Protocol of the Febuxostat versus Allopurinol Streamlined Trial (FAST):a large prospective, randomised, open, blinded endpoint study comparing the cardiovascular safety of allopurinol and febuxostat in the management of symptomatic hyperuricaemia

Introduction: Gout affects 2.5% of the UK's adult population and is now the most common type of inflammatory arthritis. The long-term management of gout requires reduction of serum urate levels and this is most often achieved with use of xanthine oxidase inhibitors, such as allopurinol. Febuxostat is the first new xanthine oxidase inhibitor since allopurinol and was licensed for use in 2008. The European Medicines Agency requested a postlicensing cardiovascular safety study of febuxostat versus allopurinol, which has been named the Febuxostat versus Allopurinol Streamlined trial (FAST).<p></p> Methods and analysis: FAST is a cardiovascular safety study using the prospective, randomised, open, blinded endpoint design. FAST is recruiting in the UK and Denmark. Recruited patients are aged over 60 years, prescribed allopurinol for symptomatic hyperuricaemia and have at least one additional cardiovascular risk factor. After an allopurinol lead-in phase where the dose of allopurinol is optimised to achieve European League against Rheumatism (EULAR) urate targets (serum urate <357 µmol/L), patients are randomised to either continue optimal dose allopurinol or to use febuxostat. Patients are followed-up for an average of 3 years. The primary endpoint is first occurrence of the Anti-Platelet Trialists’ Collaboration (APTC) cardiovascular endpoint of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary endpoints are all cause mortality and hospitalisations for heart failure, unstable, new or worsening angina, coronary or cerebral revascularisation, transient ischaemic attack, non-fatal cardiac arrest, venous and peripheral arterial vascular thrombotic event and arrhythmia with no evidence of ischaemia. The primary analysis is a non-inferiority analysis with a non-inferiority upper limit for the HR for the primary outcome of 1.3

Nutrition of preterm infants in relation to bronchopulmonary dysplasia

<p/> <p>Background</p> <p>The pathogenesis of bronchopulmonary dysplasia (BPD) is multifactorial. In addition to prenatal inflammation, postnatal malnutrition also affects lung development.</p> <p>Methods</p> <p>A retrospective study was performed to analyse during the first two weeks of life the total, enteral and parenteral nutrition of premature infants (<31 weeks, birth weight ≤1500 g) born between 08/04 and 12/06.</p> <p>Results</p> <p>Ninety-five premature infants were analysed: 26 with BPD (27 ± 1 weeks) and 69 without BPD (28 ± 1 weeks). There was no statistical significant difference in the total intake of fluids, calories, glucose or protein and weight gain per day in both groups. The risk of developing BPD was slightly increased in infants with cumulative caloric intake below the minimal requirement of 1230 kcal/kg and a cumulative protein intake below 43.5 g/kg. Furthermore, the risk of developing BPD was significantly higher when infants had a cumulative fluid intake above the recommended 1840 ml/kg. In infants who developed BPD, the enteral nutrition was significantly lower than in non-BPD infants [456 ml/kg (IQR 744, 235) vs. 685 (IQR 987, 511)]. Infants who did not develop BPD reached 50% of total enteral feeding significantly faster [9.6 days vs. 11.5].</p> <p>Conclusions</p> <p>Preterm infants developing BPD received less enteral feeding, even though it was well compensated by the parenteral nutrient supply. Data suggest that a critical minimal amount of enteral feeding is required to prevent development of BPD; however, a large prospective clinical study is needed to prove this assumption.</p

Thromboelastometry (ROTEM®) in children: age-related reference ranges and correlations with standard coagulation tests

Background The small sample volume needed and the prompt availability of results make viscoelastic methods like rotational thromboelastometry (ROTEM®) attractive for monitoring coagulation in small children. However, data on reference ranges for ROTEM® parameters in children are scarce. Methods Four hundred and seven children (ASA I and II) undergoing elective surgery were recruited for this prospective, two-centre, observational study. Subjects were grouped as follows: 0-3, 4-12, 13-24 months, 2-5, 6-10, and 11-16 yr. Study objectives were to establish age-dependent reference ranges for ROTEM® assays, analyse age dependence of parameters, and compare ROTEM® data with standard coagulation tests. Results Data from 359 subjects remained for final analysis. Except for extrinsically activated clot strength and lysis, parameters for ROTEM® assays were significantly different among all age groups. The most striking finding was that subjects aged 0-3 months exhibited accelerated initiation (ExTEM coagulation time: median 48 s, Q1-Q3 38-65 s; P=0.001) and propagation of coagulation (α angle: median 78o, Q1-Q3 69-84o; P<0.001) and maximum clot firmness (median 62 mm, Q1-Q3 54-74 mm), although standard plasma coagulation test results were prolonged (prothrombin time: median 13.2 s, Q1-Q3 12.6-13.6 s; activated partial thromboplastin time: median 42 s, Q1-Q3 40-46 s). Lysis indices of <85% were observed in nearly one-third of all children without increased bleeding tendency. Platelet count and fibrinogen levels correlated significantly with clot strength, and fibrinogen levels correlated with fibrin polymerization. Conclusions Reference ranges for ROTEM® assays were determined for all paediatric age groups. These values will be helpful when monitoring paediatric patients and in studies of perioperative coagulation in childre

Improving transparency and scientific rigor in academic publishing.

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories

Liver Enzymes: Interaction Analysis of Smoking with Alcohol Consumption or BMI, Comparing AST and ALT to γ-GT

A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT) has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT), routine liver markers less prone to enzyme induction.<0.0001). The interactions all were in the same directions as for γ-GT, i.e. synergistic with alcohol and opposite with BMI.The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for γ-GT. This renders enzyme induction a less probable mechanism for these associations, whereas it might implicate exacerbated hepatocellular vulnerability and injury

Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms

A scanning electron microscope survey was initiated to determine if the previously reported findings of “dinosaurian soft tissues” could be identified in situ within the bones. The results obtained allowed a reinterpretation of the formation and preservation of several types of these “tissues” and their content. Mineralized and non-mineralized coatings were found extensively in the porous trabecular bone of a variety of dinosaur and mammal species across time. They represent bacterial biofilms common throughout nature. Biofilms form endocasts and once dissolved out of the bone, mimic real blood vessels and osteocytes. Bridged trails observed in biofilms indicate that a previously viscous film was populated with swimming bacteria. Carbon dating of the film points to its relatively modern origin. A comparison of infrared spectra of modern biofilms with modern collagen and fossil bone coatings suggests that modern biofilms share a closer molecular make-up than modern collagen to the coatings from fossil bones. Blood cell size iron-oxygen spheres found in the vessels were identified as an oxidized form of formerly pyritic framboids. Our observations appeal to a more conservative explanation for the structures found preserved in fossil bone

Antibody dynamics and spontaneous viral clearance in patients with acute hepatitis C infection in Rio de Janeiro, Brazil

Submitted by Sandra Infurna ([email protected]) on 2017-01-18T10:31:05Z No. of bitstreams: 1 clara_yoshida_etal_IOC_2011.pdf: 146042 bytes, checksum: 8ec889224534b76d755828a99d0660c2 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-01-18T10:59:52Z (GMT) No. of bitstreams: 1 clara_yoshida_etal_IOC_2011.pdf: 146042 bytes, checksum: 8ec889224534b76d755828a99d0660c2 (MD5)Made available in DSpace on 2017-01-18T10:59:52Z (GMT). No. of bitstreams: 1 clara_yoshida_etal_IOC_2011.pdf: 146042 bytes, checksum: 8ec889224534b76d755828a99d0660c2 (MD5) Previous issue date: 2011Innsbruck Medical University. Department of Medical Statistics, Informatics and Health Economics. Innsbruck, Austria.Harvard Medical School. Boston, MA, USA / Massachussets General Hospital. Division of Infectious Diseases. Boston, MA, USA.Harvard Medical School. Boston, MA, USA / Massachussets General Hospital. Gastrointestinal Unit. Boston, MA, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Laboratório Central de Saúde Pública Noel Nutels. Divisão de Hepatites. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil / Universidade Federal do Estado do Rio de Janeiro. Hospital Universitário Gaffrée Guinle. Unidade de Hepatologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Desenvolvimento Tecnológico em Virologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Universitätsklinikum Eppendorf. Medizinische Klinik I. Hamburg, Germany.Fondation Merieux. Emerging Pathogens Laboratory. Lyon, France.University of Innsbruck. Institute of Statistics. Innsbruck, Austria.National Institute on Aging. Gerontology Research Center. Baltimore, USA.Innsbruck Medical University. Department of Medical Statistics, Informatics and Health Economics. Innsbruck, Austria.Innsbruck Medical University. Department of Medical Statistics, Informatics and Health Economics. Innsbruck, Austria.Innsbruck Medical University. Department of Medical Statistics, Informatics and Health Economics. Innsbruck, Austria.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hepatites Virais. Rio de Janeiro, RJ. Brasil.Background: The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period. Methods: We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up. Results: Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8- 111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]. Conclusion: Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection

Normal kidney size and its influencing factors - a 64-slice MDCT study of 1.040 asymptomatic patients

<p>Abstract</p> <p>Background</p> <p>Normal ultrasound values for pole-to-pole kidney length (LPP) are well established for children, but very little is known about normal kidney size and its influencing factors in adults. The objectives of this study were thus to establish normal CT values for kidney dimensions from a group of unselected patients, identify potential influencing factors, and to estimate their significance.</p> <p>Methods</p> <p>In multiphase thin-slice MDCTs of 2.068 kidneys in 1.040 adults, the kidney length pole to pole (LPP), parenchymal (PW) and cortical width (CW), position and rotation status of the kidneys, number of renal arteries, pyelon width and possible influencing factors that can be visualized, were recorded from a volume data set. For length measurements, axes were adjusted individually in double oblique planes using a 3D-software. Analyses of distribution, T-tests, ANOVA, correlation and multivariate regression analyses were performed.</p> <p>Results</p> <p>LPP was 108.5 ± 12.2 mm for the right, and 111.3 ± 12.6 mm for the left kidney (p < 0.0001 each). PW on the right side was 15.4 ± 2.8 mm, slightly less than 15.9 ± 2.7 mm on the left side (p < 0.0001), the CW was the same (6.6 ± 1.9 mm). The most significant independent predictors for LPP, CW, and PW were body size, BMI, age, and gender (p < 0.001 each). In men, the LPP increases up to the fifth decade of life (p < 0.01). It is also influenced by the position of the kidneys, stenoses and number of renal arteries (SRA/NRA), infarctions suffered, parapelvic cysts, and absence of the contralateral kidney; CW is influenced by age, position, parapelvic cysts, NRA and SRA, and the PW is influenced in addition by rotation status (p < 0.05 each). Depending on the most important factors, gender-specific normal values were indicated for these dimensions, the length and width in cross section, width of the renal pelvis, and parenchyma-renal pyelon ratio.</p> <p>Conclusions</p> <p>Due to the complex influences on kidney size, assessment should be made individually. The most important influencing factors are BMI, height, gender, age, position of the kidneys, stenoses and number of renal arteries.</p