Hamilotn, Canada

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

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).

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.

A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer

Kinematic and Mechanical Alignment Randomized Trial

Total Knee Arthroplasty (TKA) is recognized as a highly effective procedure for alleviating pain and restoring function in patients with knee arthritis. Despite its high success rate, approximately 20% of patients remain dissatisfied with the outcomes, primarily due to loss of functional outcomes, persistent pain, and reduced knee range of motion. This has sparked a debate on the optimal surgical alignment technique in TKA-whether mechanical alignment (MA), or personalized alignment philosophies such as kinematic alignment (KA) or restricted kinematic alignment (rKA) provides superior patient outcomes. MA traditionally targets a neutral 180-degree hip-knee-ankle (HKA) axis, as it was taught traditionally that this approach focuses on the longevity and stability of the implant. However, this one-size-fits-all philosophy overlooks individual anatomical differences. Personalized alignments such as KA customize the placement of prosthetic components to replicate each patient's unique knee geometry and ligament tensions. Personalized alignment philosophies aim to achieve a more natural knee motion, which may enhance patient satisfaction. The precision provided by robotic-assisted surgery has increasingly facilitated the implementation of personalized alignment philosophies in TKA. Recent evidence suggests that while MA and KA yield comparable outcomes in terms of knee functionality and motion, KA may improve satisfaction and the natural feel of the knee in certain groups, particularly those without severe preoperative deformities. There is also the emerging approach of restricted kinematic alignment (rKA) which aims to provide a compromise by aligning the prosthesis within safe anatomical limits, thus avoiding the extremes of anatomical variation. This approach tailors the surgery more closely to the individual's anatomy without the risks associated with the broader variances permitted in pure KA. Hypothetically, KA and rKA techniques should more closely replicate natural knee biomechanics and improve waking gait. There are advantages and disadvantages to these alignment philosophies which should be addressed with high-quality research. While there have been several previous randomized trials on MA vs KA and its variations, the evidence is still unclear with meta-analyses having conflicting findings. Patients will be randomly assigned to either mechanical alignment or restricted kinematic alignment. All participants will receive robot-assisted TKA using the Stryker Mako surgical robot and Stryker implants. Perioperative care, postoperative pain medications, and rehabilitation will be standardized according to local standard care.

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.

MolecuLightDX Measurement Feature Clinical Validation

The study compares the accuracy of wound measurements (area, length, and width) obtained using the ruler (standard of care) method and the MolecuLightDX device with a ground truth measurement (reference standard) derived from an expert panel.

NSCLC Liquid Biopsies and Exhaled VOC

Circulating tumor DNA (ctDNA) is increased in patients with lung cancer, and may allow detecting minimal residual disease and disease recurrence, preceding radiological detection. Detecting ctDNA in bronchoalveolar lavage/Sputum was never validated and may offer advantages over blood ctDNA, and serve as a novel biomarker for lung cancer surveillance. Lung cancer detection is possible with eNose systems with a high negative predictive value and allows prediction of treatment response to PD1 inhibitors, monitoring response to PD1 inhibitors and predicting the presence of EGFR mutations. it is reasonable to anticipate exhaled VOC to aid in detection of cancer recurrence. The study propulsion is patients undergoing surgical resection with curative intent for NSCLC, adenocarcinoma subtype at St. Joseph's Healthcare Hamilton and the Firestone Institute of Respiratory Health , above 18 years, able to provide consent. The study procedure is collecting blood, sputum, BAL samples, exhaled VOC will be collected at the following time-points/visits: (i) Visit 1 (V1): pre surgical resection; (ii) V2: immediately before discharge from hospital post-resection; (iii) V3,4,5 : 6, 12, 24 months post-surgery; (iv) V6: unscheduled at any sign of recurrence. to note, blood sputum and BAL will be collected at visit 1 and 2 from everyone and at visits 3-6 only from those who harbor a mutation of interest.

EMG Biofeedback Training to Improve Balance in Individuals with Multiple Sclerosis

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.