The effect of adding inhaled corticosteroids to tiotropium and long-acting beta(2)-agonists for chronic obstructive pulmonary disease (Review)

BackgroundLong-acting bronchodilators comprising long-acting beta(2)-agonists and the anticholinergic agent tiotropiumare commonly used, either on their own or in combination, for managing persistent symptoms of chronic obstructive pulmonary disease. Patients with severe chronic obstructive pulmonary disease who are symptomatic and who suffer repeated exacerbations are recommended to add inhaled corticosteroids to their bronchodilator treatment. However, the benefits and risks of adding inhaled corticosteroid to tiotropium and long-acting beta2-agonists for the treatment of chronic obstructive pulmonary disease are unclear.ObjectivesTo assess the relative effects of adding inhaled corticosteroids to tiotropium and long-acting beta2-agonists treatment in patients with chronic obstructive pulmonary disease.Search strategyWe searched the Cochrane Airways Group Specialised Register of trials (February 2011) and reference lists of articles.Selection criteriaWe included parallel group, randomised controlled trials of three months or longer comparing inhaled corticosteroid and long-acting beta(2)-agonist combination therapy in addition to inhaled tiotropium against tiotropium and long-acting beta2-agonist treatment for patients with chronic obstructive pulmonary disease (COPD).Data collection and analysisTwo review authors independently assessed trials for inclusion and then extracted data on trial quality and the outcome results. We contacted study authors for additional information. We collected information on adverse effects from the trials.Main resultsOne trial (293 patients) was identified comparing tiotropium in addition to inhaled corticosteroid and long-acting beta(2)-agonist combination therapy to tiotropium plus long-acting beta2-agonist. The study was of good methodological quality, however it suffered from high and uneven withdrawal rates between the treatment arms. There is currently insufficient evidence to know how much difference the addition of inhaled corticosteroids makes to people who are taking tiotropium and a long-acting beta(2)-agonist for COPD.Authors' conclusionsThe relative efficacy and safety of adding inhaled corticosteroid to tiotropium and a long-acting beta(2)-agonist for chronic obstructive pulmonary disease patients remains uncertain and additional trials are required to answer this question

Combination formoterol and budesonide as maintenance and reliever therapy versus combination inhaler maintenance for chronic asthma in adults and children.

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness and cough. Treatment with inhaled steroids and bronchodilators often results in good control of symptoms, prevention of further morbidity and mortality and improved quality of life. Several steroids and beta2-agonists (long- and short-acting) as well as combinations of these treatments are available in a single inhaler to be used once or twice a day, with a separate inhaler for relief of symptoms when needed (for patients in Step three or higher, according to Global Initiative for Asthma (GINA) guidelines). Budesonide/formoterol is also licenced for use as maintenance and reliever therapy from a single inhaler (SiT; sometimes referred to as SMART therapy). SiT can be prescribed at a lower dose than other combination therapy because of the additional steroid doses being received as reliever therapy. It has been suggested that using SiT improves compliance and hence reduces symptoms and exacerbations, but it is unclear whether it increases side effects associated with the use of inhaled steroids. OBJECTIVES: To assess the efficacy and safety of budesonide/formoterol in a single inhaler (SiT) to be used for both maintenance and reliever therapy in asthma in comparison with maintenance treatment provided through combination inhalers with a higher maintenance steroid dose (either fluticasone/salmeterol or budesonide/formoterol), along with additional fast-acting beta2-agonists for relief of symptoms. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, online trial registries and drug company websites. The most recent search was conducted in November 2013. SELECTION CRITERIA: We included parallel-group, randomised controlled trials of at least 12 weeks' duration. Studies were included if they compared single-inhaler therapy with budesonide/formoterol (SiT) versus combination inhalers at a higher maintenance dose of steroids than was given in the SiT arm (either salmeterol/fluticasone or budesonide/formoterol). DATA COLLECTION AND ANALYSIS: We used standard methods expected by The Cochrane Collaboration. Primary outcomes were exacerbations requiring hospitalisation, exacerbations requiring oral corticosteroids and serious adverse events (including mortality). MAIN RESULTS: Four studies randomly assigning 9130 people with asthma were included; two were six-month double-blind studies, and two were 12-month open-label studies. No trials included children younger than age 12. Trials included more women than men, with mean age ranging from 38 to 45, and mean baseline steroid dose (inhaled beclomethasone (BDP) equivalent) from 636 to 888 μg. Mean baseline forced expiratory volume in one second (FEV1) percentage predicted was between 70% and 73% in three of the trials, and 96% in another. All studies were funded by AstraZeneca and were generally free from methodological biases, although the two open-label studies were rated as having high risk for blinding, and some evidence of selective outcome reporting was found. These possible sources of bias did not lead us to downgrade the quality of the evidence. The quantity of inhaled steroids, including puffs taken for relief from symptoms, was consistently lower for SiT than for the comparison groups.Separate data for exacerbations leading to hospitalisations, to emergency room (ER) visits or to a course of oral steroids could not be obtained. Compared with higher fixed-dose combination inhalers, fewer people using SiT had exacerbations requiring hospitalisation or a visit to the ER (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57 to 0.90; I(2) = 0%, P = 0.66), and fewer had exacerbations requiring a course of oral corticosteroids (OR 0.75, 95% CI 0.65 to 0.87; I(2) = 0%, P = 0.82). This translates to one less person admitted to hospital or visiting the ER (95% CI 0 to 2 fewer) and two fewer people needing oral steroids (95% CI 1 to 3 fewer) compared with fixed-dose combination treatment with a short-acting beta-agonist (SABA) reliever (per 100 treated over eight months). No statistical heterogeneity was observed in either outcome, and the evidence was rated of high quality. Although issues with blinding were evident in two of the studies, and one study recruited a less severe population, sensitivity analyses did not change the main results, so quality was not downgraded.We could not rule out the possibility that SiT increased rates of serious adverse events (OR 0.92, 95% CI 0.74 to 1.13; I(2) = 0%, P = 0.98; moderate-quality evidence, downgraded owing to imprecision).We were unable to say whether SiT improved results for several secondary outcomes (morning and evening peak expiratory flow (PEF), rescue medication use, symptoms scales), and in cases where results were significant, the effect sizes were not considered clinically meaningful (predose FEV1, nocturnal awakenings and quality of life). AUTHORS' CONCLUSIONS: SiT reduces the number of people having asthma exacerbations requiring oral steroids and the number requiring hospitalisation or an ER visit compared with fixed-dose combination inhalers. Evidence for serious adverse events was unclear. The mean daily dose of inhaled corticosteroids (ICS) in SiT, including the total dose administered with reliever use, was always lower than that of the other combination groups. This suggests that the flexibility in steroid administration that is possible with SiT might be more effective than a standard fixed-dose combination by increasing the dose only when needed and keeping it low during stable stages of the disease. Data for hospitalisations alone could not be obtained, and no studies have yet addressed this question in children younger than age 12

Oxygen Fugacity of the Upper Mantle of Mars. Evidence from the Partitioning Behavior of Vanadium in Y980459 (Y98) and other Olivine-Phyric Shergottites

Using partitioning behavior of V between olivine and basaltic liquid precisely calibrated for martian basalts, we determined the redox state of primitive (olivine-rich, high Mg#) martian basalts near their liquidus. The combination of oxidation state and incompatible element characteristics determined from early olivine indicates that correlations between fO2 and other geochemical characteristics observed in many martian basalts is also a fundamental characteristic of these primitive magmas. However, our data does not exhibit the range of fO2 observed in these previous studies.. We conclude that the fO2 for the martian upper mantle is approximately IW+1 and is incompatible-element depleted. It seems most likely (although clearly open to interpretation) that these mantle-derived magmas assimilated a more oxidizing (>IW+3), incompatible-element enriched, lower crustal component as they ponded at the base of the martian crust

Learning a novel technique to identify possible melanomas: are Australian general practitioners better than their U.K. colleagues?

Abstract Background Spectrophotometric intracutaneous analysis (SIAscopy™) is a multispectral imaging technique that is used to identify 'suspicious' (i.e. potentially malignant) pigmented skin lesions for further investigation. The MoleMate™ system is a hand-held scanner that captures SIAscopy™ images that are then classified by the clinician using a computerized diagnostic algorithm designed for the primary health care setting. The objectives of this study were to test the effectiveness of a computer program designed to train health care workers to identify the diagnostic features of SIAscopy™ images and compare the results of a group of Australian and a group of English general practitioners (GPs). Methods Thirty GPs recruited from the Perth (Western Australia) metropolitan area completed the training program at a workshop held in March 2008. The accuracy and speed of their pre- and post-test scores were then compared with those of a group of 18 GPs (including 10 GP registrars) who completed a similar program at two workshops held in Cambridge (U.K.) in March and April, 2007. Results The median test score of the Australian GPs improved from 79.5% to 86.5% (median increase 5.5%; p < 0.001) while the median test score of the English GPs improved from 74.5% to 86.5% (median increase 9.5%; p < 0.001). The Australian GPs had significantly higher pre-test scores but there were no significant differences in post-test scores between the Australian and English GPs or between the GPs and GP registrars. There was no significant difference in scores between GPs with previous dermoscopy experience or dermatology training. Conclusion Most of the SIAscopy™ features can be learnt to a reasonable degree of accuracy with this brief computer training program. Although the Australian GPs scored higher in the pre-test, both groups had similar levels of accuracy and speed in interpreting the SIAscopy™ features after completing the program. Scores were not affected by previous dermoscopy experience or dermatology training, which suggests that the MoleMate™ system is relatively easy to learn

Valence State Partitioning of Cr and V Between Pyroxene - Melt: Estimates of Oxygen Fugacity for Martian Basalt QUE 94201

Several studies, using different oxybarometers, have suggested that the variation of fO2 in martian basalts spans about 3 log units from approx. IW-1 to IW+2. The relatively oxidized basalts (e.g., pyroxene-phyric Shergotty) are enriched in incompatible elements, while the relatively reduced basalts (e.g., olivine-phyric Y980459) are depleted in incompatible elements. A popular interpretation of the above observations is that the martian mantle contains two reservoirs; 1) oxidized and enriched, and 2) reduced and depleted. The basalts are thus thought to represent mixing between these two reservoirs. Recently, Shearer et al. determined the fO2 of primitive olivine-phyric basalt Y980459 to be IW+0.9 using the partitioning of V between olivine and melt. In applying this technique to other basalts, Shearer et al. concluded that the martian mantle shergottite source was depleted and varied only slightly in fO2 (IW to IW+1). Thus the more oxidized, enriched basalts had assimilated a crustal component on their path to the martian surface. In this study we attempt to address the above debate on martian mantle fO2 using the partitioning of Cr and V into pyroxene in pyroxene-phyric basalt QUE 94201

Mechanisms for slow strengthening in granular materials

Several mechanisms cause a granular material to strengthen over time at low applied stress. The strength is determined from the maximum frictional force F_max experienced by a shearing plate in contact with wet or dry granular material after the layer has been at rest for a waiting time \tau. The layer strength increases roughly logarithmically with \tau -only- if a shear stress is applied during the waiting time. The mechanisms of strengthening are investigated by sensitive displacement measurements and by imaging of particle motion in the shear zone. Granular matter can strengthen due to a slow shift in the particle arrangement under shear stress. Humidity also leads to strengthening, but is found not to be its sole cause. In addition to these time dependent effects, the static friction coefficient can also be increased by compaction of the granular material under some circumstances, and by cycling of the applied shear stress.Comment: 21 pages, 11 figures, submitted to Phys. Rev.

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Diagnosis and Pharmacotherapy of Stable Chronic Obstructive Pulmonary Disease : The Finnish Guidelines

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