Objective: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the ‘ASsessment in AS’ international working group and the European ...League Against Rheumatism. Methods: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. Results: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I–IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. Conclusion: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.
Abstract An index that assesses the multidimensional components of the diet across the lifecycle is useful in describing diet quality. The purpose of this study was to use the Healthy Eating ...Index-2005, a measure of diet quality in terms of conformance to the 2005 Dietary Guidelines for Americans, to describe the diet quality of Americans by varying sociodemographic characteristics in order to provide insight as to where diets need to improve. The Healthy Eating Index-2005 scores were estimated using 1 day of dietary intake data provided by participants in the 2003-2004 National Health and Nutrition Examination Survey. Mean daily intakes of foods and nutrients, expressed per 1,000 kilocalories, were estimated using the population ratio method and compared with standards that reflect the 2005 Dietary Guidelines for Americans. Participants included 3,286 children (2 to 17 years), 3,690 young and middle-aged adults (18 to 64 years), and 1,296 older adults (65+ years). Results are reported as percentages of maximum scores and tested for significant differences ( P ≤0.05) by age, sex, race/ethnicity, income, and education levels. Children and older adults had better-quality diets than younger and middle-aged adults; women had better-quality diets than men; Hispanics had better-quality diets than blacks and whites; and diet quality of adults, but not children, generally improved with income level, except for sodium. The diets of Americans, regardless of socioeconomic status, are far from optimal. Problematic dietary patterns were found among all sociodemographic groups. Major improvements in the nutritional health of the American public can be made by improving eating patterns.
A search for neutrinoless double-β decay (0νββ) in Xe136 is performed with the full EXO-200 dataset using a deep neural network to discriminate between 0νββ and background events. Relative to ...previous analyses, the signal detection efficiency has been raised from 80.8% to 96.4±3.0%, and the energy resolution of the detector at the Q value of Xe136 0νββ has been improved from σ/E=1.23% to 1.15±0.02% with the upgraded detector. Accounting for the new data, the median 90% confidence level 0νββ half-life sensitivity for this analysis is 5.0×1025 yr with a total Xe136 exposure of 234.1 kg yr. No statistically significant evidence for 0νββ is observed, leading to a lower limit on the 0νββ half-life of 3.5×1025 yr at the 90% confidence level.
Aims/hypothesis Fenofibrate caused an acute, sustained plasma creatinine increase in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and Action to Control Cardiovascular Risk in ...Diabetes (ACCORD) studies. We assessed fenofibrate's renal effects overall and in a FIELD washout sub-study. Methods Type 2 diabetic patients (n = 9,795) aged 50 to 75 years were randomly assigned to fenofibrate (n = 4,895) or placebo (n = 4,900) for 5 years, after 6 weeks fenofibrate run-in. Albuminuria (urinary albumin/creatinine ratio measured at baseline, year 2 and close-out) and estimated GFR, measured four to six monthly according to the Modification of Diet in Renal Disease Study, were pre-specified endpoints. Plasma creatinine was re-measured 8 weeks after treatment cessation at close-out (washout sub-study, n = 661). Analysis was by intention-to-treat. Results During fenofibrate run-in, plasma creatinine increased by 10.0 μmol/l (p < 0.001), but quickly reversed on placebo assignment. It remained higher on fenofibrate than on placebo, but the chronic rise was slower (1.62 vs 1.89 μmol/l annually, p = 0.01), with less estimated GFR loss (1.19 vs 2.03 ml min⁻¹ 1.73 m⁻² annually, p < 0.001). After washout, estimated GFR had fallen less from baseline on fenofibrate (1.9 ml min⁻¹ 1.73 m⁻², p = 0.065) than on placebo (6.9 ml min⁻¹ 1.73 m⁻², p < 0.001), sparing 5.0 ml min⁻¹ 1.73 m⁻² (95% CI 2.3-7.7, p < 0.001). Greater preservation of estimated GFR with fenofibrate was observed with baseline hypertriacylglycerolaemia (n = 169 vs 491 without) alone, or combined with low HDL-cholesterol (n = 140 vs 520 without) and reductions of ≥0.48 mmol/l in triacylglycerol over the active run-in period (pre-randomisation) (n = 356 vs 303 without). Fenofibrate reduced urine albumin concentrations and hence albumin/creatinine ratio by 24% vs 11% (p < 0.001; mean difference 14% 95% CI 9-18; p < 0.001), with 14% less progression and 18% more albuminuria regression (p < 0.001) than in participants on placebo. End-stage renal event frequency was similar (n = 21 vs 26, p = 0.48). Conclusions/interpretation Fenofibrate reduced albuminuria and slowed estimated GFR loss over 5 years, despite initially and reversibly increasing plasma creatinine. Fenofibrate may delay albuminuria and GFR impairment in type 2 diabetes patients. Confirmatory studies are merited. Trial registration ISRCTN64783481 Funding The study was funded by grants from Laboratoires Fournier SA (Dijon, France; now part of Abbott Pharmaceuticals) and the National Health and Medical Research Council, Australia
Sudden cardiac death among children and young adults is a devastating event. We performed a prospective, population-based, clinical and genetic study of sudden cardiac death among children and young ...adults.
We prospectively collected clinical, demographic, and autopsy information on all cases of sudden cardiac death among children and young adults 1 to 35 years of age in Australia and New Zealand from 2010 through 2012. In cases that had no cause identified after a comprehensive autopsy that included toxicologic and histologic studies (unexplained sudden cardiac death), at least 59 cardiac genes were analyzed for a clinically relevant cardiac gene mutation.
A total of 490 cases of sudden cardiac death were identified. The annual incidence was 1.3 cases per 100,000 persons 1 to 35 years of age; 72% of the cases involved boys or young men. Persons 31 to 35 years of age had the highest incidence of sudden cardiac death (3.2 cases per 100,000 persons per year), and persons 16 to 20 years of age had the highest incidence of unexplained sudden cardiac death (0.8 cases per 100,000 persons per year). The most common explained causes of sudden cardiac death were coronary artery disease (24% of cases) and inherited cardiomyopathies (16% of cases). Unexplained sudden cardiac death (40% of cases) was the predominant finding among persons in all age groups, except for those 31 to 35 years of age, for whom coronary artery disease was the most common finding. Younger age and death at night were independently associated with unexplained sudden cardiac death as compared with explained sudden cardiac death. A clinically relevant cardiac gene mutation was identified in 31 of 113 cases (27%) of unexplained sudden cardiac death in which genetic testing was performed. During follow-up, a clinical diagnosis of an inherited cardiovascular disease was identified in 13% of the families in which an unexplained sudden cardiac death occurred.
The addition of genetic testing to autopsy investigation substantially increased the identification of a possible cause of sudden cardiac death among children and young adults. (Funded by the National Health and Medical Research Council of Australia and others.).
Aliment Pharmacol Ther 2011; 33: 225–234
Summary
Background Cough may be a manifestation of gastro‐oesophageal reflux disease (GERD). The utility of acid suppression in GERD‐related cough is ...uncertain.
Aim To assess the impact of high‐dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn.
Methods Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24‐h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough‐Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings.
Results Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively.
Conclusion In subjects with chronic cough and rare or no heartburn, high‐dose proton pump inhibitor does not improve cough‐related quality of life or symptoms.
How does trade liberalization affect wages? This is the first paper to consider in theory and data how the impact of final and intermediate input tariff cuts on workers' wages varies with the global ...engagement of their firm. Our model predicts that a fall in output tariffs lowers wages at import-competing firms but boosts wages at exporting firms. Similarly, a fall in input tariffs raises wages at import-using firms relative to those at firms that only source inputs locally. Using highly detailed Indonesian manufacturing census data for the period 1991-2000, we find considerable support for the model's predictions.
Here, we describe the Compact Array Broad-band Backend (CABB) and present first results obtained with the upgraded Australia Telescope Compact Array (ATCA). The 16-fold increase in observing ...bandwidth, from 2 × 128 to 2 × 2048 MHz, high-bit sampling and the addition of 16 zoom windows (each divided into further 2048 channels) provide major improvements for all ATCA observations. The benefits of the new system are: (1) hugely increased radio continuum and polarization sensitivity as well as image fidelity; (2) substantially improved capability to search for and map emission and absorption lines over large velocity ranges; (3) simultaneous multi-line and continuum observations; (4) increased sensitivity, survey speed and dynamic range due to high-bit sampling and (5) high-velocity resolution, while maintaining full polarization output. The new CABB system encourages all observers to make use of both spectral line and continuum data to achieve their full potential.
Given the dramatic increase of the ATCA capabilities in all bands (ranging from 1.1 to 105 GHz) CABB enables scientific projects that were not feasible before the upgrade, such as simultaneous observations of multiple spectral lines, on-the-fly mapping, fast follow-up of radio transients (e.g. the radio afterglow of new supernovae) and maser observation at high-velocity resolution and full polarization. The first science results presented here include wide-band spectra, high dynamic-range images and polarization measurements, highlighting the increased capability and discovery potential of the ATCA.
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