Indications and outcomes of antifungal therapy in French patients with haematological conditions or recipients of haematopoietic stem cell transplantation.

OBJECTIVES: Invasive fungal disease (IFD) remains a major concern in patients with haematological conditions. We describe diagnoses, therapeutic management and outcomes in unselected consecutive patients from haematological facilities treated for suspected or documented IFD. METHODS: In this observational prospective study, children/adults with haematological conditions or haematopoietic stem cell transplantation (HSCT) were recruited upon start of non-prophylactic systemic antifungal treatment in 37 French haematological facilities (December 2007 to December 2008). IFD episodes were classified according to the 2008 EORTC/MSG criteria. RESULTS: The cohort included 419 patients (298 adults and 121 children): 88% haematological malignancies, 28% HSCT recipients and 68% neutropenic. Patients had 423 IFD episodes: 21% mycologically documented (59% probable/proven aspergillosis, 32% proven candidiasis and 9% probable/proven other IFD) and 20% classified as possible IFD. The remaining cases were assigned to two groups: febrile neutropenia (34%) and unclassified (25%), 9% of which were classified as possible/probable/proven IFD by day 7. Treatment was thus initiated early in 59% of patients; liposomal amphotericin B and caspofungin were the most common single-agent therapies. The 12 week mortality was 18% for probable/proven aspergillosis, 15% for proven candidiasis, 10% for probable/proven other IFD, 9% for possible IFD, 3% for febrile neutropenia and 12% for unclassified episodes (log rank P = 0.016); it was dependent on age, complete remission of underlying haematological disease and mechanical ventilation. CONCLUSIONS: In this comprehensive sample of haematological patients receiving antifungal treatment, we observe a widespread resort to early therapy and a low mortality rate, including in patients with probable or proven IFD.

Influence of interferon-based therapy on liver fibrosis progression in HIV/HCV coinfected patients: a retrospective repeated liver biopsy analysis.

BACKGROUND & AIMS: Hepatitis C virus (HCV) coinfection is one of the leading causes of mortality in human immunodeficiency virus-infected patients. The current standard of care leads to cure only in a part of these patients. The course of the disease is determined by the rapidity of liver fibrosis progression (LFP). The influence of interferon on LFP in coinfected patients has yet not been evaluated by comparative liver biopsies. METHODS: We extracted data of patients who had serial liver biopsies from a hospital database. Histopathological findings were compared to factors possibly linked to fibrosis progression. Furthermore, we studied the impact of response to interferon treatment on fibrosis progression. RESULTS: Hundred and twenty-six patients were included, 68 had received anti-HCV treatment, and 58 had not. The median time between the first and the last biopsy was 4 years. Worsened fibrosis was observed in 35 of 58 (60%) untreated patients, and 22 of 50 (44%) patients in the nonresponder/relapser group, and in 5 out of 18 (28%) in the SVR group. Liver fibrosis evolution was significantly better in patients achieving a SVR than in untreated and NR/R patients (p<0.02, odds-ratio [95% CI] for improvement vs. stability vs. worsening=3.16 [1.24-8.07]). This result persisted after adjustment for known predictors of liver fibrosis progression, HBsAg, CD4, and alcohol consumption: adjusted odds ratio=2.89 [1.09-7.68], p=0.03. CONCLUSIONS: HCV treatment can stop fibrosis progression and induce its regression. Nonresponders to treatment may even have a fast fibrosis progression. It remains to be clarified if the same factors that induce nonresponse to treatment may also induce faster fibrosis progression.

Antioxidant supplementation increases the risk of skin cancers in women but not in men.

This research aimed to test whether supplementation with a combination of antioxidant vitamins and minerals could reduce the risk of skin cancers (SC). It was performed within the framework of the Supplementation in Vitamins and Mineral Antioxidants study, a randomized, double-blinded, placebo-controlled, primary prevention trial testing the efficacy of nutritional doses of antioxidants in reducing incidence of cancer and ischemic heart disease in the general population. French adults (7876 women and 5141 men) were randomized to take an oral daily capsule of antioxidants (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg selenium, and 20 mg zinc) or a matching placebo. The median time of follow-up was 7.5 y. A total of 157 cases of all types of SC were reported, from which 25 were melanomas. Because the effect of antioxidants on SC incidence varied according to gender, men and women were analyzed separately. In women, the incidence of SC was higher in the antioxidant group [adjusted hazard ratio (adjusted HR) = 1.68; P = 0.03]. Conversely, in men, incidence did not differ between the 2 treatment groups (adjusted HR = 0.69; P = 0.11). Despite the small number of events, the incidence of melanoma was also higher in the antioxidant group for women (adjusted HR = 4.31; P = 0.02). The incidence of nonmelanoma SC did not differ between the antioxidant and placebo groups (adjusted HR = 1.37; P = 0.22 for women and adjusted HR = 0.72; P = 0.19 for men). Our findings suggest that antioxidant supplementation affects the incidence of SC differentially in men and women.

Yearly incidence of rhinitis, nasal bleeding, and other nasal symptoms in mature women.

OBJECTIVES/HYPOTHESIS: To evaluate, by a prospective questionnaire study, the incidence of spontaneous nasal pathology in mature women over a 12-month period, in particular nasal bleeding and the relationships of these symptoms with various factors. METHODS: Participants were drawn from a sample of 12,735 adult French volunteers participating in a study of antioxidant nutrients ("SU.VI.MAX"); 3500 women aged 50-64 years were randomly selected from good responders in the SU.Vl.MAX population. The responses of 2197 women were analysed. RESULTS: Nearly 70% of subjects reported at least one episode of rhinitis, with a mean (SD) of 1.88 (2.17) episodes per subject. Rhinitis was related to passive exposure to tobacco smoke (adjusted odds ratio [OR] 1.31, 95% CI 1.05-1.63), menopause (OR 1.47, 95% CI 1.16-1.88), and occupational exposure to vapours or dusts (OR 1.55, 95% CI 1.01-2.37). Nasal bleeding was reported as traces of blood by 16.5% of subjects, and as epistaxis (significant nasal bleeding) by 7.6%. Both symptoms were related to passive exposure to tobacco smoke (OR 1.63, 95% CI 1.22-2.19; OR 1.56, 95% CI 1.05-2.32, respectively) but not to use of systemic or topical medication. CONCLUSION: A substantial number of mature women experience nasal symptoms during the course of a year. Rhinitis and nasal bleeding were correlated with passive exposure to tobacco smoke.

Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels?

The SUpplementation en VItamines et Mineraux AntioXydants (SU.VI.MAX) study, a randomised double-blind, primary-prevention trial showed that after 7.5 years, low-dose antioxidant supplementation lowered the total cancer incidence in men, but not in women. To explain this difference in the impact of antioxidant supplementation in men and women, we hypothesised that the effect of supplementation is dependent on initial antioxidant status; 12 741 French adults (7713 females aged 35--60 years; 5028 males aged 45--60 years) received daily antioxidant supplementation (120 mg vitamin C, 30 mg vitamin E, 6 mg beta-carotene, 100 microg Se, 20 mg Zn daily) or a matching placebo. Cut-off limits for baseline serum concentrations of the different antioxidant vitamins and minerals were defined as follows for both men and women: 0.3 micromol/l for beta-carotene, 11.4 micromol/l for vitamin C, 15 micromol/l for vitamin E, 0.75 micromol/l for Se and 10.7 micromol/l for Zn. The percentage of men with serum concentrations under cut-off limits was higher for vitamins C and E and beta-carotene in those who developed a cancer than in those who did not. The risk of cancer was higher in men with baseline concentrations of serum vitamin C or vitamin E under cut-off limits, but not in women. The effect of supplementation was greater in men with baseline serum concentrations of vitamin C, vitamin E and beta-carotene below the cut-off limits compared with those above it. This effect was maintained only for vitamin E after adjustment for age, tobacco, and alcohol consumption and BMI. No effect of supplementation could be seen in women. Baseline antioxidant status is related to the risk of cancer in men but not in women and therefore does not entirely explain the differences observed in the effect of antioxidant supplementation on cancer risk between sexes in the SU.VI.MAX study.

Alcohol intake in relation to body mass index and waist-to-hip ratio: the importance of type of alcoholic beverage.

OBJECTIVE: Alcohol consumption may play a role in the development of obesity but the relationship between alcohol and weight is still unclear. The aim of our study was to assess the cross-sectional association of intakes of total alcohol and of specific alcoholic beverages (wine, beer and spirits) with waist-to-hip ratio (WHR) and body mass index (BMI) in a large sample of adults from all over France. DESIGN: Cross-sectional. SETTING: Participants were free-living healthy volunteers of the SU.VI.MAX study (an intervention study on the effects of antioxidant supplementation on chronic diseases). SUBJECTS: For 1481 women aged 35-60 years and 1210 men aged 45-60 years, intakes of total alcohol and specific alcoholic beverages were assessed by six 24-hour dietary records. BMI and WHR were measured during a clinical examination the year after. RESULTS: A J-shaped relationship was found between total alcohol consumption and WHR in both sexes and between total alcohol consumption and BMI in men only (P<0.05). The same relationships were observed with wine (P<0.05); men and women consuming less than 100 g day(-1) had a lower BMI (men only) and WHR than non-drinkers or those consuming more. Spirits consumption was positively associated with BMI (linear regression coefficient beta=0.21, 95% confidence interval (CI): 0.09-0.34 and beta=0.22, 95% CI: 0.06-0.39 for men and women, respectively) and WHR (beta=0.003, 95% CI: 0.001-0.005 and beta=0.003, 95%CI: 0.0002-0.006) in both sexes in a linear fashion. No relationship between beer consumption and BMI or WHR was found. CONCLUSION: If confirmed in longitudinal studies, our results indicate that consumption of alcoholic beverages may be a risk factor for obesity.

The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals.

BACKGROUND: It has been suggested that a low dietary intake of antioxidant vitamins and minerals increases the incidence rate of cardiovascular disease and cancer. To date, however, the published results of randomized, placebo-controlled trials of supplements containing antioxidant nutrients have not provided clear evidence of a beneficial effect. We tested the efficacy of nutritional doses of supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and ischemic cardiovascular disease in the general population. METHODS: The Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study is a randomized, double-blind, placebo-controlled primary prevention trial. A total of 13 017 French adults (7876 women aged 35-60 years and 5141 men aged 45-60 years) were included. All participants took a single daily capsule of a combination of 120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 mug of selenium, and 20 mg of zinc, or a placebo. Median follow-up time was 7.5 years. RESULTS: No major differences were detected between the groups in total cancer incidence (267 [4.1%] for the study group vs 295 [4.5%] for the placebo group), ischemic cardiovascular disease incidence (134 [2.1%] vs 137[2.1%]), or all-cause mortality (76 [1.2%] vs 98 [1.5%]). However, a significant interaction between sex and group effects on cancer incidence was found (P = .004). Sex-stratified analysis showed a protective effect of antioxidants in men (relative risk, 0.69 [95% confidence interval [CI], 0.53-0.91]) but not in women (relative risk, 1.04 [95% CI, 0.85-1.29]). A similar trend was observed for all-cause mortality (relative risk, 0.63 [95% CI, 0.42-0.93] in men vs 1.03 [95% CI, 0.64-1.63] in women; P = .11 for interaction). CONCLUSIONS: After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene.

Sociodemographic and geographic correlates of meeting current recommendations for physical activity in middle-aged French adults: the Supplémentation en Vitamines et Minéraux Antioxydants (SUVIMAX) Study.

OBJECTIVE: We evaluated the characteristics of French subjects meeting current public health recommendations for physical activity. METHODS: We assessed leisure-time physical activity cross-sectionally in 7404 adults aged 45 to 68 years with applied logistic regression models. RESULTS: Meeting the recommended physical activity levels was more likely in subjects aged 60 years and older and in women with higher education levels or living in rural areas and was less likely in smokers. No association was found with time spent watching television. The contribution of vigorous activity to total time spent being active was approximately 2 times higher in subjects meeting recommendations. CONCLUSIONS: Participation in some vigorous activity may be viewed as a "facilitator" to attain physical activity recommendations. Relationships with physical environment variables in Europe need further investigation.

Relationship between serum, red cell, urinary and dietary magnesium in a middle-aged French adult population.

Magnesium (Mg) is the second most common intracellular electrolyte; in the body. Few data are available in general population studies on the assessment of Mg status and its relationship to dietary intake. We explored the relationship between several biological Mg surrogates (serum, red cell, and urinary), Mg intake, age, alcohol intake, and mean energy intake in a large sample of French adults issued from the SUVIMAX study. Serum Mg was positively correlated with red cell Mg in men and women (r = 0.17; p < 0.001) whereas no association was found between urinary Mg and red cell Mg nor between urinary Mg and serum Mg. Age was positively correlated with serum and red cell Mg in women (p < 0.001) and negatively correlated with urinary Mg in both genders (p < 0.001). Finally, a negative correlation was found between dietary intake and red cell Mg in women (r = -0.06; p < 0.05). Among the biological Mg surrogates, an association was found between serum Mg and red cell Mg. Further investigations should be conducted in order to determine the role played by dietary Mg intake in the relationship between health status and several biological Mg measurements.