Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study

Introduction

We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β₂-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD.

Methods

This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV₁) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy. Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa. The primary end point was the change from baseline in trough FEV₁ at week 8 with a noninferiority margin of ? 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed.

Results

In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV₁ at week 8 [FEV₁ change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28–77 mL); p < 0.001]. Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV₁ at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34–3.14). Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group.

Conclusion

In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV₁ at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. Both treatments had similar safety profiles. These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class.

Trial Registration

ClinicalTrials.gov identifier NCT02799784.

Funding

GlaxoSmithKline.

     

A green metal–organic framework to monitor water contaminants

The CIM-80 material (aluminum(iii)-mesaconate) has been synthetized in high yield through a novel green procedure involving water and urea as co-reactants. The CIM-80 material exhibits good thermal stability with a working range from RT to 350 °C with a small contraction upon desolvation. Moreover, this material is stable in water at different pH values (1–10) for at least one week, and shows a LC₅₀ value higher than 2 mg mL⁻¹. The new material has been tested in a microextraction methodology for the monitoring of up to 22 water pollutants while presenting little environmental impact: only 20 mg of CIM-80 and 500 μL of acetonitrile are needed per analysis. The analytical performance of the CIM-80 in the microextraction strategy is similar to or even better for several pollutants than that of MIL-53(Al). The average extraction efficiencies range from ∼20% for heavy polycyclic aromatic hydrocarbons to ∼70–100% for the lighter ones. In the case of the emerging contaminants, the average extraction efficiency can reach values up to 70% for triclosan and carbamazepine.

A low cytotoxic MOF prepared with an environmental-friendly approach, as a novel extractant of water pollutants using a microextraction method.     

A hazardous link between malnutrition, inflammation and oxidative stress in renal patients

BackgroundAtherosclerosis is the main cause of mortality in end stage renal disease (ESRD) patients.Design and methodsMalnutrition, inflammation and diminished paraoxonase activity were used to calculate the sum of risk factors for atherosclerosis development in a cohort of 141 chronic renal disease patients. Kaplan–Meier survival analysis was implemented to assess risk of death.ResultsKaplan–Meier analysis (Log rank = 12.06, P = 0.0072) showed higher risk of death with increasing number of risk factors in haemodialysis patients.ConclusionsMalnutrition in combination with inflammation and oxidative stress is associated with higher mortality in patients on long-term haemodialysis.     

Knowledge, attitude and practices regarding condom use among women prisoners: the prevention of STD/HIV in the prison setting

The objective of this study was to evaluate the knowledge, attitude and practices of women prisoners regarding the use of female and male condoms as a means of prevention against STD/HIV. This quantitative and evaluative Knowledge, Attitude and Practice (KAP) study included 155 female prisoners. Data collection was performed between January and March 2010 at the State of Ceará Women's Penitentiary. Although the women had heard of and/or knew about the purposes of the use of condoms, only 35 (22.6%) had appropriate knowledge regarding male condoms, and 11 (7.1%) in regards to the use of female condoms. Their attitudes were less favorable regarding oral sex. Appropriate practice was not significantly representative, particularly regarding the female condom. Homo/bisexuality, gender issues, lack of knowledge, and the difficult access to condoms are obstacles that must be considered in the promotion of sexual health in the studied group.     

Improved Quality of Anorectal Endoluminal Ultrasonography Using Emulsion of Dimethicone

PURPOSE: This study was designed to show the benefits of filling echography probes with water mixed with dimethicone to preclude artifacts caused by bubbles. METHODS: One hundred consecutive healthy volunteers (42 males; mean age, 46 years; range, 17–72 years) were blindly randomized to undergo rectal ultrasonography using conventional degassed water or degassed aqueous solution made of 40 ml of water and 10 ml of dimethicone emulsion (1 ml/100 mg). All examinations performed by the same surgeon—unaware of nature of filler liquid—for ten minutes, and number of rectal ultrasonographies with artifacts attributable to air bubbles was recorded. RESULTS: Endoluminal ultrasonography performed with conventional degassed water presented artifacts attributed to presence of air bubbles in 30 of 50 examinations (60 percent). When degassed aqueous solution was used, only 5 of 50 examinations showed artifacts caused by presence of air bubbles (10 percent). This difference was statistically significant (P < 0.0005). The use of conventional fluid was associated with artifacts secondary to the presence of air bubbles, adjusted odds ratio 13.5 (95 percent confidence interval, 4.56–39.88). During this experience, the solution did not damage ultrasound scanner. CONCLUSIONS: We found that use of a dimethicone-degassed water mixture is simple, not expensive, safe, effective, and may reduce frequency of sonographic distortion in presence of air bubbles.     

A Symbol Digit Modalities Test version suitable for functional MRI studies

The Symbol Digit Modalities Test is an easy test used to assess cognitive impairment in a wide range of neurological diseases, like multiple sclerosis. We adapted the oral version of this cognitive task making it suitable for functional Magnetic Resonance Imaging studies. Symbol Digit Modalities Test performance was associated with increased brain activity in frontal and parietal areas involved in selective attention and working memory functions. These may provide the basis for future studies assessing potential abnormal cortical activations in multiple sclerosis patients and other clinical populations.