Off-Hour Admission and Outcomes in Patients with Acute Intracerebral Hemorrhage in the INTERACT2 Trial

BACKGROUND Conflicting data exist of an association between off-hour (weekend, holiday, or night-time) hospital admission and adverse outcome in intracerebral hemorrhage (ICH). We determined the association between off-hour admissions and poor clinical outcome, and of any differential effect of early intensive blood pressure (BP) lowering treatment between off- and on-hour admissions, among participants of the Intensive BP Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS Subsidiary analysis of INTERACT2, a multinational, multicenter, clinical trial of patients with spontaneous ICH with elevated systolic BP, randomly assigned to intensive (target systolic BP <140 mm Hg) or guideline-based (<180 mm Hg) BP management. Primary outcome was death or major disability (modified Rankin scale of 3-6) at 90 days. Off-hour admission was defined as night-time (4:30 p.m. to 8:30 a.m.) on weekdays, weekends (Saturday and Sunday), and public holidays in each participating country. RESULTS Of 2,794 patients with information on the primary outcome, 1,770 (63%) were admitted to study centers during off-hours. Off-hour admission was not associated with risk of poor outcome at 90 days (53% off-hour vs. 55% on-hour; p = 0.49), even after adjustment for comorbid risk factors (odds ratio 0.92; 95% CI 0.76-1.12). Consistency exists in the effects of intensive BP lowering between off- and on-hour admission (p = 0.85 for homogeneity). CONCLUSIONS Off-hour admission was not associated with increased risks of death or major disability among trial protocol participants with acute ICH. Intensive BP lowering can provide similar treatment effect irrespective of admission hours.

The Early Spörer Minimum – A Period of Extraordinary Climate and Socio-economic Changes in Western and Central Europe

Throughout the last millennium, mankind was affected by prolonged deviations from the climate mean state. While periods like the Maunder Minimum in the 17th century have been assessed in greater detail, earlier cold periods such as the 15th century received much less attention due to the sparse information available. Based on new evidence from different sources ranging from proxy archives to model simulations, it is now possible to provide an end-to-end assessment about the climate state during an exceptionally cold period in the 15th century, the role of internal, unforced climate variability and external forcing in shaping these extreme climatic conditions, and the impacts on and responses of the medieval society in Central Europe. Climate reconstructions from a multitude of natural and human archives indicate that, during winter, the period of the early Spörer Minimum (1431–1440 CE) was the coldest decade in Central Europe in the 15th century. The particularly cold winters and normal but wet summers resulted in a strong seasonal cycle that challenged food production and led to increasing food prices, a subsistence crisis, and a famine in parts of Europe. As a consequence, authorities implemented adaptation measures, such as the installation of grain storage capacities, in order to be prepared for future events. The 15th century is characterised by a grand solar minimum and enhanced volcanic activity, which both imply a reduction of seasonality. Climate model simulations show that periods with cold winters and strong seasonality are associated with internal climate variability rather than external forcing. Accordingly, it is hypothesised that the reconstructed extreme climatic conditions during this decade occurred by chance and in relation to the partly chaotic, internal variability within the climate system.

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

Der Berner Stichprobenplan – Ein Vorschlag für eine effiziente Klumpenstichprobe am Beispiel der Schweiz

Die meisten Bevölkerungsumfragen in der Schweiz beruhen auf Stichproben, die aus dem Telefonregister gezogen werden. Da solche Stichproben bezüglich der Abdeckung der Grundgesamtheit als problematisch anzusehen sind, diskutiere ich hier ein alternatives, von Fritschi et al. (1976) entwickeltes Stichprobenverfahren, bei dem in einem ersten Schritt Gemeinden ausgewählt und dann die Adressen der Zielpersonen über die Einwohnerregister bestimmt werden. Das Verfahren ist dabei so angelegt, dass die Stichprobe ähnlich wie bei einer einfachen Klumpenstichprobe auf eine relativ geringe Anzahl Gemeinden verdichtet wird, die Stichprobe aber trotzdem eine möglichst hohe statistische Effizienz beibehält. Eine Analyse der theoretischen Eigenschaften des Berner Stichprobenplans zeigt, dass das ursprüngliche Verfahren zu leicht verzerrten Stichproben führt. Eine korrigierende Modifikation des Verfahrens wird vorgeschlagen. Zudem wird ein alternativer Ansatz mit verbesserten Eigenschaften, die ex ante geteilte Stichprobe, vorgestellt. Mit Hilfe einer Simulationsstudie werden sodann die Vorzüge des Berner Stichprobenplans gegenüber einer einfachen Klumpenstichprobe illustriert.