Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the d: a: d study.

BACKGROUND The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. METHODS Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). RESULTS A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. CONCLUSIONS Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

Der allergische Notfall: Adrenalin das Mittel der Wahl bei der Anaphylaxie

Although allergic emergencies do not occur every day, they are as unpredictable as the course of the reaction, and require rapid treatment. Anaphylaxis is a life-threatening general reaction that usually manifests within a few minutes after a known or potential antigen contact. While sole cutaneous symptoms are not sufficient to diagnose anaphylaxis, an episode of acute bronchospasm or hypotension in rare cases may be the only symptom. Almost always two or more organ systems are affected and usually the skin and/or mucous membranes are involved. Epinephrine (adrenaline) is the most important and effective drug in the treatment of anaphylaxis. Since there is no absolute contraindication, epinephrine should be administered intramuscularly at the first signs of anaphylaxis. However, there is a gap between the international treatment guidelines and the daily practice in the treatment of acute allergic, particularly anaphylactic, reactions. This is due not least to the fact that anaphylaxis, the most severe form of allergy, is not sufficiently clear or uniformly defined. After a systemic allergic reaction, all patients should be equipped with emergency medications, appropriately instructed obtain a complete allergy work-up.

Safety profile of prasugrel and clopidogrel in patients with acute coronary syndromes in Switzerland.

OBJECTIVE To assess safety up to 1 year of follow-up associated with prasugrel and clopidogrel use in a prospective cohort of patients with acute coronary syndromes (ACS). METHODS Between 2009 and 2012, 2286 patients invasively managed for ACS were enrolled in the multicentre Swiss ACS Bleeding Cohort, among whom 2148 patients received either prasugrel or clopidogrel according to current guidelines. Patients with ST-elevation myocardial infarction (STEMI) preferentially received prasugrel, while those with non-STEMI, a history of stroke or transient ischaemic attack, age ≥75 years, or weight <60 kg received clopidogrel or reduced dose of prasugrel to comply with the prasugrel label. RESULTS After adjustment using propensity scores, the primary end point of clinically relevant bleeding events (defined as the composite of Bleeding Academic Research Consortium, BARC, type 3, 4 or 5 bleeding) at 1 year, occurred at a similar rate in both patient groups (prasugrel/clopidogrel: 3.8%/5.5%). Stratified analyses in subgroups including patients with STEMI yielded a similar safety profile. After adjusting for baseline variables, no relevant differences in major adverse cardiovascular and cerebrovascular events were observed at 1 year (prasugrel/clopidogrel: cardiac death 2.6%/4.2%, myocardial infarction 2.7%/3.8%, revascularisation 5.9%/6.7%, stroke 1.0%/1.6%). Of note, this study was not designed to compare efficacy between prasugrel and clopidogrel. CONCLUSIONS In this large prospective ACS cohort, patients treated with prasugrel according to current guidelines (ie, in patients without cerebrovascular disease, old age or underweight) had a similar safety profile compared with patients treated with clopidogrel. CLINICAL TRIAL REGISTRATION NUMBER SPUM-ACS: NCT01000701; COMFORTABLE AMI: NCT00962416.

Der Spinozismus im Jüdenthumb, oder, Die von dem heütigen Jüdenthumb und dessen Geheimen Kabbala vergötterte Welt : an Mose Germano sonsten Johan Peter Speeth ...

befunden und widerleget von Johann Georg Wachter

PTT: Progress Test Tiermedizin

Studierende der Tiermedizin fokussieren sich im Studium oft auf den bloßen Wissenserwerb und nehmen dabei weniger wahr, was sie bereits erreicht haben. Mit dem Progress Test Tiermedizin (PTT) kann der Lernfortschritt von Studienanfang bis zum Erreichen des Berufsabschlusses als Tierärztin/Tierarzt dargestellt werden. Das Konzept des PTT soll in diesem Artikel erläutert werden

Separation of the Ribbon from globally distributed energetic neutral Atom Flux using the first five Years of Ibex Observations

The Interstellar Boundary Explorer (IBEX) observes the IBEX ribbon, which stretches across much of the sky observed in energetic neutral atoms (ENAs). The ribbon covers a narrow (~20°-50°) region that is believed to be roughly perpendicular to the interstellar magnetic field. Superimposed on the IBEX ribbon is the globally distributed flux that is controlled by the processes and properties of the heliosheath. This is a second study that utilizes a previously developed technique to separate ENA emissions in the ribbon from the globally distributed flux. A transparency mask is applied over the ribbon and regions of high emissions. We then solve for the globally distributed flux using an interpolation scheme. Previously, ribbon separation techniques were applied to the first year of IBEX-Hi data at and above 0.71 keV. Here we extend the separation analysis down to 0.2 keV and to five years of IBEX data enabling first maps of the ribbon and the globally distributed flux across the full sky of ENA emissions. Our analysis shows the broadening of the ribbon peak at energies below 0.71 keV and demonstrates the apparent deformation of the ribbon in the nose and heliotail. We show global asymmetries of the heliosheath, including both deflection of the heliotail and differing widths of the lobes, in context of the direction, draping, and compression of the heliospheric magnetic field. We discuss implications of the ribbon maps for the wide array of concepts that attempt to explain the ribbon's origin. Thus, we present the five-year separation of the IBEX ribbon from the globally distributed flux in preparation for a formal IBEX data release of ribbon and globally distributed flux maps to the heliophysics community.

Long-term outcomes of patients with Wilson disease in a large Austrian cohort

BACKGROUND & AIMS Wilson disease is an autosomal recessive disorder that affects copper metabolism, leading to copper accumulation in liver, central nervous system, and kidneys. There are few data on long-term outcomes and survival from large cohorts; we studied these features in a well-characterized Austrian cohort of patients with Wilson disease. METHODS We analyzed data from 229 patients diagnosed with Wilson disease from 1961 through 2013; 175 regularly attended a Wilson disease outpatient clinic and/or their physicians were contacted for information on disease and treatment status and outcomes. For 53 patients lost during the follow-up period, those that died and reasons for their death were identified from the Austrian death registry. RESULTS The mean observation period was 14.8 ± 11.4 years (range, 0.5-52.0 years), resulting in 3116 patient-years. Of the patients, 61% presented with hepatic disease, 27% with neurologic symptoms, and 10% were diagnosed by family screening at presymptomatic stages. Patients with a hepatic presentation were diagnosed younger (21.2 ± 12.0 years) than patients with neurologic disease (28.8 ± 12.0; P < .001). In 2% of patients, neither symptoms nor onset of symptoms could be determined with certainty. Most patients stabilized (35%) or improved on chelation therapy (26% fully recovered, 24% improved), but 15% deteriorated; 8% required a liver transplant, and 7.4% died within the observation period (71% of deaths were related to Wilson disease). A lower proportion of patients with Wilson disease survived for 20 years (92%) than healthy Austrians (97%), adjusted for age and sex (P = .03). Cirrhosis at diagnosis was the best predictor of death (odds ratio, 6.8; 95% confidence interval, 1.5-31.03; P = .013) and need for a liver transplant (odds ratio, 07; 95% confidence interval, 0.016-0.307; P < .001). Only 84% of patients with cirrhosis survived 20 years after diagnosis (compared with healthy Austrians, P =.008). CONCLUSION Overall, patients who receive adequate care for Wilson disease have a good long-term prognosis. However, cirrhosis increases the risk of death and liver disease. Early diagnosis, at a precirrhotic stage, might increase survival times and reduce the need for a liver transplant.