[Serotin syndrome; literature overview and Lareb pharmacovigilance reports]. / Serotonerg syndroom.

Serotonin syndrome is a medication-induced clinical syndrome, caused by an increased concentration of serotonin in the central and peripheral nervous system. An excess of serotonin can be caused by the use of one or more serotinergic substances on the one hand, or by decreased clearance of these substances on the other hand We carried out a systematic literature search to make an estimation of substances and patient-related factors that might be associated with an increased risk of serotonin syndrome. We also carried out a search for all reports of serotonin syndrome in the Lareb (Netherlands pharmacovigilance centre) database. Patient-centred medication monitoring is not yet possible because there is an almost complete lack of clinical predictors. For the time being, all that treatment providers can do to help recognise serototin syndrome on time is to be extra alert in patients belonging to risk groups (the elderly, or patients with renal or hepatic insufficiency.

[John McCrae, physician and poet of "In Flanders Fields"]. / John McCrae, arts en dichter vanIn Flanders Fields.

During the Second Battle at Ypres (1915), the Canadian medical officer John McCrae was situated in an Advanced Dressing Station in Boezinge, Belgium. Heavily influenced by the suffering of the war he wrote the poem "In Flanders Fields" in May 1915. In this poem he writes about the fallen soldiers who will not rest, until others have taken over the torch of the battle. The poem has become particularly well known in the United Kingdom, Canada and the United States. For army administration, soldiers and their families this poem meant a call for more financial support and material goods to win the war. The poppy, which takes centre stage in the poem, became a worldwide symbol of the sacrifice of soldiers on the battlefield, but more recently has itself become the subject of controversy.

Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands.

UNLABELLED: OBJECTIVE To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS). DESIGN: A prospective observational study. MATERIALS AND METHODS: We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems. RESULTS: The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug-(drug) interaction (9.9% vs 14.8%; p<0.05), drug-age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05). CONCLUSION: The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice.

Drug treatment-related factors of inadequate seizure control.

To optimize seizure control it is important to identify modifiable factors. We conducted a case-control study to explore to what extent drug treatment-related factors are associated with seizures. Eighty-six patients with epilepsy were evaluated: 45 cases (recently experienced a seizure) and 41 controls (seizure-free for at least 2 months). There was a significant association between low AED serum concentration and seizures (odds ratio (OR)=8.9, 95% confidence interval (CI)=1.7-47.8), compliance was not associated with seizures (OR=0.9, 95% CI=0.2-4.0), and changes in medication (mainly non-AEDs) were more frequently observed in the case group than in the control group (OR=4.1, 95% CI=0.9-18.3). These findings indicate that patients with low AED serum levels have a nine times higher risk of seizures compared with patients with therapeutic AED levels and that changes in medication regimens in patients with epilepsy should be made with care.

Influence of chemical structure on hypersensitivity reactions induced by antiepileptic drugs: the role of the aromatic ring.

OBJECTIVE: Antiepileptic drugs (AEDs) can cause various 'idiosyncratic' hypersensitivity reactions, i.e. the mechanism by which AEDs induce hypersensitivity is unknown. The aim of this study was to assess whether the presence of an aromatic ring as a commonality in chemical structures of AEDs can explain symptoms of hypersensitivity. METHODS: Between January 1985 and January 2007, all adverse drug reactions (ADRs) reported to the Netherlands Pharmacovigilance Centre Lareb related to AEDs as suspected drugs were included in this study. ADRs were analysed using a case/non-case design. Cases were defined as those patients with ADRs involving symptoms of hypersensitivity. Non-cases were patients with all other ADR reports. Symptoms of hypersensitivity were classified according to the Gell and Coombs classification (type I-IV) and the organ involved (e.g. cutaneous, hepatic). AEDs were classified as aromatic anticonvulsant if their chemical structure contained at least one aromatic ring. All other AEDs were classified as non-aromatic. We assessed the strength of the association between aromatic AEDs versus non-aromatic AEDs and reported hypersensitivity reactions with logistic regression analysis and expressed these as reporting odds ratios (RORs). RESULTS: In total, 303 cases of hypersensitivity associated with the use of AEDs were reported. Aromatic AEDs were suspected in 64.4% of these reports versus 41.3% (574/1389) of the non-hypersensitivity reports. A significant ROR of 2.15 (95% CI 1.63, 2.82) was found for aromatic AEDs and all hypersensitivity reactions. Aromatic AEDs were significantly associated with immunoglobin E-mediated type I hypersensitivity reactions (ROR 2.15; 95% CI 1.23, 3.78) and T-cell-mediated type IV reactions (ROR 6.06; 95% CI 3.41, 10.75). Type II and III reactions did not show an association. Cutaneous symptoms represented 39.9% of the hypersensitivity-related ADRs. Aromatic AEDs were significantly associated with cutaneous hypersensitivity reactions (ROR 5.81; 95% CI 3.38, 9.99). CONCLUSION: This study confirms that the presence of an aromatic ring as a common feature in chemical structures of AEDs partly explains apparent 'idiosyncratic' hypersensitivity reactions. Symptoms of hypersensitivity were reported twice as frequently with aromatic AEDs than with non-aromatic AEDs. Strong associations for aromatic AEDs versus non-aromatic AEDs were found for T-cell-mediated (type IV) reactions, as well as for cutaneous reactions.

Changes in medication associated with epilepsy-related hospitalisation: a case-crossover study.

AIM: To assess the association between changes in medication and epilepsy-related hospitalisation. METHODS: Data were obtained from the PHARMO Record Linkage System (Jan 1998 to Dec 2002). We conducted a case-crossover study among patients with a first epilepsy-related hospital admission who had continuously used at least one antiepileptic drug (AED) during a 28-week period before admission. For each patient, changes in medication in a 28-day window before hospitalisation were compared with changes in four earlier 28-day windows. Evaluated changes were: changes in AEDs (pattern and dosage), changes in interacting co-medication and changes in non-interacting co-medication (i.e. introduction of non-interacting drugs). The strength of the association between changes in medication and epilepsy-related hospitalisation was estimated using conditional logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Out of 1185 patients with a first epilepsy-related hospitalisation, 217 patients met the inclusion criteria. Of the changes in antiepileptic therapy, discontinuation showed a trend towards an increased risk of hospitalisation (OR: 2.57; 95%CI: 0.81-8.17). Drug interactions influencing antiepileptic therapy rarely occurred. Introduction of three or more non-interacting drugs was significantly associated with epilepsy-related hospitalisation (OR: 4.80; 95%CI: 2.12-10.87). Of individual drugs, addition of antimicrobial agents was significantly associated with epilepsy-related hospitalisation (OR: 1.99; 95%CI: 1.06-3.75). CONCLUSIONS: Changes in AED therapy were not significantly associated with epilepsy-related hospitalisation and few drug interactions influencing antiepileptic therapy occurred. However, patients starting three or more new non-AEDs had a nearly five times increased risk of epilepsy-related hospital admission.

Harvesting autologous fascia lata for pelvic reconstructive surgery: techniques and morbidity.

OBJECTIVE: To determine donor site morbidity associated with harvesting of fascia lata. STUDY DESIGN: We reviewed medical records and evaluated responses to mailed questionnaires from all patients who underwent fascia lata harvesting during a 54-month period. Data were collected about immediate complications and long-term morbidity related to the donor site. RESULTS: The study comprised 71 patients. Immediate postoperative complications were limited to 1 (1%) hematoma that required drainage, 2 (3%) seromas, and 5 (7%) cases of cellulitis that required oral antibiotics. Questionnaire response rate was 77%, with a mean follow-up of 25 months. Of the responders, 22 (40%) reported mild symptoms, 3 (5%) reported clinically significant symptoms related to the donor leg, and 7 (13%) expressed dissatisfaction because of unacceptable cosmesis (n = 5), leg discomfort (n = 5), or both. CONCLUSION: There was little immediate postoperative morbidity. Although many patients may be expected to report long-term symptoms related to the donor leg, these symptoms are generally mild, and the incidence of patient dissatisfaction is relatively low.

Endometriosis: correlation between histologic and visual findings at laparoscopy.

OBJECTIVE: The purpose of this study was to correlate the diagnosis of endometriosis on the basis of visualization at laparoscopy with the pathologic diagnosis. STUDY DESIGN: A prospective study of 44 patients undergoing laparoscopy for the evaluation of chronic pelvic pain was carried out. All areas suggestive of endometriosis were excised and examined pathologically. Peritoneal biopsy specimens were obtained from areas of normal-appearing peritoneum to rule out microscopic endometriosis. All lesions were identified by anatomic site. Visual and histologic American Fertility Society scores were compared. The positive predictive value, sensitivity, negative predictive value, and specificity were determined for visually identified endometriosis versus the histologic correlate. RESULTS: The mean prevalence of abnormalities visually consistent with endometriosis was 36%, with 18% confirmed histologically. The positive predictive value was 45%; sensitivity, 97%; negative predictive value, 99%; and specificity, 77%; for visual versus histologic diagnosis of endometriosis. Thirty-six percent of the diagnoses were downstaged on the basis of histologic findings. CONCLUSION: A diagnosis of endometriosis should be established only after histologic confirmation.

Electrochemical recognition of charged species using quaternary ammonium binaphthyl salts.

The effects of ionic analytes on the electrochemical properties of quaternary ammonium binaphthyl salts are described in this work. The stability of the binaphthyl radicals and hence the reversibility of the electrochemical response are discussed in terms of molecular structure. The ability of azacrown derivatised binaphthyl salts to act as amperometric receptors is ascribed to the strain imparted in the cyclic ammonium ring when Li+ ions complex with them. It is also shown that the redox properties of quaternary ammonium binaphthyl salts are pH dependent in aqueous solutions, but that reversible redox properties can be observed in extremely basic solutions. The effect of anions binding to the quaternary ammonium cation can be seen in the redox properties of the binaphthyl moiety and the use of a chiral binding site for enantiomeric recognition is also demonstrated.