Small dense lipoproteins, apolipoprotein B, and risk of coronary events in HIV-infected patients on antiretroviral therapy: the Swiss HIV Cohort Study.

OBJECTIVES: HIV infection and exposure to certain antiretroviral drugs is associated with dyslipidemia and increased risk for coronary events. Whether this risk is mediated by highly atherogenic lipoproteins is unclear. We investigated the association of highly atherogenic small dense low-density lipoproteins (LDLs) and apolipoprotein B and coronary events in HIV-infected individuals receiving antiretroviral therapy. METHODS: We conducted a case-control study nested into the Swiss HIV Cohort Study to investigate the association of small dense LDL and apolipoprotein B and coronary events in 98 antiretroviral drug-treated patients with a first coronary event (19 fatal and 79 nonfatal coronary events with 53 definite and 15 possible myocardial infarctions, 11 angioplasties or bypasses) and 393 treated controls matched for age, gender, and smoking status. Lipids were measured by ultracentrifugation. RESULTS: In models including cholesterol, triglycerides, high-density lipoprotein cholesterol, blood pressure, central obesity, diabetes, and family history, there was an independent association between small dense LDL and coronary events [odds ratio (OR) for 1 mg/dL increase: 1.06, 95% confidence interval (CI): 1.00 to 1.11] and apolipoprotein B (OR for 10 mg/dL increase: 1.16, 95% CI: 1.02 to 1.32). When adding HIV and antiretroviral therapy-related variables, ORs were 1.04 (95% CI: 0.99 to 1.10) for small dense LDL and 1.13 (95% CI: 0.99 to 1.30) for apolipoprotein B. In both models, blood pressure and HIV viral load was independently associated with the odds for coronary events. CONCLUSIONS: HIV-infected patients receiving antiretroviral therapy with elevate small dense LDL and apolipoprotein B are at increased risk for coronary events as are patients without sustained HIV suppression.

Low income, community poverty and risk of end stage renal disease

BACKGROUND: The risk of end stage renal disease (ESRD) is increased among individuals with low income and in low income communities. However, few studies have examined the relation of both individual and community socioeconomic status (SES) with incident ESRD. METHODS: Among 23,314 U.S. adults in the population-based Reasons for Geographic and Racial Differences in Stroke study, we assessed participant differences across geospatially-linked categories of county poverty [outlier poverty, extremely high poverty, very high poverty, high poverty, neither (reference), high affluence and outlier affluence]. Multivariable Cox proportional hazards models were used to examine associations of annual household income and geospatially-linked county poverty measures with incident ESRD, while accounting for death as a competing event using the Fine and Gray method. RESULTS: There were 158 ESRD cases during follow-up. Incident ESRD rates were 178.8 per 100,000 person-years (105 py) in high poverty outlier counties and were 76.3 /105 py in affluent outlier counties, p trend = 0.06. In unadjusted competing risk models, persons residing in high poverty outlier counties had higher incidence of ESRD (which was not statistically significant) when compared to those persons residing in counties with neither high poverty nor affluence [hazard ratio (HR) 1.54, 95% Confidence Interval (CI) 0.75-3.20]. This association was markedly attenuated following adjustment for socio-demographic factors (age, sex, race, education, and income); HR 0.96, 95% CI 0.46-2.00. However, in the same adjusted model, income was independently associated with risk of ESRD [HR 3.75, 95% CI 1.62-8.64, comparing the < $20,000 income group to the > $75,000 group]. There were no statistically significant associations of county measures of poverty with incident ESRD, and no evidence of effect modification. CONCLUSIONS: In contrast to annual family income, geospatially-linked measures of county poverty have little relation with risk of ESRD. Efforts to mitigate socioeconomic disparities in kidney disease may be best appropriated at the individual level.

Ageing with HIV: medication use and risk for potential drug-drug interactions.

OBJECTIVES: To compare the use of co-medication, the potential drug-drug interactions (PDDIs) and the effect on antiretroviral therapy (ART) tolerability and efficacy in HIV-infected individuals according to age, ≥ 50 years or <50 years. METHODS: All ART-treated participants were prospectively included once during a follow-up visit of the Swiss HIV Cohort Study. Information on any current medication was obtained by participant self-report and medical prescription history. The complete treatment was subsequently screened for PDDIs using a customized version of the Liverpool drug interaction database. RESULTS: Drug prescriptions were analysed for 1497 HIV-infected individuals: 477 age ≥ 50 and 1020 age <50. Older patients were more likely to receive one or more co-medications compared with younger patients (82% versus 61%; P < 0.001) and thus had more frequent PDDIs (51% versus 35%; P < 0.001). Furthermore, older patients tended to use a higher number of co-medications and certain therapeutic drug classes more often, such as cardiovascular drugs (53% versus 19%; P < 0.001), gastrointestinal medications (10% versus 6%; P = 0.004) and hormonal agents (6% versus 3%; P = 0.04). PDDIs with ART occurred mainly with cardiovascular drugs (27%), CNS agents (22%) and methadone (6%) in older patients and with CNS agents (27%), methadone (15%) and cardiovascular drugs (11%) in younger patients. The response to ART did not differ between the two groups. CONCLUSIONS: The risk for PDDIs with ART increased in older patients who take more drugs than their younger HIV-infected counterparts. However, medication use in older and younger patients did not differ in terms of effect on antiretroviral tolerability and response.

Postmenopausal circulating levels of 2- and 16α-hydroxyestrone and risk of endometrial cancer.

Background:It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the 2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.Methods:We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.Results:Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.Conclusion:Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.

Startegy selection during exploratory behavior: sex differences, uncertainty and risk managment

This study deals with the psychological processes underlying the selection of appropriate strategy during exploratory behavior. A new device was used to assess sexual dimorphisms in spatial abilities that do not depend on spatial rotation, map reading or directional vector extraction capacities. Moreover, it makes it possible to investigate exploratory behavior as a specific response to novelty that trades off risk and reward. Risk management under uncertainty was assessed through both spontaneous searching strategies and signal detection capacities. The results of exploratory behavior, detection capacities, and decision-making strategies seem to indicate that women's exploratory behavior is based on risk-reducing behavior while men behavior does not appear to be influenced by this variable. This difference was interpreted as a difference in information processing modifying beliefs concerning the likelihood of uncertain events, and therefore influencing risk evaluation.

Psychometric properties of the french translation of the constructive thinking inventory in a sample of adolescents and young adults

The Constructive Thinking Inventory (CTI) measures cognitive coping strategies used in everyday problem solving. The main objective of this study was to assess the factorial structure, the internal consistency, the correspondence with the American normative values, and the discriminant validity of the French translation. A community sample of 777 students aged 12 to 26 years, recruited from schools, colleges and universities, answered the 108item selfreport CTI questionnaire during a class period. A sample of 60 male adolescent offenders aged 13 to 18 years, recruited from two institutions for juvenile offenders, answered the CTI during an individual interview. Results show that the French translation of the CTI follows an identical factorial structure as the Epstein's American version in both adolescents and young adults, and that its internal consistency is satisfactory. Differences in Constructive Thinking profiles according to gender and age and between Swiss and American samples, are discussed. Juvenile offenders differed from community youths on most of the scales, speaking for a good discriminant validity of the CTI. In conclusion, the French translation of the CTI appears to preserve the original version's psychometric properties. The present study provides normative values from a community sample of Swiss adolescents and young adults.

Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese pre-menopausal women.

OBJECTIVE: To evaluate, during the first postoperative year in obese pre-menopausal women, the effects of laparoscopic gastric banding on calcium and vitamin D metabolism, the potential modifications of bone mineral content and bone mineral density, and the risk of development of secondary hyperparathyroidism. SUBJECTS: Thirty-one obese pre-menopausal women aged between 25 and 52 y with a mean body mass index (BMI) of 43.6 kg/m(2), scheduled for gastric banding were included. Patients with renal, hepatic, metabolic and bone disease were excluded. METHODS: Body composition and bone mineral density (BMD) were measured at baseline, 6 and 12 months after gastric banding using dual-energy X-ray absorptiometry. Serum calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bilirubin, urea, creatinine, uric acid, proteins, parathormone, vitamin D(3), IGF-1, IGF-BP3 and telopeptide, as well as urinary telopeptide, were measured at baseline and 1, 3, 6, 9 and 12 months after surgery. RESULTS: After 1 y vitamin D3 remained stable and PTH decreased by 12%, but the difference was not significant. Serum telopeptide C increased significantly by 100% (P<0.001). There was an initial drop of the IGF-BP3 during the first 6 months (P<0.05), but the reduction was no longer significant after 1 y. The BMD of cortical bone (femoral neck) decreased significantly and showed a trend of a positive correlation with the increase of telopeptides (P<0.06). The BMD of trabecular bone, at the lumbar spine, increased proportionally to the reduction of hip circumference and of body fat. CONCLUSION: There is no evidence of secondary hyperparathyroidism 1 y after gastric banding. Nevertheless biochemical bone markers show a negative remodelling balance, characterized by an increase of bone resorption. The serum telopeptide seems to be a reliable parameter, not affected by weight loss, to follow up bone turnover after gastroplasty.

The epidemiologic transition to chronic diseases in developing countries: cardiovascular mortality, morbidity, and risk factors in Seychelles (Indian Ocean).

The occurrence of cardiovascular diseases (CVD) and related risk factors was evaluated in Seychelles, a middle level income country, as accumulating evidence supports increasing rates of CVD in developing countries. CVD mortality was obtained from vital statistics for two periods, 1984-5 and 1991-3. CVD morbidity was estimated by retrospective review of discharge diagnoses for all admissions to medical wards in 1990-1992. Levels of CVD risk factors in the population were assessed in 1989 through a population-based survey. In 1991-93, standardized mortality rates were in males and females respectively, 80.9 and 38.8 for cerebrovascular disease and 92.9 and 47.0 for ischemic heart disease. CVD accounted for 25.2% of all admissions to medical wards. Among the general population aged 35-64, 30% had high blood pressure, 52% of males smoked, and 28% of females were obese. These findings substantiate the current health transition to CVD in Seychelles. More generally, epidemiologic data on CVD mortality, morbidity, and related risk factors, as well as similar indicators for other chronic diseases, should more consistently appear in national and international reports of human development to help emphasize, in the health policy making scene, the current transition to chronic diseases in developing countries and the subsequent need for appropriate control and prevention programs.

Self-selection and risk selection on the Swiss health insurance market

Abstract This thesis presents three empirical studies in the field of health insurance in Switzerland. First we investigate the link between health insurance coverage and health care expenditures. We use claims data for over 60 000 adult individuals covered by a major Swiss Health Insurance Fund, followed for four years; the data show a strong positive correlation between coverage and expenditures. Two methods are developed and estimated in order to separate selection effects (due to individual choice of coverage) and incentive effects ("ex post moral hazard"). The first method uses the comparison between inpatient and outpatient expenditures to identify both effects and we conclude that both selection and incentive effects are significantly present in our data. The second method is based on a structural model of joint demand of health care and health insurance and makes the most of the change in the marginal cost of health care to identify selection and incentive effects. We conclude that the correlation between insurance coverage and health care expenditures may be decomposed into the two effects: 75% may be attributed to selection, and 25 % to incentive effects. Moreover, we estimate that a decrease in the coinsurance rate from 100% to 10% increases the marginal demand for health care by about 90% and from 100% to 0% by about 150%. Secondly, having shown that selection and incentive effects exist in the Swiss health insurance market, we present the consequence of this result in the context of risk adjustment. We show that if individuals choose their insurance coverage in function of their health status (selection effect), the optimal compensations should be function of the se- lection and incentive effects. Therefore, a risk adjustment mechanism which ignores these effects, as it is the case presently in Switzerland, will miss his main goal to eliminate incentives for sickness funds to select risks. Using a simplified model, we show that the optimal compensations have to take into account the distribution of risks through the insurance plans in case of self-selection in order to avoid incentives to select risks.Then, we apply our propositions to Swiss data and propose a simple econometric procedure to control for self-selection in the estimation of the risk adjustment formula in order to compute the optimal compensations.

Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies.

Background Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association with at least one carotenoid, although the specific carotenoid has varied across studies. Methods We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided. Results Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, Ptrend = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, Ptrend = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, Ptrend = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, Ptrend = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, Ptrend = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, β-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, Ptrend = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, Ptrend = .06; Pheterogeneity = .01). Conclusions This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.

Previous thyroid disease and risk of thyroid cancer in Switzerland

A hospital-based case-control study of 86 cases of thyroid cancer and 317 controls was done in the Swiss Canton of Vaud. Patients with thyroid cancer tended to be better educated (odds ratio [OR] 2.1 for greater than or equal to 14 vs. less than or equal to 8 years of education 95% CI 1.1-4.1) and of higher social class than controls. Cases more often had a history of benign thyroid nodules (OR 25.2, 95% CI 7.6-83.6) and non-toxic goitre (OR 5.3, 95% CI 2.5-11.2). Furthermore, patients with thyroid cancer were more likely to have resided in endemic goitre areas (OR 1.7, 95% CI 1.0-3.0) and to have had first-degree relatives affected by benign thyroid disease (OR 3.9, 95% CI 2.1-7.1). Therefore, this study offers quantitative evidence of the association between various thyroid diseases and the risk of thyroid cancer which, despite difficulties in the classification of benign and malignant thyroid diseases, is remarkably consistent in studies from different countries.

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.