Long-Term Prospective, Randomized, Controlled Study Using Repetitive Education at Six-Month Intervals and Monitoring for Adherence in Heart Failure Outpatients The REMADHE Trial

Background-The effectiveness of heart failure disease management proarams in patients under cardiologists` care over long-term follow-up is not established. Methods and Results-We investigated the effects of a disease management program with repetitive education and telephone monitoring on primary (combined death or unplanned first hospitalization and quality-of-life changes) and secondary end points (hospitalization, death, and adherence). The REMADHE [Repetitive Education and Monitoring for ADherence for Heart Failure] trial is a long-term randomized, prospective, parallel trial designed to compare intervention with control. One hundred seventeen patients were randomized to usual care, and 233 to additional intervention. The mean follow-up was 2.47 +/- 1.75 years, with 54% adherence to the program. In the intervention group, the primary end point composite of death or unplanned hospitalization was reduced (hazard ratio, 0.64; confidence interval, 0.43 to 0.88; P=0.008), driven by reduction in hospitalization. The quality-of-life questionnaire score improved only in the intervention group (P<0.003). Mortality was similar in both groups. Number of hospitalizations (1.3 +/- 1.7 versus 0.8 +/- 1.3, P<0.0001), total hospital days during the follow-up (19.9 +/- 51 versus 11.1 +/- 24 days, P<0.0001), and the need for emergency visits (4.5 +/- 10.6 versus 1.6 +/- 2.4, P<0.0001) were lower in the intervention group. Beneficial effects were homogeneous for sex, race, diabetes and no diabetes, age, functional class, and etiology. Conclusions-For a longer follow-up period than in previous studies, this heart failure disease management program model of patients under the supervision of a cardiologist is associated with a reduction in unplanned hospitalization, a reduction of total hospital days, and a reduced need for emergency care, as well as improved quality of life, despite modest program adherence over time. (Circ Heart Fail. 2008;1:115-124.)

Impact of gender on benefits of exercise training on sympathetic nerve activity and muscle blood flow in heart failure

We compared the effects of exercise training on neurovascular control and functional capacity in men and women with chronic heart failure (HF). Forty consecutive HF outpatients from the Heart Institute, University of Sao Paulo, Brazil were divided into the following four groups matched by age: men exercise-trained (n = 12), men untrained (n = 10), women exercise-trained (n = 9), women untrained (n = 9). Maximal exercise capacity was determined from a maximal progressive exercise test on a cycle ergometer. Forearm blood flow was measured by venous occlusion plethysmography. Muscle sympathetic nerve activity (MSNA) was recorded directly using the technique of microneurography. There were no differences between groups in any baseline parameters. Exercise training produced a similar reduction in resting MSNA (P = 0.000002) and forearm vascular resistance (P = 0.0003), in men and women with HF. Peak VO(2) was similarly increased in men and women with HF (P = 0.0003) and VE/VCO(2) slope was significantly decreased in men and women with HF (P = 0.0007). There were no significant changes in left-ventricular ejection fraction in men and women with HF. The benefits of exercise training on neurovascular control and functional capacity in patients with HF are independent of gender.

Bronchoscopic lung-volume reduction with Exhale airway stents for emphysema (EASE trial): randomised, sham-controlled, multicentre trial

Background Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema. Methods We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of >= 0.65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0.965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612. Findings All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0.749, below the Bayesian success threshold of 0.965). The 6-month composite primary safety endpoint was 14.4% (30 of 208) for airway bypass versus 11.2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1.00 [Bayesian success threshold >0.95]). Interpretation Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema.

A practical approach to assess depression risk and to guide risk reduction strategies in later life

Background: Many factors have been associated with the onset and maintenance of depressive symptoms in later life, although this knowledge is yet to be translated into significant health gains for the population. This study gathered information about common modifiable and non-modifiable risk factors for depression with the aim of developing a practical probabilistic model of depression that can be used to guide risk reduction strategies. \Methods: A cross-sectional study was undertaken of 20,677 community-dwelling Australians aged 60 years or over in contact with their general practitioner during the preceding 12 months. Prevalent depression (minor or major) according to the Patient Health Questionnaire (PHQ-9) assessment was the main outcome of interest. Other measured exposures included self-reported age, gender, education, loss of mother or father before age 15 years, physical or sexual abuse before age 15 years, marital status, financial stress, social support, smoking and alcohol use, physical activity, obesity, diabetes, hypertension, and prevalent cardiovascular diseases, chronic respiratory diseases and cancer. Results: The mean age of participants was 71.7 +/- 7.6 years and 57.9% were women. Depression was present in 1665 (8.0%) of our subjects. Multivariate logistic regression showed depression was independently associated with age older than 75 years, childhood adverse experiences, adverse lifestyle practices (smoking, risk alcohol use, physical inactivity), intermediate health hazards (obesity, diabetes and hypertension), comorbid medical conditions (clinical history of coronary heart disease, stroke, asthma, chronic obstructive pulmonary disease, emphysema or cancers), and social or financial strain. We stratified the exposures to build a matrix that showed that the probability of depression increased progressively with the accumulation of risk factors, from less than 3% for those with no adverse factors to more than 80% for people reporting the maximum number of risk factors. Conclusions: Our probabilistic matrix can be used to estimate depression risk and to guide the introduction of risk reduction strategies. Future studies should now aim to clarify whether interventions designed to mitigate the impact of risk factors can change the prevalence and incidence of depression in later life.

Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans

The adenovirus type 5 (Ad5)-based vaccine developed by Merck failed to either prevent HIV-1 infection or suppress viral load in subsequently infected subjects in the STEP human Phase 2b efficacy trial. Analogous vaccines had previously also failed in the simian immunodeficiency virus (SIV) challenge-rhesus macaque model. In contrast, vaccine protection studies that used challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P) in macaques did not predict the human trial results. Ad5 vector -based vaccines did not protect macaques from infection after SHIV89.6P challenge but did cause a substantial reduction in viral load and a preservation of CD4(+) T cell counts after infection, findings that were not reproduced in the human trials. Although the SIV challenge model is incompletely validated, we propose that its expanded use can help facilitate the prioritization of candidate HIV-1 vaccines, ensuring that resources are focused on the most promising candidates. Vaccine designers must now develop T cell vaccine strategies that reduce viral load after heterologous challenge.

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

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. 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). 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). 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.

Monolithic CAD/CAM Lithium Disilicate Versus Veneered Y-TZP Crowns: Comparison of Failure Modes and Reliability After Fatigue

Purpose: The aim of this research was to evaluate the fatigue behavior and reliability of monolithic computer-aided design/computer-assisted manufacture (CAD/CAM) lithium disilicate and hand-layer-veneered zirconia all-ceramic crowns. Materials and Methods: A CAD-based mandibular molar crown preparation, fabricated using rapid prototyping, served as the master die. Fully anatomically shaped monolithic lithium disilicate crowns (IPS e.max CAD, n = 19) and hand-layer-veneered zirconia-based crowns (IPS e.max ZirCAD/Ceram, n = 21) were designed and milled using a CAD/CAM system. Crowns were cemented on aged dentinlike composite dies with resin cement. Crowns were exposed to mouth-motion fatigue by sliding a WC-indenter (r = 3.18 mm) 0.7 mm lingually down the distobuccal cusp using three different step-stress profiles until failure occurred. Failure was designated as a large chip or fracture through the crown. If no failures occurred at high loads (> 900 N), the test method was changed to staircase r ratio fatigue. Stress level probability curves and reliability were calculated. Results: Hand-layer-veneered zirconia crowns revealed veneer chipping and had a reliability of < 0.01 (0.03 to 0.00, two-sided 90% confidence bounds) for a mission of 100,000 cycles and a 200-N load. None of the fully anatomically shaped CAD/CAM-fabricated monolithic lithium disilicate crowns failed during step-stress mouth-motion fatigue (180,000 cycles, 900 N). CAD/CAM lithium disilicate crowns also survived r ratio fatigue (1,000,000 cycles, 100 to 1,000 N). There appears to be a threshold for damage/bulk fracture for the lithium disilicate ceramic in the range of 1,100 to 1,200 N. Conclusion: Based on present fatigue findings, the application of CAD/CAM lithium disilicate ceramic in a monolithic/fully anatomical configuration resulted in fatigue-resistant crowns, whereas hand-layer-veneered zirconia crowns revealed a high susceptibility to mouth-motion cyclic loading with early veneer failures. Int J Prosthodont 2010; 23: 434-442.

Effect of framework design on crown failure

This study evaluated the effect of core-design modification on the characteristic strength and failure modes of glass-infiltrated alumina (In-Ceram) (ICA) compared with porcelain fused to metal (PFM). Premolar crowns of a standard design (PFMs and ICAs) or with a modified framework design (PFMm and ICAm) were fabricated, cemented on dies, and loaded until failure. The crowns were loaded at 0.5 mm min(-1) using a 6.25 mm tungsten-carbide ball at the central fossa. Fracture load values were recorded and fracture analysis of representative samples were evaluated using scanning electron microscopy. Probability Weibull curves with two-sided 90% confidence limits were calculated for each group and a contour plot of the characteristic strength was obtained. Design modification showed an increase in the characteristic strength of the PFMm and ICAm groups, with PFM groups showing higher characteristic strength than ICA groups. The PFMm group showed the highest characteristic strength among all groups. Fracture modes of PFMs and of PFMm frequently reached the core interface at the lingual cusp, whereas ICA exhibited bulk fracture through the alumina core. Core-design modification significantly improved the characteristic strength for PFM and for ICA. The PFM groups demonstrated higher characteristic strength than both ICA groups combined.

Mechanisms of exercise training in patients with heart failure

Background The reduction of exercise capacity because of fatigue and dyspnea in patients with heart failure can be improved with exercise training. We sought to examine the mechanisms of exercise training, as an adjunctive treatment strategy for patients with heart failure. Methods a reviewed the published data on the possible mechanisms of effect of exercise training in heart failure. Results Symptoms of heart failure may be explained on the basis of abnormal skeletal muscle perfusion and structure and endothelial function. Exercise training has been shown to engender changes in muscle structure and biochemistry and vascular function, although effects on cardiac function have not been detected uniformly and may require longer training periods. Conclusions A suitable, long-term program of exercise training may reverse unfavorable interactions among the heart, vessels, and skeletal muscles. These improvements may be preserved with an ongoing maintenance program.

Survival Analysis Employed in Predicting Corporate Failure: A Forecasting Model Proposal

In face of the current economic and financial environment, predicting corporate bankruptcy is arguably a phenomenon of increasing interest to investors, creditors, borrowing firms, and governments alike. Within the strand of literature focused on bankruptcy forecasting we can find diverse types of research employing a wide variety of techniques, but only a few researchers have used survival analysis for the examination of this issue. We propose a model for the prediction of corporate bankruptcy based on survival analysis, a technique which stands on its own merits. In this research, the hazard rate is the probability of ‘‘bankruptcy’’ as of time t, conditional upon having survived until time t. Many hazard models are applied in a context where the running of time naturally affects the hazard rate. The model employed in this paper uses the time of survival or the hazard risk as dependent variable, considering the unsuccessful companies as censured observations.

Increase of the delivered energy probability in DES using a fuzzy probabilistic modeling

The paper proposes a methodology to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The proposed methodology is based on statistical failure and repair data of distribution components and it uses a fuzzy-probabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A mixed integer nonlinear programming optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.

Fuzzy Monte Carlo model for transmission power systems reliability based decision making

This thesis presents the Fuzzy Monte Carlo Model for Transmission Power Systems Reliability based studies (FMC-TRel) methodology, which is based on statistical failure and repair data of the transmission power system components and uses fuzzyprobabilistic modeling for system component outage parameters. Using statistical records allows developing the fuzzy membership functions of system component outage parameters. The proposed hybrid method of fuzzy set and Monte Carlo simulation based on the fuzzy-probabilistic models allows catching both randomness and fuzziness of component outage parameters. A network contingency analysis to identify any overloading or voltage violation in the network is performed once obtained the system states. This is followed by a remedial action algorithm, based on Optimal Power Flow, to reschedule generations and alleviate constraint violations and, at the same time, to avoid any load curtailment, if possible, or, otherwise, to minimize the total load curtailment, for the states identified by the contingency analysis. For the system states that cause load curtailment, an optimization approach is applied to reduce the probability of occurrence of these states while minimizing the costs to achieve that reduction. This methodology is of most importance for supporting the transmission system operator decision making, namely in the identification of critical components and in the planning of future investments in the transmission power system. A case study based on Reliability Test System (RTS) 1996 IEEE 24 Bus is presented to illustrate with detail the application of the proposed methodology.

Modified Discrete PSO to Increase the Delivered Energy Probability in Distribution energy Systems

This paper proposes a PSO based approach to increase the probability of delivering power to any load point by identifying new investments in distribution energy systems. The statistical failure and repair data of distribution components is the main basis of the proposed methodology that uses a fuzzyprobabilistic modeling for the components outage parameters. The fuzzy membership functions of the outage parameters of each component are based on statistical records. A Modified Discrete PSO optimization model is developed in order to identify the adequate investments in distribution energy system components which allow increasing the probability of delivering power to any customer in the distribution system at the minimum possible cost for the system operator. To illustrate the application of the proposed methodology, the paper includes a case study that considers a 180 bus distribution network.

MONTENEGRO SKIN TEST AND AGE OF SKIN LESION AS PREDICTORS OF TREATMENT FAILURE IN CUTANEOUS LEISHMANIASIS

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

Differing phagocytic function of monocytes and neutrophils in Chagas' cardiopathy according to the presence or absence of congestive heart failure

We evaluated the in vitro phagocytic function and the production of microbicidal oxygen radicals by monocytes and neutrophils of 9 Chagas' heart disease subjects with heart failure and 9 without the syndrome in comparison with 11 healthy subjects, by assessing phagocytosis of Saccharomyces cerevisiae and NBT reduction by peripheral blood phagocytes. Phagocytic index of monocytes of chagasics without heart failure was significantly 6.7 and 10.6 times lower than those of controls and chagasics with the congestive syndrome, respectively, due to a lesser engagement in phagocytosis and to an inability of these cells to ingest particles. Neutrophils also show in chagasics without heart failure PI 11.2 and 19.8 times lower than that of controls and chagasics with heart failure, respectively. The percent of NBT reduction was normal and similar for the three groups. Balanced opposite effects of cardiovascular and immune disturbances may be acting in Chagas' disease subjects with heart failure paradoxically recovering the altered phagocytic function.