[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.

Deprescribing in Newly Admitted Psychogeriatric Nursing Facility Patients.

OBJECTIVE: To determine whether advised changes as a result of structured medication reviews in psychogeriatric patients were implemented and if the implemented changes were maintained. DESIGN: Prospective cohort study. SETTING: Three nursing facilities in The Netherlands. PATIENTS, PARTICIPANTS: Newly admitted psychogeriatric residents. INTERVENTION: After admission, a structured medication review was performed by a pharmacist and physician resulting in a treatment plan that was approved by the patient's legal representative and implemented. MAIN OUTCOME MEASURE(S): The percentage of advised changes approved (= approval rate) and the percentage of implemented medication changes still present 90 days after approval (= 90-day implementation rate). RESULTS: A total of 45 patients were included who used a total number of 333 drugs (mean ± standard deviation 7.4 ± 3.3 drugs). Changes were advised to 159 medications used by 42 patients. Of these changes, 150 were approved (approval rate 94.3%). Finally, 105 were implemented, and 89 were still implemented after 90 days (90-day implementation rate 84.8%). Overall, 59.7% of the advised changes concerned deprescribing (stopping or dose reduction). The proportion of advised changes implemented was similar for symptommodifying and risk-modifying drugs, namely, almost 85%. Overall, 55.3% of the recommended changes to deprescribe concerned 10 drug groups. CONCLUSION: Medication could be successfully deprescribed from psychogeriatric patients after structured medication reviews performed by pharmacists and nursing facility physicians. More than 50% of the advised changes to deprescribe involved 10 drug groups, which raises the question whether the structured medication review can be performed more efficiently by focusing on the most common problems.

[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.