Implementation of the Participatory Approach for Supervisors to Increase Self-Efficacy in Addressing Risk of Sick Leave of Employees: Results of a Cluster-Randomized Controlled Trial.

Purpose To study the effectiveness of a multifaceted strategy to implement the participatory approach (PA) for supervisors to increase their self-efficacy in addressing risk of sick leave of employees. Methods Supervisors from three organizations were invited to participate. Randomization was performed at department level. Supervisors (n = 61) in the intervention departments received the implementation strategy consisting of a working group meeting, supervisor training in PA application, and optional supervisor coaching. Supervisors in the control departments (n = 55) received written information on PA. The primary outcome was supervisors' self-efficacy to apply the PA, measured at baseline and 6 months' follow-up. The number of employees with whom supervisors discussed work functioning problems or (risk of) sick leave was also assessed. Effects were tested using multilevel analyses. Results The strategy did not increase self-efficacy to apply the PA. Subgroup analyses showed that self-efficacy increased for supervisors who at baseline reported to have discussed (risk of) sick leave with less than three employees during the last 6 months (B = 1.42, 95 % CI 0.34-2.50). Furthermore, the implementation strategy increased the number of employees with whom supervisors discussed work functioning problems or risk of sick leave (B = 1.26, 95 % CI 0.04-2.48). Conclusion Although the implementation strategy cannot be recommended for all supervisors, for supervisors who less frequently discuss (risk of) sick leave with employees the implementation strategy might be helpful. Trial registration NTR3733.

Employees' Perceptions of Social Norms as a Result of Implementing the Participatory Approach at Supervisor Level: Results of a Randomized Controlled Trial.

Purpose A multifaceted implementation strategy was targeted at supervisors to encourage them to apply a participatory approach (PA) in dealing with employees' work functioning problems due to health concerns. This paper assesses the effect on employees' perceived social norms regarding the use of the PA to deal with work functioning problems. Methods Three organizations participated in a cluster randomized controlled trial, with randomization at the department level. Supervisors in the PA intervention departments received the implementation strategy consisting of a working group meeting, supervisor training, and optional coaching. Supervisors in the control departments received written information about the PA only. In two of the organizations, employees were invited to complete surveys at baseline and at 6-month follow-up. The primary outcome was perceived social norms regarding the use of the PA to deal with work functioning problems. Secondary measures included attitudes and self-efficacy, and intention regarding joint problem solving, and sick leave data. Effects were analyzed using multilevel analyses to account for nesting of cases. Results At baseline, 273 employees participated in the survey, with follow-up analyses of 174 employees. There were no statistically significant group effects on employee outcome measures. The intervention group showed a larger reduction in mean sick days (from 4.6 to 2.4 days) versus the control group (from 3.8 to 3.6 days), but this difference did not reach statistical significance (p > .05). Conclusion The multifaceted strategy to implement the participatory approach for supervisors did not show effects on outcomes at the employee level. To gain significant effects at the employee level, may require that an implementation strategy not only targets management and supervisors, but also employees themselves. TRIAL REGISTRATION: NTR3733.

Pharmacokinetic-pharmacodynamic modelling of fluvoxamine 5-HT transporter occupancy in rat frontal cortex.

BACKGROUND AND PURPOSE: The pharmacokinetic-pharmacodynamic (PK-PD) correlation of fluvoxamine 5-HT transporter (SERT) occupancy was determined in rat frontal cortex ex vivo. EXPERIMENTAL APPROACH: Rats (n=47) with permanent arterial and venous cannulas received a 30 min intravenous infusion of fluvoxamine (1 or 7.3 mg kg(-1)). At various time points after dosing, brains were collected for determination of fluvoxamine concentration and SERT occupancy. In addition, the time course of fluvoxamine concentration in plasma was determined up to the time of brain collection. In a separate study (n=26), the time course of fluvoxamine concentration in brain extracellular fluid (ECF) and plasma was determined. The results of the investigations were interpreted by nonlinear mixed effects modeling. KEY RESULTS: Highest SERT occupancy was reached at the first time point (10 or 15 min) and maintained for 1.5 and 7 h after 1 and 7.3 mg kg(-1), respectively. Thereafter, SERT occupancy decreased linearly at a rate of 8% h(-1). SERT occupancy could be directly related to plasma, brain ECF and brain tissue concentrations by a hyperbolic function (Bmax model). Maximal SERT occupancy (Bmax) was 95%. Estimated concentrations at half-maximal SERT occupancy (EC50) in plasma, ECF and brain tissue were 0.48, 0.22 and 14.8 ng mL(-1) respectively. The minimum value of the objective function decreased 12 points for ECF and brain tissue concentrations relative to plasma (P<0.01), presumably as a result of nonlinear brain distribution. CONCLUSIONS AND IMPLICATIONS: The proposed PK-PD model constitutes a useful basis for prediction of the time course of ex vivo SERT occupancy in behavioural studies with selective serotonin reuptake inhibitors.

Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines.

Quaternized modifications of chitosan present characteristics that might be useful in DNA condensing and efficient gene delivery. Trimethylated chitosan (TMO) was synthesized from oligomeric chitosan (<20 monomer units). TMOs spontaneously formed complexes (chitoplexes) with RSV-alpha3 luciferase plasmid DNA. These complexes were characterized by photon correlation spectroscopy and were investigated for their ability to transfect COS-1 and Caco-2 cell lines in the presence and absence of fetal calf serum and compared with DOTAP (N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium sulphate) lipoplexes. Additionally, their effect on the viability of the respective cell cultures was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. Results showed that quaternized chitosan oligomers were able to condense DNA and form complexes with a size ranging from 200 to 500 nm. Chitoplexes proved to transfect COS-1 cells, however, to a lesser extent than DOTAP-DNA lipoplexes. The quaternized oligomer derivatives appeared to be superior to oligomeric chitosan. The presence of fetal calf serum (FCS) did not affect the transfection efficiency of the chitoplexes, whereas the transfection efficiency of DOTAP DNA complexes was decreased. Cells remained 100% viable in the presence of chitosan oligomers whereas viability of DOTAP treated cells decreased to approximately 50% in both cell lines. Both DOTAP-DNA lipoplexes and chitoplexes resulted in less transfection efficiency in Caco-2 cell cultures than in COS-1 cells; however quaternized chitosan oligomers proved to be superior to DOTAP. Effects on the viability of Caco-2 cells were similar to the effects observed in COS-1 cells. We conclude that trimethylated chitosan-DNA complexes present suitable characteristics and the potential to be used as gene delivery vectors.

Clinical methods to determine coronary flow and myocardial perfusion.

In this overview, currently available clinical methods to measure flow in the coronary circulation will be discussed. Methods only applicable in the experimental laboratory or in the anaesthetized patient during cardiac surgery, will not be described. We distinguish between methods that measure global blood flow, and methods that determine regional flow, either at the level of the coronary arteries or at the level of the myocardium. Since it is difficult to measure coronary flow in absolute values, 'flow reserve' is often used as an alternative. Flow reserve is calculated by dividing maximal flow, usually pharmacologically induced, by basal flow. Consequently, assessment of flow reserve requires only measurements of relative changes of coronary flow. The applicability and relative merits and limitations of the techniques are discussed.

Comparison between regional myocardial perfusion reserve and coronary flow reserve in the canine heart.

Diameter stenosis and flow reserve are indices of morphological and functional severity of coronary artery stenosis. Flow reserve can be determined at coronary arterial or at myocardial level. In the presence of functional collateral circulation, coronary flow reserve and myocardial perfusion reserve may differ. We studied coronary flow, coronary flow reserve and myocardial perfusion reserve in an open chest dog model with intact collateral circulation, before and after induction of coronary artery stenosis. Coronary flow was determined with perivascular ultrasonic flow probes and myocardial perfusion reserve from digital angiographic images, in the stenotic as well as the adjacent non-stenotic coronary arteries. Before induction of a stenosis, a significant correlation existed between coronary flow reserve and myocardial perfusion reserve of the left anterior descending (r = 0.59; P < 0.005) and the left circumflex arteries (r = 0.84, P < 0.005). In stenotic arteries, coronary flow reserve and myocardial perfusion reserve decreased significantly (P < 0.005), but in the adjacent non-stenotic arteries coronary flow reserve was not affected. Myocardial perfusion reserve in the non-stenotic adjacent left anterior descending artery decreased significantly (P < 0.05) and no correlation was found between coronary flow reserve and myocardial perfusion reserve, whereas in the adjacent non-stenotic left circumflex artery there was no statistically significant decrease (4.1 +/- 1.6 --> 3.5 +/- 1.4) but there was a good correlation between coronary flow reserve and myocardial perfusion reserve (r = 0.85; P < 0.005). This study demonstrates that, in the presence of a stenosis and functioning collateral circulation, coronary flow reserve is not a reliable predictor of myocardial perfusion reserve; both parameters provide mutually complementary information.