Saviese, Switzerland

E²-RADIatE: EORTC-ESTRO RADiotherapy InfrAstrucTure for Europe

Implementing a Case-management Intervention for Frequent Users of the Emergency Department in French-speaking Switzerland

Frequent users of the emergency departments (FUEDs) and other health care services are of much interest to clinicians, administrators and researchers. Emergency department (ED) overuse is linked to ED overcrowding, which in turn has a negative impact on patients and health system outcomes. There are over 1.4 million annual ED visits in Switzerland, with 84% of EDs reporting overcrowding. FUEDs made up 4.4% of the patient population and made 12.1% of all visits at the Lausanne University Hospital ED. Driving this high use of health care services is the fact that FUEDs often suffer from chronic medical diseases, including heart disease, pulmonary disease and cancer, at high rates, in addition to mental illness and substance use disorders. CM has been shown to be a promising intervention to reduce ED overuse by frequent users in research settings; however, there is limited knowledge about how to disseminate and implement a CM intervention for FUEDs on a large scale to diverse clinical settings, including community hospitals and non-academic centers. The research project has the following three specific aims: 1. Develop and disseminate a practical CM intervention for FUEDs to several hospitals in the French-speaking region of Switzerland. 2. Study the process of implementation of the intervention. 3. Study FUEDs' trajectories on health outcomes (e.g., ED use, health care reorientation and quality of life) after receiving the CM intervention. This research project is an observational study with a hybrid study design, measuring both implementation variables and clinical outcomes relating to the dissemination and implementation of the CM intervention. The implementation part of the study uses a mixed methods design (i.e., using both qualitative and quantitative analyses) to describe both qualitatively and quantitatively factors that may influence implementation process. The clinical part of the study uses a within-subject (pre-post intervention) design to evaluate participants' trajectories after receiving the CM intervention. The whole research project will take place over five phases. Phases 1-2. Development and exploration Procedures. The I-CaM research team will develop the CM Toolkit, the implementation program, the team member selection-support materials and the informational announcement to be disseminated to hospitals in the French-speaking region of Switzerland. Specifically, the research team will develop and send by email a survey aiming to gauge interest and needs regarding the CM intervention to all eligible hospitals (to key staff, Chief of Emergency Department). The I-CaM research team will follow up with more information about the CM intervention and the study procedures. Then, interested parties will participate in a one-day workshop at Lausanne University Hospital, during which key staff will receive training on the CM intervention, on the implementation science and on the study procedures in general. Following the workshop, all sites agreeing to participate will a) be included in the study and b) complete a questionnaire and participate in a semi-structured interview (assessing implementation outcomes). Further, the same assessment will be conducted with hospitals not interested in participating in the study, in face-to-face or by phone and mail depending upon possibilities (i.e., disinterest analysis). Phase 3. Preparation Procedures. Included sites will then prepare for implementation of the CM intervention; sites will first identify CM intervention team members, including strategical and operational champions and clinicians. Whereas the strategical champion (i.e., leader) will promote and hold the implementation project, the operational champion will support its implementation and application and supervise clinicians who will be in charge of the CM intervention administration. Next, available resources will be established at each source and data collection and storage systems will be finalized to gather data on health service and implementation outcomes by the research team. The I-CaM research team will also conduct trainings for the CM team to relevant local staff. Finally, at the end of the preparation phase, champions and clinicians involved in the project on-site will complete a questionnaire. Phase 4. Operation The operation phase. The CM intervention will be implemented at all sites included in the study. At each site, patients fulfilling the inclusion criteria will be contacted by the case managers. The number of participants included will depend upon each site resources. If possible (depending upon resources on each site), eligible patients having been treated in the ED in the 10 days prior the recruitment window will be contacted by phone and proposed to come back to the ED to participate in the study. Remaining FUEDs (i.e., the FUEDs not invited to participate in the study) will receive usual care. When first meeting the participant, the case managers will present the study and examine the exclusion criterion. If the patient does not have any exclusion criteria and is interested in participating, the case managers will conduct the informed consent process. After providing written consent, participants will receive the CM intervention. After each inclusion on site, the case managers will up-date the I-CaM research team in charge of the clinical assessment (i.e., baseline and follow-up assessments of the clinical variables to describe participants' trajectories). The I-CaM research team will contact participants and conduct the baseline assessment within 10 days following the inclusion. Participants will then complete follow-up assessments at 3, 6 and 12 months post-baseline. Other clinical variables will be directly extracted from medical records on-site by the I-CaM research team. At the end of the operation phase, the research team will conduct semi-structured interviews with case managers and champions. Both champions and case managers will also complete a questionnaire. Phase 5. Sustainability Procedures. Following the implementation of the CM intervention, the sites will continue the CM programs at their discretion. The I-CaM research team will monitor the activity at each site and will be available for as-needed support to all sites. Clinical outcomes (i.e., ED use, quality of life, etc.) will not be measured over this finale phase. At the end of the sustainability phase, the research team will conduct a semi -structured interview with clinicians and champions. Both champions and clinicians will also complete a survey. - The development and exploration phases (no patient recruited) started in August 2017 and will end in September 2018. - The preparation phase (no patient recruited) started in March 2018 and will end in December 2018. - The operation phase (patients' recruitment start; assessment of health-related outcomes) will start in October 2018 and end in April 2019. - The sustainability phase (patients receive the CM intervention but health-related outcomes are not assessed) will start in April 2019 and end in November 2020. Data Analysis Plan Implementation measures analysis. Descriptive statistics will be used to describe participants' characteristics and to report implementation outcomes. The investigators will also test implementation measure changes over time. Given the expected small sample size regarding implementation outcomes, these analyses will be triangulated with qualitative data. Specifically, interview contents will be transcribed and explored to identify participants' recurring codes and categories; the investigators will use conventional content analysis (i.e., a systematic process of coding and classification) [1] using a qualitative software (i.e., Atlas.ti or NVivo) to examine qualitative data. Clinical outcomes. Data will be screened for missing cases, outliers, and normality of distributions using descriptive statistics and plots. The investigators will take appropriate steps to deal with missing data. First, they will conduct analyses to detect missingness patterns and test whether they may be considered "ignorable."[2] If more than 5% of outcome data are missing,[3] the sample will be divided into 2 groups (i.e., missing, not missing), and fully observed variables to predict missingness on the affected outcome will be used. If fully observed variables are not significant predictors, missingness may be considered as "observed at random" and fulfilling some criteria for "missing completely at random" (MCAR) assumptions. In that case, the investigators will use multiple imputations procedures for measured outcomes and direct maximum likelihood estimation for structural models. If data missingness is non ignorable (MNAR), pattern-mixture models with multiple imputation to model the missingness mechanism will be used. Main analyses will comprise multilevel models (i.e., MLM; mixed effects model) [4] utilizing appropriate distributions for the outcome variables (e.g., Poisson, negative binomial, normal). MLM examine the effect of time (after receiving the CM intervention) on clinical outcomes (e.g., quality of life, self-efficacy). MLM is appropriate to handle nonindependence data. Specifically, data will be clustered by participants (i.e., repeated measures) and by hospitals. MLM does not assume independence of observations. Dependence is modeled through random effects (representing different sources of variability in the data). The investigators will include sources of random variability at the group level accounting for between-group differences and another random effects for the individual accounting for within-person differences in the repeated measures. MLM will be adjusted for demographic variables (i.e., age and gender), health-care utilization (including ED use), at-risk behaviors (e.g., alcohol use disorders) and health status. Descriptive statistics will be conducted on SPSS and MLM on STATA. The significance level will be set at p = .05.

Swiss Severe Asthma Register

The overall objective is to establish a clinical register for patients with severe asthma. Since the number of patients with severe asthma at a single center is usually low, it will be important to collect data in a multi-center system to optimize the diagnostic evaluation and treatment of patients with severe asthma. So far, there is little reliable information about the frequency, phenotype and therapy of patients with severe asthma. The construction of a clinical register should close this gap. The primary objective is to show changes in symptoms control during follow up period and at study end by using the Asthma Control Test (ACT). Secondary endpoints are to collect data to better understand asthma's natural history in patients with severe asthma. The examination will be based on the assessment of the parameters specified under "outcomes". Patients presenting to participating study center (pulmonologists in private practice or in pulmonary departments in hospital within Switzerland) with severe asthma will be asked to take part in this study when corresponding to the eligibility criteria. All patients with severe asthma will be included in the register only after detailed information and written consent. After four months (for specific therapies) and after 12 months, patients should be re-evaluated for up to 15 years. These follow-up data will also be recorded in the register. During the follow-up visits, the same parameters will be collected as during the initial Baselineexamination (some parameters will be omitted, for example, therapy received or requested for the defined period of the last 12 months, etc.). Severe asthma patients receiving a new specific therapy, e.g. obtained with antibodies, but who cannot be included in the register with the complete parameter profile due to time or capacity reasons of the centers, should be recorded at least with defined basic data and a reduced number of parameters in the register. These parameters include according to the specific asthma approved specific therapies, socio-demographic data, lung function values, laboratory values, parameters of asthma control, smoking status and add-on- therapy. This should make it possible to record a subgroup of severe asthmatics that are suitable for antibody therapy and at the same time offer the attending physician the opportunity to adequately document these complex and expensive therapies by recording the defined parameters. In these patients, an evaluation of the therapy response should be carried out after four months and documented in the register. Thereafter, there is an annual follow-up. At any time, these patients can be transferred to the full version of the register by entering the missing parameters. Patients for whom only the basic data is available (basic version) as well as patients with complete parameter profile in the register are kept in the same database and can be evaluated together. In general, no register-specific examinations will be carried out, but only parameters anyway recorded routinely. Since this is a cohort study, no sample size calculation can be calculated. Evaluations are carried out continuously. The collective of the data should be described by descriptive statistics concerning the basic data as well as the data of the function diagnostics. Subentities of severe asthma should be identified by a cluster analysis.

Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury

Long-Term Real-World Outcomes Study on Patients Implanted With a Neurostimulator

This study has broad inclusion criteria and minimal exclusion criteria to ensure the results are representative of the real-world use of these devices. Enrollment caps will be implemented to ensure patients from approved indications are represented. Individuals who are scheduled to receive an implantable Abbott neurostimulation system are eligible for study consideration. The study will enroll up to 2,000 subjects from up to 100 participating centers. Subject enrollment is expected to be completed within 7 years; subjects will be followed for 5 years. The total duration of the study is expected to be 13 years, including enrollment, data collection from all subjects, and study close out.

Swiss Trauma Registry

Tailored Axillary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (TAXIS)

The removal of all lymph nodes in the armpit through conventional axillary dissection has been standard care for all patients with breast cancer for almost a century. In the nineties, the sentinel lymph node procedure, which involves the selective removal of the first few affected lymph nodes, was introduced in clinical practice. Today, conventional axillary dissection is still performed on many women with breast cancer that has spread to the nodes. It is the cause for relevant morbidity in the form of lymphedema, impairment of shoulder mobility, sensation disorders and chronic pain in as much as one third of all women undergoing the procedure. The TAXIS trial will evaluate the optimal treatment for breast cancer patients in terms of surgery and radiotherapy. In particular, it will investigate the value of tailored axillary surgery (TAS), a new technique that aims at selectively removing the positive lymph nodes. TAS combines the removal of palpably suspicious nodes with the sentinel procedure. TAS is a promising procedure that may significantly decrease morbidity in breast cancer patients by avoiding surgical overtreatment. This trial has the potential to establish a new worldwide treatment standard with hopefully less side effects and a better quality of life, while keeping the same efficacy as provided by radical surgery. The main objective of the trial is to show that TAS and axillary radiotherapy (RT) is non-inferior to ALND in terms of disease-free survival of node positive breast cancer patients at high risk of recurrence in the era of effective systemic therapy and extended regional nodal irradiation.

High Dose Steroids in Children With Stroke

Background: Arterial ischemic stroke (AIS) is a rare but devastating condition affecting 2-5/100,000 children/year. Children do not recover better than adults with 2/3 suffering long term neurological, cognitive and behavioural problems. The economic cost of stroke is substantial. Arteriopathy is identified as AIS aetiology in 60-80% of previously healthy children and is the strongest predictor of recurrent events. 30-40% of these children will have a focal cerebral arteriopathy (FCA). FCA in childhood is shown to be an inflammatory vessel wall pathology provoked by infections. This encourages treatment with steroids, despite lack of evidence. Rationale: There is increasing evidence that etiologically inflammatory processes play a crucial role in childhood stroke, and influence outcome. Retrospective analyses suggest improved outcome and less recurrence with steroid treatment. With the exception of sickle cell disease, this study will be the first randomized clinical trial in children with arterial ischemic stroke. It will provide high-level evidence for the most appropriate treatment for children with AIS due to FCA. Alignment of interventions and outcome as well as pooled analysis with the planned Focal Cerebral Arteriopathy Steroid (FOCAS) study in North America will allow pooled analysis results.This is very important in view of the marked neurological, social and economic burden of childhood AIS for patients and families. This project has been identified as the most important AIS treatment trial by a Delphi survey of international paediatric stroke experts and is one of the most important research priorities identified by parents. In addition, the study will provide insights into the pathogenesis of inflammatory vasculopathies.The objective of this trial is to show that children with first stroke event due to unilateral FCA treated with a combination of high dose steroid and aspirin will have better and quicker recovery of arteriopathy, better clinical functional outcome, and less recurrence compared to children treated with aspirin alone. The proposed study is a prospective multicentre, parallel group, two-arm, randomized controlled, open-label clinical trial with blinded outcome assessment, comparing a high dose course of methylprednisolone / prednisolone plus standard of care with standard of care alone in children with unilateral arteriopathy and acute ischemic stroke. Measurements and procedures: Participants will be randomized within 48 hours after diagnosis (maximum 96 hours after stroke onset) to standard of care (SC) alone (control group) or SC plus steroids (experimental group). SC will be harmonized among the study centres to include aspirin treatment. Patients will be assessed at 1, 3, 6 and 12 months. Magnetic imaging and angiography (MRI/MRA) will be done at 1, (3) and 6 months. Number of Participants: 70 participants in total, 35 per treatment arm Study duration: 48 months Study Centre(s): International multi-centre study with approximately 20 to 30 centres Participating countries:Switzerland, Germany, France, Austria, Great Britain & Australia Centres in additional countries might be considered. Statistical Considerations: The sample size is based on the comparison of the primary outcome - the change in FCASS from baseline to 1 month - between the two treatment groups. The standard deviation from 13 patients of a retrospective study was calculated. The standard deviation of the baseline and follow-up FCASS was 3.0 and 3.3, respectively. The standard deviation of the change in FCASS from baseline was 2.8. Based on the standard deviation of 2.8 and a two-sample means test, 64 patients (32 in each group) are required to detect a difference of 2.0 with a power of 80% at a two-sided alpha-level of 0.05. To account for dropouts (8%), we enlarge the sample size to 70 patients (35 in each group). The primary analysis will follow the intention-to-treat (ITT) principle, i.e. all patients will be analysed in the allocated group regardless of any protocol violations such as cross-overs. The primary outcome (change in FCASS from baseline to 1 month) as well as other secondary continuous score outcomes that are measured multiple times during follow-up (RRQ, mRS, Pediatric Stroke Outcome Measure (PSOM), VABS, modAspect) will be assessed in a repeated-measure, mixed-effects linear model. Good Clinical Practice (GCP) Statement: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH-GCP) as well as all national legal and regulatory requirements.

Longitudinal Follow-up Study About Complex Regional Pain Syndrome (CRPS) Patients

The first aim will be to monitor the evolution of the following parameters in CRPS patients: - Quality of life - Symptoms and signs of CRPS - Severity of CRPS - Working status - Pain - Disability - Anxiety and depression - Kinesiophobia - Catastrophism - Activity patterns with chronic pain during the two years follow-up. Every parameter will be evaluated with a questionnaire that allows assigning scores to each patient. Additionally sociodemographic data will be collected to characterize the patients (age, gender, marital status, educational level). The health status, treatment and medication of the patients will also be recorded with a medical follow-up during the two years. The aim is to know if the following parameters and their evolution: - Sociodemographic factors, - Pain, - Disability, - Anxiety and depression, - Kinesiophobia, - Catastrophism, - Activity patterns with chronic pain are associated with the recovery, which is evaluated with - Quality of life, - Severity of CRPS, - And working status. Potential associations between the different parameters will be tested (Pearson's correlation coefficient). The second aim will be to assess, in blood samples, the expression levels of specific molecules (miRNAs and a selection of cytokines) in patients diagnosed with acute CRPS. Comparison with healthy controls will be performed at the first measurement time (T0) . In a second time, miRNAs and cytokines profiles will be compared between acute and chronic (CRPS still diagnosed 6 months after the first diagnosis) CRPS patients. The measured proteins will include: C-reactive protein, tumor necrosis factor-alpha (TNF), interleukin-2 [IL-2], IL-6, IL-8, IL-10, CD40 ligand (pro- and anti-inflammatory proteins associated with pain), gene related peptide (CGRP), bradykinins and substance P. The screening, recruitment and enrolment of the patients will be done by the referring physician in daily clinical practice, during the consultation. The physician will explain to each participant the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits and any discomfort it may entail. Each participant will be informed that the participation in the study is voluntary and that he/she may withdraw from the study at any time and that withdrawal of consent will not affect his/her subsequent medical assistance and treatment. All participants for the study will be provided with a participant information sheet,a consent form describing the study and providing sufficient information for participant to make an informed decision about their participation in the study and a prepaid envelope. Each patient may decide separately to participate in a) longitudinal follow-up questionnaires, b) blood tests or c) both parts of the study (questionnaire and blood samples). The delay for reflection will be 24 h. Once this period has expired, if the patient agrees to participate in the study, he or she is asked to return the consent form in the prepaid envelope. If he or she has not been send back after one week, the physician will call the patient by phone to make sure that it is not an omission. The patient information sheet and the consent form are submitted to the Ethic comitee to be reviewed and approved. The formal consent of a participant, using the approved consent form, must be obtained before the participant is submitted to any study procedure. The participant should read and consider the statement before signing and dating the informed consent form, and should be given a copy of the signed document. If the patient sent back the informed consent, a next appointment will be scheduled at the CRR where he or she will be asked to submit the signed consent form. The consent form must also be signed and dated by the investigator (or his designee) and it will be retained as part of the study records. The total duration of the project is planned over a six years period (2019-2024). The study will be proposed to every CRPS ambulatory patient in the CRR (2019-2022), inclusion period). The study will also be proposed to the patients during the last two years (2023-2024) but only partially, since that last questionnaires will be sent in December 2024. The CRPS patients are monitored on a regular and long-term basis at the CRR. The physician see them very regularly at the beginning (about once a month) and then the visits space a little out. Thus, our study fits into routine procedure and should not imply additional visits. At the first visit at the clinic, the physician will proposed the study to the patient. Upon acceptance, the patient will be included into the study. It consists in five measurement times: - T0: During the days following the first visit to the clinic - T1: Follow up visit 3 months later - T2: Follow up visit 6 months later - T3: Follow up visit 12 months later - T4: Follow up visit 24 months later

Hallucinations in Parkinson's Disease

Parkinson's Disease (PD) is a condition mostly known and characterized by motor symptoms, such as tremors, rigidity, bradykinesia, amongst others. Yet, recent bodies of research have identified a significant number of non-motor symptoms that also accompany the unfolding of this disease. These non-motor symptoms mainly focus on hallucinations that will develop with the course of the disease, and will affect approximately 50% of the patients suffering from Parkinson's. This number rises to 70% if minor hallucinations, mild phenomena and poorly-structured hallucinations, are included. Despite the potential impact in the patients' lives, and previous efforts to study these phenomena, the brain changes that underly hallucinations in PD are still poorly understood. With the current study the investigators aim to improve this understanding, by studying the most common minor hallucination in Parkinson's Disease, the Presence Hallucination (PH), which can be defined as the strange sensation of perceiving someone behind when no one is actually there. To study it in a controlled manner, the investigators will induce this hallucination with an extensively verified paradigm, which gives rise to this sensation through robotically-mediated sensorimotor stimulation, in both healthy individuals, and PD patients. The researchers intend to discern the sensitivity of different groups of PD patients to the induction of this hallucination, by targeting PD patients, with hallucinations including PH, with hallucinations but without PH, without any hallucinations, and an aged match control group with no neurological comorbidities. The investigators intended to extend previous work on the induction of the PH in PD patients, by identifying the neural correlates of this induction in these patients, in a similar fashion to previous work in healthy individuals. Moreover, the researchers also intend to extend the general understanding of the basis for hallucinations in PD by extending what was done in previous work, to more stratified cohorts of PD patients, that will not only be analysed in terms of static during rest, but also in terms of dynamic connectivity, and will also perform the PH-inducing task in the scanner, as mentioned before.