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The present article addresses clinical challenges associated with the choice of the anticoagulant agent, the definition of the duration of anticoagulant treatment and the assessment of the risk-to-benefit ratio of prolonged anticoagulation for patients with pulmonary embolism (PE).Anticoagulation is performed with unfractionated heparin (UFH) in hemodynamically unstable patients and with low molecular weight heparins (LWMH) or fondaparinux in normotensive patients. In patients with high or intermediate clinical probability of pulmonary embolism, anticoagulation should be initiated without delay while awaiting the results of diagnostic tests. LMWH and fondaparinux are preferred over UFH in the initial anticoagulation of PE since they are associated with a lower risk of bleeding.All patients with PE require therapeutic anticoagulation for at least three months. The current 2019 guidelines of the European Society of Cardiology (ESC) recommend that all eligible patients should be treated with a non-vitamin K antagonist oral anticoagulant (NOAC) in preference to a vitamin K antagonist (VKA). In patients with active cancer, Apixaban, Edoxaban and Rivaroxaban are effective alternatives to treatment with LMWH.The decision on the duration of anticoagulation should consider both, the individual risk of PE recurrence and the individual risk of bleeding. The risk for recurrent PE after discontinuation of treatment is related to the features of the index PE event. While patients with a strong transient risk factor have a low risk of recurrence and anticoagulation can be discontinued after three months, patients with strong persistent risk factor (such as active cancer) have a high risk of recurrence and thus should receive anticoagulant treatment of indefinite duration. Given the favourable safety profile of NOACs (especially if a reduced dosage of Apixaban or Rivaroxaban is initiated after at least six months of therapeutic anticoagulation), extended oral anticoagulation of indefinite duration should be considered for all patients with intermediate risk of recurrence.

Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011.The European guidelines presented here were prepared by a panel of experts nominated by the European Dermatology Forum (EDF) and European Academy of Dermatology and Venereology (EADV). The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN.The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.

The central circadian pacemaker in the suprachiasmatic nucleus and interaction of clock genes with the hypothalamus pituitary adrenal axis are responsible for very distinct cortisol concentrations. Unphysiologically high doses of glucocorticoids that do not follow the circadian rhythm lead to increased rates of morbidity, mortality and reduced quality of life.Does a switch to modified-release hydrocortisone in multimorbid elderly patients offer benefits compared to a conventional therapy regime?Evaluation, analysis and discussion of statistics, recent research results and expert advice.Overdosage and unphysiological timing of cortisol administration result in higher incidences of obesity, hypertension, hyperglycemia, coronary heart disease and cardiac events. Body weight, body mass index and HbA1c decline with Plenadren® (Shire Pharmaceuticals Ireland Limited, Dublin, Ireland) treatment compared to conventional therapy. CD16+ natural killer cells and natural killer cytotoxycity are reduced, and the incidence of respiratory-tract infections is increased, with conventional therapy compared to Plenadren®. Cortisol influences sleep pattern and sleep quality by its circadian secretion.Novel modified-release hydrocortisone preparations offer diverse benefits with regard to their effect on metabolism, cardiovascular risk, immunity and sleep, which might be beneficial in particular in multimorbid elderly.

Glucocorticoids (GC) have been proven drug substances in rheumatology for more than 70 years. They act very rapidly in high doses through membrane stabilizing effects. Genomic therapeutic effects of GC even in very low doses are mainly due to inhibition of the functions of the transcription factor nuclear factor kappa B (NFkB), which promotes the synthesis of proinflammatory mediators, adhesion molecules and other regulatory proteins. Indications for the use of GC in high doses in rheumatology are always given when a life-threatening, dangerous or treatment-resistant situation is involved. Lower doses of GC, usually administered orally, are particularly used in rheumatoid arthritis, vasculitis and collagenosis. In clinical practice the general principle is to use the smallest possible effective dose of GC for the shortest possible time in order to achieve the therapeutic effect of GC without running the risk of unacceptably severe side effects.

Dyspnea is a leading symptom in COPD. Bronchodilators (long acting anticholinergics and long acting beta agonists) are the mainstay of medical treatment. Non pharmacological therapies like pulmonary rehabilitation, long-term oxygen therapy or lung volume reduction can help to further improve dyspnea. Nevertheless, patients with advanced disease may develop refractory dyspnea. Randomized controlled trials demonstrated that the palliative treatment with low-dose systemic opioids is an effective treatment option in these patients. A low starting dose (e. g. 1.0 mg morphine, immediate release) is recommended. Subsequent doses are titrated to achieve the lowest effective dose based on whether dyspnea relief has been achieved and whether any side effects have developed. This low-dose opioid treatment has been demonstrated to be safe for symptom reduction in severe COPD and is not associated with increased hospital admissions or deaths. Physicians should offer a trial of low-dose oral opioids to patients with refractory dyspnea that affects their daily activities and quality of life.

The present article is a recommendation of the Austrian Diabetes Association for the practical use of insulin in type 2 diabetes, including the various insulin regimens.

Aims Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG). Methods and results In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose–response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P Conclusion We show for the first time that genetic factors underlie the variability of cardiac electrical response to SCB. PRSBrS, family history, and a baseline ECG can predict the development of a diagnostic drug-induced Type I BrS ECG with clinically relevant accuracy. These findings could lead to the use of PRS in the diagnosis of BrS and, if confirmed in population studies, to identify patients at risk for toxicity when given SCB.

Cause of Death: 'Intoxication' - a Matter of the Concentration? Abstract. Elucidation of the cause of death is one of the main reasons for medico-legal investigations. In clinical toxicology, the severity of a given poisoning is typically assessed with the blood concentration of a pharmacologically or toxicologically active compound. Such an interpretation proves to be difficult or even impossible in postmortem toxicology. Numerous biochemical and biological processes beginning immediately after death may render the calculated drug concentration unreliable. Concentrations obtained from postmortem samples do not necessarily reflect the blood concentration at the time of death. A prediction if and to what extent such postmortem changes might have occurred is still impossible for individual cases. Interpretation therefore needs to be done with care, considering case circumstances and all available information.Zusammenfassung. Die Beantwortung der Frage nach der Todesursache stellt eine wesentliche Indikation für eine rechtsmedizinische Untersuchung dar. Zur Abklärung einer möglichen Intoxikation wird bei Lebenden üblicherweise die im Blut gemessene Konzentration einer pharmakologisch/toxikologisch aktiven Substanz beurteilt. Eine analoge Beurteilung ist postmortal oft nicht so einfach möglich. Bereits unmittelbar nach dem Todeseintritt kommt es zu einer Reihe biochemischer Prozesse, welche die Blutkonzentration massiv verändern können und die Interpretation erschweren oder sogar verunmöglichen. Die Blutkonzentration postmortal widerspiegelt somit mit hoher Wahrscheinlichkeit nicht jene im Zeitpunkt des Todes. Eine Vorhersage, ob und in welchem Ausmass solche Veränderungen im Einzelfall aufgetreten sind, ist bis heute nicht möglich. Interpretationen müssen daher mit entsprechender Vorsicht und unter Berücksichtigung aller vorhandenen Fallumstände erfolgen.

Safinamide (XadagoProspective, observational study in unselected patients in line with safinamide product specifications.Of the 299 patients included (65.9 % males, age 72.7 ± 9.0 years, duration of disease 7.8 ± 5.9 years), at the beginning of the documentation 229 patients (81.2 %) received L-dopa, 108 (39.3 %) combination drugs containing L-dopa, 172 (59.3 %) a dopamine agonist and 23 (8.3 %) a COMT inhibitor. Of these, 203 patients were followed-up over a period of 6 months. The MDS-UPDRS Part III score for motor symptoms decreased from a baseline value of 48.2 ± 22.1 points by 6.8 ± 14.5 points at the end of the study. The Non-Motor Symptoms Scale score indicating the presence or absence of motor symptoms decreased from a baseline value of 57.6 ± 42.1 by 9.3 ± 2.1 points, the Abnormal Involuntary Movement Score from 4.6 ± 5.8 points by 0.9 ± 2.7 points.The Parkinson's Disease Score (PDQ-8) for assessing quality of life decreased from a baseline value of 39.4 ± 18.2 points by 4.3 ± 13.7 points, reflecting an improvement. In total, 300 adverse events were classified as related to safinamide in 132 patients (44.1 %). Fifty-three events were serious (in 15 patients; 5 %). Seventy-four patients (24.7 %) discontinued safinamide therapy because of adverse drug reactions.Safinamide therapy improved the motor and non-motor symptoms as well as the quality of life in PD. Most patients tolerated the therapy well. The only side effects that occurred are those described in the patient information leaflet.ZIEL: Safinamid (XadagoProspektive Beobachtungsstudie bei unselektierten Patienten unter Beachtung der Produktspezifikationen mit deskriptiver Auswertung.Von den eingeschlossenen 299 Patienten (65,9 % Männer, Alter 72,7 ± 9,0 Jahre, Krankheitsdauer 7,8 ± 5,9 Jahre) erhielten zu Dokumentationsbeginn 229 Patienten L-Dopa, 108 ein L-Dopa enthaltendes Kombinationsmedikament, 172 einen Dopaminagonisten und 23 einen COMT-Hemmer. 203 Patienten wurden über 6 Monate nachbeobachtet. Der MDS-UPDRS Part III Score für motorische Symptome verringerte sich von einem Ausgangswert von 48,2 ± 22,1 Punkten zum Studienende um 6,8 ± 14,5 Punkte, der Non-Motor Symptoms Scale Score für das Vorhandensein bzw. die Schwere von nicht-motorischen Symptomen von 57,6 ± 42,1 Punkten um 9,3 ± 2,1 Punkte, und der Abnormal Involuntary Movement Score von 4,6 ± 5,8 Punkten um 0,9 ± 2,7 Punkte. Der Parkinson’s Disease Score (PDQ-8) zur Beurteilung der Lebensqualität nahm als Ausdruck einer Verbesserung von 39,4 ± 18,2 Punkten bei Beobachtungsbeginn um 4,3 ± 13,7 Punkte ab. Insgesamt wurden 300 unerwünschte Ereignisse (UAW) bei 132 Patienten, davon 53 SAEs bei 15 Patienten, als mit Safinamid in Zusammenhang stehend klassifiziert. Wegen UAW beendeten 74 Patienten die Safinamid-Therapie vorzeitig.Unter Safinamid-Therapie verbesserten sich die motorischen und nicht-motorischen Symptome sowie die Lebensqualität. Die meisten Patienten vertrugen die Therapie gut; es traten nur Nebenwirkungen auf, die bereits in der Patienteninformation gelistet waren.

Since March 2016, a new treatment option for adult patients with narcolepsy – with or without cataplexy – has been granted marketing authorization in Europe. Pitolisant (Wakix®) is an inverse agonst at the histamine-3 (H3) receptor. In clinical studies, tests for measurement of wakefulness and attention, pitolisant showed significantly better results in comparison with placebo and similar results in comparison with modafinil. Pitolisant is well tolerated. Postmarketing analyses have to collect data about the long-term safety of pitolisant when used in a real-life setting.

CME: Adrenal Insufficiency Abstract. Patients suffering from adrenal insufficiency (AI) often present with unspecific symptoms. Therefore, the diagnosis of AI, a potential life-threatening condition, can be missed. Lab tests, especially the ACTH-stimulation test, play a crucial role in the diagnosis of AI. According to the different etiologies, AI can be grouped into a primary (adrenal) or central (hypothalamic or pituitary, respectively) form. However, the most common cause is the treatment with glucocorticoids, which can lead to central AI. Patients suffering from AI are given hydrocortisone. The chronic replacement dose should be as low as possible, in acute situations, a rapid and sufficient increase of the hydrocortisone dose is necessary to prevent adrenal crisis. Replacement therapy with fludrocortisone is only necessary in patients with primary AI.Zusammenfassung. Die Nebennierenrindeninsuffizienz (NNR-IS) kann im klinischen Alltag aufgrund der häufig unspezifischen Symptome verpasst werden und ist bei fehlender Behandlung eine potenziell lebensbedrohende Erkrankung. Die Labordiagnostik spielt eine zentrale Rolle, wobei häufig ein ACTH-Stimulationstest zur Sicherung der Diagnose notwendig ist. Die NNR-IS kann je nach Ätiologie in eine primäre (adrenale) oder eine zentrale (hypothalamisch bzw. hypophysäre) Form eingeteilt werden. Die häufigste Ursache einer NNR-IS überhaupt ist die medikamentöse Behandlung mit Glukokortikoiden, die zur zentralen NNR-IS führt. Die Ersatztherapie erfolgt mit Hydrocortison. Die Glukokortikoiddosis in der chronischen Ersatztherapie muss so hoch wie nötig, aber so tief wie möglich gewählt werden. In Akutsituationen muss jedoch eine zügige und genügend hohe Steigerung der Hydrocortisondosis erfolgen. Damit wird die Entwicklung einer Addison-Krise verhindert. Die Ersatztherapie mit Fludrocortison ist nur bei einer primären Nebennierenrindeninsuffizienz notwendig.

Combination therapies such as Dara-Rd and Dara-Vd show significantly higher survival rates after 12 months than the respective therapies without Daratumumab. The initial infusion of Daratumumab is associated with a high incidence of IRR. Dosage and speed of infusion of Daratumumab have to be strictly controlled. Any suspicion of even low IRR requires corrections. Concomitant medication before and after Daratumumab administration is required. For this purpose, various preparations have been tested in everyday clinical practice. Eight hours of infusion may be required. This does not only overwhelm the patient, but also the most ambulant structures. The split-dose concept means to divide the dose into infusions on different days. Again, the dosage is crucial for good compatibility.

USP2a is a deubiquitinating protease that rescues its target proteins from destruction by the proteasome by reversing the process of protein ubiquitination. USP2a shows oncogenic properties in vivo and has been found to be a specific activator of cyclin D1. Many types of cancers are addicted to cyclin D1 expression. Targeting USP2a is a promising strategy for cancer therapy but little progress has been made in the field of inhibition of USP2a. Using NMR-based fragment screening and biophysical binding assays, we have discovered small molecules that bind to USP2a. Iterations of fragment combination and structure-driven design identified two 5-(2-thienyl)-3-isoxazoles as the inhibitors of the USP2a-ubiquitin protein-protein interaction. The affinity of these molecules for the catalytic domain of USP2a parallels their ability to interfere with USP2a binding to ubiquitin in vitro. Altogether, our results establish the 5-(2-thienyl)-3-isoxazole pharmacophore as an attractive starting point for lead optimization.

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.

At the end of August 2017 the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) published new joint guidelines for the treatment of valvular heart disease. These guidelines incorporate the scientific progress since the last version of the guidelines published in 2012. This article reviews current guideline recommendations for antiplatelet and anticoagulative therapy after surgical/interventional treatment of the aortic and mitral valves and discusses the underlying scientific evidence.

NATüRLICHER VERLAUF DER ICVT: Die isolierte Wadenvenenthrombose hat ein bewiesenermaßen geringeres Schadenspotenzial für den Patienten als eine proximale Beinvenenthrombose. EVIDENZ FüR DIE THERAPIE: Für die Gesamtheit aller Fälle von ICVT wächst die Evidenz, dass die Antikoagulation weitere VTE-Ereignisse in der Häufigkeit reduziert. Die „number needed to treat“ ist jedoch bedeutend höher als für die proximale TVT. Es gibt eine Patientengruppe von ICVT mit so niedrigem Risiko, dass sie keiner Behandlung bedarf. Ihre Charakterisierung ist wenig datenbasiert. Aktuelle Leitlinien lassen einen Korridor, Patienten mit ICVT nicht zu antikoagulieren.

Rivaroxaban, ein oraler Faktor Xa Inhibitor, ist zur Behandlung venöser Thromboembolien zugelassen. Es ist unklar, ob die Dosis bei einem Body-Mass-Index (BMI) 40 kg/m Die 45-jährige Patientin wurde wegen zunehmender Atemnot stationär aufgenommen. In der Anamnese fand sich eine Pulmonalembolie vor 30 Monaten, eine Faktor V Leiden-Mutation und mehrere stationäre Aufenthalte wegen Dermatomykosen. Die Patientin stand unter einer oralen Antikoagulationsbehandlung mit Rivaroxaban 20 mg. Sechs Monate vor der Aufnahme hatte die Patientin wegen eines zahnärztlichen Eingriffs Rivaroxaban pausiert und eine Rezidiv-Pulmonalembolie erlitten. Im Status finden sich eine morbide Adipositas mit einem BMI von 59,3 kg/m Nach Einleitung einer Therapie mit niedermolekularem Heparin besserte sich die Atemnot. In den folgenden Tagen wurde eine Therapie mit Phenprocoumon begonnen und die Patientin nach 7 Tagen entlassen. Es lässt sich mit hoher Wahrscheinlichkeit vermuten, dass die Pulmonalembolie zu einem Zeitpunkt aufgetreten ist, in dem die Rivaroxaban-Plasmakonzentration in einem Bereich lag, der als therapeutisch angenommen wird. Da es nur wenige Daten über den Einsatz von Rivaroxaban und anderen nicht Vitamin-K-Antagonisten (NOAKs) bei Patienten mit morbider Adipositas gibt sollten die Empfehlungen der „International Society for Thrombosis and Haemostasis” befolgt werden: Rivaroxaban und andere NOAKs sollen bei Patienten mit einem BMI 40 kg/m

Due to their unique therapeutic effects and high efficacy, lithium salts are recommended in guidelines, particularly for the treatment of mood disorders; however, despite the therapeutic efficacy lithium treatment is underutilized in the treatment of these disorders. The therapeutic efficacy of lithium is contrasted by a narrow therapeutic range and a potential risk of intoxication, which is why close drug monitoring is necessary during lithium treatment. Furthermore, lithium therapy requires well-founded knowledge about patient selection with respect to approved areas of administration and indications. This review article summarizes clinically relevant knowledge of lithium treatment to improve treatment of patients with mood disorders and to increase patient safety when using lithium.

Topical therapy is an important domain in the treatment of dermatological diseases in the 21st century. Because multiresistant bacteria are becoming an increasing issue in medical care of chronic diseases, it is important to develop appropriate therapeutic management for acute and chronic dermatoses. The current discussion about the skin microbiota shows the importance of preserving the resident skin flora. There is a need for alternatives to topical antibiotics, e. g. topical antiseptics, which should be safe, fast, and effective but not allergenic or toxic. Even with frequent and prolonged application it is important that they do not develop a resistance. This article focusses on the use of antiseptics for medical indications. Mechanisms of action, tolerability, maximum concentrations, and possible contraindications are discussed and examples of extemporaneous antiseptic preparations are provided.

A young male with schizophrenia, dependence syndrome (multiple drug use) and a severe depressive episode develops a serotonin syndrome with Sertraline and Ziprasidone. Making the correct diagnosis, although potentially challenging, remains vital.Ein junger Patient mit paranoider Schizophrenie, Abhängigkeitserkrankung und schwerer depressiver Episode entwickelt ein serotonerges Syndrom während einer Kombinationsbehandlung mit Sertralin und Ziprasidon. Die korrekte diagnostische Einordnung der klinischen Symptome ist, obwohl häufig schwierig, von größter Bedeutung.

Amiodarone has multiple and complex electrophysiological effects that render it a very effective antiarrhythmic drug for the treatment of both, supraventricular and ventricular arrhythmias. Proarrhythmic effects of amiodarone in patients with structural heart disease are rare. However, extracardiac adverse effects occurring in association with amiodarone treatment are frequent and feared. These adverse effects have usually been related to total amiodarone exposure (i. e., dose and duration of treatment). Parallel to a more frequent use of lower amiodarone maintenance doses (100-200 mg/day), the incidence of severe unwanted extracardiac side effects has decreased. High-dose maintenance regiments (daily dose ≥300 mg) are usually obsolete. This paper discusses recommendations regarding the monitoring of cardiac and extracardiac side effects of amiodarone. They need to be regarded by physicians using amiodarone to ensure long-term safety of amiodarone therapy.

In patients with keratoconus, a progressive, ectatic disease of the cornea, the shape of the cornea is continuously changing leading to a reduction in visual acuity by progressive myopia and more and more (irregular) astigmatism. The symptomatic treatment consists of the prescription of glasses or special gas-permeable rigid contact lenses. Corneal tomography is generally used for diagnosis. After initial diagnosis of keratoconus, regular tomographic follow-ups should be performed. If clinically significant progression is found and confirmed by repeated measurements, riboflavin UVA collagen crosslinking should be offered to the patients. The aim of riboflavin UVA collagen crosslinking is to halt the progression of the disease to avoid further complications. The therapeutic principle is a combined effect of the photosensitizer riboflavin and UVA light. This stiffening effect of the corneal tissue halts the progression of keratoconus. The efficacy of this treatment has been demonstrated in various randomized, controlled trials.

With the recent approval of the fourth direct non vitamin K dependent oral anticoagulant (NOAC) edoxaban the range of available NOACs for the treatment of venous thromboembolism (VTE) has expanded. Shortly thereafter, two updated guidelines for the prevention and treatment of VTE have been published. In these NOACs are listed as equal anticoagulants to low-molecular weight heparin (LMWH), or fondaparinux (FDX), and VKA for the initial or maintenance treatment of VTE. All NOACs are approved for the maintenance therapy after VTE and two NOACs (rivaroxaban and apixaban) for the initial treatment in addition in an increased dose.NOACs differ in their pharmacodynamic and pharmacokinetic properties. In patients with renal insufficiency the dose of all NOACs should be reduced similarly to NMH/FDX. In contrast to VKAs, bridging with NOACs in case of surgical interventions is generally dispensable. Similar to NMHs or FPX renal function and individual bleeding risk dependent dose intermission is generally sufficient. Conventional coagulation parameters like aPTT and INR are not suitable for the monitoring of NOACs. Only in seldom cases, laboratory monitoring with use of adjusted anti-Xa testing or diluted thrombin time (dabigatran) may be helpful.Mit der kürzlich erfolgten Zulassung des vierten direkten, neuen nicht-Vitamin-K-abhängigen oralen Antikoagulans (NOAK) Edoxaban hat sich die Palette der verfügbaren NOAKs zur Therapie der venösen Thromboembolie (VTE) erweitert. Kurz danach sind zwei aktualisierte Leitlinien zur Prophylaxe und Therapie der VTE veröffentlicht worden, in denen NOAKs als gleichwertige Antikoagulanzien zu niedermolekularem Heparin (NMH), Fondaparinux (FDX) und VKA gelistet sind. Alle NOAKs sind für die Erhaltungstherapie nach VTE verfügbar. Darüber hinaus sind zwei NOAKs in erhöhter Dosis auch für die Initialtherapie (Rivaroxaban und Apixaban) zugelassen.Zwischen den einzelnen NOAKs gibt es pharmakokinetische und pharmakodynamische Unterschiede. Wie bei NMH/FDX muss bei allen NOAKs die Dosis bei relevanter Niereninsuffizienz verringert werden. Ein Bridging im Falle operativer Eingriffe ist dagegen – anders als bei VKA – generell nicht notwendig. Eine Dosispause, deren Dauer von der Nierenfunktion und dem individuellen Blutungsrisiko abhängt, ist, wie bei NMH bzw. FPX, in der Regel ausreichend. Die üblichen Gerinnungsparameter aPTT und INR sind für ein Monitoring ungeeignet. Ein Labormonitoring ist bei Xabanen mittels adjustierten Anti-Xa-Testen, bei Dabigatran mittels der verdünnten Thrombinzeit nur in Ausnahmesituationen, z. B. bei individuell stark erhöhtem Blutungsrisiko oder Fehleinnahmeverdacht, hilfreich.

Für die Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) stehen inzwischen mehrere moderne Wirkstoffe zur Verfügung. Sie verdrängen zunehmend die aufgrund mangelnder Alternativen lange Jahre üblichen sekundären Hormonmanipulationen, denn neuere Substanzen konnten - im Gegensatz zu den konventionellen antihormonellen Therapien - das Überleben in Phase-III-Studien verlängern. So ist der Beginn der mCRPC-Therapie gemäß Leitlinie der European Association of Urology in den letzten Jahren im Krankheitsverlauf nach vorne gerückt. Für den Androgen-Biosynthese-Inhibitor Abirateronacetat, einen dieser modernen Wirkstoffe, liefern mehrere Analysen zusätzliche Hinweise, wann die Behandlung begonnen werden könnte.

Abirateronacetat, das in Kombination mit Prednison/Prednisolon verabreicht wird, spielt eine wichtige Rolle in der Therapie des metastasierten kastrationsresistenten Prostatakarzinoms. Im Folgenden wurden besondere Aspekte der Therapie im klinischen Alltag zusammengestellt. Sie betreffen unter anderem die Dosierung - auch vor dem Hintergrund der Markteinführung einer neuen Formulierung von Abirateronacetat. Hinzu kommt die Verträglichkeit, vor allem in Bezug auf kardiovaskuläre und Kortikoid-bedingte Nebenwirkungen. Des Weiteren werden Kriterien genannt, nach denen die Therapie nicht zu früh umgestellt werden sollte.

A precondition for the successful treatment of headaches is the correct headache diagnosis. Triptans are effective for attack treatment of migraine and cluster headache. However, there are not effective for the treatment of tension-type headache. For the prevention of frequent episodic migraine betablockers, flunarizine, topiramate and amitriptyline are recommended. For the prevention of chronic migraine evidence is only available for onabotulinumtoxinA and topiramate. For prophylactic treatment of tension-type headaches tricyclic antidepressants are used. In cluster headache verapamil (in combination with steroids) is the most frequently used prophylactic agent. This article focusses on the current acute and prophylactic treatment of common headache syndromes.

Critically ill patients need fast, effective and safe pharmacotherapy. The pharmacokinetics and pharmacodynamics of the administered drugs are influenced by numerous individual conditions. Genetic factors mainly determines drug metabolism. However, therapeutic decisions are not yet guided by genetic analyses. In elderly patients, the volume of distribution can be altered and renal elimination may be delayed. Drug-drug interactions involving current medications can increase the incidence of adverse effects from treatment in the intensive care unit. In early severe sepsis, plasma levels of water-soluble drugs can be decreased because of enhanced volume of distribution and increased renal clearance. Later on, drug elimination can be impaired by deterioration of liver and renal function. Furthermore, the pharmacokinetic effects of continuous renal replacement therapy have to be considered. Plasma levels of critically ill patients show increased variability in comparison with healthy subjects or other patient groups. The therapeutic effect of antibiotics and of many other drugs cannot be assessed immediately. As dosage of these medications cannot be guided by their clinical efficacy, insufficient exposure or overdosage accompanied by toxic side effects may result. Standard dose recommendations that were developed in healthy volunteers or noncritically ill patients must be adapted to individual conditions and requirements of critically ill patients.

Since the 1960s many substance classes have been introduced for treatment of idiopathic Parkinson's disease. The most important and effective medication is levodopa (L-dopa) always in combination with a decarboxylase inhibitor. In addition, dopamine agonists, monoamine oxidase B (MAO-B) inhibitors, catechol-o-methyltransferase (COMT) inhibitors, N‑methyl-D-aspartate (NMDA) antagonists and very rarely anticholinergics are administered depending on the motor symptoms, age and a multitude of other factors. Fortunately, within the substance classes there are various preparations, which also have different effects. In order that the advantages of the individual medications can be exploited and undesired effects and interactions can be avoided, one must come to terms with the complex data and the pharmacology of the medication. In addition important aspects are interactions and reciprocal actions. In the foreseeable future, different substance classes are to be expected.

Various hair-related diseases, systemic dermatoses as well as parasitic diseases are treated via topical application of active substances. The density of hair follicles and the consequential special conditions for diffusion require specific galenic concepts that can vary considerably depending on the respective therapeutic purpose. Both the physicochemical properties of the active ingredient and the nature of the application area must be considered when choosing an appropriate galenic base. Highly relevant here are hairiness, scarring, hyperkeratosis and exoserosis. Low-viscosity bases and foams are often preferred because of their good spreadability. Packages with nozzle tip or comb-shaped dispensers are user-friendly and can significantly enhance patient adherence to topical treatment.

Urologic tumors are frequently treated by multimodal therapeutic strategies with the consequence of an increasing number of adverse events. The most common chemotherapy-induced side effects are neutropenia, stomatitis, mucositis, diarrhea, and emesis. The efficacy of tumor therapy can be improved by good prophylaxis and standardized management of side effects.

Interventions of acute and chronic pain treatment are associated with risks. Therefore, it is important to know about treatment side effects in order to avoid unnecessary complications and therapy interruption. This knowledge, however, is not to prevent/abandon this treatment altogether. Rather, it is intended to use pain treatment interventions rationally. The following article is to deepen the knowledge of unintended effects of analgetic treatments. Moreover, it will help find an optimal pain therapy in terms of efficacy and tolerable risks as well as limitations. Nonopiates have organ toxic side effects. It is imperative to observe the maximum daily dose and comorbidity. Opioids can have either central or peripheral side effects. Patients suffer, among others, from addiction, breath depression, and tolerance as well as from obstipation, concentration disorders, and an increased risk of falling. Psychiatric drugs, corticosteroids, ketamine, bisphosphonates, and lidocaine are co-analgetics. Besides adverse effects connected to their specific substances, these drugs have partially additive effects on complications of classic analgetics (e. g., gastrointestinal ulceration, renal insufficiency, constipation, and concentration deficits). Invasive procedures (such as epidural catheter) call for an interdisciplinary collaboration. To know about unintended effects helps to avoid dramatic complications (e. g., paraplegia). A sufficient pain therapy, therefore, is more than sufficient analgesia. It also includes the reduction of side effects and complications.

Androgen deprivation is still standard therapy for prostate cancer, either as primary androgen deprivation therapy or with the use of secondary hormonal drugs including abiraterone and enzalutamide. However, especially the clinically occult side effects like metabolic changes or cardiovascular complications and effects on the psyche of the patient are often not recognized in daily practice. Active monitoring of such side effects is essential for prevention and early intervention. In addition, the efficacy of androgen deprivation therapies is limited by primary and secondary resistance. The underlying molecular mechanism including splice variants of the androgen receptor in contrast to mutations are usually reversible and should be regarded as a sign of efficacy of the current treatment. Therefore, the clever, timely use of androgen deprivation or even the use of a bipolar androgen therapy should enable reversal of resistance to again render tumor cells sensitive to androgen-deprivation therapy.

After immune checkpoint inhibitor therapy was approved for renal cell carcinoma last year, this new immune therapy has spread to urology. Further approvals (atezolizumab, nivolumab, pembrolizumab) are expected in 2017 for metastatic urothelial carcinoma that has progressed following treatment with platinum-based chemotherapy. With expanding use of immune checkpoint inhibitors, experience in diagnosing and managing immune-mediated adverse events increases. Although of low incidence, grade 3/4 toxicities play a central role. Organs most common for immune-mediated adverse events are skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis), and endocrine organs (hyper-, hypothyroidism and hypophysitis). Diagnostic workup includes routine laboratory tests (including liver function tests) and may be supplemented with hormone values. In cases of pneumonitis or hypophysitis, imaging (high-resolution CT, MRI) can confirm diagnoses. Immune-mediated toxicities are treated with therapy interruption and administration of corticosteroids (and in individual cases additional immunosuppression). Dose modification is not intended!