Patients perspectives on drug shortages in six European hospital settings - a cross sectional study.

BACKGROUND: It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients' awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. METHODS: A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher's exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher's test. Post-hoc hospital-wise analyses were performed using Fisher's exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). RESULTS: 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p < 0.001) while the fewest patients were in H-SE (1 %, N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. CONCLUSIONS: Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.

Incompatible intravenous drug combinations and respective physician and nurse knowledge: a study in routine paediatric intensive care.

OBJECTIVES: To identify incompatible intravenous drug combinations in routine paediatric intensive care and evaluate physician and nurse knowledge. METHODS: In a university paediatric intensive care unit, intravenous drug incompatibilities were analysed using a database and physician and nurse knowledge of incompatibilities was assessed using a questionnaire. RESULTS: We analysed 665 prescriptions in 87 patients. Incompatible drug administration was identified in 9 (10%) of the 87 patients with a median of 3 different incompatibilities per patient (Q25/Q75: 1/3). We found 26 incompatible combinations. The most frequently involved drugs were cefotaxime, pantoprazole and vancomycin. A median of 10 of the 15 drug combinations were correctly assessed as compatible or incompatible (Q25/Q75: 8/11). Pantoprazole had a low number (20%) of correct answers. CONCLUSIONS: One in 10 patients in paediatric intensive care was affected by drug incompatibility, with knowledge deficits seen in a third of assessed combinations. This indicates quality improvement strategies should be urgently implemented by pharmacists.

ROCK-ALS: Protocol for a Randomized, Placebo-Controlled, Double-Blind Phase IIa Trial of Safety, Tolerability and Efficacy of the Rho Kinase (ROCK) Inhibitor Fasudil in Amyotrophic Lateral Sclerosis.

Objectives: Disease-modifying therapies for amyotrophic lateral sclerosis (ALS) are still not satisfactory. The Rho kinase (ROCK) inhibitor fasudil has demonstrated beneficial effects in cell culture and animal models of ALS. For many years, fasudil has been approved in Japan for the treatment of vasospasm in patients with subarachnoid hemorrhage with a favorable safety profile. Here we describe a clinical trial protocol to repurpose fasudil as a disease-modifying therapy for ALS patients. Methods: ROCK-ALS is a multicenter, double-blind, randomized, placebo-controlled phase IIa trial of fasudil in ALS patients (EudraCT: 2017-003676-31, NCT: 03792490). Safety and tolerability are the primary endpoints. Efficacy is a secondary endpoint and will be assessed by the change in ALSFRS-R, ALSAQ-5, slow vital capacity (SVC), ECAS, and the motor unit number index (MUNIX), as well as survival. Efficacy measures will be assessed before (baseline) and immediately after the infusion therapy as well as on days 90 and 180. Patients will receive a daily dose of either 30 or 60 mg fasudil, or placebo in two intravenous applications for a total of 20 days. Regular assessments of safety will be performed throughout the treatment period, and in the follow-up period until day 180. Additionally, we will collect biological fluids to assess target engagement and evaluate potential biomarkers for disease progression. A total of 120 patients with probable or definite ALS (revised El Escorial criteria) and within 6-18 months of the onset of weakness shall be included in 16 centers in Germany, Switzerland and France. Results and conclusions: The ROCK-ALS trial is a phase IIa trial to evaluate the ROCK-inhibitor fasudil in early-stage ALS-patients that started patient recruitment in 2019.

Is there a need for a hospital pharmacy common training framework? Review of the literature on the impact of educational interventions on health outcome.

BACKGROUND: With the update of the directive 2005/36/EU on the recognition of professional qualifications (2013/55/EU), the European Union (EU) legislation opened also to pharmacists the possibility to define specialisations via a common training framework (CTF). OBJECTIVE: The aim of this study was to review, synthesise and present published evidence on the impact of health educational interventions targeting healthcare professionals on patients' health outcomes that support a hospital pharmacy CTF in EU. METHOD: The search was carried out in Medline and Cumulative Index to Nursing & Allied Health Literature and was limited to English language full review articles or primary research published since 2000. Data were extracted independently and compared by three of the researchers. RESULTS: Ten papers (9 primary research studies and one literature review) were identified. Almost one-third of the studies (30%, n=3) targeted pharmacists in their research. The majority of studies (80%, n=8) have shown that higher education levels among healthcare professionals improved patient outcomes. No study discussed the importance of a CTF. CONCLUSION: The review of the literature has demonstrated the need for education and training of health personnel to improve patient outcome. Controlled studies about pharmacist education and training in European countries showed that the benefit of a CTF is lacking.

A stability study of amphotericin B, colistin and tobramycin in a hydrophilic suspension commonly used for selective decontamination of the digestive tract by HPLC and in vitro potency measurements.

OBJECTIVES: A suspension for oral use which consists of three non-absorbable antibiotics (amphotericin B, colistin and tobramycin) is often used in clinical practice for the selective decontamination of the digestive tract (SDD) of patients in intensive care. Such a therapy is a preventive tool to minimise the risk of pneumonia and bacteraemia in intubated patients. The administration and the treatment results are controversially discussed. One limiting factor for a unique SDD treatment in the hospitals is a lack of adequate data regarding batch formula and stability for such a formulation. Since no detailed procedures, specifications or stability data are available for manufacturing this formulation there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this research was to collect the physicochemical and microbiological stability data of a developed, stable standard formulation under defined storage conditions. The effectiveness of the SDD suspension should be preferably proven over a long period. This would help guarantee that all patients receive the same preparation, therefore, ensuring similar efficacy and improved safety. METHODS: An adequate formulation composed of the registered, marketed medicinal product Ampho-Moronal suspension (Dermapharm AG, Germany) and a buffered, preserved aqueous solution of colistin and tobramycin both as sulfates has been developed. A stability study has been performed on two batches of the formulation. During the storage, samples were taken and compatibility was verified by physicochemical and microbiological testing in stability-indicating terms of colour, odour, flavour, pH, chemical and microbiological purity as well as in vitro potency. The test methods were built and tailored to be suitable, reliable and precise for the test needs. RESULTS: The results show the physicochemical and microbiological stability of the described formulation for defined storage conditions. CONCLUSIONS: A standardised formulation with a proven stability for at least 6 months under fridge (5°C±3°C) conditions for the SDD of patients in intensive care was established.

Handling of hazardous drugs - Effect of an innovative teaching session for nursing students.

BACKGROUND: Imparting knowledge and practical skills in hazardous drug handling in nursing students' education is essential to prevent hazardous exposure and to preserve nurses' health. OBJECTIVES: This study aimed at comparing routine nursing education with an additional innovative teaching session. DESIGN: A prospective controlled study in nursing students was conducted in two study periods: (i) a status-quo period (routine education on handling hazardous drugs) followed by (ii) an intervention period (additional innovative teaching session on handling hazardous drugs). SETTINGS/PARTICIPANTS: Nursing students at a vocational school were invited to participate voluntarily. METHODS: In both study periods (i) and (ii), the following factors were analysed: (a) knowledge of hazardous drug handling by questionnaire, (b) practical skills in hazardous drug handling (e.g. cleaning) by a simulated handling scenario, (c) contamination with drug residuals on the work surface by fluorescent imaging. RESULTS: Fifty-three nursing students were enrolled. (a) Median knowledge improved from status-quo (39% right answers) to intervention (65%, p<0.001), (b) practical skills improved from status-quo (53% of all participants cleaned the work surface) to intervention (92%, p<0.001). (c) Median number of particles/m2 decreased from status-quo to intervention (932/97, p<0.001). CONCLUSIONS: Compared with routine education, knowledge and practical skills in hazardous drug handling were significantly improved after an innovative teaching session. Additionally, the amount of residuals on the work surface decreased. This indicates a lower risk for hazardous drug exposure.

Standardising analgesic administration for nurses: a prospective intervention study.

Background Uncontrolled pain reduces quality of life, delays recovery from surgery and can potentially contribute to the development of chronic pain. Strategies to improve pain management are desirable in view of these detrimental outcomes, yet frequently they are predominately medically based despite nurses playing key roles in pain assessment and analgesic administration. Objective To develop an algorithm-based guidance addressing nurses' pain assessment and analgesic administration and investigating its impact on quality of pain management. Setting Two orthopaedic units in a university hospital. Method An interdisciplinary expert panel consisting of physicians, nurses and clinical pharmacists developed an algorithm-based guidance in analgesic administration for nurses. The guidance was based on current guidelines addressing the appropriate use of analgesics. In a prospective intervention study, clinical pharmacists acted as independent monitors who assessed nurses' pain assessment and analgesic administration before (control period: usual care without any further support) and after implementation of the algorithm-based guidance (intervention period). We evaluated patient-nurse contacts for guideline adherence. We predefined guideline adherence (main outcome) as fulfilling all three of the following criteria: (A) nurses' pain intensity assessment, (B) their assessment of the patients' need for analgesics, and (C) analgesic administration depending on patients' individual pain intensity (including choice of prescribed analgesics). Main outcome measure Adherence to pain management guidelines. Results We analysed 706 patient-nurse contacts with 162 patients in the control and 748 contacts with 168 patients in the intervention period. Without support, guidelines were followed in 6 % of the patient contacts. We achieved an increase to 54 % (p < 0.001) after guidance implementation (main outcome). Guideline adherence decreased with rising pain intensity (slope coefficient -0.763, p < 0.001). Conclusion Especially in patients suffering from severe pain, current guidelines were not strictly followed by nurses when administering analgesics. Guideline adherence improved eightfold by implementing an algorithm-based guidance.

Administration of anticonvulsive rescue medication in children-discrepancies between parents' self-reports and limited practical performance.

UNLABELLED: Quality of parents' performance in administering anticonvulsive rescue medication to their children suffering from seizures is unknown. After obtaining ethical approval, we used a questionnaire to ask parents of children with seizures, who had been prescribed rescue medications, about their experience in administering those. To assess the frequency of actually committed drug-handling errors, we let them administer rescue medications to dummy dolls. An expert panel rated the clinical risk of handling errors from "1" (lowest) to "6" (highest). Eighty-one parents completed the study. In the questionnaire, 85 % (100 %) of parents that already conducted rectal (buccal) administration reported that they had never experienced problems. The number of rectal administrations with at least one handling error (97 %, 58/60) was higher than in buccal administration (58 %; 14/24; p < 0.001). According to logistic regressions, previous use of rescue medication was not a predictor of the number of committed errors per process (n. s.). All errors were rated with a high clinical risk (class 4-6). CONCLUSION: By observing parents' administration of rescue medication to dummy dolls, we found a high frequency of clinically relevant drug-handling errors. Most parents, however, self-reported to have never experienced problems while administering rescue medications to their children. WHAT IS KNOWN: • For seizures with duration of more than 5 min, the administration of anticonvulsive rescue medication is recommended. • Outside the hospital, the administration of rescue medication to children is performed most frequently by their parents. What is New: • Most of the parents reported that they had never experienced problems in handling anticonvulsive rescue medication. • But in the observed drug-handling performances, identified errors committed by parents were alarmingly frequent and pose a high clinical risk according to an expert panel.

Managing of oral medicines in paediatric oncology: can a handbook and a pharmaceutical counselling intervention for patients and their parents prevent knowledge deficits? A pilot study.

OBJECTIVES: To assess knowledge deficits of patients/parents and prevention strategies. METHODS: After receiving ethics approval, we performed a controlled, quasi-randomised, prospective intervention study. We enrolled patients/parents involved in managing oral medicines in three groups: control (routine care only), handbook intervention and pharmaceutical counselling intervention group. At baseline and after the interventions, we assessed patients'/parents' knowledge deficits (incorrect or missing answers) by questionnaire. RESULTS: We enrolled 64 patients/parents. At baseline, knowledge deficits among the groups were similar: 17% in controls, 22% in the handbook group and 24% in the pharmaceutical counselling group. After the intervention, knowledge deficits decreased to 13% in the handbook group and to 8% in the pharmaceutical counselling group (NS; p=0.003 compared with controls, respectively). For controls, knowledge deficits remained almost unchanged (19%). Results for the pharmaceutical counselling group showed a strong correlation between baseline knowledge deficits and the extent of the deficit decrease after the intervention (τ=-0.74; p<0.001), whereas no significant correlation was found in the control or handbook group. CONCLUSIONS: In paediatric oncology, patients'/parents' knowledge of managing oral medicines was improved. Pharmaceutical counselling substantially reduced high knowledge deficits but no significant improvement was seen with the handbook approach. Pharmaceutical counselling should be offered to patients/parents with high knowledge deficits to reduce errors in managing medicines and increase safety.

Hospital and Community Pharmacists' Perceptions of Which Competences Are Important for Their Practice.

The objective of the PHAR-QA (Quality assurance in European pharmacy education and training) project was to investigate how competence-based learning could be applied to a healthcare, sectoral profession such as pharmacy. This is the first study on evaluation of competences from the pharmacists' perspective using an improved Delphi method with a large number of respondents from all over Europe. This paper looks at the way in which hospital pharmacists rank the fundamental competences for pharmacy practice. European hospital pharmacists (n = 152) ranked 68 competences for pharmacy practice of two types (personal and patient care), arranged into 13 clusters. Results were compared to those obtained from community pharmacists (n = 258). Generally, hospital and community pharmacists rank competences in a similar way. Nevertheless, differences can be detected. The higher focus of hospital pharmacists on knowledge of the different areas of science as well as on laboratory tests reflects the idea of a hospital pharmacy specialisation. The difference is also visible in the field of drug production. This is a necessary competence in hospitals with requests for drugs for rare diseases, as well as paediatric and oncologic drugs. Hospital pharmacists give entrepreneurship a lower score, but cost-effectiveness a higher one than community pharmacists. This reflects the reality of pharmacy practice where community pharmacists have to act as entrepreneurs, and hospital pharmacists are managers staying within drug budgets. The results are discussed in the light of a "hospital pharmacy" specialisation.

[Electronic drug prescription - auto pilot for drug therapy?]. / Elektronische Arzneimittelverordnung - Autopilot in der Arzneimitteltherapie? Eine Literatur- und Datenanalyse.

In tertiary care, computerized physician order entries may improve performance, cross-linking, and documentation when prescribing drugs. A clinical decision support integrated in these systems is discussed to prevent additional medication errors. For an optimal performance, the implementation into the clinical information systems is required to gain access to patient data (e. g. from laboratory). In routine care, the question rises whether a benefit of the systems can be proven in clinical studies and whether there is a difference between the systems. To achieve optimal results, these systems should also consider specific requirements, i. e. the patient groups and prescribed drugs in the local setting. We performed a systematic literature evaluation searching for published data in the topic electronic prescribing to assess them in a structured analysis considering medical-pharmaceutical aspects. Additionally, we assessed three databases in German language and one in English language taking drug-drug-interactions as an example to compare the identification of drug-related problems. Medication data from our own patients in a paediatric intensive care unit of a university hospital were analysed by the systems. Our results revealed strengths but also limitations of electronic prescribing.

Use of Levetiracetam in Neonates in Clinical Practice: A Retrospective Study at a German University Hospital.

OBJECTIVE: We performed a retrospective chart analysis in neonates routinely treated with levetiracetam (LEV) in a university setting. Patients and Methods We assessed clinical characteristics of the included neonates. Documented LEV doses and the duration of treatment were evaluated. To assess LEV effectiveness, we compared the need of any additional anticonvulsant as co- and rescue therapies before and following the initiation of LEV treatment. To assess LEV tolerance, we sought to identify documented adverse drug reactions resulting in a termination of LEV treatment. RESULTS: We analyzed a total of 72 neonates receiving LEV with a median gestational age at initiation of LEV treatment of 30 (4/7) gestational weeks (min., 24(5/7)/max., 43(0/7) weeks). LEV was applied in target doses of 41.7 mg/kg/d (min., 14.4/max., 106.2 mg/kg/d). Patients received LEV treatment at hospital for a median of 28 days (min., 1/max., 195 days). Additional anticonvulsant therapy decreased a week after LEV treatment was initiated (p = 0.008). We did not find any cases of terminated LEV treatment resulting from adverse drug reactions. CONCLUSION: Long term use of high LEV doses is rather frequent in immature neonates. Our data indicate good effectiveness and a low risk of adverse drug reactions.

Purity determination of amphotericin B, colistin sulfate and tobramycin sulfate in a hydrophilic suspension by HPLC.

A suspension comprising of the three antibiotic substances amphotericin B, colistin sulfate and tobramycin sulfate is often used in clinical practice for the selective decontamination of the digestive tract of patients in intensive care. Since no detailed procedures, specifications or stability data are available for manufacturing this suspension, there may be discrepancies regarding formulation and stability of suspensions prepared in different pharmacies. The aim of this work is to develop a standardized formulation and to determine its stability under defined storage conditions. This would help guarantee that all patients receive the same preparation, therefore ensuring similar efficacy and improved safety. The first step in this process is to develop the required analytical tools to measure the content and purity of the drug substances in this complex mixture. In this paper, the development and validation of these tools as well as the development of the drug suspension formulation is described. The formulation comprises of Ampho-Moronal(®)-Suspension (Dermapharm) and a buffered, preservated aqueous solution of colistin sulfate and tobramycin sulfate. Two simple, well established high-performance liquid chromatography (HPLC) methods in the European Pharmacopoeia (EP) for impurity profiling of the two active ingredients amphotericin B and colistin sulfate were combined with a newly developed sample extraction procedure for the suspension. Sufficient selectivity and stability-indicating power have been demonstrated. Additionally, a new robust routine method was developed to determine possible degradation products of tobramycin sulfate in the investigated suspension. The specificity, precision, accuracy and linearity of the analytical procedures were demonstrated. The recovery rate was in the range of 90-110%. The precision results for the calculated impurities showed variation coefficients of <10%. The calibration curves were found to be linear with correlation of greater than 0.9994 for all components. The results show the suitability of the methods for the quality control analysis of the suspension.

Case report of a medication error by look-alike packaging: a classic surrogate marker of an unsafe system.

BACKGROUND: The acronym LASA (look-alike sound-alike) denotes the problem of confusing similar- looking and/or sounding drugs accidentally. The most common causes of medication error jeopardizing patient safety are LASA as well as high workload. CASE PRESENTATION: A critical incident report of medication errors of opioids for postoperative analgesia by look-alike packaging highlights the LASA aspects in everyday scenarios. A change to a generic brand of medication saved costs of up to 16% per annum. Consequently, confusion of medication incidents occurred due to the similar appearance of the newly introduced generic opioid. Due to consecutive underdosing no life-threatening situation arose out of this LASA based medication error. CONCLUSIONS: Current recommendations for the prevention of LASA are quite extensive; still, in a system with a lump sum payment per case not all of these security measures may be feasible. This issue remains to be approached on an individual basis, taking into consideration local set ups as well as financial issues.

How to improve prescription of inhaled salbutamol by providing standardised feedback on administration: a controlled intervention pilot study with follow-up.

BACKGROUND: The effectiveness of inhaled salbutamol in routine care depends particularly on prescribed dosage and applied inhalation technique. To achieve maximum effectiveness and to prevent drug-related problems, prescription and administration need to work in concert. METHODS: We performed a controlled intervention pilot study with 4 consecutive groups in a general paediatric unit and assessed problems in salbutamol prescribing and administration. Control group [i]: Routine care without additional support. First intervention group [ii]: We carried out a teaching session for nurses aimed at preventing problems in inhalation technique. Independently from this, a pharmacist counselled physicians on problems in salbutamol prescribing. Second intervention group [iii]: Additionally to the first intervention, physicians received standardised feedback on the inhalation technique. Follow-up group [iv]: Subsequently, without any delay after the second intervention group had been completed, sustainability of the measures was assessed. We performed the chi-square test to calculate the level of significance with p ≤ 0.05 to indicate a statistically significant difference for the primary outcome. As we performed multiple testing, an adjusted p ≤ 0.01 according to Bonferroni correction was considered as significant. RESULTS: We included a total of 225 patients. By counselling the physicians, we reduced the number of patients with problems from 55% to 43% (control [i] vs. first intervention [ii], n.s.). With additional feedback to physicians, this number was further reduced to 25% ([i] vs. [iii], p < 0.001). In the follow-up [iv], the number rose again to 48% (p < 0.01 compared to feedback group). CONCLUSIONS: Teaching nurses, counselling physicians, and providing feedback on the quality of inhalation technique effectively reduced problems in salbutamol treatment. However, for success to be sustained, continuous support needs to be provided. TRIAL REGISTRATION: German Clinical Trials register: DRKS00006792 .

[An interdisciplinary concept to optimize patient safety--a pilot study]. / Ein interdisziplinäres Konzept zur Optimierung der Patientensicherheit - Eine Pilotstudie.

OBJECTIVE: Which effects has the interdisciplinary collaboration including pharmacists and psychologists in depressive patients? METHODS: In a 3-arm (each N = 10) randomized pilot study, we compared SC (standard care by specialized physicians in a tertiary care center) with SC + pharmaceutical medication management and SC + psychological counselling in respect to the number of drug-drug interactions, guideline conformity, patient knowledge, and medication adherence (according to MARS). RESULTS: The number of drug-drug interactions decreased by the MM up to 67 % (p < 0.05). Guideline conformity was fulfilled in all groups before and after intervention. Patient knowledge and medication adherence were not influenced by additional medication management or psychological counselling. CONCLUSION: In a greater patient group, these explorative results should now be verified.

Initial anticonvulsant monotherapy in routine care of children and adolescents: levetiracetam fails more frequently than valproate and oxcarbazepine due to a lack of effectiveness.

Since anticonvulsants such as valproate or oxcarbazepine have quite a disadvantageous profile of possible adverse drug events (ADEs), safer alternatives are being sought. The newer anticonvulsant levetiracetam is often considered advantageous. We performed a chart review of children and adolescents aged from 0.5 to 16.9 years, who had been started on an initial monotherapy with levetiracetam, valproate, or oxcarbazepine between 2007 and 2011, in order to analyze the therapy's failure rate during the first year. We differentiated failure of monotherapy due to a lack of effectiveness and due to ADEs. No psychometric tests were performed. Lack of effectiveness and inacceptable ADEs were assumed according to the judgment of physicians and families. Anticonvulsive monotherapy failed in 29/61 (48 %) levetiracetam patients and in 18/49 (37 %) valproate patients (for focal and generalized epilepsies; n.s.). This was caused by a lack of effectiveness in 25/61 (41 %) levetiracetam patients and in 11/49 (22 %) valproate patients (p ≤ 0.05). A modification of therapy due to ADEs was performed in 4/61 (7 %) levetiracetam patients and in 7/49 (14 %) valproate patients (n.s.). An anticonvulsive monotherapy failed in 21/42 (50 %) patients treated with levetiracetam and in 10/34 (29 %) patients treated with oxcarbazepine (for focal epilepsies; n.s.). Changes of monotherapy were caused by a lack of effectiveness in 17/42 (40 %) of levetiracetam patients and in 6/34 (18 %) of oxcarbazepine patients (p ≤ 0.05). ADEs leading to changes in therapy were reported for 4/42 (10 %) of levetiracetam and 4/34 (12 %) of oxcarbazepine patients (n.s.). An initial monotherapy of levetiracetam failed more frequently due to a lack of effectiveness than a monotherapy with valproate or oxcarbazepine. We found no significant difference in therapy failure due to ADEs.