San Pablo City, Laguna, Philippines

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.

A Clinical Study to Evaluate DNTH103 in Adults with Multifocal Motor Neuropathy

CIFeR - A Clinician-led Intervention to Address Fear of Cancer Recurrence

STUDY DESIGN: The study is designed as a parallel cluster-randomized controlled trial with oncologists (cluster unit) treating breast, ovarian, and prostate cancer at the oncology departments at Aarhus University Hospital (AUH), Vejle Hospital (VH), Aalborg University Hospital (AAUH), and Copenhagen University Hospital (CUH), and randomized 1:1 to intervention versus active control. Participants: All oncologists treating breast, ovarian, and prostate cancer at the participating departments are eligible for the study and will be recruited by our collaborators at the participating departments. Eligible patients score >= 13 on the FCRI-SF and have completed their primary treatment i.e., surgery, adjuvant chemotherapy, and/or radiotherapy, for breast, ovarian, lung and prostate cancer at the participating departments between three weeks and three months previously. Procedure: Patients scheduled for a follow-up visit with the participating oncologists will receive a secure e-mail invitation to participate in the study and a link to a RedCap questionnaire. Patients willing to participate will provide their informed consent electronically and complete the 9-item FCRI-SF. Patients scoring >= 13 are provided with additional information about the study and asked for their consent to participate. One week before the planned follow-up consultation, they will be asked to complete a RedCap baseline questionnaire (T1). One week and three months after the consultation, the patients will be asked to complete the RedCap post-intervention (T2) and follow-up questionnaires (T3). Oncologists will complete a RedCap baseline questionnaire assessing age, gender, years of experience, and self-efficacy in managing patient FCR. Oncologists will then be allocated to the intervention or active control arm using a stratified randomization sequence generated by the Aarhus University clinical trial unit ensuring a balanced allocation of oncologists according to the cancer type treated. Oncologists will then receive a link to online CIFeR training and report their post-training self-efficacy for managing patient FCR. During the consultation, the oncologist will deliver the CIFeR intervention and complete a brief 5-item checklist on whether they delivered all five components and, if not, why. After including all patients, the oncologist is asked to complete a follow-up RedCap questionnaire on self-efficacy in managing patient FCR. The CIFeR intervention: The intervention includes five components informed by theoretical models and existing interventions for FCR: 1) FCR normalization: reassurance that FCR is a common and normal phenomenon after treatment for cancer, 2) Providing prognostic information: asking patients whether they would like information about their risk of recurrence and, if yes, providing this information, 3) Providing education and take-home information on red-flag recurrence symptoms, 4) Brief advice on managing worry: distraction, meditation, mindfulness, reassurance, and links to online resources to manage FCR, and 5) referral to a psychologist if FCR is high (FCRI-SF >= 22), or if deemed helpful by the patient or clinician. Access will be provided to ConquerFear-Group delivered online by trained psycho-oncologists. Outcome measures: Patients: The primary outcome is the change in FCR, assessed with the 9-item Fear of Cancer Recurrence Inventory Short Form (FCRI-SF). Secondary outcomes include a) anxiety and depression assessed with the The Hospital Anxiety and Depression Scale (HADS), b) patient reported intervention usefulness assessed with the Patient Centered Communication Scale (PCC), c) metacognition assessed with the metacognitions questionnaire (MCQ-30), d) unmet needs assessed with Subscale of the Survivors Unmet Need Survey (SUNS-8), e) rumination assessed with the Penn State Worry Questionnaire (PSWQ), and f) General Quality of Life (QoL) assessed with the EQ-5D for later use in cost-effectiveness analysis. All measures will be completed at all three time-points (T1-T3). At six months, the investigators will ask a subset of 15-20 patients to participate in a semi-structured phone interview about their experience with the intervention. Oncologists: Oncologists complete a general item on self-efficacy in managing patient FCR together with the 27-item Self-efficacy in Patient-Centeredness Questionnaire (SEPCQ-27) at baseline, post-training (only oncologists in the intervention group), and after completed inclusion. Based on a suggested framework for implementation outcomes, the investigators will assess with 11-point scales: 1) acceptability, 2) appropriateness, 3) feasibility, together with 4) fidelity, measured as the average number of components oncologists report having delivered to patients, and 5) sustainability measured as the proportion of oncologists in the intervention group who report having used CIFeR at least once within the last three months, measured six months after completed inclusion. Six months after the inclusion of their last patient, all oncologists will be asked to participate in a semi-structured interview and provide feedback on the CIFeR-training and their experiences with the intervention, including perceived utility and the perceived barriers and facilitators to implementing CIFeR in routine care. The investigators will also examine CIFeR e-training analytics regarding access and time spent on the various parts.

RESPONSE: Colorectal Cancer Survivors' Follow-up Care - Now Digital and Need-based

Background: Colorectal cancer (CRC) screening was implemented in Denmark in 2014 and has effectively shifted the CRC stage at the time of diagnosis from late stage (III and IV) to earlier stages (I and II)[1]. Consequently, more patients are offered curative intended treatment, which increases the number of survivors in postoperative follow-up care: In 2020, 65% of Danish patients with CRC, potentially eligible for follow-up care, had stage I-II disease[1]. The current follow-up for CRC survivors is recurrence-focused, with computed tomography (CT) imaging at 12 and 36 months[2] as early recurrence detection is critical to increase the possibility of curative treatment: The 5-year survival rate for patients treated for recurrence with curative intent is ~40% compared to <10% for patients managed with palliative or best supportive care[3-6]. However, the risk of recurrence strongly depends on the CRC stage: The 3-year cumulative recurrence rate is only 4.5%-7.9% for stage I and 10%-16% for stage II[7-9]. Consequently, the resources allocated to CRC follow-up in Denmark are primarily dissipated on patients who will never experience a recurrence. Hence, the challenge remains to distinguish between high- and low-risk patients, i.e., tailor the follow-up program to the personal risk of recurrence instead of "one-size-fits-all". A promising and novel surveillance method for CRC recurrence is to screen longitudinally collected blood samples for the presence of circulating tumor DNA (ctDNA). Serial ctDNA analyses detect recurrence with high sensitivity (88%) and specificity (97%) independent of the stage (hazard ratio (HR)=40.7; 95% confidence interval (CI): 11.6-143) and with a median lead-time of 7-10 months compared to current standard-of-care follow-up[10-13]. Thus, serial ctDNA analyses have the potential to efficiently identify the 4.5%-16% of stage I-II patients, who should be offered CT imaging, whereas the remaining 84-95% of patients are spared unnecessary CT imaging. CRC survivors with a low risk of recurrence may perceive other challenges than CRC recurrence as equally or more important in everyday life. Such challenges may include the psychological distress related to the CRC diagnosis, exaggerated fear of cancer recurrence (FCR) regardless of the actual risk of recurrence, and the presence of treatment-related organ-specific late effects, which may negatively impact their quality of life (QoL). Independently of stage, 13% of patients with CRC report persistently low QoL and/or high levels of psychological distress, e.g., impaired emotional well-being and/or high FCR[14]. Approximately half of CRC survivors suffer from organ-specific late effects, e.g., bowel, urinary, or sexual dysfunction[15-18]. In a recent study, 20% of colon cancer patients and 30% of rectal cancer patients expressed a wish for help managing their organ-specific late effects[19]. Besides organ-specific late effects, many CRC survivors experience one or more persistent general symptoms and late effects after their cancer treatment including psychological distress, depression, anxiety, insomnia, fatigue, pain, and impaired cognitive function. While the management of these so-called biopsychosocial late effects has received only little attention until recently, a growing body of evidence suggests that these issues can be treated effectively with cognitive behavioral approaches[20-24]. However, none of these challenges are addressed by today's recommended follow-up care program. To improve the management of follow-up care, recent studies have demonstrated the benefit of high patient satisfaction with electronic Patient-Reported Outcome Measures (ePROMs)[25]. Furthermore, it has been shown that 80% of Danish patients with CRC respond to ePROMs and that those with organ-specific late effects and/or biopsychosocial late effects can effectively be identified using ePROMs[19]. Hence, ePROMs have the potential to help clinicians stratify CRC survivors to postoperative surveillance or interventions for treating both organ-specific late effects and biopsychosocial late effects. New technology further facilitates the management of follow-up care: the use of digital care-guides has become increasingly popular in the Danish Health care system. One example is a framework based on a smartphone app that enables implementation of a comprehensive digital care guide in the follow-up program for CRC (Emento)[26]. This app can help maintain patient autonomy, acting as both a reference work and a timed tool to inform, educate, and guide the patient through the follow-up program. RESPONSE proposes to use each of the elements described above in a new, individualized follow-up program for CRC. All elements have already been tested and have shown their great potential in separate efficacy trials[11-13,19,23,25]. However, the impact of combining all four elements in a single follow-up program has never previously been investigated. Aim: The overall aim of this study was to investigate whether the combination of the above elements in recurrence surveillance, could improve health-related QoL (HRQoL), without compromising overall survival (OS) and recurrence-free survival (RFS) or increasing costs. Thus, our study objective was to design a surveillance program fulfilling these criteria. Further, the objective was to conduct a trial where this program could be compared to standard-of-care recurrence surveillance. The new follow-up program includes: 1) serial ctDNA monitoring to identify individuals with high risk of recurrence, 2) serial ePROMs monitoring to identify 'organ-specific late effects' and 'biopsychosocial late effects', 3) planned and systematic management/intervention of recurrence and late effects, and 4) personalized self-managed follow-up by a digital care guide as a smartphone application. Study design: This new program will be compared to the standard-of-care imaging-based recurrence surveillance in a Danish multicenter, interventional effectiveness trial, including 392 patients from 11 surgical centers. The patients will be divided into two arms: the intervention group (IG) and the standard-of-care group (SG). IG patients (n=196) will receive all the following at 3-,12-,24-, and 36-months post-surgery: 1. Recurrence risk stratification by plasma ctDNA. 1. If ctDNA becomes positive, CT imaging of the thorax and abdomen will be performed. This enables the CT imaging resources to be directed at the high-risk individuals (=ctDNA positive) only. 2. The results of the CT imaging are discussed at the usual MDT at the responsible surgical department, where pathologists, oncologists, CRC surgeons, and radiologists are present. The MDT decides whether further diagnostic initiatives should be taken, e.g., endoscopy or further imaging. 3. If recurrent disease is detected, the patient is treated according to the national Danish guidelines, and the outcome is registered in the RESPONSE trial. 4. If a recurrence is NOT detected by imaging or subsequent clinical examinations, the patient returns to the RESPONSE trial with increased ctDNA testing frequency every four months. 5. If longitudinal ctDNA tests become negative, the patient returns to the default ctDNA test frequency. 6. If longitudinal ctDNA tests are repeatedly positive, CT imaging will be prompted and discussed at MDT until a site of recurrence can be confirmed. 2. Personalized self-managed follow-up care, using a digital platform with longitudinal collection of ePROMs to identify 1. whether patients suffer from organ-specific late effects and/or biopsychosocial late effects 2. whether this impacts patients' overall HRQoL. 3. Intervention for organ-specific late effects and/or biopsychosocial late effects if needed. SG patients (n=196) will receive standard follow-up with CT imaging at 12- and 36-months post-surgery, at the surgical departments according to Danish national guidelines. Any local variation/addition to the standard follow-up program will be allowed. All SG patients will have longitudinal blood samples collected at the same time points as IG patients but only analyzed after the end of the trial, to enable comparison of ctDNA vs. CT imaging as a recurrence predictor. Furthermore, SG patients will receive similar ePROMs as IG patients to collect information at the same time points. However, these will only be analyzed after the end of the trial. Outcomes and power calculation: The primary study outcome will be the difference in HRQoL between groups. This will be calculated as the difference in EORTC-QLQ-C30 (global health/QoL domain) between IG and SG at 36 months. A mean global score of 61 points in the SG is assumed. A score difference of 7 or more between groups will be considered as the minimal clinical important difference (MID). Thus, 170 patients are required in each group to detect an increase of 7 for a mean global score of 68 in the IG with 80% power and 5% significance level. Expecting a drop-out rate of 10%, 189 patients need to be included in each group. For the secondary objective, OS and RFS, the difference in cumulative RFS and OS between groups will be calculated at 3 and 5 years. Expectantly the cumulative RFS will be 93% in the SG and 92% in the IG. With 196 patients in each group, a decrease in RFS of 9% in IG can be shown with 80% power at a 5% significance level. Thus, the number of included patients is increased to 196 in each group. Non-inferiority will be declared if the difference in RFS is within this limit. The mean OS in the groups is expectantly 77,5%. With 196 patients in each group, an increase of 10% in OS for the IG can be shown with 70% power at a 5% significance level. Data analyses and statistics: All data will be presented using descriptive statistics. The ePROM scores will be calculated according to the scoring guidelines for each of the questionnaires. Missing PRO data in form of missing items within an ePROM assessment will be imputed according to the questionnaire's scoring guideline. The incremental cost-effectiveness ratio (ICER) will be calculated as ∆cost/∆effect. QALY will be calculated as life expectancy x HRQoL, as determined by the Danish value set for EQ-5D-5L. Kaplan-Meier estimates will be used for the estimation of median times to clinical recurrence, disease, or death, and their confidence intervals stratified according to follow-up intensity. The difference in clinical recurrence versus molecular recurrence will be compared using paired t-tests and regression analyses. Data will be analyzed as intention-to-treat and per-protocol. Interim analyses will be made when 50% of patients in each group have been included, and when 100% in each group have been included and have completed a one-year follow-up. Quality insurance and ethics: Data completeness and quality will be monitored by the RESPONSE steering committee, and The General Data Protection Regulation, the Danish Data Protection Act, the Health Act, and the Helsinki II declaration will be complied with unconditionally. The results of the RESPONSE study are expected to be published in international scientific journals. The reporting will follow the CONSORT guidelines for reporting randomized controlled trials.

The GLACE Study: Evaluating CLAAS With ICE Guided LAA Closure

The ctDNA-RECIST Trial Part One

Background: Circulating tumor DNA, (ctDNA) has the potential to better monitor treatment efficacy compared to imaging, possibly sparing the patient for ineffective treatment and their associated toxicity an allowing for an early change of the treatment approach. Based on multiple dataset we have defined ctDNA-RECIST - the ctDNA response evaluation criteria. Aim: This phase II randomized trial evaluates the use of ctDNA Response Evaluation Criteria in Solid Tumors (ctDNA-RECIST) versus standard imaging-based RECIST to guide treatment decisions in patients with metastatic gastrointestinal cancers. Design: Patients are randomized 1:1. Patients in Arm A are offered standard treatment with response evaluation according to the RECIST criteria based on imaging, and treatment pauses according to institutional guidelines. In Arm B, treatment response is evaluated based on change in ctDNA between the baseline sample and the evaluation and confirmation sample, according to ctDNA-RECIST: - Progressive disease: An increase of ctDNA above the previous value with no overlap of the two CI's - Stable disease: A value within CI of the previous value. The category also includes samples with both previous and present value being 0 (undetectable). - Partial Response: A decrease below the previous value with no overlap of the two CI'S but the lower CI does not overlap 0. - Complete response: Decreasing value to an undetectable level - Near complete response: A decrease below the previous value with no overlap of the two CI'S and with the lower CI overlapping 0 Complete and near complete response can be combined and classified as maximal response. The study is initiated as a feasibility study (part one)and will continue into the expansion trial after interim analysis.(part two)

Danish Evaluation of Early Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure

Atrial fibrillation (AF) is the most common arrhythmia in patients with heart failure (HF), with rates ranging between 20-65%, depending on age, severity of HF, subtypes of HF and duration of HF. The two conditions have an intricate and often overlapping pathophysiology, with each condition leading to development of the other, as well as progression of disease. Studies have shown that the presence of AF in HF patients is associated with increased morbidity and mortality, deterioration in HF, exacerbated HF symptoms, and reduced quality of life. The optimal treatment of AF in the presence of HF remains unknown. Currently, there is a pull towards catheter ablation as first-line therapy for AF in HF patients. However, there is no solid scientific evidence to support this approach. Furthermore, it is unknown whether early rhythm control by catheter ablation in HF patients is beneficial. The investigators aim to conduct a pragmatic, randomized clinical trial designed to evaluate the efficacy and safety of early catheter ablation for AF in patients with HF compared with standard treatment. Eligible patients with HF and AF will be prospectively screened from all Danish hospitals and randomized 1:1 to early catheter ablation with pulmonary vein isolation (within 6 weeks) or standard guideline directed treatment for AF. Patients with reversible causes for AF, conditions that preclude the use of catheter ablation or previous catheter ablation for AF will be excluded from the study. Randomization and follow-up will be conducted at six specialized sites in Denmark. There will be one scheduled on-site 12-months follow-up visit after randomization. All clinical follow-up will be conducted at the patient's local hospital, according to standard practice and out of trial setting. Information regarding hospital visits/admissions, events, adverse events, changes in medication, cross-over, heart rhythm and rate, and results of relevant blood-work will be ascertained through systematic patient chart-review at pre-specified time-points. The results from this trial will mold future treatment of AF in HF patients. The investigators hypothesize that early catheter ablation reduces the risk of HF hospitalizations and mortality when compared with standard treatment, thereby significantly improving the clinical prognosis for patients with HF and AF.

Inflammation's Impact on Heart Disease and Diabetes

The goal of this observational study is to investigate the relationship between treatment responsiveness and inflammation both systemically in blood, and peripherally in tissue biopsies, focusing on its relevance to cardiometabolic disease and associated conditions. The study aims to develop a predictive model to identify individuals most likely to benefit from anti-inflammatory treatments, thus supporting personalized therapeutic strategies. Main research questions: 1. To investigate if the therapeutic agents modulate the inflammatory response linked to obesity and cardiometabolic disease 2. To determine the underlying factors that contribute to variations in individual responses to anti-inflammatory drugs Study design: The study will involve two participant groups: - Healthy control group, composedrised of normal weight individuals - Obese adult patients, scheduled to undergo bariatric surgery. Participant procedures: - Baseline testing: An initial test will evaluate treatment responsiveness. - Tissue sampling: Tissue biopsies are obtained during surgery and undergo detailed analyses, including ex vivo treatments - Follow-up assessments: Participants will be reassessed a year after surgery to evaluate long-term outcomes. Methods: - Molecular studies: Whole blood and peripheral tissue biopsies (adipose tissue, liver, muscle and intestinal biopsies) will be analyzed to identify cellular and molecular pathways associated with treatment responsiveness. - Predictive modeling: Clinical, molecular, and biochemical data will be integrated to create a model predicting individual responsiveness. - Insulin sensitivity analysis: Advanced imaging techniques will measure tissue-specific glucose uptake. Hypotheses: Impaired ability to regulate the inflammatory response correlates with cardiometabolic disease. Anticipated Outcomes: The study seeks to support precision medicine approaches for addressing cardiometabolic disease. This research builds on previous findings about the role of inflammation in cardiometabolic dysfunction. By differentiating responders from non-responders, the study aims to support targeted therapeutic strategies for inflammation and cardiometabolic health.

Probiotic Treatment of Orthodontic Patients

Safety and Performance of UCon Patch Electrode

The overall purpose of this pivotal clinical investigation is to evaluate the UCon device with a Patch Electrode with respect to clinical safety and device performance in a cohort of 180 patients with OAB/BD over a period of 12 weeks. The participants participate in a 12-week intervention period. For weeks 1-6, participants will be randomized (2:1 randomization) to either a treatment group using UCon-Patch with Time Limited stimulation or a sham group using UCon-Sham with sham stimulation. Participants in the treatment group will receive the actual stimulation with the intent of improving their symptoms, whereas those in the sham group will receive sham stimulation for short periods of time believed not to be capable of improving their symptoms. For weeks 7-12 of the intervention periods, the treatment group has the opportunity to add Urge stimulation to the Time Limited stimulation, while the sham group shifts to using UCon-Patch Time Limited stimulation. To assess the safety and performance of the UCon device on equal terms with similar devices in the market, the full intervention period with UCon will be conducted over 12 weeks, evaluating safety aspects of UCon on longer terms and confirming continued effects after 6 weeks in the treatment group. Additional analyses on data related to primary and secondary endpoints with safety and performance data from the 12-week follow-up will also be performed, but the primary analysis will focus on baseline and 6-week follow-up data.