Copeptin and risk stratification in patients with ischemic stroke and transient ischemic attack: The CoRisk Study

RATIONALE: Copeptin independently predicts functional outcome and mortality at 90 days and one-year after ischemic stroke. In patients with transient ischemic attack, elevated copeptin values indicate an increased risk of further cerebrovascular events. AIMS: The Copeptin Risk Stratification (CoRisk) study aims to validate the predictive value of copeptin in patients with ischemic stroke and transient ischemic attack. In patients with ischemic stroke, the CoRisk study aims to further explore the effect of treatment (i.e. thrombolysis) on the predictive value of copeptin. DESIGN: Prospective observational multicenter study analyzing three groups of patients, i.e. patients with ischemic stroke treated with and without thrombolysis and patients with transient ischemic attack. OUTCOMES: Primary end-point: In patients with ischemic stroke, the primary end-point includes disability (modified Rankin scale from 3 to 5) and mortality (modified Rankin scale 6) at three-months after stroke. In patients with transient ischemic attack, the primary end-point is a recurrent ischemic cerebrovascular event (i.e. ischemic stroke or recurrent transient ischemic attack). Secondary end-point: In patients with ischemic stroke, the secondary end-points include in-house complications (i.e. symptomatic intracerebral hemorrhage, malignant edema, aspiration pneumonia or seizures during hospitalization, and in-house mortality).

Plaque Characteristics of Asymptomatic Carotid Stenosis and Risk of Stroke

The optimal treatment of asymptomatic carotid stenosis (ACS) is controversial. To optimize the risk-benefit ratio of carotid artery revascularization, it is crucial to identify ACS patients who are at increased stroke risk. Recent data suggest that plaque vulnerability depends on its composition. Therefore, we assessed plaque composition in ACS to determine predictors for ipsilateral cerebrovascular events.

Antimicrobial resistance in Swiss laying hens, prevalence and risk factors

Antimicrobial resistance is an emerging concern to public health, and food-producing animals are known to be a potential source for transmission of resistant bacteria to humans. As legislation of the European Union requires to ban conventional cages for the housing of laying hens on the one hand, and a high food safety standard for eggs on the other hand, further investigations about the occurrence of antimicrobial resistance in alternative housing types are required. In this study, we determined antimicrobial resistance in indicator bacteria from 396 cloacal swabs from 99 Swiss laying hen farms among four alternative housing types during a cross-sectional study. On each farm, four hens were sampled and exposure to potential risk factors was identified with a questionnaire. The minimal inhibitory concentration was determined using broth microdilution in Escherichia coli (n=371) for 18 antimicrobials and in Enterococcus faecalis (n=138) and Enterococcus faecium (n=153) for 16 antimicrobials. All antimicrobial classes recommended by the European Food Safety Authority for E. coli and enterococci were included in the resistance profile. Sixty per cent of the E. coli isolates were susceptible to all of the considered antimicrobials and 30% were resistant to at least two antimicrobials. In E. faecalis, 33% of the strains were susceptible to all tested antimicrobials and 40% were resistant to two or more antimicrobials, whereas in E. faecium these figures were 14% and 39% respectively. Risk factor analyses were carried out for bacteria species and antimicrobials with a prevalence of resistance between 15% and 85%. In these analyses, none of the considered housing and management factors showed a consistent association with the prevalence of resistance for more than two combinations of bacteria and antimicrobial. Therefore we conclude that the impact of the considered housing and management practices on the egg producing farms on resistance in laying hens is low.

A pilot case-control study of behavioral aspects and risk factors in Swiss climbers

Climbing is a popular sport in Switzerland, with approximately 100 000 active participants. There is an inherent risk of falls, overuse and stress-related trauma, with a reported injury rate of 4.2 injuries per 1000 climbing hours.

Obesity and risk of recurrence or death after adjuvant endocrine therapy with letrozole or tamoxifen in the breast international group 1-98 trial

To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up.

Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis

The benefit of the coronary collateral circulation (natural bypass network) on survival is well established. However, data derived from smaller studies indicates that coronary collaterals may increase the risk for restenosis after percutaneous coronary interventions. The purpose of this systematic review and meta-analysis of observational studies was to explore the impact of the collateral circulation on the risk for restenosis.

Unhealthy alcohol use, HIV infection and risk of liver fibrosis in drug users with hepatitis C

Aim To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values. Conclusions Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations.

Compensation, Incentives and Risk: Economic Theory and Russian Practise

Mr. Pechersky set out to examine a specific feature of the employer-employee relationship in Russian business organisations. He wanted to study to what extent the so-called "moral hazard" is being solved (if it is being solved at all), whether there is a relationship between pay and performance, and whether there is a correlation between economic theory and Russian reality. Finally, he set out to construct a model of the Russian economy that better reflects the way it actually functions than do certain other well-known models (for example models of incentive compensation, the Shapiro-Stiglitz model etc.). His report was presented to the RSS in the form of a series of manuscripts in English and Russian, and on disc, with many tables and graphs. He begins by pointing out the different examples of randomness that exist in the relationship between employee and employer. Firstly, results are frequently affected by circumstances outside the employee's control that have nothing to do with how intelligently, honestly, and diligently the employee has worked. When rewards are based on results, uncontrollable randomness in the employee's output induces randomness in their incomes. A second source of randomness involves the outside events that are beyond the control of the employee that may affect his or her ability to perform as contracted. A third source of randomness arises when the performance itself (rather than the result) is measured, and the performance evaluation procedures include random or subjective elements. Mr. Pechersky's study shows that in Russia the third source of randomness plays an important role. Moreover, he points out that employer-employee relationships in Russia are sometimes opposite to those in the West. Drawing on game theory, he characterises the Western system as follows. The two players are the principal and the agent, who are usually representative individuals. The principal hires an agent to perform a task, and the agent acquires an information advantage concerning his actions or the outside world at some point in the game, i.e. it is assumed that the employee is better informed. In Russia, on the other hand, incentive contracts are typically negotiated in situations in which the employer has the information advantage concerning outcome. Mr. Pechersky schematises it thus. Compensation (the wage) is W and consists of a base amount, plus a portion that varies with the outcome, x. So W = a + bx, where b is used to measure the intensity of the incentives provided to the employee. This means that one contract will be said to provide stronger incentives than another if it specifies a higher value for b. This is the incentive contract as it operates in the West. The key feature distinguishing the Russian example is that x is observed by the employer but is not observed by the employee. So the employer promises to pay in accordance with an incentive scheme, but since the outcome is not observable by the employee the contract cannot be enforced, and the question arises: is there any incentive for the employer to fulfil his or her promises? Mr. Pechersky considers two simple models of employer-employee relationships displaying the above type of information symmetry. In a static framework the obtained result is somewhat surprising: at the Nash equilibrium the employer pays nothing, even though his objective function contains a quadratic term reflecting negative consequences for the employer if the actual level of compensation deviates from the expectations of the employee. This can lead, for example, to labour turnover, or the expenses resulting from a bad reputation. In a dynamic framework, the conclusion can be formulated as follows: the higher the discount factor, the higher the incentive for the employer to be honest in his/her relationships with the employee. If the discount factor is taken to be a parameter reflecting the degree of (un)certainty (the higher the degree of uncertainty is, the lower is the discount factor), we can conclude that the answer to the formulated question depends on the stability of the political, social and economic situation in a country. Mr. Pechersky believes that the strength of a market system with private property lies not just in its providing the information needed to compute an efficient allocation of resources in an efficient manner. At least equally important is the manner in which it accepts individually self-interested behaviour, but then channels this behaviour in desired directions. People do not have to be cajoled, artificially induced, or forced to do their parts in a well-functioning market system. Instead, they are simply left to pursue their own objectives as they see fit. Under the right circumstances, people are led by Adam Smith's "invisible hand" of impersonal market forces to take the actions needed to achieve an efficient, co-ordinated pattern of choices. The problem is that, as Mr. Pechersky sees it, there is no reason to believe that the circumstances in Russia are right, and the invisible hand is doing its work properly. Political instability, social tension and other circumstances prevent it from doing so. Mr. Pechersky believes that the discount factor plays a crucial role in employer-employee relationships. Such relationships can be considered satisfactory from a normative point of view, only in those cases where the discount factor is sufficiently large. Unfortunately, in modern Russia the evidence points to the typical discount factor being relatively small. This fact can be explained as a manifestation of aversion to risk of economic agents. Mr. Pechersky hopes that when political stabilisation occurs, the discount factors of economic agents will increase, and the agent's behaviour will be explicable in terms of more traditional models.

Hepatocellular toxicity of clopidogrel: Mechanisms and risk factors

Clopidogrel is a prodrug used widely as a platelet aggregation inhibitor. After intestinal absorption, approximately 90% is converted to inactive clopidogrel carboxylate and 10% via a two-step procedure to the active metabolite containing a mercapto group. Hepatotoxicity is a rare but potentially serious adverse reaction associated with clopidogrel. The aim of this study was to find out the mechanisms and susceptibility factors for clopidogrel-associated hepatotoxicity. In primary human hepatocytes, clopidogrel (10 and 100μM) was cytotoxic only after cytochrome P450 (CYP) induction by rifampicin. Clopidogrel (10 and 100μM) was also toxic for HepG2 cells expressing human CYP3A4 (HepG2/CYP3A4) and HepG2 cells co-incubated with CYP3A4 supersomes (HepG2/CYP3A4 supersome), but not for wild-type HepG2 cells (HepG2/wt). Clopidogrel (100μM) decreased the cellular glutathione content in HepG2/CYP3A4 supersome and triggered an oxidative stress reaction (10 and 100µM) in HepG2/CYP3A4, but not in HepG2/wt. Glutathione depletion significantly increased the cytotoxicity of clopidogrel (10 and 100µM) in HepG2/CYP3A4 supersome. Co-incubation with 1μM ketoconazole or 10mM glutathione almost completely prevented the cytotoxic effect of clopidogrel in HepG2/CYP3A4 and HepG2/CYP3A4 supersome. HepG2/CYP3A4 incubated with 100μM clopidogrel showed mitochondrial damage and cytochrome c release, eventually promoting apoptosis and/or necrosis. In contrast to clopidogrel, clopidogrel carboxylate was not toxic for HepG2/wt or HepG2/CYP3A4 up to 100µM. In conclusion, clopidogrel incubated with CYP3A4 is associated with the formation of metabolites that are toxic for hepatocytes and can be trapped by glutathione. High CYP3A4 activity and low cellular glutathione stores may be risk factors for clopidogrel-associated hepatocellular toxicity.