Hannoversch Mã¼nden, Germany

Paresthesia-free Peripheral Nerve Field Stimulation for Trigeminal Neuralgia (FreeST Trial)

Background: Peripheral Nerve Field Stimulation (PNFS) has been utilized for the treatment of facial pain for around 60 years, and the commercial devices needed to deliver PNFS have been available for around 30 years. The safety and efficacy of the procedure has been demonstrated by various uncontrolled observational studies. It serves as a part of daily neurosurgical practice for selected patients in UHN Toronto Western Hospital. This therapeutic modality involves subcutaneous implantation of electrodes in the vicinity of trigeminal nerve branches and application of electrical current using a permanently implanted pulse generator (IPG). Similar to other forms of neuromodulation, PNFS is non-ablative, reversible, adjustable and associated with a relatively low risk of severe complications. A meta-analysis of paresthesia-inducing (PI) PFNS studies in the literature revealed a treatment efficacy of 75% decrease in VAS scores (mean difference: -6.32 out of 10) with PNFS utilization for facial pain. (PMID: 35180702) Study design: Patients who underwent a successful unilateral PNFS implantation surgery (trial and permanent implantation) for a facial pain syndrome as a standard of care treatment, will be screened for inclusion after permanent implantable pulse generator (IPG) implantation. Upon consent, the investigators will set up participants' IPG to deliver stimulation with parameters tested during the trial period (paresthesia-inducing parameters) for 2 weeks. The participants will come back to hospital at postoperative week 2 and will be randomized (1:1 ratio) between the two arms of the study (Group 1= sham, Group 2= paresthesia-free (PF) stimulation). Each participant will consecutively experience all two stimulation groups by 2-week periods in a crossover design. Both participants and clinical investigators that will assess the pain will be blind during the study period (between postoperative week 2 and 6). After 6 weeks, the treatment arms will be merged and all the participants will receive any stimulation parameter that they feel more benefit from ("best" parameter). Outcomes will be assessed 6 and 12 months post-operatively.

Relieving Chronic Pain in Older Adults with Transcranial Direct Current Stimulation

Rationale : Chronic pain is the leading cause of disability and affects a large number of seniors. Transcranial direct current stimulation (tDCS), which provides non-invasive stimulation of the brain, is a promising avenue for relieving pain that is refractory to traditional treatments. To date, however, its clinical efficacy has yet to be confirmed in the elderly. Objectives : The primary objective of this study is to determine, in a healthcare setting, the effectiveness of actual tDCS in reducing pain compared with placebo tDCS. Secondary objectives are to assess the effect of tDCS on pain-related interference and the relationship between the response to tDCS and the integrity of pain control systems (descending pathways controlling pain circuits). Methods : This is a multicenter randomized controlled trial with parallel groups (real tDCS vs. placebo) blinded to participants, assessors and tDCS providers. The real tDCS group will receive a daily 20-minute session of tDCS (current intensity = 2 mA), for 5 consecutive days, while the placebo tDCS group will receive an equivalent treatment, but the current will be stopped after the first 30 seconds. The study will take place in 5 rehabilitation clinics in 3 Quebec regions: Sherbrooke (n=1), Quebec City (n=2), Montreal (n=2). One hundred and fifty (150) seniors aged 65 years or older with chronic (> 6 months), moderate to severe musculoskeletal pain will be recruited (50 participants/region). Follow-ups will take place at 1 week and 3 months post-treatment. The primary dependent variable is pain intensity (numerical scale from 0 to 10). Secondary variables will be measured using standardized and validated questionnaires: 1) pain-related interferences (physical function, mood, quality of life) and 2) perception of post-TDCS changes. Neurophysiological measures (pain control pathways), i.e., the integrity of corticothalamic and corticospinal projections will be tested by diffusion MRI and transcranial magnetic stimulation. Anticipated results: Our hypotheses are that (i) real tDCS will be more effective in reducing pain intensity than placebo tDCS at 1 week post-treatment. This reduction in pain will be maintained at the 3-month post-treatment follow-up of real tDCS. (ii) Real tDCS will be more effective than placebo treatment in reducing pain interference with physical function, mood and quality of life. Perceived improvement with the treatment received will also be greater for real tDCS. (iii) Individuals with stronger cortico-thalamic and corticospinal projections in pre-tDCS will be more relieved by actual tDCS than those with less strong projections. Ultimately, this study will allow us to evaluate the effectiveness of tDCS in the care setting for the relief of chronic musculoskeletal pain in the elderly and to identify those individuals most likely to respond to this type of treatment based on potential biomarkers related to the integrity of the pain control system.

Deep Brain Stimulation for Refractory Trigeminal Neuralgia with a Pontine Lesion

Mirvetuximab Soravtansine With Bevacizumab Versus Bevacizumab as Maintenance in Platinum-sensitive Ovarian, Fallopian Tube, or Peritoneal Cancer

Mirvetuximab Soravtansine (MIRV) is an investigational antibody drug conjugate designed to selectively kill cancer cells. The antibody (protein) part of MIRV targets tumors by delivering a cell-killing drug to the tumor cells carrying a tumor-associated protein called folate receptor alpha (FRα). It is being developed as maintenance therapy for the treatment of subjects with recurrent platinum-sensitive, highgrade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression. Patients must have confirmation of FRα positivity by the Ventana FOLR1 Assay.

Prospective Pilot ATOMS vs AUS

Chemotherapy for the Treatment of Patients With Newly Diagnosed Very Low-Risk and Low Risk Fusion Negative Rhabdomyosarcoma

PRIMARY OBJECTIVES: I. To evaluate the failure free survival (FFS) of patients with very low-risk (VLR) rhabdomyosarcoma (RMS) (fusion negative [FN], stage 1, clinical group [CG] I, MYOD1 wildtype [WT], TP53 [WT]) when treated with 24 weeks of vincristine and dactinomycin (VA). II. To evaluate the FFS of patients with low-risk (LR) RMS (FN, stage 1 CG II, or stage 2 CG I/II or CG III [orbit only], MYOD1 WT, TP53 WT) when treated with 12 weeks of vincristine, dactinomycin and cyclophosphamide (VAC) followed by 12 weeks of VA. SECONDARY OBJECTIVES: I. To evaluate the overall survival (OS) of patients with VLR RMS treated with 24 weeks of VA. II. To evaluate the OS of patients with LR RMS treated with 12 weeks of VAC followed by 12 weeks of VA. III. To demonstrate the feasibility of central molecular risk stratification of patients with newly diagnosed RMS in the context of a prospective clinical trial. EXPLORATORY OBJECTIVES: I. To collect blood and tissue samples for banking at baseline, during treatment, at the end of therapy, and at the time of progression to bank for future research. II. To describe the methylation array profile of patients with fusion negative, low-risk rhabdomyosarcoma. III. To describe the outcomes of patients with VLR or LR RMS and MYOD1 or TP53 mutations treated with intensified therapy. OUTLINE: Patients are assigned to 1 of 2 regimens based on clinical features. Patients with positive mutation status are transitioned to a third regimen, Regimen M. REGIMEN VA: Patients with VLR RMS receive vincristine intravenously (IV) on day 1 of each cycle and days 8 and 15 of cycles 1, 3, 5, and 7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). REGIMEN VAC/VA: Patients with LR RMS receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 1-3. Patients also receive dactinomycin IV over 1-5 minutes or 10-15 minutes and cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 5-7 and dactinomycin IV over 1-5 minutes or over 10-15 minutes on day 1 of each cycle. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with MYOD1 or TP53 mutated tumors transition to Regimen M at cycle 2 (if mutation status is determined to be positive at week 3) or cycle 3 (if mutation status is determined to be positive after week 3). Patients may also undergo radiation therapy at cycle 5. REGIMEN M: Patients receive vincristine IV on day 1 of each cycle and days 8 and 15 of cycles 2-4, 7-8, and 11-12 and dactinomycin IV over 1-5 minutes or 10-15 minutes on day 1 of cycles 2-5 and 8-14. Patients also receive cyclophosphamide IV over 60 minutes on day 1 of each cycle. Treatment repeats every 21 days for 12-13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo radiation therapy at cycle 5. Patients undergo computed tomography (CT) scan, magnetic resonance imaging (MRI), bone scan, positron emission tomography (PET) scan and tumor biopsy throughout the study.

Training Intervention and Program of Support (TIPS): Fostering Family-centred Telehealth in Pediatric Rehabilitation

INTRODUCTION Timely access to family-centred services for children with disability and their families is crucial to support their development and well-being. Currently, many children face long wait times (i.e., up to 2 years) and organizational, geographic and/or cultural barriers to services. Lack of access can lead to negative developmental, health and social consequences for children (e.g., suboptimal development, academic difficulties) and their families (e.g., stress). The COVID-19 pandemic further exacerbated these issues, as rehabilitation support for children was lost, increasing parental mental health burden (e.g., increased stress, depression). To minimize the negative impacts of these service disruptions, therapists were required to shift to telehealth service delivery. Evidence exists of the efficacy of telehealth to improve service access, children's outcomes, and family satisfaction and acceptability, supporting the integration of telehealth as a key element of Family Centred Services (FCS) in pediatric rehabilitation. Telehealth can be defined as 'any asynchronous or real time clinical intervention provided remotely by therapists to patients and/or caregivers. It has been recognized as an important alternative for families living in underserved or remote areas. However, some families in well-served urban locations also prefer the convenience of telehealth over in-person visits (e.g., less travel time, schedule flexibility). Prior to the pandemic, a systematic review of pediatric rehabilitation telehealth randomized controlled trials supported the efficacy of such interventions for a wide range of outcomes and diverse populations. Further publications demonstrated the efficacy and acceptability of telehealth, further supporting its integration into comprehensive FCS models. The established efficacy of telehealth highlights a critical knowledge-to-practice gap. Before the pandemic, the adoption of telehealth was low in pediatric rehabilitation. In an international survey conducted in August 2019 (1,133 pediatric therapists from 76 countries), 3.9% were using telehealth; a follow-up survey with a subsample in May 2020 highlighted that 70.1% had adopted telehealth. Many reported doing so without prior experience, and lacked confidence, knowledge, and training in effective intervention strategies. When asked what support was required to implement telehealth, training was by far the most frequently cited - and included communication skills with families over the phone and internet, safe and effective use of platforms, reliable assessment, and intervention strategies with children of various ages and health conditions. Although therapists' knowledge, skills and attitudes toward telehealth can improve with time and experience, training and support are required for behavioural changes to occur. Unfortunately, there is a paucity of evidence related to how personal and contextual factors may influence telehealth training and support. Targeting therapists' knowledge, skills, and attitudes, associated with their intention to adopt telehealth, and their professional role within FCS, appear vital to the implementation of telehealth. For the purposes of this study, family-centred telehealth (FCT) is defined as pediatric rehabilitation which uses family-centred care (FCC) practices while working with families remotely. FCC is recognized as a best practice approach in pediatric rehabilitation. Described as a partnership approach, FCC is based on the belief that the child's well-being and care needs are best supported within the family context through effective family-provider collaborations. Moreover, FCC's central tenet is the assumption that the processes of care delivery are as important to the child and family outcomes as the specific characteristic of the clinical intervention delivered. It is characterized by practices that promote clinical flexibility, respect and dignity for families' perspectives, knowledge, strengths and characteristics, effective information sharing (general and specific), partnership and collaboration between parties to support decision making, and coordinated and comprehensive care delivery. Furthermore, FCC occurs in the therapeutic environment that optimizes the development of a collaborative family-provider relationship, where parents are active participants in collaborative goal-setting, therapy planning, implementation, and evaluation, and where activities are integrated within daily routines and contexts (e.g., home and community). Compared to more traditional service delivery methods, telehealth offers opportunities to enhance FCC practices. It provides alternate, convenient, and flexible ways to partner with families, respecting their characteristics (e.g., single parenting) and constraints (e.g., geographical, temporal, financial), allows real-time knowledge acquisition and information sharing about the child within their contexts, supports family decision making and parents' psychosocial well-being (i.e., decreasing anxiety, stress, and depression), and has been recognized as an important addition to comprehensive care coordination and service delivery. Considerable momentum exists supporting the uptake of FCT and fostering its ongoing sustainable use within accessible and supportive services for the families of children with disability following the pandemic. Pediatric rehabilitation therapists, service managers, professional associations, policy makers, and patients alike are calling for resistance to "returning to normal", and instead are requesting help to sustain telehealth as part of the FCS continuum of care. The proposed study aims to evaluate the implementation and effectiveness of a Training Intervention and Program of Support (TIPS) to enhance the adoption of FCT in pediatric rehabilitation centres across Canada. RESEARCH QUESTIONS AND OBJECTIVES The main research question is: Can TIPS be co-adapted to enhance the adoption of FCT interventions by therapists working in different contexts? Primary objectives are to: 1. Evaluate the implementation with regard to: 1. Therapists' intention to adopt vs actual adoption of FCT practices 2. Fidelity of FCT practices Secondary objectives are to: 2. Document the contextual variations required to co-adapt the TIPS to meet each site's needs 3. Identify factors influencing FCT adoption and fidelity 4. Evaluate the effectiveness with regards to: 1. Service wait-times 2. Families' perception of service quality (i.e., family-centredness) 3. Changes in service delivery 5. Evaluate the costs (and possible cost savings) related to increased use of FCT The primary hypotheses are that therapists' intention to adopt FCT and fidelity of FCT practices will (i) improve minimally in the short term (i.e., one-month post-TIPS), yet (ii) will improve significantly post-implementation of TIPS, (iii) while actual adoption and engagement will fluctuate over time, across sites and therapists, and will depend on therapist-, client-, organizational- and system-factors. For the secondary hypotheses, the investigators expect that, for sites with the largest effect change in intention to adopt and fidelity of FCT practices, (iv) wait times will significantly decrease and (v) families' perceptions of service quality will significantly improve post-implementation of TIPS. METHODS Implementation science conceptual framework The study framework builds on implementation science frameworks that aim to accelerate the translational research pipeline, bridging the current knowledge-to-practice gap. Specifically, the Consolidated Framework for Implementation Research (CFIR) will guide the identification of factors influencing adoption of FCT and will help engage leaders in participating sites in adapting the TIPS to their own contextual drivers, while maintaining the FCT key ingredients. A hybrid design will be used, as recommended when the traditional research pipeline efficacy-effectiveness-implementation is too time consuming, and considered unethical, failing to adequately respond to the urgency of the expressed need. A Type 3 hybrid design was chosen, primarily focusing on implementation indicators, while also collecting some effectiveness outcomes, with comparative assessments occurring at the therapist, service and/or family level. This design is recommended when there is: 1) momentum for implementation within the health care system; 2) strong face validity and indirect evidence for the clinical intervention and implementation strategy to support generalizability; 3) minimal risk associated with the clinical intervention and the implementation strategy; and 4) evidence of feasibility for the implementation strategy and support in the clinical and organization context under study. The present study meets all these criteria, as there is: 1) momentum for the sustainability of telehealth implemented during and following the COVID-19 pandemic; 2) strong and growing evidence of effectiveness for telehealth, as well as for training and support knowledge translation strategies; 3) promising results from our studies supporting the safe use of TIPS to implement FCT; and 4) well-established evidence of implementation feasibility of telehealth. Design A 4-year pan-Canadian stakeholder-oriented, mixed-method implementation-effectiveness design will be used. TIPS will be implemented in all sites in a same region during the same month, and sequentially introduced across all regions, 2 months apart. An interrupted time series (ITS) was selected to assess primary implementation outcomes (obj. 1), as recommended for research in real-world settings. An ITS consists of observing the same dependent variables over time, with a break in the series of observations corresponding to the introduction of an intervention. If the intervention is effective, a change in the series' pre- and post-intervention averages will be observed. Intervention Informed by implementation strategies recognized as effective in pediatric rehabilitation, TIPS is a multifaceted intervention, comprised of the following components: 1) a 10-hour intensive training program offered to participating therapists at each site over a one-month period, which includes 4 hours of self-paced learning modules and a 6-hour mandatory interactive webinar; and 2) an 11-month program of support which is composed of monthly mentoring meetings at each site led by the local therapist champion, and a national virtual community of practice (vCoP) facilitated by 3 national knowledge brokers (KBs) - an occupational therapist (OT), a physiotherapist (PT) and a speech-language pathologist (SLP) - experienced in FCT in pediatric rehabilitation, offered simultaneously to all participating therapists across Canada. The TIPS self-paced learning modules are informed by contemporary frameworks of FCC, and relevant family-oriented services. More specifically, they will address the key ingredients associated with the FCT processes and provide practice examples. These key ingredients include: 1) service operations (e.g., service coordination, organization and structures, care planning and goal setting), 2) participatory (e.g., parent engagement, focus on individual family's needs) and 3) relational (e.g., active listening, respect, empathy, reciprocity) caregiving, 4) communicating general (e.g., access to current and future services, parent groups) and specific (e.g., co-morbidities associated with child's condition) information, as well as 6) coaching (e.g., parent task analysis, caregiver implemented strategies with natural contexts, solution-focused coaching)., and 7) engagement strategies. Multimedia (e.g., videos, presentations) content for the asynchronous training modules will be developed by several members of the study team, through ongoing consultation with experts in the field, using education course creation software. The curriculum will then be uploaded to a password protected online platform, for which a unique username and password will be required. Knowledge acquisition, based on the specified learning objectives and the key messages targeted in each training module, will be assessed through short pedagogical quizzes. Completion of the asynchronous modular training and knowledge assessment will be recommended prior to undertaking the synchronous webinar(s). A 6-hour synchronous webinar component will also be delivered by members of the research team and the 3 national KBs. These webinars will engage therapists in discussion (e.g., case studies), interactive activities (e.g., role play, simulations) to build their critical thinking on how to implement these practices in their context. The webinar content will be adapted for each site in consultation with the Local Leadership Team, (i.e., the site manager, a therapist champion, and a parent/patient partner). This co-adaptation phase will ensure content is tailored to individual site contexts (e.g., engagement practices, site clinical goal-setting processes, service coordination as per team procedures), learner-centred and clinically relevant. The FCT interventions can be implemented using a variety of technologies, including various videoconferencing options, online platforms, websites, email systems, and even telephone. Therapists will be encouraged to consider various asynchronous and real-time technologies, which best respond to families' needs and preferences, and those approved by their organizations. The research team will refrain from recommending specific technologies. There is no prescribed frequency or duration for the FCT interventions; therapist participants will work with families according to their goals and preferences, and organizational policies. Finally, a program of support will be offered for the remaining year via monthly videoconference mentoring meetings, and access to the vCoP also housed on the password-protected platform. Monthly meetings will focus on sharing site-specific successes, challenges, proposing solutions and reporting results, as well as sharing useful and practical resources. The vCoP will be used to canvas for solutions to address challenges at a national level, share successes, discuss specific cases for guidance, feedback and input, and to share useful tips and tricks, and resources. The structure of our vCoP was informed by previous work related to vCoP and KBs (i.e., individuals with content and leadership expertise, who foster information sharing and research evidence use). Study Settings Participating sites are publicly funded organizations providing outpatient pediatric rehabilitation services to children aged 0-12 years with or at risk of disability. 'Disability' is used inclusively to recognize all medical diagnoses resulting in limitations in function, such as cerebral palsy and autism spectrum disorder. The term "at risk" includes children presenting with delayed development who may not yet have a diagnosis but have clear functional limitations and qualify for rehabilitation services. The upper age limit of 12 years was chosen, as best practices regarding transition of care suggest that different relationships should be fostered with adolescents over 12 years. The 20 participating sites selected based on various characteristics (e.g., populations, size, services provided, catchment area) thought to influence outcomes, the effect of which will be explored, are clustered into 6 provincial regions. TIPS will be sequentially introduced (i.e., 2 months apart) to each of the regions. To limit the risk of contamination, TIPS will be introduced to all sites in the same region in the same month. However, training will be conducted on a site-by-site basis to create team cohesion. The 2-month interval for implementation between regions gives flexibility for organizing implementation and data collection activities based on site availability and vacation schedules. Study participants Participants will belong to at least one of the following categories: 1. Managers (n=20, one per site): Person responsible for rehabilitation services at the site, or their delegate. The managers were identified during the selection of study sites. As members of the Local Leadership Team, managers participate in the co-adaptation of TIPS to their site and could be called upon to contribute to their site's monthly mentoring meetings. They will aid in the recruitment of therapists, parents, a therapist-champion, and a parent-partner for their site. 2. Therapists (n=600 with 50% anticipated response; n=300): PTs, OTs, SLPs providing outpatient pediatric rehabilitation services to children aged 0-12 years in each site, recruited via the managers and interested in utilizing FCT. Therapists will participate in the TIPS program, complete data collection instruments as prescribed, and aid in the recruitment of parents. 3. Parents (n=20/therapist with an anticipated response rate of 33%; n=2000 families per assessment time point): One-time data collection will be undertaken with two samples (one pre-, the other post-implementation) of parents or caregivers who received services (either in-person, virtually, or both) from at least one participating therapist in the previous 3 months. 4. Therapist-champion (n=20, one per site): Therapist selected based on their telehealth experience and on peer recognition within their organization. Therapist-champions are members of the Local Leadership Team participating in the co-adaptation of TIPS to their site and will oversee the monthly mentoring meetings. 5. Parent/patient-partner (n=20, one per site): Parent/patient-partners will primarily be recruited from family, parent or patient advisory committees at the participating sites or, in the absence of such initiatives, from regional, provincial, or national patient engagement programs. As members of the Local Leadership Team, parent/patient-partners participate in the co-adaptation of TIPS to their site and could be called upon to contribute to their site's monthly mentoring meetings. Recruitment procedures will be flexible and will be adapted to the preferences, policies and procedures at each site. The recruitment of participants may be undertaken by email, sent directly to the potential participant by the research team (ex: therapists) or by the manager or therapist on behalf of the research team (e.g., parents). Data collection Implementation data will be collected at least three times during each study period: pre-, per-, and post-implementation of TIPS. The additional data collection time point at 1 month per-TIPS will allow the documentation of the short-term impact of TIPS. Statistical analysis models will account for the inequivalent time intervals across study periods. A pre-post design was chosen to measure the intervention effectiveness outcomes and costs, using easily accessible service indicators and questionnaires administered to parents (obj. 4 + obj. 5), as per Type 3 hybrid designs. Qualitative data will be collected during (i.e., recording of monthly local mentoring meetings, and other meetings (as deemed appropriate by the therapist champion), in the vCoP discussions (as threads) and after (i.e., interviews with managers, therapist-champions, therapists and families) the implementation of TIPS. Sample size justification Number of sites: A total of 20 sites across 8 Canadian provinces (grouped in 6 regions for the roll out of the intervention) are included in the study. Whenever possible, at least 3 sites per province were included to ensure sample diversity and enable the exploration of the provincial health systems' effects on the outcomes as well as to estimate site-related variations in outcomes. Five regions will include sites in the same province, while one region will consist of sites from 3 provinces where only one rehabilitation program was available. Number of therapists: At the therapist level, implementation outcomes will be assessed 3 times during each period (pre-, per-, and post-TIPS implementation). Assuming an autocorrelation of repeated measures of r<0.3, data collected from 300 therapists will provide >80% power to detect moderate effect sizes (Cohen's d ≥ 0.5), employing a first-order autoregressive segmented regression model and a global type I error level of 5% accounting for multiplicity of outcome assessments (Sidak's correction). Number of families: With a minimum expected sample size of 20 families per therapist being assessed pre- and/or post-TIPS implementation, statistical power will be >90% to detect even small effect-sizes (0.1< Cohen's d < 0.3) for the effectiveness outcomes i.e., change in wait times and change in families' perceptions of service quality. Data analysis To evaluate the implementation (obj. 1), longitudinal mixed modeling accounting for and considering potential methodological issues associated with ITS analysis (e.g., auto-correlation, time-varying confounders) will be used to analyse implementation indicators (i.e., ADOPT-VR (Assessing Determinants of Prospective Take-up of Virtual Reality), therapists' self-reported FCT frequency, FCT fidelity self-perceived checklist, PRIME-SP). Changes will be documented short term (i.e., one month after the introduction of the TIPS) and long term (i.e., at the end of the TIPS, 12 months after its introduction). Models will be covariate-adjusted to reduce potential confounding bias, including the therapists' characteristics (e.g., gender, years of experience) and site characteristics (e.g., service provided, geography, general patients characteristics) to estimate associations of key explanatory variables alongside TIPS. Secondary analyses will explore heterogeneity in changes of outcome measures across genders, sites, therapists, and health jurisdiction levels. To document site-specific co-adaptations of TIPS (obj. 2), proposed adaptations and decisions made by Local Leadership Team committee members will be documented during the discussion group in real-time on the logic model and in the TIPS training materials. To identify factors influencing adoption and fidelity (obj. 3), recordings of monthly therapists' meetings, potential meetings between KBs and therapist champions) will be analyzed thematically, using a deductive-inductive approach guided by the Consolidated Framework for Implementation Research (CFIR) domains. Guided by an exploratory mixed methods approach, qualitative findings will be integrated with quantitative questionnaire results to further detail inferences. To evaluate effectiveness (obj. 4) via estimated change in wait times (pre vs post), the confounder-adjusted analysis using generalized linear mixed effect models (GLMM) will employ a log-link function to account for the typically right-skewed nature of time data. Estimated fixed (intervention) effects for the effectiveness outcomes will be reported with Sidak-corrected 95% confidence intervals. To evaluate effectiveness via MPOC-20 (Measure of Process of Care - 20 questions) data, GLMM with nested random effects (families within therapists within sites) will be employed to control for the correlated nature of the data (i.e., the possibility that families have responded once or twice to the MPOC-20) and to account for therapist and site cluster effects. Analyses will be conducted for each of the five MPOC-20 domains and controlled for the same confounding variables described in the analysis for objective 1, as well as for family level variables (e.g., sociocultural background, child's age and gender). Video-recorded interview data from therapists, managers, and parents will be analysed thematically using an inductive approach to better understand the breadth and depth of changes to pediatric rehabilitation service delivery, according to various stakeholder perspectives. Integration of quantitative and qualitative data using the aforementioned explanatory approach will allow us to uncover the plethora of effects of FCT on pediatric rehabilitation service delivery. Total system costs related to the implementation of the TIPS, as well as the costs per participating therapist and per site, accounting for different organizational characteristics, will be calculated. Relative cost, an estimation of costs per client seen by therapist, and incremental ratios (i.e., change in costs to use the TIPS divided by change in the primary implementation indicators and secondary effectiveness outcomes) will also be calculated. Finally, societal costs, including families' costs and savings, will also be computed. Ethical considerations The research ethics committees overseeing the 20 participating sites will approve this research project and be informed of any potential revisions of the protocol. Informed consent will be sought prior to data collection from participating managers, therapists, and parents. Participants will be assigned a unique identification number for denominalization purposes. Whenever posting content to the vCoP, therapists will be encouraged to use their name to promote open exchanges on the platform, but all users will also have the option of using a pseudonym if they prefer. The implementation of the TIPS (e.g., training, meetings) and all data collection (surveys, vCoP, interviews) will take place entirely online. Secure data collection and management solutions (e.g., REDCap, PIERCE) will be used to collect and store study data on institutional servers. The implementation of TIPS will be gradual across regions, thus ensuring that the sites within the region are ready to participate in the project, taking into consideration institutional challenges such as availability of personnel or timeliness of the implementation of new telehealth modalities. Participants will be informed that study data will not constitute an evaluation of their professional performance. Some concerns are present in the literature that telehealth could increase health inequity and that wealthier families might benefit more from it. This project aims to support the use of FCT interventions with all Canadians families with a child with, or at risk of disability, while considering the interactions between personal, socio-economic, and cultural characteristics, as recommended. The team delivering TIPS is fully bilingual. TIPS and the study's data collection will be available in Canada's two official languages. A pre- and per-implementation consultation process will also be undertaken with First Nations Elders in order to take into account the needs of indigenous communities when delivering TIPS. KNOWLEDGE TRANSFER In addition to the Local Leadership Team and the support provided to therapist champions, patient-oriented principles will be used within an integrated knowledge translation (iKT) approach to collaborate with knowledge users throughout the research process in order to inform research decisions. Specifically, four members of the research team (two parent-partner and two rehabilitation managers) have specifically been involved as knowledge users, and will be part of the study's Steering Committee. Principles for engaging with non-researchers in research will be respected (e.g., reviewing mutual expectations, providing meeting flexibility and clarification opportunities). The impact of the iKT approach will be assessed, using patient and organizational engagement criteria. Expected knowledge translation strategies include the presentation of study and site-specific data via a webinar for each participating site, as well as the publication of study findings via peer-reviewed publications and via public-facing publications on the research team's and project partners' websites, social media, and newsletters. EXPECTED OUTCOMES This study will generate knowledge about how to implement family-centred telehealth and rehabilitation practices, inclusive of all families of children with, or at risk of, disability. The knowledge will be contextualized to support therapists working in varied settings and will contribute to building local capacity to sustain the use of FCT interventions. All training materials will be available across Canada and beyond. By increasing therapists' ability to provide telehealth services, the investigators hope to contribute to the transformation of pediatric rehabilitation service delivery, improve access to services, and foster greater well-being for families of children with, or at risk of, disability.

Using Peripheral Neurostimulation to Improve Work Rehabilitation

Problem and hypotheses: In 2019, the proportion of Canadians aged 55 and over who were employed was 35.9%, the highest rate recorded to date since 1976. Despite their willingness to remain employed, seniors are more prone to work disability and early retirement. Older workers with disabilities are particularly vulnerable to job retention. In Quebec, the average length of absence following a work-related injury is 134 days for workers aged 55 and over, while it is less than 50 days for those aged 15 to 24. This difference can be explained in part by the presence of persistent pain that disproportionately affects older individuals and can significantly impede rehabilitation to work. The indirect costs associated with unemployment and absenteeism of people living with chronic pain were estimated to be $22.5 billion in Canada in 2019. A recent review conducted and published by our team found that strategies to reduce pain are one of the most important elements to consider in enabling workers to remain in the workplace after an episode of musculoskeletal disorder. Exercise plays a central role in chronic pain management and work rehabilitation. However, pain can be a major barrier to physical activity. Therefore, finding ways to reduce pain during and after exercise is essential to facilitate rehabilitation. Peripheral neurostimulation (TENS) - an electrotherapeutic modality that uses an electrical current to depolarize peripheral nerve fibers with electrodes applied directly to the skin - is effective in temporarily relieving pain. It represents an interesting avenue for increasing exercise tolerance associated with exercise in the pain subject. To date, 3 studies have investigated the use of TENS during exercise, all showing positive results. None, however, have yet investigated this strategy (TENS + exercise) in aging workers living with persistent pain. We postulate that telerehabilitation treatments (therapeutic exercises) provided concurrently with actual TENS will be more effective in reducing the biopsychological impacts of pain than the same rehabilitation treatments paired with placebo TENS. Thus, our hypothesis is that the experimental treatment will cause participants to enter a "virtuous circle": the TENS will allow for a punctual reduction of pain and kinesiophobia, which will encourage the realization/resumption of activity and lead to sustained benefits (e.g., physical function, pain, mood). Objectives: The primary objective of this pilot study is to explore the feasibility and acceptability of using real TENS, compared to placebo TENS, as a complementary treatment to a telerehabilitation exercise program, in workers who are off work. The secondary objective is to compare the effect of the two types of intervention (real TENS + exercises vs. placebo TENS + exercises) on clinical outcomes (e.g. pain intensity, functioning in vocational rehabilitation, etc.). Methods and analysis: Design: This project consists of a randomized controlled trial following a quadruple blind design. Participants: The target population is aging workers who are off work due to a musculoskeletal injury. Sampling and recruitment procedures: Participants will be recruited at the ISO-SANTÉ and Physio-Atlas clinics in Sherbrooke, which specialize in work rehabilitation (volunteer, non-probability sampling). The recruitment of individuals will be done through posters and with the help of clinicians who will be invited to talk to patients about the project. Conduct of the study: The purpose of this study is to recruit 24 participants who will take part in an exercise program spread over 3 weeks, with 3 sessions per week. The duration of each session is 30 minutes. The exercise program will be determined by the research team, in collaboration with clinic health professionals, and the exercises will be delivered via the TeraPlus telerehabilitation platform. The TENS (real or simulated) will be worn by participants throughout their telerehabilitation exercises, under the supervision of the student researcher.

A Phase II Trial of Bicalutamide in Patients Receiving Intravesical BCG for Non-muscle Invasive Bladder Cancer

Bladder cancer is the second most common urological cancer after prostate cancer. Non-muscle invasive bladder cancer (NIMBC) is the most common form (~ 75%). The standard treatment involves the use of intravesical instillation of bacillus Calmette-Guérin (BCG). Nonetheless, 30-40% of the patients still relapse or progress. Clinical and laboratory research suggests that medications targeting the androgen receptor, such as bicalutamide, combined with the standard treatment with BCG may decrease the recurrence rate of NMIBC. The study is composed of two cohort A (open-label, around 40 patients) and B (double-blind, with placebo, around 120 patients). In the cohort A, the participants will be randomized to either the treatment with 1) daily intake of 150 mg bicalutamide for 3 months overlapping with the 6 cycles of intravesical instillations of BCG or 2) the standard of care of 6 cycles of intravesical instillation BCG. In the cohort B, the participants will be randomized to either the treatment with 1) daily intake of 150 mg bicalutamide for 3 months overlapping with the 6 cycles of intravesical instillations of BCG or 2) daily intake of 150mg placebo for 3 months + the standard of care of 6 cycles of intravesical instillation BCG. The participation in this trial should last 36 months from the screening visit to the last follow-up visit.

Effects of an Educational Tool on Knowledge and Risk Retention About Epidural Analgesia in Parturients.

Discussing the risk and benefits of an epidural to a laboring woman can be a difficult task. Obtaining consent for the procedure whilst the pain, the anxiety, and the necessity of acting fast because of an active labor are added to the overwhelming quantity of information a laboring woman receive is among the challenges anesthesiologist must face before doing an epidural. The validity of the consent of a labouring women has already been proven in several studies. Indeed, it has been shown by that pain, either mild or severe, has no impact on the retention of epidural risks that have been explained. However, there is a significant variability regarding risk disclosure within different practice settings, particularly with respect to the incidence of serious complications. In studies, knowledge about the epidural and retention of information given at the time of consent remains poor, but could be improved by a learning tool (e.g., video, explanatory leaflet) At the investigators's institution, standardized risks are exposed to the patient during the epidural technique. The five risks mentioned are hypotension, lumbar pain, failure (10%), risk of dura mater puncture (1%) and post-puncture headache as well as severe nerve injury up to paralysis (1/200 000). These risks are checked off on the anesthesia sheet when discussed with the patient. Groupe "before" will be asked about recall of risk and information giving after standard consent counseling. Groupe "after" will be exposed to an informative document explaining the risk as soon as active labour was confirmed. Participants will also have usual consent information standardized by local practice. On post-partum day 1, participants will be asked about the risks exposed at the moment of consent regarding epidural analgesia by means of a questionnaire. The questionnaire distributed to patients contains true and false statement about the epidural and they will be asked about the truth of information. No additional information about the epidural will be disclose to the patients during the questionnaire. Group "before" will also be asked questions about how they would like to receive information concerning epidural and group "after" will be asked about if they appreciate receiving an informative brochure. The informative document will be created by the study team and sent to the anesthesia and obstetrics teams in at study team's hospital for pre-approval. The maternity nurses will be asked to give the document as soon as the patient will be admitted to the ward. Before being recruited, parturient will have to ensure that they had indeed read the document before receiving epidural analgesia. The aim of this before-and-after study is to evaluate the impact of adding an information document available at the admission for active labour on improving the knowledge of patients receiving epidural anesthesia as well as its effectiveness on retention of the risks explained at the time of consent. In addition, one of the sub-objectives is to identify which factors influence risk retention in order to eventually better adapt our pre-epidural counseling.