Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK--a nested case-control analysis.

AIMS: To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS: Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS: Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS: Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Antidepressant prescribing in five European countries: application of common definitions to assess the prevalence, clinical observations, and methodological implications.

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.

Incidence of cancer in the general population and in patients with or without atopic dermatitis in the U.K.

BACKGROUND: Atopic dermatitis (AD) affects approximately 20% of children and 1-3% of adults in developed countries. OBJECTIVE: To study the incidence of cancer in patients with AD in the U.K. general population. METHODS: We conducted a follow-up study in the U.K. using The Health Improvement Network (THIN) database. We calculated the incidence rate (IR) of the first occurrence of overall cancer, lymphoma, melanoma and nonmelanoma skin cancer (NMSC) in the general population, in patients with AD and in individuals without AD. In addition we calculated the IR ratio (IRR) of overall cancer and subtypes of cancer in patients with AD vs. those without. RESULTS: The study population included 4,518,131 patients [2,336,230 (51·7%) female]. There were 129,972 subjects [68,688 (52·8%) female] with a diagnosis of cancer (excluding NMSC). The IR (per 10,000 person-years) of cancer (excluding NMSC) was 42·41 [95% confidence interval (CI) 42·18-42·64]; of lymphoma 1·70 (95% CI 1·65-1·74); of skin melanoma 1·71 (95% CI 1·67-1·76) and of NMSC 11·76 (95% CI 11·64-11·88). The age- and sex-adjusted IRR for cancer (excluding NMSC) was 1·49 (95% CI 1·39-1·61); for lymphoma 2·21 (95% CI 1·65-2·98); for melanoma 1·74 (95% CI 1·25-2·41); and for NMSC 1·46 (95% CI 1·27-1·69). CONCLUSIONS: Our results indicate an increased incidence of cancer overall as well as of specific cancer subtypes, including lymphoma, in patients with AD. Further studies are needed to disentangle the effects of treatment for AD from AD itself.

Risk of cataract in patients treated with statins.

BACKGROUND: Studies in dogs showed that some hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are associated with cataract when administered in excessive doses. Clinical safety data of statins regarding cataract development in humans have been of limited value so far. OBJECTIVE: To determine whether long-term use of statins is associated with an increased risk of cataract. METHODS: We conducted a case-control analysis using data from the United Kingdom-based General Practice Research Database. The main outcome was a first-time diagnosis of cataract and/or cataract extraction in patients aged 40 to 79 years. Controls were matched to cases on age, sex, practice, calendar time, and duration of medical history in the database. Use of statins, fibrates, or other lipid-lowering drugs was compared with nonuse of any lipid-lowering drug, stratified by exposure duration and dose. RESULTS: We identified 7405 cases and 28 327 controls. Long-term use of statins (eg, > or =30 prescriptions) was not associated with an increased cataract risk (adjusted odds ratio [OR], 0.9; 95% confidence interval [CI], 0.5-1.6), nor was use of fibrates or of other lipid-lowering drugs (adjusted OR, 0.5; 95% CI, 0.3-1.1; and OR, 0.7; 95% CI, 0.1-5.6, respectively). We found evidence that concomitant use of simvastatin and erythromycin, a potent inhibitor of simvastatin metabolism, is associated with an increased cataract risk (adjusted odds ratio, 2.2; 95% confidence interval, 1.2-4.1). CONCLUSIONS: Our study provides evidence that long-term use of therapeutic statin doses does not increase the risk of developing cataract. Concomitant use of erythromycin and simvastatin may increase the cataract risk.

Lamotrigine-associated anticonvulsant hypersensitivity syndrome.

We systematically reviewed and analyzed published and unpublished cases of lamotrigine-associated adverse drug reactions consistent with the features of the anticonvulsant hypersensitivity syndrome (AHS) to identify characteristics of the syndrome. We identified 26 cases (mean age, 28+/-18 years; range, 3.5 to 74 years; 54% female), of which nine were published. The characteristics of the syndrome associated with lamotrigine are comparable to AHS induced by older aromatic anticonvulsants.

Pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration in healthy subjects.

Clomethiazole, a sedative-hypnotic and anticonvulsant drug, has been successfully administered orally and intravenously, but in cases where either of these methods presents complications, rectal administration may represent a practical alternative. We sought to compare the single-dose pharmacokinetics and pharmacodynamics of clomethiazole after oral and rectal administration. Ten healthy adult volunteers were given 600 mg clomethiazole edisylate (corresponding to 390 mg clomethiazole base) in 2 capsules as a single oral or rectal dose in a double-masked, double-dummy, crossover fashion. Serum concentrations were measured up to 10 hours after administration using a specific high-performance liquid chromatography method. Computerized reaction-time measurement and visual analogue scales (VAS) were used to assess drug effects. Peak serum concentrations were significantly higher after oral administration (mean +/- SEM, oral 1.76 +/- 0.47 microg/mL vs rectal 0.48 +/- 0.14 microg/mL; P = 0.03) and appeared earlier (55 +/- 12 vs 89 +/- 11 min; P = 0.04). Area under the concentration-time curve values were similar after administration by both routes (oral 116 +/- 20.6 vs rectal 105 +/- 36.0 microg x min/mL), with a relative rectal bioavailability of 90% compared with oral administration. The objective pharmacodynamic effects on reaction time (increase of 104 +/- 26 vs 66 +/- 22 ms, oral vs rectal) and working speed (decrease of 132 +/- 38 vs 97 +/- 32 ms, oral vs rectal) were not significantly different. Subjective pharmacodynamic effects, as measured on the VAS, were comparable with both routes of administration. Clomethiazole was well tolerated, with a similar adverse effect profile for both routes of administration. The effects of rectal dosing of clomethiazole were similar to those of oral dosing but appeared to occur later. Our results suggest that rectal administration of a single 600-mg clomethiazole edisylate dose bears no safety risk. Therefore, rectal administration could be considered when neither oral nor parenteral administration is possible and a later onset of effect is not critical.

[Management of adverse drug effects]. / Umgang mit unerwünschten Arzneimittelwirkungen.

Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

[Torsade de pointes during anti-arrhythmia treatment with amiodarone]. / Torsade de pointes unter antiarrhythmischer Behandlung mit Amiodaron.

Torsade de pointes, a polymorphous ventricular tachycardia, is a well-known but rarely occurring cardiac adverse drug reaction under amiodarone, a class-III antiarrhythmic agent. We report the case of a 60-year-old male patient who developed a life-threatening torsade after three weeks of amiodarone therapy. Considering some potential risk factors, amiodarone is an effective and safe antiarrhythmic agent for ventricular and supraventricular tachycardia. In most patients, Amiodarone can be used safely even in those who had developed a torsade de pointes with other antiarrhythmic agents.

[Drug-induced Stevens-Johnson syndrome in a patient with AIDS]. / Medikamentös bedingtes Stevens-Johnson-Syndrom bei einem Patienten mit Aids.

The Stevens-Johnson syndrome is a severe potentially life-threatening form of the erythema multiforme, affecting both skin and mucous membranes. We present a case of a 49-year-old male patient with AIDS who developed a Stevens-Johnson syndrome while being treated with pyrimethamine, sulfadiazine and phenytoin for cerebral toxoplasmosis. Further diagnostic evaluation of this dangerous cutaneous affection may prove difficult for several reasons. In particular, in patients with AIDS who are more susceptible for adverse drug reactions and who are simultaneously receiving a variety of drugs with a considerable potential of cutaneous side effects, therapy cannot be withhold for lack of therapeutic alternatives. Moreover, the low lymphocyte count in this case may have made reliable testing with lymphocyte transformation studies impossible. The evaluation and the differential diagnosis of the drug-induced Stevens-Johnson syndrome are discussed. Especially long- and moderately long-acting sulfonamides belong to the most important agents that can cause a drug-induced Stevens-Johnson syndrome. The pathogenesis and the risk factors for cutaneous hypersensitivity reactions in HIV-infected patients are only poorly understood. These kind of reactions, however, seem to occur more often in patients with a more advanced immunodeficiency.

[Prevalence of potential drug-drug interactions in ambulatory patients with statin therapy]. / Prävalenz potentieller Arznei- mittelinteraktionen bei ambulanten Patienten unter Statin-Therapie.

AIM: To asses the prevalence of potentially critical drug-drug interactions (DDIs) in outpatients treated with a statin. PATIENTS/METHODS: Data of patients (e.g. age, sex, comorbidities, individual statin, number of drugs, number of diagnoses) were collected from 242 Swiss practitioners. The medication was screened electronically for potentially critical DDIs. RESULTS: We included 2742 statin-treated patients (mean age 65.1 +/- 11.2 [SD] years, 3.2 +/- 1.6 diagnoses, 4.9 +/- 2.4 drugs prescribed) from the German (53.3%), French (36%) or Italian speaking (10.7%) part of Switzerland. Of those, 401 (14.6%) had a total of 591 potentially severe DDIs; 190 patients (6.9%) had potential statin DDIs, 288 (10.5%) potential non-statin DDIs, mainly due to pharmacodynamic mechanisms. The prevalence of potential DDIs was similar between regions, except for a trend for a higher prevalence of drug-statin interactions in the French-speaking part. The number of drugs per patient and a diagnosis of arrhythmia or heart failure were identified as risk factors for DDIs. CONCLUSIONS: Drug combinations with potentially severe DDIs are common in patients treated with statins due to pharmacotherapy of their co-morbidities. Special attention in this specific population should be drawn on patients with polypharmacy and those with drug treatments for arrhythmia or heart failure.

Antiepileptic drug hypersensitivity syndrome.

The antiepileptic drug hypersensitivity syndrome (AHS) is an adverse drug reaction associated with the aromatic antiepileptic drugs (AEDs) phenytoin (PHT), carbamazepine (CBZ), phenobarbital (PB), and primidone. The syndrome is defined by the triad of fever, skin rash, and internal organ involvement. It can also be caused by other drugs, such as sulfonamides, dapsone, minocycline, terbinafine, azathioprine, and allopurinol. Diagnosis of AHS may be difficult because of the variety of clinical and laboratory abnormalities and manifestations and because the syndrome may mimic infectious, neoplastic, or collagen vascular disorders. The incidence is approximately 1 in 3,000 exposures. AHS starts with fever, rash, and lymphadenopathy, within the first 2-8 weeks after initiation of therapy. Internal manifestations include, among others, agranulocytosis, hepatitis, nephritis, and myostitis. AHS is associated with a relative excess of reactive oxidative metabolites of the AED. Insufficient detoxification may lead to cell death or contribute to the formation of antigen that triggers an immune reaction. Crossreactivity among PHT, CBZ, and PB is as high as 70-80%.

[SIADH with epileptic seizures and coma in fluoxetine therapy]. / SIADH mit epileptischen Anfällen und Koma unter Fluoxetin-Therapie.

Hyponatremia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been associated with several psychotropic drugs e.g., carbamazepine, neuroleptics, tricyclic antidepressants and more recently selective serotonin reuptake inhibiting (SSRI) antidepressants. SSRIs have gained widespread use in elderly depressed patients because of their favourable adverse effect profile. However, SSRIs have recently been associated increasingly with SIADH. We describe a 82-year old patient who was hospitalised after witnessed convulsions ten days after initiation of fluoxetine therapy for depression. She had hyponatremia and increased urine osmolarity suggesting SIADH. Using this case we discuss the clinical symptoms, aetiology, differential diagnosis and therapy of drug-induced SIADH.

Minocycline-induced lupus. A systematic review.

BACKGROUND: Minocycline has increasingly been associated with different adverse auto-immune reactions including drug-induced lupus. OBJECTIVE: To identify the scope of minocycline-induced lupus and to characterise its typical features. METHODS: Comprehensive Medline and Embase search of the English and non-English literature for case reports of minocycline-induced lupus. RESULTS: We included 57 cases of minocycline-induced lupus (mean age +/- SD at onset: 21.6+/-8.6 years, median time of exposure: 19 months, range 3 days to 6 years). All patients showed the clinical features of polyarthralgia/polyarthritis often accompanied by liver abnormalities. Twelve patients had evidence of dermatological manifestations (i.e rash, livedo reticularis, oral ulceration, subcutaneous nodules, alopecia). The ANA test was positive in all patients. CONCLUSION: Long-term exposure to minocycline may be associated with drug-induced lupus. Baseline and periodic liver function and ANA tests accompanied by appropriate clinical monitoring are suggested for patients receiving long-term minocycline therapy.

Use of selective serotonin reuptake inhibitors and risk of developing first-time acute myocardial infarction.

AIMS: Selective serotonin reuptake inhibitors (SSRIs) have been associated with serotonin depletion in platelets, potentially leading to abnormal aggregation and prolonged bleeding time. In view of the importance of serotonin in coronary thrombosis, and decreased platelet serotonin concentrations associated with SSRIs, the present study was performed to test the hypothesis of a decreased risk of acute myocardial infarction (AMI) associated with SSRIs. METHODS: We conducted a population-based case-control analysis using the UK General Practice Research Database (GPRD). A total of 3319 patients aged 75 years or younger free of clinical conditions predisposing to ischaemic heart disease, with a first-time diagnosis of AMI between 1992 and 1997, and 13 139 controls without AMI matched to cases for age, sex, general practice attended, and calendar time were included. Conditional logistic regression was used to estimate relative risks. RESULTS: Adjusted odds ratios (with 95% CI) for current use of SSRIs, non-SSRIs, or other antidepressants, compared to the group of nonusers of antidepressants were 0.9 (95% CI 0.5,1.8), 0.9 (95% CI 0.7,1.2), and 1.3 (95% CI 0.6,2.8), respectively. As compared with nonuse of SSRIs, current use (regardless of any other antidepressants used) resulted in an adjusted OR of 1.1 (95% CI 0.7,1.6). CONCLUSIONS: The current analysis provides evidence that SSRI exposure does not substantially decrease the risk of developing first-time AMI in patients free of factors predisposing to ischaemic heart disease. However, due to relatively small numbers of exposed subjects and the resulting wide confidence intervals, further studies may be needed to document a lack of effect of SSRIs in subjects without pre-existing diseases predisposing to AMI.

Lamotrigine-induced severe cutaneous adverse reactions.

PURPOSE: We systematically reviewed and analyzed published and unpublished cases of Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN) associated with lamotrigine (LTG) therapy to identify characteristics of these reactions. METHODS: We performed a MEDLINE search (January 1985 to April 1998) and citation tracking for published reports. In addition, reports were requested from the Uppsala Monitoring Centre of the World Health Organization (WHO). Published and WHO cases of LTG-associated SJS or TEN were included if the causal relationship was assessed as either possible, probable, or definite. RESULTS: We identified a total of 57 cases (43 cases of SJS, 14 cases of TEN), of which 13 (23%) were published. Cases in the SJS group were significantly younger than in the TEN group (21 years vs. 31 years). The median time to onset (17 days for SJS and TEN) and the median dosage at onset (50 mg vs. 87.5 mg) for SJS and TEN did not differ significantly. Concomitant use of valproate (VPA) was reported in 74% of the SJS cases and 64% of the TEN cases. In three cases, TEN was the cutaneous manifestation of the antiepileptic drug hypersensitivity syndrome (AHS). CONCLUSIONS: The main features of severe cutaneous drug reactions, such as dosage, onset, and concomitant VPA use, do not differ in patients with LTG-induced SJS or TEN. SJS or TEN may also be the cutaneous manifestations of LTG-induced AHS. Further epidemiologic studies are needed to identify the incidence of severe LTG-induced cutaneous adverse reactions and the relative risk compared with other AEDs.

HMG-CoA reductase inhibitors and the risk of fractures.

CONTEXT: Recent animal studies have suggested that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) increase bone formation, volume, and density. It is unknown whether use of statins is associated with a decreased risk of fractures in humans. OBJECTIVE: To determine whether exposure to statins, fibrates, or other lipid-lowering drugs is associated with reduced bone fracture risk. DESIGN: Population-based, nested case-control analysis. SETTING: The UK-based General Practice Research Database (GPRD), comprising some 300 practices, with data collection from the late 1980s until September 1998. SUBJECTS: Within a base population of 91,611 individuals aged at least 50 years (28,340 individuals taking lipid-lowering drugs, 13,271 untreated individuals with a diagnosis of hyperlipidemia, and 50,000 randomly selected individuals without diagnosis of hyperlipidemia), we identified 3940 case patients who had a bone fracture and 23,379 control patients matched for age (+/-5 years), sex, general practice attended, calendar year, and years since enrollment in the GPRD. MAIN OUTCOME MEASURES: Use of statins, fibrates, or other lipid-lowering drugs in case patients vs control patients. RESULTS: After controlling for body mass index, smoking, number of physician visits, and corticosteroid and estrogen use, current use of statins was associated with a significantly reduced fracture risk (adjusted odds ratio [OR], 0.55; 95% confidence interval [CI], 0.44-0.69) compared with nonuse of lipid-lowering drugs. Current use of fibrates or other lipid-lowering drugs was not related to a significantly decreased bone fracture risk (adjusted OR, 0.87; 95% CI, 0.70-1.08 and adjusted OR, 0.76; 95% CI, 0.41-1.39, respectively). CONCLUSIONS: This study suggests that current exposure to statins is associated with a decreased risk of bone fractures in individuals age 50 years and older. This finding has a potentially important public health impact and should be confirmed further in controlled prospective trials. JAMA. 2000;283:3205-3210

Seizures associated with therapeutic doses of venlafaxine and trimipramine.

OBJECTIVE: To report a patient having a first-time seizure after receiving venlafaxine and trimipramine for depression. CASE SUMMARY: A 25-year-old white woman with chronic depression was treated with venlafaxine 150 mg/d and trimipramine 50 mg/d. Eleven days after increase of the trimipramine dosage to 100 mg/d, she was hospitalized because of seizures suggesting a secondary generalized grand-mal episode. The electroencephalogram showed a pathologic pattern with several generalized epileptiform discharges. Because of suspected drug-induced seizures, both antidepressants were stopped. After antidepressant drug cessation, the patient was symptom free and had no further seizure episodes within the following 12 months of follow-up. No other potential cause for the seizure episode could be identified. DISCUSSION: Both venlafaxine and trimipramine have been associated with seizures, mainly after overdose. Venlafaxine-associated seizures at therapeutic doses have not been reported in the literature. We hypothesize that a pharmacodynamic or pharmacokinetic drug interaction between venlafaxine and trimipramine involving the CYP2D6 isoenzyme may have played a role in inducing the seizures. CONCLUSIONS: Clinicians should be aware of the proepileptogenic effect of venlafaxine and trimipramine at therapeutic doses and that this combination may eventually increase the risk of seizures.

[Clinico-pharmacological case (4). Epileptic seizure as an unwanted drug effect on theophylline poisoning]. / Der klinisch-pharmakologische Fall (4). Epileptischer Anfall als unerwünschte Arzneimittelwirkung bei Theophyllinintoxikation.

In spite of the better understanding of the pharmacokinetics and optimized galenics of oral theophylline formulations, therapy with this bronchodilator still bears risks because of its narrow therapeutic window combined with substantial inter- and intra-individual variability of theophylline metabolism. In particular, the comedication with a variety of drugs inhibiting theophylline metabolism requires consideration as a potential source of toxicity. Besides mild, self-limited adverse effects, potentially life-threatening toxic manifestations such as ventricular tachyarrhythmias, shock, and seizures can occur especially with high plasma concentrations. We report the case of a 72-year-old patient with chronic obstructive pulmonary disease who was admitted for surgical treatment of an ulcer of the foot. During combined therapy with theophylline and ciprofloxacin he developed signs of theophylline toxicity with a single episode of partial seizures. These symptoms rapidly improved with repetitive application of activated charcoal and sorbitol. Clinically relevant drug-drug interactions with theophylline and the role and mechanism of action of activated charcoal in intoxicated patients are discussed.

Academic detailing improves identification and reporting of adverse drug events.

In a prospective, crossover study, we assessed the impact of a clinical pharmacist on identification and reporting of adverse drug events (ADEs) in hospitalized patients. The study was conducted on four units of a medical ward of a university hospital, with two units serving as test, the other two as control units. After 12 months, test and control units were switched. In the test units, a pharmacist participated in daily ward rounds, solicited additional information from physicians and nurses, and reviewed the charts of all patients. In control units, information on ADEs was based solely on voluntary reports from physicians and nurses. A total of 1,959 patients (941 in test, 1,018 in control units) were hospitalized during the study period. In 137 test units patients, 224 ADEs (14.6%; 95%-CI: 12.3%-16.9%) were detected (8 severe, 60 moderate, 156 mild), while 25 ADEs (1 severe, 11 moderate, 13 mild) occurring in 21 patients (2.1%; 95%-CI: 1.2%-3.0%) were reported from the control units (p < 0.0001). Of the ADEs in the test units, 51% were reported spontaneously, 39% were identified on rounds, and 10% by chart review. After changing the status of test and control units, the number of identified ADEs returned to preintervention levels. Clinical pharmacists as part of the medical care team can improve the identification of ADEs which may ultimately translate into improved quality of care.

[Anticonvulsant hypersensitivity syndrome. 2 case reports and an overview]. / Antikonvulsiva Hypersensitivitäts-Syndrom. Zwei Fallbeschreibungen und eine Ubersicht.

Anticonvulsants with aromatic ring structure such as phenytoine, carbamazepine, phenobarbital and lamotrigine can induce a drug hypersensitivity syndrome ("anticonvulsant hypersensitivity syndrome", AHS). Though the incidence of AHS is low, correct and early diagnosis are crucial to stop further progression by immediately withholding the causative drug. AHS usually starts within the first 2-8 weeks after initiation of therapy with fever, followed over the next 1-2 days by a cutaneous reaction and lymphadenopathy. The skin reaction is usually exanthematous but can also manifest itself as Stevens-Johnson or Lyell syndrome. AHS is commonly associated with symptomatic or asymptomatic internal organ involvement usually affecting the liver, although haematologic, renal or pulmonary impairment may also occur. We report two cases illustrating the clinical course and discuss theories about the potential pathogenesis and the treatment of AHS.