Rade, Norway

Efficacy and Safety of KBP-336 in Obese Individuals with Osteoarthritis

Hemodynamic Determinants of Urine Output During Spinal Anesthesia

The proposed clinical trial aims to explore the relationship between urine output and mean arterial pressure (MAP) during spinal anesthesia, a subject that has not been thoroughly studied in humans despite previous research under general anesthesia. Studies have demonstrated that the diuretic response to intravenous volume loading, using Ringer's solution or 20% albumin, varies with MAP levels. Specifically, Ringer's solution shows a greater diuretic effect when MAP exceeds 70 mmHg, whereas 20% albumin is more effective at lower pressures. This differential response highlights the importance of considering MAP in the choice of fluid for managing hypovolemia and oliguria. The study's relevance is highlighted by the physiological dynamics at play, particularly how high levels of anesthesia, which influence the sympathetic nervous system from the mid-thoracic region, might reduce MAP and consequently decrease urine output. While this hypothesis has been examined in animal studies, its validity in humans remains unconfirmed. To address this, the trial will measure hemoglobin levels, MAP, and urine output simultaneously, aiming to establish a clear correlation among these variables during spinal anesthesia. This methodical approach seeks to yield significant insights with minimal additional effort, contrasting with the complexities inherent in more elaborate study designs.

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

Study of Eftilagimod Alfa (Efti) in Combination With Pembrolizumab and Chemotherapy Versus Placebo in Combination With Pembrolizumab and Chemotherapy in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC) (TACTI-004)

TACTI-004 is a double-blinded, randomized phase 3 trial in patients with advanced/metastatic non-small cell lung cancer (NSCLC) receiving eftilagimod alfa (major histocompatibility complex (MHC) class II agonist) in combination with pembrolizumab (programmed cell death protein 1 (PD-1) antagonist) and chemotherapy. The proposed clinical trial aims to compare the efficacy and to demonstrate the superiority of efti combined with standard of care (SoC, pembrolizumab and histology-based chemotherapy) compared to placebo combined with SoC in programmed death-ligand 1 (PD-L1) unselected population as assessed by: - Overall survival [OS] - Progression-free survival [PFS] per RECIST 1.1 The trial is planned to be conducted in countries in Asia, Australia, Europe and North and South America in approximately 175 experienced clinical sites.

NOL Index in Response to Pacemaker Stimulation

The Nociception Level Index (NOL Index) represents an innovative approach to monitoring nociception during general anesthesia, utilizing a combination of signals from photoplethysmography, accelerometry, thermometry, and skin conductance to assess the balance between nociceptive and antinociceptive states. Research has already established how the NOL Index correlates with both nociceptive stimuli and opioid levels, providing valuable insights into patient responses. However, the impact of changes in heart rate, specifically through isolated cardiac pacing, on the NOL Index is not yet clear. The primary goal of this study is to explore and understand how cardiac pacing might influence the readings of the NOL Index, potentially offering a new dimension to managing anesthesia effectively.

Effect of Proactive Therapeutic Drug Monitoring on Maintenance of Sustained Disease Control in Adults With Rheumatoid Arthritis on a Subcutaneous TNF Inhibitor: The Rheumatoid Arthritis Therapeutic DRUg Monitoring Trial (RA-DRUM)

There is a considerable variation in serum drug levels among rheumatoid arthritis (RA) patients on tumor necrosis factor inhibitors (TNFi), and a high number develop neutralizing anti-drug antibodies (ADAb). Sub-therapeutic drug levels and ADAb formation are major contributors to TNFi treatment failure and disease flare. Proactive therapeutic drug monitoring (TDM), i.e., individualized drug dosing based on regular assessments of serum drug levels and ADAb, has the potential to optimize the efficacy and safety of TNFi treatment. The aim of the RA-DRUM trial is to assess whether TDM is superior to standard of care in order to maintain sustained disease control without flares in patients with RA treated with the SC TNFi adalimumab. Participants will be randomized to: - Administration of TNFi based on proactive TDM (TDM group) - Administration of TNFi based on standard of care without knowledge of serum drug levels or ADAb status (Standard of care group) Participants will be followed for 18 months with on-site visits at baseline, 4, 8, 12 and 18 months and digital visits at 2, 6, 10, 14, and 16 months. Blood sampling for serum drug levels and anti-drug antibodies will be done at all visits.

Efficacy And Safety of An IRE System For Treatment of Inferior Turbinate Hypertrophy

The purpose of the IRE System is to address the clinical need for reducing the volume of hypertrophic inferior turbinate(s) causing nasal obstruction while minimizing side effects and complications. Procedure time will also be reduced. The IRE System is designed to be more comfortable for patients, as it employs a noninvasive procedure using a high voltage pulsed electric field to create irreversible nanopores in the cell membrane, leading to cell death and the reduction of tonsil volume. On basis of these finding and in view of the known safety profile (refer to Chen et.al ) and efficacy of current technologies, the purpose of the current study is to prospectively determine the efficacy and safety of the IRE System in interior turbinate reduction.

Oral Health and Dental Caries Prevention Intervention for Children in Romania

Until recently, Romania has lacked baseline data regarding the oral health status of children. A previous study by Petersen et al. was conducted in the 1990s covering only five major cities and without taking into account rural areas. Some local papers described a high caries prevalence. Only one longitudinal study assesses caries trends in Romanian schoolchildren. A contemporary assessment was therefore mandatory in order to advance scientific understanding and allow for the development of adequate public health policies. During 2019-2020, the National Oral Health Survey financed by The Borrow Foundation, evaluated a significant sample of children aged 5, 6 and 12 years, gathering baseline data on oral health according to the WHO guidelines. The data was used to estimate the distribution and severity of dental caries, the need for community-oriented disease prevention and health promotion, and the nature and urgency of the oral health intervention(s) required. The survey also established how younger age groups can be reached and evaluated. Unpublished data show that only 14% of 6 years old children have dmft 0 and the SiC index of the same sample is 9.83. High prevalence of tooth decay with high severity scores, significant inequalities in oral health and poor use and access to services showed the need for a child oral health programme. The main objectives of the program are to: 1. Reorient the traditional curative approach, which is basically pathogenic, and move towards a preventive promotional approach 2. Strengthen cross-sectoral collaboration across key settings, such as schools, communities and workplaces to promote habits and healthy lifestyles, integrating teachers and the family; 3. Raising the priority accorded to the prevention and control of oral diseases in regional and national agendas and development goals, through strengthened cooperation and advocacy. The programme is designed to deliver additional clinical prevention activities through dental hygienists, aimed at children aged three years and above attending priority nursery establishments in order to improve oral health of young children, and complemented the established national toothpaste/toothbrushing scheme. The programme will be implemented for a period of 24 months, under guidance from the WHO Collaborative Centre for Epidemiology and Community Dentistry Milan, Italy. Consent from the national and regional authorities will be obtained, nurseries will be informed and the informed consent of the parents will be asked. The total sample size will be calculated according to the WHO guidelines using a stratified sampling technique for examination sites in Bucharest, Timisoara, Cluj-Napoca, Craiova, Iasi, Targu Mures and the surrounding geographical area. The programme will be conducted in collaboration with the Universities of Medicine in the capital and the cities mentioned above, under supervision of the university staff. Data collection points will be 4 kindergartens in the Capital or metropolitan areas, 2 kindergartens in each of 2 large cities, and 1 kindergarten in each 4 villages from different geographic areas. The programme fits in the Oral Health Resolution of the Seventy-fourth World Health Assembly (WHA 74.5 - 31.05.2021) aiming at: - understanding and addressing the key risk factors for poor oral health and associated burden of disease; - fostering the integration of oral health within their national policies, including through the promotion of articulated interministerial and intersectoral work; - reorienting the traditional curative approach, which is basically pathogenic, and move towards a preventive promotional approach with risk identification for timely, comprehensive and inclusive care; - strengthen cross-sectoral collaboration across key settings, such as schools, communities and workplaces to promote habits and healthy lifestyles, integrating teachers and the family; The study design takes into consideration all principles stated in the WHO Implementation Manual "Ending childhood caries": Early diagnosis of caries lesions through clinical examinations in the nurseries, control of risk factors trough the evaluation of oral health related knowledge and behaviours and health education, arresting caries through the application of fluoride varnishes, developing primary care teams by introducing a new workforce - dental hygienists, building a framework to integrate prevention and control of dental caries into general health interventions. The project will be implemented in collaboration with the universities of Medicine and Pharmacy in the country to ensure a homogeneous distribution of evaluation sites. Selection of nurseries will be done according to the pathfinder sampling technique. This survey design is suitable for collection of data for planning purposes and monitoring of oral health programmes in all countries regardless of the level of disease, availability of resources or complexity of care. The principles of the sampling techniques are the following: - The study supposes a sample of 460 children; - There are 6 universities involved in data collection; - Data will be collected from 3 types of residential areas: metropolitan areas (180 evaluations); big cities (180 evaluations), rural areas (100 evaluations); - In metropolitan areas and big cities, 25 children have to be evaluated in the same kindergarten. - In rural areas, more than one kindergarten can be evaluated until the desired number of evaluations is obtained for the specific region. This principle has been added because kindergarten is not mandatory in Romania and the number of children enrolled in kindergarten in rural areas is quite low in some regions of the country. Distribution of data collection points: - University of Medicine and Pharmacy Bucharest will provide: - 25 evaluations in one kindergarten in Bucharest; - 25 evaluations in rural areas of surrounding counties - University of Medicine and Pharmacy Cluj will provide: - 25 evaluations in one kindergarten in Cluj Napoca; - 25 evaluations in rural areas of surrounding counties; - University of Medicine and Pharmacy Craiova will provide: - 25 evaluations in 2 kindergartens in Drobeta-Turnu Severin; - 25 in rural areas of surrounding counties; - University of Medicine and Pharmacy Iași will provide: - 25 evaluations in 2 kindergartens in Iași (2 X 25 = 50); - 25 in rural areas of surrounding counties; - University of Medicine and Pharmacy Targu Mures will provide: - 25 evaluations in one kindergarten in Targu Mures; - 25 evaluations Miercurea Ciuc; - University of Medicine and Pharmacy Timișoara will provide: - 25 evaluations in one kindergarten in Timișoara; - 25 evaluations in 2 kindergartens in Arad; According to the WHO STEPS approach, results from the first two steps - self-evaluation and collection of clinical data will be used to plan and evaluate further health interventions. Volunteer dental hygienists students will be trained deliver oral health promotion to nursery educators and oral health promotion activities for children, focusing on tailoring of key messages to the specific age and on practical preparation for delivering interventions in the nurseries along with implementing the toothpaste/tooth brushing scheme involving free daily tooth brushing to every 3 and 4-year old child attending nursery. The evaluation of the programme consolidates and builds upon previous evaluation work of the National Oral Health Survey for children. Due to the fact that it is a pilot programme aiming to be further implemented at national level, an evolving model of evaluation is appropriate. This allows the evaluation to be responsive to issues emerging from its implementation and develops the programme as a result of the evaluation findings. Methods used in the evaluation have to be formative - to adapt the programme, and summative - to assess its impact. Evaluation activity includes the collection of routine monitoring data linked with national data sets from the previous survey, assessment of the programme's impact at different time-intervals, and assessment of economical outcomes. One of the outcomes will be to assess oral health practices of children using the previously designed questionnaire from the National Oral Health Survey, meaning to describe oral health behaviour of the evaluated children in correlation to the 'County Development Index', residential area, type of residence, characteristics of the parents (education, working status) and characteristics of the child (age, gender). The County Developmental Index is a sociological index that combines county-level variables: education stock, life expectancy at birth, medium age of adult population, average living space, number of private cars to 1000 inhabitants, and average household gas consumption. Another secondary outcome will establish correlations between the levels of oral health knowledge and clinically detected oral health status and assess the impact of the intervention on the oral and general health status. Monitoring the quality of the intervention delivered by dental hygienist students will assure the necessary information to change/adapt their education to the necessary actions. Short term outcomes will be: - Increased level of knowledge and improved oral health behaviours for children in this age group - Reduced risk of new carious lesions and progression of existing lesions - Improved skills of a new profession - dental hygienists and shift of workforce - Improvement of the existing data base and implementation of a monitoring activity at national level Other potential outcomes: - Improved knowledge and behaviour within the families which might lead to an improvement of oral but also general health status - Reduced inequalities in oral health care - Reduced treatment needs and therefore reduced costs for dental treatment The research team proposed to incorporate sustainability into the process taking into account the fact that health interventions often include a number of unquantifiable variables, which add a layer of complexity in terms of environmental appraisals. The discrepancy between the existence of evidence-based health promotion interventions and their use in practice is present in almost all medical fields, but has been widely recognized as a challenge in dentistry. Clearly, the traditional modes of spreading information through scientific publication channels and passive instruction are not sufficient to reliably initiate and sustain new practices. In order to move evidence-based approaches into practice, more careful examinations of methods to introduce and sustain effective oral health practices are needed. For this project we suggested a framework multi-staged approach. This resource is designed to interweave with the many other point of the project that have been developed to guide oral health professionals and dental organizations.

Assessment of PK Similarity of FYB206 in Comparison With Keytruda in Resected Stage II or III Melanoma Patients

Clinical Epidemiology in Contemporary Patients With Myelofibrosis.

Myeloproliferative neoplasms (MPNs) are rare bone marrow disorders characterized by clonal proliferation of hematopoietic cell lineages, and include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). MF has worse prognosis, with main causes of death including acute leukemia transformation, comorbid conditions, and consequences of cytopenia. MF is characterized by progressive anemia, bone marrow fibrosis, and extramedullary hematopoiesis with splenomegaly. Moreover, the disease is associated with a heavy symptom burden including night sweats, fever, bone pain, and weight loss and worsening the quality of life. On the beginning of 2013 the European Registry for Myeloproliferative Neoplasms (ERNEST) observational study was launched and approved by several IRBs of European hematological centers. The study focused on overt Primary (PMF) and Secondary myelofibrosis (SMF; i.e., post-Essential Thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia (post-PV MF)) and aimed at describing the clinical epidemiology of large series of patients observed in clinical practice. This research was justified as the landscape of both pathophysiological and clinical knowledge in MPNs was rapidly evolving, prompting to revise diagnostic criteria, prognostication and therapy recommendations. ERNEST retrospectively enrolled 1292 patients in whom the proposed prognostic models were confirmed to differentiate treatments in clinical practice, while ERNEST-2 reported results on critical events observed in 1010 of these cases during a median follow-up period of 5.4 years.4,5 The two studies closed in December 2022. In the last decade, new diagnostic and prognostic findings have been accumulated and the availability of new approved drugs, based on results of several new clinical trials, influenced the therapy decision making in the real-world clinical practice. Therefore, the continuation of observational studies in present ERNEST-3 on large multicenter case series of patients with MF is timely and might refine the results of clinical trials. The purpose of this study observational retrospective/prospective study is to gain information on MF associated cytopenias that represent a significant challenge in the contemporary patients with MF. Currently, there are few agents aimed at treating cytopenic MF, including immunomodulatory drugs, hypomethylating agents, and JAK inhibitors such as momelotinib and pacritinib, and development of new agents specifically tailored to this patient population remains an unmet need. Therefore, this study can provide data on these patients, focusing on clinical status, quality of life, comorbidities, and treatment results over time.