Clinical trials

The goal of this randomized clinical trial is to evaluate whether continuous glucose monitoring (CGM) can be used to guide glucose management in patients with type 2 diabetes who are admitted with an acute ischemic stroke and undergo endovascular therapy. Hyperglycemia frequently occurs during hospitalization in stroke and is associated with worse neurological and clinical outcomes. In current clinical practice, glucose levels are monitored using intermittent point-of-care testing (POCT) with finger-prick measurements, which may miss clinically relevant glucose fluctuations. CGM provides continuous glucose measurements and may allow earlier detection of hyperglycemia and more timely glucose management. This study is designed as a non-inferiority randomized controlled trial comparing CGM-guided glucose management with standard POCT-guided glucose management. The primary objective is to determine whether CGM-guided glucose management is non-inferior to POCT-guided management in terms of percentage time spent in hyperglycemia (glucose \>10 mmol/L) during the first 72 hours of hospitalization. Researchers will compare CGM-guided glucose management to POCT-guided glucose management to evaluate whether CGM can be used as an alternative strategy to guide glucose control in hospitalized stroke patients. Participants will: * Be randomly assigned to either CGM-guided glucose management or standard POCT-guided glucose management * Have their glucose levels continuously monitored (blinded in the POCT-guided group) during hospitalization * Receive glucose management according to the assigned monitoring strategy, based on the hospital insulin protocol

This study is an interventional, explorative, prospective study to show whether shortening of infusion times for patients using nivolumab, pembrolizumab, ipilimumab, trastuzumab, bevacizumab, durvalumab or atezolizumab continues to be associated with an acceptable safety profile. Infusion times will be gradually shortened if tolerability allowes.

Changes in intrapleural pressure after lung volume reduction in Chronic Obstructive Pulmonary disease (COPD) patients can lead to complications, including an increased risk of pneumothorax. This procedure, intended to improve lung function, may disturb the pressure balance within the pleural space, potentially precipitating pneumothorax. Careful monitoring of intrapleural pressure could help predict patients at risk. However, intrapleural pressure can currently only be measured invasively. Diaphragm shear-wave elastography (SWE) has been shown to reflect transdiaphragmatic pressure during isovolumetric inspiratory efforts and ventilation against inspiratory loading, and therefore may serve as a non-invasive surrogate for intrapleural pressure. This project outlines a stepwise study plan to evaluate SWE as a tool for intrapleural pressure monitoring (Figure 1). The project only moves to the next phase is the study previous phase was achieved successfully. The current protocol involves the first phase: to validate diaphragm SWE against transdiaphragmatic pressure and assess measurement reliability for local ultrasound systems in healthy adults.This prospective, single-centre, observational validation study will include twelve healthy adult volunteers. During a single study session, participants will perform standardized inspiratory efforts while simultaneous measurements of diaphragm SWE, transdiaphragmatic pressure (via esophageal and gastric balloon catheters), and mouth pressures are obtained. These methods are routinely applied in physiological research and carry minimal risk. Apart from brief nasal or throat discomfort during catheter placement, no significant adverse effects are expected. By establishing the relationship between diaphragm SWE, transdiaphragmatic pressure, and mouth pressures, this study aims to provide the essential validation step for future clinical research in COPD patients following lung volume reduction.

3.1 Introduction and rationale In 2020 an estimate of 562.700 people had Chronic Obstructive Pulmonary Disease (COPD) in the Netherlands, resulting in 21.335 hospital admissions.\[1\] An acute exacerbation COPD (AECOPD) in combination with hospital admission is associated with high mortality and morbidity. \[2\] Noninvasive ventilation (NIV) has been very effective in the context of AECOPD, since it efficiently offloads respiratory muscles and counteracts dynamic hyperinflation. This method often prevents intubation as a bridge to administering effective therapies (e.g., glucocorticoids, bronchodilators, and antibiotic agents)\[3\], and may reduce mortality.\[4\] Current guidelines recommend NIV for the treatment of acute respiratory failure in patients with respiratory distress, pH \< 7.35, and PaCO2 \> 6 kPA (with exclusion of patients requiring invasive ventilation, see guideline).\[5,6\] National guidelines do not recommend NIV in AECOPD with increased work of breathing without respiratory acidosis due to lack of evidence. \[5\] Ultrasound of the diaphragm can identify atrophy and impaired motion or contractility of the diaphragm\[10\], and has been shown to predict mortality and NIV failure during NIV treatment for respiratory acidosis due to AECOPD.\[11-15\] Whether ultrasound of the diaphragm may predict mortality or need for (non-)invasive ventilation in AECOPD without respiratory acidosis on initial presentation is unknown. During exploratory analysis of a previous study (unpublished; NCT05671198) we might have found a marker that has the potential to predict progression to NIV or death during hospitalization for AECOPD without respiratory acidosis: The difference between diaphragm motion during tidal breathing and maximal breathing, used as a surrogate for inspiratory reserve volume (IRV), was significantly lower in patients requiring NIV or who died in-hospital compared to those who did not (1.59 cm, SD 1.91 vs. 3.14 cm, SD 2.45; p = 0.033). We performed a ROC curve analysis to assess the predictive value of these variables, which yielded an area under the ROC curve (AUROC) of 0.752 (95% CI: 0.535 - 0.968, p = 0.033), indicating a statistically significant discriminatory ability. The best cut-off value, as determined with the Youden's J statistic, was 1.74 cm, with a sensitivity of 86% and specificity of 70% for predicting NIV requirement or inhospital death. However, the number of events was low and the study was primarily powered for another outcome. Therefore, prospective validation is needed before we impose treatment based on this marker. In case the suggested ultrasound measurement (see introduction) proofs to be a discriminatory marker for deterioration during hospitalization or predictive of progression to Non-Invasive Ventilation, we hope to be able to perform a follow-up study in which patient will be randomized to either standard of care or 'elective' NIV (to avoid emergency NIV need) based on yet to determine cut-off values. 3.2 Design (including population, method, confounders and outcomes) A multi-center, prospective observational cohort study conducted at Isala Hospital and UMCG aimed at determining the value of the sonographic motion ratio (tidal/maximum) of the diaphragm in AECOPD after hospital admission. After enrollment, the sonographic diaphragm motion will be assessed as additional measurement during standard-of-care lung ultrasound (POCUS), after which hospital outcomes will be registered. Primary outcome will be the sensitivity of this ultrasound marker for in-hospital deterioration (progression to NIV of death). Secondary analysis will include predictive models. 3.3 Research question What is the sensitivity of the diaphragm motion ratio (tidal/maximum) during ultrasound for in-hospital deterioration (progression to NIV or death) in AECOPD.

The goal of this clinical trial is to learn if early provision of mindfulness based cognitive therapy can prevent psychological distress in adult patients with cancer one year after diagnosis. Researchers will compare mindfulness based cognitive therapy to usual care to see if psychological distress is lower in patients that followed mindfulness. Participants will follow 8 weekly sessions of mindfulness and fill in questionnaires.

This study will compare postoperative pain, health related quality of life (HRQoL), function, rehabilitation, urinary incontinence, muscle atrophy and component positioning in total hip arthroplasty (THA) using the posterolateral approach (PLA) or the direct superior approach (DSA). In addition, the CT images will be used to validate a new metal artefact reduction technique.

ULTRA-CTO is a prospective multicentre non-randomised investigator-initiated trial designed to enrol 200 subjects with an indication for percutaneous coronary intervention (PCI) of chronic total occluded (CTO) coronary artery. The main objective of the study is to assess the predictive value of post-PCI resting full-cycle ratio (RFR) and fractional flow reserve (FFR) with regard to Fractional flow reserve (SSR) in CTO patients.

The study will be conducted as a single-center, prospective cohort study. The primary objective of this study is to investigate the responsiveness of sonographic parameters of diaphragm to detect change in Borg score for dyspnea during hospitalisation for AECOPD without respiratory acidosis.