Hellevoetsluis, Netherlands

Statins in Frail Older Patients with Ischemic Stroke or Transient Ischemic Attack - the Prospective Cohort Study

The stroke incidence strongly increases with age.Many of the older individuals that suffered a stroke will have to live with stroke sequelae and will need lifelong care, either at home or in a nursing facility. Hence, secondary prevention strategies are of the highest importance. Statins are used for the prevention of subsequent cardiovascular events in ischemic stroke and TIA patients. The efficacy of statin therapy has been firmly established in middle-aged stroke patients. However, despite the high prevalence of stroke in older people, the evidence for the efficacy of statin therapy in older individuals that suffered an ischemic stroke or TIA is sparse. This primarily arises from the underrepresentation of older patients in statin trials. In a recent meta-analysis, it was found that in people aged 70 and above, statin use lowered the annual incidence of major vascular events with approximately one percent. However, the trials in this meta-analysis mostly included fit, non-frail older adults. Frailty is a geriatric condition characterized by an increased vulnerability to external stressors, linked to adverse outcomes, including premature mortality. A considerable proportion of the older population is frail. However, since trials that include older individuals often focus on fit, non-frail older adults, there is currently no evidence for the most effective treatment strategy in the frail older group. While it might be tempting to extrapolate the benefits of statin therapy from younger patients to frail older patients, it is vital to acknowledge the considerable disparities between these groups. Firstly, frail older stroke survivors may not have a life-expectancy longer than the time to benefit. Secondly, due to the high percentage of polypharmacy in frail older people, this patient group has a higher risk for the occurrence of drug-drug interactions and adverse effects, which have the ability to significantly affect the quality of life. The limited body of evidence regarding the effectiveness of statins in the older population, combined with their higher susceptibility to side effects and drug interactions, results in uncertainty for patients as well as for doctors and policymakers when deciding how to treat this patient group.This uncertainty is clearly reflected in the two Dutch guidelines ("Herseninfarct en Hersenbloeding" and "Cardiovascular Risk Management (CVRM)" respectively), providing conflicting advice on optimal statin treatment in older patients. The investigators hypothesize that in frail older patients with a recent ischemic stroke or TIA, discontinuing statins will increase health-related quality of life (HrQoL) without a substantial decrease in Major Adverse Cardiovascular Events (MACE) free survival, which includes cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. In this prospective cohort study, no intervention will be implemented. Participants will be followed for two years (and for the patients included in the first years of the inclusion period - three). During this time, data is collected including questionnaires on quality of life, occurrence of MACE or falls, and possible changes in statin treatment.

Power2Walk: the Impact of Functional Power Training on Participation and Activity in Children with Cerebral Palsy.

Children with cerebral palsy (CP) experience limitations in walking ability due to functional motor impairments caused by neurodevelopmental damage during fetal or early child development that may result in spasticity, dyskinesia, or ataxia. Due to these motor impairments, children with CP struggle to keep up with typically developing peers when participating in physical and/or social activities. Yet, participation is a key factor in child development, mainly because it is instrumental in enhancing mental well-being through building friendships, developing a personal identity, optimizing physical growth, and increasing motor control. Earlier studies concluded that children with CP are indeed at an elevated risk for reduced physical activity and participation. Consequently, the development of these children may be hampered. Therefore, targeted interventions that increase physical activity and participation are essential for supporting the general development of children with CP. A large number of treatments have been developed for children with CP, ranging from pharmacological agents that manage tone to invasive surgical interventions. Whilst many of these treatments effectively improve motor control, very few address the underlying fatigue that is typically seen in these children, which causes a vicious cycle of reduced physical fitness, early onset of fatigue, and decreased physical activity levels. This decline in physical fitness is ultimately detrimental to participation, and therefore a wide variety of exercise-related treatment options are being explored to improve motor control, physical fitness, and participation. Recently, functional power training (FPT) emerged as a potentially successful supplementary treatment method to improve participation in children with CP. This type of strength training combines high velocity movements with progressive resistance to mimic and train the demands of playing activities like playground running and sprinting in games and sports. Indeed, a previous double-baseline study indicated that FPT improves physical fitness, muscle strength, activity, and participation in ambulatory children with CP. This is unlike progressive resistance training (PRT), which increases muscle strength but not walking ability, anaerobic capacity, and ultimately participation. This discrepancy is likely explained by the functional nature of FPT, which specifically trains activities of daily living and not only muscle strength. Moreover, power training may be more effective than strength training as power training incorporates high intensity, explosive-like contractions that are required in daily living situations. Consequently, FPT is more effective than PRT in improving walking ability, thereby better supporting participation in ambulatory children with CP. Nevertheless, high-level scientific evidence underpinning the efficacy of FPT on walking ability, aerobic endurance, anaerobic capacity, and participation in ambulant children with CP is still lacking. Furthermore, it remains unclear what predictive factors best identify which children with CP benefit most from FPT. Additionally, it remains unknown whether the potential benefits of FPT on walking ability, aerobic endurance, anaerobic capacity, and participation in children with CP are maintained when FPT is discontinued.

Chronic Fatigue in the Internal Medicine Outpatient Clinic: a Mixed-methods Quantitative and Qualitative Study

Chronic fatigue is a prevalent and challenging symptom, affecting an estimated 30% of the general population in the Netherlands for periods longer than six months. Despite its frequency, only a small proportion of patients presenting with fatigue receive a somatic or psychosocial diagnosis, leaving many cases unexplained. This underscores the complexity and subjective nature of fatigue, as well as the need for better understanding and management of this condition in secondary care settings. The aim of this study is twofold. First, it seeks to determine the effectiveness of diagnostic procedures performed during fatigue consultations at an internal medicine outpatient clinic in contributing to a somatic diagnosis. Second, it aims to explore the experiences of patients for whom these consultations, including diagnostic testing, do not lead to a definitive diagnosis. This mixed-method study combines quantitative and qualitative approaches. A retrospective analysis of medical records will assess the proportion of fatigue consultations where diagnostics, ie. blood work, an EKG and an X-thorax, result in a somatic diagnosis. Additionally, qualitative interviews will provide insight into the experiences of patients who leave the consultation without a diagnosis. The interviews will have an open characters, based ons principles of "Grounded Theory" (a qualitative research approach that generates theories from data through iterative processes of coding, comparison, and analysis, rather than testing existing hypotheses) The study will include adult patients referred to an internal medicine outpatient clinic for unexplained fatigue. Data collection will encompass both diagnostic outcomes and patient perceptions, with findings aimed at improving care pathways and diagnostic approaches for individuals with chronic fatigue. The study will contribute to a deeper understanding of the diagnostic process for fatigue in secondary care and offer insights into the patient experience. This knowledge has the potential to enhance clinical practices and improve patient-centered care for individuals presenting with unexplained fatigue.

Towards Novel BIOmarkers to Diagnose SEPsis on the Emergency Room

Sepsis will be defined in accordance with the current Sepsis 3.0 criteria as a(n) (suspected) infection with evidence of organ failure, as reflected by a SOFA (Sequential Organ Failure Assessment) score of ≥2. Notably, a molecular definition of sepsis does not exist and there is no pathological gold standard; therefore, in accordance with the current international consensus, the investigators consider the commonly used clinical organ failure (SOFA) criteria as the best option. The SOFA score is composed of six organ dysfunctions (cardiovascular, pulmonary, renal, hepatic, coagulation and neurological). The SOFA score was developed for ICU patients, but its components can be easily scored in an ED (and hospital ward) setting with the exception of the pulmonary component; this pulmonary dysfunction score is based on the PaO2/FiO2 (PF) ratio, wherein PaO2 is the partial pressure of oxygen in arterial blood and FiO2 the fraction of inspired oxygen. Measurement of the PaO2 requires an arterial blood puncture, which is not routinely done on the ER or hospital ward. Therefore, the investigators will use an alternative method to determine the respiratory SOFA by determining the SpO2/FiO2 (SF) ratio, wherein SpO2 is peripheral oxygen saturation. SpO2 is routinely measured by finger pulse oximeter in patients with suspected infection; FiO2 is 21% when breathing room temperature and increases by 4% with each liter of oxygen provided per minute to a patient via a nasal cannula. Cut-off values for SF ratios correlating with SOFA pulmonary scores based on PF ratios have been validated in large data sets.

FeAsiBility of a Treatment Free Interval in Newly Diagnosed MM Patients Treated With Daratumumab-lenalidomide-dexamethasone (HOVON174MM)

Circulating Tumor DNA Based Adjuvant Chemotherapy in Stage II Colon Cancer Patients: the MEDOCC-CrEATE Trial

OPTImaL:Optimisation of Treatment for Patients With Low Stage Triple-negative Breast Cancer With High Stromal Tumor-infiltrating Lymphocytes

HOspitalized Patients and Clinical flUid Status, Assessment Using Point Of Care UltraSound

The study will be carried out on patients over the age of 18 who were admitted to the general ward between for at least 24 hours and who had a clinical indication for an IVC ultrasound. Patients are informed through an informed consent form and are given the opportunity to opt-out. When there are no objections, the patient's data is collected for the study. Patients who are using vasopressors at the time of the ultrasound are excluded from the study. In addition, patients who require invasive or non-invasive ventilation (optiflow, CPAP, BPAP) are also excluded. The ultrasounds are performed by trained physicians based on a standard operating procedure. The longitudinal portion of the IVC is scanned and a cine loop of 10 seconds is made during a respiratory cycle to determine the diameter of the IVC (dIVC). After the recording is paused, the dIVC will be measured 2 cm caudal to the junction of the hepatic vein and IVC to standardize the measurements. Measurements are taken at peak expiration (dIVCe) and inspiration (dIVCi) by measuring the vein lumen at one respiratory cycle from one interior wall to the opposite interior wall. Data is collected at the time of admission and after 48 hours (or prematurely if the patient is discharged). During the initial assessment, the patient's demographics, clinical data, physical examination, vitals , laboratory parameters, and the POCUS IVC (minimal and maximal diameter, percentage collapse) are registered. The Charlson Comorbidity Index is used to quantify the severity of comorbidities in the patients. Additionally, the patient's overall health status is measured by the ECOG Performance Status Scale. Once the initial measurements are done, a clinical diagnosis of the patient's volume status will be established. 48 hours later, more data will be gathered for the follow-up. The data includes vitals and laboratory parameters. It is also noted whether the POCUS influenced the management of treatment (IV fluid or diuretic therapy) of each patient. Following this assessment, a clinical diagnosis in retrospect at the time of the ultrasound at baseline about the volume status is established. The diagnostic accuracy for hypovolemia and hypervolemia cases are analyzed. The sensitivity, specificity, positive predictive value, and negative predictive value are also determined. Furthermore, the area under the curve (AUC) for hypo- and hypervolemia were computed. A descriptive analysis of the changes over time will be carried out in the subgroup with follow-up measurements. The interpretation of the images at the time of the ultrasound serves as the foundation for the main analysis. A second assessor will verify the images retrospectively in a subset, recalculating the diameter and evaluating their quality. A descriptive analysis will be conducted on the quality of measurements. Moreover, an exploratory analysis will be carried out to ascertain the best location and cutoff points for identifying volume status.

Peppermint Oil for the Treatment of Irritable Bowel Syndrome or Functional Abdominal Pain in Children: the MINT Study

The objective of the MINT study is to investigate the effectiveness of peppermint oil capsules compared to placebo capsules in reducing abdominal pain intensity in children with IBS or FAP-NOS. In addition, we evaluate the effect of peppermint oil capsules compared to placebo capsules on other disease-related outcome measures such as anxiety & depression, quality of life, absenteeism from school, and healthcare costs. The second aim is to explore the effectiveness of regular mints in reducing abdominal pain intensity compared to peppermint oil capsules and placebo capsules and the effect of mints on secondary outcome parameters.

MAD Trial: Myopia Atropine Dose

With the current worldwide myopia boom the frequency of high myopia will also increase, and potentially blinding complications such as myopic macular degeneration, retinal detachment, and glaucoma will occur more often. In the Netherlands high myopia will become the most important cause of low vision and blindness by 2050. As treatment options are limited once the eye is fully grown, prevention of a long axial length at childhood is the only way to counteract this prospect. Pharmacological interventions have shown a high efficacy in stopping eye growth, in particular eye drops with high dose Atropine (0.5%, 1%). Nevertheless, the high frequency of side effects (photophobia, reading problems) of these Atropine concentrations has favoured the use of low dose Atropine. Atropine 0.01% is the most commonly used and lowest dosage; it has shown stability of refractive error, but not of axial length. Recent studies have shown that Atropine 0.05% has low risk of side effects, but a higher efficacy than 0.01%. Many ongoing trials are now comparing various low dose Atropine to placebo, but none are comparing the highest low dose to the lowest high dose Atropine.