A Dutch Survey on Medication Adjustments after Metabolic and Bariatric Surgery: Experiences of Bariatric Surgeons, Internists, Pharmacists, and General Practitioners.

BACKGROUND: As metabolic and bariatric surgery (MBS) can alter the pharmacokinetics of drugs, post-bariatric surgery patients may require medication adjustments and monitoring. To improve pharmacotherapy in these patients, we aimed to understand the beliefs, attitudes, knowledge, and concerns of healthcare professionals who treat these patients. METHODS: A survey by means of an online questionnaire was divided into six sections. It was sent to bariatric surgeons, internists, pharmacists, and general practitioners in the Netherlands. RESULTS: Out of 229 returned surveys, 222 were included. Virtually all respondents (98%) expected MBS to influence the effect of medication. Both reduced efficacy (23%) and more adverse events or medication-related complications (21%) were recognized. Two-thirds of the respondents felt competent to prescribe or to provide advice regarding medication in post-bariatric surgery patients. Most of the respondents (95%) believed that other healthcare professionals should be aware of the contraindication "bariatric surgery". Of the respondents, 37% indicated that they were not aware of the medication advice incorporated in the electronic health record systems. Almost half of the respondents (48%) indicated that they documented changes in drug effects. Most respondents answered that these ought to be registered in the pharmacovigilance database or national registry. CONCLUSIONS: The majority of prescribers and pharmacists believe that patients will receive better pharmacotherapy if healthcare professionals take MBS into account. However, not all prescribers think they are competent to act adequately. To improve this, information on changed drug effects after MBS should be more widely shared among healthcare professionals via resources that are easily accessible.

Impact of bariatric surgery on oral anticancer drugs: an analysis of real-world data.

PURPOSE: The number of patients with bariatric surgery who receive oral anticancer drugs is rising. Bariatric surgery may affect the absorption of oral anticancer drugs. Strikingly, no specific drug dosing recommendations are available. We aim to provide practical recommendations on the application of oral anticancer drugs in patients who underwent bariatric surgery. METHODS: Patients with any kind of bariatric surgery were extracted retrospectively in a comprehensive cancer center. In addition, a flowchart was proposed to assess the risk of inadequate exposure to oral anticancer drugs in patients who underwent bariatric surgery. Subsequently, the flowchart was evaluated retrospectively using routine Therapeutic drug monitoring (TDM) samples. RESULTS: In our analysis, 571 cancer patients (0.4% of 140.000 treated or referred patients) had previous bariatric surgery. Of these patients, 78 unique patients received 152 oral anticancer drugs equaling an overall number of 30 unique drugs. The 30 different prescribed oral anticancer drugs were categorized as low risk (13%), medium risk (67%), and high risk (20%) of underdosing. TDM plasma samples of 25 patients (82 samples) were available, of which 21 samples post-bariatric surgery (25%) were below the target value. CONCLUSIONS: The proposed flowchart can support optimizing the treatment with orally administered anticancer drugs in patients who underwent bariatric surgery. We recommend performing TDM in drugs that belong to BCS classes II, III, or IV. If more risk factors are present in BCS classes II or IV, a priori switches to other drugs may be advised. In specific cases, higher dosages can be provided from the start (e.g., tamoxifen).

Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

Impact of Bariatric Surgery in the Short and Long Term: A Need for Time-Dependent Dosing of Drugs.

Sparse information is available on pharmacokinetic changes of drugs over time after bariatric surgery. By reviewing the literature on the short- and long-term pharmacokinetic changes of drugs, several patterns were identified for 39 drugs. No relevant pharmacokinetic changes were identified for roughly a third of the drugs. Of the remaining drugs, levels were variable and partly unpredictable shortly after the surgery. In the long term, most of the drug levels remain altered, but in some cases they returned to preoperative values. Based on the changes and the efficacy-safety balance of each drug, clinicians may need to perform additional clinical monitoring for specific drugs, including measuring drug levels. This review provides suggestions for clinicians and pharmacists for specific time-dependent drug dosing advice.

Patients with bariatric surgery: Urgent need for accurate registration of the contraindication to enable safe pharmacotherapy in hospital and primary care.

PURPOSE: To enable the use of automatic clinical decision support for pharmacotherapy in patients with bariatric surgery, it is necessary to register the contraindication "bariatric surgery" in the hospital, general practitioner (GP), and community pharmacy electronic health record systems. The aim of this research was to quantify the correct registration of this contraindication in hospital, GP, and community pharmacy records. Furthermore, we investigated whether the registration status in primary care was dependent on the registration status in the hospital. METHODS: From patients who underwent bariatric procedures performed in the Albert Schweitzer Hospital (Dordrecht, the Netherlands) between 2018 and 2021, the percentage of registered contraindications in hospital medical records was assessed. Due to feasibility reasons, a subset of the patients' data was created for assessing the percentage of registered contraindications in GP and community pharmacy records. RESULTS: Out of 664 patients who underwent bariatric surgery, the contraindication bariatric surgery was registered in 69.1% of the cases. Out of 552 patients, 28.3% and 25.1% were correctly registered in GP and community pharmacy records, respectively. There was no correlation between registration status in the hospital EHR and registration status in GP practices or community pharmacies. CONCLUSIONS: The percentage of correct registration of bariatric surgery in hospital, GP, and community pharmacies is low. To avoid doctors prescribing and pharmacists dispensing drugs to post-bariatric patients without knowing that they have undergone this procedure, better registration of the contraindication is required to enable optimal use of clinical decision support systems for the pharmacotherapy of patients after bariatric surgery.

Extracellular vesicles in the circulation: are erythrocyte microvesicles a confounder in the plasma haemoglobin assay?

Blood contains a mixture of extracellular vesicles from different cell types, primarily platelets, endothelial cells, leucocytes and erythrocytes. Erythrocytes are the most abundant cell type in blood and could, especially in certain pathologies, represent an important source of vesicles. Since erythrocytes contain the haemoglobin components iron and haem, which are potentially toxic, it is important to investigate the contribution of vesicle-associated haemoglobin to total cell-free haemoglobin levels. To our knowledge, this is the first time that cell-free plasma haemoglobin has been differentiated into vesicle-associated and molecular species. We investigated the contribution of vesicle-associated haemoglobin in residual patient material that was routinely analysed for total cell-free plasma haemoglobin. All patient samples included in the study were haemolytic with total cell-free haemoglobin concentration ranging from 80 to 2500 mg/l. In the majority of the samples, total cell-free haemoglobin concentration was between 100 and 200 mg/l. No haemoglobin could be detected in the vesicle fraction, indicating that the contribution of vesicle-associated haemoglobin to total cell free-haemoglobin levels in plasma is negligible. It is important to investigate whether erythrocyte vesicles are not formed in blood or that their production is not increased during pathologies associated with haemolysis or that the clearance rate of the vesicles surpasses the formation rate.