van Jasper Doormaal

Abnormal endothelium-dependent microvascular reactivity in recently preeclamptic women

OBJECTIVE: To assess endothelial function at the level of skin microvasculature, using iontophoretic administration of acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator), in women who recently had a preeclamptic pregnancy. METHODS: Microvascular skin reactivity was assessed by laser Doppler perfusion monitoring and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) in 25 women with a history of early onset preeclampsia and 23 women with previous uncomplicated pregnancies, all of whom were between 3 and 11 months postpartum. RESULTS: Mean (± standard error of the mean) ACh-mediated vasodilatation, expressed as a percentage increase in flux, was higher in women who recently had a preeclampsia than in controls (535 ± 46% versus 314 ± 29%, P < .001). In contrast, SNP-mediated vasodilatation was not significantly different (560 ± 71% versus 483 ± 69%, P = .4) in both groups. Linear regression analysis revealed that the difference in ACh-mediated vasodilatation was explained by preeclampsia (P = .004), whereas vascular risk factors such as maternal age, diastolic blood pressure, and family history of premature cardiovascular diseases had no significant effect. CONCLUSION: The increased ACh-mediated vasodilatation in the microcirculation of recently preeclamptic women indicates abnormal endothelial function. Furthermore, it may represent a compensatory response to an impaired vasodilatory response of the macrocirculation, thereby supporting the hypothesis of an underlying (micro)angiopathy. LEVEL OF EVIDENCE: II-2

Correlates of endothelial function and their relationship with inflammation in patients with familial hypercholesterolaemia.

Atherosclerosis is characterized by a low-grade systemic inflammatory response and endothelial dysfunction. The aim of the present study was to investigate a possible relationship between systemic markers of inflammation, serum markers of endothelial activation and endothelium-dependent vasodilatation in a group of high-risk patients, and to evaluate the effects of intervention with high doses of simvastatin on these parameters. In patients with heterozygous familial hypercholesterolaemia, without atherosclerotic events, flow-mediated vasodilatation (FMD) of the brachial artery was measured after a wash-out period for lipid-lowering drugs (baseline) and after 6 weeks of treatment with simvastatin 80 mg daily. Levels of C-reactive protein (CRP), soluble intercellular cell-adhesion molecule (s-ICAM) and soluble E-selectin (s-E-selectin) were determined at baseline and again after 6 weeks and 12 months of therapy. A total of 35 subjects participated in the study (mean age 42 years; 60% male). When divided into tertiles according to FMD (<3.9%, 3.9-9.0% and >9.0%), no differences in levels of CRP, s-ICAM-1 and/or s-E-selectin were detected between the groups. Moreover, no changes in FMD, levels of CRP or levels of s-ICAM-1 and/or s-E-selectin were found during treatment with simvastatin. We conclude that endothelial function, as reflected by FMD, does not seem to be related to markers of inflammation in familial hypercholesterolaemia subjects at high risk of, but without clinically overt signs of, atherosclerosis. Moreover, aggressive lipid-lowering therapy with simvastatin does not result in improved endothelial function or in a reduction of markers of inflammation in these patients.

Reliability of the assessment of preventable adverse drug events in daily clinical practice

To determine the reliability of the assessment of preventable adverse drug events (ADEs) in daily practice and to explore the impact of the assessors professional background and the case characteristics on reliability.

Comparison of methods for identifying patients at risk of medication-related harm

Background With the introduction of Computerised Physician Order Entry (CPOE) in routine hospital care, a great deal of effort has been put into refining Clinical Decision Support Systems (CDSS) to identify patients at risk of preventable medication-related harm. Objectives This study compared a CPOE with basic CDSS and 16 clinical rules with a manual pharmacist medication review to detect overdose and drug–drug interactions that actually required a change in medication. Methods The study involved the review of 313 patients admitted over 5u2005months at an internal medicine ward where a change in medication as a result of dosing of therapeutic errors was detected by a manual medication review by a trained pharmacist. Subsequently, all these patients medication orders (MOs) were entered into the authors CPOE with basic CDSS. Medication orders with a safety alert indicating overdose and drug–drug interactions generated by the authors CPOE with basic CDSS were compared with the same type of medication errors identified through manual review. The positive predictive value (PPV), sensitivity and specificity compared with manual review were determined. Second, a set of 16 clinical rules was applied to the patient and prescribing data. The overlap between the clinical rules and manual review was determined by comparing patients triggered by the clinical rule with patients with a corresponding error in the manual medication review. Results Manual medication review identified 57 medication errors involving overdose and 143 therapeutic errors of which 46 were drug–drug interactions. The CPOE with basic CDDS generated 297 safety alerts involving overdose (PPV 0.06, sensitivity 0.32, specificity 0.92) and 365 safety alerts involving drug–drug interactions (PPV 0.12, sensitivity 0.96, specificity 0.91). The clinical rules generated 313 safety alerts identifying 39% of all the overdoses and therapeutic errors found in the manual review at which they were targeted. In 23% of the alerts generated by a clinical rule, the patients actually required a change of medication as indicated by the manual review. When CPOE with basic CDSS and the rules were combined, 66% of the overdoses and therapeutic errors were identified. Conclusions The authors CPOE with basic CDSS and the clinical rules are useful early strategies for preventing medication-related harm. They could be a first step towards more advanced decision support. These computerised systems will be even more useful in daily practice, once they are further fine-tuned to decrease the number of alerts that need no clinical action.

Skin Autofluorescence as Marker of Tissue Advanced Glycation End-Products Accumulation in Formerly Preeclamptic Women

Condensation. In women with a history of preeclampsia skin autofluorescence as marker of tissue AGEs accumulation is increased, supporting a common causal metabolic or vascular link between preeclampsia and cardiovascular diseases. Objective. To investigate whether skin autofluorescence (AF), as marker of tissue accumulation of advanced glycation end-products (AGEs), is elevated in women with a 4-year history of severe preeclampsia. Methods. About 17 formerly preeclamptic women and 16 controls were included. Skin AF and several traditional cardiovascular risk factors were recorded. Results. In comparison to controls, formerly preeclamptic women had higher skin AF of the legs, body mass index (BMI), blood pressure, and high-sensitivity C-reactive protein (hsCRP), HbA1C, and triglycerides in serum. Conclusion. Skin AF as well as cardiovascular risk factors is elevated in formerly preeclamptic women. These results suggest a common causal vascular link between preeclampsia and cardiovascular diseases.

Computerized physician order entry (CPOE) system

OBJECTIVESnTo explore physicians and nurses expectations before and experiences after the implementation of a computerized physician order entry (CPOE) system in order to give suggestions for future optimization of the system as well as the implementation process.nnnMETHODnOn four internal medicine wards of two Dutch hospitals, 18 physicians and 42 nurses were interviewed to measure expectations and experiences with the CPOE system. Using semi-structured questionnaires, expectations and experiences of physicians and nurses with the CPOE system were measured with statements on a 5-point Likert scale (1 = completely disagree, 5 = completely agree). The percentage respondents agreeing (score of 4 or 5) was calculated. Chi-squared tests were used to compare the expectations versus experiences of physicians and nurses and to assess the differences between physicians and nurses.nnnRESULTSnIn general, both physicians and nurses were positive about CPOE before and after the implementation of this system. Physicians and nurses did not differ in their views towards CPOE except for the overview of patients medication use that was not clear according to the nurses. Both professions were satisfied with the implementation process. CPOE could be improved especially with respect to technical aspects (including the medication overview) and decision support on drug-drug interactions.nnnCONCLUSIONnOverall we conclude that physicians and nurses are positive about CPOE and the process of its implementation and do accept these systems. However, these systems should be further improved to fit into clinical practice.

Periodontal disease and pre-eclampsia

AIMnThis review evaluates the possible relationship between periodontal disease and pre-eclampsia, a major pregnancy complication. A generalized inflammatory response plays an important role in the pathogenesis of pre-eclampsia. Because periodontal disease is a low-grade inflammatory state, periodontal disease might contribute to the pathogenesis of pre-eclampsia.nnnMAIN FINDINGS AND CONCLUSIONnA literature search of PubMed, EMBASE and CINAHL until August 2010 revealed 12 eligible observational studies and three randomized-controlled trials (RCTs). It appeared difficult to compare these studies, due to variations in definitions of periodontal disease and pre-eclampsia, timing of periodontal examination and inadequate control for confounding factors. Eight observational studies reported a positive association, while four studies found no association. None of the RTCs reported reductions in pre-eclamptic rate after periodontal therapy during pregnancy. Therefore, it is questionable whether periodontal disease plays a causal role in the pathogenesis of pre-eclampsia. The observed association in eight observational studies might be the result of induction of periodontal disease due to the pre-eclamptic state or it may be an epiphenomenon of an exaggerated inflammatory response to pregnancy. Larger RCTs with pre-eclampsia as the primary outcome and pathophysiological studies are required to explore causality and to dissect biological mechanisms involved.