Coquitiam, Canada

A Digital Support to Facilitate Sustainable Return to Work for Persons With Chronic Pain and Their Employers

A Clinical Trial for Chlorhexidine as Treatment for Vulvovaginal Candidiasis

The study is a 6 months clinical Phase II trial to compare if 1% chlorhexidine gluconate vaginal cream (Hibitane®) is at least as effective and safe as fluconazole (reference treatment) for culture-verified recurrent vulvovaginal candidiasis. The study is a randomized open non-inferiority trial with parallel treatment groups. The trial is not possible to blind for neither participants nor investigators due to the differences between study treatments. There is low risk of bias since the primary outcome variable is objective (negative vaginal culture for Candida albicans). The participants will be randomization to; - Investigational medication with Hibitane® vaginal cream 8 ml every night for a week and then prophylactic treatment with 8 ml/week for another 11 weeks or - Reference treatment with Fluconazole® 150 mg (oral capsule) every 3 days for the first 3 doses, then prophylactic treatment with 150 mg/week for another 11 weeks. The randomization ratio between the treatment groups will be 1:1. A computer generated block randomization of 15 participants will be performed by the research midwife. Allocation to the study medications will be carried out via opening of opaque sealed envelopes in consecutive order. All women will be identified through a patient log with name and Swedish personal identification number and the randomization number. The randomization number will be used on all paper and CRFs. Five research visits are planned: Visit 1 Screening - oral and written study information, signing of informed consent, vaginal culture for Candida albicans and chlamydia/gonorrhea (PCR test). Visit 2 Inclusion (baseline), within 1 week after Visit 1. Control for inclusion/exclusion criteria, randomization to study medication after positive culture for Candida albicans and negative chlamydia/gonorrhea (PCR test) - health survey, control of concomitant medications, examination, pregnancy test and control of adequate contraceptive methods to avoid pregnancy throughout the study. Visit 3 1 week (+2 days) after completed treatment. Control of AE, culture for Candida albicans and examination. Visit 4 After 12 weeks (+ 1 week) from inclusion when prophylactic treatment is completed. Control of AE and relapses, culture for Candida albicans and examination. Visit 5 Follow-up 6 months (+ 1-2 weeks) from baseline/inclusion. Control of AE and relapses, culture for Candida albicans and examination. End of study. A weekly web-based dairy (eCRF (Entermedic)) will be used for follow-up of treatment compliance, efficacy and adverse events. During the prophylactic treatment (Visits 2-3) and during the observational phase of the study (Visit 4-5), the participants are asked to report any suspicious relapses in the dairy and contact the research midwife if needed. They will also receive equipment for vaginal cultures that can be used for self-sampling at home to detect true relapses. In case of positive cultures for Candida albicans, they will be offered the same medication as previously used in the study if the treatment was effective and no adverse events occurred. Otherwise, an individual treatment option will be used. The end of study is defined as completion of the last visit of the last subject. The sponsor and the investigators reserve the rights to discontinue the study at any time for safety reasons or other reasons jeopardizing the justifications of the study. Supply, labelling, handling and storage: Chlorhexidine gluconate (Hibitane®) vaginal cream is commercially available in Sweden and will be prescribed from the hospital pharmacy for each participant. It will be stored and kept according to the instructions of the manufacturer. - Participants randomized to Hibitane® will receive a bottle (250ml) with the vaginal cream together with 10 ml syringes for vaginal administration. The Hibitane® bottle can be stored in the fridge at home between use. Women will receive specific written information as well as oral information on how to self-administer drug vaginally with the syringe. - Participants randomized to Fluconazole® will receive 14 oral capsules of 150 mg according to the dosage describe above. Compliance: Compliance will be evaluated at the follow up visits and the participants will fill out a dairy how the study medications have been taken. Data collection and data handling: Every participant will be given an individual, study specific number (i.e. study identifying code) at the time of inclusion. A code key with each individual personal data connected to the identifying code will be created (i.e. patient identification log) and stored separately at the research department at the department of Obstetrics and Gynecology, Danderyd Hosptial, Stockholm, Sweden. Data will be recorded on individual printed case report forms (CRFs) after which they will be entered into a computerized database before statistical analyses. The database will contain information on demographic variables, type of treatment and measurements in addition to the variables above.

Instructed Home-based Physical Exercise for Patients With Liver Cirrhosis

Neurotomy to Treat Synkinesis Following Peripheral Facial Palsy

Patients with severe synkinesis treated at Karolinska University Hospital with Botox injections with unsatisfying results are invited to participate in this study aiming to evaluate surgical neurotomy to synkinesis causing branches of the facial nerve. Surgical procedure: Small branches of the facial nerve are identified under microscopic magnification. Using a precise nerve stimulator the movement each nerve branch elicits is evaluated as normal or synkinetic. Pathological branches are then parted while normal functioning nerve branches are left intact. Evaluation procedure: Study participants are measured in a multimodal manner at 5 different time points during the study period; at study start, with and without Botox effect before surgery, and at 6 and 12 months after surgery. Evaluation methods: - Clinical evaluation with Sunnybrook facial grading scale, blinded to observer from video recordings at the end of the study - Neurophysiological measurements, - Quality of life, measured with validated questionnaires FaCE, FDI, SAQ - Reports of potential side effects, using Clavien-Dindo classification as well as free text

Registry for Advanced Endoscopy

Physical Exercise During Preoperative Chemotherapy for Breast Cancer

The Neo-ACT assesses the primary endpoint pathological complete response (pCR) and the secondary endpoints Residual Cancer Burden (RCB), objective tumour response (RECIST), all-cause, breast cancer-specific, and recurrence-free survival at 2, 5 and 10 years, health-related quality of life assessed by the EORTC QLQ-C30 and BR23 questionnaires, self-reported physical activity (Modified Godin Leisure Time Physical activity questionnaire), toxicity-related outcomes (chemotherapy completion rates, number of unplanned hospital admissions during NACT, objective cognitive dysfunction (Amsterdam Cognition Scan), cardiac toxicity and sick leave), device-measured physical activity level (Fitbit activity tracker), muscle strength (handgrip strength test and hypothetical 1-RM maximal leg muscle strength tests), and cardiorespiratory fitness (Ekblom-Bak submaximal cycle test). Participants randomized to the exercise group will complete 120 min exercise sessions per week from initiation of NACT to surgery (approx. five months): - Progressive home exercise program by an individualised mobile phone application, supported by local physiotherapists - Initial exercise intensity individually tailored to each patient's fitness at baseline and rate of perceived exertion during the program and adapted if required - Sessions will begin with a 3-minute moderate intensity (12-13 on Borg's Rate of Perceived Exertion (RPE) scale) warm-up.

MYTHS - MYocarditis THerapy With Steroids

Acute myocarditis (AM) is a common condition characterized by histological evidence of inflammatory infiltrates associated with myocyte necrosis of non-ischemic origin. Clinical presentation spans from indolent form to cardiogenic shock also called fulminant myocarditis (FM). Patients can be stratified on the basis of their clinical presentation: patients with left ventricular (LV) ejection fraction (EF)<50% at first echocardiogram, and those with sustained ventricular arrhythmias, called complicated AM, have a worse prognosis compared with uncomplicated cases with preserved left ventricular ejection fraction (LVEF) and without arrhythmias. Among complicated AM, FM patients are those ones at the highest risk, presenting with severely impaired LVEF (generally <40%), and with need for inotropes and/or temporary mechanical circulatory supports (t-MCS).The pathogenesis of AM is felt to be due to an immune-mediated response against the myocardium. As such, the overall objective is to evaluate the efficacy of pulsed IV corticosteroids therapy for the treatment of AM. It is proposed to test the efficacy of pulsed IV methylprednisolone in a single blind randomized controlled trial versus standard therapy on top of maximal support. The rationale for using pulsed corticosteroid therapy in the acute setting (within 3 weeks from cardiac symptoms' onset) to reduce myocardial inflammatory infiltrates favoring recovery appears strong. Nevertheless, no trial has tested this hypothesis in the very acute phase of AM, despite the high mortality rate of this condition and the fact that AM mainly affects young patients. Currently, no specific medications in the acute phase of lymphocytic AM are recommended beyond supportive therapy with inotropes and t-MCS. One Cochrane review on corticosteroids showed that almost all studies focused on inflammatory cardiomyopathies with 6 months of symptoms of heart failure (HF), and despite an improvement of cardiac function observed in low quality and small size studies, there was no improvement in the survival. In the past, only one study assessed the efficacy of immunosuppression in AM, the Myocarditis Treatment Trial (MTT) that reported no benefit from immunosuppression. Neutral results in the MTT could be ascribed to a delay in the initiation of this potentially effective treatment. Thus, 55% of patients started immunosuppressive therapy after 1 month from the onset of myocarditis, when the left ventricle (LV) was already dilated, as highlighted by a mean LV end-diastolic diameter (EDD) of 64 mm. It is expected that patients with FM have normal LV dimension during the acute phase despite severe LV systolic dysfunction. Based on a study from PI group, it was observed that FM patients recover most of the LVEF in the first 2 weeks after admission, with a median absolute increase of 30%. This finding further suggests that an immunosuppressive treatment should be started as soon as possible to demonstrate effectiveness. As little has changed in the medical treatment of this condition in the last 30 years, identification of effective drugs is needed. Patients admitted to hospital for suspected AM complicated by acute HF/cardiogenic shock and LV systolic dysfunction will be screened for randomization. Patients will be randomized in the two arms in a 1:1 ratio (Pulsed methylprednisolone therapy vs Placebo). Randomization will be performed with stratification by country. The primary objective is to demonstrate a reduction in the rate of the primary composite endpoint on patients treated with pulsed methylprednisolone therapy vs. standard therapy and maximal supportive care. Endpoints will be analyzed according to the following principles: - Intention-to-treat (ITT) population - Per Protocol (PP) population: - "Safety population" - A sensitivity analysis will also be performed on the previously defined populations after excluding patients (1) with histological diagnosis of giant cell myocarditis (GCM) or (2) who did not reach the final diagnosis of acute myocarditis based on CMRI or histology. Sample size calculation: we plan to recruit a total of 360 patients, and we expect that about 20% of these patients or local physicians will refuse randomization. This would leave a total of 288 randomized patients (144 per arm). Considering as relevant a reduction in the probability to reach the primary endpoint at 6 months from 25% in the standard therapy on top of maximal supportive care arm to 12% in the pulsed corticosteroid therapy arm (absolute risk reduction of 13% in absolute corresponding to a hazard ratio (HR) pulsed corticosteroid therapy vs. standard therapy of 0.44), the planned sample size will allow achieving a power of 0.80 with a one-sided log-rank test and an overall type I error of 0.025. The 25% figure considered for the standard therapy derives from a retrospective analysis of the patient's cohort spanning over 20 years. The calculation includes an interim analysis planned at 50% recruitment (O&#39;Brien-Fleming method). This interim analysis is accounted for in the sample size calculation with an alpha level of 0.001525 (final analysis 0.023475 alpha level) and is planned on the primary endpoint to assess a possible early treatment effect. No specific stopping rules are planned, given the multiplicity of aspects involved, but the report on safety will be reviewed by the Data and Safety Monitoring Committee (DSMC) will advise on possible aspects of the trial that need reconsideration. Sample size adaptation: We will consider, based on the DSMC advise an adaptive approach to sample size in two regards: 1. At the interim analysis, if the baseline incidence is lower than the expected 25%, the sample size calculation may be re-evaluated keeping the same HR of 0.44. For instance, if the observed incidence is 20%, maintaining the same HR of 0.44 (corresponding to an incidence of 9% in the pulsed corticosteroid therapy group, i.e. 11% in absolute risk reduction) the effective sample size needed to achieve 80% power should be increased to 360 patients. If the baseline incidence is higher than 25%, the planned actual sample size will achieve a power greater than 80% to detect a HR of 0.44 and no action will be taken. 2. Based on the conditional power method, and on the DSMC advise, we may reconsider if a less promising result than HR=0.4444 is worth pursuing, given the current observed estimate. This case would require an increase in sample size that will be discussed in terms of relevance and feasibility. For example, if at the planned interim analysis, the estimated absolute risk reduction is at least 10% (HR=0.56) with 25% baseline, and the conditional power of meeting this 10% target (instead of the planned 13%) would be at least 60%, the sample size may be increased to reach the 80% desired power. In this case, the final effective sample size should be increased to 254 patients per arm to preserve an 80% power of demonstrating the less marked difference. The flexibility allowed in the sample size estimate will be considered based on the evaluation of the interim report by the DSMC and no data will be disclosed on interim treatment estimates to the study coordinator and steering committee. The overall duration of the study from first patient first visit to last patient last visit will be 39 months. The follow-up will be up to 6 months and with additional 3 months to lock the database. Enrollment will last 30 months. In parallel, there will be a prospective registry of patients that are eligible for the trial, but they are not randomized. A second registry, called MYOCARDITIS REGISTRY will prospectively recruit all patients with acute myocarditis demonstrated by CMRI or EMB who are not eligible for randomization (not all centers will take part in this registry). The study is supported by a grant from Italian Ministry of Health (GR-2019-12368506) and Lombardy Region. Exemption from the investigational new drug (IND) regulations by FDA on August 2nd, 2021 (PIND: 15727) EudraCT identifier: 2021-000938-34

A Safety Study of Lactobacillus Reuteri BGP-014 in Patients With Ulcerative Colitis

Randomized Ablation-based AF Rhythm-control Versus Rate-control in Patients With HF and High-burden AF Extend

The RAFT-AF Extend Trial is a continued follow up of patients enrolled in the original RAFT-AF Study (ClinicalTrials.gov, NCT01420393), which evaluated whether ablation-based rhythm-control compared to rate-control improves clinical outcomes in patients with heart failure and atrial fibrillation. It was a randomised, open-label clinical trial, with blinded endpoint adjudication, conducted in 21 institutions in four countries. Patients with atrial fibrillation, New York Heart Association class II-III heart failure, and elevated NT-proBNP were included. Patients were randomized (1:1) to ablation-based rhythm-control or rate-control, stratified by left ventricular ejection fraction (≤45% and >45%). Ablation-based rhythm-control consisted of pulmonary vein isolation in paroxysmal atrial fibrillation, and additional ablation for persistent atrial fibrillation. Rate-control included AV-nodal blocking agents and AV node ablation with permanent pacing. The primary outcome was a composite of mortality and heart failure events, with a minimum follow up of two years. Secondary outcomes included left ventricular ejection fraction, quality of life, six-minute walk test and NT-proBNP. The primary analysis was intention-to-treat. From December 1, 2011, to January 20, 2018, 411 patients were randomised to ablation-based rhythm-control (n=214) or rate-control (n=197). The primary outcome occurred in 50 (23·4%) patients in the ablation-based rhythm-control group and 64 (32·5%) patients in the rate-control group (hazard ratio 0·71 95% CI (0·49, 1·03), p=0·066). Quality of life, six-minute walk distance, left ventricular ejection fraction, and NT-proBNP demonstrated greater improvements in the ablation-based rhythm-control group. In patients with high burden atrial fibrillation and heart failure, there was no statistically significant reduction of all-cause mortality or heart failure events with ablation-based rhythm-control versus rate-control. With the hazard ratio equivalent to the minimal clinically important difference and the result near statistical significance, there is a probable clinically important benefit of ablation-based rhythm-control over rate-control. This RAFT-AF Extend study is to extend follow up in RAFT-AF patients for an additional 24 months in order to have sufficient power to definitely determine if ablation-based rhythm control of atrial fibrillation is superior to rate control for the reduction of the primary outcome of all-cause mortality or heart failure event in patient with atrial fibrillation and heart failure.

Treatment of Post-covid Syndrome in Patients Treated in Intensive Care

This is a pilot RCT aiming to intervene in symptoms of poor mental health in COVID survivors at 12 months after ICU care for the COVID infection. Based on the uncertain number of patents who screen positive for mental health problems 12 months after ICU care, based on the novelty of the condition assessed, and the uncertainty about which treatment effects to expect on mental health outcomes, the study was designed as a pilot study, with feasibility measures (consent, adherence and satisfaction with the treatment) as the primary variables, and with effects on mental health symptoms as secondary variables. The study plans to assess and randomize a convenience sample of patients, as it can not be estimated which numbers can be expected, but it is aimed to include at least 40 patients in the study (20 in the intervention group and 20 in the control group). Specifically, the present study aims to 1. investigate early predictors (during ICU-care) of post-covid syndrome occurring at 3-6 months, 12 months, and 36 months, respectively, including cognitive and mental health problems, 2. deepen the understanding of mental health symptoms in ICU-treated COVID-19 survivors, mental health-related treatment seeking, changes in addictive behaviors, and the diagnostic meaning of mental health symptoms expressed in COVID-19 survivors, and 3. conduct a clinical treatment study with the following research question: for patients with post-covid mental health symptoms after 12 months, is an intervention of Cognitive Behavioral Therapy (CBT) with Acceptance and Commitment Therapy (ACT), when compared to standard clinical care (referral to primary care), feasible and associated with improved patient adherence and patient satisfaction, and secondly, does it improve the outcome of post-covid anxiety symptoms and secondary other symptoms of poor mental health and quality of life?