Low and Highly Variable Exposure to Prophylactic LMWH Nadroparin in Critically Ill Patients: Back to the Drawing Board for Prophylactic Dosing?

Background And Objective: Low-molecular-weight heparins are routinely administered to patients in the intensive care unit to prevent venous thromboembolisms. There is considerable evidence that low-molecular-weight heparin doses should be personalised based on anti-Xa levels, but pharmacokinetic data in intensive care unit patients are lacking. This study aimed to characterise the pharmacokinetics and associated variability of the low-molecular-weight heparin nadroparin in critically ill patients.

An Update on the Use of Allometric and Other Scaling Methods to Scale Drug Clearance in Children: Towards Decision Tables.

Introduction: When pediatric data are not available for a drug, allometric and other methods are applied to scale drug clearance across the pediatric age-range from adult values. This is applied when designing first-in-child studies, but also for off-label drug prescription.

Areas Covered: This review provides an overview of the systematic accuracy of allometric and other pediatric clearance scaling methods compared to gold-standard PBPK predictions.

Outcome measurement instruments for peripheral vascular malformations and an assessment of the measurement properties: a systematic review.

Purpose: The Outcome measures for vascular malformation (OVAMA) group reached consensus on the core outcome domains for the core outcome set (COS) for peripheral vascular malformations (venous, lymphatic and arteriovenous malformations). However, it is unclear which instruments should be used to measure these domains. Therefore, our aims were to identify all outcome measurement instruments available for vascular malformations, and to evaluate their measurement properties.

Increased Metformin Clearance in Overweight and Obese Adolescents: A Pharmacokinetic Substudy of a Randomized Controlled Trial.

Background: In view of the increased use of metformin in obese adolescents, the aim of this study was to determine the pharmacokinetics of metformin in overweight and obese adolescents.

Methods: In overweight and obese adolescents receiving metformin 500 or 1000 mg twice daily for 37 weeks during a clinical trial, blood samples were collected over 8 h during an oral glucose tolerance test. Population pharmacokinetic modeling was performed using NONMEM.

Outcome Measurement for Vascular Malformations of the Head and Neck.

Vascular malformations are congenital anomalies of the vascular and/or lymphatic system that affect the head and neck region. The most common treatment options are sclerotherapy, laser therapy, surgery, and embolization. Because vascular malformations are variable in type, size, extent, and location, it is a challenge to select methods for evaluation of treatment outcome.

Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults.

Background: The clearance of cytochrome P450 (CYP) 3A substrates is reported to be reduced with lower age, inflammation and obesity. As it is unknown what the overall influence is of these factors in the case of obese adolescents vs. morbidly obese adults, we studied covariates influencing the clearance of the CYP3A substrate midazolam in a combined analysis of data from obese adolescents and morbidly obese adults.

Exposure to acetaminophen and all its metabolites upon 10, 15, and 20 mg/kg intravenous acetaminophen in very-preterm infants.

BackgroundExposure to acetaminophen and its metabolites in very-preterm infants is partly unknown. We investigated the exposure to acetaminophen and its metabolites upon 10, 15, or 20 mg/kg intravenous acetaminophen in preterm infants.MethodsIn a randomized trial, 59 preterm infants (24-32 weeks' gestational age, postnatal age <1 week) received 10, 15, or 20 mg/kg acetaminophen intravenously.

Does Weight Impact Anidulafungin Pharmacokinetics?

Bodyweight has been shown to influence anidulafungin exposure, but data from obese patients are lacking. We determined anidulafungin pharmacokinetics (100-mg single dose) in eight morbidly obese subjects (body mass index >40 kg/m(2)). Anidulafungin exposure was on average 32.

Morbidly Obese Patients Exhibit Increased CYP2E1-Mediated Oxidation of Acetaminophen.

Introduction: Acetaminophen (paracetamol) is mainly metabolized via glucuronidation and sulphation, while the minor pathway through cytochrome P450 (CYP) 2E1 is held responsible for hepatotoxicity. In obese patients, CYP2E1 activity is reported to be induced, thereby potentially worsening the safety profile of acetaminophen. The aim of this study was to determine the pharmacokinetics of acetaminophen and its metabolites (glucuronide, sulphate, cysteine and mercapturate) in morbidly obese and non-obese patients.

Population Pharmacokinetic Model Characterizing 24-Hour Variation in the Pharmacokinetics of Oral and Intravenous Midazolam in Healthy Volunteers.

Daily rhythms in physiology may affect the pharmacokinetics of a drug. The aim of this study was to evaluate 24-hour variation in the pharmacokinetics of the CYP3A substrate midazolam. Oral (2 mg) and intravenous (1 mg) midazolam was administered at six timepoints throughout the 24-hour period in 12 healthy volunteers.

Educational Inequalities in Exit from Paid Employment among Dutch Workers: The Influence of Health, Lifestyle and Work.

Background: Individuals with lower socioeconomic status are at increased risk of involuntary exit from paid employment. To give sound advice for primary prevention in the workforce, insight is needed into the role of mediating factors between socioeconomic status and labour force participation. Therefore, it is aimed to investigate the influence of health status, lifestyle-related factors and work characteristics on educational differences in exit from paid employment.

The Pharmacokinetics of the CYP3A Substrate Midazolam in Morbidly Obese Patients Before and One Year After Bariatric Surgery.

Purpose: Bariatric surgery is nowadays commonly applied as treatment for morbid obesity (BMI > 40 kg/m(2)). As information about the effects of this procedure on a drug's pharmacokinetics is limited, we aimed to evaluate the pharmacokinetics of CYP3A probe substrate midazolam after oral and intravenous administration in a cohort of morbidly obese patients that was studied before and 1 year post bariatric surgery.

Methods: Twenty morbidly obese patients (aged 26-58 years) undergoing bariatric surgery participated in the study of which 18 patients returned 1 year after surgery.

Population pharmacokinetics of midazolam and its metabolites in overweight and obese adolescents.

Aim: In view of the increasing prevalence of obesity in adolescents, the aim of this study was to determine the pharmacokinetics of the CYP3A substrate midazolam and its metabolites in overweight and obese adolescents.

Methods: Overweight (BMI for age ≥ 85(th) percentile) and obese (BMI for age ≥ 95(th) percentile) adolescents undergoing surgery received 2 or 3 mg intravenous midazolam as a sedative drug pre-operatively. Blood samples were collected until 6 or 8 h post-dose.

How needs and preferences of employees influence participation in health promotion programs: a six-month follow-up study.

Background: Low participation in health promotion programs (HPPs) might hamper their effectiveness. A potential reason for low participation is disagreement between needs and preferences of potential participants and the actual HPPs offered. This study aimed to investigate employees' need and preferences for HPPs, whether these are matched by what their employers provide, and whether a higher agreement enhanced participation.

Low mean impedance in 24-hour tracings and esophagitis in children: a strong connection.

Esophageal multiple intraluminal impedance baseline is an additional impedance parameter that was recently related to esophageal integrity. The aim of this study was to assess the relationship between mean esophageal impedance value and endoscopic findings in a large group of children. Children with symptoms of gastroesophageal reflux submitted to both endoscopy and impedance were included.

Drug disposition in obesity: toward evidence-based dosing.

Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date.

Midazolam pharmacokinetics in morbidly obese patients following semi-simultaneous oral and intravenous administration: a comparison with healthy volunteers.

Background: While in vitro and animal studies have shown reduced cytochrome P450 (CYP) 3A activity due to obesity, clinical studies in (morbidly) obese patients are scarce. As CYP3A activity may influence both clearance and oral bioavailability in a distinct manner, in this study the pharmacokinetics of the CYP3A substrate midazolam were evaluated after semi-simultaneous oral and intravenous administration in morbidly obese patients, and compared with healthy volunteers.

Methods: Twenty morbidly obese patients [mean body weight 144 kg (range 112-186 kg) and mean body mass index 47 kg/m(2) (range 40-68 kg/m(2))] participated in the study.

The contribution of work engagement to self-perceived health, work ability, and sickness absence beyond health behaviors and work-related factors.

Objective: To investigate whether work engagement influences self-perceived health, work ability, and sickness absence beyond health behaviors and work-related characteristics.

Methods: Employees of two organizations participated in a 6-month longitudinal study (n = 733). Using questionnaires, information was collected on health behaviors, work-related characteristics, and work engagement at baseline, and self-perceived health, work ability, and sickness absence at 6-month follow-up.

The importance of internal health beliefs for employees' participation in health promotion programs.

Objective: To investigate associations between employees' health locus of control (HLOC) and self-perceived health, health behaviors, and participation in health promotion programs (HPPs) and the mediating effect of self-perceived health and health behaviors on the relation between HLOC and participation.

Method: Between 2010 and 2012, a six-month longitudinal study was conducted among 691 Dutch employees. Using questionnaires, information was collected on health behaviors, self-perceived health, HLOC, and intention to participate at baseline.

Barriers and facilitators for participation in health promotion programs among employees: a six-month follow-up study.

Background: Health promotion programs (HPPs) are thought to improve health behavior and health, and their effectiveness is increasingly being studied. However, participation in HPPs is usually modest and effect sizes are often small. This study aims to (1) gain insight into the degree of participation of employees in HPPs, and (2) identify factors among employees that are associated with both their intention to participate and actual participation in HPPs.

Influence of work-related characteristics and work ability on changing employer or leaving the profession among nursing staff.

Aim: To investigate how work-related characteristics and work ability influence nursing staff decisions to change employer or leave the profession.

Background: Previous cross-sectional studies have indicated that decreased work ability and unfavourable work-related characteristics are important determinants for the intention to leave the profession among nursing staff.

Methods: A 1-year longitudinal study, using data from the European Nurses' Early Exit Study.