Adverse drug reactions to tocolytic treatment for preterm labour: prospective cohort study

Objective To evaluate the incidence of serious maternal complications after the use of various tocolytic drugs for the treatment of preterm labour in routine clinical situations

Induction of labor with a Foley catheter and the risk of subsequent preterm birth: A follow-up study of two randomized controlled trials (PROBAAT-1 and -2)

OBJECTIVE:The objective of this study was to evaluate the preterm birth rate in a subsequent pregnancy in women who had undergone term induction with a Foley catheter in comparison to induction with prostaglandins. METHODS:This was a follow-up study of two large randomized controlled trials. In the original trials (PROBAAT-1 and PROBAAT-2), women with a term, singleton pregnancy in cephalic presentation with an indication for labor induction were randomized to either a 30cc Foley catheter or prostaglandins (i.e. vaginal prostaglandin E2 in PROBAAT 1 and oral misoprostol in PROBAAT 2). The main outcome measures were preterm birth <37 weeks gestation and preterm birth <34 weeks gestation. Data were collected from hospital charts on subsequent pregnancies from hospitals participating in this follow-up study. RESULTS:14 hospitals agreed to participate in this follow-up study. Of the 1142 eligible women, 162 women (14%) were lost to follow-up. Of the 572 women randomized to a Foley catheter, 251 women had a subsequent pregnancy beyond 16 weeks gestation, versus 258 women of the 570 women who received prostaglandins. There were no differences in baseline characteristics. The overall preterm birth rate was 9/251 (3.6%) in the Foley catheter group versus 10/258 (3.9%) in the prostaglandin group (RR 0.93; 95%CI 0.38-2.24), with spontaneous preterm birth rates of 5/251 (2.0%) versus 5/258 (1.9%) respectively (RR 1.03, 95%CI 0.30-3.51). CONCLUSIONS:In women with a singleton term pregnancy, induction of labor with a 30cc Foley catheter is not associated with an increased risk of preterm birth in a subsequent pregnancy as compared to induction of labor with prostaglandins. This article is protected by copyright. All rights reserved.M. D. T. de Vaan, D. Blel, K. W. M. Bloemenkamp, M. Jozwiak, M. L. G. ten Eikelder ... B. W. Mol ... et al

On-line electrochemistry–bioaffinity screening with parallel HR-LC-MS for the generation and characterization of modified p38α kinase inhibitors

In this study, an integrated approach is developed for the formation, identification and biological characterization of electrochemical conversion products of p38α mitogen-activated protein kinase inhibitors. This work demonstrates the hyphenation of an electrochemical reaction cell with a continuous-flow bioaffinity assay and parallel LC-HR-MS. Competition of the formed products with a tracer (SKF-86002) that shows fluorescence enhancement in the orthosteric binding site of the p38α kinase is the readout for bioaffinity. Parallel HR-MSn experiments provided information on the identity of binders and non-binders. Finally, the data produced with this on-line system were compared to electrochemical conversion products generated off-line. The electrochemical conversion of 1-{6-chloro-5-[(2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazine-1-carbonyl]-3aH-indol-3-yl}-2-morpholinoethane-1,2-dione resulted in eight products, three of which showed bioaffinity in the continuous-flow p38α bioaffinity assay used. Electrochemical conversion of BIRB796 resulted, amongst others, in the formation of the reactive quinoneimine structure and its corresponding hydroquinone. Both products were detected in the p38α bioaffinity assay, which indicates binding to the p38α kinase

Looking for interaction: quantitative measurement of research utilization by Dutch local health officials

Background: In the Netherlands, local authorities are required by law to develop local health memoranda, based on epidemiological analyses. The purpose of this study was to assess the actual use of these epidemiological reports by municipal health officials and associated factors that affect this use.Method: Based on a conceptual framework, we designed a questionnaire in which we operationalized instrumental, conceptual, and symbolic use, the interaction between researchers and local health officials, and four clusters of barriers in this interaction process. We conducted an internet survey among 155 Dutch local health officials representing 35% of all Dutch municipalities. By means of multiple regression analyses, we gained insight into the related factors for each of the three types of research utilization.Results: The results show that local health officials use epidemiological research more often in a conceptual than an instrumental or symbolic way. This can be explained by the complexity of the local policy process which is often linked to policies in other areas, and the various policy actors involved. Conceptual use was statistically associated with a presentation given by the epidemiologist during the policy process, the presence of obstructions regarding the report's accessibility, and the local official's personal belief systems and interests originating from different professional values and responsibilities. Instrumental and symbolic use increased with the involvement of local officials in the research process.Conclusions: The results of this study provide a partial solution to understanding and influencing research utilization. The quantitative approach underpins earlier qualitative findings on this topic. The outcomes suggest that RPHS epidemiologists can use different strategies to improve research utilization. 'Blurring the boundaries', and the enhancement of interfaces between epidemiologists and local health officials, like direct interactions into each other's work processes, is expected to create better possibilities for optimizing research use

Phase I and pharmacokinetic study of irinotecan in combination with R115777, a farnesyl protein transferase inhibitor

The aims of this study were to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetics of irinotecan given with oral R115777 (tipifarnib), a farnesyl protein transferase inhibitor. Patients were treated with escalating doses of irinotecan with interval-modulated dosing of R115777 (continuously or on days 1-14, and repeated every 21 days). In total, 35 patients were entered onto the trial for a median duration of treatment of 43 days (range, 5-224 days). Neutropenia and thrombocytopenia were the dose-limiting toxicities; other side effects were mostly mild. The MTD was established at R115777 300 mg b.i.d. for 14 consecutive days with irinotecan 350 mg m-2 given every 3 weeks starting on day 1. Three patients had a partial response and 14 had stable disease. In the continuous schedule, the area under the curves of irinotecan and its active metabolite SN-38 were 20.0% (P = 0.004) and 38.0% (P < 0.001) increased by R115777, respectively. Intermittent dosing of R115777 at a dose of 300 mg b.i.d. for 14 days every 3 weeks is the recommended dose of R115777 in combination with the recommended single-agent irinotecan dose of 350 mg m-2