Use of AST platelet ratio index (APRI Score) as an alternative to liver biopsy for treatment indication in chronic hepatitis C

Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.

Efficacy and safety of entecavir for chronic HBV in HIV/HBV coinfected patients receiving lamivudine as part of antiretroviral therapy

Background: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining Suppression of plasma HIV RNA less than 400 copies/ml. Methods: Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout. Results: At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log(10) - copies/ml versus 9.27 log(10) copies/ml for placebo, and at week 48, it was 4.79log(10) copies/ml versus 5.63log(10) copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log(10) copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34%. of patients (versus 8% for placebo, P=0.08)At 48 weeks, mean change in HBV DNA reached -4.20log(10) copies/ml inpatients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell Counts were identified. Conclusion: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment. (C) 2008 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Long-term safety and efficacy of percutaneous coronary intervention with stenting and coronary artery bypass surgery for multivessel coronary artery disease - A meta-analysis with 5-year patient-level data from the ARTS, ERACI-II, MASS-II, and SoS trials

Background-Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results-We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P = 0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions-In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.

(Review) Body mass index and risk of diabetes mellitus in the Asia-Pacific region

Few prospective data from the Asia Pacific region are available relating body mass index to the risk of diabetes. Our objective was to provide reliable age, sex and region specific estimates of the associations between body mass index and diabetes. Twenty-seven cohort studies from Asia, New Zealand and Australia, including 154,989 participants, contributed 1,244,793 person-years of follow-up. Outcome data included a combination of incidence of diabetes (based on blood glucose measurements) and fatal diabetes events. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. During follow-up (mean = 8 years), 75 fatal diabetes events and 242 new cases of diabetes were documented. There were continuous positive associations between baseline body mass index and risk of diabetes with each 2 kg/m(2) lower body mass index associated with a 27% (23-30%) lower risk of diabetes. The associations were stronger in younger age groups, and regional comparisons demonstrated slightly stronger associations in Asian than in Australasian cohorts (P = 0.04). This overview provides evidence of a strong continuous association between body mass index and diabetes in the Asia Pacific region. The results indicate considerable potential for reduction in incidence of diabetes with population-wide lowering of body mass index in this region.

Laparoscopic treatment of type 2 diabetes mellitus for patients with a body mass index less than 35

Background Type 2 diabetes mellitus (T2DM) is a common disease with numerous complications. Bariatric surgery is an efficient procedure for controlling T2DM in morbidly obese patients. In T2DM, the incretin effect is either greatly impaired or absent. This study aimed to evaluate the preliminary results from interposing a segment of ileum into the proximal jejunum associated with a sleeve or diverted sleeve gastrectomy to control T2DM in patients with a body mass index (BMI) less than 35 kg/m(2). Methods For this study, 39 patients (16 women and 23 men) underwent two laparoscopic procedures comprising different combinations of ileal interposition into the proximal jejunum via a sleeve or diverted sleeve gastrectomy. The mean age of these patients was 50.3 years (range, 36-66 years). The mean BMI was 30.1 kg/m(2) (range, 23.4-34.9 kg/m(2)). All the patients had a diagnosis of T2DM that had persisted for at least 3 years and evidence of stable treatment with oral hypoglycemic agents or insulin for at least 12 months. The mean duration of T2DM was 9.3 years (range, 3-22 years). Results The mean operative time was 185 min, and the median hospital stay was 4.3 days. Four major complications occurred in the short term (30-days), and the mortality rate was 2.6%. The mean postoperative follow-up period was 7 months (range, 4-16 months), and the mean percentage of weight loss was 22%. The mean postoperative BMI was 24.9 kg/m(2) (range, 18.9-31.7 kg/m2). An adequate glycemic control was achieved for 86.9% of the patients, and 13.1% had important improvement. The patients whose glycemia was not normalized were using a single oral hypoglycemic agent. No patient needed insulin therapy postoperatively. All the patients except experienced normalization of their cholesterol levels. Targeted triglycerides levels were achieved by 71% of the patients, and hypertension was controlled for 95.8%. Conclusions The laparoscopic ileal interposition via either a sleeve gastrectomy or diverted sleeve gastrectomy seems to be a promising procedure for the control of T2DM and the metabolic syndrome. A longer follow-up period is needed.

Correlation between the Body Mass Index (BMI) of Pregnant Women and the Development of Hypotension after Spinal Anesthesia for Cesarean Section

Nani FS, Torres MLA - Correlation between the Body Mass Index (BMI) of Pregnant Women and the Development of Hypotension after Spinal Anesthesia for Cesarean Section. Background and objectives: Very few publications correlate hypotension in obese pregnant women, and especially morbidly obese, after spinal anesthesia for cesarean section. The objective of the present study was to evaluate the incidence of hypotension according to the BMI. Methods: Forty-nine patients with pregestational BMI below 25 kg.m(-2) were included in the Eutrophia group, and 51 patients with BMI >= 25 kg.m(-2) were included in the Overweight group. After spinal anesthesia, blood pressure, volume of crystalloid infused, and dose of vasopressors used until delivery were recorded. A fall in systolic blood pressure below 100 mmHg or 10% reduction of the initial systolic blood pressure (SBP) was considered as hypotension and it was corrected by the administration of vasopressors. Results: Episodes of hypotension were fewer in the Eutrophia group (5.89 +/- 0.53 vs. 7.80 +/- 0.66, p = 0.027), as well as the amount of crystalloid administered (1,298 +/- 413.6 mL vs. 1,539 +/- 460.0 mL; p = 0.007), and use of vasopressors (5.87 +/- 3.45 bolus vs. 7.70 +/- 4.46 bolus; p = 0.023). As for associated diseases, we observed higher incidence of diabetes among obese pregnant women (29.41% vs. 9.76%, RR 1.60, 95%CI: 1.15-2.22, p = 0.036), however, differences in the incidence of pregnancy-induced hypertension (PIN) were not observe between both groups (overweight: 21.57%, normal weight: 12.20%, RR 1.30, 95%CI: 0.88-1.94, p = 0.28). Conclusions: In the study sample, pregestational BMI >= 25 kg.m(-2) was a risk factor for hypotension after spinal anesthesia in patients undergoing cesarean section. The same group of patients required higher doses of vasopressors. Those results indicate that the anesthetic techniques in those patients should be improved to reduce the consequences of post-spinal anesthesia hypotension, both in pregnant women and fetuses.

Analysis of dynamic process models for structural insight and model reduction .1. Structural identification measures

An important consideration in the development of mathematical models for dynamic simulation, is the identification of the appropriate mathematical structure. By building models with an efficient structure which is devoid of redundancy, it is possible to create simple, accurate and functional models. This leads not only to efficient simulation, but to a deeper understanding of the important dynamic relationships within the process. In this paper, a method is proposed for systematic model development for startup and shutdown simulation which is based on the identification of the essential process structure. The key tool in this analysis is the method of nonlinear perturbations for structural identification and model reduction. Starting from a detailed mathematical process description both singular and regular structural perturbations are detected. These techniques are then used to give insight into the system structure and where appropriate to eliminate superfluous model equations or reduce them to other forms. This process retains the ability to interpret the reduced order model in terms of the physico-chemical phenomena. Using this model reduction technique it is possible to attribute observable dynamics to particular unit operations within the process. This relationship then highlights the unit operations which must be accurately modelled in order to develop a robust plant model. The technique generates detailed insight into the dynamic structure of the models providing a basis for system re-design and dynamic analysis. The technique is illustrated on the modelling for an evaporator startup. Copyright (C) 1996 Elsevier Science Ltd

Anti-Lipoprotein Lipase Antibodies in Patients with Hypertriglyceridemia without Associated Autoimmune Disease

Background: Anti-lipoprotein lipase antibodies have been described in rare cases of patients with hypertriglyceridemia. However, no systematic study evaluating these antibodies in patients with this lipid abnormality has been undertaken. Objectives: To analyze the correlation of anti-lipoprotein lipase (anti-LPL) antibodies with other laboratory findings in patients with hypertriglyceridemia but no autoimmune disease. Methods: We evaluated 44 hypertriglyceridemic patients without autoimmune disease. Clinical and laboratory evaluations included analyses of comorbidities, fasting lipid profile and anti-LPL antibodies. Results: Mean patient age was 55 +/- 10 years; 46% of the patients were female and 64% were Caucasian. The mean disease duration was 94.4 months and mean body mass index 28.7 +/- 3.6 kg/m(2); 34.0% were diabetic, 25.0% were obese, 72.7% had systemic arterial hypertension, 75% were sedentary, 15.9% were smokers, 56.8% had a family history of dyslipidemia, 45.5% had a family history of coronary insufficiency, 20.5% had acute myocardial infarction, 9.0% had undergone revascularization and 11.0% angioplasty, 79.5% were being treated with statins and 43.2% were taking fibrates. Median triglyceride levels were 254 mg/dl (range 100-3781 mg/dl), and total cholesterol level was 233 +/- 111 mg/dl. High-density lipoprotein was 42.6 +/- 15.4 mg/dl, low-density lipoprotein 110.7 +/- 42.4 mg/dl and very low-density lipoprotein 48 +/- 15 mg/dl. Anti-LPL antibodies were identified in 2 patients (4.5%), both of whom had a family history of dyslipidemia, coronary insufficiency and acute myocardial infarction; one had undergone myocardial revascularization and percutaneous transluminal coronary angioplasty, and both were using fibrates and had normal triglyceride levels. Conclusions: Our findings demonstrate a correlation between the immune response and dyslipoproteinemia in hypertriglyceridemic patients, suggesting that autoimmune disease contributes to the dyslipidemia process.

Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases

Background Despite the WHO recommendation that the 2010-2011 trivalent seasonal flu vaccine must contain A/California/7/2009/H1N1-like virus there is no consistent data regarding its immunogenicity and safety in a large autoimmune rheumatic disease (ARD) population. Methods 1668 ARD patients (systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic sclerosis, psoriatic arthritis (PsA), Behcet`s disease (BD), mixed connective tissue disease, primary antiphospholipid syndrome (PAPS), dermatomyositis (DM), primary Sjogren`s syndrome, Takayasu`s arteritis, polymyositis and Granulomatosis with polyangiitis (Wegener`s) (GPA)) and 234 healthy controls were vaccinated with a non-adjuvanted influenza A/California/7/2009(H1N1) virus-like strain flu. Subjects were evaluated before vaccination and 21 days post-vaccination. The percentage of seroprotection, seroconversion and the factor increase in geometric mean titre (GMT) were calculated. Results After immunisation, seroprotection rates (68.5% vs 82.9% p < 0.0001), seroconversion rates (63.4% vs 76.9%, p < 0.001) and the factor increase in GMT (8.9 vs 13.2 p < 0.0001) were significantly lower in ARD than controls. Analysis of specific diseases revealed that seroprotection significantly reduced in SLE (p < 0.0001), RA (p < 0.0001), PsA (p=0.0006), AS (p=0.04), BD (p=0.04) and DM (p=0.04) patients than controls. The seroconversion rates in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p=0.0006) patients and the increase in GMTs in SLE (p < 0.0001), RA (p < 0.0001) and PsA (p < 0.0001) patients were also reduced compared with controls. Moderate and severe side effects were not reported. Conclusions The novel recognition of a diverse vaccine immunogenicity profile in distinct ARDs supports the notion that a booster dose may be recommended for diseases with suboptimal immune responses. This large study also settles the issue of vaccine safety. (ClinicalTrials.gov #NCT01151644)

Human immunodeficiency virus test-seeking blood donors in a large blood bank in Sao Paulo, Brazil

BACKGROUND: Persons with human immunodeficiency virus (HIV) risk behaviors are excluded from donation to reduce the risk of transfusion-transmitted infection. Persons donating to be tested for HIV may therefore deny risk behaviors. STUDY DESIGN AND METHODS: A random sample of donors completed a survey on motivations, knowledge, and attitudes on the screening process. Donors were considered test seekers if they agreed with two statements ""I think that blood donation is a good, fast, and anonymous way to get my blood tested"" and ""I donate to get my test results."" This study was conducted from June to November 2006 at the largest blood bank in Sao Paulo, Brazil. RESULTS: Of 3061 participants, 208 (7%) were test seekers. They tended to be male and had a lower educational level. They were more likely to have incorrect knowledge about blood safety (e.g., not knowing that a unit can test antibody negative and still transmit infection, 60% vs. 42%, p = 0.02), express dissatisfaction with screening questions (e.g., feeling that important questions were not asked, 14% vs. 5%, p < 0.01), and concur that donors do not answer questions truthfully (e.g., donors have more sexual partners than they admit, 29% vs. 18%, p < 0.01). Test seekers were more likely to believe that it is acceptable to donate blood to get tested for HIV (41% vs. 10%, p < 0.01). CONCLUSIONS: Test-seeking motivation, coupled with low knowledge of window period risk, is counter to improving blood safety and to donor prevention needs. Donor education needs to be improved along with availability of appropriate HIV counseling and testing.

Outcomes and safety of drug provocation tests

Drug provocation tests (DPTs) are considered the gold standard for identifying adverse drug reactions (ADRs). The aim of this study was to analyze DPT results and discuss severe systemic reactions associated with them. This was a retrospective analysis of 500 patients with ADRs who sought treatment and were submitted to DPTs when indicated between 2006 and 2010. We performed DPTs according to the European Network for Drug Allergy recommendations. Single-blind, placebo-controlled DPTs were performed with antibiotics, local anesthetics, and nonsteroidal anti-inflammatory drugs, as well as with other drugs. Patient characteristics, DPT results, and reactions were analyzed. The sample comprised 198 patients (80.8% of whom were female patients) submitted to 243 DPTs. Ages ranged from 9 to 84 years (mean, 39.9 years). The 243 DPTs were performed with local anesthetics (n = 93), antibiotics (n = 19), acetaminophen (n = 44), benzydamine (n = 33), COX-2 inhibitors (n = 26), dipyrone (n = 7), aspirin (n = 4), or other drugs (n = 17). The results of 4 tests (1.6%) were inconclusive, whereas those of 10 (4.1%) revealed positive reactions to antibiotics (2/19), COX-2 inhibitors (2/26), acetaminophen (3/44), and local anesthetics (3/93). Two severe reactions were observed: cephalexin-induced anaphylactic shock and bupivacaine-induced anaphylaxis without shock. Four patients (2.0%) reacted to the placebo before administration of the drug. Drug provocation tests are safe for use in clinical practice but they should be placebo-controlled and should be performed under the supervision of an allergist. To confirm a presumptive diagnosis and to manage allergies appropriately, it is crucial to perform DPTs. (Allergy Asthma Proc 32:301-306, 2011; doi: 10.2500/aap.2011.32.3450)

The relationship between body mass index and the variation in plasma levels of triglycerides after short-term red wine consumption

BACKGROUND: Alcoholic beverages may have protective cardiovascular effects but are known to increase the plasma levels of triglycerides (TG). Both TG and the ratio of TO to high-density lipoprotein cholesterol (TG/HDL-cholesterol) are associated with increased cardiovascular risk. OBJECTIVES: To determine the predictive factors for variations in plasma levels of TO and the TG/HDL-cholesterol ratio in patients after they had consumed red wine for 14 days. METHODS: Forty-two subjects (64% men, 46 +/- 9 years, baseline body mass index [BMI] 25.13 +/- 2.76 kg/m(2)) were given red wine (12% or 12.2% alc/vol, 250 mL/day with meals). Plasma concentration of lipids and glucose were measured before and after red wine consumption. Blood was collected after 12 hours of fast and alcohol abstention. RESULTS: Red wine increased plasma levels of TO from 105 +/- 42 mg/dL to 120 +/- 56 mg/dL (P = .001) and the TG/HDL-cholesterol ratio from 2.16 +/- 1.10 to 2.50 +/- 1.66 (P = .014). In a multivariate linear regression model that included age, baseline BMI, blood pressure, lipids, and glucose, only BMI was independently predictive of the variation in plasma TO after red wine (beta coefficient 0.592, P < .001). BMI also predicted the variation in TG/HDL-cholesterol ratio (beta coefficient 0.505, P = .001, adjusted model). When individuals were divided into three categories, according to their BMI, the average percentage variation in TG after red wine was -4%, 17%, and 33% in the lower (19.60-24.45 kg/m(2)), intermediate, and greater (26.30-30.44 kg/m(2)) tertiles, respectively (P = .001). CONCLUSIONS: Individuals with higher BMI, although nonobese, might be at greater risk for elevation in plasma TO levels and the TG/HDL-cholesterol ratio after short-term red wine consumption. (C) 2011 National Lipid Association. All rights reserved.

beta-Blocker Therapy and Mortality of Patients With Chagas Cardiomyopathy A Subanalysis of the REMADHE Prospective Trial

Background-Peculiar aspects of Chagas cardiomyopathy raise concerns about efficacy and safety of sympathetic blockade. We studied the influence of beta-blockers in patients with Chagas cardiomyopathy. Methods and Results-We examined REMADHE trial and grouped patients according to etiology (Chagas versus non-Chagas) and beta-blocker therapy. Primary end point was all-cause mortality or heart transplantation. Altogether 456 patients were studied; 27 (5.9%) were submitted to heart transplantation and 202 (44.3%) died. Chagas etiology was present in 68 (14.9%) patients; they had lower body mass index (24.1+/-4.1 versus 26.3+/-5.1, P=0.001), smaller end-diastolic left ventricle diameter (6.7+/-1.0 mm versus 7.0+/-0.9 mm, P=0.001), smaller proportion of beta-blocker therapy (35.8% versus 68%, P<0.001), and higher proportion of spironolactone therapy (74.6% versus 57.8%, P=0.003). Twenty-four (35.8%) patients with Chagas disease were under beta-blocker therapy and had lower serum sodium (136.6+/-3.1 versus 138.4+/-3.1 mEqs, P=0.05) and lower body mass index (22.5+/-3.3 versus 24.9+/-4.3, P=0.03) compared with those who received beta-blockers. Survival was lower in patients with Chagas heart disease as compared with other etiologies. When only patients under beta-blockers were considered, the survival of patients with Chagas disease was similar to that of other etiologies. The survival of patients with beta-blockers was higher than that of patients without beta-blockers. In Cox regression model, left ventricle end-diastolic diameter (hazard ratio, 1.78; CI, 1.15 to 2.76; P=0.009) and beta-blockers (hazard ratio, 0.37; CI, 0.14 to 0.97; P=0.044) were associated with better survival. Conclusions-Our study suggests that beta-blockers may have beneficial effects on survival of patients with heart failure and Chagas heart disease and warrants further investigation in a prospective, randomized trial.