ACE inhibitor use in patients with myocardial infarction. Summary ofevidence from clinical trials

Experimental evidence for the beneficial effects on heart failure of chronic treatment with ACE inhibitors accumulated from early 1980 in experimental models of LV dysfunction secondary to AMI. These studies demonstrated an improvement in hemodynamics, LV remodeling, and mortality with ACE inhibitor treatment. The effect of ACE inhibitors during the acute phase of AMI was less clear, although there was evidence of protection from ischemic damage, possibly mediated by an increase in collateral coronary blood flow

Non-medical risk factors as avoidable determinants of excess mortality in children with chronic kidney disease. A prospective cohort study in Nicaragua, a model low income country

Background: The widely recognized clinical and epidemiological relevance of the socioeconomic determinants of health-disease conditions is expected to be specifically critical in terms of chronic diseases in fragile populations in low-income countries. However, in the literature, there is a substantial gap between the attention directed towards the medical components of these problems and the actual adoption of strategies aimed at providing solutions for the associated socioeconomic determinants, especially in pediatric populations. We report a prospective outcome study on the independent contribution and reciprocal interaction of the medical and socioeconomic factors to the hard end-point of mortality in a cohort of children with chronic kidney disease in Nicaragua. Methods and Findings: Every child (n = 309) diagnosed with chronic kidney disease (CKD) and referred to the tertiary unit of Pediatric Nephrology in Managua (Nicaragua) from a network of nine hospitals serving 80% of the country's pediatric population was registered between January 2005 and December 2013. The three main socioeconomic determinants evaluated were family income, living conditions and the family's level of education. Further potential determinants of the outcomes included duration of exposure to disease, CKD stage at the first visit as suggested by the KDOQI guidelines in children, the time it took the patients to reach the reference centre and rural or urban context of life. Well-defined and systematically collected medical and socioeconomic data were available for 257 children over a mean follow-up period of 2.5\ub12.5 years. Mortality and lost to follow-up were considered as outcome endpoints both independently and in combination, because of the inevitably progressive nature of the disease. A high proportion (55%) of children presented in the advanced stages of CKD (CKD stage IV and V) at the first visit. At the end of follow-up, 145 (57%) of the 257 cohort children were alive, 47 (18%) were lost to follow-up and 65 (25%) had died. Cox regression analysis showed an independent contribution to mortality of CKD stage at diagnosis and of level of education, with overlapping HR values (HR and 95%CI: 2.66; 1.93-3.66 and 2.72; 1.71-4.33, respectively). Conclusions: The unfavourable socioeconomic and cultural background of the pediatric study cohort and the severity of kidney damage at diagnosis were the key determinants of the clinical risk conditions at baseline and of the mortality outcome. Long-term structural interventions on such backgrounds must be adopted to assure effectiveness of medical care and to assure an earlier diagnosis of CKD in these patients. The translation-extension of our results is currently underway with an agenda which includes: 1) better integration of chronic pediatric conditions into primary care strategies to promote prevention and early timely referral; 2) the consideration of socioeconomic conditions as a mandatory component of the packages of best-care; 3) the formulation and flexible adaptation of guidelines and educational programs, based on the information generated by a context-specific, epidemiological monitoring of needs and outcomes, guaranteed by an effective database

Effects of clopidogrel in addition to aspirin in patients with acutecoronary syndromes without ST-segment elevation.

Background: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. Methods: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. Results: The first primary outcome -- a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome -- the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86, P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.1 percent vs. 1.8 percent, P=0.13) or hemorrhagic strokes. Conclusions: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel. (N Engl J Med 2001;345:494-502.) Copyright (C) 2001 Massachusetts Medical Society

Social factors, diet and breast cancer in a northern Italian population.

The relation of breast cancer to social and dietary variables was evaluated in a case-control study of 368 women with breast cancer admitted to the General Hospital of Pordenone (a town in the eastern side of Northern Italy) and 373 age-matched controls. Occupation was related to the risk of breast cancer, housewives and non-manual workers (teachers and other professionals, clerical workers, etc.) showing relative risks of 1.7 and 2.4 respectively when compared to women occupied in agriculture. The role of education was apparently less important, and not statistically significant. The risk was higher in women who were obese, the trend of increasing risk with increasing body mass index being confined to post-menopausal women. When indicators of dietary fat intake were analysed, a significantly increased risk was found with more frequent consumption of milk and dairy products but the risk estimates were only slightly above unity with reference to meat consumption. Women who drank alcoholic beverages showed a relative risk of 2.5 compared to women who had never drunk, when allowance was made for all identified potential confounding factors. The association between alcohol and breast cancer was not explained by the other dietary variables considered, and the risk estimates were higher for women who drank more wine, or more than one type of alcoholic beverage. Thus, the findings of the present study give evidence in favour of the hypothesis that alcohol consumption is related to the risk of breast cancer

Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study.

We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04 (95% confidence interval (CI) 0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer

Direct comparison of B-Type Natriuretic Peptide (BNP) and amino-terminal proBNP in a large population of patients with chronic and symptomatic heart failure: the Valsartan Heart Failure (Val-HeFT) data

Background: The B-type or brain natriuretic peptides (BNP) and the amino-terminal probrain natriuretic peptide (NT-proBNP) are good markers of prognosis and diagnosis in chronic heart failure (HF). It is unclear, however, whether differences in their biological characteristics modify their clinical correlates and prognostic performance in HF. This work aimed to provide a direct comparison of the prognostic value of BNP and NTproBNP in patients with chronic and stable HF. Methods: We measured BNP and NT-proBNP at baseline in 3916 patients enrolled in the Valsartan Heart Failure Trial. To identify the variables associated with both peptides, we conducted simple and multivariable linear regression analyses. We used Cox multivariable regression models to evaluate the independent prognostic value for all-cause mortality, mortality and morbidity, and hospitalization for HF. Prognostic performance was assessed by pairwise comparisons of the area under the curve of receiver-operator characteristic curves. Results: NT-proBNP and BNP had similar relationships with age, left ventrical ejection fraction, and internal diameter and creatinine clearance. Either peptide ranked as the first independent predictor of outcome after adjustment for major confounding clinical characteristics. ROC curves were almost superimposable for all-cause mortality (area under the curve (SE): BNP 0.665 (0.011) vs NT-proBNP 0.679 (0.011); P 0.0734), but NT-proBNP was superior to BNP for predicting mortality and morbidity (P 0.032) or hospitalization for HF (P 0.0143). Overall sensitivity and specificity ranged from 0.590 to 0.696. Conclusions: The natriuretic peptides BNP and NTproBNP showed subtle differences in their relation to clinical characteristics and prognostic performance in a large population of patients with chronic and stable HF. They were the most powerful independent markers of outcome in HF

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

In pres

Evaluation of self-absorption of manganese emission lines in Laser Induced Breakdown Spectroscopy measurements

This paper is part of a more general study aimed to the determination of the best experimental procedures for reliable quantitative measurements of Fe-Mn alloys by LIBS. In this work, attention is pointed on the self-absorption processes, whose effect deeply influences the LIBS measurements, reflecting in non-linear calibration curves. The effect of self-absorption on the line intensity can be quantified by defining a self absorption coefficient, that measures the deviation of the line intensity from the linear extrapolation of the curve of growth in the optically thin regime. The authors demonstrated in a previous paper that self absorption coefficients could be calculated once the electron density of the plasma is known and the Stark coefficients of the lines are available. However, when the Stark coefficients of the lines of interest are not known, a different approach is needed. In this work a new method for evaluation of self absorption coefficients in LIBS measurements is presented, which does not require the knowledge of Stark coefficients. In order to understand the basic principles and setting out the theoretical tools that will be used for the analysis o f the alloys, a preliminary study was done on pure Mn; LIBS spectra were acquired in different experimental conditions, at different laser energies and different delays after the laser irradiation o f the sample. Moreover, collinear double pulse measurements were also performed. Analytical relations were derived and experimental procedures devised for evaluation o f the self absorption coefficients of several Mn lines, which are important for characterization and control of the experimental conditions in which the analysis is performed