Cost-Utility Model of Nirmatrelvir/Ritonavir in Brazil: Analysis of a Vaccinated Population.

OBJECTIVES: The aim of this study is to conduct a cost-utility analysis of the use of the antiviral nirmatrelvir/ritonavir, applied to a vaccinated Brazilian population against COVID-19, from the perspective of the Brazilian Public Health System (SUS). METHODS: A microsimulation model was created with individual-level data and daily cycles, with a 1-year time horizon, to compare the current scenario of standard care with a scenario in which nirmatrelvir/ritonavir is offered to the population. Adults of any age group that received ≥2 doses of the COVID-19 vaccine formed the investigated population. Direct medical costs of the outpatients and inpatients admitted to the ward or intensive care unit were included. The effectiveness of the model was measured in quality-adjusted life-years (QALYs). RESULTS: In all simulations, the use of nirmatrelvir/ritonavir resulted in incremental costs per patient of US dollar (USD)245.86 and incremental effectiveness of 0.009 QALY, over a year. The incremental cost-utility ratio was USD27 220.70/QALY. The relative risk of the vaccinated population was the factor that affected the outcome most, according to the univariate sensitivity analysis. The probabilistic sensitivity analysis resulted in 100% of the simulations being more costly and effective, but that only 4% of them were below the established cost-effectiveness threshold of USD24 000.00/QALY. In the scenario considering only the population over 60 years old and immunosuppressed (of any age), the incremental cost-utility ratio was USD7589.37/QALY. CONCLUSIONS: The use of nirmatrelvir/ritonavir in the treatment of COVID-19 in a vaccinated population was cost-effective only for immunosuppressed individuals and people over 60 years of age.

Acute cardiac injury in patients with COVID-19.

INTRODUCTION: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. METHODS: A systematic review with a meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independent reviewers evaluated the selected manuscripts for the outcome "myocardial injury", defined by troponin elevation above the 99th percentile. The study heterogeneity and risk of bias were evaluated. RESULTS: Eight studies, with a total of 1,229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9%-27%). The heterogeneity among the studies was high (93%). CONCLUSIONS: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% according to current studies. Continuous research is needed to update these findings as the pandemic evolves and to define the implications of myocardial injury in the context of this infection.

Optimal testing policies for diagnosing patients with intermediary probability of disease.

This paper proposes a stochastic shortest path approach to find an optimal sequence of tests to confirm or discard a disease, for any prescribed optimality criterion. The idea is to select the best sequence in which to apply a series of available tests, with a view at reaching a diagnosis with minimum expenditure of resources. The proposed approach derives an optimal policy whereby the decision maker is provided with a test strategy for each a priori probability of disease, aiming to reach posterior probabilities that warrant either immediate treatment or a not-ill diagnosis.

Health-related quality of life and utility values associated to hypoglycemia in patients with type 1 diabetes mellitus treated in the Brazilian Public Health System: a multicenter study.

BACKGROUND: Hypoglycemia is a critical and limiting factor of a good metabolic control and can adversely affect the quality of life of diabetic patients. The aim of the study was to evaluate the health-related quality of life and calculate utilities values associated with hypoglycemia in patients with type 1 diabetes mellitus (T1DM). METHODS: A multicenter, cross-sectional and observational study with T1DM patients from reference centers of the Brazilian public health system was conducted in three cities. Demographic and clinical data were collected, besides details on the frequency and severity of hypoglycemia. Health-related quality of life was assessed using EQ-5D instrument and utility values generated. RESULTS: 221 patients (107 women, 114 men), aged 29.8 ± 11.6 and disease duration of 14.2 ± 9.1 years were included. Most patients (n = 214, 96.8%) reported at least one symptomatic hypoglycemia in the last three months, 68% (n = 150) reported nocturnal episodes and 34.8% (n = 77) reported severe episodes. High frequency (daily or weekly) was observed in 38.6 and 26% of those reporting nocturnal or severe hypoglycemia, respectively. The median visual analog scale was 70 [60-85] for all patients, with differences between those with and without severe hypoglycemia (70 [60-80] vs 80 [61-90]; p = 0.006) and those with high and low frequency (62.5 [50-72.25] vs 70 [60-80]; p = 0.007). The median utility values was 0.801 [0.756-1.000] for all patients, with difference between those with high and low frequency of severe episodes (0.737 [0.628-1.000] vs 0.801 [0.756-1.000]; p = 0.02). CONCLUSIONS: This study shows the high frequency of hypoglycemia in a sample of T1DM patients treated in three reference centers of the Brazilian public health system and the impact of severe episodes on health-related quality of life. Utility values were generated and can be used in economic analysis for treatments that could decrease hypoglycemia and consequently improve quality of life.

EFFICACY OF CARPENTIER-EDWARDS PERICARDIAL PROSTHESES: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVES: The Carpentier-Edwards pericardial (CEP) prostheses are the type of bioprostheses most used worldwide. Although they were designed to minimize the rate of valve deterioration and reoperation, their clinical superiority over other prostheses models still lacks confirmation. The objective of this study was to evaluate its effectiveness. METHODS: We performed a systematic review and meta-analysis in the PubMed, Embase, Cochrane, and Lilacs databases. Operative mortality, overall mortality and reoperation rates after heart valve surgery were compared between the use of CEP and other cardiac prostheses. Two independent reviewers screened studies for inclusion and extracted the data. Disagreements were resolved by consensus. The GRADE criterion was used to assess the evidence quality. RESULTS: A total of twenty-eight studies were selected, including 19,615 individuals. The studies presented a high heterogeneity and low quality of evidence what limited the reliability of the results. The pooled data from the selected studies did not demonstrate significant differences between CEP and porcine, pericardial or stentless prostheses regarding operative mortality, overall mortality and reoperation rates. However, the pooled data from 3 observational trials pointed out a higher risk for reoperation after valve replacement using CEP prostheses against mechanical prostheses (OR 4.92 [95 percent confidence interval 2.43-9.96]). CONCLUSIONS: The current data present in the literature still does not support a clinical advantage for the use of CEP prostheses over other bioprostheses. The quality of the studies in the literature is limited and further studies are needed to address if CEP prostheses will have a clinical advantage over other prostheses.

Pharmacologic prevention and treatment of delirium in intensive care patients: A systematic review.

PURPOSE: The purpose of the study is to determine if pharmacologic approaches are effective in prevention and treatment of delirium in critically ill patients. MATERIALS AND METHODS: We performed a systematic search to identify publications (from January 1980 to September 2014) that evaluated the pharmacologic interventions to treat or prevent delirium in intensive care unit (ICU) patients. RESULTS: From 2646 citations, 15 studies on prevention (6729 patients) and 7 studies on treatment (1784 patients) were selected and analyzed. Among studies that evaluated surgical patients, the pharmacologic interventions were associated with a reduction in delirium prevalence, ICU length of stay, and duration of mechanical ventilation, but with high heterogeneity (respectively, I(2) = 81%, P = .0013; I(2) = 97%, P < .001; and I(2) = 97%). Considering treatment studies, only 1 demonstrated a significant decrease in ICU length of stay using dexmedetomidine compared to haloperidol (Relative Risk, 0.62 [1.29-0.06]; I(2) = 97%), and only 1 found a shorter time to resolution of delirium using quetiapine (1.0 [confidence interval, 0.5-3.0] vs 4.5 [confidence interval, 2.0-7.0] days; P = .001). CONCLUSION: The use of antipsychotics for surgical ICU patients and dexmedetomidine for mechanically ventilated patients as a preventive strategy may reduce the prevalence of delirium in the ICU. None of the studied agents that were used for delirium treatment improved major clinical outcome, including mortality.

Impact of improvement in preoperative oral health on nosocomial pneumonia in a group of cardiac surgery patients: a single arm prospective intervention study.

PURPOSE: To evaluate the effects of an oral health protocol on the incidence of postoperative pneumonia in patients submitted to coronary artery bypass grafting and to valve surgery. METHODS: All patients admitted to a public cardiac surgery hospital were examined by a dentist and had a thorough dentistry anamnesis and an intraoral exam focusing on teeth, gums, and tongue. Patients were taught how to brush their teeth and tongue and how to clean their jugal and palatal membranes. Chlorhexidine gluconate (CXG) 0.12% oral rinse twice a day was used until surgery. Data on age, sex, comorbidities, oral evaluation, type of surgery, and development of pneumonia were obtained. Statistical analysis was done on these variables to evaluate the impact of the study protocol. RESULTS: A total of 226 patients were enrolled, 136 male (60.2%). The median age was 59 years. There were 123 (54.4%) patients with coronary artery disease and 103 (45.6%) with valve disease. There were 18/226 (8%) postoperative pneumonias (PP), nine in each group. Ten occurred in dentate patients and eight in edentulous ones. Oral health optimization was achieved in 208/226 (92%) of patients in the preoperative period. The presence of tongue plaque (OR 17, P < 0.001) and of poor hygiene of the total superior dentures (OR 25, P < 0.001) in the preoperative period significantly increased the chance of PP. The use of CXG 0.12% in the preoperative period (OR 0.06, P < 0.001) and on the day of surgery (OR 0.002, P < 0.001) was protective against PP. Mortality in patients without pneumonia was 9/208 (4.32%) vs. 6/19 (33.3%) in those with pneumonia. The presence of pneumonia increased the chances of death by 11 times (P < 0.001). The mean pneumonia rate in ICU in the 6 months before the study protocol was 32 per 1,000 ventilator-days, 24 during the 6-month intervention period, and 10 during the next 6 months following the study. CONCLUSIONS: PP rates were reduced using a simple and efficient protocol of dental care that improved oral hygiene in the preoperative period of cardiac surgery patients.

Cell therapy in Chagas cardiomyopathy (Chagas arm of the multicenter randomized trial of cell therapy in cardiopathies study): a multicenter randomized trial.

BACKGROUND: Previous studies suggested that transplantation of autologous bone marrow-derived mononuclear cells (BMNCs) improves heart function in chronic chagasic cardiomyopathy. We report the results of the first randomized trial of BMNC therapy in chronic chagasic cardiomyopathy. METHODS AND RESULTS: Patients 18 to 75 years of age with chronic chagasic cardiomyopathy, New York Heart Association class II to IV heart failure, left ventricular ejection fraction (LVEF) <35, and optimized therapy were randomized to intracoronary injection of autologous BMNCs or placebo. The primary end point was the difference in LVEF from baseline to 6 and 12 months after treatment between groups. Analysis was by intention to treat and powered to detect an absolute between-group difference of 5. Between July 2005 and October 2009, 234 patients were enrolled. Two patients abandoned the study and 49 were excluded because of protocol violation. The remaining 183 patients, 93 in the placebo group and 90 in the BMNC group, had a trimmed mean age of 52.4 years (range, 50.8-54.0 years) and LVEF of 26.1 (range, 25.1-27.1) at baseline. Median number of injected BMNCs was 2.20×10(8) (range, 1.40-3.50×10(8)). Change in LVEF did not differ significantly between treatment groups: trimmed mean change in LVEF at 6 months, 3.0 (1.3-4.8) for BMNCs and 2.5 (0.6-4.5) for placebo (P=0.519); change in LVEF at 12 months, 3.5 (1.5-5.5) for BMNCs and 3.7 (1.5-6.0) for placebo (P=0.850). Left ventricular systolic and diastolic volumes, New York Heart Association functional class, Minnesota quality-of-life questionnaire, brain natriuretic peptide concentrations, and 6-minute walking test did also not differ between groups. CONCLUSION: Intracoronary injection of autologous BMNCs does not improve left ventricular function or quality of life in patients with chronic chagasic cardiomyopathy.

Risk factors for long-term mortality in a large cohort of patients wait-listed for liver transplantation in Brazil.

Liver donor shortage and long waiting times are observed in many liver transplant programs worldwide. The aim of this study was to evaluate the wait list in a developing country, before and after the introduction of the MELD scoring system. In addition, the MELD score ability to predict mortality in this setting was assessed. A single-center retrospective study of patients wait-listed for liver transplantation between 1997 and 2010 was undertaken. There were 1339 and 762 patients on the list in pre-MELD and MELD era, respectively. A competitive risk analysis was performed to assess age, gender, disease diagnosis, serum sodium, MELD, Child-Pugh, ABO type, and body mass index. Also, MELD score predictive ability at 3, 6, 12, and 24 months after list enrollment was evaluated. The overall mortality rates on waiting list were 31.0% and 28.1% (P = 0.16), and the median waiting times were 412 and 952 days (P < 0.001), in pre and MELD eras, respectively. The competitive risk analysis yielded the following significant P values for both eras: HCC (0.03 and <0.001), MELD (<0.001 and 0.002), sodium level (0.002 and <0.001), and Child-Pugh (0.02 and <0.001). The MELD mortality predictions at 3, 6, 12, and 24 months were similar. In conclusion, in a liver transplant program with long waiting times, the MELD system introduction did not improve mortality rate. In either pre and MELD eras, HCC diagnosis, serum sodium, Child-Pugh, and MELD were significant predictors of prognosis. Short- and long-term MELD based mortality predictions were similarly accurate. Strategies for increasing the liver donor pool should be implemented to improve mortality.

Ultrasound imaging in an experimental model of fatty liver disease and cirrhosis in rats.

BACKGROUND: Domestic dogs and cats are very well known to develop chronic hepatic diseases, including hepatic lipidosis and cirrhosis. Ultrasonographic examination is extensively used to detect them. However, there are still few reports on the use of the ultrasound B-mode scan in correlation with histological findings to evaluate diffuse hepatic changes in rodents, which represent the most important animal group used in experimental models of liver diseases. The purpose of this study was to determine the reliability of ultrasound findings in the assessment of fatty liver disease and cirrhosis when compared to histological results in Wistar rats by following up a murine model of chronic hepatic disease. RESULTS: Forty Wistar rats (30 treated, 10 controls) were included. Liver injury was induced by dual exposure to CCl4 and ethanol for 4, 8 and 15 weeks. Liver echogenicity, its correlation to the right renal cortex echogenicity, measurement of portal vein diameter (PVD) and the presence of ascites were evaluated and compared to histological findings of hepatic steatosis and cirrhosis. Liver echogenicity correlated to hepatic steatosis when it was greater or equal to the right renal cortex echogenicity, with a sensitivity of 90%, specificity of 100%, positive and negative predictive values of 100% and 76.9% respectively, and accuracy of 92.5%. Findings of heterogeneous liver echogenicity and irregular surface correlated to liver cirrhosis with a sensitivity of 70.6%, specificity of 100%, positive and negative predictive values of 100% and 82.1% respectively, and accuracy of 87.5%. PVD was significantly increased in both steatotic and cirrhotic rats; however, the later had greater diameters. PVD cut-off point separating steatosis from cirrhosis was 2.1 mm (sensitivity of 100% and specificity of 90.5%). One third of cirrhotic rats presented with ascites. CONCLUSION: The use of ultrasound imaging in the follow-up of murine diffuse liver disease models is feasible and efficient, especially when the studied parameters are used in combination. The potential implication of this study is to provide a non-invasive method that allows follow-up studies of fatty liver disease and cirrhosis of individual rats for pre-clinical drug or cell based therapies.

B-type natriuretic peptide: a strong predictor of early and late mortality in patients with acute chest pain without ST-segment elevation in the emergency department.

BACKGROUND: The prognostic importance of early measurement of B-type natriuretic peptide (BNP) in patients with acute chest pain while the diagnosis is still uncertain is unknown. We determined the prognostic value of BNP in these patients immediately after presenting to the emergency department. METHODS: Seven hundred and twenty-three consecutive individuals with suspicious ischemic acute chest pain and no ST-segment elevation were prospectively evaluated using a systematic diagnostic strategy and followed for 1 year. Acute coronary syndrome was diagnosed in 326 patients during their hospital stay. RESULTS: In the follow-up, 15 (2.1%) patients of the whole cohort died of cardiac cause at 1 month and 51 (7.1%) at 1 year. Patients who died had significantly higher admission BNP levels than survivors and this correlation proved linear according to quartile levels. Patients with BNP greater than 101 pg/ml had 13 times higher rate of 1-month mortality (P<0.0001) and 5.3 times higher rate of 1-year mortality (P<0.0001) than patients with BNP of 101 pg/ml or less. Multiple logistic regression analysis disclosed BNP as a strong independent predictor of 1-month and 1-year mortality adding significant prognostic information over traditional risk markers. CONCLUSION: Admission BNP is an independent and powerful marker of early and late cardiac mortality in patients with acute chest pain without ST-segment elevation. These results suggest that BNP should be measured upon arrival at the emergency department for risk stratification in all these patients.

Is myocardial performance index an independent echocardiographic marker of death in children with idiopathic dilated cardiomyopathy?

BACKGROUND: Myocardial performance index (MPI) was reported as a parameter of ventricular systolic and diastolic function, as well as a useful tool to predict the outcome in patients with ventricular dysfunction. HYPOTHESIS: To compare MPI with classical echocardiographic parameters as an independent marker of death in children with idiopathic dilated cardiomyopathy (IDCM). METHODS: Fifty-five children (13 deaths) underwent 104 echocardiograms from January 1996 to May 2005. Right ventricle (RV) MPI and left ventricle (LV) MPI, and 9 classical echocardiographic parameters (left atrium [LA]/body surface area [BSA], distance between mitral E point and ventricular septum, LV mass/body surface area, RV shortening fraction, LV end-systolic and end-diastolic dimensions/body surface area, LV ejection fraction, fiber circumferential shortening velocity, and mitral deceleration time) were compared. Statistical analysis was performed by chi-square, Pearson's correlation and Student t-test, Kaplan-Meier method, Cox's method, and receiver operating curve (ROC). Statistical significance was considered with alpha<0.05 and p=0.80]. RESULTS: Univariate analysis showed that all studied parameters were markers of death. There was a high correlation between RVMPI and LVMPI (r=0.847]-p=0.0001]); therefore, to avoid bias, RVMPI was discharged from multivariate analysis. In the deceased group, moderate/severe mitral regurgitation was frequent (76.9%; confidence interval [CI[ 95%=46.2%- 94.9%) and it was considered in multivariate analysis. In Cox's multivariate analysis, LVMPI was the only independent marker of death (p=0.0213]). The ideal cut-off was 0.63 with 92.3% sensitivity, 66.7% specificity, and fitted ROC area=0.918]. CONCLUSIONS: In children with IDCM, LVMPI is an independent marker of death.

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study.

BACKGROUND: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. METHODS: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). IMPLICATIONS: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required. TRIAL REGISTER: This trial is registered at the NIH registry under the number NCT00350766.

A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units.

BACKGROUND: Sepsis has a high prevalence within intensive care units, with elevated rates of morbidity and mortality, and high costs. Data on sepsis costs are scarce in the literature, and in developing countries such as Brazil these data are largely unavailable. OBJECTIVES: To assess the standard direct costs of sepsis management in Brazilian intensive care units (ICUs) and to disclose factors that could affect those costs. METHODS: This multicentre observational cohort study was conducted in adult septic patients admitted to 21 mixed ICUs of private and public hospitals in Brazil from 1 October 2003 to 30 March 2004. Complete data for all patients admitted to the ICUs were obtained until their discharge or death. We collected only direct healthcare-related costs, defined as all costs related to the ICU stay. Enrolled patients were assessed daily in terms of cost-related expenditures such as hospital fees, operating room fees, gas therapy, physiotherapy, blood components transfusion, medications, renal replacement therapy, laboratory analysis and imaging. Standard unit costs (year 2006 values) were based on the Brazilian Medical Association (AMB) price index for medical procedures and the BRASINDICE price index for medications, solutions and hospital consumables. Medical resource utilization was also assessed daily using the Therapeutic Intervention Scoring System (TISS-28). Indirect costs were not included. RESULTS: With a mean (standard deviation [SD]) age of 61.1 +/- 19.2 years, 524 septic patients from 21 centres were included in this study. The overall hospital mortality rate was 43.8%, the mean Acute Physiology And Chronic Health Evaluation II (APACHE II) score was 22.3 +/- 5.4, and the mean Sequential Organ Failure Assessment (SOFA) score at ICU admission was 7.5 +/- 3.9. The median total cost of sepsis was $US 9632 (interquartile range [IQR] 4583-18 387; 95% CI 8657, 10 672) per patient, while the median daily ICU cost per patient was $US 934 (IQR 735-1170; 95% CI 897, 963). The median daily ICU cost per patient was significantly higher in non-survivors than in survivors, i.e. $US 1094 (IQR 888-1341; 95% CI 1058, 1157) and $US 826 (IQR 668-982; 95% CI 786, 854), respectively (p < 0.001). For patients admitted to public and private hospitals, we found a median SOFA score at ICU admission of 7.5 and 7.1, respectively (p = 0.02), and the mortality rate was 49.1% and 36.7%, respectively (p = 0.006). Patients admitted to public and private hospitals had a similar length of stay of 10 (IQR 5-19) days versus 9 (IQR 4-16) days (p = 0.091), and the median total direct costs for public ($US 9773; IQR 4643-19 221; 95% CI 8503, 10 818) versus private ($US 9490; IQR 4305-17 034; 95% CI 7610, 11 292) hospitals did not differ significantly (p = 0.37). CONCLUSIONS: The present study provides the first economic analysis of direct costs of sepsis in Brazilian ICUs and reveals that the cost of sepsis treatment is high. Despite similar ICU management, there was a significant difference regarding patient outcome between private and public hospitals. Finally, the median daily costs of non-survivor patients were higher than survivors during ICU stay.

Outcome factors of idiopathic dilated cardiomyopathy in children - a long-term follow-up review.

BACKGROUND: Idiopathic dilated cardiomyopathy in children has a high rate of mortality. Cardiac transplantation is the treatment of choice in those who fail to respond to therapeutics. Several studies have been carried out to determine unfavourable prognoses, and to provide an early indication for cardiac transplantation. Nevertheless, no consensus has been reached on the matter. OBJECTIVE: To propose predictors of death in children with idiopathic dilated cardiomyopathy. METHODS: We reviewed data extending over 22 years from 142 consecutive children with idiopathic dilated cardiomyopathy, of whom 36 died. The criteria for inclusion were the presence of congestive heart failure or cardiomegaly in a routine chest X-ray, confirmed by enlargement and hypo kinesis of the left ventricle in the echocardiogram. We included asymptomatic children in functional class I. Based on Cox's analysis of clinical and laboratory data, we sought any predictors of death. RESULTS: In univariate analysis, the predictors were functional class IV at presentation (p equal to 0.0001), dyspnoea (p equal to 0.0096), and reduced pedal pulses (p equal to 0.0413). In chest X-ray, they were maximal cardiothoracic ratio (p equal to 0.0001) and pulmonary congestion (p equal to 0.0072). In the electrocardiogram, right atrium overload (p equal to 0.0118), ventricular arrhythmias (p equal to 0.0148) and heart rate (p equal to 0.027). In the echocardiogram, mitral regurgitation of grade 3 to 4 (p equal to 0.002), the left atrial to aortic ratio (p equal to 0.0001), and left ventricle ejection fraction (p equal to 0.0266). In multivariate analysis, the independent predictors were maximum cardiothoracic ratio (p equal to 0.0001), left ventricle ejection fraction (p equal to 0.0013), mitral regurgitation of grade 3 or 4 (p equal to 0.0017), functional class IV at presentation (p equal to 0.0028), and ventricular arrhythmias (p equal to 0.0253). CONCLUSION: Children, who have these predictors of death should be considered for early heart transplantation when no improvement is observed in clinical treatment.

Multicenter randomized trial of cell therapy in cardiopathies - MiHeart Study.

BACKGROUND: Cardiovascular diseases are the major cause of death in the world. Current treatments have not been able to reverse this scenario, creating the need for the development of new therapies. Cell therapies have emerged as an alternative for cardiac diseases of distinct causes in experimental animal studies and more recently in clinical trials. METHOD/DESIGN: We have designed clinical trials to test for the efficacy of autologous bone marrow derived mononuclear cell therapies in four different cardiopathies: acute and chronic ischemic heart disease, and Chagasic and dilated cardiomyopathy. All trials are multicenter, randomized, double-blind and placebo controlled. In each trial 300 patients will be enrolled and receive optimized therapy for their specific condition. Additionally, half of the patients will receive the autologous bone marrow cells while the other half will receive placebo (saline with 5% autologous serum). For each trial there are specific inclusion and exclusion criteria and the method for cell delivery is intramyocardial for the chronic ischemic heart disease and intracoronary for all others. Primary endpoint for all studies will be the difference in ejection fraction (determined by Simpson's rule) six and twelve months after intervention in relation to the basal ejection fraction. The main hypothesis of this study is that the patients who receive the autologous bone-marrow stem cell implant will have after a 6 month follow-up a mean increase of 5% in absolute left ventricular ejection fraction in comparison with the control group. DISCUSSION: Many phase I clinical trials using cell therapy for cardiac diseases have already been performed. The few randomized studies have yielded conflicting results, rendering necessary larger well controlled trials to test for efficacy of cell therapies in cardiopathies. The trials registration numbers at the NIH registry are the following: Chagasic cardiomyopathy (NCT00349271), dilated cardiomyopathy (NCT00333827), acute myocardial infarction (NCT00350766) and Chronic Ischemic Heart Disease (NCT00362388).

Effect of periodontal treatment on oral anticoagulation in patients with heart disease.

UNLABELLED: In recent decades, there have been several studies on the correlation between periodontal disease (PD) and cardiovascular disease, but the influence of PD on the effect of oral anticoagulant drugs has not been reported. OBJECTIVE: To assess the influence of PD on oral anticoagulation in patients with heart disease. METHODS: Dental treatment for patients of the Anticoagulation Clinic of the Instituto Nacional de Cardiologia Laranjeiras (INCL), receiving warfarin as a prophylactic treatment for thromboembolic events, was performed without suspending the drug and according to the INCL's "Protocol of dental treatment for patients with acquired coagulopathy". A therapeutic anticoagulation level was maintained and was assessed using the international normalized ratio (INR) on the of the patient's visit. The patient was thus protected against thromboembolic events and could undergo dental treatment, even oral surgery. Our study comprised 40 patients who underwent prospective oral assessment and were divided into two groups: Group I--20 patients with PD; and Group II--20 patients without PD. Dental treatment was performed in the two groups as follows: PD control in Group I and treatment of dental caries in Group II. The INR of the patients was assessed before each dental consultation, to guarantee hemostasis during the procedures and to monitor the anticoagulation level obtained. INR prior to the dental intervention was then compared with that after the intervention in both groups. An INR increase of > or =50% was considered significant. RESULTS: In Group I, all patients showed an increase in INR after the dental treatment, which was significant in 15 (75%). In Group II, only 8 patients had increased INR, which was significant in 5 (25%) (p = 0.002). Considering the oral health of the two groups,. the extent of tissue injury in the oral cavity was not significant compared to the INR increase; however, comparison between the two groups showed significant INR increase mainly in patients with PD (p = 0.002). CONCLUSION: This study showed that dental treatment in patients with any type of PD significantly increases INR.

[The impact of malnutrition on idiopathic dilated cardiomyopathy in children]. / O impacto da desnutrição na cardiomiopatia dilatada idiopática na infância.

OBJECTIVE: To analyze the prognostic value of malnutrition in children with idiopathic dilated cardiomyopathy. METHODS: This is a retrospective study of 165 patients with idiopathic dilated cardiomyopathy, diagnosed from September 1979 to March 2003. It analyzed the following variables: gender, age, previous viral illness in the preceding 3 months, functional class according to the New York Heart Association (NYHA), evaluation of nutritional status (normal vs. malnutrition), percentile and standard deviation (z index) of weight. Weight was measured 744 times during the first 72 months, 93 during the first month. Statistical analysis was performed by Chi Squared, Student t test and analysis of variance for repeated measures (ANOVA). Ninety-five percent confidence intervals (CI95) and odds ratios (OR) were calculated. An alpha value of 0.05 and beta of 0.80 were used. RESULTS: Mean age at presentation was 2.2+/-3.2 years with higher incidence in those younger than 2 years (75.8%-CI95 = 68.5% to 82.1%) (p < 0.0001). NYHA classes III and IV were observed in 81.2% (CI95 = 74.4% to 86.9%) (p < 0.0001) and all 40 deaths were this group (p = 0.0008). At presentation, myocarditis occurred in 39.4% (CI95 = 31.9% to 47.3%) (p = 0.0001) and a high level of association between myocarditis and previous viral illness was observed (p = 0.0005) (OR = 3.15-CI95 = 1.55 to 6.44). Malnutrition at presentation did not influence death (p = 0.10), however progressive malnutrition was a marker for death (p = 0.02) (OR = 3.21-CI95 = 1.04 to 9.95). No significant differences weight percentiles (p = 0.15) or in z scores (p = 0.14) were observed. Observed mean weight percentiles (34.9+/-32.6 vs. 8.6+/-16.0) (p < 0.0001) and z scores (-0.62+/-1.43 vs. -2.02+/-1.12) (p < 0.0001) during the study period were greater among survivors. ANOVA demonstrated significant differences in weight percentile progression (p = 0.0417) and z scores (p = 0.0005) from the first month onwards. CONCLUSION: The evaluation of nutritional status is easy to perform, it does not imply additional costs and should become routine for children with chronic heart failure.

O impacto da desnutrição na cardiomiopatia dilatada idiopática na infância / The impact of malnutrition on idiopathic dilated cardiomyopathy in children

OBJETIVO: Determinar a importância da desnutrição como marcadora e preditora do óbito na cardiomiopatia dilatada idiopática na infância. MÉTODOS: Este é um estudo retrospectivo envolvendo 165 pacientes (setembro de 1979 a março de 2003). As variáveis analisadas foram sexo, idade e história de infecção viral nos últimos 3 meses, classe funcional da New York Heart Association (NYHA), percentil e desvio padrão do peso (índice z) e avaliação do estado nutricional. Foram realizadas 744 pesagens nos primeiros 72 meses e 93 no primeiro mês de evolução. Análise estatística: qui-quadrado, teste t de Student e análise de variância. Foram utilizados o valor alfa de 0,05 e o valor beta de 0,80. RESULTADOS: A idade no diagnóstico foi de 2,1±3,2 anos, com maior incidência nos menores de 2 anos (75,8 por cento; IC95 = 68,5-82,1 por cento) (p < 0,0001). A classe funcional III e IV foi observada em 81,2 por cento (IC95 = 74,4-86,9 por cento) (p < 0,0001), tendo todos os 40 óbitos ocorrido neste grupo (p = 0,0008). Na apresentação, a miocardite ocorreu em 39,4 por cento (IC95 = 31,9-47,3 por cento) (p = 0,0001). Houve forte associação entre miocardite e doença viral prévia (p = 0,0005) (RC = 3,15; IC95 = 1,55-6,44). A desnutrição na apresentação não influenciou o óbito (p = 0,10), porém a desnutrição evolutiva foi marcadora de óbito (p = 0,02) (RC = 3,21; IC95 = 1,04-9,95). Não houve diferença significativa no percentil de peso (p = 0,15) ou no índice z (p = 0,14) na apresentação. A média do percentil de peso e do índice z foram superiores nos sobreviventes (34,9+32,6 versus 8,6+16,0 e -0,62+1,43 versus -2,02+1,12) (p < 0,0001). A análise de variância demonstrou diferença significativa na evolução para o percentil de peso (p = 0,0417) e para o índice z (p = 0,0005) desde o primeiro mês de evolução. CONCLUSAO: A avaliação do estado nutricional é de fácil execução, não implica ônus adicional e deve tornar-se rotina no seguimento do paciente com insuficiência cardíaca crônica.

[Prognostic value of chest roentgenograms in children with idiopathic dilated cardiomyopathy]. / O valor prognóstico da telerradiografia de tórax na cardiomiopatia dilatada idiopática na infância.

OBJECTIVE: To analyze the prognostic value of cardiomegaly, pulmonary congestion and cardiothoracic ratio as indicators of death and survival in children with idiopathic dilated cardiomyopathy. METHODS: We carried out a retrospective review of 152 patients with idiopathic dilated cardiomyopathy diagnosed between September 1979 and March 2003. In the first 72 months, 722 exams were performed (100 in the first 15 days). STATISTICAL ANALYSIS: chi-square, Student's t test, ANOVA and Kaplan-Meier curves. Alpha = 0.05; beta = 0.80. RESULTS: The mean age at presentation was 2.2+/-3.2 years. Idiopathic dilated cardiomyopathy incidence was higher in children younger than 2 years (76.3% - 95% CI = 68.7% to 82.8%) (p < 0.0001). Sex (p = 0.07) and color (p = 0.11) were not significant and mortality was not influenced by age (p = 0.73), sex (p = 0.78) or color (p = 0.20). Most patients were severely ill (84.2% - 95% CI = 77.4% to 89.6%; functional class III and IV; p < 0.0001). All 43 deaths occurred in this group (p = 0.0008). Cardiomegaly at presentation was observed in 94.1% (95% CI = 89.1% to 97.2%) (p < 0.0001), and pulmonary congestion in 75.6% (95% CI = 68.0% to 82.2%) (p < 0.0001). Pulmonary congestion and cardiomegaly were more frequent in functional class III/IV patients (RC = 8.03 - 95% CI = 2.85% to 23.1%) (p < 0.0001). Pulmonary congestion was a marker of death (RC = 3.16 - 95% CI = 1.06% to 10.07) (p = 0.0222), but not cardiomegaly (p = 0.1185). Survival was influenced by both cardiomegaly (p = 0.0189) and pulmonary congestion (p = 0.0050). Mean and maximum cardiothoracic ratio were higher in the death group (0.749+/-0.053 vs. 0.662+/-0.080) (p < 0.0001) and (0.716+/-0.059 vs. 0.620+/-0.085) (p < 0.0001). ANOVA revealed a progressive decrease in cardiothoracic ratio in the survival group (p < 0.0001). CONCLUSIONS: In children with idiopathic dilated cardiomyopathy, the presence of pulmonary congestion at presentation and increased cardiothoracic ratio are associated with poor survival.