Predictive value of the CHA2DS2-VASc score in atrial fibrillation patients at high risk for stroke despite oral anticoagulation

Introduction and objectives

The risk of stroke in atrial fibrillation is heterogeneous and depends upon underlying clinical conditions included in current risk stratification schemes. Recently, the CHA₂DS₂-VASc score has been included in guidelines to be more inclusive of common stroke risk factors seen in everyday clinical practice, and useful in defining “truly low risk” subjects. We aimed to assess the usefulness of CHA₂DS₂-VASc score to give us an additional prognostic perspective for adverse events and mortality among “real world” anticoagulated patients with atrial fibrillation who are often elderly with many comorbidities.

Methods

Consecutive outpatients with permanent/paroxysmal nonvalvular atrial fibrillation with CHA₂DS₂-VASc≥2 and stabilized oral anticoagulation (international normalized ratio 2.0-3.0) for at least the preceding 6 months were recruited. Patients with CHA₂DS₂-VASc≥2 were selected. Adverse cardiovascular events including stroke, acute coronary syndrome, or heart failure; major bleeds; and mortality were recorded during more than 2.5-year-follow-up.

Results

Of 933 patients (93.5%) assessed, 432 were males, median age 76 (71-81) years. After a follow-up of 946 (782-1068) days, 109 patients (11.7%) had adverse cardiovascular events, 80 patients (8.6%) had major bleeds, 101 patients (10.8%) died, and 230 (24.6%) had major adverse events (composite end-point). Increasing CHA₂DS₂-VASc score by 1 point had a significant impact on the occurrence of cardiovascular events (hazard ratio=1.27; 95% confidence interval, 1.13-1.44; P<.001), mortality (hazard ratio=1.36; 95% confidence interval, 1.19-1.54; P<.001); and major adverse events (hazard ratio=1.23; 95% confidence interval, 1.13-1.34; P<.001). CHA₂DS₂-VASc score was not associated with major bleeding episodes.

Conclusions

Among high risk atrial fibrillation patients on oral anticoagulation, CHA₂DS₂-VASc successfully predicts cardiovascular events and mortality, but not major bleeds.Full English text available from:www.revespcardiol.org     

Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients

Background

The current gold-standard for diagnosing heparin-induced thrombocytopenia is the detection of platelet-activating antibodies by means of functional assays which, since they are time consuming and not widely available, are not suited to guiding acute treatment decisions. The objective of our study was to assess the ability of more rapid immunoassays to predict the presence of functionally relevant anti-platelet factor 4/heparin-antibodies.

Design and Methods

We analyzed 1,291 of 1,383 (93.4%) patients consecutively evaluated for suspected heparin-induced thrombocytopenia at our institution. Clinical pre-test probability was defined by the 4T-score. Anti-platelet factor 4/heparin-antibodies were measured with three immunoassays (ID-H/PF4-PaGIA, Asserachrom-HPIA, and GTI-PF4) and their functional relevance was assessed by a two-point heparin-induced platelet aggregation test. Performance of the immunoassays was evaluated by receiver operating characteristic analysis.

Results

Among 1,291 patients, 96 (7.4%) had a positive heparin-induced platelet aggregation-test: 7 of 859 (0.8%) with a low, 50 of 358 (14.0%) with an intermediate, and 39 of 74 (52.7%) with a high 4T-score. Receiver operating characteristics analysis indicated that best immunoassay thresholds for predicting a positive platelet aggregation test were: Titer of 4 or more (ID-H/PF4-PaGIA), optical density more than 0.943 (Asserachrom-HPIA) and more than 1.367 (GTI-PF4). A 100% negative predictive value was observed at the following thresholds: Titer of 1 or under (ID-H/PF4-PaGIA), optical density less than 0.300 (Asserachrom-HPIA) and less than 0.870 (GTI-PF4). A 100% positive predictive value was reached only by ID-H/PF4-PaGIA, at titers of 32 or over. Positive and negative likelihood ratios were calculated for results between the thresholds with 100% negative or positive predictive value.

Conclusions

We show that: i) negative and weak positive results of immunoassays detecting anti-platelet factor 4/heparin-antibodies exclude heparin-induced thrombocytopenia; ii) anti-platelet factor 4/heparin-antibody titers of 32 or over (ID-H/PF4-PaGIA) have a 100% positive predictive value for functionally relevant antibodies; iii) combining the clinical pre-test probability with the likelihood ratio of intermediate immunoassay results allows assessment of post-test probability for heparin-induced thrombocytopenia in individual patients.     

Ocular surface evaluation in patients treated with a fixed combination of prostaglandin analogues with 0.5% timolol maleate topical monotherapy: a randomized clinical trial

OBJECTIVES:

To compare ocular surface changes induced via glaucoma treatment in patients using fixed combinations of prostaglandin analogues (travoprost, latanoprost and bimatoprost) with 0.5% timolol maleate

METHODS:

A prospective, multicenter, randomized, parallel group, single-blind clinical trial was performed in 33 patients with ocular hypertension or open angle glaucoma who had not been previously treated. The ocular surface was evaluated prior to and three months after treatment, with a daily drop instillation of one of the three medications. The main outcome measurements included the tear film break-up time, Schirmer''s test, Lissamine green staining, the Ocular Surface Disease Index questionnaire, impression cytology using HE and PAS and immunocytochemistry for interleukin-6 and HLA-DR. Ensaiosclinicos.gov.br: UTN - U1111-1129-2872

RESULTS:

All of the drugs induced a significant reduction in intraocular pressure. Decreases in the Schirmer''s test results were observed with all of the drugs. Decreases in tear-film break-up time were noted with travoprost/timolol and latanoprost/timolol. An increase in the Lissamine green score was noted with travoprost/timolol and bimatoprost/timolol. The Ocular Surface Disease Index score increased after treatment in the travoprost/timolol group. Impression cytology revealed a significant difference in cell-to-cell contact in the same group, an increase in cellularity in all of the groups and an increase in the number of goblet cells in all of the groups. The fixed combinations induced an increase in IL-6 expression in the travoprost/timolol group, in which there was also an increase in HLA-DR expression.

CONCLUSIONS:

All of the fixed combinations induced a significant reduction in intraocular pressure, and the travoprost/timolol group showed increased expression of the inflammatory markers HLA-DR and interleukin-6. All three tested medications resulted in some degree of deterioration in the ocular surface after three months of glaucoma treatment.     

Recombinant Secreted Antigens from Mycoplasma hyopneumoniae Delivered as a Cocktail Vaccine Enhance the Immune Response of Mice

Mycoplasma hyopneumoniae is the etiological agent of porcine enzootic pneumonia (EP), which is a respiratory disease responsible for huge economic losses in the pig industry worldwide. The commercially available vaccines provide only partial protection and are expensive. Thus, the development of alternatives for the prophylaxis of EP is critical for improving pig health. The use of multiple antigens in the same immunization may represent a promising alternative. In the present study, seven secreted proteins of M. hyopneumoniae were cloned, expressed in Escherichia coli, and evaluated for antigenicity using serum from naturally and experimentally infected pigs. In addition, the immunogenicity of the seven recombinant proteins delivered individually or in protein cocktail vaccines was evaluated in mice. In Western blot assays and enzyme-linked immunosorbent assays, most of the recombinant proteins evaluated were recognized by convalescent-phase serum from the animals, indicating that they are expressed during the infectious process. The recombinant proteins were also immunogenic, and most induced a mixed IgG1/IgG2a humoral immune response. The use of these proteins in a cocktail vaccine formulation enhanced the immune response compared to their use as antigens delivered individually, providing evidence of the efficacy of the multiple-antigen administration strategy for the induction of an immune response against M. hyopneumoniae.     

The Number of Bleaching Sessions Influences Pulp Tissue Damage in Rat Teeth

Introduction

Hydrogen peroxide tooth bleaching is claimed to cause alterations in dental tissue structures. This study investigated the influence of the number of bleaching sessions on pulp tissue in rats.

Methods

Male Wistar rats were studied in 5 groups (groups 1S–5S) of 10 each, which differed by the number (1–5) of bleaching sessions. In each session, the animals were anesthetized, and 35% hydrogen peroxide gel was applied to 3 upper right molars. Two days after the experimental period, the animals were killed, and their jaws were processed for light microscope evaluation. Pulp tissue reactions were scored as follows: 1, no or few inflammatory cells and no reaction; 2, <25 cells and a mild reaction; 3, between 25 and 125 cells and a moderate reaction; and 4, 125 or more cells and a severe reaction. Results from each experimental group were compared between groups and within groups to the corresponding unbleached upper left molars and analyzed for significant differences using the Kruskal-Wallis test (P < .05).

Results

All tissue sections showed significant bleaching-induced changes in the dental pulp. After 1 bleaching session, necrotic tissue in the pulp horns and underlying inflammatory changes were observed. The extent and intensity of these changes increased with the number of bleaching sessions. After 5 sessions, the changes included necrotic areas in the pulp tissue involving the second third of the radicular pulp and intense inflammation in the apical third.

Conclusions

The number of bleaching sessions directly influenced the extent of pulp damage.     

Exercise Prevents Fructose-Induced Hypertriglyceridemia in Healthy Young Subjects

Excess fructose intake causes hypertriglyceridemia and hepatic insulin resistance in sedentary humans. Since exercise improves insulin sensitivity in insulin-resistant patients, we hypothesized that it would also prevent fructose-induced hypertriglyceridemia. This study was therefore designed to evaluate the effects of exercise on circulating lipids in healthy subjects fed a weight-maintenance, high-fructose diet. Eight healthy males were studied on three occasions after 4 days of 1) a diet low in fructose and no exercise (C), 2) a diet with 30% fructose and no exercise (HFr), or 3) a diet with 30% fructose and moderate aerobic exercise (HFrEx). On all three occasions, a 9-h oral [¹³C]-labeled fructose loading test was performed on the fifth day to measure [¹³C]palmitate in triglyceride-rich lipoprotein (TRL)-triglycerides (TG). Compared with C, HFr significantly increased fasting glucose, total TG, TRL-TG concentrations, and apolipoprotein (apo)B48 concentrations as well as postfructose glucose, total TG, TRL-TG, and [¹³C]palmitate in TRL-TG. HFrEx completely normalized fasting and postfructose TG, TRL-TG, and [¹³C]palmitate concentration in TRL-TG and apoB48 concentrations. In addition, it increased lipid oxidation and plasma nonesterified fatty acid concentrations compared with HFr. These data indicate that exercise prevents the dyslipidemia induced by high fructose intake independently of energy balance.It is currently suspected that overconsumption of fructose, in the form of either sugar or high-fructose corn syrup, may promote obesity and favor the development of metabolic diseases such as type 2 diabetes and dyslipidemia (1,2). This is supported by a large number of studies in rodents, which demonstrate that a high-sucrose diet causes obesity, diabetes, dyslipidemia, and hepatic steatosis (3) and that this effect is mainly due to the fructose component of sucrose (4,5). Consistent with this hypothesis, epidemiological studies have shown that high intakes of sugar, fructose, or sweetened beverages are associated with the development of obesity (6,7), diabetes (8), hypertriglyceridemia (9), an increase in small dense atherogenic LDL particles (10), high blood pressure (11), albuminuria (12), and nonalcoholic fatty liver diseases (13). Several short-term studies have further documented that hypercaloric, high-fructose diets can cause increases in a number of cardiometabolic risk factors in humans, such as fasting and postprandial hypertriglyceridemia (14–18), ectopic lipid deposition in liver cells (19,20), impaired postprandial glucose homeostasis (18), and hepatic insulin resistance (21,22). Some of these effects may be related, at least in part, to the fact that fructose can be converted into fatty acids, which has been demonstrated after both acute (23) and chronic (18) fructose feeding. Exercise is very efficient at reducing the metabolic dysfunctions associated with obesity (24,25), and although many of these effects appear to be related to enhanced energy expenditure and improved energy balance (26,27), there is growing evidence that such improvements are independent of the changes in energy balance or body composition (28,29). Exercise has also been shown to prevent the accumulation of triglyceride-rich lipoprotein (TRL)-triglycerides (TG) and improve the plasma atherogenic lipid profile in healthy subjects fed a high-carbohydrate diet (30). The purpose of this study was to investigate whether exercise would similarly prevent fructose-induced metabolic effects.     

Hope, HIV and health: a prospective study

In this study we examined the impact of trait hope on the health of 16 HIV+ individuals. In 2006, hopefulness was assessed with a comprehensive measure derived from an integrative theory of hope. At this time, we also collected self-reported health data as well as blood samples that provided an index of immunological status (CD4). Subsequently, at 8, 24, and 48 months we obtained follow-up CD4 levels. To rule out a potential confound, we computed and found, no significant correlations between self-reports of hope or heath, and blind ratings of illness denial provided by a case manager. Total hope scores as well as hope sub-scores were significantly correlated with various dimensions of self-reported health as well as CDC established CD4 classification levels, both concurrently and prospectively.