Chronic cough and esomeprazole: A double-blind placebo-controlled parallel study

Background and objective: Gastro-oesophageal reflux has been implicated in the pathogenesis of chronic cough. Guidelines on management suggest a therapeutic trial of anti-reflux medication. Esomeprazole is a proton pump inhibitor licensed for the long-term treatment of acid reflux in adults and we compared the effects of esomeprazole and placebo on patients with chronic cough. Methods: This was a prospective, single-centre, randomized, double-blind, placebo-controlled, parallel group study conducted over 8 weeks. Fifty adult non-smokers with chronic cough and normal spirometry were randomized. Patients completed cough-related quality-of-life and symptom questionnaires and subjective scores of cough frequency and severity at the beginning and end of the study. They also kept a daily diary of symptom scores. Citric acid cough challenge and laryngoscopic examination were performed at baseline and the end of the study. The primary outcome was improvement in cough score. Results: There were no differences in cough scores in the placebo and treatment arms of the study although some significant improvements were noted when compared to baseline. In the cough diary scores there was a trend towards greater improvement in the treatment arm in patients with dyspepsia. Conclusions: Esomeprazole did not have a clinically important effect greater than placebo in patients with cough. It suggests a marked placebo effect in the treatment of cough. There is paucity of evidence on which to base the treatment of reflux-associated cough. We demonstrate that acid suppressive therapy does not lead to a significant clinical effect in these patients. There may be some improvement in those with coexisting dyspeptic symptoms and therapy should be restricted to this group. © 2011 Asian Pacific Society of Respirology

Regulations and productivity growth in banking

This paper examines the relationship between the regulatory and supervision framework and the productivity of banks in 22 countries over the period 1999-2006. We follow a semi-parametric two-step approach that combines Malmquist index estimates with bootstrap regressions. The results indicate that regulations and incentives that promote private monitoring have a positive impact on productivity. Restrictions on banks’ activities relating to their involvement in securities, insurance, real estate and ownership of non-financial firms also have a positive impact. However, regulations relating to the first and second pillars of Basel II, namely capital requirements and official supervisory power do not appear to have a statistically significant impact on productivity.Banks; Basel II; Productivity; Regulations

Escort tug at large yaw angle: comparison of CFD predictions with experimental data

Escort tugs operate at high yaw angles in order to produce forces to steer and stop the vessel they are escorting in an emergency. In this paper, RANS predictions of forces and flow patterns around the hull of an escort tug model are compared with experimental data. Two alternative meshing strategies were used, one using tetrahedral elements with triangular faces and one using hexahedral elements with quadrilateral faces. Experiments were carried out with and without the low aspect ratio fin that is typical of many escort tugs. Lift and drag forces were measured experimentally for yaw angles from 15 to 45 degrees. Flow measurements around the tug at 45 degrees yaw were obtained using a stereoscopic particle image velocimetry (PIV) system. The results from each CFD simulation were compared to the measured flow patterns using a numerical procedure that led to a quantitative measure of the accuracy of the predicted results. The analysis of the flow patterns indicated that the main features of the flow were predicted, and that on average, the predicted velocity magnitudes were within 10% of the measured values. Neither mesh approach had a significant effect on the accuracy of the flow pattern predictions. The hexahedral mesh gave more accurate force predictions that the tetrahedral mesh. Forces were predicted by the CFD code with this mesh to within 5 % of the experimentally obtained values

Flow Vectors Around an Escort Tug at a Large Yaw Angle

The flow around a ship at yaw angles beyond those encountered during manoeuvres has not been the subject of much research reported in the literature. These conditions are particularly important for an escort tug, since it uses large yaw angles to generate hydrodynamic forces that are used to control a ship (normally a tanker) in the event of an emergency. This paper presents CFD predictions for the flow around an escort tug at a yaw angle of 45 degrees and compares them to PIV measurements of the flow patterns. The CFD code predicts the essential features measured within the flow, such as the separation of the flow from the upstream bilge, and the formation of a large vortex generated by the low aspect ratio fin. The predicted vectors were compared with the measured ones using a numerical technique, and the agreements were found, on average, to be within 10%. This level of agreement was within the estimated uncertainty of the PIV system used for the experiments

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding

Working with Concepts: The Role of Community in International Collaborative Biomedical Research

The importance of communities in strengthening the ethics of international collaborative research is increasingly highlighted, but there has been much debate about the meaning of the term ‘community’ and its specific normative contribution. We argue that ‘community’ is a contingent concept that plays an important normative role in research through the existence of morally significant interplay between notions of community and individuality. We draw on experience of community engagement in rural Kenya to illustrate two aspects of this interplay: (i) that taking individual informed consent seriously involves understanding and addressing the influence of communities in which individuals’ lives are embedded; (ii) that individual participation can generate risks and benefits for communities as part of the wider implications of research. We further argue that the contingent nature of a community means that defining boundaries is generally a normative process itself, with ethical implications. Community engagement supports the enactment of normative roles; building mutual understanding and trust between researchers and community members have been important goals in Kilifi, requiring a broad range of approaches. Ethical dilemmas are continuously generated as part of these engagement activities, including the risks of perverse outcomes related to existing social relations in communities and conditions of ‘half knowing’ intrinsic to processes of developing new understandings

Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi

Limited data address the impact of HIV co-infection on the pharmacokinetics of anti-tuberculosis drugs in Sub-Saharan Africa. 47 Malawian adults underwent rich pharmacokinetic sampling at 0-0.5-1-2-3-4-6-8 and 24 hours post-dose. 51% were male; mean age was 34 years. 65% were HIV-positive with a mean CD4 count of 268 cells/μL. Anti-tuberculosis drugs were administered as fixed-dose combinations (rifampicin150mg/isoniazid75mg/pyrazinamide400mg/ethambutol275mg) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampicin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analysed by non-compartmental methods and analysis of variance of log-transformed summary parameters. Pharmacokinetic parameters were: rifampicin Cmax 4.129 (2.474-5.596)μg/mL, AUC0-24 21.32 (13.57-28.60)μg/mL*h, half-life 2.45 (1.86-3.08)h; isoniazid Cmax 3.97 (2.979-4.544)μg/mL, AUC0-24 22.5 (14.75-34.59)μg/mL*h, half-life 3.93 (3.18-4.73)h.; pyrazinamide Cmax 34.21 (30.00-41.60)μg/mL, AUC0-24 386.6 (320.0-463.7)μg/mL*h, half-life 6.821 (5.71-8.042)h; ethambutol Cmax 2.278 (1.694-3.098)μg/mL, AUC0-24 20.41 (16.18-26.27)μg/mL*h, half-life 7.507 (6.517-8.696)h. Isoniazid PK data analysis suggested that around two-thirds were slow acetylators. Dose, weight and weight-adjusted dose were not significant predictors of PK exposure probably due to weight-banded dosing. In this first pharmacokinetic study of tuberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with other studies for all first line drugs except for rifampicin, for which Cmax and AUC0-24 were notably lower. Contrary to some earlier observations, HIV status did not significantly affect AUC of any of the drugs. Increasing the dose of rifampicin could be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in half-life of isoniazid of 41% (p=0.022). Possible competitive interactions between isoniazid and sulphamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further