Sweden, Sweden

The Role of Occupational Therapy for Improving Medication Management for Persons With AMD

Many clients with low vision are unaware of OT, or the services OT can provide to assist with low vision needs. During the times designated for low vision care at The Eye and Vision Center of MCPHS, clients with Age-related Macular Degeneration (AMD) will be offered a one hour OT session to provide traditional OT interventions which they would not normally receive unless referred to a community based organization offering occupational therapy services. Clients with AMD who choose to receive the one hour OT service will be provided with 1:1 education regarding the devices and strategies that may improve their ability to perform medication management skills. Clients will complete the MediCog and the Revised-Self-Report Assessment of Functional Visual Performance (R-SRAFVP) assessment tools with the assistance of the OT. These tools will inform the therapist to areas of client needs and allow for focus on intervention to support these challenges. Follow up in OT 4 weeks post intervention will allow therapist to reassess the effectiveness of interventions provided via a phone or in-person interview as well as provide the assessments again. Second set of data from these assessments will be compared to initial findings obtained.

Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder

From Day 1 to Day 7, TM buprenorphine and randomized INDV-2000/Placebo will be administered, INDV-2000/Placebo will be administered alone from Day 8 onward. The randomized treatment period starts when the participant receives randomized treatment (at Day 1) and ends at his/her last study visit, if on INDV-2000/Placebo alone, or ends when starting buprenorphine rescue therapy.

REBYOTA™ Prospective Registry

Cold Agglutinin Disease Real World Evidence Registry

A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation

This is a multicenter, prospective study of up to 150 relapsing-remitting MS participants/ The study is looking to see if patients who have not had a relapse in the past year would benefit from switching to ofatumumab. After giving consent, participants will have a 1 week screening/qualification period. If they qualify to continue, they will start a a six month run-in period during which lab samples will be collected. Patients that are relapse-free during the run-in period will continue into next period of the study in which they will be randomized to either ofatumumab or continued therapy for the next 15 months. Every 3 out of 5 randomized participants will be selected to wear a digital study watch to collect physical activity, sleep, and vitals during this 15 month period. The study watch will be worn 24 hours a day, 7 days a week but can be removed during showers/bathing. At the end of the 15 month period, a study completion visit will be held. The total study duration is 21 months plus 1 week for screening/qualification.

Mino-Lok Therapy (MLT) for the Treatment of CRBSI/CLABSI

This is a Phase 3, multi-center, randomized, double-blind study to determine the efficacy and safety of MLT, a novel antibiotic lock therapy that combines minocycline with edetate disodium in 25% ethanol solution. Mino-Lok Therapy is being developed as an adjunctive therapy for the treatment of catheter-related or central line associated bloodstream infection (CRBSI/CLABSI) in combination with appropriate systemic antibiotic(s), to preserve central venous access and to avoid the complications and morbidities associated with catheter removal and reinsertion. Approximately 144 subjects who have been diagnosed with CRBSI/CLABSI and who meet all necessary criteria for the study will be randomized in a 1:1 ratio to 1 of 2 treatment arms: - MLT Arm: MLT + SOC intravenous (IV) antibiotic therapy; or - Control Arm (subjects randomized to the Control Arm will receive treatment based on the type and virulence of the infecting organism as documented by the Investigator prior to randomization): The antibiotic lock should be comprised of the best available therapy at the sites. Prior to randomization, the Investigator at each site will determine the antibiotic used in the lock, the dose, the dwell time, and the number of days of administration (minimum of 7 days) based on standard institutional practices or recommendations from the Infectious Diseases Society of America (IDSA) guidelines. In the event that the subject is being treated with more than 1 systemic SOC IV antibiotic, the Investigator will specify a single antibiotic that should be used for the antibiotic lock. It is acceptable for the SOC antibiotic lock to differ from the SOC IV antibiotics, as necessary per local SOC. All infecting organism types are permitted (eg, S. aureus, S. epidermidis, Candida spp., Pseudomonas aeruginosa). Randomization will be stratified by type of CVC, presence of neutropenia, and by virulence of the infecting organism. The primary endpoint for this study is the time (in days following randomization) to a catheter failure event between randomization and TOC (Week 6) in the Intent-to-Treat (ITT) Population. A catheter failure event is ANY of the following: - All-cause mortality at TOC (Week 6). The event time is the day of death; - Catheter removal for any infection-related reasons (including worsening of symptoms or failure to eradicate the infection). The event time is the day the catheter is removed; - Inability to administer study drug. The event time is the day the Investigator determines the catheter is no longer functional; - Worsening of systemic signs and symptoms of infection that result in change in systemic anti infective treatment. Note that changes in treatment based on susceptibility data will be permitted. The event time is the day the treatment is changed; - Demonstration that the baseline pathogen is not eradicated from the blood culture collected within 72 hours following randomization despite 72 hours of antibiotic therapy to which the infecting organism is susceptible. Best clinical practice and subject safety may dictate changes in treatment prior to 72 hours. The event time is the day of the positive culture; - Demonstration that the baseline pathogen has recurred based on blood culture results by Week 6 of the study. The event time is the day of the positive blood culture documenting the recurrence. If a subject does not show any signs and symptoms of an infection and there is a negative blood culture prior to Week 6, then a blood culture does not have to be performed at Week 6. Subjects whose catheter was removed for reasons not related to the baseline infection also do not need to have a blood culture at Week 6; or - Demonstration that the baseline pathogen is part of a newly diagnosed deep-seated infection by Week 6 of the study. The event time is the day of the new diagnosis. Removal of the CVC prior to TOC because the catheter is no longer needed will not be considered a catheter failure and these subjects will be censored at the time of catheter removal.

Ultrasound Guided Femoral Nerve Block

In this proposed protocol the investigators will conduct a prospective, randomized control trial comparing the efficacy of Ultrasound Guided Femoral Nerve Blockade (USFNB) versus the standard of care pain management by parenteral injection of opioid pain medication of patients presenting with hip fracture at the BIDMC ED. We hypothesize that USNFB approach will be non-inferior in achieving pain control (efficacy) and superior in the total dose of opioids (lower amount) as compared to the standard protocol. The enrolled population will be randomized 1:1 using a simple balanced randomization scheme. Participants will be surveyed six times 6 times on a Visual Analog Scale (VAS)* on their pain intensity reduction over 4 hours. Physicians performing the block will be surveyed promptly following the procedure regarding difficulty performing the block and its efficacy. Specific Aim #1: The investigators hypothesize that in patients presenting to the ED with hip fracture, USFNB will demonstrate equal efficacy in pain relief with fewer side effects when compared to conventional parenteral opioid therapy. The investigators evaluate this hypothesis by monitoring Visual Analogue Scales (VAS) in patients receiving either USGFNB or opioid therapy over the first 4 hours of observation. The side effects will be noted during the same interval of time. Specific Aim #2: The investigators hypothesize that in patients presenting to the ED with hip fracture, USFNB will reduce the amount of narcotic used to control pain. The investigators will evaluate this by studying narcotic use over the first 4 hours of evaluation.

Biomarkers in Infection

The body's immune system and a subsequent inflammatory response are triggered during infection. The detection of an activated immune system, and an indication of the degree of the host response, is helpful to the clinician both in assessing the severity of infection and in patient treatment and management. Currently, the white blood cell count and the differential are the most common laboratory parameters for measuring host response. The sedimentation rate and CRP are also used to detect inflammation. However, these tests are all imperfect predictors, and a test providing a better assessment of immune response would be helpful to the clinician in patient care. Additionally, understanding host response to infection may be helpful in understanding the biology and pathophysiology of sepsis. There are other biomarkers and inflammatory markers that may be found early in the initial presentation of infection such as cytokines (VEGF IL-1,IL-4,IL-6, IL-10, PAF, TNF, lectins iNoS,etc.) and clotting factors (protein C, d-dimer, complements involved in the clotting cascade, CRP, etc) that may provide a means of early detection of systemic inflammation, cell dysfunction, and related conditions. Early identification of patients at risk for systemic inflammatory syndromes, sepsis and septic shock may help direct patients to earlier antibiotic administration and early intervention with goal directed therapy. It may also serve as a tool for risk stratification when components such as age, comorbid illness and infection type are included. The endothelium and endothelial cell markers are important in sepsis, yet a somewhat under-studied field of research. Additionally, the endothelium is a key regulator of the microcirculation, a place where oxygen diffusion occurs. One focus of this study is to measure endothelial markers (ie VEGF) and other cytokines with the goal of correlating these markers with severity of sepsis. Another focus is to study the response of various components in the blood, including the leukocytes, red cells, the endothelium, as well as cellular components such as the mitochondria. We will specifically look at alterations in thiamine, Vitamin D, CoQ10,l-carnitine and other nutrients as part of (and as related to) the body's response. Recently, a non-invasive method of assessing microvascular circulation by orthogonal polarization spectral (OPS) imagery has become available using a non-invasive technology known as orthogonal polarization spectroscopy. This technique enables direct visualization and quantification of microcirculatory blood flow, and represents an important surrogate outcome to which endothelial cell marker may be correlated. This will involve placing the microscopy probe gently against the sublingual mucosa and collecting a videotape of the circulation lasting about twenty seconds. This process involves minimal (or no) risk - it is akin to taking a temperature and uses no radiation. This videotape will be examined later by a novel software program that quantifies the circulation and used as an important surrogate outcome measure. Additionally, we are going to perform echocardiography to better understand the heart's response to sepsis, and correlated the molecular responses that we find with the changes in the responses by the heart. In addition, we will assess microvascular flow in the skeletal muscle in the forearm using diffuse correlation spectroscopy (DCS). DCS is a novel technique that can be used to measure peripheral tissue perfusion noninvasively and has the potential to provide insight into microcirculatory health and end-organ perfusion. DCS measurement is performed using a small sensor, similar to a pulse oximeter sensor, that attaches to the skin using adhesive. It uses near-infrared light to illuminate the tissue. The change in the transmitted light through the tissue due to the moving red blood cells is characterized to quantify the microvascular flow. DCS is noninvasive, uses no radiation, and involves minimal (or no) risk. DCS measurement will be performed in conjunction with vascular occlusion test (VOT), which involves having a blood pressure cuff placed on the upper arm to cause occlusion and reperfusion of blood flow distally to measure dynamic changes in microvascular flow. We will measure endothelial glycocalyx degradation products (e.g. heparin sulfate, syndecan, etc) in the urine. This is a multicenter, observational pilot study which aims to evaluate how early biomarkers of infection an inflammation perform in identifying patients at risk for poor outcomes in sepsis and septic shock. The study will utilize a cohort of patients presenting to the ED with suspected infection as well as non-infected control population. These patients will be compared with a non-infected population. Enrolled subjects in the infected group will have blood samples and chart review obtained at enrollment, 24, 48 and 72 hours. For the control group, only a single blood draw will be collected at enrollment. Urine may be collected in a convenience sample of patients Enrolled subjects will also undergo physiologic assessments using echocardiography, Microscan, Non-invasive cardiac output monitor (NICOM), DCS, extremity temperature as well as End-Tidal C02 measurements if a trained researcher is present.

Integrated Cancer Repository for Cancer Research

The integrated Cancer Repository for Cancer Research (iCaRe2 http://icare2project.org) is a unique sociotechnical resource for the collection and management of cancer and health-related data at the Fred & Pamela Buffett Cancer Center at University of Nebraska Medical Center (UNMC). The iCaRe2 is a multi-center, semantically-interoperable and easily-customizable cancer data resource which is aimed at collecting, managing, mining and sharing the comprehensive, multi-dimensional cancer-related data on cancer patients and biospecimens (such as tumor specimens, germ line DNA, serum, urine, and plasma) collected from those individuals. The iCaRe2 provides: (i) a HIPAA compliant, secure, efficient and user-friendly mechanism for data and validation; (ii) utilization of standard vocabulary and data elements; and (iii) the ad-hoc data reporting capabilities. The iCaRe2 serves as a collaboration platform for studies (including clinical trials) performed in centers with expertise in cancer biology, pathology, epidemiology, genetics, early detection, and patient care. The iCaRe2 has been developed as an expansion of the biocomputing framework that initially included four multi-center collaborative registries: (i) the Pancreatic Cancer Collaborative Registry (PCCR) established in 2001, (ii) the Breast Cancer Collaborative Registry (BCCR) established in 2006, (iii) the Thyroid Cancer Collaborative Registry (TCCR) established in 2006, and (iv) the Great Plains Health Informatics Database (GPHID) established in 2011, to enroll subjects who have no personal history of cancer diagnosis at the time of enrollment. At present, this framework has been incrementally expanded to include the Thoracic Oncology Collaborative Registry (TOCR), GenitoUrinary Cancer Collaborative Registry (GUCARE), Head and Neck Cancer Collaborative Registry (HNCCR), Gastrointestinal & Abdominal Cavity Cancer Collaborative Registry (GACCaRe), Central Nervous System Tumor Collaborative Registry (CTCR), Leukemia and Myeloid Neoplasm Registry (LEMN) , Gynecological Cancer Collaborative Registry (GCCR), Sarcoma Collaborative Registry (SARCR), Melanoma Collaborative Registry (MELCR), Plasma Cell Dyscrasias Collaborative Registry (PDCR), Neuroendocrine Collaborative Registry (NETR), Non-Melanoma Skin Cancer Registry (NMSC) and Auxiliary Cancer Registry (ACR). The iCaRe2 group elected to use a "confederation model", as opposed to a traditional registry or network model. It was felt that these latter models implied that the registry or network would assume control of an individual Center's database. The major advantages of a confederation model include the flexibility to use selected Centers for different research projects based on a Center's resources and expertise and the ability to have different strategies to address various research questions. It was also recognized that for this model to be successful, it is essential to have a standardized approach to data collection (patient information and biospecimen annotation) and reporting. A confederation would also encourage participation of any interested Center, irrespective of its size or location. A web-based registry iCaRe2 was developed and made available to any Center to participate in data collection and storage of cancer related data.

Glufosfamide Versus 5-FU in Second Line Metastatic Pancreatic Cancer