Bouctouche, Canada

Long-term Safety of Nipple Sparing Mastectomy in Women With GPV in Breast Cancer

4D-150 in Patients With Macular Neovascularization Secondary to Age-Related Macular Degeneration

My MS and My Menstrual Cycle

Pharmacogenetic-Guided Antidepressant Prescribing in Adolescents With Anxiety and Depression

Goal: To test the efficacy of pharmacogenetic-guided antidepressant prescribing for adolescents with depression. Background: For an adolescent with depression and anxiety, antidepressant medication is prescribed, often in combination with psychotherapy. The class of antidepressants recommended for use is selective serotonin reuptake inhibitors (SSRIs) with fluoxetine recommended as the first-line medication, and four other SSRIs recommended for consideration (sertraline, citalopram, escitalopram, fluvoxamine) if the adolescent does not respond or tolerate fluoxetine. For most adolescents, medication prescribing, and monitoring will be managed by a primary care physician or community pediatrician rather than by a mental health care provider, and guidelines exist to support this management. However, current prescribing guidelines/recommendations do not account for SSRI metabolism phenotypes that could change whether the SSRI selected is efficacious or tolerated. Our team of researchers, clinician scientists, patient partners, and primary care providers has designed a trial to test the impact of accounting for metabolism phenotypes, through pharmacogenetic-guided antidepressant prescribing, on adolescent outcomes, experiences, and health care utilization. Principal Question: Compared to current prescribing guideline/recommendation informed prescribing, does pharmacogenetic-guided prescribing for adolescents with depression and/or anxiety have superior efficacy following 12-weeks of therapy with a SSRI? The Trial: This is a parallel arm randomized controlled trial. Adolescents aged 12-17 years (n=452) who are starting or changing a SSRI for depression and/or anxiety will be randomly allocated to receive pharmacogenetic-guided antidepressant therapy (experimental intervention) or current prescribing guideline/recommendation guided prescribing (control intervention). Participants and prescribing physicians will be blinded to which intervention was received. The primary outcome is depressive symptom remission at 12 weeks measured using the Quick Inventory of Depressive Symptomatology - Adolescent (17-item) (QIDS-A17) and anxiety symptom remission at 12 weeks measures using the Screen for Child Anxiety Related Disorders (SCARED). Secondary outcomes include side effects, role functioning, medication adherence, and health-related quality of life measured 4-, 8-, and 12-weeks after intervention initiation as well as cost-effectiveness.

Therapeutic Effects of Electrical Vestibular Stimulation (EVS) on Balance and Gait

Background and Rationale Standing balance and stable gait are maintained through the integration of sensory feedback from the visual, somatosensory (muscle, skin, tendon, and joint receptors), and vestibular systems. The quality of this feedback, and the ability of the central nervous system (brain and spinal cord) to integrate these signals and generate appropriate motor responses dictates balance and gait performance. Age-related balance decline, clinically known as presbystasis, is one of the most visible and debilitating signs of aging. More than 60 million people in the U.S. over the age of 40 live with age-related balance impairments that increase their risks of fall-related injuries and make it increasingly difficult to continue living actively and independently. 1-in-3 adults above the age of 65 falls each year and falls are the leading cause of death in seniors. But there are less than 20,000 clinical specialists in the U.S. with the tools to diagnose balance impairments, so for most people, little is done to address declining balance until after a fall-related injury occurs. The solution offered to most older adults is a mechanical balance aid such as a walker, whose prolonged use only further destabilizes balance. Vestibular dysfunction has been identified as the primary cause of balance decline in more than 55% of adults over age 50, or around 34 million people in the U.S. This dysfunction impacts both the peripheral vestibular organs in the inner ear and central vestibular processing in the brain, and it has also been linked to cognitive decline. Current therapeutic options to restore lost balance function are limited to high-risk surgical vestibular implants. The current standard of care is exercise-based therapy that aims to help compensate for vestibular balance decline, but there remains a critical gap: no widely available non-invasive solution exists to restore lost vestibular function or prevent further deterioration. A growing body of research indicates that low-level, non-invasive electrical stimulation of the vestibular balance system (EVS) can induce neuroplastic changes at both cellular and circuit levels, effectively restoring peripheral and central vestibular functions. Restored vestibular function has also been linked to restored cognitive function. The investigators have developed a novel sub-threshold wideband stochastic EVS (swsEVS) neuroplastic stimulation, which targets peripheral and central vestibular pathways. Multiple studies have demonstrated that the swsEVS frequencies and current levels are safe, comfortable, well-tolerated, and have no adverse side effects. These studies have also demonstrated that a therapeutic treatment protocol with 18 twenty-minute swsEVS sessions delivered over a 5-6-week period resulted in significant improvements in balance performance in otherwise healthy adults aged 50-98 years old. These improvements are attributed to neuroplastic restoration of both peripheral and central vestibular function. The observed improvements persisted for at least 3-6 months and were sufficient to recategorize high fall risk individuals to lower fall risk. Objectives With the proposed pre-clinical study, the investigators aim to determine the safety, feasibility, efficacy, and persistence of the above non-invasive swsEVS to improve balance and gait performance in healthy individuals across the lifespan. Specifically, our objective is to measure balance and gait performance before, during and after exposure to single sessions and across repeated sequences of swsEVS at multiple study partner sites. The investigators predict that swsEVS-induced neuroplasticity may promote recovery of vestibular function via documented mechanisms that include: 1) regeneration of vestibular hair cells; 2) an increase in synaptic gain in the vestibular system, 3) an increase in vestibular afferent/efferent nerve fibre conductivity and excitability, and 4) increased central neural integration of sensory signals (vestibular, visual, somatosensory) for motor control. As such, our main hypothesis with this research is that exposure to repeated sequences of swsEVS will enhance balance and gait performance (e.g., walking cadence, stability, etc.). A secondary objective of this study is to determine if changes in vestibular function are accompanied by measurable changes in cognitive function. Finally, a tertiary objective of this research is to determine if swsEVS has any potential benefit for participants suffering from occasional headaches. There is some anecdotal evidence that EVS could help with headaches, particularly for so-called "vestibular migraines"; however, to date this has not been formally studied. Participants Healthy young and older adult participants (18 - 100 years of age) will be recruited in this study. Participants will be recruited at each study site from their local community by word of mouth, study ad postings, and the UCalgary Participate website. All participants will be given detailed written and oral explanations of experimental goals and procedures, and the protocol will be approved by UCalgary's Clinical Health Research Ethics Board (CHREB). Participants will provide written informed consent prior to participation. Methodology Participation in this experiment will involve 18 testing sessions over a 5-6- week period, as well as 3-week, 6-week, 3-month, and 6-month follow up sessions. Each testing and follow-up session will last under 1-hour. The proposed project will employ six primary techniques: (i) electrical vestibular stimulation (swsEVS); (ii) accelerometry; (iii) smartphone app-based gait and balance tests; (iv) clinician-administered Functional Gait Assessments; (v) static and dynamic balance tests using an instrumented balance platform; (vi) cognitive assessments. swsEVS test administrators will also collect information about any adverse events during each visit and since the last visit. Participants will also complete questionnaires upon entering and exiting the study to assess the prevalence and severity of headaches, cognition, dizziness, level of physical activity, as well as to determine if these headaches are causing any notable disability. (i) Electrical Vestibular Stimulation (EVS) involves electrically activating the peripheral vestibular system by passing small electrical currents through electrodes placed on the mastoid processes (behind the ears) via battery powered, constant current isolated stimulators. This non-invasive, safe and painless bioelectronic stimulation technique commonly utilizes either a stochastic signal (white noise) or monopolar or bipolar square- or sine-wave pulses. EVS typically used different bandwidths of stimulation, from broad-band (0-1 kHz) to narrow-band (0-2 Hz).EVS may also be applied at different stimulation amplitudes, ranging from those that are below the level of evoking any sensation by the participant ("sub-threshold"; typically < 0.5 mA), to those that evoke overt vestibular sensations and balance responses ("supra-threshold"; > 0.5 mA). The swsEVS neuroplastic restoration in the present study delivers subthreshold, wideband, stochastic stimuli via 2 pairs of disposable single-use electrodes attached to each mastoid and the back of the neck. EVS does not ever exceed +/- 3 mA (hardware and software limited), giving it an excellent safety profile across a large and growing body of scientific literature. (ii) Accelerometry: Participants will be instrumented with wearable accelerometers (Phybrata Sensor; PROTXX Inc.) on their head over top of the right mastoid process, as well as on the top of each foot. The sensor placed on the head has been validated as a measure of gait and balance performance in multiple previous studies. The sensors placed on the top of the foot will be used to reconstruct step-by-step foot placement kinematics during gait testing. Sensors attached to the head will be affixed to the skin with disposable double-sided medical adhesive tape, after cleaning the skin with an alcohol swab. Sensors applied to the foot during gait testing will be affixed with medical tape. The accelerometers automatically collect and relay the kinematic data to a smartphone app-based system. (iii) Smartphone App-Based Gait and Balance Testing: Gait and balance assessments will be performed using a smartphone app developed by PROTXX Inc. The app guides the user through the experimental procedures through on-screen instructions and auditory beeps. Investigators will use the app to perform assessments of quiet standing (3 x 2 min intervals of standing still and relaxed with their arms at their sides; 1 min eyes open, 1 min eyes closed), as well as the standard Timed Up and Go (TUG) task and an over-ground walking task. For the TUG task, participants will start seated in a chair, then when prompted by the app, will stand up, walk 3 m forward to a pilon on the floor, turn around 180 degrees, then return to the chair and sit down. For the over-ground walking task, participants will simply start standing with their toes over a tape line on the floor, then they will walk forward (< 50') to an end target pilon. (iv) Functional Gait Assessment (FGA): The investigators will have trained clinicians administer the FGA, which involves timing 10 different tests of mobility, including: 1) level surface walking (20'), 2) 'change-in-gait-speed' task alternating between 'slow' and 'fast' speeds (5' each), 3) walking with horizontal head turns every 3 steps (20'), 4) walking with vertical head turns every 3 steps (20'), 5) walking with pivot turn to reverse direction and stop (5'), 6) walking with a step over a 9" obstacle (i.e., the height of 2 shoe boxes), 7) walking with narrow base of support (i.e., stepping 'heel-to-toe') for 10 steps, 8) walking with eyes closed (20'), 9) walking backwards (20'), and 10) walking up and down a set of 4 steps, using a railing if necessary. (v) Cognitive Assessments: Cognitive assessments will utilize paper-based questionnaire forms of the Symbol Digit Matching Task (SDMT) and the Montreal Cognitive Assessment (MoCA). Experiment Overview During their initial intake session at the study site, all participants will undergo EVS threshold testing to determine normalized levels of EVS that result in balance perturbations. This EVS threshold testing will be carried out by administering very low currents (starting at ~0.1 mA) to participants standing with their eyes closed and increasing the current level across trials until an EVS balance threshold is determined. During all 18 subsequent testing sessions, participants will perform gait and balance tests administered via a smartphone app (see below) before and after a single continuous session of swsEVS (<20 min). During each swsEVS session, participants will alternate between sitting, standing on the hard floor, and standing on a foam pad, with intervals of having their eyes open and closed. An investigator will always be nearby the participants to protect them from falling and provide postural support if needed. Cognitive testing and headache questionnaires will be completed during the first and last of the 18 treatment sessions. During the 3-week, 6-week, 3-month, and 6-month follow up sessions, participants will repeat gait and balance tests to assess the persistence of any performance improvements measured after the 18 testing sessions. Statistical Design To determine the therapeutic efficacy of repeated EVS sessions, dependent variables will be submitted to repeated measures ANCOVA with stimulation type ('sub-threshold', 'supra-threshold') and sex ('male', 'female') as between subject factors, and age as a covariate. Further exploratory analysis of relationships between age and different dependent variables will be performed using Pearson correlations. An alpha level of 0.05 will be used as the statistical significance threshold for all testing.

The Dragon PLC Trial (DRAGON-PLC)

Primary liver cancer (PLC) is the third most common cause of cancer death worldwide. Surgical resection is the mainstay for a curative approach as contemporary chemotherapy and immune-based therapies only lead to a median survival of 10-14 months. A complete surgical resection increases the median survival to 42 months (range 32-52 months). However, PLC is mainly diagnosed at an advanced stage and >70% of PLC patients are ineligible for an immediate surgical approach. There are different reasons that make a patient ineligible for surgery, one important reason is the risk of liver failure after the surgery due to a small remnant liver. This study aims to improve the oncological, radiological and surgical strategy to allow more patients to undergo liver resection safely, to improve quality of life and to extend overall survival at acceptable costs. Adequate function of the future liver remnant (FLR) is a prerequisite for surgical resectability. This is necessary in order to avoid liver failure after surgery, a major cause of morbidity (38%) and mortality (27%). To mitigate this risk, regenerative strategies based on preoperative calculation of the FLR volume and function are essential. Patients with technically resectable disease but predicted insufficient FLR volume or function are referred to as primarily unresectable or potentially resectable (PU/PR). These patients can undergo strategies that capitalize on the regenerative capacity of the liver which aim to preoperatively increase the FLR volume and function in order to allow surgery. Many of the patients that are primarily unresectable due to an insufficient FLR can become ultimately and safely resectable after the induction of adequate FLR-hypertrophy by the current standard, portal vein embolisation (PVE). However, 25% of patients do not show sufficient FLR growth after PVE and are unable to safely undergo resection. A new approach has been developed to improve this. Combined portal and hepatic vein embolisation (PVE/HVE) has great promise in terms of increasing FLR growth, resection rate (RR), safety and potentially, overall survival. Establishing PVE/HVE as the new standard could result in increased survival and a better quality of life (QoL) for patients.

Clinical Utility of ClarityDX Prostate

When stratifying patients for prostate cancer, it is ideal to avoid delay in treating high-risk participants that do require a biopsy, while avoiding unnecessary procedures in low-risk patients. The purpose of this study is to investigate in a real-world setting whether the use of ClarityDX Prostate would further reduce potentially unnecessary healthcare utilization of men referred to urology clinics with suspicion of prostate cancer.

Comparative Effectiveness of Prophylactic ICD Versus Non-ICD Therapy

The proposed CONTEMP-ICD trial is a prospective, multicenter, open-label, randomized controlled trial; enrolling 3290 participants with HFrEF, on stable and optimal guideline-directed medical therapy (GDMT), who are eligible for a primary prevention ICD, but have a low predicted arrhythmic risk. Enrolled participants will be randomized in a 1:1 ratio to non-ICD vs. ICD treatment arms. The investigators hypothesize that, in participants with HFrEF who have a low predicted arrhythmic risk, non-ICD vs. ICD is non-inferior with respect to the primary endpoint of all-cause mortality and superior survival free of major cardiovascular (CV) events. This study will recruit adults 18 years of age and older with heart failure. Participants will be asked to complete questionnaires. Information from medical records will be gathered including medical history, physical exam, medications, blood work results, and imaging. Visits will be at initial, three, six months, and every six months beyond six months. For those who get an ICD device an interrogation will be collected at the visits.

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

Low-value Care, and Variation in Practice for Children Hospitalized With Bronchiolitis

Background: Low-value care is defined as the use of a health service, such as diagnostics and treatments, for which the harms or costs outweigh the benefits. Reducing low-value care is important in improving the health of Canadians and achieving a sustainable, high-quality healthcare system. Bronchiolitis is among the most common and most costly causes of hospitalizations in children. Most healthcare costs associated with bronchiolitis are related to hospitalization, and these costs have been increasing. Supportive care is recommended by national guidelines for the treatment of bronchiolitis, and many commonly used diagnostics and treatments in bronchiolitis are considered low-value, making it a great model to study low-value care in pediatrics. To develop effective interventions to reduce low-value care, and ensure the right resources go to the right patient at the right time, it is crucial to develop a better understanding of inpatient management of bronchiolitis in Canada. The goal of this prospective multi-site observational study is to analyze the use of 6 low-value healthcare services in children diagnosed with bronchiolitis, their costs, and measure the variability in practice of these services. Specific objectives: Among infants admitted with bronchiolitis at 15 Canadian hospitals with pediatric admissions, to: 1. Measure the incidence, patterns, and predictors of use of 6 low-value care health services and their costs in children hospitalized for bronchiolitis, namely 1) respiratory virus testing; 2) chest x-rays; 3) continuous pulse oximetry; 4) short-acting beta-agonists; 5) systemic corticosteroids; and 6) antibiotics; 2. Estimate the extent of practice variation in the use of 6 low-value health services between hospitals; 3. Determine whether differences in use of low-value health services are associated with patient and family characteristics (e.g., race and ethnicity, socioeconomic status, language), and whether these contribute to disparities in care. Design: A multi-centre (n=15), prospective observational cohort study of children hospitalized with bronchiolitis. Data will be obtained from medical charts and entered into a central, web-based REDCap database. A health equity questionnaire will be completed by participants once during their child's admission and then again 30 days later to inquire on additional medical care required post-admission. Secondary outcomes and covariates will also be collected which include but are not limited to duration of ICU stay, use of mechanical ventilation, cardiac arrest, length of hospital stay, disease severity, clinician years of experience, and death. Analysis of the primary outcome will be descriptive for each low-value health service, overall and stratified by sex. Costs of hospitalization will be assessed from a healthcare institution perspective. Cost of each of low-value health service will be described and compared between one another and across sites to identify key differences which may be targets for process change. This study will provide important data to understand the use of low-value care in bronchiolitis treatment in Canada, and will inform our approach to addressing low-value care in bronchiolitis and in other common conditions.