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.

Snoring in preschool children: prevalence, severity and risk factors

Epidemiological data on snoring from preschool children are scarce, although habitual snoring (snoring on almost all nights) has been associated with poor long-term outcomes. In a population survey of 6,811 children aged 1-4 yrs (from Leicestershire, UK) the present authors determined prevalence, severity and risk factors for snoring, especially habitual snoring. In 59.7% of the children, parents reported snoring in the previous 12 months, including 7.9% with habitual snoring and 0.9% with habitual snoring and sleep disturbance. Prevalence of habitual snoring increased with age from 6.6% in 1-yr-olds to 13.0% in 4-yr-olds. Habitual snoring was associated with: one and both parents smoking (adjusted odds ratio (OR) 1.46 and 2.09, respectively); road traffic (OR 1.23); single parent (OR 1.60); and in White but not South Asian children, socioeconomic deprivation (OR 1.25 and 2.03 for middle and upper thirds of Townsend score, respectively). Respiratory tract symptoms related to atopic disorders and to respiratory infections were strongly associated with snoring; however, body mass index was not. In conclusion, habitual snoring is common in preschool children with one-third of cases attributable to avoidable risk factors. The strong association with atopic disorders, viral infections and environmental exposures suggests a complex aetiology, based on a general vulnerability of the respiratory tract.

Low awareness of transient ischemic attacks and risk factors of stroke in a Swiss urban community

BACKGROUND AND PURPOSE: Time delays from stroke onset to arrival at the hospital are the main obstacles for widespread use of thrombolysis. In order to decrease the delays, educational campaigns try to inform the general public how to act optimally in case of stroke. To determine the content of such a campaign, we assessed the stroke knowledge in our population. METHODS: The stroke knowledge was studied by means of a closed-ended questionnaire. 422 randomly chosen inhabitants of Bern, Switzerland, were interviewed. RESULTS: The knowledge of stroke warning signs (WS) was classified as good in 64.7%. A good knowledge of stroke risk factors (RF) was noted in 6.4%. 4.2% knew both the WS and the RF of stroke indicating a very good global knowledge of stroke. Only 8.3% recognized TIA as symptoms of stroke resolving within 24 hours, and only 2.8% identified TIA as a disease requiring immediate medical help. In multivariate analysis being a woman, advancing age, and having an afflicted relative were associated with a good knowledge of WS (p = 0.048, p < 0.001 and p = 0.043). Good knowledge of RF was related to university education (p < 0.001). The good knowledge of TIA did not depend on age, sex, level of education or having an afflicted relative. CONCLUSIONS: The study brings to light relevant deficits of stroke knowledge in our population. A small number of participants could recognize TIA as stroke related symptoms resolving completely within 24 hours. Only a third of the surveyed persons would seek immediate medical help in case of TIA. The information obtained will be used in the development of future educational campaigns.

Cardiovascular disease and periodontitis: an update on the associations and risk

BACKGROUND: Associations between periodontitis and cardiovascular diseases have been recognized. MATERIAL AND METHODS: New literature since the last European Workshop on Periodontology has been reviewed. RESULTS: The lack of reliable epidemiological data on disease prevalence makes an assessment of the associations and risks between periodontitis and cardiovascular diseases difficult. Two recent meta-analysis reports have identified associations between periodontitis and cardiovascular diseases (odds ratios: 1.1-2.2). Different surrogate markers for both disease entities, including serum biomarkers, have been investigated. Brachial artery flow-mediated dilatation, and carotid intima media thickness have in some studies been linked to periodontitis. Studies are needed to confirm early results of improvements of such surrogate markers following periodontal therapy. While intensive periodontal therapy may enhance inflammatory responses and impair vascular functions, studies are needed to assess the outcome of periodontal therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may also reduce the systemic inflammatory burden of individuals with severe periodontitis. The role of confounders remain unclear. CONCLUSIONS: Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case-control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases.

Erosion--diagnosis and risk factors

Dental erosion is a multifactorial condition: The interplay of chemical, biological and behavioural factors is crucial and helps explain why some individuals exhibit more erosion than others. The erosive potential of erosive agents like acidic drinks or foodstuffs depends on chemical factors, e.g. pH, titratable acidity, mineral content, clearance on tooth surface and on its calcium-chelation properties. Biological factors such as saliva, acquired pellicle, tooth structure and positioning in relation to soft tissues and tongue are related to the pathogenesis of dental erosion. Furthermore, behavioural factors like eating and drinking habits, regular exercise with dehydration and decrease of salivary flow, excessive oral hygiene and, on the other side, an unhealthy lifestyle, e.g. chronic alcoholism, are predisposing factors for dental erosion. There is some evidence that dental erosion is growing steadily. To prevent further progression, it is important to detect this condition as early as possible. Dentists have to know the clinical appearance and possible signs of progression of erosive lesions and their causes such that adequate preventive and, if necessary, therapeutic measures can be initiated. The clinical examination has to be done systematically, and a comprehensive case history should be undertaken such that all risk factors will be revealed.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

GOAL OF THE WORK: Anemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy. MATERIALS AND METHODS: We evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression. MAIN RESULTS: Among the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar. CONCLUSIONS: Moderate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

A multicenter, cross-sectional study on the prevalence and risk factors for nasal colonization with Staphylococcus aureus in patients admitted to children's hospitals in Switzerland

The rate of nasal carriage of Staphylococcus aureus and associated risk factors were determined in a cross-sectional study involving Swiss children's hospitals. S. aureus was isolated in 562 of 1363 cases. In a stepwise multivariate analysis, the variables age, duration of antibiotic use, and hospitalization of a household member were independently associated with carriage of S. aureus.