Highlighting the Undetectable - Fluorescence Molecular Imaging in Gastrointestinal Endoscopy.

Flexible high-definition white-light endoscopy is the current gold standard in screening for cancer and its precursor lesions in the gastrointestinal tract. However, miss rates are high, especially in populations at high risk for developing gastrointestinal cancer (e.g., inflammatory bowel disease, Lynch syndrome, or Barrett's esophagus) where lesions tend to be flat and subtle. Fluorescence molecular endoscopy (FME) enables intraluminal visualization of (pre)malignant lesions based on specific biomolecular features rather than morphology by using fluorescently labeled molecular probes that bind to specific molecular targets. This strategy has the potential to serve as a valuable tool for the clinician to improve endoscopic lesion detection and real-time clinical decision-making. This narrative review presents an overview of recent advances in FME, focusing on probe development, techniques, and clinical evidence. Future perspectives will also be addressed, such as the use of FME in patient stratification for targeted therapies and potential alliances with artificial intelligence. KEY MESSAGES: • Fluorescence molecular endoscopy is a relatively new technology that enables safe and real-time endoscopic lesion visualization based on specific molecular features rather than on morphology, thereby adding a layer of information to endoscopy, like in PET-CT imaging. • Recently the transition from preclinical to clinical studies has been made, with promising results regarding enhancing detection of flat and subtle lesions in the colon and esophagus. However, clinical evidence needs to be strengthened by larger patient studies with stratified study designs. • In the future fluorescence molecular endoscopy could serve as a valuable tool in clinical workflows to improve detection in high-risk populations like patients with Barrett's esophagus, Lynch syndrome, and inflammatory bowel syndrome, where flat and subtle lesions tend to be malignant up to five times more often. • Fluorescence molecular endoscopy has the potential to assess therapy responsiveness in vivo for targeted therapies, thereby playing a role in personalizing medicine. • To further reduce high miss rates due to human and technical factors, joint application of artificial intelligence and fluorescence molecular endoscopy are likely to generate added value.

[A female patient with liver failure and pseudocirrhosis]. / Een patiënte met leverfalen en pseudocirrose.

BACKGROUND: Acute-on-chronic liver failure encompasses an acute deterioration of liver function in patients with pre-existent cirrhosis. Sometimes the clinical picture of acute-on-chronic liver failure is misleading and may not be secondary to primary liver disease, as described in our case. CASE DESCRIPTION: A 65-year-old woman with cirrhosis was transferred to our transplantation centre because of suspected acute-on-chronic liver failure. Given her medical history of breastcancer and suspicious laboratory results, we performed a liver biopsy. This showed diffuse metastases of mammary carcinoma. Earlier CT-scans showed features of cirrhosis without signs of malignancy: a misleading phenomenon called pseudocirrhosis. CONCLUSION: Diffuse malignant hepatic infiltration can resemble cirrhosis and acute-on-chronic liver failure, both in clinical presentation as in imaging. Liver transplantation is contraindicated in malignant liver failure. To assure a solid indication for transplantation, a liver biopsy has to be considered, even in emergency situations.

Budget Impact Analysis of a Renal Point-of-Care Test in Dutch Community Pharmacies to Prevent Antibiotic-Related Hospitalizations.

OBJECTIVES: Medication errors that lead to adverse drug reactions are a key cause of unintentional patient harm and subsequent economic burden. To prevent this, measurement of renal function could be considered. The aim of this study was to determine the budget impact of obtaining and evaluating renal function in community pharmacies in the Netherlands to prevent antibiotic-related hospitalizations. METHODS: A decision model was built to simulate the process of antibiotic prescriptions in community pharmacies with and without the use of a point-of-care test (PoCT) in patients aged 65 years and older. By using a PoCT, the number of patients with renal function values available increases, leading to the possibility of dose adjustment when necessary. In turn, this might avoid hospitalizations. For this study, real-life patient data were used from 351 community pharmacies. Direct costs of renal function screening, antibiotic treatments, and medical care due to antibiotic-related hospitalization were included. RESULTS: The budget impact analysis showed annual cost-savings of €86 per patient through the availability of renal function values in Dutch community pharmacies. Savings were mostly due to avoided hospitalizations. CONCLUSION: Obtaining and evaluating renal function in community pharmacies by point of care tests is expected to be cost-saving in the Netherlands.

Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study on drug-related problems in the Netherlands.

BACKGROUND: Knowledge of drug-related problems (DRPs) identified in the medication of home-dwelling elderly patients with polypharmacy has been based predominantly on medication reviews conducted in research settings rather than in daily practice. OBJECTIVE: To evaluate the prevalence of DRPs identified by means of a clinical medication review (CMR) and the implementation rate of proposed interventions in a large group of older patients with polypharmacy in the daily practice of community pharmacies. SETTING: 318 Dutch community pharmacies. METHOD: A cross-sectional study based on CMR-data of 3807 older patients (≥65 years) with polypharmacy (≥5 drugs) completed between January and August 2012. Data were extracted from community pharmacists' databases and entailed: year of birth, gender, dispensing data, number and nature of identified DRPs, consultations performed, proposed and implemented interventions. Main outcome measure Prevalence of DRPs, drug classes involved in overtreatment and undertreatment, and proposed and implemented interventions. RESULTS: A median of two DRPs (interquartile range 1-4; mean 3.0) was identified per patient. The DRP-categories overtreatment (25.5 %) and undertreatment (15.9 %) were found most frequently. 46.2 % of the proposed interventions to solve DRPs were implemented as proposed, in 22.4 % of cases, the intervention differed from the proposal. In 31.3 % of cases no intervention was implemented. CONCLUSION: By conducting a CMR community pharmacists identified a median of two DRPs in older patients with polypharmacy. Overtreatment and undertreatment accounted for 41.4 % of the DRPs identified. In dealing with DRPs, pharmacists proposed a variety of interventions of which the majority (69.9 %) was either implemented or led to alternative interventions. A set of explicit criteria should be applied during a CMR to solve and prevent DRPs.

Large scale implementation of clinical medication reviews in Dutch community pharmacies: drug-related problems and interventions.

BACKGROUND: Research on the benefits of clinical medication reviews (CMRs) performed by pharmacists has been conducted mostly in controlled settings and has been widely published. Less is known of the effects after large scale implementation in community pharmacies. An online CMR tool enabled the systematic registration of drug-related problems (DRPs) and implemented interventions derived from CMRs in daily practice. OBJECTIVE: To describe the effects of CMRs on pharmacy practice after large-scale implementation in the Netherlands. SETTING: 268 community pharmacies. Pharmacists were trained on CMRs with a patient centred approach. METHOD: Retrospective analyses of DRPs, pharmacists' proposals and implemented interventions recorded between January 1st and September 1st 2012. MAIN OUTCOME MEASURE: Frequencies of DRPs, intervention proposals, implemented interventions, and drugs involved. RESULTS: 4,579 CMRs were analysed. On average 2.9 (SD 2.1) DRPs per review were identified. 4,123 (31 %) of the DRPs led to medication changes. Stopping a drug (16 %) was more frequent than starting a drug (8.1 %). Drugs related to cardiovascular risk management, diabetes and osteoporosis were most frequently involved. CONCLUSION: This study is the largest analysis of pharmacists-initiated CMRs in the Netherlands to date. The findings demonstrate the potential to reduce medication-related errors through pharmacist involvements in complex pharmacotherapy and the positive impact on the quality of drug therapy through making necessary medication changes. The data also support the need for large-scale implementation of pharmacists-initiated CMRs in the presence of proper training programmes.