Medication use in a cohort of adults with chronic intestinal failure: A prospective cross-sectional study.

BACKGROUND: Oral drug therapy may be compromised in chronic intestinal failure (IF) because of alterations in absorption and transit. Only scarce literature is available on which medication patients with chronic IF take in daily life. The aim was to describe the medication use in these patients. METHODS: A medication history was obtained from adults with chronic IF treated in our tertiary care IF center. Degree of polypharmacy, drug classes, Biopharmaceutics Classification System classes, route of administration, and formulation of drugs were analyzed. RESULTS: From October 2019 until December 2020, 72 patients (35 patients with short bowel syndrome [SBS] and 37 patients without SBS) were included. Polypharmacy was seen in 85.7% of patients with SBS and 75.7% of patients without SBS. The top three drug classes were proton-pump inhibitors, vitamin D or acetaminophen, and antimotility medication or laxatives/benzodiazepines. Approximately 25% of the drugs were classified as Biopharmaceutics Classification System class I drugs. In patients with SBS (78%) and patients without SBS (74.9%), most medication was taken orally, requiring gastrointestinal absorption of the active substance to be pharmacologically active. Most of these medications (77% in patients with SBS and 80.8% in patients without SBS) were formulated as a capsule or tablet, requiring disintegration and dissolution in the gastrointestinal tract before absorption can take place. CONCLUSION: Polypharmacy was observed in most patients with chronic IF. Most medication was taken orally in formulations requiring disintegration, dissolution, and gastrointestinal absorption, which could be compromised in chronic IF.

Offering Guidance and Learning to Prescribers to Initiate Parenteral Nutrition using a Validated Electronic Decision TREE (OLIVE TREE).

Parenteral nutrition (PN) is recommended in patients nutritionally at risk and unable to receive oral or enteral nutrition. A standardized electronic PN order format could enhance appropriate PN prescribing. We developed the OLIVE TREE (Offering guidance and Learning to prescribers to Initiate PN using a Validated Electronic decision TREE), embedded in our electronic health record. We aimed to evaluate its validity and impact on physicians' prescribing behavior. A non-randomized before-after study was carried out in a tertiary care center. The OLIVE TREE comprises 120 individual items. A process validation was performed to determine interrater agreement between a pharmacist and the treating physician. To estimate the proportion of patients for whom the OLIVE TREE had an effective and potential impact on physicians' prescribing behavior, a proof of concept study was conducted. The proportion of patients for whom PN was averted and the proportion of decisions not in line with the recommendation were also calculated. The process validation in 20 patients resulted in an interrater agreement of 95.0%. The proof of concept in 73 patients resulted in an effective and potential impact on prescribing behavior in 50.7% and 79.5% of these patients, respectively. Initiation of PN was not averted and recommendations of the OLIVE TREE were overruled in 42.5% of the patients. Our newly developed OLIVE TREE has a good process validity. A substantial impact on prescribing behavior was observed, although initiation of PN was not avoided. In the next phase, the decision tree will be implemented hospital-wide.

Pharmacokinetic drug evaluation of letermovir prophylaxis for cytomegalovirus in hematopoietic stem cell transplantation.

INTRODUCTION: Letermovir is a new antiviral approved to prevent cytomegalovirus infection in hematopoietic stem cell transplant recipients. It has a distinct mechanism of action as it acts as a terminase complex inhibitor, and shows some advantages compared to the current treatment options for cytomegalovirus infection. Areas covered: This review focuses on the efficacy, safety, pharmacokinetics, pharmacodynamics, and drug-drug interactions of letermovir. Expert opinion: Letermovir is a new antiviral to prevent cytomegalovirus infection. Unlike the currently used polymerase inhibitors, it has a distinct mechanism of action with better safety, limited resistance, and no cross-resistance. Although a lot of research on pharmacokinetics and drug-drug interactions has already been performed, it might be useful to clarify the effect of letermovir on voriconazole exposure, the drug-drug interaction between caspofungine and letermovir and the effect of statins on letermovir exposure. Also, the lack of an exposure-response relationship should be confirmed in large real-life post-marketing studies in order to be able to lower the intravenous dose of letermovir.

A safety assessment of biological therapies targeting the IL-23/IL-17 axis in inflammatory bowel diseases.

INTRODUCTION: Many different compounds targeting the interleukin 23/17 axis have been developed and successfully studied in several autoimmune diseases, including inflammatory bowel diseases. Nevertheless, interfering with key immunological pathways raises potential safety concerns. This review focuses on the safety profile of these novel biological therapies. Areas covered: A literature search until March 2017 was performed to collect safety data on different compounds targeting this pathway, with emphasis on ustekinumab and secukinumab. Firstly, the authors discuss briefly how genetics can inform about potential safety issues. Secondly, they extensively describe safety issues (common adverse events, infections, malignancies…), immunogenicity, exposure to ustekinumab in specific populations and provide advice for vaccination. Finally, they address safety profiles of secukinumab and other biological targeting the IL-23/17 axis in IBD. Expert opinion: Current evidence suggests that ustekinumab therapy overweigh the potential drug-related risks. Additional safety data beyond randomized-controlled trials, derived from statistically powered, large prospective studies with long-term follow-up are urgently needed to assess the real-life ustekinumab-related risks and to establish the correct position of these novel class of biologicals in IBD treatment. Combining immunomodulators with ustekinumab seems to be safe, though prospective data specifically addressing this topic are currently missing. Similarly, the combination of different biological therapies still has to be studied.

An unusual cause of severe, persistent diarrhoea.

We present two cases of patients with severe persistent diarrhoea, in whom duodenal biopsies revealed villous atrophy that could be attributed to the use of olmesartan. The differential diagnosis of villous atrophy without serological markers of celiac disease should include drugs as possible cause, with olmesartan as a recently discovered culprit. Gastroenterologist should be aware of this entity.

Evaluation of parenteral nutrition use in patients undergoing major upper gastro-intestinal surgery.

BACKGROUND: After major upper gastro-intestinal surgery, enteral feeding is often hampered. There is still no consensus on which route of nutrition is preferable in patients undergoing this type of surgery. Current ESPEN guidelines recommend parenteral nutrition in undernourished patients, if caloric requirements cannot be met orally/enterally within 7 days and enteral nutrition is contraindicated. OBJECTIVE: The current practice of systematic parenteral nutrition at the thoracic surgery ward of the University Hospitals Leuven was evaluated based on the ESPEN guidelines. METHOD: This prospective observational study included patients undergoing upper gastro-intestinal surgery and receiving postoperative parenteral nutrition. Parenteral nutrition use was considered appropriate when patients were undernourished and unable to obtain adequate caloric requirements by oral or enteral feeding within 7 days. RESULTS: Twenty-five out of 35 patients were nutritionally at risk. In 9 of 25 patients, the indication for parenteral nutrition was considered justified. As the intestinal tract below the anastomosis site remains accessible in the total studied population, enteral nutrition might be an option. Unfortunately, an appropriate jejunostomy tube was not available at our institution. CONCLUSION: In accordance to the ESPEN guidelines, enteral nutrition can replace parenteral nutrition in most thoracic surgery patients, but only if an appropriate enteral access is available.