Multicenter Randomized Controlled Trial of Withdrawal of Inhaled Corticosteroids in Cystic Fibrosis

Rationale: Lung inflammation and injury is critical in cystic fibrosis. An ideal antiinflammatory agent has not been identified but inhaled corticosteroids are widely used despite lack of evidence.

Objectives: To test the safety of withdrawal of inhaled corticosteroids with the hypothesis this would not be associated with an earlier onset of acute chest exacerbations.

Methods: Multicenter randomized double-blind placebo-controlled trial in 18 pediatric and adult UK centers. Eligibility criteria included age > 6.0 yr, FEV1 ? 40% predicted, and corticosteroid use > 3 mo. During the 2-mo run-in period, all patients received fluticasone; they then took either fluticasone or placebo for 6 mo.

Measurements and Main Results: Fluticasone group: n = 84, median age 14.6 yr, mean (SD) FEV1 76% (18); placebo group: n = 87, median age 15.8 yr, mean (SD) FEV1 76% (18). There was no difference in time to first exacerbation (primary outcome) with hazard ratio (95% confidence interval) of 1.07 (0.68 to 1.70) for fluticasone versus placebo. There was no effect of age, atopy, corticosteroid dose, FEV1, or Pseudomonas aeruginosa status. There was no change in lung function or differences in antibiotic or rescue bronchodilator use. Fewer patients in the fluticasone group withdrew from the study due to lung-related adverse events (9 vs. 15%); with a relative risk (95% confidence interval) of 0.59 (0.23–1.48) fluticasone versus placebo.

Conclusions: In this study population (applicable to 40% of patients with cystic fibrosis in the UK), it appears safe to consider stopping inhaled corticosteroids. Potential advantages will be to reduce the drug burden on patients, reduce adverse effects, and make financial savings.

Limiting withdrawal rate and maximum film thickness during dip-coating of titania sols onto a Si substrate

The article highlights new insights into production of thin titania films widely used as catalyst support in many modern reactors including capillary microreactors, microstructured fixed-bed reactors and falling film microreactors. Dip-coating of a Mania sol onto a Si substrate has been studied in the range of the sol viscosities of 1.5-2.5 mPa s and the sol withdrawal rates of 0.2-18 mm/s. Different viscosities of sols were created by addition of desired amounts of nitric acid to the synthesis mixture of titanium isopropoxide and Plutonic F127 in ethanol which allowed to control the rate of the condensation reactions. Uniform inesoporous titania coatings were obtained at the solvent withdrawal rates below 10 mm/s at sol viscosities in the range from 1.6 mPa s to 2.5 mPa s. There exists a limiting withdrawal rate corresponding to a capillary number of ca. 0.01 beyond which uniform titania films cannot be obtained. Below the limiting withdrawal rate, the coating thickness is a power function of the sol viscosity and withdrawal rate, both with an exponent of 2/3. The limiting withdrawal rate increases as the solvent evaporation rate increases and it decreases as the sol viscosity increases. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.

OBSERVATIONS ON THE EFFECTS OF LONG-TERM WITHDRAWAL ON CARCASS COMPOSITION AND RESIDUE CONCENTRATIONS IN CLENBUTEROL-MEDICATED CATTLE

The detection of the illegal use of clenbuterol (CBL) as a growth promoter has relied on detecting residual concentrations of the drug in body fluids or tissues. Analysis of retinal extracts has recently been shown to considerably extend the detection period following withdrawal. The withdrawal periods required to eliminate residues from the liver and retina were investigated by medicating 20 cattle with CBL for 30 days; 6 control animals remained unmedicated. Residual concentrations were monitored throughout this period and for the subsequent 140 days. Concurrent changes in muscle areas and backfat thicknesses were recorded by ultrasound.

Withdrawal of Antidementia Drugs in Older People: Who, When and How?

The evidence base to guide withdrawal of antidementia medications in older people with dementia is limited; while some randomised controlled studies have considered discontinuation of cholinesterase inhibitors, no such studies examining discontinuation of the N-Methyl-D-aspartate receptor antagonist memantine have been conducted to date. The purpose of this opinion article was to summarise the existing evidence on withdrawal of cholinesterase inhibitors and memantine, to highlight the key considerations for clinicians when making these prescribing decisions and to offer guidance as to when and how treatment might be discontinued. Until the evidence-base is enhanced by the findings of large scale randomised controlled discontinuation trials of ChEIs and memantine which use multiple, clinically relevant cognitive, functional and behavioural outcome measures, clinicians’ prescribing decisions involve balancing the risks of discontinuation with side-effects and costs of continued treatment. Such decisions must be highly individualised and patient-centred.