Validation of an LC-MS/MS assay for rapid and simultaneous quantification of 21 kinase inhibitors in human plasma and serum for therapeutic drug monitoring.

Kinase inhibitors have revolutionized cancer treatment in the past 25 years and currently form the cornerstone of many treatments. Due to the increasing evidence for therapeutic drug monitoring (TDM) of kinase inhibitors, the need is growing for new assays to rapidly evaluate kinase inhibitor plasma concentrations. In this study, we developed an LC-MS/MS assay for the rapid and simultaneous quantification of 21 kinase inhibitors.

Ultra-high throughput dual channel liquid chromatography with tandem mass spectrometry for quantification of four immunosuppressants in whole blood for therapeutic drug monitoring.

Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is the golden standard for immunosuppressants analyses, where optimising throughput by parallel chromatography can reduce costs and turnaround time. We aimed to double our system throughput using a dual LC-MS/MS setup. Therefore, two independent UPLC systems were hyphenated to one triple quadrupole MS, with staggered injections from one autosampler on alternating columns.

Expeditious quantification of plasma tacrolimus with liquid chromatography tandem mass spectrometry in solid organ transplantation.

Traditionally, tacrolimus is assessed in whole blood samples, but this is suboptimal from the perspective that erythrocyte-bound tacrolimus is not a good representative of the active fraction. In this work, a straightforward and rapid method was developed for determination of plasma tacrolimus in solid organ transplant recipients, using liquid chromatography tandem mass spectrometry (LC-MS/MS) with heated electrospray ionisation. Sample preparation was performed through protein precipitation of 200 µl plasma with 500 µl stable isotopically labelled tacrolimus I.

Continuous versus intermittent infusion of cefotaxime in critically ill patients: a randomized controlled trial comparing plasma concentrations.

Background: In critical care patients, reaching optimal β-lactam concentrations poses challenges, as infections are caused more often by microorganisms associated with higher MICs, and critically ill patients typically have an unpredictable pharmacokinetic/pharmacodynamic profile. Conventional intermittent dosing frequently yields inadequate drug concentrations, while continuous dosing might result in better target attainment. Few studies address cefotaxime concentrations in this population.

A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects.

The aim of this study was to develop and validate a LC-MS/MS assay for tacrolimus, sirolimus, everolimus, cyclosporin A and mycophenolic acid using volumetric absorptive microsampling tips as a sampling device and to investigate the effect on the recoveries of the analyte concentration in combination with the hematocrit (HT), which included temsirolimus (a structural analog). The maximum observed overall bias was 9.6% for the sirolimus LLOQ, while the maximum overall coefficient of variation was 8.

Correction to: Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy.

The Abstract section and the in the Results sections of the original version of this article, unfortunately, contained errors. The correct data are now shown in this article.

Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy.

Poor self-management contributes to insufficient glycemic control in adolescents with type 1 diabetes (T1DM). We assessed the effects on glycemic control of adherence to self-measurement of blood glucose (SMBG) and insulin boluses in 90 adolescents with T1DM on insulin pump therapy over a 2-month period. We compared the number of insulin boluses and SMBGs around main meals to the "gold standard" of optimal diabetes management (SMBGs and a bolus before each main meal and SMBG before bedtime).

Diagnosing orthostatic hypotension with continuous and interval blood pressure measurement devices.

Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure (SBP) of ≥20 mm Hg and/or a drop in diastolic blood pressure (DBP) of ≥10 mm Hg within 3 min of standing. The international guidelines recommend ideally diagnosing OH with a continuous blood pressure (BP) measurement device, although in daily practice interval BP measurement devices are used more often. We aimed to investigate the difference in observed prevalence of OH between an interval and a continuous BP measurement device.

Gender differences in the evaluation of care for patients with type 2 diabetes: a cross-sectional study (ZODIAC-52).

Background: Little is known about the association between patient-related factors and patients' evaluation of care. Aim was to investigate which patient-related factors are associated with patients' evaluation of care in men and women with type 2 diabetes (T2D) in primary care.

Methods: This cross-sectional study included 1102 patients with T2D from 52 general practices.

Association between body mass index and obesity-related cancer risk in men and women with type 2 diabetes in primary care in the Netherlands: a cohort study (ZODIAC-56).

Objective: To investigate the relationship between body mass index (BMI) and obesity-related cancers in men and women with type 2 diabetes (T2D).

Design: Observational cohort study.

Setting: Primary care.

Sex differences in survival of patients with type 2 diabetes in primary care (ZODIAC-50).

Objective: To investigate sex differences in survival of primary care treated patients with type 2 diabetes (T2D) in the Netherlands.

Setting: Primary care.

Participants: A total of 1815 patients who participated in a prospective observational cohort study (Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC)) were included of which 56% was female.

Dried Blood Spot Analysis for Therapeutic Drug Monitoring of Clozapine.

Background: Schizophrenia is a psychiatric disorder that affects approximately 0.4%-1% of the population worldwide. Diagnosis of schizophrenia is based primarily on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.

Within-class differences in cancer risk for sulfonylurea treatments in patients with type 2 diabetes (ZODIAC-55) - a study protocol.

Background: Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world's population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers.

Pharmacokinetics of Levofloxacin in Multidrug- and Extensively Drug-Resistant Tuberculosis Patients.

Pharmacodynamics are especially important in the treatment of multidrug- and extensively drug-resistant tuberculosis (M/XDR-TB). The free area under the concentration time curve in relation to MIC (AUC/MIC) is the most relevant pharmacokinetic (PK)-pharmacodynamic (PD) parameter for predicting the efficacy of levofloxacin (LFX). The objective of our study was to assess LFX PK variability in M/XDR-TB patients and its potential consequence for AUC/MIC ratios.

Target attainment with continuous dosing of piperacillin/tazobactam in critical illness: a prospective observational study.

Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population. Several studies have shown intermittent dosing to often yield inadequate drug concentrations. Continuous dosing is an attractive alternative from a pharmacodynamic point of view.

Is orthostatic hypotension related to falling? A meta-analysis of individual patient data of prospective observational studies.

Background: orthostatic hypotension (OH) is one out of many risk factors believed to contribute to an increased fall risk in elderly subjects but it is unclear whether an independent association between OH and falling exists.

Objectives: to perform an individual patient data (IPD) meta-analysis of prospective observational studies investigating the relationship between OH and falling.

Design: MEDLINE, EMBASE, the Cochrane Library and the abstracts of annual meetings of selected hypertension societies were searched.

Lifestyle and emotional well-being in men and women with type 2 diabetes (e-VitaDM-4; ZODIAC-48).

Background: Whether lifestyle is associated with well-being in patients with type 2 diabetes (T2D) is largely unknown. Uncovering and clarifying associations between these constructs may lead to new strategies for improving both.

Objectives: The aim was to investigate the relationship between lifestyle and well-being, focussing on gender differences.

Standing orthostatic blood pressure measurements cannot be replaced by sitting measurements.

As many elderly patients are not able to stand for several minutes, sitting orthostatic blood pressure (BP) measurements are sometimes used as an alternative. We aimed to investigate the difference in BP response and orthostatic hypotension (OH) prevalence between the standard postural change to the sitting and the standing position in a cross-sectional observational study. BP was measured with a continuous BP measurement device during two postural changes, from supine to the sitting and from supine to the standing position.

The clinical relevance of orthostatic hypotension in elderly patients.

Aim: Orthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints.

Association Between Orthostatic Hypotension and Handgrip Strength With Successful Rehabilitation in Elderly Hip Fracture Patients.

Objective: To investigate the relationship between orthostatic hypotension (OH) and muscle strength versus time to successful rehabilitation within elderly patients with hip fracture.

Design: A prospective, observational cohort study. Handgrip strength was measured at the day of admission and OH as soon as possible after surgery.

Patient Activation in Type 2 Diabetes: Does It Differ between Men and Women?

Aim was to investigate whether the degree of patient activation of patients with type 2 diabetes (T2D) is different between men and women. Furthermore, we investigated which factors are associated with patient activation in men and women. This cross-sectional study included 1615 patients with T2D from general practices.