An unhealthy lifestyle may contribute to ill health, absence due to sickness, productivity loss at work, and reduced ability to work. Workplace health promotion programs (WHPPs) aim to improve ...lifestyle and consequently improve health, work ability, and work productivity. However, systematic reviews on intervention studies have reported small effects, and the overall evaluation of effectiveness of WHPPs is hampered by a large heterogeneity in interventions and study populations. This systematic review aims to investigate the influence of population, study and intervention characteristics, and study quality on the effectiveness of workplace health promotion programs.
A systematic literature search was conducted identifying RCTs, published before June 2012, evaluating the effect of a WHPP aimed at smoking cessation, physical activity, healthy nutrition, and/or obesity on self-perceived health, work absence due to sickness, work productivity, or work ability. Studies were included in the meta-analyses if quantitative information was present to calculate an effect size (ES). A meta-analysis, stratified meta-analyses, and meta-regression analyses were performed in Spring 2012 using Comprehensive Meta-analysis software 2.0 and PAWS 17.0.2.
In 18 studies describing 21 interventions, the overall effect of a WHPP was small (ES=0.24, 95% CI=0.14, 0.34). The effectiveness of a WHPP was larger in younger populations, in interventions with weekly contacts, and in studies in which the control group received no health promotion. A 2.6-fold lower effectiveness was observed for studies performing an intention-to-treat analysis and a 1.7-fold lower effectiveness for studies controlling for confounders. Studies of poor methodologic quality reported a 2.9-fold higher effect size of the WHPP.
The effectiveness of a WHPP is partly determined by intervention characteristics and statistical analysis. High-quality RCTs reported lower effect sizes. It is important to determine the effectiveness of WHPPs in RCTs of high quality.
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. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.
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.
Critically ill adult patients who were admitted to the intensive care unit and received nadroparin for prophylaxis of venous thromboembolism were included in a study. Population pharmacokinetic analysis was performed by means of parametric non-linear mixed-effects modelling (NONMEM).
A total of 30 patients were enrolled with 12 patients undergoing continuous veno-venous hemodialysis and 18 patients not undergoing continuous veno-venous hemodialysis. Very high variability in pharmacokinetics was observed with an inter-individual variability in the volume of distribution of 63.7% (95% confidence interval 46.5-90.6), clearance of 166% (95% confidence interval 84.7-280) and relative bioavailability of 40.2% (95% confidence interval 29.5-52.6). We found that standard doses of 2850 IE and 5700 IE of nadroparin resulted in sub-prophylactic exposure in critically ill patients.
Low exposure and highly variable pharmacokinetics of nadroparin were observed in intensive care unit patients treated with a prophylactic dose. It can be debated whether nadroparin is currently dosed optimally in intensive care unit patients and our findings encourage the investigation of higher and tailored dosing of nadroparin in the critically ill.
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.
Employees of two organizations were invited to participate in a six-month follow-up study (n = 744). Using questionnaires, information on participation in HPPs was collected in two categories: employees' intention at baseline to participate and their actual participation in a HPP during the follow-up period. The following potential determinants were assessed at baseline: social-cognitive factors, perceived barriers and facilitators, beliefs about health at work, health behaviors, and self-perceived health. Logistic regression analyses, adjusted for demographics and organization, were used to examine associations between potential determinants and intention to participate, and to examine the effect of these determinants on actual participation during follow-up.
At baseline, 195 employees (26%) expressed a positive intention towards participation in a HPP. During six months of follow-up, 83 employees (11%) actually participated. Participants positively inclined at baseline to participate in a HPP were more likely to actually participate (OR = 3.02, 95% CI: 1.88-4.83). Privacy-related barriers, facilitators, beliefs about health at work, social-cognitive factors, and poor self-perceived health status were significantly associated with intention to participate. The odds of employees actually participating in a HPP were higher among participants who at baseline perceived participation to be expected by their colleagues and supervisor (OR = 2.87, 95% CI: 1.17-7.02) and among those who said they found participation important (OR = 2.81, 95% CI: 1.76-4.49).
Participation in HPPs among employees is limited. Intention to participate predicted actual participation in a HPP after six months of follow-up. However, only 21% of employees with a positive intention actually participated during follow-up. Barriers, facilitators, beliefs about health at work, social-cognitive factors, and a poor self-perceived health status were associated with intention to participate, but hardly influenced actual participation during follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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. All patients received a midazolam 7.5 mg oral and 5 mg intravenous dose (separated by 159 ± 67 min) and per patient 22 samples over 11 h were collected. Data from 12 healthy volunteers were available for a population pharmacokinetic analysis using NONMEM
®
.
Results
In the three-compartment model in which oral absorption was characterized by a transit absorption model, population mean clearance (relative standard error %) was similar 0.36 (4 %) L/min, while oral bioavailability was 60 % (13 %) in morbidly obese patients versus 28 % (7 %) in healthy volunteers (
P
< 0.001). Central and peripheral volumes of distribution increased substantially with body weight (both
P
< 0.001) and absorption rate (transit rate constant) was lower in morbidly obese patients 0.057 (5 %) vs. 0.130 (14 %) min
–1
,
P
< 0.001.
Conclusions
In morbidly obese patients, systemic clearance of midazolam is unchanged, while oral bioavailability is increased. Given the large increase in volumes of distribution, dose adaptations for intravenous midazolam should be considered. Further research should elucidate the exact physiological changes at intestinal and hepatic level contributing to these findings.
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.
This review provides an overview of the systematic accuracy of allometric and other pediatric clearance scaling methods compared to gold-standard PBPK predictions. The findings are summarized in decision tables to provide a priori guidance on the selection of appropriate pediatric clearance scaling methods for both novel drugs for which no pediatric data are available and existing drugs in clinical practice.
While allometric scaling principles are commonly used to scale pediatric clearance, there is no universal allometric exponent (i.e. 1, 0.75, or 0.67) that can accurately scale clearance for all drugs from adults to children of all ages. Therefore, pediatric scaling decision tables based on age, drug elimination route, binding plasma protein, fraction unbound, extraction ratio, and/or isoenzyme maturation are proposed to a priori select the appropriate (allometric) clearance scaling method, thereby reducing the need for full PBPK-based clearance predictions. Guidance on allometric scaling when estimating pediatric clearance values is provided as well.
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.
Employees of two organizations participated in a six-month follow-up study (n = 738). At baseline, information was collected on employees' needs and preferences for the topic of the HPP (i.e. physical activity, healthy nutrition, smoking cessation, stress management, general health), whether they favored a HPP via their employer or at their own discretion, and their preferred HPP regarding three components with each two alternatives: mode of delivery (individual vs. group), intensity (single vs. multiple meetings), and content (assignments vs. information). Participation in HPPs was assessed at six-month follow-up. In consultation with occupational health managers (n = 2), information was gathered on the HPPs the employers provided. The level of agreement between preferred and provided HPPs was calculated (range: 0-1) and its influence on participation was studied using logistic regression analyses.
Most employees reported needing a HPP addressing physical activity (55%) and most employees preferred HPPs organized via their employer. The mean level of agreement between the preferred and offered HPPs ranged from 0.71 for mode of delivery to 0.84 for intensity, and was 0.47 for all three HPP components within a topic combined. Employees with a higher agreement on mode of delivery (OR: 1.72, 95% CI: 0.87-3.39) and all HPP components combined (OR: 2.36, 95% CI: 0.68-8.17) seemed to be more likely to participate in HPPs, but due to low participation these associations were not statistically significant.
HPPs aimed at physical activity were most needed by employees. The majority of employees favor HPPs organized via the employer above those at their own discretion, supporting the provision of HPPs at the workplace. This study provides some indications that a higher agreement between employees' needs and preferences and HPPs made available by their employers will enhance participation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Methods
Data from 19 obese adolescents 102.7 kg (62–149.5 kg) and 20 morbidly obese adults 144 kg (112–186 kg) receiving intravenous midazolam were analysed, using population pharmacokinetic modelling (NONMEM 7.2). In the covariate analysis, the influence of study group, age, total body weight (TBW), developmental weight (WT
for age and length
) and excess body weight (WT
excess
= TBW − WT
for age and length
) was evaluated.
Results
The population mean midazolam clearance was significantly higher in obese adolescents than in morbidly obese adults 0.71 (7%) vs. 0.44 (11%) L/min;
p
< 0.01. Moreover, clearance in obese adolescents increased with TBW (
p
< 0.01), which seemed mainly explained by WT
excess
, and for which a so-called ‘excess weight’ model scaling WT
for age and length
to the power of 0.75 and a separate function for WT
excess
was proposed.
Discussion
We hypothesise that higher midazolam clearance in obese adolescents is explained by less obesity-induced suppression of CYP3A activity, while the increase with WT
excess
is explained by increased liver blood flow. The approach characterising the influence of obesity in the paediatric population we propose here may be of value for use in future studies in obese adolescents.
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 32.5 % lower compared with the general patient population, suggesting dose increases may be required in this population.
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