Augmentation in restless legs syndrome is associated with low ferritin

BACKGROUND AND PURPOSE: Augmentation is a major problem with dopaminergic therapy for restless legs syndrome (RLS), and predictors of augmentation have not yet been identified. We aimed to analyze the relationship between baseline ferritin level and occurrence of augmentation in a retrospective analysis of a prospective double-blind trial of cabergoline versus levodopa on augmentation in RLS. PATIENTS AND METHODS: Patients who experienced augmentation were compared to patients who did not experience augmentation. RESULTS: Augmentation symptoms causing premature discontinuation from the study or which were tolerated (n=36, ferritin: 85+59 ng/ml) were associated with lower levels of serum ferritin compared to patients without augmentation (n=302, ferritin: 118+108 ng/ml, p=0.0062). CONCLUSIONS: Ferritin as a marker of iron storage may play an important role in the pathophysiology of RLS and may prove to be a biomarker for the development of augmentation under dopaminergic therapy.     

One year open-label safety and efficacy trial with rotigotine transdermal patch in moderate to severe idiopathic restless legs syndrome

BackgroundLong-term efficacy and tolerability data are not yet available for patch formulations of dopamine agonists in restless legs syndrome.MethodsEfficacy and safety of rotigotine (0.5–4 mg/24 h), formulated as a once-daily transdermal system (patch), were investigated in an open extension (SP710) of a preceding 6-week placebo-controlled trial (SP709, 341 randomized patients) in patients with idiopathic restless legs syndrome. For efficacy assessment the international RLS severity scale (IRLS), the RLS-6 scales, the clinical global impressions (CGI) and the QoL-RLS questionnaire were administered. In addition, long-term tolerability and safety were assessed.ResultsOf 310 patients who finished the controlled trial, 295 (mean age 58 ± 10 years, 66% females) with a mean IRLS score of 27.8 ± 5.9 at baseline of SP709 were included. We report results after one year of this ongoing long-term trial. Two hundred twenty patients (retention rate = 74.6%) completed the 12-month follow-up period. The mean daily dose was 2.8 ± 1.2 mg/24 h with 4 mg/24 h (40.6%) being the most frequently applied dose; 14.8% were sufficiently treated with 0.5 or 1.0 mg/24 h. The IRLS total score improved by −17.4 ± 9.9 points between baseline and end of Year 1 (p < 0.001). The other measures of severity, sleep satisfaction and quality of life supported the efficacy of rotigotine (p < 0.001 for pre-post-comparisons of all efficacy variables). The tolerability was described as “good” or “very good” by 80.3% of all patients. The most common adverse events were application site reactions (40.0%), which led to withdrawal in 13.2%. Further relatively frequent adverse events were nausea (9.5%) and fatigue (6.4%). Two drug-related serious adverse events, nausea and syncope, required hospitalization. Symptoms of augmentation were not reported by the patients.ConclusionRotigotine provided a stable, clinically relevant improvement in all efficacy measures throughout one year of maintenance therapy. The transdermal patch was safe and generally well tolerated by the majority of patients. Comparable to any transdermal therapy, application site reactions were the main treatment complication.     

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome: a randomised, double-blind, placebo-controlled trial

BACKGROUND: Continuous administration of a dopamine agonist could be used to treat patients with restless legs syndrome. Our aim was to investigate the efficacy of transdermal rotigotine in the treatment of idiopathic restless legs syndrome. METHODS: In this randomised, double-blind, placebo-controlled trial, 458 patients with moderate-to-severe idiopathic restless legs syndrome (average baseline International Restless Legs Syndrome Study Group severity rating scale [IRLS] sum score of 28.1) were randomly assigned to receive transdermal rotigotine 1 mg over 24 h (n=115), 2 mg over 24 h (n=112), or 3 mg over 24 h (n=114), or to receive placebo (n=117). Study medication was delivered via patches, applied once a day for 6 months. Randomisation was done with a computer-generated randomisation list, stratified by centre. Primary efficacy outcomes were absolute change from baseline to end of maintenance in IRLS sum score and in the clinical global impressions (CGI) item 1 score, assessed by analysis of covariance in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT00136045. FINDINGS: Efficacy analyses were done on 112 patients in the 1 mg group, 109 in the 2 mg group, 112 in the 3 mg group, and 114 in the placebo group. Mean change in IRLS sum score from baseline at the end of the maintenance phase was -13.7 (SE 0.9) in the 1 mg group, -16.2 (0.9) in the 2 mg group, -16.8 (0.9) in the 3 mg group, and -8.6 (0.9) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Mean change in CGI item 1 score from baseline at the end of the maintenance phase was -2.09 (0.14) in the 1 mg group, -2.41 (0.14) in the 2 mg group, -2.55 (0.14) in the 3 mg group, and -1.34 (0.14) in the placebo group (p<0.0001 for treatment difference vs placebo with each dose). Skin reactions, mostly mild or moderate, were seen in 145 (43%) of 341 patients who received rotigotine and in two (2%) of 117 who received placebo. Ten patients had serious adverse event that were deemed to be related to rotigotine: elevation of liver enzymes (one patient), worsening of tinnitus (one patient), non-response to anticoagulation (one patient), electrocardiogram changes (one patient), and application-site reactions (six patients). No admissions to hospital were needed for the application-site reactions, and they all resolved within a short time of patch removal without any other therapeutic intervention. The rate of typical dopaminergic side-effects in patients who received rotigotine was low; no signs of augmentation were noted. INTERPRETATION: 24 h transdermal delivery of low-dose rotigotine could be used to relieve the night-time and daytime symptoms of restless legs syndrome. FUNDING: Schwarz Biosciences.     

Impact of DMEK on visual quality in patients with Fuchs’ endothelial dystrophy

Graefe's Archive for Clinical and Experimental Ophthalmology - To investigate short-term (3&nbsp;months follow-up) changes in visual quality following Descemet membrane endothelial...     

Eine neue kombinierte chirurgisch-interventionelle Methode zur univentrikul?ren Palliation angeborener Herzfehler

Eine Vielzahl von Patienten mit angeborenen Herzfehlern bedürfen einer univentrikul?ren Korrektur nach Fontan bzw. einer totalen cavopulmonalen Anastomose. Patienten mit Risikofaktoren für diesen Eingriff werden in der Regel durch mehrere Operationen schrittweise einer Kreislauftrennung mit totaler cavo-pulmonaler Anastomose unterzogen. Wir entwickelten eine neue, kombiniert chirurgisch-interventionelle Methode zur Palliation von Patienten mit funktionell univentrikul?ren Herzen, mit der die Operationsh?ufigkeit reduziert und die Fontan-Zirkulation interventionell komplettiert werden kann. Methoden Zur chirurgischen Konditionierung wurde bei 10 Schafen eine Glenn-Anastomose ohne Herz-Lungenmaschine angelegt. Die Vena cava superior wurde oberhalb des cavo-atrialen übergangs mit 6,0 Prolene auf ein minimales Lumen geb?ndelt, die Einmündung der Vena cava inferior in das rechte Atrium wurde mit einer Gore-Tex?-Manschette von 1,5 cm versehen. Zur interventionellen Komplettierung wurde das Banding der oberen Hohlvene dilatiert und ein gecoverter Stent (Aneurx?) zwischen der unteren Hohlvene und der oberen Hohlvene implantiert, hierbei diente die Gore-Tex?-Manschette als Widerlager. Ergebnisse Bei allen 10 Schafen war auf diese Weise die Anlage einer totalen cavo-pulmonalen Anastomose ohne perioperative bzw. periinterventionelle Mortalit?t m?glich. Schlussfolgerung Eine totale cavo-pulmonale Anastomose kann durch ein kombiniertes chirurgisch-interventionelles Vorgehen geschaffen werden. Hierdurch kann die Anzahl der Operationen bei Risikopatienten reduziert, intrakradiale N?hte vermieden und der Einsatz der Herz-Lungen-Maschine verringert werden.