For patients with treatment-resistant depression (TRD), a single low dose of intravenous (IV) ketamine can help relieve symptoms as quickly as 24 hours later. The main problem with IV ketamine for TRD is that the effect is short-lived, lasting only days to 1 or 2 weeks. Furthermore, IV ketamine is a resource-intensive treatment, and the safety of long-term, repeated use for depression is unknown. To provide this treatment in a safe and cost-effective way, Investigators must allocate it efficiently to those patients who have the greatest need and probability of benefit. Therefore, this project aims to find clinical features (signs, symptoms, and parts of a patient's history) that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD. This will help guide patient selection and triaging. Investigators will recruit 40 participants with TRD over one year, and randomize them to one of two conditions (ketamine followed by an active placebo 3-weeks later, or vice versa). With clinical data collected through detailed interviews, questionnaires, actigraphy, speech sampling, electroencephalography (EEG), and computerized tasks, this study design will let us evaluate how well such factors predict (A) rapid response at 24-hours, and (B) sustained response at 7 and 14 days.

This is a 12-month, single center, three-arm parallel design, double-blind, randomized clinical trial, to compare the effects of supplemental dietary fiber and metformin (MET) alone and in combination over 12 months on glucose metabolism (insulin resistance \[IR\]), inflammation and BMI in adolescents with obesity and IR, and to assess the relationship between therapeutic intervention(s) and changes in gut microbiome composition and function. Since MET and FIBER have been shown to reduce weight and increase insulin sensitivity through distinct but overlapping mechanisms of action, our central hypothesis is that the combination of FIBER + MET will have a synergistic effect and be more effective than FIBER or MET alone in improving metabolic function (IR) and reducing BMI and inflammation in adolescents with obesity, IR and family history (FM) of T2DM. .

Congenital plasminogen deficiency causes impaired wound healing and growth of pseudomembranous lesions over multiple parts of the body. The most common lesions involve eyes and are known as Ligneous conjunctivitis. These can cause scarring of the sclera, vision loss and even blindness. These pseudomembranous lesions are recur after surgical excisions, administration of intra-ocular cyclosporine, autologous serum drops or corticosteroids. Clinical data shows that these growths do not worsen and do not recur after administration of plasminogen (either as concentrate or as plasma) in the eyes, locally or intravenously. As plasminogen is not available as concentrate, we are using aliquoted allogenic plasma provided by Canadian Blood Services for intra-ocular application. These will be applied to eyes multiple times a day for a period of 2 to 6 months depending on disease severity and patient response. These may be used again if ligneous conjunctivitis recurs. The patient will be followed for a period of 2 years at least. All serious adverse events will be reported to Canadian Blood Services and Health Canada as appropriate.

Background Effective management of spasticity, a debilitating and challenging condition afflicting many recovering from and living with neurological conditions, may reduce long term consequences such as limb contracture, skin breakdown, compromised mobility, caregiver burden and discomfort. In rehabilitation, spasticity represents a significant barrier to successful rehabilitation outcomes. Effective spasticity management can increases the length of individual functional status, reduces equipment/care needs, hospital admissions and extends the time people can stay safely at home, which would represent an economic benefit to the health system. Extra-corporeal Shock Wave Therapy (ESWT), an intense short energy wave delivered directly at the region of affected muscles has, in past randomized controlled studies, demonstrated positive outcomes for this population (spastic stroke population, TBI), on its own and as an adjunct to current modalities. In fact, one retrospective observational study demonstrated an increased efficacy of Toxin botulinum at 1 month when combined with ESWT. Where existing treatment options may be limited by coverage, access to delivery, complications and side effects, ESWT represents a potential to be a safe, low cost, efficacious alternative that can be administered by any trained clinician. Aims The aims of this pilot study will be to explore the hypothesis that adding ESWT to Botulinum Neurotoxin A (BoNTA) in spasticity post-stroke (TBI)will demonstrate greater clinical and patient reported outcomes compared to standard treatment with BoNTA alone, a comparison only once previously studied. Methods Incorporating randomization and placebo control (n= 20 in each arm), this patient-centric study will examine treatment goals and holistic perception of benefit after the treatment experience. We will use patient reported outcomes at baseline and at defined intervals after intervention. We will test our hypothesis using clinical and patient reported scales, such as the patient reported numeric rating scale (NRS) and goniometric range for spasticity as our primary outcome in conjunction with measures of muscle stiffness, quality of life, feasibility and acceptability of the protocol to help inform future study direction.

Sleep-disordered breathing (SDB) is prevalent in children and adolescents and untreated SDB impacts key indicators of physical and psychosocial health. Positive airway pressure (PAP) therapy is highly effective for the treatment of SDB and is associated with favorable clinical outcomes but is limited by poor adherence. Emerging literature in adults suggests that intolerance to PAP therapy may be related to coexisting insomnia. However, the presence of insomnia in children with known SDB as well as its impact on PAP adherence have not been explored. This proposal will explore the association of coexisting insomnia on PAP adherence in children with SDB using a cross-sectional study design. The investigators will assess the association between insomnia and PAP therapy adherence, measured as the mean minutes of nightly PAP usage over 6 months of use on objective downloads.

In recent years, there has been a significant improvement in understanding the biology of cancer and this information has been used to improve cancer care and patient outcome. Research has shown that changes in some genes and/or proteins may be important indicators for certain cancers and response to treatments. Genes are molecules made up of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). DNA contain instructions for the development and functioning of the cells in the body and are passed down from parent to child. RNA is involved with producing proteins in the body. Further research is needed to better understand the changes found in cancer cells and how to target them to stop or reduce cancer growth. A drug that may be able to block certain specific cancer cell changes is called "targeted therapy". Different people with the same type of cancer receiving the same drug could have different responses to it. For example, one person may experience a reduction of their tumor while another person's cancer may worsen. The reason for this is still not well understood and could lie in gene changes. Understanding these changes may allow researchers to predict how treatments may work in guiding decisions around choice of drugs. The purpose of the study is to learn more about gene changes or protein expression (levels) of tumors to better understand the behavior of gynecological diseases and, if possible, better address participants' cancer care now or in the future.

Chronic olfactory dysfunction, both hyposmia and parosmia, from the COVID-19 pandemic is a growing public health crisis, affecting up to 1.2 million people in the United States. Olfactory dysfunction significantly impacts one's quality of life by decreasing the enjoyment of foods, creating environmental safety concerns, and affecting one's ability to perform specific jobs. Olfactory loss is also an independent predictor of anxiety, depression, and mortality. Recent research suggests that parosmia, more so than hyposmia, can increase anxiety, depression, and even suicidal ideation. While the pandemic has advanced the scientific community's interest in combating the burgeoning health crisis, few effective treatments currently exist for olfactory dysfunction. Persistent symptoms after an acute COVID-19 infection, or "Long COVID" symptoms, have been hypothesized to result from sympathetic nervous system dysfunction. Stellate ganglion blocks have been proposed to treat this hyper-sympathetic activation by blocking the sympathetic neuronal firing and resetting the balance of the autonomic nervous system. Studies before the COVID-19 pandemic have supported a beneficial effect of stellate ganglion blocks on olfactory dysfunction, and recent news reports and a published case series have described a dramatic benefit in both olfactory function and other long COVID symptoms in patients receiving stellate ganglion blocks. A previous pilot study using stellate ganglion blocks of 20 participants with persistent COVID-19 olfactory dysfunction resulted in modest improvements in subjective olfactory function, smell identification, and olfactory-specific quality of life, but it lacked a control group. Therefore, we propose a double-blinded, placebo-controlled, randomized clinical trial assessing the efficacy of a stellate ganglion block with Lidocaine versus saline injection in up to 50 participants with persistent COVID-19-associated olfactory dysfunction.

Emergent experimental and anecdotal evidence has indicated that critically ill COVID-19 patients demonstrate two patient sub-types (called phenotypes). In one group the disease progresses slowly and patients have a low potential of developing mild respiratory failure, but in the other group, an exaggerated immune response (hyper-inflammation/cytokine storm) may be linked to the onset of precipitous respiratory failure, termed acute respiratory distress syndrome. This syndrome is responsible for a large portion of COVID-19 associated mortality. Thus, determining links between hyper-inflammation and acute respiratory distress syndrome in COVID-19 patients is of immediate importance. Blood samples will undergo a number of analyses to help us to understand as much as possible about COVID-19. We will also study any differences in physiologic and cytokine levels before and after patients are treated with immunomodulatory therapies as part of clinical care in COVID-19 patients.

Fitness is an important determinant for health and influenced by using large muscles. Muscles respond to training. We want to know if adding arm exercise to leg exercise can provide a better training session for healthy individuals. If the strategy shows promise for healthy people then it might work for people with lung disease who have trouble training because of difficulty breathing. The purpose of this first study is to evaluate, in healthy people, a unique approach to training by determining if adding arm exercise to leg exercise can be endured longer than leg exercise alone.

As antibiotic resistance increases globally, it becomes more difficult to select empiric antibiotic therapy, particularly in patients with sepsis who stand to benefit from early adequate treatment. In particular it is difficult for clinicians to balance antibiotic stewardship principles (the need to avoid unnecessary prescribing of antibiotics that have an excessively broad spectrum of activity that favour resistance development) and under treatment. The integration of multiple risk variables for resistance are hard for clinicians to translate into clinical action, and is seemingly at odds with the natural inclination to provide heuristic/emotion-based antibiotic selection. The inappropriate treatment of sepsis is not uniformly too broad, or too narrow, and there is a need to optimize and tailor selection of antibiotic therapy to each patient, such that those that are at risk for resistant organisms receive broad therapy, and those that are not at risk, receive narrower antibiotic agents. Clinicians need support picking the right antibiotic for each patient, and from this they can potentially drive reduction of unnecessarily broad antibiotic prescribing while preserving adequacy of treatment. Individualized clinical prediction models and decision support interventions are promising approaches that meet these needs by improving the classification of patient risk for antibiotic resistant or susceptible infections in sepsis. Unfortunately, few have been validated in the clinical setting and larger rigorous studies are needed to provide the evidence to support broader clinical adoption. The investigators will perform a cluster randomized cross-over trial of an individualized antibiotic prescribing decision support intervention for providers treating hospitalized patients with suspected sepsis. The aim of this trial is to determine whether a stewardship led clinical decision support intervention can improve antibiotic de-escalation in patients with sepsis while maintaining or improving adequacy of antibiotic coverage. This decision support intervention will be based on a combination of proven decision heuristics (for Gram-positive organisms) and modelled predicted susceptibilities (for Gram-negative organisms) that are individualized to the patient. The primary outcome will be the proportion of patients de-escalated from their initial empiric regimen at 48 hours.