Comparison of the effects of salmeterol/fluticasone propionate with fluticasone propionate on airway physiology in adults with mild persistent asthma

<p>Abstract</p> <p>Background</p> <p>This study compared the effect of inhaled fluticasone propionate (FP) with the combination of salmeterol/fluticasone propionate (SFC) on lung function parameters in patients with mild asthma.</p> <p>Methods</p> <p>Adult patients with mild persistent asthma (≥ 80% predicted FEV₁) receiving 200–500 μg of BDP or equivalent were randomised to receive either FP 100 μg or SFC 50/100 μg twice daily from a Diskus^®inhaler for four weeks. The primary outcome was the change from baseline in airway resistance (sRaw) at 12 hrs post dose measured by whole body plethysmography. Impulse oscillometry and spirometry were also performed.</p> <p>Results</p> <p>A comparison of the geometric mean sRaw at 12 hrs post dose in the SFC group to the FP group gave a ratio of 0.76 (0.66 – 0.89, p < 0.001) at week 2 and 0.81 (0.71 – 0.94, p = 0.006) at week 4. Similarly, significant results in favour of SFC for oscillometry measurements of resistance and reactance were observed. FEV₁was also significantly superior at week 2 in the SFC group (mean difference 0.16L, 95% CI; 0.03 – 0.28, p = 0.015), but not at week 4 (mean difference 0.17L, 95% CI -0.01 – 0.34, p = 0.060).</p> <p>Conclusion</p> <p>SFC is superior to FP in reducing airway resistance in mild asthmatics with near normal FEV₁values. This study provides evidence that changes in pulmonary function in patients with mild asthma are detected more sensitively by plethysmography compared to spirometry</p> <p>Trial registration number</p> <p>NCT00370591.</p

Barriers to and facilitators of interventions to counter publication bias: thematic analysis of scholarly articles and stakeholder interviews.

BACKGROUND: When the nature and direction of research results affect their chances of publication, a distortion of the evidence base - termed publication bias - results. Despite considerable recent efforts to implement measures to reduce the non-publication of trials, publication bias is still a major problem in medical research. The objective of our study was to identify barriers to and facilitators of interventions to prevent or reduce publication bias. METHODS: We systematically reviewed the scholarly literature and extracted data from articles. Further, we performed semi-structured interviews with stakeholders. We performed an inductive thematic analysis to identify barriers to and facilitators of interventions to counter publication bias. RESULTS: The systematic review identified 39 articles. Thirty-four of 89 invited interview partners agreed to be interviewed. We clustered interventions into four categories: prospective trial registration, incentives for reporting in peer-reviewed journals or research reports, public availability of individual patient-level data, and peer-review/editorial processes. Barriers we identified included economic and personal interests, lack of financial resources for a global comprehensive trial registry, and different legal systems. Facilitators identified included: raising awareness of the effects of publication bias, providing incentives to make data publically available, and implementing laws to enforce prospective registration and reporting of clinical trial results. CONCLUSIONS: Publication bias is a complex problem that reflects the complex system in which it occurs. The cooperation amongst stakeholders to increase public awareness of the problem, better tailoring of incentives to publish, and ultimately legislative regulations have the greatest potential for reducing publication bias

Improving vasomotor symptoms; psychological symptoms; and health-related quality of life in peri- or post-menopausal women through yoga: An umbrella systematic review and meta-analysis

ObjectivesVasomotor symptoms (VMS), commonly reported during menopausal transition, negatively affect psychological health and health-related quality of life (HRQoL). While hormone therapy is an effective treatment, its use is limited by concerns about possible harms. Thus, many women with VMS seek nonhormonal, nonpharmacologic treatment options. However, evidence to guide clinical recommendations is inconclusive. This study reviewed the effectiveness of yoga, tai chi and qigong on vasomotor, psychological symptoms, and HRQoL in peri- or post-menopausal women.DesignMEDLINE, Cochrane Database of Systematic Reviews, EMBASE, CINAHL and the Allied and Complementary Medicine Database were searched. Researchers identified systematic reviews (SR) or RCTs that evaluated yoga, tai chi, or qigong for vasomotor, psychological symptoms, and health-related quality of life (HRQoL) in peri- or post-menopausal women. Data were abstracted on study design, participants, interventions and outcomes. Risk of bias (ROB) was assessed and updated meta-analyses were performed.ResultsWe identified one high-quality SR (5 RCTs, 582 participants) and 3 new RCTs (345 participants) published after the SR evaluating yoga for vasomotor, psychological symptoms, and HRQoL; no studies evaluated tai chi or qigong. Updated meta-analyses indicate that, compared to controls, yoga reduced VMS (5 trials, standardized mean difference (SMD) -0.27, 95% CI -0.49 to -0.05) and psychological symptoms (6 trials, SDM -0.32; 95% CI -0.47 to -0.17). Effects on quality of life were reported infrequently. Key limitations are that adverse effects were rarely reported and outcome measures lacked standardization.ConclusionsResults from this meta-analysis suggest that yoga may be a useful therapy to manage bothersome vasomotor and psychological symptoms

A novel approach for biomarker selection and the integration of repeated measures experiments from two assays

Background: High throughput 'omics' experiments are usually designed to compare changes observed between different conditions (or interventions) and to identify biomarkers capable of characterizing each condition. We consider the complex structure of repeated measurements from different assays where different conditions are applied on the same subjects

Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: current and future agents

<p>Abstract</p> <p>Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and debilitating symptoms. For patients with moderate-to-severe COPD, long-acting bronchodilators are the mainstay of therapy; as symptoms progress, guidelines recommend combining bronchodilators from different classes to improve efficacy. Inhaled long-acting β₂-agonists (LABAs) have been licensed for the treatment of COPD since the late 1990s and include formoterol and salmeterol. They improve lung function, symptoms of breathlessness and exercise limitation, health-related quality of life, and may reduce the rate of exacerbations, although not all patients achieve clinically meaningful improvements in symptoms or health related quality of life. In addition, LABAs have an acceptable safety profile, and are not associated with an increased risk of respiratory mortality, although adverse effects such as palpitations and tremor may limit the dose that can be tolerated.</p> <p>Formoterol and salmeterol have 12-hour durations of action; however, sustained bronchodilation is desirable in COPD. A LABA with a 24-hour duration of action could provide improvements in efficacy, compared with twice-daily LABAs, and the once-daily dosing regimen could help improve compliance. It is also desirable that a new LABA should demonstrate fast onset of action, and a safety profile at least comparable to existing LABAs.</p> <p>A number of novel LABAs with once-daily profiles are in development which may be judged against these criteria. Indacaterol, a LABA with a 24-hour duration of bronchodilation and fast onset of action, is the most advanced of these. Preliminary results from large clinical trials suggest indacaterol improves lung function compared with placebo and other long-acting bronchodilators. Other LABAs with a 24-hour duration of bronchodilation include carmoterol, vilanterol trifenatate and oldaterol, with early results indicating potential for once-daily dosing in humans.</p> <p>The introduction of once-daily LABAs also provides the opportunity to develop combination inhalers of two or more classes of once-daily long-acting bronchodilators, which may be advantageous for COPD patients through simplification of treatment regimens as well as improvements in efficacy. Once-daily LABAs used both alone and in combination with long-acting muscarinic antagonists represent a promising advance in the treatment of COPD, and are likely to further improve outcomes for patients.</p