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The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horses (7%). Many of the reports in dogs involved the application of combined vaccines against canine distemper, hepatitis, parvovirosis and parainfluenza in combination with canine leptospira components, in cats against cat flu and feline panleukopenia in combination with feline leukaemia virus infection. Causality assessments were done according to the international ABON system. In 27% of the reported cases, the causality assessments between the vaccination and the reaction described were evaluated as being probable (ABON A), in 44% as possible (ABON B).Das Ziel des Vaccinovigilancemeldesystems ist die Erfassung und Klassifizierung von unerwünschten Arzneimittelwirkungen (UAW) nach der Anwendung von immunologischen Tierarzneimitteln (TAM) in der Schweiz. Dazu zählt auch eine vermutete ungenügende Wirksamkeit von Impfstoffen. Als Zulassungsstelle für immunologische TAM ist die Impfstoffkontrolle des Instituts für Virologie und Immunologie (IVI) auch zuständig für das Vaccinovigilancemeldesystem. 130 UAW Meldungen zu zugelassenen immunologischen TAM wurden im Jahr 2020 erfasst (5% weniger als 2019). Am häufigsten betrafen die Meldungen Kleintiere: Hunde (41%) und Katzen (25%), gefolgt von Rindern (18%) und Pferden (7%). Beim Hund basierten die meisten UAW auf der Anwendung von Impfstoffen gegen Staupe, Hepatitis, Parvovirose und Parainfluenza in Kombination mit Leptospirose, bei der Katze waren es Impfstoffe gegen Katzenschnupfen und -seuche kombiniert mit Feliner Leukämievirusinfektion. Die Meldungen wurden gemäss dem internationalen ABON System klassifiziert. In 27% aller eingegangenen Fälle wurde ein kausaler Zusammenhang zwischen der Impfung und der Impfreaktion als wahrscheinlich (ABON A), in 44% als möglich (ABON B) beurteilt.L’objectif du système de vaccinovigilance en Suisse est l’évaluation et la classification des effets indésirables suspectés signalés en rapport à des médicaments vétérinaires immunologiques, y compris le manque présumé d’efficacité attendue. L’Institut de virologie et d’immunologie (IVI) est l’autorité compétente pour les autorisations de mise sur le marché des médicaments immunologiques vétérinaires en Suisse et est responsable du système de vaccinovigilance. En 2020, 130 déclarations d’effets indésirables ont été reçues (5% de moins par rapport à 2019). Les signalements concernaient principalement les chiens (41%) et les chats (25%) suivis des bovins (18%) et des chevaux (7%). Chez les chiens, ces annonces impliquaient principalement l’application de vaccins combinés contre la maladie de Carré, l’hépatite, la parvovirose et la parainfluenza en combinaison avec la leptospirose, chez les chats contre le coryza et la panleucopénie féline en association avec la leucose féline. Les évaluations de causalité ont été effectuées selon le système international ABON. Dans 27% des cas rapportés, les évaluations de causalité entre la vaccination et la réaction décrite ont été évaluées comme probables (ABON A), dans 44% comme possibles (ABON B).Lo scopo del sistema di notifica di vaccinovigilanza è di identificare e classificare le reazioni avverse di un farmaco che possono sorgere dopo l’uso di medicamenti veterinari (MVet) immunologici in Svizzera. Questo include anche il sospetto di un’insufficiente efficacia dei vaccini. L’Istituto di Virologia e Immunologia (IVI), in qualità di ufficio di omologazione dei Mvet immunologici, è responsabile anche del sistema di notifica di vaccinovigilanza. Nel 2020 sono state registrate 130 notifiche di Mvet immunologici omologati (5% in meno del 2019). Le notifiche riguardavano per la maggior parte piccoli animali: cani (41%) e gatti (25%), seguiti da bovini (18%) e cavalli (7%). Nei cani la maggioranza delle reazioni avverse erano conseguenti all’uso di vaccini contro cimurro, epatite, parvovirosi e parainfluenza in combinazione con la leptospirosi, nei gatti invece le reazioni avverse erano in relazione a vaccini contro la rinite felina e la gastroenterite felina combinata con l’infezione virale della leucemia felina. Le notifiche sono state classificate secondo il sistema internazionale ABON. Nel 27% dei casi inoltrati è stata considerata una relazione causale tra la vaccinazione e la risposta alla vaccinazione come probabile (ABON A), e nel 44% come possibile (ABON B).

Differential diagnosis of muscle pain and weakness is extensive, including neurological, vertebral, arthrogenic, vascular, traumatic, immunological, endocrine, genetic and infectious aetiologies, as well as medication or toxin-related causes. Muscles are highly sensitive to a large number of drugs, especially with high doses. Although many drug classes can cause toxic myopathy, a significant number of cases are caused by lipid-lowering drugs, long-term use of corticosteroids, and, most often, alcohol misuse. Some drug interactions, e.g. those that are metabolised via the enzyme CYP3A4, can increase the serum levels of the drugs and drug-induced toxicity. A careful history of patient's drug and alcohol consumption is therefore vital. Clinical symptoms depend on the drug, dosage and patient's sensitivity. They can vary from asymptomatic increase in serum levels of creatine kinase, mild myalgia and cramps to muscle weakness, rhabdomyolysis, kidney failure and even death. The pathogenesis is often only partially known and multifactorial. Toxic myopathy is often reversible once the drug is discontinued, alternative drug therapy is started or a different dosage regimen is chosen. Complications such as acute kidney failure must be avoided, and analgesic therapy may be indicated.Die Differenzialdiagnose von Muskelschmerzen und Muskelschwäche ist umfangreich und umfasst neurologische, vertebragene, arthrogene, vaskuläre, traumatische, immunologische, endokrine, genetische und infektiöse Ätiologien sowie medikamentöse oder durch Toxine bedingte Ursachen. Die Muskeln reagieren sehr empfindlich auf eine Vielzahl von Arzneistoffen, insbesondere bei hohen Dosen. Obwohl viele Wirkstoffklassen eine toxische Myopathie verursachen können, wird diese vor allem durch Statine, langfristig eingenommene Kortikosteroide und am häufigsten durch Alkohol hervorgerufen. Einige Wechselwirkungen zwischen Arzneimitteln, die z. B. über das Enzym CYP3A4 metabolisiert werden, können die Serumspiegel und damit die Toxizität der Substanzen erhöhen. Eine sorgfältige Anamnese des Medikamenten- und Alkoholkonsums ist daher geboten. Die klinischen Symptome hängen vom Arzneistoff ab, von der Dosierung und von der individuellen Empfindlichkeit. Sie reichen von asymptomatisch erhöhten Kreatinkinase-Serumspiegeln, leichten Muskelschmerzen und Krämpfen bis hin zu Muskelschwäche, Rhabdomyolyse, Nierenversagen oder sogar Tod. Die Pathogenese ist oft nur z. T. bekannt und multifaktoriell. Die toxische Myopathie ist häufig reversibel, sobald das Medikament abgesetzt, eine alternative medikamentöse Therapie gestartet oder ein anderes Dosierungsschema gewählt wird. Ein akutes Nierenversagen muss verhindert werden. Eine analgetische Therapie kann indiziert sein.

Chemosaturation percutaneous hepatic perfusion (CS-PHP) allows selective intrahepatic delivery of high dose cytotoxic melphalan in patients with curatively untreatable liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. Aim of this study was to investigate the response to therapy, survival and safety of the CS-PHP procedure in patients with liver-dominant metastatic uveal melanoma (UM). Overall response rate (ORR) and disease control rate (DCR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median overall survival (mOS), median progression-free survival (mPFS) and hepatic progression-free survival (mhPFS) were analyzed using Kaplan-Meier estimation. Adverse events were evaluated with Common Terminology Criteria for Adverse Events (CTCAE) v5. Overall, 30 patients were treated with 70 CS-PHP in a salvage setting from October 2014 to January 2019. In total, ORR and DCR were 42.3 % and 80.8 %, respectively. Overall, mOS was 12 (95 % confidence interval (CI) 7-15) months, and both, mPFS and mhPFS were 6 months, respectively (95 % CI 4-10; 95 % CI 4-13). Adverse events (AE) most frequently included significant but transient hematologic toxicities (87 % of grade 3/4 thrombocytopenia), less frequent AEs were hepatic injury extending to liver failure (3 %), cardiovascular events including one case of ischemic stroke (3 %). Salvage treatment with CS-PHP is effective in selected patients with UM. The interventional procedure is safe. Serious hepatic and cardiovascular events, although rare, require careful patient selection and should be closely monitored. · CS-PHP is safe for selected patients with liver-dominant metastatic uveal melanoma.. · CS-PHP resulted in hepatic disease control in 80 % of patients.. · Hematologic events following CS-PHP are common but manageable..· Dewald CL, Hinrichs JB, Becker LS et al. Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma. Fortschr Röntgenstr 2021; 193: 928 - 936.ZIEL: Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit. · CS-PHP ist eine sichere Behandlungsform für selektierte Patienten mit hepatisch metastasiertem Aderhautmelanom.. · CS-PHP führte bei 80 % der Patienten zu einer intrahepatischen Krankheitsstabilisierung.. · Hämatologische Nebenwirkungen nach CS-PHP sind häufig, aber therapierbar..· Dewald CL, Hinrichs JB, Becker LS et al. Chemosaturation with Percutaneous Hepatic Perfusion: Outcome and Safety in Patients with Metastasized Uveal Melanoma. Fortschr Röntgenstr 2021; 193: 928 – 936.

Eruptive Epidermoidzysten stellen eine seltene Nebenwirkung von Imiquimod zur Behandlung von Basalzellkarzinomen dar. Bis dato wurden 8 Fälle in der Literatur beschrieben. Wir präsentieren den Fall einer 75-jährigen kaukasischen Patientin mit einem 8‑mal rezidivierten Basalzellkarzinom der Nase. Nach mehrfachen Exzisionen und Therapie mit Vismodegib erhielt die Patientin schließlich Imiquimod 5 % Creme in der Standarddosierung 5‑mal wöchentlich für die Dauer von 6 Wochen. Zwei Monate nach dem Absetzen von Imiquimod zeigten sich eruptive Epidermoidzysten.

Adriamycin (doxorubicin) is a chemical substance in the anthracycline class with a wide range of applications in oncology and hematology. The mechanism of action of Adriamycin is related to formation of irregular bonds between nucleobases of DNA and inhibition of key enzymes of DNA synthesis - topoisomerase I and II as well as to formation of free radicals damaging DNA. A major limitation in the drug use is associated with its adverse effects such as cardiotoxicity and hepatotoxicity. The mechanism of myocardial injury by Adriamycin is linked to an increase in oxidative stress associated with impaired mitochondrial function and structure. Cardiotoxicity of anthracyclines is classified as: acute, chronic or late (delayed). Hepatotoxicity of Adriamycin as a damage of the liver is associated with a dysfunction of this organ. Adriamycin studies have shown increased level of transaminase present in 40% of patients treated with Adriamycin. The state was transient and asymptomatic, returning to the initial level even when treatment continued. Knowledge of cancer diseases contributed to a successive creation of two improved forms of Adriamycin (doxorubicin) – nonpegylated and pegylated formulas of the drug. The mechanism of anticancer effects of liposomal Adriamycin is similar to the mechanism of conventional Adriamycin, but placement of the molecules of active substance in liposomes has significant influence on the distribution of the drug. In order to increase the distribution of the drug, a special form of liposomal Adriamycin has been created by covering the surface of the liposomes with a hydrophilic polymer - (MPEG). This process, known as pegylation, decreases the interactions between the lipid bilayer membrane and the plasma components. Pegylated form of the drug is associated with a higher incidence of acute complications.

The aim of the Vaccinovigilance system is the identification of adverse reactions and rare events after the use of immunological veterinary medicinal products. In the year 2017, 128 reports of adverse reactions following the application of various authorized vaccines were received and evaluated. The notifications were submitted primarily by marketing authorization holders (96) or veterinarians (27) and private persons (5). As in previous years, dogs were involved in most of the adverse effects (55%), followed by cattle (18%) and swine (10%). Unlike the previous years, significantly fewer reports were submitted on cats (8%). The correlation between reaction and vaccination was considered probable in 43% of the - cases.Ziel des Vaccinovigilance-Meldesystems ist die Identifizierung unerwünschter Wirkungen, welche nach einer Anwendung von immunologischen Tierarzneimitteln (TAM) auftreten können. Im Jahr 2017 sind 128 Meldungen von im Handel zugelassenen immunologischen TAM eingereicht worden. Diese wurden entweder von den Zulassungsfirmen (96), praktizierenden Tierärzten (27) oder Privatpersonen (5) eingesandt. Wie in früheren Jahren betrafen die unerwünschten Wirkungen vorwiegend Hunde (55%) gefolgt von Rindern (18%) und Schweinen (10%). Im Gegensatz zu den Vorjahren liegen deutlich weniger Meldungen zu Katzen (8%) vor. In 43% aller eingegangenen Fälle wurde der Zusammenhang zwischen Reaktion und Impfung als wahrscheinlich beurteilt.L’objectif du système d’annonces de vaccinovigilance est d’identifier les effets indésirables pouvant survenir à la suite de l’utilisation de médicaments vétérinaires immunologiques. En 2017, 128 notifications concernant des médicaments vétérinaires immunologiques approuvées commercialement ont été soumises. Elles ont été envoyés soit par les sociétés d’enregistrement (96), les vétérinaires praticiens (27) ou des particuliers (5). Comme les années précédentes, les effets indésirables concernent principalement les chiens (55%), suivis des bovins (18%) et des porcs (10%). Contrairement aux années précédentes, il y a beaucoup moins de rapports sur les chats (8%). Dans 43% des cas, la relation entre la réaction et le vaccin a été jugée probable.Lo scopo del sistema di notifica di vaccinovigilanza è di identificare gli effetti indesiderati che possono sorgere dopo l’uso di medicamenti veterinari (Mvet) immunologici. Nel 2017 sono state presentate 128 notifiche di medicamenti immunologici per uso veterinario approvati commercialmente. Queste notifiche sono state inviate da società di omologazione (96), da veterinari (27) o da privati (5). Come negli anni precedenti, gli effetti indesiderati interessavano principalmente i cani (55%), seguiti dai bovini (18%) e dai suini (10%). Rispetto agli anni passati le segnalazioni per i gatti (8%) sono regredite notevolmente. Nel 43% dei casi ricevuti, la relazione tra la reazione e la vaccinazione è stata valutata come probabile.

Background: Adverse reactions associated with Chinese herbal medicines (CHMs) are usually the result of unpredictable active/toxic ingredients, inaccurate or mistaken beliefs, or poor supervision. The herb that most commonly induces severe adverse effects in Hong Kong and China is aconite root. More than 200 species of Aconitum plants are used for medicinal purposes, with aconite roots producing analgesic, anti-inflammatory, cardiotonic, and anti-tumor effects. The active components are alkaloids; these can be toxic, but CHM processing methods lower their toxicity and increase the pharmacological efficacy. However, aconite poisoning can result from inadequate decoction time or exceeding the recommended dose. Case Report: Here we report the case of a 92-year-old woman who presented with life-threatening bradycardia and hypotension. This started 1 h after she inappropriately consumed a herbal decoction containing Fuzi for mood fluctuation and health maintenance; Fuzi, an aconite root, has known cardiotoxicity. Electrocardiography showed supraventricular abnormalities, including sinus bradycardia and low-amplitude P waves. After an infusion of normal saline and inotropic agents for 25 h, the clinical manifestations subsided, her sinus rhythm returned to normal, and she was discharged. At follow-up 2 weeks later, she was in good health and had ceased taking any CHM. Conclusions: Standardized processing methods, stringent regulations, and cooperation between health professions can ensure medication safety and establish a fully-fledged operating process for these valuable drugs. We hope this report will help establish correct attitudes toward CHM and will assist Traditional Chinese Medicine practitioners to become more familiar with Aconitum plants.

Background: Cough preparations containing aqueous marshmallow root extracts (Althaea officinalis) have a long history as medicinal products in Germany. The aim of the 2 prospective, non-interventional surveys reported here was to create a better documentation of the users' impression of the effectiveness and tolerability, and user satisfaction. Methods: Consumers (n = 822) buying either lozenges or syrup of the aqueous marshmallow root extract STW42 to treat their dry cough were recruited in pharmacies in 2 independently performed surveys. They were asked to fill in a questionnaire covering a treatment duration of 7 days so that the course of symptoms could be documented, and the overall effectiveness, tolerability and satisfaction assessed. Results: This consumer-reported outcome shows that both preparations showed a good effect with respect to the symptomatic treatment of oral or pharyngeal irritation and associated dry cough with a very rapid onset of effects, in the majority of cases within 10 min. The tolerability was very good (with only 3 minor adverse events for the syrup). Conclusion: The results of the surveys justify the long-established use of both marshmallow preparations for symptomatic treatment of dry cough.

Zusammenfassung: Das chronische Schmerzsyndrom des Beckens ("chronic pelvic pain syndrome", CPPS) ist gemäß den Richtlinien der "European Association of Urology" charakterisiert als ein nicht-maligner Schmerz, der in Bezug auf die Strukturen des weiblichen oder männlichen Beckens über einen Zeitraum von mindestens 6Monaten wahrgenommen wird, ohne dass eine Infektion oder offensichtliche anderweitige Pathologie vorliegt. Das CPPS beeinträchtigt die Lebensqualität von Millionen von Menschen weltweit und hat einen ähnlich großen Einfluss wie andere chronische Krankheiten, z.B. Diabetes mellitus, Morbus Crohn oder kongestive Herzinsuffizienz. Trotz mehrerer etablierter Erstlinientherapien stellt die Behandlung des CPPS eine große Herausforderung dar, da viele Patienten therapierefraktär bleiben. Unkonventionelle Behandlungsmethoden wie Neurostimulation, Neuromodulation und Akupunktur können beim CPPS eine ausgezeichnete Wirkung zeigen und haben ein vorteilhaftes Nebenwirkungsprofil. So sollten diese vielversprechenden Therapieverfahren im klinischen Alltag vermehrt eingesetzt werden

Adverse drug reactions are among the leading causes of death. Pharmacovigilance aims to monitor drugs after they have been released to the market in order to detect potential risks. Data sources commonly used to this end are spontaneous reports sent in by doctors or pharmaceutical companies. Reports alone are rather limited when it comes to detecting potential health risks. Routine statutory health insurance data, however, are a richer source since they not only provide a detailed picture of the patients’ wellbeing over time, but also contain information on concomitant medication and comorbidities. To take advantage of their potential and to increase drug safety, we will further develop statistical methods that have shown their merit in other fields as a source of inspiration. A plethora of methods have been proposed over the years for spontaneous reporting data: a comprehensive comparison of these methods and their potential use for longitudinal data should be explored. In addition, we show how methods from machine learning could aid in identifying rare risks. We discuss these so-called enrichment analyses and how utilizing pharmaceutical similarities between drugs and similarities between comorbidities could help to construct risk profiles of the patients prone to experience an adverse drug event. Summarizing these methods will further push drug safety research based on healthcare claim data from German health insurances which form, due to their size, longitudinal coverage, and timeliness, an excellent basis for investigating adverse effects of drugs. Unerwünschte Arzneimittelwirkungen zählen zu den häufigen Todesursachen. Aufgabe der Pharmakovigilanz ist es, Arzneimittel nach der Zulassung zu überwachen, um so mögliche Risiken aufzudecken. Zu diesem Zweck werden typischerweise Spontanmelderegister genutzt, an die u. a. Ärzte und pharmazeutische Industrie Berichte über unerwünschte Arzneimittelwirkungen (UAW) melden. Diese Register sind jedoch nur begrenzt geeignet, um potenzielle Sicherheitsrisiken zu identifizieren. Eine andere, möglicherweise informativere Datenquelle sind Abrechnungsdaten der gesetzlichen Krankenversicherungen (GKV), die nicht nur den Gesundheitszustand eines Patienten im Längsschnitt erfassen, sondern auch Informationen zu Begleitmedikationen und Komorbiditäten bereitstellen. Um deren Potenzial nutzen zu können und so zur Verbesserung der Arzneimittelsicherheit beizutragen, sollen statistische Methoden weiterentwickelt werden, die sich in anderen Anwendungsgebieten bewährt haben. So steht eine große Bandbreite von Methoden für die Auswertung von Spontanmeldedaten zur Verfügung: Diese sollen zunächst umfassend verglichen und anschließend hinsichtlich ihrer Nutzbarkeit für longitudinale Daten erschlossen werden. Des Weiteren wird aufgezeigt, wie maschinelle Lernverfahren helfen könnten, seltene Risiken zu identifizieren. Zudem werden sogenannte Enrichment-Analysen eingesetzt, mit denen pharmakologische Arzneimittelgruppen und verwandte Komorbiditäten zusammengefasst werden können, um vulnerable Bevölkerungsgruppen zu identifizieren. Insgesamt werden diese Methoden die Arzneimittelrisikoforschung anhand von GKV-Routinedaten vorantreiben, die aufgrund ihres Umfangs, der longitudinalen Erfassung sowie ihrer Aktualität eine vielversprechende Datenquelle bieten, um UAWs aufzudecken.

Low back pain is common. In the acute (duration

Background and aims: Glut1 Deficiency (Glut1D) is caused by impaired glucose transport into brain. The resulting epileptic encephalopathy and movement disorders can be treated effectively by high-fat carbohydrate-restricted ketogenic diet therapies (KDT) mimicking fasting and providing ketones as an alternative cerebral fuel. Recently 6-24 months follow-ups of epileptic patients reported elevated blood lipids and intima thickening of the carotid artery raising concerns about potential cardiovascular risks by KDT. To clarify potential cardiovascular risks we performed a prospective 10 year follow up of 10 Glut1D patients.Methods: Between August 2001 and January 2016 we enrolled Glut1D patients on KDT at two hospitals in Germany in this prospective, multicenter case series. The minimal follow up was 10 years. Standard deviation scores (SDS) of body mass index (BMI), total cholesterol (TC), HDL-/LDL cholesterol, and triglycerides (TG) before initiation of KDT were compared with respective values at 6 months, 2, 5 years, and 10 years after initiation. After 10 years on KDT cardiovascular risk, assessed by BMI, carotid intima-media thickness (CIMT) measurement, and blood pressure, was compared to a healthy reference population (n = 550).Results: Baseline and 10 year follow-up investigations were available for 10 individuals with Glut1D on KDT. After two years on KDT BMI increased significantly, while total cholesterol, HDL-cholesterol, and LDL-cholesterol decreased. Within 3-5 years on KDT these differences disappeared, and after 10 years blood lipid parameters reflected the situation at initiation of KDT. Prior to KDT one child had dyslipidaemia, but no child after 10 years on KDT. No significant differences were observed with respect to BMI SDS (p = 0.26), CIMT (p = 0.63) or systolic and diastolic blood pressure (SDS p = 0.11 and p = 037, respectively) in Glut1D children treated with KDT for at least 10 years compared to healthy controls.Conclusions: In contrast to previous short-term reports on adverse effects of KDT, 10-year follow-up did not identify cardiovascular risks of dietary treatment for Glut1D. (C) 2017 The Authors. Published by Elsevier Ltd.

Background Interleukin 22 promotes epidermal hyperplasia and inhibits skin barrier function. Objective Evaluate interleukin 22 blockade in adults with moderate-to-severe atopic dermatitis (AD). Methods We performed a randomized, double-blind, placebo-controlled trial with intravenous fezakinumab monotherapy every 2 weeks for 10 weeks, with follow-up assessments until 20 weeks. The change in SCOring AD (SCORAD) score from baseline at 12 weeks served as the primary end point. Results At 12 weeks, the mean declines in SCORAD for the entire study population were 13.8 ± 2.7 in the fezakinumab arm and 8.0 ± 3.1 in the placebo arm (P = .134). In the severe AD patient subset (with a baseline SCORAD of ≥50), SCORAD decline was significantly stronger in the drug-treated patients than placebo-treated patients at 12 weeks (21.6 ± 3.8 vs 9.6 ± 4.2, P = .029) and 20 weeks (27.4 ± 3.9 vs 11.5 ± 5.1, P = .010). At 12 weeks, improvements in body surface area involvement in the entire population were significantly stronger in the drug-treated than placebo-treated patients (12.4% ± 2.4 vs 6.2% ± 2.7; P = .009), and in the severe AD subset, the decline in Investigator Global Assessment was significantly higher in the drug-treated than placebo-treated patients (0.7 ± 0.2 vs 0.3 ± 0.1; P = .034). All scores showed progressive improvements after last dosing (10 weeks) until end of study (20 weeks). Common adverse events were upper respiratory tract infections. Limitations The limited sample size and lack of assessment with Eczema Area and Severity Index and a pruritus numerical rating scale were limiting factors. Significance was primarily obtained in severe AD. Conclusion Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

In the year 2016, 107 reports of adverse reactions following the application of various authorized vaccines were received and evaluated by the IVI (Institute of Virology and Immunology). The notifications were submitted primarily by marketing authorization holders (81) or veterinarians and private persons (26). The aim of the Vigilance System is the identification of rare events to assess the individual risks of the vaccine application. During the last year, the correlation between reaction and vaccination was considered probable in 34% of the cases. As in previous years, companion animals were involved in most of the adverse effects (48% dogs, 21% cats), followed by cattle (13%). In dogs, approximately half of the reports concern the combination vaccines against distemper, hepatitis, parvovirus, parainfluenza and leptospirosis. The reported symptoms, such as itching, facial edema, acute vomiting and diarrhea, usually indicated forms of hypersensitivity. In cats, apathy was most frequently observed regardless of the vaccination.Im Jahr 2016 wurden im IVI (Institut für Virologie und Immunologie) 107 Meldungen zu Reaktionen nach Anwendung zugelassener immunologischer Tierarzneimittel (TAM) eingereicht und ausgewertet. Die Meldungen wurden primär von Vertriebsfirmen (81) oder praktizierenden Tierärzten und Privatpersonen (26) übermittelt. Das Ziel des Vigilance-Meldesystems ist die Identifizierung von seltenen Ereignissen, um die einzelnen Risiken der Impfstoffanwendung einzuschätzen. Im vergangenen Jahr wurden bei 34% der eingegangenen Fälle den Zusammenhang zwischen Reaktion und Impfung als wahrscheinlich beurteilt. Wie in früheren Jahren betrafen die unerwünschten Wirkungen vorwiegend Kleintiere (48% Hunde, 21% Katzen) gefolgt von Rindern (13%). Beim Hund handelte es sich in rund der Hälfte der Meldungen um die Kombinationsimpfstoffe gegen Staupe, Hepatitis, Parvovirose, Parainfluenza und Leptospirose. Die gemeldeten Symptome wie Juckreiz, Gesichtsödem, akutes Erbrechen und Durchfall deuteten meist auf Formen von Überempfindlichkeit hin. Bei Katzen wurde unabhängig von der verabreichten Impfung am häufigsten Apathie beobachtet.En 2016, 107 annonces de réactions après l’utilisation de médicaments immunologiques enregistrés ont été faites et analysées à l’IVI (Institut de Virologie et d’Immunologie). Ces annonces ont été faites primairement par les firmes distribuant ces produits (81) ou par les vétérinaires praticiens et des personnes privées (26). Le but du système d’annonce est d’identifier les événements exceptionnels afin d’estimer les risques individuels de l’utilisation de vaccins. L’année dernière, 34% des cas annoncés ont été considérés comme vraisemblablement en rapport avec la vaccination. Comme les années précédentes, les effets indésirables concernaient principalement les petits animaux (chiens 48%, chats 21%) suivis par les bovins (13%). Chez le chien, il s’agissait pour environ une moitié d’annonces en relation avec des vaccins combinés contre la maladie de Carré, l’hépatite, la parvovirose, la parainfluenza et la leptospirose. Les symptômes annoncés comme des démangeaisons, un oedème de la face, des vomissements aigus ou de la diarrhée indiquaient la plupart du temps des formes d’hypersensibilité. Chez les chats, indépendamment du vaccin appliqué, c’est l’apathie qui était le plus souvent rapportée.Nel 2016 sono state inoltrate all’IVI (Istituto di virologia e di immunologia) 107 notifiche per reazioni occorse dopo l’impiego di medicamenti veterinari (MVet) immunologici omologati. Le notifiche inoltrate provenivano principalmente da distributori (81) seguiti da studi veterinari e da privati (26). Scopo di questo sistema di notifiche di vigilanza è l’identificazione di reazioni rare in modo da poter valutare i singoli rischi legati all’uso del vaccino. Durante lo scorso anno, nel 34% dei casi notificati la relazione tra reazione e vaccinazione è stata valutata come probabile. Come negli anni passati gli effetti indesiderati sopravvenivano in particolare nei piccoli animali (48% cani, 21% gatti) seguiti dai bovini (13%). Circa la metà delle notifiche riguardavano la vaccinazione combinata di cimurro, epatite, parvovirosi, parainfluenza e leptospirosi nei cani. I sintomi più significativi di ipersensibilità erano prurito, edemi del muso, vomiti acuti e diarrea. Nei gatti si è potuto osservare, indipendentemente dal vaccino somministrato, dell’apatia.

Background: Disorders of the respiratory transition at birth are major reasons for neonates being admitted to intensive care units and separated from their mothers. This has potential long-lasting consequences for the mother-infant interaction as well as the long-term development of the child. There is an urgent need for effective preventive and therapeutic measures for this frequent disorder. Case Report: We report the cases of 2 newborn infants with respiratory transitional disorder treated off-label with the anthroposophic medicament Pulmo/Vivianit comp. based on pathophysiological considerations and on particular parental request. In both cases, an immediate and sustainable response could be documented without adverse effects. Conclusion: This new therapeutic approach merits further attention in clinical research but cannot be recommended for routine practice before more high-level evidence is available.

Background: The passion flower dried ethanolic extract investigated in this non-interventional study has well-documented calmative effects and good tolerability. We investigated the effects of this extract on the stress resistance (resilience) and quality of life (QoL) of patients suffering from nervous restlessness. The addiction potential of the drug and the course of symptoms were also evaluated. Methods: Adult patients aged ≤ 95 years with the diagnosis ‘nervous restlessness' were treated for 12 weeks with a dried ethanolic extract of passion flower (Passiflora incarnata L.). Standardized questionnaires were used to evaluate the resilience (RS-13), QoL (EQ-5D including EQ-VAS), and the addiction potential (BDEPQ). Results: After 12 weeks of treatment, significant (p < 0.001) improvements were measured in the patients' resilience (RS-13: from 52.1 to 67.7 points) and QoL (EQ-VAS: from 47.9 to 75.0 points). Also, the mean BDEPQ score was significantly (p < 0.001) reduced (from 23.0 to 19.3 points). The mean values of all accompanying symptoms (inner restlessness, sleep disturbance, exhaustion, fear, lack of concentration, transpiration, nausea, trembling, and palpitation) improved significantly (p < 0.001). Tolerability of treatment was rated as ‘very good' or ‘good' by the majority of the patients. Three cases of mild adverse events (tiredness) were reported. Conclusion: The passion flower extract investigated in the present study appears to be effective in improving resilience and QoL in patients suffering from nervous restlessness and is well tolerated.

Neurodermatitis (better called atopic dermatitis or atopic eczema, AE) is a chronic inflammatory skin disorder, which often appears already in early childhood and may be associated with a reduced quality of life for affected children. Research in adult patients has shown that AE often is associated with sleep problems. There is, however, little published information regarding this point in childhood. The main target of this paper is to provide an overview of the current evidence for the relation between sleep and AE in early childhood. A systematic literature research was conducted to identify relevant studies. The seven studies detected for this age group show that similar to adults, children with AE have increased sleep problems. They experience reduced sleep efficiency and sleep duration with an increased sleep fragmentation and prolonged sleep onset latency. Moreover, the severity of the disease directly influences the sleep quality. In general, there are few studies, which address the described relations in childhood. Therefore, more systematic research is required in this area. It is important to diagnose and treat chronic skin diseases such as AE early in childhood also to prevent sleep problems and related adverse effects on children's psychological well-being and on future development of children.

Among the various contaminants, the group of natural plant-derived substances in the modern food chain has been generating increasing concern in recent years. The adverse effects encountered may be diverse and pose risks of acute, subchronic or chronic toxicity. The underlying mechanisms of toxicity may be thresholded or be based on interactions with DNA, as for genotoxic carcinogens, for which the existence of a threshold cannot be assumed. This article gives an overview of the major plant-derived contaminants of present concern in the modern food chain and describes their mode of action and adverse effects.

Background Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. Patients and methods Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. Results A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54–83] and 68% (95% CI 53–81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. Conclusions No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. ClinicalTrials.gov NCT01005199.

Summary Background Given that there is no standard systemic treatment for children and adolescents with plaque psoriasis, this non-interventional, multicenter, retrospective study collected data on the efficacy and safety of long-term treatment with fumaric acid esters (FAEs) in this particular patient group. Patients and methods In patients younger than 18 years of age at the start of FAE treatment, data on efficacy and safety was retrospectively collected for at least 36 months. Results Data from 127 patients (aged 6–17 years) was collected for treatment durations of up to 60 months. Physician's Global Assessment, Psoriasis Area and Severity Index, and Body Surface Area showed marked improvement in the first six months. After 36 months, these parameters had, on average, improved by up to two-thirds of baseline values. Thirty-seven patients experienced at least one adverse event (AE), which was FAE-related in 36 individuals. Three AEs (proteinuria (one case), flushing (two cases)) persisted during the observation period while on treatment. Fifteen AEs led to the discontinuation of therapy; nearly all of these cases were related to gastrointestinal disorders. Conclusions The KIDS FUTURE study – for the first time – included a larger population of children and adolescents with psoriasis who were treated with FAEs. The data obtained suggests that long-term FAE therapy in this patient group may be effective and safe. The results are currently being verified in an ongoing clinical study.

Die Prävalenz der behavioralen und psychologischen Symptome der Demenz (BPSD) ist sehr hoch bei Betroffenen mit einer Demenz-Erkrankung. In der Pathogenese der BPSD sind Veränderungen in verschiedenen Neurotransmittersystemen involviert. Diese Symptome komplizieren die Therapie und haben schwerwiegende Folgen. Die Therapie der BPSD ist durch Multimorbidität und Polypharmazie erschwert und bedarf kontinuierlicher klinischer Beobachtung der Patienten. Nicht-pharmakologische Interventionen müssen die Therapie der ersten Wahl sein bevor Medikation eingesetzt wird und die medikamentöse Behandlung begleiten. Unterschiedliche nicht-pharmakologische Therapie-Optionen sind vorhanden und werden in den Therapieempfehlungen der Schweizerischen Fachgesellschaften diskutiert. Pharmakologische Interventionen haben bei dementen Patienten oft schwere Nebenwirkungen. Ihr Einsatz muss zeitlich und quantitativ limitiert erfolgen. Eine kritische Bestandsaufnahme der pharmakologischen Therapie-Optionen ist notwendig.

Continuous positive airway pressure (CPAP) ist eine in der Neonatologie häufig genutzte Form der Atemunterstützung. Es existieren verschiedene Möglichkeiten CPAP zu applizieren. In der Klinik für Neonatologie an der Charité Berlin Campus Mitte (CCM) werden seit 2003 sowohl das mono- als auch das binasale System eingesetzt. Es sind eine Reihe an Nebenwirkungen bekannt, die unter CPAP-Therapie auftreten können. Dazu zählen Nasenverletzungen, gastrointestinale Nebenwirkungen, Infektionen und als indirekte Nebenwirkung die Reintubation. Ziel dieser Arbeit war es, zu untersuchen, ob sich die Inzidenz an Nebenwirkungen bei bi- und mononasaler Applikation unterscheidet und ob sich die Anzahl an Nebenwirkungen mit zunehmender Erfahrung über die Jahre verändert. Außerdem wurde untersucht, welche sonstigen Risikofaktoren die Entstehung von Nebenwirkungen begünstigen. Methodik: Eingeschlossen in die Studie waren Neugeborene mit einem Geburtsgewicht, Continuous positive airway pressure (CPAP) is a common therapy for newborns with respiratory distress syndrome. CPAP can be applied mononasal via nasopharyngeal tubes or binasal via prongs. In addition to mononasal CPAP, binasal CPAP was introduced to the neonatal intensive care unit of Charité Medical Center Berlin Campus Mitte (CCM) in 2003. Adverse effects to CPAP therapy include nasal erythema, skin erosions and necrosis, CPAP-Belly, infection and reintubation. We aimed to (a) investigate if side effects to CPAP differed between binasal CPAP and mononasal CPAP, (b) if risk factors for adverse effects could be identified, and (c) if training staff on the use of binasal CPAP decreased side effects. Methods: Neonates born between 2003 and 2009 in CCM with birth weight (BW) ≤ 1500 g who received mononasal, binasal or combined CPAP were included in the study. Side effects were identified from the patient notes. For this retrospective study, the side effects were subdivided into study periods (2003 – 2004, 2005 – 2007, 2008 – 2009) and application methods (mono-, binasal, combined) Results: 413 Very low birth weight infants (VLBWI) with median (IQR) gestational age 28.6 weeks (26.7 – 30.4) and median (IQR) BW 990 g (780 – 1280) were studied. There were no significant differences in adverse effects per patients between mono- or binasal CPAP application. Compared to mononasal CPAP, infants on binasal CPAP had more nasal erythema (68 % vs. 37 %, p

Background: Pneumatic pulsation therapy may combine the effects of cupping therapy and massage. This study investigated the effect of pneumatic pulsation therapy on chronic neck pain compared to standard medical care. Methods: 50 patients (79.15% female; 46.17 ± 12.21 years) with chronic nonspecific neck pain were randomized to treatment group (TG; n = 25) or control group (CG; n = 25). The TG received 5 pneumatic pulsation treatments over a period of 2 weeks utilizing a mechanical device. Treatment was applied as a combination of moving and stationary pulsating cupping. Main outcome measure was pain intensity in pain diaries (numerical rating scale). Secondary outcome measures included functional disability (NDI), quality of life (SF-36), and pain at motion. Sensory thresholds, including pressure pain threshold, were measured at pain-related sites. Results: After the intervention, significant group differences occurred regarding pain intensity (baseline: 4.12 ± 1.45 in TG and 4.20 ± 1.57 in CG; post-intervention: 2.72 ± 1.62 in TG and 4.44 ± 1.96 in CG; analysis of covariance: p = 0.001), NDI (baseline: 25.92 ± 8.23 and 29.83; post-intervention: 20.44 ± 10.17 and 28.83; p = 0.025), and physical quality of life (baseline: 43.85 ± 7.65 and 41.66 ± 7.09; post-intervention: 47.60 ± 7.93 and 40.49 ± 8.03; p = 0.002). Further significant group differences were found for pain at motion (p = 0.004) and pressure pain threshold (p = 0.002). No serious adverse events were reported. Conclusion: Pneumatic pulsation therapy appears to be a safe and effective method to relieve pain and to improve function and quality of life in patients with chronic neck pain.

Blutungsereignisse, Arzneimittelwechselwirkungen und Therapieversagen sind relevante Risiken einer Therapie mit Plättchenaggregationshemmern. Die neuen Substanzen Prasugrel und Ticagrelor sind stärker wirksam als Clopidogrel und senken ischämische Ereignisse bei Patienten mit akutem Koronarsyndrom effizienter. Sie erhöhen allerdings potenziell auch die Blutungsraten. Eine Therapie mit Clopidogrel birgt das Risiko einer Therapieresistenz bei bis zu 20% der Patienten, die u. a. auf genetischen Polymorphismen und Arzneimittelinteraktionen beruht. Für Prasugrel und Ticagrelor bestehen keine Hinweise, dass genetische Polymorphismen die Wirksamkeit beeinflussen. In Risikosituationen muss die Therapie jedoch sorgfältig angepasst werden, um unerwünschte Wirkungen zu minimieren: So wird bei Patienten >75 Jahre und/oder einem Körpergewicht

Summary Background: Monotherapy with TNF-α inhibitors does not always produce a sufficient response in psoriasis patients. Combinations of TNF-α antagonists such as adalimumab with systemic antipsoriatic therapies such as methotrexate are not approved for use in psoriasis, and the published data are scarce. Patients and methods: The charts of 39 psoriasis patients from 6 dermatology departments were reviewed retrospectively. All patients were given adalimumbab with another systemic antipsoriatic drug. Results: Combination therapy with methotrexate was most common (n = 32), followed by acitretin (n = 4) and cyclosporine (n = 3). Combination therapy with methotrexate lasted 10.8 ± 11.2 months (mean), with cyclosporine for 6.8 ± 3.3 months, and with acitretin 12.9 ± 12.4 months. Combinations were effective in the majority of patients: 30/39 (76.9 %) had a good (n = 9) or excellent (n = 21) response. Two patients had a moderate response and 7 patients had a poor response and were switched to another treatment. Overall, safety was very good. Eighteen patients experienced 24 adverse events; none was severe and/or required hospitalization. Of these, 10/24 adverse events were infections, most often infections of the upper respiratory tract (n = 5), bronchitis (n = 2), and influenza (n = 1). Conclusions: Combinations of adalimumab with traditional systemic antipsoriatic treatments offer a promising method for managing severe or recalcitrant psoriasis. More data are needed to determine the long-term safety and efficacy of these combinations.

Hintergrund: Manuelle Medizin (MM) hat einen hohen Stellenwert in der ambulanten Versorgung von Beschwerden des Bewegungsapparats. Trotz Vorliegen zahlreicher randomisiert-kontrollierter Studien und Meta-Analysen im Bereich der MM ist die Bewertung aufgrund verschiedener Schulen und Techniken teilweise schwierig. Ziel der vorliegenden Studie war es, bei der großen Beliebtheit dieser Therapieform die Motivation und Erfahrungen von Ärzten bezüglich der Anwendung von MM in der täglichen Praxis zu ergründen. Methoden: Im Rahmen eines qualitativen Forschungsansatzes wurden 21 semi-strukturierte, telefonische Einzelinterviews mit Ärzten mit der Zusatzqualifikation für MM durchgeführt. Die Rekrutierung erfolgte über die Deutsche Gesellschaft für Manuelle Medizin sowie über einen Verteiler von Ärzten, die an Forschungsfragen zu MM interessiert sind. Die Interviews wurden aufgezeichnet, transkribiert und, unterstützt durch das Computerprogramm Atlas.ti, inhaltsanalytisch ausgewertet. Ergebnisse: Als Hauptmotivation für die Anwendung von MM wurde eine Stärkung der Arzt-Patienten-Beziehung durch einen unmittelbaren Zugang zum Patienten mit schnellen Behandlungserfolgen geschildert. Weitere beschriebene Aspekte sind die Einfachheit der Methode, die Unabhängigkeit von räumlichen oder apparativen Gegebenheiten und die damit verbundenen niedrigen Kosten. Positive, als direkt die Zufriedenheit mit MM beeinflussend beschriebene Faktoren sind die Möglichkeit, eigene Fähigkeiten zu nutzen, den Patienten zu einem gesunden Lebensstil zu motivieren und die Dankbarkeit des Patienten. Als Aspekte, welche die Zufriedenheit negativ beeinflussen, wurden die schlechte Vergütung der Therapie, die unklare Evidenzlage, die Anwendung bei oft selbstlimitierenden Krankheiten und das Risiko schwerwiegender Nebenwirkungen sowie die Gefahr einer iatrogenen Fixierung genannt. Schlussfolgerungen: Die Ergebnisse dieser Studie zeigen eine große Bandbreite von zumeist positiven Sichtweisen und Erfahrungen von Ärzten bei der Anwendung von MM. Dem Wunsch nach dem unmittelbar heilenden Handeln scheint durch MM begegnet zu werden. Die MM scheint als willkommene Abwechslung zur alltäglichen Berufsausübung zu dienen, die als distanziert wahrgenommen wird.

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is generally observed only after long term exposure to propylthiouracil or very rarely with the thioimidazoles. The teratogenic risk of the thioimidazoles is somewhat higher (Aplasia cutis congenita), that is why one generally recommends preferring propylthiouracil during pregnancy. During breast feeding both, thioimidazoles or propylthiouracil, may be administered. Nowadays, perchlorate is only used short term in case of latent hyperthyroidism before administering iodine-containing contrast agents. Therefore, the known side effects, which usually are only observed after long term treatment, are not an issue any more.

Unhindered sexuality plays an important role in the quality of life and this also holds true for patients with psychiatric illnesses. Knowledge concerning the complex neuronal and endocrine control mechanisms of sexual function reveals areas of possible dysfunction caused by the interactions between the control system, psychiatric drugs and addictive psychoactive substances. The differentiation of the cause of the dysfunction between being caused by the underlying illness and caused by other factors is difficult in practice. Both classical tri-cyclic antidepressants and selective serotonin uptake inhibitors can frequently cause adverse effects in multiple dimensions of sexual function. This same is true for neuroleptics, whereby the differentiation between symptoms of schizophrenia and side-effects from the medication can make an evaluation difficult. The medication-based strategy used to treat opiate dependency by administration of methadone causes sexual dysfunction in many cases. The consideration of medication-induced sexual dysfunction has a great importance with regard to compliance. Possible solutions can be modification of the medication regime, additional medication, e.g. partial antagonists and PD5 inhibitors, as well as dysfunction-specific psychotherapy and psychoeducation.

There is no cure for hereditary angioedema (HAE). Therapeutic approaches consist of symptomatic therapy for acute attacks, short-term prophylaxis before surgery, and long-term prophylaxis for those with frequent and severe attacks. In Germany, C1-INH concentrate and icatibant are licensed for acute therapy. C1-INH concentrate, which is obtained from human plasma, is administered intravenously to restore the deficient C1-INH activity. This therapy, which has been available for decades, is effective and well-tolerated. Batch documentation is required by German law. The synthetic decapeptide icatibant is administered subcutaneously. It competes with bradykinin, the responsible inducer of edema formation, for binding to the bradykinin B2 receptor. Icatibant is also effective and well-tolerated, even on repeated administration. An additional human C1-inhibitor, a recombinant human C1-inhibitor and the recombinant inhibitor of kallikrein ecallantide are currently under development. There are no licensed treatment options available in Germany for long- and short-term prophylaxis. Androgen derivatives are established in long-term prophylaxis. However, they are associated with many adverse effects, some of which are severe. Many drug interactions also limit their use. They are contraindicated in pregnancy, lactation, for children and in cases of prostate cancer. Antifibrinolytics have fewer adverse effects but are also less effective than androgens. They are contraindicated in thromboembolic disease and impaired vision. If androgen therapy has too negative an effect on quality of life, it may be worth reducing the dose or discontinuing therapy entirely and treating attacks with acute therapy.

The use of biologics has rapidly expanded since the introduction of the first diagnostic antibodies; they are now widely employed in oncology, autoimmune disorders, inflammatory diseases and transplantation medicine. Their widespread use has resulted in an increase in adverse drug reactions. Adverse effects result from both direct pharmacological actions and immunological actions, as well as through induction of a specific immune response. The nomenclature, particularly of the monoclonal antibodies, identifies the target structure and organ as well as the species of origin, which then helps predict their effects and antigenic properties. Depending on the extent of foreign protein, anti-allotypic or anti-idiotypic antibodies with or without neutralizing properties may be induced. Adverse drug reactions from biologics often depend on the target and may be explained by activation or inhibition of particular cytokine pathways. Adverse drug reactions are classified by their pathomechanism, which enhances understanding of the pathogenesis and facilitates both allergologic diagnostic measures and planning of premedication in future treatments. This review emphasizes immunostimulatory and hypersensitivity reactions.

Der Morbus Wilson ist eine seltene vererbte Störung des Kupferstoffwechsels, die unbehandelt innert wenigen Jahren nach Symptombeginn zum Tod führt. Die rechtzeitige Diagnose ermöglicht eine Behandlung, die Organschäden vorbeugt und zu einer normalen Lebenserwartung führt. Kupferablagerungen in Leber und Hirn können zu oft wenig spezifischen hepatischen, neurologischen und psychiatrischen Symptomen wie Ikterus, Tremor, Koordinationsstörungen und Depressionen führen. Bei unerklärten hepatischen, neurologischen und psychiatrischen Symptomen bei Patienten unter 40 Jahren muss immer an einen Morbus Wilson gedacht werden. Die Abklärung erfolgt mittels Bestimmung der Kupferausscheidung im 24-Stunden-Urin und allenfalls weiterer Untersuchungen. Nach Diagnosestellung eines Morbus Wilson muss eine lebenslange entkupfernde Behandlung eingeleitet werden. Dabei sind regelmässige klinische Kontrollen zur Erkennung von Komplikationen, unerwünschten Medikamentenwirkungen und Compliance-Problemen notwendig.

By the distribution of a questionnaire between all Swiss cattle practitioners it was possible to investigate abortions and other animal health problems related to Bluetongue vaccination 2009. The questionnaire helped to obtain plausibility and timely relation of the reported disorders. 58 abortions in cattle and different herd health problems could be examined. Because there is no possibility to show that a vaccination itself leads to an abortion the results of proven causes of abortions prior and after Bluetongue vaccination were compared regarding their diagnosis. Due to the fact that diagnosis and solving rate of abortions did not differ before and after vaccination, the vaccination itself cannot be responsible for the abortions. Evaluation of different herd health problems showed that Bluetongue vaccination was not responsible for these disorders which often existed already prior to vaccination. Herd health problems generally have multifactorial causes what makes it difficult to asses the effect of Bluetongue vaccination in some cases.

Background: Difficulties in recruiting patients for clinical trials lead to increasing costs, and prolonged implementation of evidences into medical practice. Knowledge about motivation and barriers in potential participants would be helpful to develop successful recruitment strategies. Currently, no systematic research of determining factors affecting the decision to participate in clinical studies is available from German samples. □ Methods: After been given details about a potential participation in a clinical or diagnostic study in nine study centers, patients were recruited for an additional structured questionnaire survey concerning motivation and barriers to participation. □ Results: 62 patients were included into the survey. 95.1% did not have any experience with clinical studies before. 66.1% met the physician explaining the study and asking for informed consent for the first time. Despite this, 96.6% judged the physician to be competent. Family and friends were important for decision-making about the participation in a study. Gender was only of marginal influence. The majority of patients (91.4%) expected advantages of the study for their own. 88% of the patients denominated potential advantages for other patients as an additional motivator. The possibility of adverse events was inferior for patients in decision-making about participation in a clinical trial. □ Conclusion: Physicians recruiting patients for clinical studies should be well prepared about details of the study and should have adequate time for an introductory conversation in a quiet environment. Including relatives into the introductory conversation may enhance the motivation and therefore the success of recruitment. Potential advantages of a participation for the own treatment and additionally for other patients should be highlighted. Possible side effects should be explained in a realistic manner.

Summary Background: Postherpetic neuralgia is a frequent adverse event in herpes zoster patients and difficult to treat. Conventional analgetic therapy often fails to reduce the burning pain transmitted by unmyelinated nerve fibers. These nerves express cannabinoid receptors which exert a role in modulation of nociceptive symptoms. Therefore, topical therapy with cannabinoid receptor agonist seems likely to suppress local burning pain. Patients and methods: In an open-labeled trial, 8 patients with facial postherpetic neuralgia received a cream containing the cannabinoid receptor agonist N-palmitoylethanolamine. The course of symptoms was scored with the visual analog scale. Results: 5 of 8 patients (62.5 %) experienced a mean pain reduction of 87.8 %. Therapy was tolerated by all patients. No unpleasant sensations or adverse events occurred. Conclusions: Topical cannabinoid receptor agonists are an effective and well-tolerated adjuvant therapy option in postherpetic neuralgia.

Summary Herbal treatments are becoming increasingly popular, and are often used for internal as well as dermatological conditions, both externally as well as orally. The prevalence of contact sensitization against several plants especially of the Compositae family is quite high in Europe. Sensitization seems to occur relatively frequent with a few species such as arnica, elecampane and tea tree (oil), and occurs rarely with the majority. Testing for plant allergy is problematic because of the limited number of commercially available standardized patch test substances and the danger of active sensitization when testing with plants, parts thereof, or individual extracts. Knowledge about the allergic potential of plants is limited.Although plants are regarded as critical allergens by dermatologists, the number of reported cases of contact dermatitis is relatively small.Many widely used substances are not licensed as drugs or cosmet-ics.While the positive effects are frequently questionable or limited, the side effects are often more evident. Adverse effects of herbal medicines are an important albeit neglected subject in dermatology, which deserves further systematic investigation.

Summary Background: Vitiligo is an acquired, pigmentary skin disorder which is disfiguring and difficult to treat. In an earlier open label study in adult patients with vitiligo, pimecrolimus cream 1% was reported to have similar efficacy as clobetasol propionate 0.05%. We performed a double-blind, intrapatient comparison of pimecrolimus cream 1% with placebo cream. Patients and methods: Twenty adult Caucasians with symmetrical vitiligo (predominantly on extremities, none in the face) were treated b.i.d. for 6 months left/right with pimecrolimus/vehicle (N = 10) or vehicle/pimecrolimus (N = 10), respectively. Primary efficacy endpoint was the size of the target lesion at month 6 and secondary efficacy endpoint was re-pigmentation. Results: Treatment with pimecrolimus cream 1% or vehicle resulted in no significant change in mean target lesion size. Modest repigmentation (1–25%) was noted with pimecrolimus at month 2 in 12 of 17 patients (vehicle: 9 of 17 patients). Afterwards, the number of patients who experienced an improvement of pigmentation steadily decreased (3 of 14 patients with pimecrolimus and 2 of 14 with placebo at month 6).Treatment was well tolerated.There were no treatment-related adverse events, no induction of skin atrophy nor any other application site side effects. Conclusion: In this group of adult patients with symmetrical vitiligo, treatment of body lesions (except face) with pimecrolimus cream 1% could not be shown to be effective.

The extensive and sometimes indiscriminate use of antibiotics sometimes without strict indications has led to increases in both bacterial resistance and sensitization of patients. Systemic antibiotics in skin infections are indicated when a severe local infection occurs which spreads into the surrounding tissue or when there are signs of systemic infection. There are special indications in patients with peripheral arterial occlusive disease,diabetes or immunosuppression. Topical use of antibiotics should be abandoned and replaced by antiseptics. The beta-lactam antibiotics are the antibiotics of first choice for many skin infections. They are usually effective, have a well-defined profile of adverse events and most are affordable. Penicillin G or V are the first line treatment for erysipelas. Infections with Staphylococcus aureus are usually treated with isoxazolyl penicillins or second generation cephalosporins. In mixed infections in patients with diabetes or peripheral arterial occlusive disease,the treatment of choice is metronidazole plus beta-lactam-/beta-lactamase inhibitor antibiotics, but quinolones or second generation cephalosporins can also be used, once again with metronidazole. The aim of this review is to define the indications for antibiotics in dermatology, to highlight their modes of action and adverse effects and to make suggestions for rational antibiotic therapy in cutaneous infections frequently encountered in the practice of dermatology.

Systemic administration of analgesics is still the most widely used method for postoperative pain therapy. In the concept of balanced or multimodal analgesia non-steroidal anti-inflammatory drugs (NSAIDs) play an important role besides opioids. Their analgesic effect is based on a diminished prostaglandin synthesis by inhibition of the cyclooxygenase (COX) enzyme in the arachidonic acid metabolism. The discovery of at least two COX isoenzymes led to the development of selective COX-2 inhibitors that were hypothesized to have an improved risk-benefit-ratio compared with conventional NSAIDs. In this context the analgesic efficacy and adverse effects of selective COX-2 inhibitors for postoperative pain therapy were evaluated by reviewing the pertinent literature.

Olanzapine is an effective and safe antipsychotic drug. Its pharmacokinetic properties are comparable to those of classical antipsychotics. Oxidative processes are mediated by the cytochrome P450 isoenzyme CYP1A2 and to a minor degree by CYP2D6. Olanzapine's main route of metabolism is by glucuronidation. Therapeutic doses result in a wide variability of serum levels; dose and serum concentration are linearly correlated. Smoking and carbamazepine induce cytochrome P450 isoenzymes and thus decrease olanzapine serum levels. Inhibition of CYP1A2 by fluvoxamine yields increased concentrations; however, clinically relevant CYP2D6 inhibition was observed only in combination with additional disposition factors, such as female gender or old age. As a rule dose adjustment is not necessary but moderate renal or hepatic impairment calls for control of serum levels to provide maximal safety during olanzapine therapy. Therapeutic drug monitoring (TDM) and toxicology studies are carried out by HPLC methods using UV or MS detection. The optimal therapeutic range of olanzapine serum levels is 20 to 40 ng/ml. Concentrations of 80 ng/ml are considered threshold for the occurrence of adverse events; however, toxicological studies showed that postmortem plasma levels are higher than antemortem levels. Lethality of high olanzapine was only observed in combination with other drugs. Moderate increases of prolactin levels were detected during administration of olanzapine. In relation to olanzapine therapy, several case reports of neutropenia and agranulocytosis appeared in the literature. Weight gain in olanzapine-treated patients does not correlate with serum levels. Olanzapine response is augmented when patients' serum levels are titrated to 20 to 40 ng/ml thereby minimizing the occurrence of side effects, thus TDM is recommended for patients treated with olanzapine.

Eine Hypokaliämie tritt mit einer dosisabhängigen Häufigkeit von 2–11% bei niedrigen bis moderaten Dosen von Thiazid- und Schleifendiuretika auf. Eine zusätzliche Hypomagnesiämie besteht in etwa 40% der Patienten mit Hypokaliämie. Insbesondere früher verwendete Hochdosisschemata in der diuretischen Therapie bei Hypertonie und Herzinsuffizienz gingen mit vermehrten ventrikulären Herzrhythmusstörungen und plötzlichem Herztod einher. Niedrigdosierte Thiaziddiuretika gegebenenfalls in Kombination mit einem kaliumsparenden Diuretikum haben diese schweren Nebenwirkungen nicht mehr, sondern bieten im Gegenteil sogar deutliche Verbesserungen bezüglich des Überlebens und der Verminderung kardiovaskulärer Ereignisse beim hypertensiven Patienten. Die für die Behandlung der schweren Herzinsuffizienz häufig notwendigen höheren Diuretikadosen gehen heutzutage in aller Regel nicht mehr mit einer Hypokaliämie/Hypomagnesiämie einher bei nahezu immer gleichzeitig bestehender Therapie mit einem ACE-Hemmer und niedrigdosiertem Spironolacton.

Systemic analgesia is used in obstetrics to alleviate the pain in labour and to prevent adverse effects on the fetus due to maternal pain and stress and subsequent complications such as prolonged labour. To supplement psychological support tranquillizers such as diazepam are useful in allaying anxiety and increasing patients' acceptance of labour. Possible side-effects include neonatal hypothermia and poor muscle tone of the newborn when large doses are given. When pain is more severe opioids should be administered, since less potent analgesics cannot provide adequate pain relief in obstetrics. The most important side effect of opioids is the dose-related respiratory depression, which can be harmful to the neonate. Therefore, large doses (>150 mg pethidine) should be avoided. However, even moderate doses (100 mg pethidine) may adversely affect infant neurobehaviour. Thus, in many cases adequate pain relief afforded to parturients by systemic analgesia may result in altered adaptive functions of the newborn. This makes it reasonable to consider alternative methods, including epidural anaesthesia, which is highly effective and fairly unproblematic. Drug administration in the management of labour pain can be recommended if only small doses are needed and in parturients who refuse regional anaesthesia or for whom it is contraindicated or not available.