A Sustained Virologic Response Is Durable in Patients With Chronic Hepatitis C Treated With Peginterferon Alfa-2a and Ribavirin

BACKGROUND & AIMS: A sustained virologic response (SVR) to therapy for hepatitis C virus (HCV) infection is defined as the inability to detect HCV RNA 24 weeks after completion of treatment. Although small studies have reported that the SVR is durable and lasts for long periods, it has not been conclusively shown. METHODS: The durability of treatment responses was examined in patients originally enrolled in one of 9 randomized multicenter trials (n = 1343). The study included patients who received pegylated interferon (peginterferon) alfa-2a alone (n = 166) or in combination with ribavirin (n = 1077, including 79 patients with normal alanine aminotransferase levels and 100 patients who were coinfected with human immunodeficiency virus and HCV) and whose serum samples were negative for HCV RNA (<50 IU/mL) at their final assessment. Patients were assessed annually, from the date of last treatment, for a mean of 3.9 years (range, 0.8-7.1 years). RESULTS: Most patients (99.1%) who achieved an SVR had undetectable levels of HCV RNA in serum samples throughout the follow-up period. Serum samples from 0.9% of the patients contained HCV RNA a mean of 1.8 years (range, 1.1-2.9 years) after treatment ended. It is not clear if these patients were reinfected or experienced a relapse. CONCLUSIONS: In a large cohort of patients monitored for the durability of an SVR, the SVR was maintained for almost 4 years after treatment with peginterferon alfa-2a alone or in combination with ribavirin. In patients with chronic hepatitis C infection, the SVR is durable and these patients should be considered as cured.

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.

Microbiological indicators for the assessment of performance in the hazard analysis and critical control points (HACCP) system in meat lasagna production

The HACCP system is being increasingly used to ensure food safety. This study investigated the validation of the control measures technique in order to establish performance indicators of this HACCP system in the manufacturing process of Lasagna Bolognese (meat lasagna). Samples were collected along the manufacturing process as a whole, before and after the CCPs. The following microorganism s indicator (MIs) was assessed: total mesophile and faecal coliform counts. The same MIs were analyzed in the final product, as well as, the microbiological standards required by the current legislation. A significant reduction in the total mesophile count was observed after cooking (p < 0.001). After storage, there was a numerical, however non-significant change in the MI count. Faecal coliform counts were also significantly reduced (p < 0.001) after cooking. We were able to demonstrate that the HACCP system allowed us to meet the standards set by both, the company and the Brazilian regulations, proved by the reduction in the established indicators

Determination of the minimum value of the safety factor from geodesic Alfven eigenmodes in Joint European Torus

An analysis of the experimental conditions under which low-frequency (70-150 kHz) Alfven eigertmodes (AE) are excited during the monster sawtooth in Joint European Torus [F Romanelli et al, Proceedings of the 22nd IAEA Fusion Energy Conference, Geneva, Switzerland, 2008] is presented for the specific case of a discharge with ion cyclotron heating (5 MW) Using a simplified AE model for modes excited at the Alfven wave continuum maximum with geodesic corrections taken into account, the temporal evolution of the value of the safety factor q(0) at the magnetic axis is determined We describe a new scheme to determine the time variation of q(0) that works under conditions in which other standard diagnostics, such as the motional Stark effect do not give reliable results such as during a monster sawtooth [doi 10 1063/1 3494212]

A safety assessment methodology applied to CNS/ATM-based air traffic control system

In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm, based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining ""absolute"" and ""relative"" safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 [14], using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the ""Automatic Dependent Surveillance-Broadcasting"" (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric. (C) 2011 Elsevier Ltd. All rights reserved.

In vitro safety assessment of papain on human skin: A qualitative Light and Transmission Electron Microscopy (TEM) study

Papain is a thiol proteolytic enzyme widely used in dermatology that found applications in wound treatment. Recently, papain was also used as absorption enhancer which can modify the peptide/ protein material in the bilayer domain. We investigated papain safety using human skin that was exposed to papain in vitro at different times: 4, 24 and 48 hours. The samples were examined using Light and Transmission Electron Microscopy (TEM) to study of the mechanisms involved in enhancer-skin interaction. After 24 hours, changes occurred in corneosomes. However, samples of 48 hours did not show major changes in agreement with the control. These findings indicated that papain could be used safely onto the skin.

Chemical analysis of dairy cattle feed from Brazil

The bovine dairy cattle demand diets of high nutritional value being essential to know chemical composition of feed supplied to cows to achieve high levels of quality, safety and productivity of milk. Different roughages and concentrates from Minas Gerais and Rio Grande do Sul states, Brazil, were analyzed by instrumental neutron activation analysis (INAA) and inductively coupled plasma mass spectrometry (ICP-MS). Concentrate and roughage samples were differentiated by mass fractions of As, Ba, Mg, P, Rb and Sr. Samples of concentrate from both origins were differentiated by mass fractions of As, Cd, Co, Cr, Cs, Ni and Rb.

Efficacy and safety of iodopovidone pleurodesis in malignant pleural effusions

Background and objective: Pleurodesis is one of the best methods of controlling malignant pleural effusions (MPE), a distressing complication of metastatic disease. In recent studies of a wide range of pleural diseases, iodopovidone was used as a sclerosing agent for pleurodesis and demonstrated good results with low morbidity. The aim of this study was to evaluate the efficacy and safety of iodopovidone pleurodesis in MPE. Methods: A retrospective analysis was performed on patients with MPE who underwent pleurodesis at our institution between 2005 and 2008. All patients underwent instillation of 20 mL of 10% iodopovidone, 80 mL of normal saline and 2 mg/kg of lidocaine through a chest tube, which was clamped for 2 h. The tube was removed when the daily output of fluid was < 200 mL. Data on the requirement for additional pleural procedures, adverse events and survival were collected. Results: Sixty-one pleurodesis procedures were performed in 54 patients. No procedure-related mortality was observed. Adverse events occurred after 11 (18%) pleurodesis procedures. The most frequent complication was mild thoracic pain that occurred immediately after 10 (16.4%) procedures, and one patient developed pleural empyema that was treated with drainage and antibiotics. A success rate of 98.4% was observed. Except for the patient who developed pleural empyema, none of the other patients had recurrences of pleural fluid or required additional pleural procedures during the follow-up period (mean of 5.6 months). Conclusions: Iodopovidone pleurodesis was successful and was associated with only a few minor complications. It appears to be a good option for the management of recurrent MPE.

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)

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)

An ergonomic approach to reorganize parking inspection agents` work productivity, health and safety in Sao Paulo, Brazil

Objective: The Traffic Engineering Company of the City of Sao Paulo (Brazil) observed a decrease in productivity, and an increase in sick leave, accidents and psychological distress among their parking inspection agents. To document this situation, qualitative research was undertaken to obtain an in-depth comprehension of work activity. Participants: Workers, managers and health and safety professionals contributed to the documentation of the problem and to the proposal of possible solutions. Methods: Ergonomic work analysis focusing on real work activity, as well as interviews with individual or groups of stakeholders, were conducted. Results: This research revealed that political-economic factors gradually contributed to: 1) an increasing work load; 2) growing fatigue throughout the day, increasing the workers` vulnerability to incidents and accidents and their tendency to react inappropriately to violence experienced on the street; and 3) excessive individual responsibility to manage dangerous situations. Conclusions: Recommendations to ameliorate the situation are proposed. These suggestions are discussed in terms of feasibility given the impact of macro social factors upon micro work activity, and the associated potential expansion of the ergonomist`s role.

To treat or not to treat? A meta-analysis of the use of cholinesterase inhibitors in mild cognitive impairment for delaying progression to Alzheimer`s disease

Individual randomized clinical trials (RCTs) with cholinesterase inhibitors (ChEIs) aiming to delay the progression from mild cognitive impairment (MCI) to Alzheimer`s disease (AD) have not found significant benefit of their use for this purpose. The objective of this study is to meta-analyze the RCTs conducted with ChEIs in order to assess whether pooled analysis could show the benefit of these drugs in delaying the progression from MCI to AD. We searched for references of published and unpublished studies on electronic databases (Medline, Embase, Web of Science, and Clinical Trial Database Registry, particularly the Clinicaltrials.gov-http://www.clinicaltrials.gov). We retrieved 173 references, which yielded three references for data extraction. A total of 3.574 subjects from four RCTs were included in the meta-analysis. Among 1,784 subjects allocated in the ChEI-treatment group, 275 (15.4%) progressed to AD/dementia, as opposed to 366 (20.4%) out of 1,790 subjects in the placebo group. The relative risk (RR) for progression to AD/dementia in the ChEI-treated group was 0.75 [CI(95%) 0.66-0.87], z = -3.89, P < 0.001. The patients on the ChEI group had a significantly higher all-cause dropout risk than the patients on the placebo group (RR = 1.36 CI(95%) [1.24-1.49]; z = 6.59, P < 0.001). The RR for serious adverse events (SAE) in the ChEI-treated group showed no significantly statistical difference from the placebo group (RR = 0.95 [CI(95%) 0.83-1.09], z = -0.72, P = 0.47). The subjects in the ChEI-treated group had a marginally, non-significant, higher risk of death due to any cause than those in the placebo-treated group (RR = 1.04, CI(95%) 0.63-1.70, z = 0.16, P = 0.86). The long-term use of ChEIs in subjects with MCI may attenuate the risk of progression to AD/dementia. This finding may have a significant impact on public health and pharmaco-economic policies.

Cost-effectiveness analysis of routine rotavirus vaccination in Brazil

Objective. The objective of this study was to conduct a cost-effectiveness analysis of a universal rotavirus vaccination program among children : 5 years of age in Brazil. Methods. Considering a hypothetical annual cohort of approximately 3 300 000 newborns followed over 5 years, a decision-tree model was constructed to examine the possible clinical and economic effects of rotavirus infection with and without routine vaccination of children. Probabilities and unit costs were derived from published research and national administrative data. The impact of different estimates for key parameters was studied using sensitivity analysis. The analysis was conducted from both healthcare system and societal perspectives. Results. The vaccination program was estimated to prevent approximately 1735 351 (54%) of the 3 210 361 cases of rotavirus gastroenteritis and 703 (75%) of 933 rotavirus-associated deaths during the 5-year period. At a vaccine price of 18.6 Brazilian reais (R$) per dose, this program would cost R$121 673 966 and would save R$38 536 514 in direct costs to the public healthcare system and R$71 778 377 in direct and indirect costs to society. The program was estimated to cost R$1 028 and R$1 713 per life-years saved (LYS)from the societal and healthcare system perspectives, respectively. Conclusions. Universal rotavirus vaccination was a cost-effective strategy for both perspectives. However, these findings are highly sensitive to diarrhea incidence rate, proportion of severe cases, vaccine coverage, and vaccine price.

Safety of the etonogestrel-releasing implant during the immediate postpartum period: a pilot study

Background: The effects of etonogestrel (ETG)-releasing contraceptive implant during the immediate postpartum period on maternal safety are unknown. Study design: Forty healthy women exclusively breastfeeding were randomized to receive either ETG-releasing implant 24-48 h after delivery (n=20) or depot medroxyprogesterone acetate (DMPA group; n=20) at the sixth week postpartum. We measured blood pressure, maternal and neonatal weight, body mass index (BMI; kg/m(2)), waist circumference (WC), complete blood count, C-reactive protein, interleukin-6, tumor necrosis factor (TNF-alpha), lipid profile, fasting serum glucose and maintenance of exclusive lactation up to the 12th week postpartum. Results: Decreases in mean maternal weight, BMI (kg/m(2)) and WC were significantly greater in the ETG-releasing implant group than in the MPA group during the first 6 weeks postpartum (-4.64 +/- 2.71 kg vs. -2.6 +/- 2.45 kg mean +/- SD, p=.017; -1.77 +/- 1.06 kg/m(2) vs. -0.97 +/- 0.95 kg/m(2), p=.026; -15.3 +/- 6.72 cm vs. -9.05 +/- 5.84 cm, p=.003, respectively). In addition, total cholesterol and HDL, were lower in DMPA users, and TNF-alpha and leukocytes were higher in DMPA users compared to in the implant group, between 6 and 12 weeks after delivery. The newborns of implant users showed a trend towards gaining more weight, as compared with the infants of the DMPA mothers during the first 6 weeks of life (implant group: +1460.50 +/- 621.34 g vs. DMPA group: +1035.0 +/- 562.43 g, p=.05). The remaining variables, including the duration of exclusive breastfeeding, were similar between the groups. Conclusion: The insertion of ETG-releasing contraceptive implant during the immediate postpartum period was not associated with deleterious maternal clinical effects or with significant maternal metabolic alterations or decreased infant weight gain. (C) 2009 Elsevier Inc. All rights reserved.

Evaluation of Efficacy and Safety of Zinc Gluconate Associated with Dimethyl Sulphoxide for Sexually Mature Canine Males Chemical Neutering

Contents The aim of this research was to evaluate the efficacy of zinc gluconate associated with dimethyl sulphoxide (DMSO) for chemical neutering in canine males. Fifteen sexually mature male dogs were divided in two groups, named control and treated. An injection was administered to both testicles, at a concentration of 26.2 mg zinc gluconate per ml and 0.5% DMSO in the treated group (11 dogs). The control group was given injections of saline solution (four dogs). Clinical examination and blood collection for a haemogram were done both before and after drug injection. There were 12 spermograms performed to analyse sperm motility, sperm vigour, ejaculate volume, testicle size, pathology and sperm concentrations. Libido was also measured. An ultrasound examination and histopathology were performed at the end of the experiment. Dogs` libido after chemical injection was reduced by over 50%. The spermogram analysis showed final mean results of 14.54% for sperm motility, 0.72 of sperm vigour and 37 150 per million spermatozoa per millilitre, values considered below the necessary levels at which fertilization can occur. Ultrasound and histopathology analyses of testicles for the treated group revealed more intense injuries when compared with the control group, with compromised testicular parenchyma and a decrease of germ cell number leading to total atrophy, indicating that the treatment reduced the fertilizing potential of male dogs, promoting a possible subfertile status.