Caspase-3 Protects Stressed Organs against Cell Death.

The ability to generate appropriate defense responses is crucial for the survival of an organism exposed to pathogenesis-inducing insults. However, the mechanisms that allow tissues and organs to cope with such stresses are poorly understood. Here we show that caspase-3-knockout mice or caspase inhibitor-treated mice were defective in activating the antiapoptotic Akt kinase in response to various chemical and environmental stresses causing sunburns, cardiomyopathy, or colitis. Defective Akt activation in caspase-3-knockout mice was accompanied by increased cell death and impaired survival in some cases. Mice homozygous for a mutation in RasGAP that prevents its cleavage by caspase-3 exhibited a similar defect in Akt activation, leading to increased apoptosis in stressed organs, marked deterioration of their physiological functions, and stronger disease development. Our results provide evidence for the relevance of caspase-3 as a stress intensity sensor that controls cell fate by either initiating a RasGAP cleavage-dependent cell resistance program or a cell suicide response.

Inventory and perspectives of chronic disease management programs in Switzerland: an exploratory survey.

OBJECTIVE: To describe chronic disease management programs active in Switzerland in 2007, using an exploratory survey. METHODS: We searched the internet (Swiss official websites and Swiss web-pages, using Google), a medical electronic database (Medline), reference lists of pertinent articles, and contacted key informants. Programs met our operational definition of chronic disease management if their interventions targeted a chronic disease, included a multidisciplinary team (>/=2 healthcare professionals), lasted at least six months, and had already been implemented and were active in December 2007. We developed an extraction grid and collected data pertaining to eight domains (patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment, clinical outcomes). RESULTS: We identified seven programs fulfilling our operational definition of chronic disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, psychosis and breast cancer. Interventions were multifaceted; all included education and half considered planned follow-ups. The recipients of the interventions were patients, and healthcare professionals involved were physicians, nurses, social workers, psychologists and case managers of various backgrounds. CONCLUSIONS: In Switzerland, a country with universal healthcare insurance coverage and little incentive to develop new healthcare strategies, chronic disease management programs are scarce. For future developments, appropriate evaluations of existing programs, involvement of all healthcare stakeholders, strong leadership and political will are, at least, desirable.

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

Chagas heart disease (CHD) results from infection with the protozoan parasite Trypanosoma cruzi and is the leading cause of infectious myocarditis worldwide. It poses a substantial public health burden due to high morbidity and mortality. CHD is also the most serious and frequent manifestation of chronic Chagas disease and appears in 20-40% of infected individuals between 10-30 years after the original acute infection. In recent decades, numerous clinical and experimental investigations have shown that a low-grade but incessant parasitism, along with an accompanying immunological response [either parasite-driven (most likely) or autoimmune-mediated], plays an important role in producing myocardial damage in CHD. At the same time, primary neuronal damage and microvascular dysfunction have been described as ancillary pathogenic mechanisms. Conduction system disturbances, atrial and ventricular arrhythmias, congestive heart failure, systemic and pulmonary thromboembolism and sudden cardiac death are the most common clinical manifestations of chronic Chagas cardiomyopathy. Management of CHD aims to relieve symptoms, identify markers of unfavourable prognosis and treat those individuals at increased risk of disease progression or death. This article reviews the pathophysiology of myocardial damage, discusses the value of current risk stratification models and proposes an algorithm to guide mortality risk assessment and therapeutic decision-making in patients with CHD.

All-around care for patients with Chagas disease: a challenge for the XXI century

In 1987, the University of Pernambuco's Oswaldo Cruz Hospital in Recife, Brazil opened its Chagas Disease and Heart Failure Outpatient Clinic with the aim of providing its patients all-around care through adoption of a biopsychosocial model of care. All-around care involves caring for the patient as a whole human being in the context of the biological, psychological and social factors present, which are an inherent part of the human condition. One prerequisite for the proposed model of care is the participation of a multidisciplinary team of trained technical staff committed to this framework. Although the main focus of the service is on care, teaching and research are also an important part of its work. The Pernambuco Association of Chagas Disease Patients is guided by the same model of care and has been carrying out educational activities relating to the disease, its treatment and support for patients and family members for several years. This Association plays an important role in advocating to public authorities on behalf of patients. The accumulated experience of the past 22 years has shown us that a broad vision of health care can help clinicians and policy makers to make decisions that are more in tune with the everyday reality of the patient, which in turn has a positive impact on adherence to treatment and quality of life.

Cellular and genetic mechanisms involved in the generation of protective and pathogenic immune responses in human Chagas disease

Perhaps one of the most intriguing aspects of human Chagas disease is the complex network of events that underlie the generation of protective versus pathogenic immune responses during the chronic phase of the disease. While most individuals do not develop patent disease, a large percentage may develop severe forms that eventually lead to death. Although many efforts have been devoted to deciphering these mechanisms, there is still much to be learned before we can fully understand the pathogenesis of Chagas disease. It is clear that the host's immune response is decisive in this process. While characteristics of the parasite influence the immune response, it is becoming evident that the host genetic background plays a fundamental role in the establishment of pathogenic versus protective responses. The involvement of three complex organisms, host, parasite and vector, is certainly one of the key aspects that calls for multidisciplinary approaches towards the understanding of Chagas disease. We believe that now, one hundred years after the discovery of Chagas disease, it is imperative to continue with highly interactive research in order to elucidate the immune response associated with disease evolution, which will be essential in designing prophylactic or therapeutic interventions.

Comprehensive heart disease action plan for Andalusia 2005-2009 : Andalusian Public Health System

The Comprehensive Heart Disease Action Plan for Andalusia 2005-2009 has been prepared within the framework of the presentations made both in the 3rd Andalusian Health Action Plan and in the Quality Plan of the Public Health System. Consequently, as with these two referral instruments, the improvement in the health results for the citizens of Andalusia continues to be sought without wavering, specifically with regard to meeting the needs and expectations of the population affected by health problems in this area.

Validation and clinical use of the CECA, a disease-specific quality of life questionnaire for patients with anogenital Condylomata Acuminata

The aim of this validation study was to assess the measurement properties of the CECA (Spanish acronym for the Specific Questionnaire for Condylomata Acuminata) in patients with anogenital condylomas. A total of 247 patients aged > 18 years completed the questionnaire on 2 occasions as well as the Dermatology Life Quality Index (DLQI). The CECA questionnaire showed good internal consistency (Cronbach's alpha values of 0.86 and 0.91 in the emotional and sexual activity dimensions) and good testretest reliability (intraclass correlation coefficient 0.76 emotional dimension, 0.82 sexual activity dimension). Patients with de novo lesions and those with more extensive lesions and larger number of warts showed poorer health-related quality of life. CECA and DLQI scores correlated moderately. Patients whose lesions cleared at follow-up or with a reduction of >or= 50% showed a better improvement of health-related quality of life. The CECA questionnaire is a valid, reliable and sensitive tool for the assessment of health-related quality of life in patients with anogenital warts.

Clinical predictors for fatal pulmonary embolism in 15520 patients with venous thromboembolism - Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry

BACKGROUND Clinical predictors for fatal pulmonary embolism (PE) in patients with venous thromboembolism have never been studied. METHODS AND RESULTS Using data from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry about patients with objectively confirmed symptomatic acute venous thromboembolism, we determined independent predictive factors for fatal PE. Between March 2001 and July 2006, 15520 consecutive patients (mean age+/-SD, 66.3+/-16.9 years; 49.7% men) with acute venous thromboembolism were included. Symptomatic deep-vein thrombosis without symptomatic PE was observed in 58.0% (n=9008) of patients, symptomatic nonmassive PE in 40.4% (n=6264), and symptomatic massive PE in 1.6% (n=248). At 3 months, the cumulative rates of overall mortality and fatal PE were 8.65% and 1.68%, respectively. On multivariable analysis, patients with symptomatic nonmassive PE at presentation exhibited a 5.42-fold higher risk of fatal PE compared with patients with deep-vein thrombosis without symptomatic PE (P<0.001). The risk of fatal PE was multiplied by 17.5 in patients presenting with a symptomatic massive PE. Other clinical factors independently associated with an increased risk of fatal PE were immobilization for neurological disease, age >75 years, and cancer. CONCLUSIONS PE remains a potentially fatal disease. The clinical predictors identified in the present study should be included in any clinical risk stratification scheme to optimally adapt the treatment of PE to the risk of the fatal outcome.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Cardiac patient

Patients with cardiac disease can develop two types of malnutrition: cardiac cachexia, which appears in chronic congestive heart failure, and malnutrition due to the complications of cardiac surgery or any other type of surgery in patients with heart disease. Early enteral nutrition should be attempted if the oral route cannot be used. When cardiac function is severely compromised, enteral nutrition is feasible, but supplementation with parenteral nutrition is sometimes required. Sustained hyperglycemia in the first 24 hours in patients admitted for acute coronary syndrome, whether diabetic or not, is a poor prognostic factor for 30-day mortality. In critically-ill cardiac patients with stable hemodynamic failure, nutritional support of 20-25 kcal/kg/day is effective in maintaining adequate nutritional status. Protein intake should be 1.2-1.5 g/kg/day. Routine polymeric or high protein formulae should be used, according to the patient's prior nutritional status, with sodium and volume restriction according to the patient's clinical situation. The major energy source for myocytes is glutamine, through conversion to glutamate, which also protects the myocardial cell from ischemia in critical situations. Administration of 1 g/day of omega-3 (EPA+DHA) in the form of fish oil can prevent sudden death in the treatment of acute coronary syndrome and can also help to reduce hospital admission for cardiovascular events in patients with chronic heart failure.

Gender differences in HIV-positive persons in use of cardiovascular disease-related interventions : D:A:D study

INTRODUCTION: There is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV-positive individuals. We investigated whether such differences exist in the D:A:D study. MATERIALS AND METHODS: Follow-up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10-year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors. RESULTS: At enrolment, women (n=13,039; median (interquartile range) 34 (29-40) years) were younger than men (n=36,664, 39 (33-46) years, p=0.001), and were less likely to be current smokers (29% vs. 39%, p=0.0001), to have diabetes (2% vs. 3%, p=0.0001) or to have hypertension (7% vs. 11%, p=0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high-risk group, initiation rates of most interventions (with the exception of anti-hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1). CONCLUSION: Use of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions.

Improved prediction of coronary heart disease with markers of atherosclerosis and of inflammation in older adults?

Background: Several markers of atherosclerosis and of inflammation have been shown to predict coronary heart disease (CHD) individually. However, the utility of markers of atherosclerosis and of inflammation on prediction of CHD over traditional risk factors has not been well established, especially in the elderly. Methods: We studied 2202 men and women, aged 70-79, without baseline cardiovascular disease over 6-year follow-up to assess the risk of incident CHD associated with baseline noninvasive measures of atherosclerosis (ankle-arm index [AAI], aortic pulse wave velocity [aPWV]) and inflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP], tumor necrosis factor-a [TNF-a]). CHD events were studied as either nonfatal myocardial infarction or coronary death ("hard" events), and "hard" events plus hospitalization for angina, or the need for coronary-revascularization procedures (total CHD events). Results: During the 6-year follow-up, 283 participants had CHD events (including 136 "hard" events). IL-6, TNF-a and AAI independently predicted CHD events above Framingham Risk Score (FRS) with hazard ratios [HR] for the highest as compared with the lowest quartile for IL-6 of 1.95 (95%CI: 1.38-2.75, p for trend <0.001), TNF-a of 1.45 (95%CI: 1.04-2.02, p for trend 0.03), of 1.66 (95%CI: 1.19-2.31) for AAI 0.9, as compared to AAI 1.01-1.30. CRP and aPWV were not independently associated with CHD events. Results were similar for "hard" CHD events. Addition of IL-6 and AAI to traditional cardiovascular risk factors yielded the greatest improvement in the prediction of CHD; C-index for "hard"/total CHD events increased from 0.62/0.62 for traditional risk factors to 0.64/0.64 for IL-6 addition, 0.65/0.63 for AAI, and 0.66/0.64 for IL-6 combined with AAI. Being in the highest quartile of IL-6 combined with an AAI 0.90 or >1.40 yielded an HR of 2.51 (1.50-4.19) and 4.55 (1.65-12.50) above FRS, respectively. With use of CHD risk categories, risk prediction at 5 years was more accurate in models that included IL-6, AAI or both, with 8.0, 8.3 and 12.1% correctly reclassified, respectively. Conclusions: Among older adults, markers of atherosclerosis and of inflammation, particularly IL-6 and AAI, are independently associated with CHD. However, these markers only modestly improve cardiovascular risk prediction beyond traditional risk factors.

Intake and home use of olive oil or mixed oils in relation to healthy lifestyles in a Mediterranean population. Findings from the prospective Pizarra study.

Discordances exist in epidemiological studies regarding the association between the intake of nutrients and death and disease. We evaluated the social and health profile of persons who consumed olive oil in a prospective population cohort investigation (Pizarra study) with a 6-year follow-up. A food frequency questionnaire and a 7 d quantitative questionnaire were administered to 538 persons. The type of oil used in food preparation was determined by direct measurement of the fatty acids in samples obtained from the kitchens of the participants at baseline and after follow-up for 6 years. The fatty acid composition of the serum phospholipids was used as an endogenous marker of the type of oil consumed. Total fat intake accounted for a mean 40 % of the energy (at baseline and after follow-up). The concordance in intake of MUFA over the study period was high. The fatty acid composition of the serum phospholipids was significantly associated with the type of oil consumed and with fish intake. The concentration of polar compounds and polymers, indicative of degradation, was greater in oils from the kitchens where sunflower oil or refined olive oil was used, in oils used for deep frying and in oils that had been reused for frying five times or more. Consumption of olive oil was directly associated with educational level. Part of the discordance found in epidemiological studies between diet and health may be due to the handling of oils during food preparation. The intake of olive oil is associated with other healthy habits.

Pre-hospital antibiotic treatment and mortality caused by invasive meningococcal disease, adjusting for indication bias.

Background: Mortality from invasive meningococcal disease (IMD) has remained stable over the last thirty years and it is unclear whether pre-hospital antibiotherapy actually produces a decrease in this mortality. Our aim was to examine whether pre-hospital oral antibiotherapy reduces mortality from IMD, adjusting for indication bias. Methods: A retrospective analysis was made of clinical reports of all patients (n = 848) diagnosed with IMD from 1995 to 2000 in Andalusia and the Canary Islands, Spain, and of the relationship between the use of pre-hospital oral antibiotherapy and mortality. Indication bias was controlled for by the propensity score technique, and a multivariate analysis was performed to determine the probability of each patient receiving antibiotics, according to the symptoms identified before admission. Data on in-hospital death, use of antibiotics and demographic variables were collected. A logistic regression analysis was then carried out, using death as the dependent variable, and prehospital antibiotic use, age, time from onset of symptoms to parenteral antibiotics and the propensity score as independent variables. Results: Data were recorded on 848 patients, 49 (5.72%) of whom died. Of the total number of patients, 226 had received oral antibiotics before admission, mainly betalactams during the previous 48 hours. After adjusting the association between the use of antibiotics and death for age, time between onset of symptoms and in-hospital antibiotic treatment, pre-hospital oral antibiotherapy remained a significant protective factor (Odds Ratio for death 0.37, 95% confidence interval 0.15–0.93). Conclusion: Pre-hospital oral antibiotherapy appears to reduce IMD mortality.

Consumption of fried foods and risk of coronary heart disease: Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study.

OBJECTIVE To assess the association between consumption of fried foods and risk of coronary heart disease. DESIGN Prospective cohort study. SETTING Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. PARTICIPANTS 40 757 adults aged 29-69 and free of coronary heart disease at baseline (1992-6), followed up until 2004. MAIN OUTCOME MEASURES Coronary heart disease events and vital status identified by record linkage with hospital discharge registers, population based registers of myocardial infarction, and mortality registers. RESULTS During a median follow-up of 11 years, 606 coronary heart disease events and 1135 deaths from all causes occurred. Compared with being in the first (lowest) quarter of fried food consumption, the multivariate hazard ratio of coronary heart disease in the second quarter was 1.15 (95% confidence interval 0.91 to 1.45), in the third quarter was 1.07 (0.83 to 1.38), and in the fourth quarter was 1.08 (0.82 to 1.43; P for trend 0.74). The results did not vary between those who used olive oil for frying and those who used sunflower oil. Likewise, no association was observed between fried food consumption and all cause mortality: multivariate hazard ratio for the highest versus the lowest quarter of fried food consumption was 0.93 (95% confidence interval 0.77 to 1.14; P for trend 0.98). CONCLUSION In Spain, a Mediterranean country where olive or sunflower oil is used for frying, the consumption of fried foods was not associated with coronary heart disease or with all cause mortality.

Social inequalities and mortality in Europe-results from a large multi-national cohort

BACKGROUND Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.