Kita-azumi, Japan

Pericardiotomy in Cardiac Surgery

Approximately 30% of cardiac surgical patients develop post-operative atrial fibrillation (POAF). Its incidence varies depending on the type of cardiac operation. POAF is associated with short- and long-term adverse events, including mortality, stroke, and heart failure. POAF has also been significantly associated with unplanned hospitalization for heart failure. During cardiac surgery, pericardial fluid tends to collect posterior to the left atrium. Even small amounts of fluid may trigger atrial arrhythmias. A posterior left pericardiotomy is a surgical procedure that involves cauterizing an opening between the left inferior pulmonary vein and the diaphragm. This procedure may allow for more prolonged drainage of the pericardial fluid into the left pleural space. Recent research evidence found that posterior pericardiotomy was associated with a significantly lower incidence of POAF. The existing data on posterior pericardiotomy is promising for a reduction in POAF. However, no high-quality study has demonstrated that this reduction improves clinical outcomes in the years after cardiac surgery. The PRINCE trial's long-term follow-up of patients randomized to left posterior pericardiotomy could conclusively demonstrate whether the relationship of POAF to post-discharge clinical outcomes is causal and modifiable. The PRINCE trial will evaluate the effectiveness and safety of posterior left pericardiotomy in preventing POAF and improving post-discharge clinical outcomes in a broad spectrum of cardiac surgery patients. The intervention under investigation is left posterior pericardiotomy which is compared to no posterior pericardiotomy during cardiac surgery. The early co-primary outcome is in-hospital POAF, and the late co-primary outcome is the hierarchical composite of time to all-cause death, time to ischemic stroke, time to systemic arterial embolism, time to unplanned hospital visit/readmission for cardiac reasons, and time to atrial fibrillation after index hospital discharge. The study will enrol 1400 patients from 30 centres, globally. Follow-up visits will be performed in person or by telephone 1 and 6 months post-randomization (+7 days), and then every 6 months (+30 days) until an average follow-up of 5 years for the study participants (estimated to be 4 years after completion of enrolment).

SCORE! ACTIVE Trial

The investigators will conduct a pragmatic, stepped-wedge cluster randomized trial in 14 neighbourhoods to determine the impact of SCORE! ACTIVE trial on the primary outcome of PA self-efficacy among 5-11-year-old children. The SW-CRT involves the sequential transition of clusters, in this case neighbourhoods, from control to intervention conditions in a randomized order. In this case, the method is pragmatic because recruitment and initial baseline measures in each community will occur just before the initiation of the intervention. There have been methodological challenges noted with SW-CRT including identification and recruitment bias, within cluster bias, and secular trends. However, this design is ideal for the implementation of the SCORE! ACTIVE trial because for practical reasons, it is not possible to deliver the intervention to many clusters at the same time. The trial will be reported using CONSORT guidelines and extension of SW-CRT.

Perioperative Anticoagulant Use for Surgery Evaluation -Virtual Visit (PAUSE-Virtual)

The Clinical Problem: The management of patients who are taking warfarin or a direct oral anticoagulant (DOAC) and need an elective surgery/procedure is a common and important clinical problem: (i) ~200,000 patients/yr are assessed in Canada for such management and this will increase due to an ageing population and an increase in anticoagulant use; and (ii) if anticoagulants are not managed carefully, with evidence-based protocols, patients can be exposed to an increased risk for disabling stroke if anticoagulant interruption is too long or life-threatening bleeding if interruption is too short. The Healthcare Delivery Problem: Perioperative management of anticoagulant therapy has been traditionally done in an in-person setting where patients receive instructions about when to stop and restart anticoagulants and, if needed, to receive teaching to self-administer heparin bridging. The COVID pandemic has upended this healthcare delivery model, necessitating virtual management by phone/video. Virtual patient care to manage perioperative anticoagulation has the potential to be an efficient and patient-friendly standard post-pandemic. However, to attain this objective, it must be reliably shown that virtually-administered, standardized, perioperative anticoagulation management is: (i) safe, with acceptably low rates of stroke and bleeding; (ii) easy to apply in practice; and (iii) acceptable to patients. The foundation for this study is based on prior work by the investigator: (i) The investigator has led multicenter clinical trials (BRIDGE, PAUSE) that provide benchmarks for safe perioperative management of patients who are receiving warfarin or a DOAC; (ii) the management protocols from these trials were incorporated into a clinical decision tool that is available (cost-free) by Thrombosis Canada (www.thrombosiscanada.ca). This point-of-care app allows input of patient-specific information to manage individual patients with atrial fibrillation/flutter (AF) who are receiving warfarin or a DOAC and require an elective surgery/procedure. At the end of the assessment, a care-path summary is available as a PDF for clinicians and patients for downloading and printing. The Opportunity: The pandemic has necessitated the adoption of virtual perioperative anticoagulant management but also has provided the opportunity to re-evaluate how such care can be safely delivered. Given that (i) perioperative anticoagulant interruption/resumption and heparin bridging protocols are standardized, and (ii) there is an easy-to-use, point-of-care, management app available, the investigator has a unique opportunity to apply evidence-informed protocols with user-friendly knowledge translation tools to assess the safety and acceptability to patients of virtual perioperative anticoagulant management. The Solution: A prospective cohort study (non-RCT) assessing standardized virtual perioperative management in 2 cohorts of patients on warfarin or a DOAC who require an elective surgery/procedure. Hypothesis & Postulates: (i) the investigator hypothesizes that virtual perioperative management will be safe for patient care, with 30-day postoperative rates of stroke/systemic embolism (SSE) ≤0.5% and major bleeding (MB) ≤1.5%. With a sample size of 847 patients in Cohort 1 and in Cohort 2, the investigator will have 90% power at the 95% level of significance to reject the null hypothesis that the observed rates are ≥1.5% for SSE and ≥3% for MB in each cohort. (ii) The investigator postulates (a) that virtual management will be as safe as in matched historical control groups who received benchmark in-person management, (b) that virtual management will reduce healthcare costs and costs to patients, and (c) that patients will be satisfied with virtual management and will be willing to receive this methods of healthcare delivery post-pandemic. Significance: PAUSE-Virtual will shift perioperative anticoagulant management from a resource-intensive in-person model to a patient-friendly virtual model, establishing a standard-of-care option for 200,000 patients/yr in Canada. The investigator is a leading group in perioperative anticoagulant management worldwide, having done the landmark BRIDGE1 and PAUSE2 trials. There is no other research group (that the investigator knows of) that will do this trial, and it will not be funded by industry (no commercial interest).

A Study of Retatrutide (LY3437943) in the Maintenance of Weight Reduction in Individuals With Obesity

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.

Health Literacy in Geriatric Patients

As treatments become more sophisticated and the healthcare system becomes more complex, health literacy (HL) assumes an ever-greater importance in the therapeutic alliance between healthcare professionals and patients. Limited health literacy causes difficulty in understanding one's health condition. As a result, it is associated with less adherence to self-care behaviours, increased mortality, increased hospitalizations, other adverse health outcomes, and high healthcare costs. In those over aged 65, health literacy is positively influenced by levels of educational attainment and literacy practices in the home, male gender, and weakly by informal learning and self-study and adult education experience. Negative associations include being foreign-born and failure to learn from exposure to various contexts. Understanding the health literacy of patients is particularly vital for geriatricians as older adults referred to geriatric medicine clinics already experience barriers to high quality care due to the frequent presence of cognitive impairment and multiple comorbidities. The interaction among these variables and health literacy in a tertiary care setting for older adults with cognitive impairment remains under-explored. Given the dependent state of many cognitively impaired individuals, the responsibility lies with geriatricians to adjust their communication and care strategies according to the HL levels of their patients. Studying the association between the accuracy of geriatrician-perceived HL and health outcomes could reveal the extent to which physician communication impacts these outcomes. Given these intertwined factors, a 6-month follow-up is crucial to capture the longitudinal associations of HL on patient outcomes, providing a more comprehensive picture of how these variables interact over time. This study's primary outcome is the evaluation of patient health literacy and the level of agreement between the geriatric team's perception and objectively measured health literacy. The secondary outcome is assessing how patient health literacy is associated with medication adherence and future planning. As well, the investigators hope to assess how patient health literacy is associated with emergency department visits, hospitalizations, hospital length of stay, remaining home, long-term care admission and mortality within 6 months.

AIRE-2 Device for Study of Breath Analysis in IBD

Study Design Type: Prospective single-blinded intervention feasibility study Methodology/Study Design: A cohort of IBD patients and their healthy household controls will be recruited for this study. You will be instructed to use a handheld breathalyzer device, AIRE-2, to measure exhaled H2 and CH4 gas production, and its smartphone app, FoodMarble, will be used to log your diet and symptoms for a period of 5 weeks, as follows: AIRE-2 will be used before and after two meals each day - the first meal and the last meal of the day. You will breathe into the AIRE-2 device before eating to obtain the baseline value. After the meal, you will breathe into the AIRE-2 60 minutes postprandially. The exhaled H2 and CH4 measurements will be automatically logged into the FoodMarble app, which is connected via Bluetooth. You will log your food intake and symptoms in FoodMarble. Symptoms scores will be recorded at the same time that the AIRE- 2 device is being used - 60 minutes postprandial. You will be asked not to drink alcohol during the meals that will be recorded, as this will skew the device results. You will be informed that you can consume alcoholic drinks after doing the postprandial breath test. Study procedure: 1. Study Enrolment and Familiarization Period: At visit 1, you will be trained to use the AIRE-2 device which McMaster has purchased from the FoodMarble company and will be provided to you. You will also be trained to use the FoodMarble app. The FoodMarble company is the owner of the AIRE-2 device which is being used in the present study, the company wouldn't have access to resulting data other than publication. Demographics, medical history, disease activity, Gastrointestinal symptom rating scale (GSRS), Bristol stool type, medications, supplements, perceived food intolerances and general dietary patterns will be recorded at baseline. We shall assist you in inputting some GI and extra-intestinal symptoms (headache, foggy mind, numbness of joints, joint pain, fainting, oral lesions, dermatitis) manually in the FoodMarble app from the GSRS symptom questionnaire as all symptoms are not mentioned in the app and there is a provision to edit the symptom list. After visit 1, you will have 3 days to use the device and app in order to become familiar with its use and report any challenges and difficulties to us in visit 2 (online via McMaster Zoom). At the end of the familiarization period, you are expected to be comfortable using the AIRE-2 device and the FoodMarble app. No data reported during this period will be used for the purpose of analysis or outcomes evaluation. 2. Baseline Period: This period starts after the familiarization week and runs for one week, representing the beginning of the data tracking collection. During the baseline period, you will eat your normal, typical diet, while collecting your breath test, food and symptoms as described above. The baseline period serves to capture the natural fluctuations of breath H2 and CH4 of each individual and to explore the correlations with diet and symptoms. You will be instructed to take the breath test before and 60 minutes after two major meals, every day. You will also collect the baseline stool sample and drop it off at the study location during visit 3, at the end of this period. You will be handed the low FODMAP diet chart which will be required in discovery period. 3. Discovery Period: This period starts after the baseline period and runs for four weeks. During this period, you will document your responses to challenges with four specific FCHOs)- Lactose, Fructose, Sorbitol, and Inulin ("Food Intolerance Kit", FoodMarble Inc, Dublin, Ireland). The quantities of each FCHO challenge are as follows: lactose and fructose sachets, 25g each. A sachet of lactose roughly equal to amount of lactose present in 1 large glass of milk. A sachet of fructose is roughly equal to amount of fructose present in 2 large apples. Sorbitol and inulin sachets contain 10g each. A sachet of sorbitol is roughly equal to the amount of sorbitol present in 3 pears or 1 prune. A sachet of inulin is roughly equal to the amount of inulin present in 1 head of garlic. Each sachet has to be dissolved in 250 ml of lukewarm water. Before each challenge, you will follow a low FODMAP diet for 24h to facilitate clearance of any FCHOs from the intestine. You will be guided by a registered dietitian (RD) regarding an appropriate low FCHO diet, supported by the FoodMarble app, which provides a large database of low FODMAP meals and recipes. You will log all meals during the 24h low FCHO period using the FoodMarble app. The meals will be analyzed by the RD and scored, on a 4-point scale (poor, moderate, good, excellent) for adherence to the low FCHO diet. Exhaled H2 and CH4 will be measured before and 60 min after the first and last meal during this period, as usual. After the 24h low FCHO diet, you will consume one FCHO challenge in the morning (after the baseline breath test) and take the postprandial breath test 60 min later. You will be required to record the breath test for 3 hours after every 15 minutes as per the protocol of the kit. You will then collect the first stool sample after the challenge and submit it to us in visit 4. Symptoms and meals will continue to be logged in the FoodMarble app. You will also be instructed to fill in a validated questionnaire to assess symptoms before and after the FCHO challenge (Adult Carbohydrate Perception Questionnaire). This questionnaire will be given to you in paper form. A 6-day washout period will be implemented in between the FCHO challenges. During the washout period, you will follow your typical diet. The 24h low Fodmap day, FCHO challenge, 6-day washout cycle and submission of stool samples (visit 4-7) will be repeated until all 4 FCHO challenges have been completed. The order of the FCHO challenges will be randomized and will be kept constant between all of you to minimize potential co-founding factors related to the order of the intervention. However, you will be blinded to the order. 4. End of the study: At the end of the discovery period, you will answer a feedback survey to report their experience using AIRE-2 and FoodMarble.

Analytical Validation of Stream™ Platform

This is a multi-center study, being conducted to facilitate the Analytical Validation of Stream™ Platform. This includes precision evaluation assessing repeatability and reproducibility of the pH measurements conducted by Origin™, tests evaluating the linearity of measurements, analytical specificity (interference testing), and method comparison studies. The tests described under this study will be completed using commercially available calibration fluids, and peritoneal drainage samples collected from patients that undergo gastrointestinal surgery. Simulated peritoneal fluids, adjusted to the required pH may be utilized in some cases. Additionally, peritoneal drainage samples may be used for testing, verification, and validation of novel Origin™features, designed to improve user workflow. The following patient populations will be eligible for the collection of abdominal drainage samples: colorectal, hepatobiliary, and trauma and acute care patients. This study will require collection of peritoneal drainage fluid of subjects that undergo gastrointestinal surgery. One sample will be collected per day and will be labelled with a study ID, date and time of collection, and then frozen. The sample will be supplied to FluidAI team. The team at FluidAI will conduct the laboratory assessments required for analytical validation of pH measurements of Origin™. This study does not pose any risk to participants as abdominal drainage fluid is routinely discarded as it is considered a waste product. No personal health information will be collected from the participants, and the study requires no follow up. Participation from subjects will be deemed complete when they are discharged from the hospital, or when their abdominal drain is removed as determined by their surgeon.

A Study of TAK-279 in Participants With Moderate-to-Severe Plaque Psoriasis

This study consists of 2 parts: Part A and Part B. Part A: Participants who did not participate in either parent study (TAK-279-3001 [NCT06088043] or TAK-279-3002 [NCT06108544]) may be enrolled and will be treated for up to 52 weeks. Participants who successfully complete Part A of the study are eligible to continue in Part B, but investigators must confirm their eligibility to continue in Part B. Part B: Participants who complete the treatment period of TAK-279-3001 (NCT06088043) or TAK-279-3002 (NCT06108544) parent studies or who complete Part A are eligible to enroll directly into open label extension treatment in Part B and will be treated for up to 156 weeks.

Longitudinal Study on Bacterial Production of LPC and LPA in Patients With Inflammatory Bowel Disease

The human body is inhabited by a complex community of microbes, collectively referred to as "microbiota". A vast majority of these bacteria are found in the lumen of the gastrontestinal tract (colon, small intestine, stomach and esophagus). Several lines of evidence indicate that changes in microbiota (bacteria) may be involved in the origin of different gastrointestinal diseases, including inflammatory Bowel Disease (IBD), with its two main types: Crohn´s disease and Ulcerative colitis. Our recent data suggest that the gut bacteria have the capability to produce lysophosphatidylcholine (LPC) and its derivative, lysophosphatidic acid (LPA), small lipid molecules that are were shown previously to be involved in the genesis and maintenance of chronic pain. We found that these molecules are higher in stool of patients with Inflammatory Bowel Disease (IBD), but it is unclear whether 1) they are produced by gut bacteria, and 2) whether their production underlies chronic pain in patients with IBD. The purpose of our study is to determine whether the gut bacteria produce LPC and LPA and induce chronic abdominal pain, which is common in many patients with IBD, even when their colitis is in remission (absence of overt gut inflammation). In this exploratory longitudinal study, we will recruit patients with IBD, aged 18-70 years, of both sexes, with a history of moderate to severe chronic abdominal pain (as defined by their gastroenterologist), which persists during remission of colitis (absence of overt inflammation on CT or MRI imaging, and baseline fecal calprotectin <200 μg/g of stool) or while having only mild gut inflammation, defined by either colonoscopy (Endoscopic Mayo score: 0-1 or Simple Endoscopic Score for Crohn's Disease score: 0-10). We will recruit 15 patients with baseline stool LPC >200 μg/mg and LPA >100 μg/mg levels after first assessment in screening visit. Recruitment will take place at McMaster University IBD clinic, currently caring for over 1600 patients with IBD (https://www.mcmasteribd.com). After study participant meets the eligibility criteria and signs the informed consent, we will collect stool and urine samples and abdominal pain scores for 3 weeks, Monday to Friday each week. Daily stool and urine samples (first stool of the day and morning (overnight) urine) will be collected, and LPC/LPA measured by ELISA. Abdominal pain will be assessed daily with a visual analogue scale (VAS). In addition, clinical symptoms will be evaluated by PROMIS (GI Belly Pain, Diarrhea, Constipation and Bloating) and DASS-21 questionnaires at the end of each week, as they assess symptoms during the preceding 7 days. Dietary intake will be assessed at the beginning of each week by a 3-day food diary. The clinical surveys will be provided online, using RedCap software and secure servers already operational within McMaster.