Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers.

Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7-14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD

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

Cell cycle phase perturbations and apoptosis in tumour cells induced by aplidine

Aplidine, dehydrodidemnin B, is a marine depsipeptide isolated from the Mediterranean tunicate Aplidium albicans currently in phase II clinical trial. In human Molt-4 leukaemia cells Aplidine was found to be cytotoxic at nanomolar concentrations and to induce both a G1 arrest and a G2 blockade. The drug-induced cell cycle perturbations and subsequent cell death do not appear to be related to macromolecular synthesis (protein, RNA, DNA) since the effects occur at concentrations (e.g. 10 nM) in which macromolecule synthesis was not markedly affected. Ten nM Aplidine for 1 h inhibited ornithine decarboxylase activity, with a subsequently strong decrease in putrescine levels. This finding has questionable relevance since addition of putrescine did not significantly reduce the cell cycle perturbations or the cytotoxicity of Aplidine. The cell cycle perturbations caused by Aplidine were also not due to an effect on the cyclin-dependent kinases. Although the mechanism of action of Aplidine is still unclear, the cell cycle phase perturbations and the rapid induction of apoptosis in Molt-4 cells appear to be due to a mechanism different from that of known anticancer drugs

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