Mechanism-based PK/PD modeling of selective serotonin reuptake inhibitors

The main objective of the investigations was to explore the PK/PD correlations of fluvoxamine, as a prototype for the Selective Serotonin Reuptake Inhibitors (SSRIs). In the various investigations, a spectrum of different biomarkers was used, each reflecting a specific process on the causal path between drug administration and response. The effects of fluvoxamine have been explored in six investigation steps; from the relatively simple description of the pharmacokinetics of fluvoxamine in plasma and brain to the more complex relationships with the effects on SERT occupancy, 5-HT and 5-HIAA levels and REM sleep. In the PCA study, a categorical PK/PD model was proposed for the effects of fluvoxamine on PCA induced behavioral effects as a kind of intermediary biomarker. There appeared to be important aspects in the PK/PD relationships of fluvoxamine, which was already indicated in the well-known delayed therapeutic effect of SSRIs. The cascading PK/PD model enables the prediction of the effects of functional adaptation upon long-term administration. For SSRIs, adaptation may occur at various levels in the biological system. The various studied biomarkers provide a basis to determine at which level of the biological system functional adaptation occurs (i.e. target site distribution, target expression, turnover of neurotransmitters, transduction mechanisms).Johnson & Johnson, Pharmaceutical Research and Development, a Division of Janssen Pharmaceutica N.V. (Beerse, Belgium)UBL - phd migration 201

When I receive the SMS, it is a sign of love: Symbolic Connotations of SMS messages for People living with HIV in Burkina Faso

Mobile health (mHealth) has gained considerable interest recently due to its potential to improve health outcomes in developing countries with high outreach yet low costs. Several studies have explored the use of short message service (SMS) reminders to improve antiretroviral (ARV) retention and adherence, with mixed results. The majority of these studies has a quantitative nature and employs randomized designs, which do not provide further qualitative insights about other possible impacts of the messages. Based on the qualitative assessment of an SMS intervention in Burkina Faso, which complemented a (quantitative) Randomized Controlled Trial (RCT), we show that beyond the functional role of improving ARV retention and adherence, SMS messages can also play important symbolic roles in offering psychosocial support to people living with HIV (PLHIV) and improving their perception of life. Concomitantly, we show that sufficient (ICT) literacy skills cannot be taken for granted in resource-poor settings. Yet, regardless of (ICT) literacy skills, the symbolism of care was perceived. Furthermore, we highlight the importance of complementing quantitative evidence of mHealth interventions with qualitative assessments

Reconstructing Van Gogh’s palette to determine the optical characteristics of his paints

The colors of Field with Irises near Arles, painted by Van Gogh in Arles in 1888, have changed considerably. To get an idea of how this painting, as well as other works by Van Gogh, looked shortly after their production, the Revigo (Re-assessing Vincent van Gogh’s colors) research project was initiated. The aim of this project was to digitally visualize the original colors of paintings and drawings by Vincent van Gogh, using scientific methods backed by expert judgement where required. We adopted an experimental art technological approach and physically reconstructed Van Gogh’s full palette of oil paints, closely matching those he used to paint Field with Irises near Arles. Sixteen different paints were reconstructed, among which the most light-sensitive pigments and linseed oil, which is prone to yellowing, were produced according to 19th century practice. The resulting pigments and oils were chemically analyzed and compared to those used by Van Gogh. The ones that resembled his paints the most were used in the paint reconstructions. Other pigments were either obtained from the Cultural Heritage Agency’s collection of historical pigments, or purchased from Kremer Pigmente. The reconstructed paints were subsequently used to calculate the absorption K and scattering S parameters of the individual paints. Using Kubelka–Munk theory, these optical parameters could in turn be used to determine the color of paint mixtures. We applied this method successfully to digitally visualize the original colors of Field with Irises near Arles. Moreover, the set of optical parameters presented here can similarly be applied to calculate digital visualizations of other paintings by Van Gogh and his contemporaries

Toward the use of diffuse reflection spectroscopy for intra-operative tissue discrimination during sarcoma surgery

Significance: Accurately distinguishing tumor tissue from normal tissue is crucial to achieve complete resections during soft tissue sarcoma (STS) surgery while preserving critical structures. Incomplete tumor resections are associated with an increased risk of local recurrence and worse patient prognosis. Aim: We evaluate the performance of diffuse reflectance spectroscopy (DRS) to distinguish tumor tissue from healthy tissue in STSs. Approach: DRS spectra were acquired from different tissue types on multiple locations in 20 freshly excised sarcoma specimens. A k -nearest neighbors classification model was trained to predict the tissue types of the measured locations, using binary and multiclass approaches. Results: Tumor tissue could be distinguished from healthy tissue with a classification accuracy of 0.90, sensitivity of 0.88, and specificity of 0.93 when well-differentiated liposarcomas were included. Excluding this subtype, the classification performance increased to an accuracy of 0.93, sensitivity of 0.94, and specificity of 0.93. The developed model showed a consistent performance over different histological subtypes and tumor locations. Conclusions: Automatic tissue discrimination using DRS enables real-time intraoperative guidance, contributing to more accurate STS resections.</p

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th

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