Kogarah, Australia

Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias

The investigators will perform a registry-based standardized prospective Natural History Study (NHS) in SPAX and related disorders. Participants will be seen annually. At study visits a standardized clinical examination will be performed including application of clinical rating scales (selection of rating scales may vary depending on the individual phenotype and specific genotype); data will be entered into a clinical database (HSP Registry; https://www.hsp-registry.net and ARCA Registry; www.ARCA-registry.org). At all study visits, patients will be asked to donate biosamples; biomaterial collection is optional and participants can elect to participate in sampling of blood, urine, CSF, and/or a skin biopsy. Optionally, additional examinations may be performed including imaging, quantitative movement analysis, neuropsychological examinations, analysis of patient or observer reported outcomes and OMICS analysis to characterize molecular biomarkers. In participants without a genetic diagnosis, next generation sequencing may be performed. Thus this study will establish a model of disease progression and mechanistic evolution in SPAX, which will allow to track and understand selective as well as overlapping dysfunction of the cerebellum and corticospinal tract. In a transatlantic natural history study we will longitudinally validate clinician- and patient-reported, digital and molecular outcomes. In addition, we will improve on existing and develop new outcome parameters that show superior sensitivity to change. These include a novel clinical SPAX composite score, a smartphone mHealth toolbox combining remote assessment of daily living by wearable sensors with app-based patient-entered outcomes (SPAX.app), and multimodal MRI radiomics with an innovative machine learning approach for multisite MRI analysis, including in particular the infratentorial space. Longitudinal validation of targeted fluid biomarker candidates will aslo be an important part.

Evaluation and Treatment of Adhesive Capsulitis Using Non-invasive Neurostimulation Devices

New Clinical Rehabilitation Approach for the Management of Falls Risks

This research program on aging to create Living Lab Sag aims at maintaining older adult's full individual and collective abilities in the Saguenay-Lac-Saint-Jean (SLSJ) region. The need for innovation and creativity aims at optimizing independence, whether for mobility, the ability to take charge of one's health, to remain at home, to have access to services, and to prevent falls in a frail and aging population. Thus, this program includes expert investigators in the areas of health, engineering and computer science, aging, neuropsychology, geriatrics, and rehabilitation/prevention within a multidisciplinary work approach for durable health for older adults in Saguenay. Living Lab Sag will be implemented based on an enriched research program, approved by the CIUSSS SLSJ (CER# 2019-008) and entitled: Development of a new clinical approach in rehabilitation for the care of older adults with a neuro-musculo-skeletal disorder and a risk of falling: Project in partnership between UQAC and the specialized geriatrics services of the CIUSSS-SLSJ. Canada census reports clearly show the demographic aging of the local population. It is predicted that people 65 years and older will comprise about 24% of the population in 2036, in Canada and Quebec. In parallel with this demographic phenomenon, 50% of Canadians live with at least one chronic disability that is often associated with advanced age, as well as with different neurological, orthopedic and cardiopulmonary degenerative diseases. Some diseases affecting the neuro-musculo-skeletal system will lead to physical disability and to a significant functional limitation in terms of balance, mobility and walking and, consequently, to an increase in the risk of falling. Falls have a significant financial effect on healthcare services. Every year, in Quebec, approximately 1/3 of people aged 65 and over will fall and, sadly, some data suggest that 424,000 people will die, worldwide, because of a fall. The present scenario also shows the importance of developing strategies to reduce the weight of falls on the healthcare system, such as the creation of Living Lab Sag where the older adults will be at the heart of the situation. With team's experience in the area, one strategy among others is the early identification of physical-functional factors leading to a fall, despite the presence of other associated extrinsic factors that are also associated with the fall (i.e., multifactor phenomenon). This identification can be realized through neurophysiological measures from valid and reliable biological signals in rehabilitation, that will help determine the neuromuscular responses associated to the level of physical frailty of the individual and his/her fall risk. However, geriatric services in general don't often have access to high-end screening tools that permit an early detection of balance problems and fall risk. Within an innovative action plan, our research program, in partnership with specialized geriatric services and researchers aims to determine the efficiency of new evaluation and intervention methods for the health of the older adults. Since 2019, this programm integrate new measures using various high-end equipment to capture biological signals enabling to perform research with patients from Hospital and patients from Parkinson Association and community local. The mission of this program is to build a new paradigm for this site while being a reference to evaluate balance/mobility and walking problems, better screen frail older adults who are at risk of falling and direct then to personalized therapy. At this time, this work will develop a longitudinal intervention study using OTAGO (PEO) exercise program. The name "OTAGO" is not an acronym, as "Otago" is a region of New Zealand located southwest of the southern island. PEO is defined by a reeducation program for strength and balance at home (or in a rehabilitation center), that is personalized, and based on conclusive data. The PEO was developed by a geriatrician (Dr. Campbell) and his team of physiotherapists in 1997, after many years of research, to identify the risks of falling and the potential interventions that could reduce these risks. The program exists worldwide but has never been tested in Québec. Although there are different fall prevention programs, conclusive data show the more frequent use of OTAGO because of its efficiency to reduce the risk of death and the incidence rate of falls over a period of one year in an aging population. This program also reduces falls by 25% according to conclusive data, which no other program in Québec and in rural areas has demonstrated until now. Finally, this program can be a cost-effective intervention for the healthcare system by reducing expenses associated to falls in rural areas, and in particular for patients in La Baie Hospital. Already used in Australia and the United States, we have yet to determine its effects in the Saguenay area. The goal is to test and show its efficiency for the fist time in the area by a random clinical trial in La Baie Hospital. This step will make it possible to advance our research program on the effective intervention plan to reduce future public healthcare expenses related to falls. The aim of this study will thus be to evaluate if the PEO, when adapted to La Baie geriatric services, is superior to conventional therapy to improve parameters of walking, balance, muscle activation, postural trunk control, mobility, force, endurance and perception of symptoms related to pain, function, fall risk and, consequently, quality of life (wellbeing), volume of medication and expenses associated to fall. In other step, the purpose is also evaluate the effect of carrying out the OTAGO exercises in an outdoor and nature modality during a feasibility study to see the impact of nature on the functional abilities of older people with neuromusculoskeletal disorders (ex. Parkinson disease).

Plantar Fasciitis Management on Postural Control

Plantar fasciopathy is a musculoskeletal disorder, known as a degeneration of the plantar fascia associated with a sensation of pain at plantar level. This disorder, for which around 2 million people a year receive treatment, has a prevalence of 3.6% to 7%, affecting both men and women between the ages of 45 and 64, and increasing with age. People aged between 25 and 65, who make up the majority of the working population, present 83% of plantar fasciopathy cases. According to CNESST statistics for 2022, 15,310 files opened concerned musculoskeletal disorders of the lower limb, 2133 of which involved the feet. There is also evidence of a possible cause-effect relationship between the number of hours spent standing or walking and the risk of developing plantar fasciopathy, which is indeed a major risk factor for many active workers. People with plantar fasciopathy will be absent from work more regularly, contributing to lower productivity at work. In addition to reduced work productivity, the cost of treatment has been estimated at US$584 million in the United States alone. In addition to pain, other deficits can be observed in people with plantar fasciopathy. A recent study also demonstrated its impact from a biomechanical point of view, notably on postural balance and gait in young adults suffering from this health problem. A number of treatments are currently used to treat this clinical foot condition, both conservatively and surgically. Among the most widely used conservative treatments, foot orthoses have been shown to be effective in reducing pain, despite the paucity of studies on the issue. Some studies have also demonstrated its effects on balance measures. Or, balance afferents originate from the somatosensory system, and tendon vibration can disrupt this system. However, few studies have measured its effects on postural control reactions via tendon vibration following orthotic use and in an ageing population, and no study has specifically investigated the effect of plantar orthoses in cases of plantar fasciopathy on gait pattern parameters in ageing workers.

Effects of a Supervised Rehabilitation Program on Disease Severity in Spastic Ataxias

A Home-based Rehabilitation in ARSACS

Co-creation phase: Preceding the intervention, a co-creation phase involving healthcare professionals (3), patient-partners (2), and ARSACS researchers (3) will be conducted to develop the exercises for the rehabilitation program and the evaluation scale to determine the level of difficulty of each exercise assigned to participants. Intervention phase: Random sampling stratified by gender and level of indoor mobility (unassisted walking, assisted walking, wheelchair) from the Neuromuscular Clinic's registry of 48 participants (24 women and 24 men) will be conducted. - Control phase: All participants will be asked to maintain their usual activities for 12 weeks. - Intervention phase: All participants recruited to the project will complete the home-based rehabilitation program assigned to them for 12 weeks, unsupervised, 20 minutes 3 times a week. Follow-up calls by a physiotherapist will be conducted at weeks 2, 4, 6, 8, 10 and 12.

Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation

[Ac-225]-PSMA-62 Trial in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer

The primary aim of the phase Ia study is to evaluate the safety and tolerability of [Ac-225]-PSMA-62 to determine the maximum tolerated dose (MTD). The primary aim of the randomized phase Ib dose optimization is to determine the recommended phase II doses (RP2D) for patients with mCRPC and OmHSPC. The aim of the phase II study for patients with mCRPC is to evaluate the efficacy of [Ac-225]-PSMA-62.