Atorvastatin as a stable treatment in bronchiectasis:a randomised controlled trial

SummaryBackgroundBronchiectasis is characterised by chronic cough, sputum production, and recurrent chest infections. Pathogenesis is poorly understood, but excess neutrophilic airway inflammation is seen. Accumulating evidence suggests that statins have pleiotropic effects; therefore, these drugs could be a potential anti-inflammatory treatment for patients with bronchiectasis. We did a proof-of-concept randomised controlled trial to establish if atorvastatin could reduce cough in patients with bronchiectasis.MethodsPatients aged 18–79 years were recruited from a secondary-care clinic in Edinburgh, UK. Participants had clinically significant bronchiectasis (ie, cough and sputum production when clinically stable) confirmed by chest CT and two or more chest infections in the preceding year. Individuals were randomly allocated to receive either high-dose atorvastatin (80 mg) or a placebo, given orally once a day for 6 months. Sequence generation was done with a block randomisation of four. Random allocation was masked to study investigators and patients. The primary endpoint was reduction in cough from baseline to 6 months, measured by the Leicester Cough Questionnaire (LCQ) score, with a lower score indicating a more severe cough (minimum clinically important difference, 1·3 units). Analysis was done by intention-to-treat. The trial is registered with ClinicalTrials.gov, number NCT01299181.FindingsBetween June 23, 2011, and Jan 30, 2011, 82 patients were screened for inclusion in the study and 22 were excluded before randomisation. 30 individuals were assigned atorvastatin and 30 were allocated placebo. The change from baseline to 6 months in LCQ score differed between groups, with a mean change of 1·5 units in patients allocated atorvastatin versus −0·7 units in those assigned placebo (mean difference 2·2, 95% CI 0·5–3·9; p=0·01). 12 (40%) of 30 patients in the atorvastatin group improved by 1·3 units or more on the LCQ compared with five (17%) of 30 in the placebo group (difference 23%, 95% CI 1–45; p=0·04). Ten (33%) patients assigned atorvastatin had an adverse event versus three (10%) allocated placebo (difference 23%, 95% CI 3–43; p=0·02). No serious adverse events were recorded.Interpretation6 months of atorvastatin improved cough on a quality-of-life scale in patients with bronchiectasis. Multicentre studies are now needed to assess whether long-term statin treatment can reduce exacerbations.FundingChief Scientist's Office

Statins in community acquired pneumonia: Evidence from experimental and clinical studies

SummaryStatins are widely used to lower cholesterol and prevent complications of cardiovascular disease. The non-lipid lowering (pleiotropic) effects of statins may also have applications to the management of infections. These include effects on endothelial function, inflammation and coagulation pathways. Several observational studies have shown a significant reduction in 30-day mortality associated with prior statin therapy in hospitalised patients with sepsis and community acquired pneumonia.This article explores the evidence for statins as novel therapy in community acquired pneumonia. Experimental and animal studies suggest statins attenuate acute lung injury by modulating neutrophil function, reducing pro-inflammatory cytokine release and reducing vascular leak. Statins reduce endothelial dysfunction and have anti-thrombotic effects that improve outcome from pneumonia and sepsis in animal models. Clinical studies have provided conflicting results, but many suggest that statins may have a role in preventing pneumonia, or improving prognosis in hospitalised patients with community-acquired pneumonia

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Not AvailableThis paper deals with obtaining A-optimal completely randomized designs for three factors after eliminating treatments associated with triple placebo and both double and triple placebos since their administration is unethical. A number of A-optimal designs have been obtained.Not Availabl

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Not AvailableLatin hypercube designs (LHD) are widely used as space-filling designs in the field of computer experiments. Most of the available methods of construction of good space-filling LHDs in literature are based on computer algorithms. In this article, we propose a general construction method of LHDs with two factors which possess good space-filling property for small number of runs.Not Availabl

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Not AvailableIn this article, the problem of obtaining efficient block designs with unequal block sizes for incomplete factorial treatment structure with two factors excluding one treatment combination for estimation of dual versus single treatment contrasts is considered. A method of construction for obtaining efficient block designs with unequal block sizes for incomplete factorial treatment structure is proposed.Not Availabl

Ferromagnetism in Oxide Nanowires: Role of Intrinsic Defects

In this report, we have investigated the origin of defect-induced room-temperature d0 ferromagnetism in pure SnO2 and ZnO nanowires (NWs) with average diameter ~ 50 nm, prepared by template assisted route. Photoluminescence (PL) and electron paramagnetic resonance (EPR) spectroscopic measurements show the singly ionized oxygen vacancy is inducing ferromagnetism in pure SnO2 NWs whereas cation (Zn) vacancy is found to responsible for the ferromagnetic behaviour in pure ZnO NWs. Besides, it is found that the Zn vacancy-induced ferromagnetism in ZnO can be tuned by substituting few percentage of nonmagnetic alkali metal like potassium (K) at Zn site. Saturation moment as well as Curie temperature has found to increase significantly with K-doping up to 4 at.% but a decrease of ferromagnetic response is observed for higher K-doping. X-ray photoelectron spectra show that K+1 ions substitute at Zn site and thus introduce hole through which a ferromagnetic interaction between Zn vacancies can be mediated. The direct correlation between the Zn vacancy concentration and the corresponding saturation moment indicates that Zn vacancyinduced ferromagnetism in ZnO can be successfully tuned by K-doping that can an exciting approach to prepare ZnO-based dilute magnetic semiconductors for modern spintronic technology

d0 Ferromagnetism in Oxide Nanowires: Role of Intrinsic Defects

In this report, we have investigated the origin of defect-induced room-temperature d0 ferromagnetism in pure SnO2 and ZnO nanowires (NWs) with average diameter ~ 50 nm, prepared by template assisted route. Photoluminescence (PL) and electron paramagnetic resonance (EPR) spectroscopic measurements show the singly ionized oxygen vacancy is inducing ferromagnetism in pure SnO2 NWs whereas cation (Zn) vacancy is found to responsible for the ferromagnetic behaviour in pure ZnO NWs. Besides, it is found that the Zn vacancy-induced ferromagnetism in ZnO can be tuned by substituting few percentage of nonmagnetic alkali metal like potassium (K) at Zn site. Saturation moment as well as Curie temperature has found to increase significantly with K-doping up to 4 at.% but a decrease of ferromagnetic response is observed for higher K-doping. X-ray photoelectron spectra show that K+1 ions substitute at Zn site and thus introduce hole through which a ferromagnetic interaction between Zn vacancies can be mediated. The direct correlation between the Zn vacancy concentration and the corresponding saturation moment indicates that Zn vacancyinduced ferromagnetism in ZnO can be successfully tuned by K-doping that can an exciting approach to prepare ZnO-based dilute magnetic semiconductors for modern spintronic technology

Block designs for incomplete factorial treatment structures with two factors

Not AvailableIn this paper, the problem of obtaining efficient block designs for incomplete factorial treatment structure with two factors excluding one treatment combination for estimation of dual versus single treatment contrasts is considered. The designs have been obtained using the A-optimal completely randomized designs and modified strongest treatment interchange algorithm. A catalog of efficient block designs has been prepared for m1 = 3, 4 and m2 = 2, b<=10 and k<= 9 and for m1 = 3,4 and m2 = 3, 4, b<=≤ 10 and k <= 10.Not Availabl

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Not AvailableLatin hypercube designs are popular now-a-days for computer experiments. We give construction methods of orthogonal Latin hypercube designs for four factors for any number of runs for which such a design exists by combining smaller orthogonal matrices. We also propose methods for obtaining orthogonal Latin hypercube designs with larger number of factors.Not Availabl

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The final enclosed is pre-print, pre-submission version. There has been revisions after submissions. For final manuscript, one may refer to the Journal.In this article, we give a complete solution to the construction problem of second order orthogonal Latin hypercube designs for any number of rows for three columns by combining smaller orthogonal designs except for the number of rows n = 4 (mod 8). However, we have given solution for first order orthogonal Latin hypercube designs for the number of rows n = 4 (mod 8) for three columns.Not Availabl