Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute kidney injury (AKI) typically within the first few days of exposure and is associated with short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage has progressed to functional impairment, when mitigation strategies are ineffective. Tests that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss would be very impactful, affording opportunities for prevention or early intervention to mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes. The field of metabolomics seeks to identify patterns of small molecules (metabolites) involved in cell or tissue metabolism related to disease states, or patient factors like lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can identify at-risk patients and reveal disease-related changes earlier than existing diagnostic methods do. In CisP-treated children and adults from across Canada, we will identify urine and plasma metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable. Our identified biomarkers will allow individualization of CisP treatment based on the level of nephrotoxicity risk and the design of trials to mitigate the progression and complications of CisP nephrotoxicity.

This is a prospective, randomised study investigating the physical and psychological experience of intermittent catheterization in adult individuals following spinal cord injury (SCI).

PALI-2108 is a new oral medication designed to treat ulcerative colitis (UC) by targeting the intestines. It works as a phosphodiesterase-4 (PDE4) inhibitor prodrug, meaning it becomes active only after being processed by bacteria in the colon. This targeted approach reduces the risk of side effects that can occur with other medications that affect the entire body. Recent studies have shown that patients with active UC, especially those with moderate to severe symptoms, have higher levels of PDE4 and related biomarkers. These biomarkers are linked to the severity of their disease, suggesting that inhibiting PDE4 could help manage UC effectively. The goal of this Phase 1 study is to evaluate the safety, tolerability, and how the body processes (pharmacokinetics) and responds to (pharmacodynamics) PALI-2108 in healthy volunteers. Although there are already PDE4 inhibitors on the market, PALI-2108 is a completely new compound that has not been tested in humans before. The study will involve two parts: first, participants will receive single doses of the drug, and then, in the second part, they will take it twice a day for seven days. The twice-daily dosing schedule is designed to maximize drug exposure in the colon. The investigators will also investigate how food affects the drug's absorption. Additionally, a small group of stable UC patients will be included in the study. These patients will also take PALI-2108 for seven days, allowing us to compare the safety and drug processing between healthy individuals and those with UC. The investigators will monitor important health markers and conduct tests on colon tissue to see how well the drug works and if it causes any changes in the tissue. Including UC patients early in this research is important for understanding how the drug performs in real-world conditions. This data will help refine our approach to identify which patients might benefit most from PALI-2108 in future studies. Overall, this study aims to gather crucial information about PALI-2108's safety and effectiveness, paving the way for new treatment options for patients with ulcerative colitis.

The purpose of this study is to test the efficacy of the 8-week Healing Hearts Together (HHT) program to improve relationship quality, mental health, quality of life (QoL), and cardiovascular health. This is a randomized controlled trial in which couples are randomly assigned to the HHT group or usual care. Changes in the outcomes of interest will be assessed at the end of the intervention (8 weeks) and 6 months later.

The objective of this study is to examine the safety profile and therapeutic efficacy of MRI-guided focused ultrasound microbubble therapy and radiotherapy in humans.

This is a Phase 1/2, multi-center, open-label, dose-escalation and expansion study to evaluate safety and tolerability, PK, pharmacodynamic, and early signal of anti-tumor activity of MDNA11 alone or in combination with a checkpoint inhibitor in patients with advanced solid tumors.

A single-centre, randomized, 2-arm clinical trial comparing follow-up consisting of tumour-specific Electronic Patient-Reported Outcomes (ePROs) with targeted symptom management versus standard of care follow-up during neoadjuvant/adjuvant systemic therapy

Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease marked by reduced exercise capacity and activity-related breathlessness (commonly termed dyspnea). Our previous work has shown that dyspnea during exercise is associated with an increased drive to breathe (inspiratory neural drive; IND). However, little work has been done to understand the mechanisms of exertional dyspnea in patients with mild IPF. The objectives of this study are to compare the acute effects of inhaled nitric oxide to placebo on ventilatory efficiency (VE/VCO2), and IND at rest and during a standard cardiopulmonary exercise test (CPET). Twenty patients with diagnosed IPF with mild (or absent) mechanical restriction and 20 healthy age- and sex-matched controls will be recruited from a database of volunteers and from the Interstitial Lung Disease and Respirology clinics at Hotel Dieu Hospital. Participants with cardiovascular, or any other condition that contributes to dyspnea or abnormal cardiopulmonary responses to exercise will be excluded. After giving written informed consent, all participants will complete 7 visits, conducted 2 to 7 days apart. Visit 1 (screening): medical history, pulmonary function testing and a symptom limited incremental CPET. Visit 2: Standard CT examination conducted at KGH Imaging. Visit 3: assessment of resting chemoreceptor sensitivity, followed by a symptom limited incremental CPET to determine peak work rate (Wmax). Visits 4 \& 5 (run-in): familiarization to standardized constant work rate (CWR) CPET to symptom limitation at 75% Wmax. Visits 6 \& 7 (Randomized \& Blinded): CWR CPET to symptom limitation while breathing a gas mixture with either 1) 40 ppm iNO or 2) placebo \[medical grade normoxic gas, 21% oxygen\]. The proposed work has the potential to provide important physiological insights into the underlying mechanisms of heightened dyspnea, as well as examine therapeutic avenues to improve quality of life in patients with IPF.

Patients diagnosed with esophageal cancer have difficulty eating, as the food pipe becomes obstructed by the cancer. This may impair the ability for the patient to receive appropriate calorie intake, especially during administration of chemotherapy and radiation therapy given prior to surgical resection. A strategy is to place a feeding tube directly in the stomach or in the small bowel to have an access to the patient's gastrointestinal tract during administration of chemo radiation therapy. However, these feeding tubes may lead to adverse events, including dislodgement, infection, the tube may be plugged, etc. If these complications were to happen, patients may have their treatment delayed, may have to come to the emergency department or even be admitted. In some cases, patients may need to have a surgery performed to treat the complication. Most centres in Canada have moved away from placement of these feeding tubes due to the high incidence of complications associated with the feeding tubes placement, and due to the high efficacy from the chemoradiation therapy in shrinking the tumour, allowing for the patient to swallow. In London, the preference from the Medical and Radiation Oncologists was to have these feeding tubes placed to avoid delay in treating the patients. There is therefore significant controversy as to what is the best approach in this patient population. Our goal is to run a feasibility randomized controlled trial studying this question.

This a stepped wedged cluster RCT with two intervention arms--Treatment As Usual (TAU) and an Integrated Care Pathway (ICP). Eligible participants are between the ages of 13 and 18, who present to community mental health agencies with depressive symptoms as the primary concern. The primary objective is to establish the clinical effectiveness of the ICP intervention in the community setting relative to TAU, with respect to reducing evaluator-rated depressive symptoms. The secondary objectives are to explore changes in clinician-rated function and caregiver-rated symptoms for youth receiving the ICP intervention relative to TAU. The third objective is to explore the implementation effectiveness of the ICP intervention, namely investigating: feasibility, fidelity, cost and acceptability. Edited on March 7th, 2024: This is a quasi-experimental, multi-site cluster controlled clinical trial design with two intervention arms--Treatment As Usual (TAU) and an Integrated Care Pathway (ICP). Eligible participants are between the ages of 13 and 18, who present to community mental health agencies with depressive symptoms as the primary concern. The primary objective is to establish the clinical effectiveness of the ICP intervention in the community setting relative to TAU, with respect to reducing evaluator-rated depressive symptoms. The secondary objectives are to explore changes in clinician-rated function and caregiver-rated symptoms for youth receiving the ICP intervention relative to TAU. The third objective is to explore the implementation effectiveness of the ICP intervention in the community setting, namely investigating: feasibility, fidelity, cost and acceptability.