Fakse, Denmark

A Feasibility Study of Nature-based Health Interventions for People With Mild to Moderate Anxiety, Depression and Stress

A Clinical Study on the Effect of Discontinuing Alendronate in Postmenopausal Women with Osteoporosis After a Treatment Period Without Fractures

FDG-PET/CT vs. CT for Monitoring Metastatic Breast Cancer

Background Breast cancer is the most commonly diagnosed cancer in Europe and worldwide. With a continuously increasing incidence, it is estimated that by 2040, the breast cancer burden will increase to more than three million new cases per year worldwide, with more than one million breast cancer-related deaths per year (50% increase). The prognosis of breast cancer is steadily improving due to the early detection of primary cancer through screening programs and revolutionising treatment development. Despite this, approximately one-third of patients diagnosed with primary breast cancer will develop metastatic disease. In the metastatic setting, therapy improvements have made breast cancer a chronic disease with declining mortality rates, and several effective treatment lines are available for metastatic breast cancer patients today and in the future. This favourable situation requires accurate methods to assess response to treatment to achieve the most effective treatment planning. FDG-PET/CT is increasingly used in cancer staging. Several studies have shown improved sensitivity of FDG-PET/CT compared with conventional imaging for diagnosing metastatic breast cancer in retrospective and smaller prospective studies. We expect FDG-PET/CT to detect disease progression earlier than CT in patients treated for metastatic breast cancer, enabling earlier start of second-line therapies. This has the potential to increase the beneficial effect of second-line therapies at the individual level and result in a delayed need for third-line therapies, prolonged overall survival, and improved quality of life compared with patients monitored with conventional CT. Currently, no specific recommendations are provided for a diagnostic modality to monitor treatment response in patients with metastatic breast cancer. European clinical practice guidelines (ESMO) state that there is no evidence of any staging or monitoring approach for metastatic breast cancer patients that provides overall survival benefit over another approach. ESMO suggests that FDG-PET/CT might provide earlier guidance in the monitoring of bone-only or bone-predominant metastasis, but it is emphasised that prospective trials are needed to study the impact of this on treatment decisions and overall survival. This is the evidence that MONITOR-RCT will deliver. Study objectives The primary objective of the MONITOR-RCT is to demonstrate that in patients with metastatic breast cancer, response monitoring based on FDG-PET/CT is superior to response monitoring based on CT with respect to overall survival. The objective will be based on applying standardized response evaluation criteria, using an appropriate adaptation of the PERCIST criteria for FDG-PET/CT and the RECIST1.1 criteria for CT. Secondary objectives of the MONITOR-RCT are to demonstrate superiority with respect to the quality of life and exposure to oncologic treatment and to investigate the cost-effectiveness. Consequently, the primary endpoint of the study is overall survival. Secondary endpoints are quality of life, exposure to oncologic treatment, and cost-effectiveness. Study design The MONITOR-RCT study will be an international multicenter study. The design will be a parallel group comparative randomized trial comparing an experimental monitoring strategy based on FDG-PET/CT with a standard monitoring strategy based on CT. Eight hospital sites in Denmark, two in Italy, and one in Germany will participate in patient recruitment and the conduction of the study. Inclusion criteria Criteria for inclusion will be: Women and men aged ≥18 years Diagnosis of distant relapsed metastatic breast cancer (biopsy-verified) or de novo breast cancer. In patients with distant relapsed metastatic breast cancer, biopsy verification from a distant metastasis is required. In patients with de novo metastatic breast cancer, biopsy verification of primary tumor and diagnostic imaging with distant metastasis with a typical pattern of metastatic breast cancer is required. Considered eligible for first-line systemic treatment Considered eligible for continuous treatment monitoring by scans. Signed informed consent Participants must have the ability to read and understand the following languages based on their country of participation: in Denmark, patients must be able to read and understand Danish; in Italy, they must be able to read and understand Italian or English; and in Germany, they must be able to read and understand German or English. Exclusion criteria Criteria for exclusion will be: Pregnant or lactating women Ongoing oncological treatment for another cancer Exclusively brain metastasis Allergy to FDG Target population Participating patients should have newly diagnosed metastatic breast cancer and be considered eligible for initiating first-line medicinal treatment and subsequent regular response monitoring. This is the patient population for whom a benefit from FDG-PET/CT-based response monitoring is expected. They are very similar to the criteria defining the populations investigated in Vogsen et al. (2023) and Naghavi-Behzad et al. (2022). Quality of life questionnaires Quality of life questionnaires will be completed at home every three months during the first year and every six months later. Two questionnaires will be used: EQ-5D-5L FACT-B In addition, patients can report complaints related to the conduct of scans in a final open question at the end of the questionnaires. Interventions The intervention of interest is the use of FDG-PET/CT for response monitoring compared with CT for response monitoring. The use of CT as a monitoring modality represents the usual care in patients with metastatic breast cancer. FDG-PET/CT scans will be evaluated using the standardized response evaluation criteria for patients with metastatic breast cancer (PREMIO criteria), whereas the CT scan will be evaluated using the RECIST 1.1 criteria. Both criteria aim at classifying the patient as having complete (metabolic) response (CR/CMR), partial (metabolic) response (PR/PMR), stable (metabolic) disease (SD/SMD), equivocal metabolic disease (EMD) or progressive (metabolic) disease (PD). The PREMIO set of response evaluation criteria is an adaptation of PERCIST (for monitoring patients with metastatic breast cancer. The PREMIO criteria are defined based on data from the MESTAR study, Vogsen et al. (2023), introducing the nadir scan for comparison in cases where the disease has regressed compared with the baseline scan. Clinical decision-making: For patients in the intervention group, clinical decision-making will be supported by FDG-PET/CT and PREMIO, while the conventional group will be supported by the CE-CT and RECIST 1.1. The decision-making will be in both groups following the current standard according to the local practice and following international guidelines. The decision-making may include a request for further imaging procedures. Parameters such as toxicity profile and the patient's general condition will also influence treatment decisions. Major components of patient management and the main reasons for treatment decisions will be registered throughout the study. Scan procedure and interpretation: All patients will have baseline scans performed before treatment and according to the randomization group. Treatment and follow-up scans will be approximated at regular intervals of 9-12 weeks or according to local guidelines. The choice of the diagnostic modality does not influence the monitoring intervals or time points. Contrast-enhanced CT of at least the thorax and abdomen will be performed using diagnostic scan quality. Pelvic CT may be added based on clinical need. The scan reports will be made by specialists in radiology with an assessment according to the RECIST 1.1 criteria. FDG-PET/CT will follow standard guidelines from the European Association of Nuclear Medicine. FDG-PET/CT scans will be conducted on EARL2 certified PET scanners, and the quantitative assessment, using the SULpeak value of the hottest metastatic lesion, will based on the EARL2 reconstruction. The CT performed along with the PET scan will be of diagnostic quality and will have contrast enhancement, if not contraindicated. The scans will be assessed by specialists in nuclear medicine according to the suggested PREMIO criteria. According to RECIST 1.1 and PREMIO, disease measurability will be evaluated at the baseline and during follow-up in each study group. In cases of no measurable disease according to the respective criteria applied, the patient's scans will be assessed qualitatively with a parallel response categorization. This categorization slightly differs from the one used in the case of measurable disease, but it still allows for the distinction of progressive disease from all other states. CT and FDG-PET/CT scans will be viewed based on the existing standard software. Viewing of FDG-PET/CT scans will be further supported by software developed as part of the establishment of the PREMIO criteria. Application of the criteria remains a task for radiologists or nuclear medicine specialists. Outcome variables The primary endpoint "Overall survival" will be addressed based on the primary outcome variable "Time from randomization until death". The secondary endpoint "Quality of life" will be addressed by two outcome variables. The first is the overall summary score of the FACT-B, the second the complaints related to the conduct of scans reported by the patients. The secondary endpoint "Exposure to oncologic treatment" will be addressed by the following outcome variables describing different aspects of oncological treatment: Experience of progression Start of a new treatment line because of progression Time to first progression Time from first to second progression Time from second to third progression Experiencing other diagnostic procedures Hospitalization The secondary endpoint "Cost-effectiveness" will be addressed based on relating the outcome variables "Overall survival" and "Quality of Life" to the outcome variable "Costs". These outcome variables correspond to the expected benefits described above. Sample size considerations Sample size considerations are based on using a direct comparison of the survival rates at 42 months. The statistical test finally used will be more powerful due to summarizing the information from all time points and adjustment for prognostic covariates. In the study of Naghavi-Behzad et al. (2022), the survival rate after 42 months was 34% in the CT group and 51% in the FDG-PET/CT group. Due to the introduction of new, more effective treatment lines in the last decade, we expect higher survival rates in this RCT. Sample size calculations are based on the assumption that true survival probabilities will be 39% and 56%, respectively. Under this assumption, we have to include overall 420 patients to reach a power of 87% (based on two-sided testing at the 5% level). According to the timeline of the study, the minimal (planned) follow-up time of the patients will be 36 months, and the maximal follow-up time will be 54 months. In the above calculations, a uniform distribution of the follow-up time was assumed. With respect to the primary outcome (survival), we do not expect drop outs, as we can rely also on national registries. Hence drop-outs are not accounted for in the sample size calculation. Significance level A significance level of 5% (two-sided) will be applied. Exposure to radiation The radiation dose is an issue of consideration. The average radiation dose per patient per scan procedure is estimated, in conventional diagnostic CT, to be 9 mSv and in conventional 18F-FDG-PET/CT to an additional 4 mSv, respectively.

45 Minutes Vs. Three Hours Educational Intervention on Communication and Play for Paediatric Healthcare Professionals

BACKGROUND: Communication is an essential skill for all healthcare professionals working with children and adolescents in hospitals. There is growing focus on child-centred communication, which emphasize communicating directly with children and adolescents in healthcare rather than focusing on the parents. However, educational programmes for this remain limited while those that exist are heterogenous and often assessed without comparison groups or validated tools. OBJECTIVE: To investigate the effect on healthcare professionals' self-efficacy of a 45-minute vs three-hour educational intervention on communication and the use of play in clinical paediatric practice INTERVENTION: This trial evaluates the educational programme "Communication and Play with Children and Adolescents in Healthcare", which focuses on age-appropriate communication with paediatric patients, including the deliberate use of play. The trial compares two educational interventions that differ in duration (45 minutes vs. three hours) and learning methods. While both interventions include didactic learning, reflection, and discussions, the three-hour session adds role-play activities, whereas the 45-minute session delivers a condensed version without role-play. DESIGN: Single-centre, randomized, controlled, two-arm, noninferiority trial. A noninferiority design is used to assess whether there is a difference between the two educational interventions or if the 45-minute educational intervention is comparable to the three-hour educational intervention. SETTING: The University Hospital of Copenhagen - Rigshospitalet, Denmark. RECRUITMENT: All healthcare professionals working in the Department of Paediatrics and Adolescent Medicine at Rigshospitalet will be eligible to participate. Potential participants will be contacted by their leaders and be informed of the study. A written consent will then be obtained. SAMPLE SIZE: The sample size calculation assumes that the 45-minute intervention is as effective as the three-hour intervention for the primary outcome (self-efficacy). A non-inferiority margin of 0.25 points is set, meaning the mean self-efficacy score for the 45-minute intervention can be up to 0.25 points lower than that of the three-hour intervention without being considered inferior. Based on a one-sided two-sample t-test with a margin of 0.25, an alpha of 0.025, a power of 80%, and a standard deviation of 0.45 derived from the pilot study, the required sample size is 52 participants per group. Since the intervention is conducted in clusters of 25 participants, the sample size calculation is adjusted for cluster randomization by multiplying by the design effect, calculated as 1 + (cluster size - 1) × ICC. Assuming an ICC of 0.01 results in a design effect of 1.24 and an adjusted sample size of 65 per group. Accounting for a 10% dropout rate, the final required sample size is 72 per group. It is planned to include a total of 150 participants. RANDOMIZATION: Eligible participants will be randomly assigned in a 1:1 ratio to either a 45-minute educational intervention or a three-hour educational intervention using computer-generated block randomization through REDCap. The randomization process will ensure an interprofessional distribution of participants in each intervention group. Both the statistician and the researchers conducting the analysis will be blinded to participant allocation. ETHICS: This trial complies with the principles outlined in the Declaration of Helsinki for biomedical research. Approval has been obtained from the Danish Data Protection Agency (P-2021-426). The study was approved but deemed exempt from requiring ethical approval by The Scientific Ethical Committees for the Capital Region of Denmark (Journal-nr.: H-21028050). Participation is entirely voluntary, and both educational interventions will take place during working hours at no cost to the participants. Participants may withdraw from the study at any time without any repercussions. To ensure confidentiality, all data will be securely stored in a protected database.

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

Blood And Tears in Alzheimer's Disease

Participants under investigation of a neurodegenerative disease who have a planned lumbar puncture in the Memory clinic will be invited to this study. On the same day of the lumbar puncture, tear fluid and dry blod spots will be collected. Tear fluid is collected using Shirmer's test. Dried blood spots are obtained by a small prick in the finger with a lancet. The blood droplet is transferred onto a special piece of filter paper, where it dries. As a sub-study, participants who have provided written consent specifically for this purpose will repeat the test with dried blood spots at home one week after participating in the study. The samples are submitted to the Memory Clinic at the participant's next scheduled appointment. Tear fluid, dried blood spots, as well as blood and cerebrospinal fluid will be examined for AD-related pathology.

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.

PEGASUS - Improving Treatment for Patients with Emotionally Unstable Personality Disorder

Background and rationale: Unmet needs for patients diagnosed with emotionally unstable personality disorder (borderline personality disorder). People with emotionally unstable personality disorder, borderline type, also known as borderline personality disorder (BPD) have substantial degrees of impairment (in educational, work, family, and social functioning) even after treatment, and they contribute very substantially to the burden of psychiatric disorders on a population level. When treatment in primary care is insufficient, these patients should be referred to psychiatric integrated care-models known as "treatment packages" in the secondary psychiatric healthcare sector. The treatment packages were introduced in Denmark in 2013. More than half of patients finishing a treatment package may still have symptoms, and it is also a clinical experience and hypothesis, that many patients will continue to receive more than one treatment package either for the same disorder or for different disorders. Furthermore, the level of functioning, particularly in BPD, often remains impaired despite symptomatic relief. Family members are often both the first and the last line of defense, as they are the people whom the patient will contact 24/7, whenever there is an obstacle or a crisis related to the mental disorder. The lives of the family members are severely affected, as they may live in constant worry for their mentally ill relative, and they may need to be ready to throw everything else aside, when there is a crisis. Moreover, they will also often play the role as self-taught lawyers or case managers to help the patient to get the necessary treatment and to avoid severe social adversities. Enhanced treatment, case management and involvement of families Over the last 25 years we have learned a great deal about the benefits of providing additional support for people with early psychosis. Our OPUS trial resulted in more than 40 publications, and has been highly cited (2700 citations, February 2023 (Web of Science)). We have learned from the OPUS trial, that prompt and skilled treatment for those with recent onset psychosis can improve health outcomes. The most important elements in the experimental OPUS-treatment were involvement of families and affiliation with a case manager. The results of the OPUS trial have been replicated in many countries, and there is now solid evidence for "Early Intervention Services", summarized in a meta-analysis and a recent Cochrane Review. A next obvious research question is, whether the same clinical approaches and treatment elements could be helpful for other mental health conditions. In a recent Australian study it was shown, that caregivers of young people with borderline personality features experience adversities similar to, or greater than, that reported by caregivers of young people with other severe illnesses. Currently, except from a single trial carried out with young people with BPD, and few trials investigating the effect of psychoeducation or group therapy with relatives, we lack an evidence base to know, if comparable comprehensive treatment packages can help the patients with BPD and their families. Participants We will recruit outpatients, who have been referred to the Psychotherapeutic Outpatient Department (POD), Mental Health Centre Glostrup, Mental Health Services of the Capital Region of Denmark. The patients must have been accepted in the treatment package for BPD. The patients will be able to bring 1-2 relatives to participate in the study. Inclusion and written consent Patients will be approached at their first meeting, after getting accepted into the treatment package program at POD. If interested, the patients will be scheduled for an inclusion meeting with a research assistant from the project, who is a trained physician. The inclusion meeting will take place uninterrupted in an office at the POD. Here participating patients will receive detailed written and oral information about participation, and give informed written consent. In addition to this, the patient's relatives' experience of the PEGASUS intervention and TAU will be evaluated. The relatives' contact information will be obtained through the participating patients. They will be contacted by phone to schedule an inclusion meeting. The inclusion meeting will take place by phone call, where the relatives will receive detailed information about study participation and sign a digital version of the written consent. The participants can withdraw their consent at any time during or after the study. Assessment We will be collecting data at inclusion to the study and at study conclusion after 9-month treatment. An additional follow up is under consideration, but not scheduled. Assessment will be conducted by semi structured interviews, questionnaires, collecting data from patient records and register based data from the Danish registers. Calculation of sample size and analysis In the main trial, we will have 90% power to detect a relevant difference of 7.2 (SD 19.2) on the WHODAS, which will require 2*150=300 participants with BPD. Based on this number of participants, it will be necessary to carry out a pilot trial with 15-20 participants in each arm. We will analyze all outcomes for safety and satisfaction. As per pilot trial guidelines, we will assess nominal differences regarding safety and acceptability. Safety will be defined through potential side effects, and whether the intervention group appears to get worse over time.

REdo Transcatheter Aortic VALVE Implantation for the Management of Transcatheter Aortic Valve Failure

To determine the acute and long-term outcomes of Redo Transcatheter Aortic Valve Implantation (TAVI) for the treatment of Bioprosthetic Valve Failure (BVF) affecting Transcatheter Aortic Heart Valves (THVs) To determine the factors which predict the acute and long-term outcomes of Redo TAVI To determine the proportion of patients presenting with BVF affecting THVs who are deemed unsuitable for Redo TAVI by the Heart Team To determine the acute and long-term outcomes of surgical explantation and surgical aortic valve replacement (SAVR) for the treatment of BVF affecting THVs To determine the survival of patients presenting with BVF affecting THVs who are managed conservatively - including optimal medical therapy (OMT) +/- balloon aortic valvuloplasty (BAV)

Cardiopulmonary Adaptations to High-intensity Interval Training (HIIT) in COPD