Multiple tests of cost-effectiveness angles.

Cost-effectiveness angles are an attractive measure of performance when comparing effects and costs of health-care therapies because they have a clear interpretation and are well suited for statistical inference. In clinical trials, a common setup is the comparison of multiple new therapies with a single control. If cost-effectiveness angles are calculated for each comparison, multiplicity issues should be taken into account when quantifying uncertainty of the point estimates. Therefore, this paper proposes a parametric test for multiple cost-effectiveness angles that guarantees strong family-wise error rate control. The idea is to replace the test of m cost-effectiveness angles as a union-intersection test of 3m linear hypotheses. Considering the correlation structure of the individual test statistics for the linear hypotheses leads to a maximum-type test for the intersection hypothesis. Inverting these test decisions then gives simultaneous CIs of cost-effectiveness angles with the appropriate coverage probabilities.

TCF7L2 promotes beta cell regeneration in human and mouse pancreas.

AIMS/HYPOTHESIS: Diabetes is characterised by loss and dysfunction of the beta cell. A major goal of diabetes therapy is to promote the formation of new beta cells. Polymorphisms of T cell factor 7-like 2 (TCF7L2) are associated with type 2 diabetes, negatively regulating beta cell survival and function. Here, we provide evidence for a role of TCF7L2 in beta cell proliferation and regeneration. METHODS: Pancreatic sections from three mouse models (high-fat diet, exendin-4 and streptozotocin-treated mice) and from healthy individuals and patients with type 2 diabetes were used to investigate the association of beta cell regeneration and TCF7L2 levels. To analyse a direct effect of TCF7L2 on duct cell to beta cell conversion, TCF7L2 was overexpressed in isolated exocrine cells. RESULTS: TCF7L2 levels correlated with beta cell compensation during high-fat diet feeding. TCF7L2 was increased together with pancreatic duct cell proliferation and differentiation. Small islet-like cell clusters (ICCs) that contained TCF7L2 originated in the vicinity of the ductal epithelium. In human isolated exocrine tissue, TCF7L2 overexpression induced proliferation of pancreatic duct cells and ICC formation next to duct cells, an effect dependent on the JAK2/STAT3 pathway. CONCLUSIONS/INTERPRETATION: The present study demonstrates that TCF7L2 overexpression fosters beta cell regeneration. Our findings imply correlation of TCF7L2 levels and new beta cell formation.

Is erectile dysfunction a predictor of cardiovascular events or stroke? A prospective study using a validated questionnaire.

Erectile dysfunction (ED) is linked to various cardiovascular risk factors and may therefore serve as a predictor of cardiovascular events. To gain further insight into this relationship, we reviewed all data regarding hospital admission for cardial or cerebral vascular disease that occurred until 2008 in a cohort of men who underwent a health investigation in 2001. Erectile function was assessed using the International Index of Erectile Function (IIEF-5) questionnaire. In total, 2506 men with a negative history of cardial or cerebral vascular disease were analysed. During the 6.5-year follow-up, 58 cardiovascular events (2.3%) occurred. Men without ED (IIEF-5 >22; n=1636) at baseline developed a cardiovascular event in 1.9% (n=32) as compared with 2.9% (+52%; n=26) in those with ED (IIEF-5 < or =22; n=670). In contrast to age (hazard ratio (HR): 1.6; 1.2-1.8 for every decade), hypertension (HR: 1.88; 1.1-3.1) and diabetes (HR: 2.6; 1.2-5.8), ED was not an independent risk factor for a cardiovascular event. Although men with ED were at increased risk for future cardiovascular events, ED was not an age-independent predictor of cardiovascular events in our cohort.

The endogenous rhythm of plasma melatonin and its regulation by light in the highveld mole-rat (Cryptomys hottentotus pretoriae): a microphthalmic, seasonally breeding rodent.

The day- and night-time levels of plasma melatonin were measured in adult male and female highveld mole-rats, Cryptomys hottentotus pretoriae. This study aimed to assess whether melatonin secretion in this nocturnal, strictly subterranean but seasonally breeding rodent has a day-night rhythm and whether that rhythm is circadian and can be modified by photoperiod. In experiment 1, a day-night rhythm of plasma melatonin was found in all animals housed on a 12L:12D schedule, with significantly higher concentrations in the dark (D) compared with the light (L) phase. The increment of plasma melatonin concentration at night was the same on days 1 and 2 for animals in the control group and animals transferred to constant dark. The animals transferred to constant light substantially reduced the amplitude of the melatonin rhythm on day 2. This suggests that the endogenous melatonin rhythm in C. h. pretoriae has a circadian pattern, which can be synchronized by photoperiod and inhibited by exposure to light at night. In experiment 2, the concentration of plasma melatonin in animals kept under 14L:10D (long day, LD) conditions differed significantly from animals on 10L:14D (short day, SD). This finding supports the notion that C. h. pretoriae is sensitive to changes in day length.

[The radiologic picture of pathomorphological changes in the intestinal wall in Crohn disease in relation to the course of the disease]. / Radiologische Darstellung pathomorphologischer Veränderungen der Darmwand bei M. Crohn in Abhängigkeit vom Krankheitsverlauf.

Crohn's disease has highly variable presentation in the x-ray examination depending on the stage of the gut wall inflammation. Our series showed that the lesions concern mainly the ileocecal region with involvement of the terminal ileum in 72.4% and of the cecum in 56.2% of the cases. In patients who required only conservative treatment mainly "cobble stone"-lesions, pseudopolyps and pseudodiverticuli could be demonstrated. Patients who needed surgical therapy showed in the first place stenosis, spicules and fistulae. Of all the studied patients 59% had to be assigned to surgery and of these 62% showed signs of relapse. The recurrence of disease occurred in 88% at the site of the anastomosis mainly in the first two years after operation. Differences in the frequency of relapse after the first or the second operation could not be seen.

[Conventional roentgen diagnosis of the proximal end of the humerus]. / Röntgen-Nativdiagnostik des proximalen Humerusendes.

Rarely the spectrum of conventional radiographic studies of the proximal humerus resp. shoulder joint is used in its full potential. This frequently results in erroneous interpretation. Five essential X-ray examinations are presented with respect to technique and diagnostic value.

[Classification of fractures of the proximal end of the humerus following prognostic and therapeutic aspects]. / Einteilung der Frakturen des proximalen Humerusendes nach prognostischen und therapeutischen Gesichtspunkten.

The classification of the proximal humeral fractures according to the four-segment concept of Neer has proven to be very useful. It not only considers the fracture itself but also lesions of the soft tissue. Adapting Neer's concept we propose a modified classification of the proximal humeral fractures which we believe is clearer and more practicable. This classification is illustrated by means of drawings and typical roentgenograms. The description of the different fracture-types includes the mean characteristics such as fragment-displacement, status of the rotator cuff and blood circulation to the head segment.

[Sonography of the thyroid gland. Volume determination and morphologic correlation of echo and tissue structures]. / Sonographie der Schilddrüse. Volumenbestimmung und morphologische Korrelation von Echo- und Gewebestruktur.

The volume of 15 autopsied thyroid glands was determined by fluid displacement and compared with their sonographically obtained stereometric volumes. Maximum variation was 8.6%. Thyroid volumes were measured by ultrasound in 100 volunteers between ages 15 and 36. Total mean value was 19.8 ml. with a mean value of 22.1 ml. in the male group and 17.8 ml. in the female group. 20 volunteers had an additional scintigraphic examination. The thyroid volumes estimated by scintiscanning differed up to 85% with the volume measurements from sonography. Sonography scans were obtained from 6 autopsied thyroid glands and compared with the corresponding tissue slices. Tissue structures were reproduced with great accuracy by ultrasound.

[Anteromedial humeral head defect in posterior subacromial shoulder dislocation--exact x-ray detection as the prerequisite to therapy planning]. / Antero-medialer Humeruskopfdefekt bei posteriorer subakromialer Schulterluxation--Exakter röntgenologischer Nachweis als Voraussetzung zur Therapieplanung.

Posterior subacromial dislocations of the shoulder are usually accompanied by compression fractures of the antero-medial part of the humeral head; the lesions have a wide variability. Four case reports are presented and the problems of radiologic analysis are discussed.

[Roentgen diagnosis of shoulder luxation and its concomitant bone injuries]. / Die Röntgendiagnostik der Schulterluxation und ihrer knöchernen Begleitverletzungen.

Among the dislocations of the larger joints of the human body, those of the shoulder are the most frequent ones. They are often associated with osseous lesions, which are of importance in treatment and prognosis. Radiologic diagnostic procedures must take this into consideration in view of the causal mechanisms of trauma. In search for the bony lesions, routine techniques of projection exist which are evidently not always used as often as would be desirable. These projections also help to detect and to accurately locate the dislocation, which may sometimes be difficult to diagnose. Posterior dislocations, for example, are misdiagnosed or overlooked radiologically (and clinically) in about 50% of the cases. This could partly be avoided by the consequent use of a few, but essential projection procedures.