chedoke-McMaster (CMSA­AI) et estimer la fiabilité de test-retest, la fiabilité interévaluateurs (entre le participant et le mandataire), ainsi que la validité de construit de l'évaluation. Méthode : des adultes victimes d'un AVC ont été évalués à l'aide du CMSA­AI lors de leur congé d'une unité de réadaptation post-AVC et interviewés par téléphone au moyen de la version téléphonique (TCMSA­AI). Deux mois après leur congé, les participants ont été évalués à l'aide du CMSA­AI et interviewés au téléphone à l'aide du TCMSA­AI à deux ou trois jours d'intervalle. Les mandataires ont été interviewés à l'aide du TCMSA­AI dans les deux à trois jours suivants. Résultats : parmi les 53 participants victimes d'un AVC, l'âge moyen était de 62 ans; 59% étaient des hommes; 43% souffraient d'une hémiparésie du côté droit; 42 ont répondu aux entrevues de suivi; et 18 avaient des mandataires qui ont également participé. En ce qui concerne la fiabilité de test-retest, un coefficient de corrélation intraclasse (intervalle de confiance de 95%) de 0,98 (0,96­0,99) a été calculé pour la note totale, de 0,96 (0,91­0,98) pour l'index de motricité globale et de 0,96 (0,91­0,98) pour l'index de marche. Quant à la fiabilité interévaluateurs (entre le participant et le mandataire), le coefficient mesuré était de 0,75 (0,28­0,90) pour la note totale. La corrélation (rho) de Spearman des notes totales CMSA­AI et TCMSA­AI s'élevait à 0,62 (limite de confiance unilatérale inférieure de 95%=0,42) au congé et de 0,90 (0,82) deux mois après le congé. Les corrélations des variations CMSA­AI et TCMSA­AI étaient de 0,50 ou moins. Conclusion : l'évaluation à distance de la mobilité fonctionnelle des victimes d'un AVC présente un potentiel en contextes clinique et de recherche.

A knowledge translation intervention to enhance clinical application of a virtual reality system in stroke rehabilitation.

BACKGROUND: Despite increasing evidence for the effectiveness of virtual reality (VR)-based therapy in stroke rehabilitation, few knowledge translation (KT) resources exist to support clinical integration. KT interventions addressing known barriers and facilitators to VR use are required. When environmental barriers to VR integration are less amenable to change, KT interventions can target modifiable barriers related to therapist knowledge and skills. METHODS: A multi-faceted KT intervention was designed and implemented to support physical and occupational therapists in two stroke rehabilitation units in acquiring proficiency with use of the Interactive Exercise Rehabilitation System (IREX; GestureTek). The KT intervention consisted of interactive e-learning modules, hands-on workshops and experiential practice. Evaluation included the Assessing Determinants of Prospective Take Up of Virtual Reality (ADOPT-VR) Instrument and self-report confidence ratings of knowledge and skills pre- and post-study. Usability of the IREX was measured with the System Usability Scale (SUS). A focus group gathered therapist experiences. Frequency of IREX use was recorded for 6 months post-study. RESULTS: Eleven therapists delivered a total of 107 sessions of VR-based therapy to 34 clients with stroke. On the ADOPT-VR, significant pre-post improvements in therapist perceived behavioral control (p = 0.003), self-efficacy (p = 0.005) and facilitating conditions (p =0.019) related to VR use were observed. Therapist intention to use VR did not change. Knowledge and skills improved significantly following e-learning completion (p = 0.001) and was sustained 6 months post-study. Below average perceived usability of the IREX (19th percentile) was reported. Lack of time was the most frequently reported barrier to VR use. A decrease in frequency of perceived barriers to VR use was not significant (p = 0.159). Two therapists used the IREX sparingly in the 6 months following the study. Therapists reported that client motivation to engage with VR facilitated IREX use in practice but that environmental and IREX-specific barriers limited use. CONCLUSIONS: Despite increased knowledge and skills in VR use, the KT intervention did not alter the number of perceived barriers to VR use, intention to use or actual use of VR. Poor perceived system usability had an impact on integration of this particular VR system into clinical practice.