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BACKGROUND It is generally accepted that a neuraxial blockade strengthens the sedative effects of propofol. Deafferentation caused by neuraxial blockade is thought to play a key role. OBJECTIVES The objective is to determine whether epidural blockade affects the bispectral index (BIS) of propofol and two other pharmacodynamic endpoints, mean arterial pressure (MAP) and cardiac output (CO). DESIGN Randomised, placebo-controlled study. SETTING University hospital. PATIENTS Patients scheduled for surgery needing epidural analgesia. INTERVENTION 28 ASA one or two patients received 0, 50, 100 or 150 mg of epidural ropivacaine. After stabilisation of the epidural blockade, propofol was given by target-controlled infusion. The propofol plasma target concentrations were increased at 6-min intervals from 0 to 1, 2.5, 4 and 6 mu g ml(-1). The study was performed before surgery. MAIN OUTCOME MEASURES Three endpoints, BIS, mean arterial blood pressure and CO were measured from baseline (prior to the administration of epidural ropivacaine) until 2 h after the start of propofol infusion. The propofol concentration-effect data were analysed to determine the interaction between epidural blockade and propofol sedation. RESULTS In the absence of propofol, the increase in number of epidural blocked segments from 0 to 15.5 (range 6 to 21) reduced the MAP by 30%, without affecting BIS or CO. In the absence of epidural blockade, the increase in propofol concentration to 6 mu g ml(-1) reduced BIS, MAP and CO. When combined, epidural anaesthesia and intravenous propofol exhibited no pharmacodynamic interaction on any of the three endpoints. In addition, epidural blockade did not affect the propofol effect-site equilibration half-life for its haemodynamic effects (11.5 +/- 0.5 min) or for its effects on the BIS (4.6 +/- 0.4 min). CONCLUSION Epidural blockade reduces the propofol requirements for sedative end points. This is not the result of a pharmacodynamic interaction.

Background and Aims: Many patients with psychotic disorders are non-adherent to antipsychotic (AP) medication(s), potentially contributing to rehospitalization. It is unknown whether non-adherence in different phases of AP use is associated with rehospitalization. The aim of this study was to assess the association between non-adherence to APs and rehospitalization in patients with psychotic disorders. Non-adherence was assessed specifically for the initiation, continued drug use and early discontinuation of AP use. Methods: A retrospective follow-up study was performed. Adult patients were included at discharge if they suffered from schizophrenia, psychotic, or bipolar I disorder; had been hospitalized in a psychiatric hospital for ⩾7 days; and were treated with oral APs. Patients discharged between January 2006 and December 2009 from Altrecht Mental Health Care were included. Non-adherence was studied in the three phases of medication use: initiation, continued drug use (implementation) and (early) discontinuation after discharge until the end of follow up or until patients were rehospitalized. Cox regression analysis was used to assess the strength of the association between non-adherence for the different phases of AP use and rehospitalization during follow up and expressed as relative risk (RR) with 95% confidence intervals (CI). Results: A total of 417 patients were included. Patients who did not initiate their APs compared with those who did in the first month (RR = 1.62, 95% CI: 1.19–2.19) and between the first and third month after discharge (RR = 1.70, 95% CI: 1.04–2.79) had the highest risk for rehospitalization during follow up. Overall, patients who did not initiate their AP medication within the first year after discharge had a RR of 2.70 (95% CI: 1.97–3.68) for rehospitalization during follow up compared with those that initiated their AP. Conclusion: Not initiating APs right after discharge was associated with an increased risk of rehospitalization. Interventions should aim to promote the initiation of APs soon after discharge to minimize the risk of rehospitalization.

Objectives: Completeness of staging is an independent prognostic factor for survival in surgical staging procedures for early ovarian cancer. Near-infrared (NIR) fluorescence imaging has the potential to improve the intraoperative assessment of metastatic spread and thus completeness of staging. Feasibility of folate receptor alpha (FR alpha) targeted fluorescence imaging using OTL-38, a folate analogue conjugated to an NIR fluorescent dye, has been previously demonstrated in advanced ovarian cancer. The present authors hypothesized that in early ovarian cancer, fluorescence imaging using OTL-38 could lead to more accurate detection of (occult) ovarian cancer metastases, allowing gynecologic surgeons to take targeted rather than blind biopsy samples. Materials and Methods: Six patients scheduled to undergo a staging procedure for suspected early stage ovarian cancer, received an intravenous infusion of 0.0125 mg/kg OTL38 2-3 hours prior to surgery. The authors assessed tolerability, pharmacokinetics, and the feasibility of intraoperative NIR fluorescence detection of ovarian cancer lesions. Feasibility was evaluated using histopathological analysis, tumor-to-background ratio, and number of false positive and negative lesions. Results: Distinction between a malignant and benign primary tumor was possible with OTL-38 based fluorescence imaging. In addition, nine fluorescent lesions, all lymph node (LN) clusters, were detected intraoperatively. Tumor cells were not demonstrated in any of the biopsy samples taken during staging procedures, including the fluorescent lesions. Therefore all fluorescent LNs were false positives. Conclusions: Metastatic lesions were not present in the patients with confirmed early ovarian cancer; hence the anticipated added value of NIR fluorescence imaging could not be demonstrated in this study. Fluorescence imaging led to resection of non-malignant LNs, as comprehensive lymph node dissection should be pursued in surgical staging procedures, this should not impede application of OTL38. Importantly, fluorescence imaging allowed distinction between a malignant and benign primary tumor and had no false negatives.

Introduction Percutaneous hepatic perfusion (PHP) with melphalan is an effective treatment for patients with hepatic metastases, but associated with high rates of bone marrow depression. To reduce systemic toxicity, improvements have been made to the filtration system. In pre-clinical studies, the Delcath System’s GEN2 filter was superior to the first-generation filters. In this clinical study, we analysed the pharmacokinetics and toxicity of PHP using the new GEN2 filter. Methods and Materials Starting February 2014, two prospective phase II studies were initiated in patients with hepatic metastases from ocular melanoma or colorectal cancer. In 10 PHP procedures performed in the first 7 enrolled patients, blood samples were obtained to determine filter efficiency and systemic drug exposure. PHP was performed with melphalan 3 mg/kg with a maximum of 220 mg. Complications were assessed according to CTCAE v4.03. Response was assessed according to RECIST 1.1. Results Pharmacokinetic analysis of blood samples showed an overall filter efficiency of 86% (range 71.1–95.5%). The mean filter efficiency decreased from 95.4% 10 min after the start of melphalan infusion to 77.5% at the end of the procedure (p = 0.051). Bone marrow depression was seen after up to 80.0% of 10 procedures, but was self-limiting and mostly asymptomatic. No hypotension-related complications or procedure-related mortality occurred. Conclusion The GEN2 filter has a higher melphalan filter efficiency compared to the first-generation filters and a more consistent performance. PHP with the GEN2 filter appears to have an acceptable safety profile, but this needs further validation in larger studies.

Bijna 70% van de patiënten stopt met het gebruik van een of meer middelen wanneer ze worden ontslagen uit een psychiatrisch ziekenhuis. Somatische middelen worden vaker gestopt dan psychiatrische middelen. Dat blijkt uit het promotieonderzoek van Heshu Abdullah-Koolmees.

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BACKGROUND: The structural measurement of the results of treatment under the Dutch mental health services and a comparison of these results between mental health centres help to provide insight into the effectiveness of treatment in general practice. AIM: To provide an overview of the issues that require attention when the results of mental health centres are being compared. METHOD: Documentation, policy information and practical experience with routine outcome monitoring were analysed. RESULTS: We describe the problems that can arise when results obtained by mental health centres are compared and we suggest some solutions for these problems. Important/actors that have emerged from our study are as follows: working with routine outcome monitoring is a process of naturalgrowth and involves experiences with several solutions and the making of definitive choices on the basis of experience. CONCLUSION: It is instructive to compare mental health centres with each other and with regards to so-called 'best practices' (benchmarking). However, mental health centres draw on a differing wide mix of patients and use different measurement procedures and instruments. In this article we express the view that in the near future it should be possible to draw meaningful comparisons.

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