The WHEAT International trial is a comparative effectiveness trial exploring whether withholding enteral feeds around the time of blood transfusion in very premature infants (\<30 weeks) will reduce the occurrence of Necrotizing Enterocolitis (NEC). Currently both continued feeding and withholding feeding are approved care practices. The current study will randomize infants from Neonatal Intensive Care Units (NICUs) across Canada and the United Kingdom (UK) into one of the two care approaches (withholding or continued feeds) to determine if any significant outcomes are found.

Burn injuries can result in long term physical and mental sequelae, not only from the scarring but also the painful dressings. The standard of care today remains use of antibiotic topical dressings while awaiting demarcation of the burn depth, with surgical excision and grafting for deep partial thickness and full thickness areas. Demarcation can be appreciated on admission for full thickness burns but is often a prolonged process that can last weeks. The clinical evaluation of the depth of the burn is a complex decision that often is made more challenging by the presence of the proteinaceous pseudoeschar and the coagulated dermis itself. Surgical debridement is relatively 'coarse' and by its very nature requires removal of a thin layer of viable tissue to reach the level that is vascularized enough to support a skin graft. There has been growing interest in the use of adjuncts to reduce the amount tissue debrided and potentially reduce the need for surgery itself. Operatively, there have been some reports that use of hydro-dissection devices (Versajet™) may allow a more controlled debridement, resulting in less viable tissue being sacrificed. There is also a growing experience with enzymatic debridement, especially with Bromolein, derived from Pineapple (NexoBrid®). Neither of these have been shown to definitively improve care in randomized controlled trials, (RCTs) and there is suggestion that in some settings may actually cause harm.

While effective interventions for depression exist, their success rates are unsatisfactory and their provision is haphazard. The Canadian Depression Research and Intervention Network (CDRIN) Maritimes Depression Hub will improve the delivery of care and the quality of outcomes for youths, adults and seniors with depression across the Maritimes. The investigators will establish an integrated system of assessment, treatment, research and education related to depression with the active involvement of those with lived experience. The establishment of a patient registry is a key step that will facilitate evaluation and reform of current services, integration of patient choice and community resources into treatment programs, monitoring long-term outcomes, and development of more effective treatment approaches through research. The registry will facilitate research that will include validation of new diagnostic and outcome measurement tools, low-cost clinical trials and collaborative projects with national and international partners. Educational programs will involve training the next generation of researchers, those with lived experience, clinicians, and health system managers in critical appraisal and will facilitate their involvement in research. The registry, the proposed systematic measurement of outcomes and the broad dissemination of information and skills will improve the quality of research and of care as well as the experience of patients and their families. The need for a registry: It is increasingly recognized that major advances in the treatment of mental disorders will require large scale clinical research. Recently demonstrated ways of completing large-scale research with finite resources include the routine use of electronic health records (EHR), data linkage and randomized registry trial. Use of EHR is the most efficient way of rapidly obtaining large amounts of information. However, EHR cannot completely exclude confounding by indication and other unmeasured variables. Therefore, tests of treatment effects require experimental designs that cannot be replaced by routine health records data. The gold standard for testing the effects of treatment in an unbiased way is the randomized controlled trial (RCT), where measured and unmeasured confounders are balanced through the randomization process and any remaining confounding is due to chance alone. RCTs are valued as the highest level of evidence, but are costly and take significant time to be completed, partly because of the need to screen a large group of individuals to identify eligible participants. The most efficient unbiased test of interventions, new treatment modalities and novel ways of treatment delivery is a method that combines EHR use with the randomized controlled trial (RCT) methodology: the randomized registry trial (RRT). The RRT takes advantage of a registry of individuals with available information to identify a large number of individuals suitable for an RCT. The RRT approach is efficient especially if the same information (e.g. diagnosis and treatment history) is used repeatedly for different purposes. The same information can be used for clinical purposes, service improvement and multiple research projects. RRT will allow obtaining answers about the efficacy of new treatments and management strategies significantly faster and at a much lower cost than traditional RCTs. Therefore, the investigators propose to establish a registry that has the capacity to conduct RRTs. The proposed registry will be integrated with similar efforts across Canada. Jointly, this collaborative network of registries will facilitate fast and economical testing of new treatments, which is urgently needed to advance the therapeutic options for people with depression and related conditions.

The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.

Awareness, or explicit recall, under sedation is often intended and expected by anesthesiologists and is assumed that does not associate with any sequelae. Thus, awareness under sedation is a common event and is estimated to occur in around one-quarter of patients in our population. However, two recent registry studies suggested some patients with awareness under sedation have comparable psychological sequelae to those patients with awareness during general anesthesia. As such, we plan to conduct a a single center, prospective cohort study to evaluate the incidence, experience and psychological consequence of awareness under sedation. In this study, we will prospectively include 2500 patients who will be scheduled to have major joint replacement surgery under regional anesthesia and sedation at University Hospital, London Health Sciences Center. All participants will be assessed at four separate time points including: 1. Enrollment/Surgical Preparatory Area (\~ 2 hours before surgery) 2. Post Anesthesia Care Unit (or up to 6 hours after surgery) 3. Postoperative day one (in hospital) 4. Postoperative 3 months (expected to be after discharge via telephone)

This is the first pilot phase II trial assessing the response of SBRT layered on Darolutamide (BAY1841788) on RPFS and deferring palliative second line systemic therapy in M0CRPC with oligoprogression.

Currently, nearly 1 million total knee arthroplasties (TKA) are performed yearly in the United States. Three million are projected to be performed in 2040. Between 15-30% of all patients who undergo TKA have continued pain, reduced quality of life and functional impairments that cannot be attributed to hardware failure/loosening or infection. Treatment options for persistent post TKA pain (failed TKA) are limited. There is a need for minimally invasive, and effective pain and disability modulating interventions for patients with failed TKA. Genicular radiofrequency ablation (GRFA) has been described, refined, and validated as an effective minimally invasive intervention to control refractory knee pain secondary to knee osteoarthritis (OA) as evidenced by three favorable meta-analyses published in 2021 alone.3-5 GRFA is a minimally invasive percutaneous procedure that utilizes thermal energy to coagulate nerves from the knee. Though sometimes used in practice, there is limited research describing and evaluating GRFA for patients with failed TKA. This will be the first trial to evaluate the safety and efficacy of GRFA in patients with failed TKA using a robust study design and up-to-date, evidence-based selection criteria and technique.

This is a Phase 3, multi-center, randomized withdrawal study to evaluate the efficacy and durability of ampreloxetine in participants with MSA and symptomatic nOH after 20 weeks of treatment. This study includes 4 periods: Screening, open label, randomized withdrawal, and long-term treatment extension (LTE).

This is a two arm RCT evaluating the effect of intravenous vitamin C versus placebo in patients with incurable non-small cell lung cancer. Participants in both arms will be receiving platinum doublet chemotherapy with or without concurrent immunotherapy as standard care. We plan to enroll 90 patients over 5 years.

This clinical trial will investigate the effects of capsules containing stool from healthy donors, called fecal microbial transplant (FMT), in rheumatoid arthritis patients.