Banska Bysterica, Slovakia

Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults.

Effectiveness of the RISE Intervention

Rationale: People who have suffered a stroke are at high risk of functional decline, recurrent stroke and premature mortality. High amounts of sedentary behaviour, accumulated in prolonged bouts and low amounts of moderate to vigorous physical activity increase the risk of cardiovascular disease. Based on earlier research it is expected that a healthier balance in the 24h activity pattern (sedentary time, physical activity and sleep) reduces the risk of a second cardiovascular event. To support patients with stroke to strike the balance in their 24h activity pattern, a behavioural change coaching intervention focusing on reducing and interrupting their sedentary time was designed. A pilot study has been performed, and the RISE intervention seems feasible in reducing sedentary behaviour in people after stroke. Objective: To determine the effectiveness of the RISE intervention on preventing major adverse cardiovascular effects (MACE), after discharge from acute hospital care in community dwelling people after first-ever stroke, who have a sedentary movement behavioural pattern. In addition, the effects on 24h activity pattern, cost-effectiveness, and usability of the RISE intervention will be investigated. Study design: In this clinical randomized controlled trial, participants with first-ever stroke and a sedentary movement pattern will be included and randomly assigned to either the experimental group who will receive RISE intervention and usual care or the control group who will receive usual care. Primary and secondary outcomes will be measured at baseline, post-treatment (four months), and six, nine, and 12 months post-randomisation. Study population: People aged over 18, who return home after acute care with a first-ever stroke, who are independent in walking with or without a walking aid, will be included in the RISE intervention study. Intervention (if applicable): Participants will receive the RISE intervention, a 15-weeks blended behavioural intervention, where a primary care physiotherapist coaches participants on striking the balance in their 24h activity pattern, with a focus on reducing and interrupting their sedentary time. This will subsequently lead to an increase in physical activity. Next to that, insights into their personal sleep pattern, sleep hygiene rules and advices will be provided. Primary care physiotherapists coach people with a first-ever stroke in their home setting by using behaviour change techniques and the RISE eCoaching system. The RISE eCoaching system consists of 1) an activity monitor, 2) a smartphone application that provides real-time feedback and contains e-learning modules, 3) a monitoring dashboard for the physiotherapist. Participants receive participatory support from someone from their social network (e.g., partner or close friend) who joins them in the intervention (see image 1). Participants in the control group receive usual care, according to hospital specific guidelines. Main study parameters/endpoints: Effectiveness of RISE intervention on preventing major adverse cardiovascular events. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden and risk of participating in the RISE intervention are considered low. The participants will receive a blended coaching intervention to reduce and interrupt their sedentary behaviour. The blended intervention includes ten face-to-face or online sessions of a primary care physiotherapist, wearing an activity monitor during the intervention period, and support from the smartphone application. During the intervention people will be encouraged to sit less and move more. The participant will participate in a baseline and post intervention measurements. This includes wearing an activity monitor, questionnaires and performing physical tests. All measurements are non-invasive. Participants can shower and perform all other daily activities while wearing the activity monitor. The other measurements will take about 3.5 hours in total, and will be carried out online or at people's homes. Included participants are physically capable of performing these physical activities and are coached by a physiotherapist. Therefore, the risk involved in participating is low. Additional burden of the intervention is low since visits of the physiotherapist will be at home or online The possible benefits of participating in the study are: 1) insights in own movement behaviour and 2) (if someone is randomized to the RISE intervention group) the RISE intervention may help to reduce sedentary time, which may lower the risk on recurrent stroke.

Effects of Active Versus Passive Recharge Burst Spinal Cord Stimulation on Pain Experience in Persistent Spinal Pain Syndrome Type 2: a Multicenter Randomized Trial (BURST-RAP Study)

This multicenter randomized clinical trial will take place in 6 Dutch hospitals: the Rijnstate Hospital (Arnhem), Bravis Hospital (Roosendaal), Elizabeth TweeSteden Hospital (Tilburg), Diakonessen Hospital (Utrecht), Alrijne Hospital (Leiden) and the Amsterdam University Medical Hospitals A-UMC). PSPS Type II2 patients (n=96) will be randomized into a group receiving either active or passive recharge burst. Following a successful trial period, patients are permanently implanted. Patients complete the pain catastrophizing score (PCS) (primary outcome at 6 months), numeric pain rating scale (NRS), patient vigilance and awareness questionnaire (PVAQ), hospital anxiety and depression scale (HADS), quality of life (EQ-5D), Oswestery disability index (ODI), patient global impression of change (PGIC) and painDETECT questionnaires (secondary outcomes) at baseline, after trial, 1, 3, 6 and 12 months following implantation.

The (Cost-)Effectiveness of Generalist Versus Specialist Treatment for Severe Personality Disorders'

Does Self-Efficacy At the Start of Treatment Influence Treatment Outcome in Patients with EDs?

Eating disorders (EDs) are severe psychiatric disorders, characterized by a persistent disturbance of eating which impairs health or psychosocial functioning and causes loss of quality of life. There are several evidence-based forms of treatment, but outcomes are mediocre at best. Previous research found better treatment outcomes with several baseline predictors, such as greater motivation to recover. Research on motivation to change has indicated that autonomous motivated (AM) individuals show better response to treatments for EDs. However, being highly motivated for change, but not experiencing the capacity to really eat more and to deal with the emotions evoked by the process of recovery, might lead to difficulty to change key-behaviors, thus leading to less positive treatment outcome. Several researchers emphasized the importance of self-efficacy as a predictor in eating attitudes and behaviors. This study focuses on whether self-efficacy at the start of treatment is predictive of treatment outcome, measured by the ED-15 questionnaire in patients with an ED. Data will be obtained during CBT-T; a brief (10 sessions) version of cognitive behavioral therapy for eating disorders like BN, BED and OSFED. In CBT-T patients are encouraged, from the start of treatment, to challenge their fears, experience the effect of exposure and motivating them to carry through. This aspect might enlarge patients' experience of self-efficacy. Patients with low level of self-efficacy at start, but higher level of self-efficacy after four sessions, might benefit better from treatment, then patients with lower levels of self-efficacy throughout the treatment. To study this potential effect of treatment on self-efficacy, self-efficacy will be measured at start of treatment, at session four and at the end of treatment. Self-efficacy, self-esteem and autonomous motivation are concepts that are closely linked to each other. To test if they are positively correlated at start of treatment, measurements covering these concepts will be included at T0. HYPOTHESES Primary hypotheses: Higher levels of self-efficacy will positively predict a more positive treatment outcome as determined by lower eating pathology levels with the ED-15. Secondary hypotheses: 1. Self-efficacy in itself will improve during treatment. 2. Autonomous motivation, self-esteem and self-efficacy will be positively correlated.

A Study of Imlunestrant Versus Standard Endocrine Therapy in Participants With Early Breast Cancer

Antibiotic Treatment foLlowing Surgical drAinage of Perianal abScess; the ATLAS Trial

Breast Reconstruction and Neoadjuvant Radiotherapy

Rationale: Treatment of patients with breast cancer requires a multimodality approach with often systemic therapy, radiotherapy (RT) and surgery. Postmastectomy radiotherapy (PMRT) reduces locoregional recurrences and improves survival, especially in patients with involved axillary nodes. However, PMRT is known to substantially increase the complication rate when combined with a breast reconstruction. Breast reconstructions can be performed within the same surgery as the mastectomy (i.e. immediate) or in a later stage where patients remain without a breast contour for several months to years before the reconstruction is completed (i.e. delayed). In the Netherlands, most patients are being withheld an immediate breast reconstruction if there is the slightest risk of PMRT, because PMRT in combination with immediate breast reconstruction is associated with a severe increase in postoperative complications, especially in case of an implant-based reconstruction: complication rates up to 40% have been reported, in comparison to less than 10% without PMRT. Short-term complications include infection and loss of implant, while long-term complications include pain, capsular contracture and fibrosis. Such complications have been shown to negatively affect quality of life, perceived body image and sexual well-being. Furthermore, PMRT after an immediate reconstruction is associated with impaired cosmetic results and lower patient satisfaction, even when no complications have occurred. If patients aim for an autologous reconstruction (i.e. use of own tissue), usually PMRT is performed first, followed by a delayed autologous reconstruction to avoid radiotherapy on the flap, thereby subjecting patients to a second major surgical procedure and a long period of living without a breast contour. The unsatisfying cosmetic results and high complication rate have led to controversy and a wide practice variation in reconstruction approaches that are being offered to this specific group of patients. Since immediate breast reconstructions have proven to yield better cosmetic outcomes, psychosocial results and reduced overall costs, solutions that would allow for an immediate breast reconstruction in combination with radiation therapy (RT), without an increase in complications, are highly needed. Previous studies in breast cancer patients indicated that neoadjuvant RT (NART) is a safe approach from an oncological perspective, and does not increase the overall post-operative complication rate. However, limited data are available on NART in combination with an immediate breast reconstruction, and no data are available on patient-reported cosmetic outcomes. Objective: The purpose of the pilot study is to assess acute post-surgical complications following mastectomy and immediate breast reconstruction after NART. The investigators hypothesize that NART will avoid the negative effects of PMRT on the capsule of an implant, or on the skin and underlying tissue of an autologous flap, and would therefore lead to better cosmetic results, better quality of life and less complications compared to PMRT. If this hypothesis is confirmed, NART would allow more patients to undergo an immediate reconstruction resulting in superior cosmetic results and quality of life. Furthermore, the use of RT in a neoadjuvant setting could potentially result in a shorter overall loco-regional treatment time from diagnosis to receiving the last locoregional treatment. However, this pilot study will mainly assess whether or not the post-surgical complications of breast reconstruction with NART are acceptable. Further study to investigate long term quality of life and oncologic follow-up results will be conducted after this pilot study, if complication rates are acceptable. Study design: The study will be conducted as a prospective multicenter single arm interventional pilot study. The primary endpoint is post-surgical complications at three months after the latest patient has received the final reconstructive surgery. Study population: Twenty breast cancer patients will be included after they have given informed consent. Patients are eligible if they have an indication for mastectomy and RT, and a wish for an immediate reconstruction, either implant-based or autologous, in MUMC, UMCU, Alexander Monro hospital and Amsterdam UMC. Intervention (if applicable): The intervention consists of NART followed by mastectomy with immediate reconstruction, where the standard treatment is mastectomy and PMRT, with an immediate or delayed reconstruction. Main study parameters/endpoints: Primary endpoint: Acute post-surgical complications at 3 months following mastectomy and immediate breast reconstruction after NART in the treatment of breast cancer. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Burden: Currently, in certain hospitals, the indication for RT is based upon the pathological nodal status of the sentinel or previously involved nodes, removed during mastectomy. Since patients in this study will receive NART, the indication for RT is not always clear prior to surgery. In those cases, an axillary staging procedure has to be performed prior to the breast surgery, to determine whether there is an indication for RT at all. This requires two separate surgical procedures, which is nowadays already common practice in several hospitals, to determine whether an immediate breast reconstruction is possible. Currently, for cT1-3N0 patients, it is known that about 25% has a positive axillary node after neoadjuvant chemotherapy and thus still requires PMRT; for patients with cT1-3N+ breast cancer, about 55-70% still have positive nodes after neoadjuvant chemotherapy requiring PMRT. Consequently, some patients that have given their informed consent for NART but will be excluded from this study if the sentinel node appears to be free of tumor cells. Another additional burden can be an additional biopsy of the tumor after neoadjuvant chemotherapy, to determine whether residual disease is present. If residual disease is present, there is also an indication for adjuvant systemic treatment in triple negative patients or her2- positive patients. Since a biopsy is not sufficiently accurate to determine pCR status, patients are excluded from the study if the biopsy does not contain tumors cells, since NART can influence the final pathological tumor status. Finally, from a patient's perspective, additional time is required for filling in questionnaires with regard to cosmetic results and quality of life (approximately 15-30 minutes). Risk Data from current pilot studies indicates that NART is at least as effective as PMRT with regard to oncologic safety. A risk that is associated with participation is the possibility of decreased vascularization of the skin (nipple) flap of the breast after a sparing mastectomy leading to early complications, especially in the implant group. However, it is anticipated that this risk of necrosis and loss of tissue expander/implant is low, since previous pilot studies showed that overall short and long-term complications were similar between PMRT and NART. Benefit and group relatedness: NART will allow patients to always receive an immediate breast reconstruction (both implant-based and autologous), even is RT is indicated. It is hypothesized that this will result in a better QoL and cosmetic outcome. Finally total treatment time will be shorter with NART.

Minimal Invasive Axillary Staging and Treatment After Neoadjuvant Systemic Therapy in Node Positive Breast Cancer

The MINIMAX is a multicenter registry study that includes node positive breast cancer patients, who are treated with NST (chemotherapy and ± immunotherapy), in order to gain insight in the oncologic safety and impact on QoL of less and more invasive axillary staging and treatment strategies. Patients who are included in this study will complete Patient Reported Outcome Measures (PROMs) at baseline (time of diagnosis), and 1 and 5 years after diagnosis to assess impact on QoL. A database will be built by the Netherlands Cancer Registry. Data on patient-, tumor-, pre-NST staging-, post-NST staging- and treatment-characteristics will be retrieved from patients' records by trained data registrars of the Netherlands Comprehensive Cancer Organisation (IKNL) using electronic case report forms (eCRFs). Five-year survival and recurrence will be evaluated to determine oncologic safety. The results will be incorporated in the national guidelines. In case of an equilibrium between less and more invasive strategies, the data of this study will at least be extremely suitable to be used in the shared decision making process.

AFT: Introduction of a Full Breast Reconstructive Method