Colchicine reduces the activation of NLRP3 inflammasome in COVID-19 patients.

OBJECTIVE: To evaluate whether colchicine treatment was associated with the inhibition of NLRP3 inflammasome activation in patients with COVID-19. METHODS: We present a post hoc analysis from a double-blinded placebo-controlled randomized clinical trial (RCT) on the effect of colchicine for the treatment of COVID-19. Serum levels of NOD-like receptor protein 3 (NLRP3) inflammasome products-active caspase-1 (Casp1p20), IL-1ß, and IL-18-were assessed at enrollment and after 48-72 h of treatment in patients receiving standard-of-care (SOC) plus placebo vs. those receiving SOC plus colchicine. The colchicine regimen was 0.5 mg tid for 5 days, followed by 0.5 mg bid for another 5 days. RESULTS: Thirty-six patients received SOC plus colchicine, and thirty-six received SOC plus placebo. Colchicine reduced the need for supplemental oxygen and the length of hospitalization. On Days 2-3, colchicine lowered the serum levels of Casp1p20 and IL-18, but not IL-1ß. CONCLUSION: Treatment with colchicine inhibited the activation of the NLRP3 inflammasome, an event triggering the 'cytokine storm' in COVID-19. TRIAL REGISTRATION NUMBERS: RBR-8jyhxh.

HbA 1c as a risk factor for heart failure in persons with diabetes: the Atherosclerosis Risk in Communities (ARIC) study.

AIMS/HYPOTHESIS: Heart failure (HF) incidence in diabetes in both the presence and absence of CHD is rising. Prospective population-based studies can help describe the relationship between HbA(1c), a measure of glycaemia control, and HF risk. METHODS: We studied the incidence of HF hospitalisation or death among 1,827 participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes and no evidence of HF at baseline. Cox proportional hazard models included age, sex, race, education, health insurance status, alcohol consumption, BMI and WHR, and major CHD risk factors (BP level and medications, LDL- and HDL-cholesterol levels, and smoking). RESULTS: In this population of persons with diabetes, crude HF incidence rates per 1,000 person-years were lower in the absence of CHD (incidence rate 15.5 for CHD-negative vs 56.4 for CHD-positive, p<0.001). The adjusted HR of HF for each 1% higher HbA(1c) was 1.17 (95% CI 1.11-1.25) for the non-CHD group and 1.20 (95% CI 1.04-1.40) for the CHD group. When the analysis was limited to HF cases which occurred in the absence of prevalent or incident CHD (during follow-up) the adjusted HR remained 1.20 (95% CI 1.11-1.29). CONCLUSIONS/INTERPRETATIONS: These data suggest HbA(1c) is an independent risk factor for incident HF in persons with diabetes with and without CHD. Long-term clinical trials of tight glycaemic control should quantify the impact of different treatment regimens on HF risk reduction.

Minor segmental wall motion abnormalities detected in patients with Chagas' disease have adverse prognostic implications.

Recent data from our laboratory have shown that patients with the indeterminate form of Chagas' disease can have impairment of left ventricular contractility, as evaluated by the slope of the left ventricle end-systolic pressure-dimension relationship. We also showed that Chagas' disease patients with minimal baseline wall motion abnormalities detected by two-dimensional echocardiography have more intense contractility impairment when compared to patients with the indeterminate form of the disease without this abnormality. The prognostic implications of these findings have not been established. We evaluated 59 patients (37-76 years, mean = 55 years) with different clinical forms of Chagas' disease, who had normal left ventricular global systolic function at baseline (57.6 +/- 6.9%) and who had at least one additional echo during clinical follow-up (0.4-17.6; mean 4.6 years). Group 1 consisted of 14 patients with minor baseline left ventricle wall motion abnormalities and group 2 consisted of 45 patients without these abnormalities. During follow-up, global left ventricle systolic function deterioration was observed in 10 group 1 patients (71.4%) and in only 10 group 2 patients (22.2%; P < 0.005). Age and duration of follow-up were not independent determinants of left ventricular function deterioration in these patients. The present data indicate that mild segmental left ventricular wall motion abnormalities are associated with worsening of systolic function in Chagas' disease patients who have normal baseline global systolic performance.

Automated grading of left ventricular segmental wall motion by an artificial neural network using color kinesis images.

The present study describes an auxiliary tool in the diagnosis of left ventricular (LV) segmental wall motion (WM) abnormalities based on color-coded echocardiographic WM images. An artificial neural network (ANN) was developed and validated for grading LV segmental WM using data from color kinesis (CK) images, a technique developed to display the timing and magnitude of global and regional WM in real time. We evaluated 21 normal subjects and 20 patients with LVWM abnormalities revealed by two-dimensional echocardiography. CK images were obtained in two sets of viewing planes. A method was developed to analyze CK images, providing quantitation of fractional area change in each of the 16 LV segments. Two experienced observers analyzed LVWM from two-dimensional images and scored them as: 1) normal, 2) mild hypokinesia, 3) moderate hypokinesia, 4) severe hypokinesia, 5) akinesia, and 6) dyskinesia. Based on expert analysis of 10 normal subjects and 10 patients, we trained a multilayer perceptron ANN using a back-propagation algorithm to provide automated grading of LVWM, and this ANN was then tested in the remaining subjects. Excellent concordance between expert and ANN analysis was shown by ROC curve analysis, with measured area under the curve of 0.975. An excellent correlation was also obtained for global LV segmental WM index by expert and ANN analysis (R2 = 0.99). In conclusion, ANN showed high accuracy for automated semi-quantitative grading of WM based on CK images. This technique can be an important aid, improving diagnostic accuracy and reducing inter-observer variability in scoring segmental LVWM.

Basic life support knowledge of first-year university students from Brazil.

We aimed to evaluate knowledge of first aid among new undergraduates and whether it is affected by their chosen course. A questionnaire was developed to assess knowledge of how to activate the Mobile Emergency Attendance Service - MEAS (Serviço de Atendimento Móvel de Urgência; SAMU), recognize a pre-hospital emergency situation and the first aid required for cardiac arrest. The students were also asked about enrolling in a first aid course. Responses were received from 1038 of 1365 (76.04%) new undergraduates. The questionnaires were completed in a 2-week period 1 month after the beginning of classes. Of the 1038 respondents (59.5% studying biological sciences, 11.6% physical sciences, and 28.6% humanities), 58.5% knew how to activate the MEAS/SAMU (54.3% non-biological vs 61.4% biological, P=0.02), with an odds ratio (OR)=1.39 (95%CI=1.07-1.81) regardless of age, sex, origin, having a previous degree or having a relative with cardiac disease. The majority could distinguish emergency from non-emergency situations. When faced with a possible cardiac arrest, 17.7% of the students would perform chest compressions (15.5% non-biological vs 19.1% biological first-year university students, P=0.16) and 65.2% would enroll in a first aid course (51.1% non-biological vs 74.7% biological, P<0.01), with an OR=2.61 (95%CI=1.98-3.44) adjusted for the same confounders. Even though a high percentage of the students recognized emergency situations, a significant proportion did not know the MEAS/SAMU number and only a minority had sufficient basic life support skills to help with cardiac arrest. A significant proportion would not enroll in a first aid course. Biological first-year university students were more prone to enroll in a basic life support course.

Relation of regional sympathetic denervation and myocardial perfusion disturbance to wall motion impairment in Chagas' cardiomyopathy.

Impairment of sinus node autonomic control and myocardial perfusion disturbances have been described in patients with chronic Chagas' cardiomyopathy. However, it is not clear how these conditions contribute to myocardial damage. In this investigation, iodine-123 (I-123) meta-iodobenzylguanidine (MIBG) and thallium-201 myocardium segmental uptake were studied in correlation with the severity of left ventricular (LV) dysfunction detected in various phases of Chagas' heart disease. Group I consisted of 12 subjects (43 +/- 4 years, 7 men) with no symptoms and no cardiac involvement on electrocardiogram (ECG) or echocardiography; group II consisted of 13 patients (48 +/- 3 years, 9 men) with abnormal resting ECG and/or echocardiographic segmental abnormalities, and LV ejection fraction of > or = 0.5; group III was comprised of 12 patients (59 +/- 3 years, 10 men) with more severe heart disease, LV dilation, and LV ejection fraction of < 0.5. Eighteen control volunteers (38 +/- 3 years, 9 men) were also included in the study. I-123 MIBG single-photon emission computed tomographic (SPECT) segmental uptake defects were observed in group I (33%), group II (77%), and group III (92%). Quantitative analysis showed mean areas of reduced LV I-123-MIBG uptake: group I was 3.7 +/- 2.1%; group II was 8.3 +/- 2.3%; and group III was 19.0 +/- 3.3%. The differences between group I and both groups II and III were statistically significant (p < 0.001, analysis of variance test). Myocardial perfusion defects (reversible, fixed, and paradox) were observed in group I (83%), group II (69%), and group III (83%). A marked topographic association between perfusion, innervation, and wall motion abnormalities (assessed by gated-SPECT perfusion studies) was observed in all the groups. Defects predominated in the inferior, posterior lateral, and apical LV regions. Thus, extensive impairment of cardiac sympathetic function at the ventricular level occured early in the course of Chagas' cardiomyopathy and was related to regional myocardial perfusion disturbances, before wall motion abnormalities. Both conditions are associated with progression of ventricular dysfunction.

Gene polymorphisms in the TNF locus and the risk of myocardial infarction.

We investigated two genetic polymorphisms in the tumor necrosis factor locus (TNF-alpha -308 G-->A and LT-alpha +252 A-->G) as risk factors for coronary atherothrombotic disease (CAD) by determining its prevalence in 148 survivors of myocardial infarction (MI) with angiographically-proven severe CAD, and in 148 age-, gender- and race-matched controls. The odds ratio (OR) for MI related to the mutant TNF-alpha and LT-alpha alleles was 0.8 (CI95: 0.4-1.3) and 1. 3 (CI95: 0.8-2.0), respectively. We also sought interaction of smoking and metabolic risk factors for MI with each mutant genotype. Smokers not carrying the LT-alpha +252 A-->G mutation had a risk of MI of 2.7 (CI95: 1.4-5.4) whereas in smoking carriers the risk was 6. 9 (CI95: 3.4-14.1). An interactive effect of the LT-alpha mutation may also exist with dyslipidemia (OR for MI in non-carriers was 12 [CI95: 3.2-41.3] and in carriers the OR was 39, [CI95: 5.1-301] and with obesity (OR for MI was 2.7, [CI95: 1-7.2] in non-carriers and in carriers the OR was 6 [CI95: 2.1-16.8]). Lastly, the OR for MI in obese non-carriers of TNF-alpha -308 G-->A was 2.8 (CI95: 1.3-6) and in obese carriers the OR was 14.5 (CI95: 1.8-113). Although significant interactive effects could not be detected, the findings suggest that interaction of polymorphisms in the TNF locus with major risk factors for CAD may exist, and should be explored in larger studies.

Effects of blood viscosity on proximal flow convergence calculations of regurgitant flow rate and jet dimensions as evaluated by color Doppler flow mapping: an in vitro study.

There are limited data on the potential influence of blood viscosity on the quantification of valvular regurgitation by color Doppler in the clinical setting. This study was designed to evaluate the effects of blood viscosity on jet dimensions and the proximal flow convergence (proximal isovelocity surface area, PISA) method of estimating valvular insufficiency severity. We used an in vitro flow model filled with human blood at varying hematocrits (15%, 35%, and 55%) and blood viscosity (blood/water viscosity: 2.6, 4.8, 9.1) in which jets were driven through a known orifice (16 mm(2)) into a 110-mL compliant receiving chamber (compliance: 2.2 mL/mm Hg) by a power injection pump. Blood injections (2 and 4 mL) at flow rates of 4, 6, 8, 10, and 12 mL/s were performed. Proximal flow convergence and spatial distribution of jets were imaged by a 3.5-MHz transducer. Pressure and volume in the flow model were kept constant before each injection. Ultrasound settings were the same for all experiments. Jet area decreased significantly with increasing blood viscosity, but the difference in jet dimensions was much larger for lower than for higher flow rates and for highest blood viscosity. Estimation of flow rate by the PISA method was not significantly influenced by blood viscosity. Blood viscosity has a major influence in jet area, especially for lower flow rates, but did not change significantly the grading of regurgitation by the PISA method. Thus this factor should be considered for determining the method of choice when quantification of valvular regurgitation is performed in patients with anemia or polycythemia.

Cardiac autonomic impairment and early myocardial damage involving the right ventricle are independent phenomena in Chagas' disease.

Cardiac autonomic impairment and right side heart failure are prominent features in patients with Chagas' disease, but no causal relationship between these phenomena has been disclosed and the pathophysiology of such manifestations is unclear. Aim of study was to assess the cardiac autonomic control and biventricular function in chagasic patients in early stages of the disease, using radionuclide angiography, Valsalva manoeuvre, head-up tilt and baroreflex sensitivity evaluation. Thirty-one chagasic patients with no clinical signs of Chagas' heart disease-16 in the indeterminate phase and 15 with sole organic digestive involvement-were studied, and results compared with those obtained in 14 normal volunteers. No significant differences were observed among the three groups, in regard to any systolic or diastolic parameter of LV function, including ejection fraction, peak ejection and filling rates and correspondent times, time to end-systole, and the standard deviation of phase values. The indeterminate and digestive groups of chagasics had significantly lower right ventricular ejection fraction (45.7 +/- 6.3 and 46.2 +/- 10.1 respectively) and peak ejection rate (respectively 2.8 +/- 0.6 and 2.9 +/- 0.6) and higher right ventricular phase standard deviation (22.4 +/- 5.9 and 20.1 +/- 5.6 degrees, respectively), as compared with the control group (53.6 +/- 4.3, 3.5 +/- 0.5, and 15.8 +/- 3.8 respectively for right ventricular ejection fraction, peak ejection rate and phase standard deviation). No significant differences were found between the results of autonomic evaluation in the control and indeterminate groups of chagasic patients. The group of digestive disease patients showed abnormally lower Valsalva ratio (1.5 +/- 0.15), baroreflex sensitivity (8.85 +/- 2.05 ms/mmHg) and parasympathetically-dependent heart rate response to tilt (8.85 +/- 8.42 beats/mm) and higher Valsalva delay (15.67 +/- 1.35 s) values, compared with the control group (respectively 1.85 +/- 0.49, 20.23 +/- 12.66 ms/mmHg, 21.61 +/- 5.77 beats/mm and 10.1 +/- 2.5 s). Thus, cardiac autonomic impairment is a prominent feature in chagasic patients with the digestive but not the indeterminate form of Chagas' disease. It bears no causative relationship to the early myocardial damage that is apparent only regarding right ventricular function, in both groups of patients. Early right ventricular dysfunction is a likely mechanism for the marked predominance of systemic over pulmonary congestion when heart failure supervenes in patients with Chagas' disease.

HFE gene mutations in coronary atherothrombotic disease.

Although iron can catalyze the production of free radicals involved in LDL lipid peroxidation, the contribution of iron overload to atherosclerosis remains controversial. The description of two mutations in the HFE gene (Cys282Tyr and His63Asp) related to hereditary hemochromatosis provides an opportunity to address the question of the association between iron overload and atherosclerosis. We investigated the prevalence of HFE mutations in 160 survivors of myocardial infarction with angiographically demonstrated severe coronary atherosclerotic disease, and in 160 age-, gender- and race-matched healthy control subjects. PCR amplification of genomic DNA followed by RsaI and BclI restriction enzyme digestion was used to determine the genotypes. The frequency of the mutant Cys282Tyr allele was identical among patients and controls (0.022; carrier frequency, 4.4%), whereas the mutant His63Asp allele had a frequency of 0.143 (carrier frequency, 27.5%) in controls and of 0.134 (carrier frequency, 24.5%) in patients. Compound heterozygotes were found in 2 of 160 (1.2%) controls and in 1 of 160 (0.6%) patients. The finding of a similar prevalence of Cys282Tyr and His63Asp mutations in the HFE gene among controls and patients with coronary atherothrombotic disease, indirectly questions the possibility of an association between hereditary hemochromatosis and atherosclerosis.

The X-X-/E+E+ genotype of the XbaI/EcoRI polymorphisms of the apolipoprotein B gene as a marker of coronary artery disease in a Brazilian sample.

Studies that consider polymorphisms within the apolipoprotein B (apo B) gene as risk factors for coronary artery disease (CAD) have reported conflicting results. The aim of the present study was to search for associations between two DNA RFLPs (XbaI and EcoRI) of the apo B gene and CAD diagnosed by angiography. In the present study we compared 116 Brazilian patients (92 men) with CAD (CAD+) to 78 control patients (26 men) without ischemia or arterial damage (CAD-). The allele frequencies at the XbaI (X) and EcoRI (E) sites did not differ between groups. The genotype distributions of CAD+ and CAD- patients were different (chi (1) = 6.27, P = 0.012) when assigned to two classes (X-X-/E+E+ and the remaining XbaI/EcoRI genotypes). Multivariate logistic regression analysis showed that individuals with the X-X-/E+E+ genotype presented a 6.1 higher chance of developing CAD than individuals with the other XbaI/EcoRI genotypes, independently of the other risk factors considered (sex, tobacco consumption, total cholesterol, hypertension, and triglycerides). We conclude that the X-X-/E+E genotype may be in linkage disequilibrium with an unknown variation in the apo B gene or with a variation in another gene that affects the risk of CAD.

Trastuzumab-induced myocardiotoxicity mimicking acute coronary syndrome.

Trastuzumab is an important biological agent in the treatment of HER2-positive breast cancer, with effects on response rates, progression-free survival, overall survival and quality of life. Although this drug is well tolerated in terms of adverse effects, trastuzumab-associated myocardiotoxicity has been described to have an incidence of 0.6-4.5% and in rare cases, the drug can trigger severe congestive heart failure with progression to death or even mimic acute coronary syndrome with complete left bundle branch blockade. In this paper is reported a case of trastuzumab-associated myocardiotoxicity manifesting as acute coronary syndrome in a 69-year-old female. The patient is currently undergoing a conservative clinical treatment that restricts overexertion.The majority of clinical studies report trastuzumab-induced cardiotoxicity as a rare event, and, when present, characterized by mild to moderate clinical signs, the ease of reversibility with pharmacological measures and the temporary discontinuation of the medication. Conversely, it is vital for the oncologist/cardiologist to consider the possibility that trastuzumab-induced cardiotoxicity may manifest itself as a severe clinical case, mimicking acute coronary syndrome, justifying careful risk stratification and adequate cardiac monitoring, especially in high-risk patients.

Can course format influence the performance of students in an advanced cardiac life support (ACLS) program?

Advanced cardiac life support (ACLS) is a problem-based course that employs simulation techniques to teach the standard management techniques of cardiovascular emergencies. Its structure is periodically revised according to new versions of the American Heart Association guidelines. Since it was introduced in Brazil in 1996, the ACLS has been through two conceptual and structural changes. Detailed documented reports on the effect of these changes on student performance are limited. The objective of the present study was to evaluate the effect of conceptual and structural changes of the course on student ACLS performance at a Brazilian training center. This was a retrospective study of 3266 students divided into two groups according to the teaching model: Model 1 (N = 1181; 1999-2003) and Model 2 (N = 2085; 2003-2007). Model 2 increased practical skill activities to 75% of the total versus 60% in Model 1. Furthermore, the teaching material provided to the students before the course was more objective than that used for Model 1. Scores greater than 85% in the theoretical evaluation and approval in the evaluation of practice by the instructor were considered to be a positive outcome. Multiple logistic regression was used to adjust for potential confounders (specialty, residency, study time, opportunity to enhance practical skills during the course and location where the course was given). Compared to Model 1, Model 2 presented odds ratios (OR) indicating better performance in the theoretical (OR = 1.34; 95%CI = 1.10-1.64), practical (OR = 1.19; 95%CI = 0.90-1.57), and combined (OR = 1.38; 95%CI = 1.13-1.68) outcomes. Increasing the time devoted to practical skills did not improve the performance of ACLS students.

Basic life support knowledge of first-year university students from Brazil

We aimed to evaluate knowledge of first aid among new undergraduates and whether it is affected by their chosen course. A questionnaire was developed to assess knowledge of how to activate the Mobile Emergency Attendance Service - MEAS (Serviço de Atendimento Móvel de Urgência; SAMU), recognize a pre-hospital emergency situation and the first aid required for cardiac arrest. The students were also asked about enrolling in a first aid course. Responses were received from 1038 of 1365 (76.04%) new undergraduates. The questionnaires were completed in a 2-week period 1 month after the beginning of classes. Of the 1038 respondents (59.5% studying biological sciences, 11.6% physical sciences, and 28.6% humanities), 58.5% knew how to activate the MEAS/SAMU (54.3% non-biological vs 61.4% biological, P=0.02), with an odds ratio (OR)=1.39 (95%CI=1.07-1.81) regardless of age, sex, origin, having a previous degree or having a relative with cardiac disease. The majority could distinguish emergency from non-emergency situations. When faced with a possible cardiac arrest, 17.7% of the students would perform chest compressions (15.5% non-biological vs 19.1% biological first-year university students, P=0.16) and 65.2% would enroll in a first aid course (51.1% non-biological vs 74.7% biological, P<0.01), with an OR=2.61 (95%CI=1.98-3.44) adjusted for the same confounders. Even though a high percentage of the students recognized emergency situations, a significant proportion did not know the MEAS/SAMU number and only a minority had sufficient basic life support skills to help with cardiac arrest. A significant proportion would not enroll in a first aid course. Biological first-year university students were more prone to enroll in a basic life support course.

How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

Amiodarone-induced thyroid dysfunction (AITD) is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 +/- 89 mg; duration of treatment = 5.3 +/- 3.9 years, range = 0.57-17 years) and with stable baseline cardiac condition. Those with no AITD were followed up for a median period of 3.2 years (range: 0.6-6.7) and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year). We applied the Cox proportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7%) of the 121 patients, amiodarone-induced hypothyroidism in 50 (41.3%) and hyperthyroidism in 9 (7.5%). Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3) cases per 1000 patients/year), 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2), and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5). Age, gender, dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9) cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study.

Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns. More than 1000 mutations have been described with the most common being F508del. It has a prevalence of 23-55% within the Brazilian population. The lack of population-based studies evaluating the incidence of cystic fibrosis in São Paulo State, Brazil, and an analysis concerning the costs of implantation of a screening program motivated the present study. A total of 60,000 dried blood samples from Guthrie cards obtained from April 2005 to January 2006 for neonatal screening at 4 reference centers in São Paulo State were analyzed. The immunoreactive trypsinogen (IRT)/IRT protocol was used with the cut-off value being 70 ng/mL. A total of 532 children (0.9%) showed IRT >70 ng/mL and a 2nd sample was collected from 418 (80.3%) of these patients. Four affected children were detected at two centers, corresponding to an incidence of 1:8403. The average age at diagnosis was 69 days, and 3 of the children already showed severe symptoms of the disease. The rate of false-positive results was 95.2% and the positive predictive value for the test was 8%. The cost of detecting an affected subject was approximately US$8,000.00 when this cystic fibrosis program was added to an existing neonatal screening program. The present study clearly shows the difficulties involved in cystic fibrosis screening using the IRT/IRT protocol, particularly in a population with no long-term tradition of neonatal screening.

Can course format influence the performance of students in an advanced cardiac life support (ACLS) program?

Advanced cardiac life support (ACLS) is a problem-based course that employs simulation techniques to teach the standard management techniques of cardiovascular emergencies. Its structure is periodically revised according to new versions of the American Heart Association guidelines. Since it was introduced in Brazil in 1996, the ACLS has been through two conceptual and structural changes. Detailed documented reports on the effect of these changes on student performance are limited. The objective of the present study was to evaluate the effect of conceptual and structural changes of the course on student ACLS performance at a Brazilian training center. This was a retrospective study of 3266 students divided into two groups according to the teaching model: Model 1 (N = 1181; 1999-2003) and Model 2 (N = 2085; 2003-2007). Model 2 increased practical skill activities to 75 percent of the total versus 60 percent in Model 1. Furthermore, the teaching material provided to the students before the course was more objective than that used for Model 1. Scores greater than 85 percent in the theoretical evaluation and approval in the evaluation of practice by the instructor were considered to be a positive outcome. Multiple logistic regression was used to adjust for potential confounders (specialty, residency, study time, opportunity to enhance practical skills during the course and location where the course was given). Compared to Model 1, Model 2 presented odds ratios (OR) indicating better performance in the theoretical (OR = 1.34; 95 percentCI = 1.10-1.64), practical (OR = 1.19; 95 percentCI = 0.90-1.57), and combined (OR = 1.38; 95 percentCI = 1.13-1.68) outcomes. Increasing the time devoted to practical skills did not improve the performance of ACLS students.

Factor XIII val34leu and the risk of myocardial infarction.

BACKGROUND AND OBJECTIVE: Recent studies have suggested an association between a genetic variation in the coagulation factor XIII (FXIII Val34Leu) and decreased risk of vascular thrombosis. DESIGN AND METHODS: We investigated the frequency of the FXIII Val34Leu polymorphism in 150 consecutive, unrelated and relatively young (<55 years) survivors of myocardial infarction (MI) with angiographically-proven severe coronary atherosclerosis and in 150 age-, gender- and race-matched controls. RESULTS: FXIII Val34Leu was detected in 54/150 patients and 73/150 controls, yielding an overall odds ratio (OR) for MI of 0.6 (CI95: 0.4-0.9). Homozygosity for FXIII Val34Leu was found in 4/150 patients and in 12/150 controls, yielding an OR for MI of 0.26 (CI95: 0.08-0.9). The OR for heterozygotes was 0.65 (CI95: 0.4-1.1). FXIII Val34Leu carriership decreased the risk of MI related to metabolic risk factors (RF) (hypertension, diabetes, dyslipidemia, and obesity): non-carriers in the presence of a metabolic RF had a 13.9-fold higher risk of MI, whereas in carriers with a metabolic RF the risk was reduced to 6.8. FXIII Val34Leu also attenuated the risk of MI among smokers. Non-carrier smokers had a 6.1-fold higher risk (CI95: 3.1-11.9), whereas the risk among smokers carrying FXIII Val34Leu was 3.9 (CI95: 1.9-8.1). INTERPRETATION AND CONCLUSIONS: FXIII Val34Leu confers a significant protective effect against the occurrence of MI in relatively young patients. FXIII Val34Leu exhibits a gene dosage effect: the protective effect was particularly strong in homozygous carriers, and heterozygosity conferred moderate protection. Finally, FXIII Val34Leu seems to reduce the risk of MI related to major cardiovascular risk factors.