How valuable are multiple treatment comparison methods in evidence-based health-care evaluation?

Objectives To compare the use of pair-wise meta-analysis methods to multiple treatment comparison (MTC) methods for evidence-based health-care evaluation to estimate the effectiveness and cost-effectiveness of alternative health-care interventions based on the available evidence. Methods Pair-wise meta-analysis and more complex evidence syntheses, incorporating an MTC component, are applied to three examples: 1) clinical effectiveness of interventions for preventing strokes in people with atrial fibrillation; 2) clinical and cost-effectiveness of using drug-eluting stents in percutaneous coronary intervention in patients with coronary artery disease; and 3) clinical and cost-effectiveness of using neuraminidase inhibitors in the treatment of influenza. We compare the two synthesis approaches with respect to the assumptions made, empirical estimates produced, and conclusions drawn. Results The difference between point estimates of effectiveness produced by the pair-wise and MTC approaches was generally unpredictable—sometimes agreeing closely whereas in other instances differing considerably. In all three examples, the MTC approach allowed the inclusion of randomized controlled trial evidence ignored in the pair-wise meta-analysis approach. This generally increased the precision of the effectiveness estimates from the MTC model. Conclusions The MTC approach to synthesis allows the evidence base on clinical effectiveness to be treated as a coherent whole, include more data, and sometimes relax the assumptions made in the pair-wise approaches. However, MTC models are necessarily more complex than those developed for pair-wise meta-analysis and thus could be seen as less transparent. Therefore, it is important that model details and the assumptions made are carefully reported alongside the results.

Stress and burnout among Swiss dental residents

Stress and burnout have been well-documented in graduate medical and undergraduate dental education, but studies among dental graduate students and residents are sparse. The purpose of this investigation was to examine perceived stressors and three dimensions of burnout among dental residents enrolled in the University of Bern, Switzerland. Thirty-six residents enrolled in five specialty programmes were administered the Graduate Dental Environment Stress (GDES30) questionnaire and the Maslach Burnout Inventory (MBI). Individual stress items and overall GDES30 scores were used to quantify perceived stress. To measure burnout, proportions of burnout "cases" and MBI subscale scores were computed in the domains of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA). Analyses relied on descriptive and bi-variate methods. The mean GDES30 score was 2.1 (SD = 0.4). "Lack of leisure time", "meeting the research requirement of the programme" and "completing graduation requirements" emerged as the top three stressors. Thirty-six percent of respondents were burnout "cases" on the PA scale, while this proportion was 17% for EE and 8% for DP. Both stress and burnout levels increased according to year of study, whereas younger residents and females had consistently higher stress and burnout scores compared to older ones and males. Overall, low levels of perceived stress and burnout were found among this group of Swiss dental residents.

Seroprevalence of Leptospira spp. in clinically healthy horses in Switzerland

A retrospective, cross-sectional study was conducted to determine the leptospiral seroprevalence in clinically healthy horses in Switzerland. A representative sample of 615 horse sera was examined by microscopic agglutination test for the presence of antibodies against 15 Leptospira spp. serovars. In total, 58.5 % (n = 360) of the horses were positive for one or more of the antigens analysed, with 20.3 % of them showing titres >= 400. The most prevalent serovar was Pyrogenes (22.6 %), followed by serovars Canicola (22.1 %) and Australis (19.2 %). Older horses, mares, ponies and animals spending increased time on pasture exhibited significantly higher prevalence rates (p < 0.05). Moreover, the prevalence was higher in summer and autumn (p = 0.003). The high seroprevalence in healthy horses indicates that they are often exposed to or infected with Leptospira spp. without developing signs of disease. Therefore, other laboratory and clinical data should always be taken into consideration when interpreting serological test results for Leptospira spp.

Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy

Puppa G, Senore C, Sheahan K, Vieth M, Lugli A, Zlobec I, Pecori S, Wang L M, Langner C, Mitomi H, Nakamura T, Watanabe M, Ueno H, Chasle J, Conley S A, Herlin P, Lauwers G Y & Risio M (2012) Histopathology Diagnostic reproducibility of tumour budding in colorectal cancer: a multicentre, multinational study using virtual microscopy Aims:  Despite the established prognostic relevance of tumour budding in colorectal cancer, the reproducibility of the methods reported for its assessment has not yet been determined, limiting its use and reporting in routine pathology practice. Methods and results:  A morphometric system within telepathology was devised to evaluate the reproducibility of the various methods published for the assessment of tumour budding in colorectal cancer. Five methods were selected to evaluate the diagnostic reproducibility among 10 investigators, using haematoxylin and eosin (H&E) and AE1-3 cytokeratin-immunostained, whole-slide digital scans from 50 pT1-pT4 colorectal cancers. The overall interobserver agreement was fair for all methods, and increased to moderate for pT1 cancers. The intraobserver agreement was also fair for all methods and moderate for pT1 cancers. Agreement was dependent on the participants' experience with tumour budding reporting and performance time. Cytokeratin immunohistochemistry detected a higher percentage of tumour budding-positive cases with all methods compared to H&E-stained slides, but did not influence agreement levels. Conclusions:  An overall fair level of diagnostic agreement for tumour budding in colorectal cancer was demonstrated, which was significantly higher in early cancer and among experienced gastrointestinal pathologists. Cytokeratin immunostaining facilitated detection of budding cancer cells, but did not result in improved interobserver agreement.

Impact of 3,4-dihydroxy-6-18F-fluoro-L-phenylalanine PET/CT on managing patients with brain tumors: the referring physician's perspective

We investigated the impact of (18)F-DOPA brain PET/CT on the clinical management of patients with known or suspected brain tumors.

Response of temperate grasslands at different altitudes to simulated summer drought differed but scaled with annual precipitation

Water is an important resource for plant life. Since climate scenarios for Switzerland predict an average reduction of 20% in summer precipitation until 2070, understanding ecosystem responses to water shortage, e.g. in terms of plant productivity, is of major concern. Thus, we tested the effects of simulated summer drought on three managed grasslands along an altitudinal gradient in Switzerland from 2005 to 2007, representing typical management intensities at the respective altitude. We assessed the effects of experimental drought on above- and below-ground productivity, stand structure (LAI and vegetation height) and resource use (carbon and water). Responses of community above-ground productivity to reduced precipitation input differed among the three sites but scaled positively with total annual precipitation at the sites (R2=0.85). Annual community above-ground biomass productivity was significantly reduced by summer drought at the alpine site receiving the least amount of annual precipitation, while no significant decrease (rather an increase) was observed at the pre-alpine site receiving highest precipitation amounts in all three years. At the lowland site (intermediate precipitation sums), biomass productivity significantly decreased in response to drought only in the third year, after showing increased abundance of a drought tolerant weed species in the second year. No significant change in below-ground biomass productivity was observed at any of the sites in response to simulated summer drought. However, vegetation carbon isotope ratios increased under drought conditions, indicating an increase in water use efficiency. We conclude that there is no general drought response of Swiss grasslands, but that sites with lower annual precipitation seem to be more vulnerable to summer drought than sites with higher annual precipitation, and thus site-specific adaptation of management strategies will be needed, especially in regions with low annual precipitation.

Small intestinal intussusception in five dogs with acute renal failure and suspected leptospirosis (L. australis)

OBJECTIVES This case series describes 5 dogs with small intestinal intussusception and acute kidney injury due to infection with Leptospira interrogans serovar Australis. CASE SERIES SUMMARY Small intestinal intussusception was observed in 4 dogs diagnosed with acute kidney injury due to leptospirosis presented between 1997 and 2005. Intussusception was diagnosed at initial presentation or later during hospitalization. An additional dog fulfilling our inclusion criteria was presented to a small animal specialty clinic nearby and was included. Upon admission, all dogs were severely azotemic and thrombocytopenic. All 5 dogs showed the strongest microscopic agglutination test serology reaction to L. interrogans serovar Australis. Two dogs survived with no apparent residual renal damage, 1 survived with subsequent mild chronic kidney disease, and 2 dogs were euthanized at the owners' request due to a guarded prognosis. NEW OR UNIQUE INFORMATION PROVIDED Intussusception can occur or may be seen in dogs with leptospirosis due to L. interrogans serovar Australis and patients should be monitored closely for this potential complication. As all 5 dogs described in this case series showed the highest titer for L. interrogans serovar Australis, these precautions may be especially applied in geographic areas where this particular serovar is seen.

Impacted maxillary canines and root resorptions of neighbouring teeth: a radiographic analysis using cone-beam computed tomography

The study analyses the location of impacted maxillary canines and factors influencing root resorptions of adjacent teeth using cone-beam computed tomography (CBCT). In addition, the interrater reliability between observers of two different dental specialties for radiographic parameters will be evaluated. CBCT images of patients who were referred for radiographic localization of impacted maxillary canines and/or suspicion of root resorptions of adjacent teeth were included. The study analysed the exact three-dimensional location of the impacted canines in the anterior maxilla, frequency and extent of root resorptions, and potential influencing factors. To assess interrater agreement, Cohen's correlation parameters were calculated. This study comprises 113 patients with CBCT scans, and 134 impacted canines were analysed retrospectively. In the patients evaluated, 69 impacted canines were located palatally (51.49 per cent), 41 labially (30.60 per cent), and 24 (17.91 per cent) in the middle of the alveolar process. Root resorptions were found in 34 lateral incisors (25.37 per cent), 7 central incisors (5.22 per cent), 6 first premolars (4.48 per cent), and 1 second premolar (0.75 per cent). There was a significant correlation between root resorptions on adjacent teeth and localization of the impacted canine in relation to the bone, as well as vertical localization of the canine. Interrater agreement showed values of 0.546-0.877. CBCT provides accurate information about location of the impacted canine and prevalence and degree of root resorption of neighbouring teeth with high interrater correlation. This information is of great importance for surgeons and orthodontists for accurate diagnostics and interdisciplinary treatment planning.

Pulmonary venous flow velocity patterns in 404 individuals without cardiovascular disease

OBJECTIVE To determine the pulmonary venous flow velocity (PVFV) values in a large normal population. DESIGN Prospective study in consecutive individuals. SETTING University hospital. METHODS Among 404 normal individuals, the flow velocity pattern in the right upper pulmonary vein was recorded in 315 subjects using transthoracic echocardiography, and in both upper pulmonary veins in 100 subjects using transoesophageal echocardiography. Subjects were divided into five age groups. The PVFV values were compared between transthoracic and transoesophageal echocardiography within the age groups, and intraindividually between the right and left upper pulmonary veins in transoesophageal echocardiography. RESULTS Normal PVFV values for the right upper pulmonary vein in transthoracic and transoesophageal echocardiography are presented. The duration of flow reversal at atrial contraction was overestimated using transthoracic echocardiography (mean (SD): 96 (21) ms in transoesophageal echocardiography, 120 (28) ms in transthoracic echocardiography, p < 0.0001). Systolic to diastolic peak flow velocity ratio (S:D) increased earlier with advancing age with transoesophageal echocardiography than with transthoracic echocardiography. Similar results were found for the corresponding time-velocity integrals. Data from the left and right upper pulmonary veins differed with respect to onset and deceleration of flow velocities, but not for flow durations or peak velocities. CONCLUSIONS Normal PVFV values generally show a wide range. The data presented will be of value in assessing left ventricular diastolic function and mitral regurgitation using the PVFV pattern.

Epidemic of Salmonellosis in Passerine Birds in Switzerland With Spillover to Domestic Cats

A die-off of passerine birds, mostly Eurasian siskins (Carduelis spinus), occurred in multiple areas of Switzerland between February and March 2010. Several of the dead birds were submitted for full necropsy. Bacteriological examination was carried out on multiple tissues of each bird. At gross examination, common findings were light-tan nodules, 1 to 4 mm in diameter, scattered through the esophagus/crop. Histologically, a necroulcerative transmural esophagitis/ingluvitis was observed. Bacterial cultures yielded Salmonella enterica subsp. enterica serovar Typhimurium. At the same time, 2 pet clinics reported an unusual increase of domestic cats presented with fever, anorexia, occasionally dolent abdomen, and history of presumed consumption of passerine birds. Analysis of rectal swabs revealed the presence of S. Typhimurium in all tested cats. PFGE (pulsed field electrophoresis) analysis was performed to characterize and compare the bacterial isolates, and it revealed an indistinguishable pattern between all the avian and all but 1 of the feline isolates. Cloacal swabs collected from clinically healthy migrating Eurasian siskins (during autumn 2010) did not yield S. Typhimurium. The histological and bacteriological findings were consistent with a systemic infection caused by S. Typhimurium. Isolation of the same serovar from the dead birds and ill cats, along with the overlapping results of the PFGE analysis for all the animal species, confirmed a spillover from birds to cats through predation. The sudden increase of the number of siskins over the Swiss territory and their persistency during the whole winter of 2009-2010 is considered the most likely predisposing factor for the onset of the epidemic.

Estándares europeos de didáctica musical y su exportación a América en el XVI

Zwar sind eine ganze Reihe von musikdidaktischen Traktaten aus dem 15. und 16. Jh. in Spanien bekannt, dennoch wissen wir sehr wenig über die tatsächliche "Lehrszene". Die Bedeutung von Oralität, von Wiederholung, der psychosolzialen Position der Musikschüler war genauso wichtig, wie die schiere Musiktheorie.

Potent innate immune response to pathogenic leptospira in human whole blood.

BACKGROUND Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. METHODOLOGY/PRINCIPAL FINDINGS We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. CONCLUSIONS/SIGNIFICANCE Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

Orthodontic retention procedures in Switzerland.

OBJECTIVE To survey retention procedures used in orthodontic practices in Switzerland. MATERIAL AND METHODS A questionnaire previously developed by Renkema et al. (2009) was sent to 223 Swiss orthodontists. The questionnaire comprised six parts, mainly containing multiple-choice questions. Information as to background education of the individual orthodontist, retention in general, frequency of different types of removable or bonded retainers that were used, retention pro- tocol, and the type and size of the wire used for bonded retainers was assessed. RESULTS The overall response rate was 65 percent. Most orthodontists placed a bonded retainer in the upper and lower arch, except when the upper arch was expanded during treatment or when extractions were performed in the upper arch, in which case they placed a combination of fixed and removable retainers. Opinions varied with regard to how many hours the removable retainers should be worn and the duration of the retention phase. As far as bonded retainers were concerned, 87 percent of the orthodontists preferred life-long retention. Ninety-three percent of the orthodontists considered that the development of a guide- line on retention procedures would be useful. CONCLUSIONS The choice of retention procedures is mostly based on orthodontists personal preference. A further research into the long-term effectiveness of individual retention protocols is needed.