Effect of smoking status on lung function, patient-reported outcomes, and safety among COPD patients treated with glycopyrrolate inhalation powder: pooled analysis of GEM1 and GEM2 studies.

BACKGROUND: Smoking is a major risk factor for COPD and may impact the efficacy of COPD treatments; however, a large proportion of COPD patients continue to smoke following diagnosis. METHODS: This post-hoc analysis of pooled data from the replicate 12-week, placebo-controlled GEM1 and GEM2 studies assessed the impact of smoking status on the efficacy and safety of glycopyrrolate 15.6 µg twice daily vs placebo in patients with moderate-to-severe COPD. Data from 867 patients enrolled in GEM1 and GEM2 were pooled for analysis and grouped by smoking status (57% current smokers, 43% ex-smokers). Forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 12 h, trough FEV1, forced vital capacity, St George's Respiratory Questionnaire (SGRQ) total score, COPD assessment test (CAT) score, transition dyspnea index (TDI) focal score, daily symptom scores, and rescue medication use were assessed in current smokers and ex-smokers. Incidences of adverse events (AEs) and serious AEs (SAEs) were also assessed. RESULTS: Treatment with glycopyrrolate resulted in significant improvements in all lung function measures, independent of smoking status. In both current and ex-smokers, changes from baseline in trough FEV1 were less marked in patients taking inhaled corticosteroids (ICS) than those not receiving ICS. Changes from baseline in SGRQ total score and rescue medication use were significantly greater with glycopyrrolate compared with placebo, regardless of smoking status. Changes in the CAT score, TDI focal score, and daily symptom scores significantly improved versus placebo, but only in current smokers. Improvements in patient-reported outcomes (PROs) with glycopyrrolate relative to placebo were numerically greater in current smokers than ex-smokers. The incidences of AEs and SAEs were similar regardless of smoking status. CONCLUSIONS: In this post-hoc analysis of GEM1 and GEM2, glycopyrrolate use led to significant improvements in lung function, independent of baseline smoking status; improvements were less marked among patients receiving background ICS, regardless of baseline smoking status. Improvements in PROs were greater with glycopyrrolate than placebo, and the magnitude of changes was numerically greater among current smokers. The safety profile of glycopyrrolate was comparable between current smokers and ex-smokers.

Efficacy of Indacaterol/Glycopyrrolate in Patients with COPD by Airway Reversibility at Baseline: A Pooled Analysis of the FLIGHT1 and FLIGHT2 12-Week Studies.

Bronchodilator reversibility occurs in patients with COPD. Pooled analysis of two 12-week, placebo-controlled randomised studies (FLIGHT1 [NCT01727141]; FLIGHT2 [NCT01712516]) assessed the effect of bronchodilator reversibility on lung function, patient-reported outcomes, and safety in 2,043 patients with moderate-to-severe COPD treated with indacaterol/glycopyrrolate (IND/GLY) 27.5/15.6 µg twice daily. Reversibility was defined as post-bronchodilator increase in forced expiratory volume in one second (FEV1) of ≥12% and ≥0.200 L. Overall, mean reversibility (mean post-bronchodilator FEV1 increase) was 22.8%, and 54.5% of patients met reversibility criteria. IND/GLY resulted in significant (p < 0.05) placebo-adjusted improvements from baseline at Week 12 in reversible and non-reversible patients in FEV1 area under the curve from 0 to 12 hours (0.308 L and 0.170 L, respectively), trough FEV1 (0.260 L and 0.174 L), St. George's Respiratory Questionnaire total score (-6.3 and -3.5), COPD Assessment Test total score (-2.3 and -1.2), daily rescue medication use (-1.52 and -0.79), and daily total symptom score (-0.86 and -0.63); Transition Dyspnoea Index focal score also showed improvements (1.93 and 1.29) at Week 12, irrespective of reversibility status. Improvements in lung function and rescue medication use were significantly (p < 0.05) greater in IND/GLY patients in the reversible subgroup compared with the non-reversible subgroup. The safety profile was similar across treatment groups and reversibility subgroups. Overall, treatment with IND/GLY led to significant improvements in lung function and PROs in patients with moderate-to-severe COPD, regardless of reversibility status, with greater improvements in the reversible subgroup. Safety profile was not affected by reversibility status.

Orthodontic and oral health literacy in adults.

OBJECTIVE: The primary aim of the study was to determine levels of literacy in both oral health and orthodontics in an adult population. The secondary study aim was to investigate differences in literacy between males and females. METHODS: Participants included individuals 18 years or older seeking dental treatment at the East Carolina University (ECU) School of Dental Medicine. To determine levels of oral health literacy (OHL) and orthodontic literacy (OrthoL), validated instruments were administered, including the Rapid Estimate of Adult Literacy in Medicine and Dentistry, the Oral Health Literacy Instrument and its separate scales, and a questionnaire on orthodontic literacy. Summary statistics were computed, and statistical significance was set at 0.05. RESULTS: One hundred seventy-two individuals participated in the study and had a mean age of 55.03 (range:18-88). Greater than 70% of the sampled population exhibited inadequate or marginal oral health knowledge. Additionally, greater than 70% of the sample possessed no more than an 8th grade reading level, with regard to basic medical and dental terms. Higher education was weakly associated with higher OrthoL and OHL. Higher age was also weakly associated with lower OrthoL and OHL. Males on average exhibited significantly higher OHL (p < .05) but there were no OrthoL differences between males and females. Dental visit frequency was not associated with OrthoL or OHL. CONCLUSION: Low levels of OrthoL and OHL were observed in the study. While males demonstrated a higher level of OHL than females, neither age nor the occurrence of dental appointments significantly influenced levels of literacy.

Effect of smoking status on lung function, patient-reported outcomes, and safety among patients with COPD treated with indacaterol/glycopyrrolate: Pooled analysis of the FLIGHT1 and FLIGHT2 studies.

BACKGROUND: Smoking continues to be a major risk factor for COPD and may impact the efficacy of COPD treatments, with guidelines supporting the crucial importance for current smokers of smoking cessation. A post-hoc analysis of the FLIGHT1 and FLIGHT2 studies assessed the impact of smoking status on the efficacy and safety of indacaterol/glycopyrrolate (IND/GLY) 27.5/15.6 µg twice daily versus its monocomponents or placebo in patients with COPD. METHODS: This post-hoc analysis of pooled data from the replicate, 12-week, placebo-controlled FLIGHT1 and FLIGHT2 studies compared the efficacy and safety of IND/GLY with that of IND, GLY, and placebo in patients with moderate-to-severe COPD. Baseline data from 2038 patients were pooled and grouped by smoking status (52% were current smokers and 48% were ex-smokers). The effects of treatment on lung function, patient-reported outcomes (PROs), and safety were evaluated by baseline smoking status. RESULTS: Treatment with IND/GLY resulted in significant improvements in lung function measurements compared with placebo, irrespective of smoking status. Improvements in St George's Respiratory Questionnaire and transition dyspnea index were significantly greater than placebo in both current and ex-smokers, whereas changes in COPD assessment test were significant only among current smokers. Improvements in lung function and PROs were greater with IND/GLY compared with its monocomponents in current and ex-smokers. The incidences of AEs and SAEs were similar between current and ex-smokers. CONCLUSIONS: IND/GLY demonstrated significant improvements in lung function and PROs, independent of baseline smoking status. The safety profile of IND/GLY did not differ between current and ex-smokers.

Efficacy and safety of glycopyrrolate in patients with COPD by reversibility: pooled analysis of GEM1 and GEM2 12-week studies.

PURPOSE: Bronchodilator reversibility has been reported in patients with COPD, although correlations between reversibility and treatment response are unclear. The effect of reversibility on lung function, health status, and dyspnea was assessed in patients with moderate-to-severe COPD receiving glycopyrrolate (GLY) 15.6 µg twice daily vs placebo in the Glycopyrrolate Effect on syMptoms and lung function 1 and 2 (GEM1 and GEM2) replicate, 12-week, placebo-controlled studies. PATIENTS AND METHODS: Reversibility was defined as a post-bronchodilator increase of ≥12% and ≥0.200 L in FEV1. FEV1 area under the curve from 0 to 12 hours (AUC0-12 h), trough FEV1, St George's Respiratory Questionnaire (SGRQ) total score, COPD Assessment Test (CAT™) score, Transition Dyspnea Index (TDI) focal score, daily symptom scores, and rescue medication use were assessed by reversibility status. Incidences of adverse events and serious adverse events were also assessed. RESULTS: Data from 846 patients enrolled in GEM1 and GEM2 with known reversibility status were pooled for post hoc analysis. GLY significantly improved FEV1 AUC0-12 h, trough FEV1, SGRQ and CAT total scores, and rescue medication use compared with placebo in reversible and nonreversible patients. Significant improvements in TDI focal score and daily symptom scores with GLY over placebo were observed only among reversible patients. Improvements in FEV1 AUC0-12 h (0.165 vs 0.078 L; P<0.001) and trough FEV1 (0.173 vs 0.070 L; P<0.001) were clinically relevant (based on minimal clinically important differences) and significantly greater in reversible compared with nonreversible patients receiving GLY. The safety profile of GLY was not affected by reversibility status. CONCLUSION: In this post hoc analysis, GLY was associated with significant improvements in lung function and patient-reported outcomes compared with placebo, mostly independent of reversibility status. In patients receiving GLY, improvements in lung function were greater in reversible compared with nonreversible patients. Reversibility status did not meaningfully impact the safety profile of GLY.

Effect of background long-acting beta2-agonist therapy on the efficacy and safety of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe COPD.

BACKGROUND: Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD. Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY. METHODS: In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily. Lung function, patient-reported outcomes, exacerbations, and safety were assessed. RESULTS: Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110 L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George's Respiratory Questionnaire total score (SGRQ; LABA-yes: -2.957 and -3.888; LABA-no: -3.301 and -2.073, respectively; P<0.05). Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo. In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no: 0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: -5.190 and -3.094; LABA-no: -4.368 and -4.821, respectively). Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups. Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup. Nebulized GLY, combined with LABA, did not generate any additional safety signals. CONCLUSION: Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA.

Applicability of passive compost bioreactors for treatment of extremely acidic and saline waters in semi-arid climates.

Extremely acidic and saline groundwater occurs naturally in south-western Australia. Discharge of this water to surface waters has increased following extensive clearing of native vegetation for agriculture and is likely to have negative environmental impacts. The use of passive treatment systems to manage the acidic discharge and its impacts is complicated by the region's semi-arid climate with hot dry summers and resulting periods of no flow. This study evaluates the performance of a pilot-scale compost bioreactor treating extremely acidic and saline drainage under semi-arid climatic conditions over a period of 2.5 years. The bioreactor's substrate consisted of municipal waste organics (MWO) mixed with 10 wt% recycled limestone. After the start-up phase the compost bioreactor raised the pH from ≤3.7 to ≥7 and produced net alkaline outflow for 126 days. The bioreactor removed up to 28 g/m(2)/d CaCO3 equivalent of acidity and acidity removal was found to be load dependent during the first and third year. Extended drying over summer combined with high salinity caused the formation of a salt-clay surface layer on top of the substrate, which was both beneficial and detrimental for bioreactor performance. The surface layer prevented the dehydration of the substrate and ensured it remained waterlogged when the water level in the bioreactor fell below the substrate surface in summer. However, when flow resumed the salt-clay layer acted as a barrier between the water and substrate decreasing performance efficiency. Performance increased again when the surface layer was broken up indicating that the negative climatic impacts can be managed. Based on substrate analysis after 1.5 years of operation, limestone dissolution was found to be the dominant acidity removal process contributing up to 78-91% of alkalinity generation, while bacterial sulfate reduction produced at least 9-22% of the total alkalinity. The substrate might last up to five years before the limestone is exhausted and would need to be replenished. The MWO substrate was found to release metals (Zn, Cu, Pb, Ni and Cr) and cannot be recommended for use in passive treatment systems unless the risk of metal release is addressed.

Chemically stable films for combinatorial fluorosensor arrays.

Sensor arrays are useful for many purposes. Our interests include quasi-distributed intrinsic fiber optic arrays, those distributed along the length of an optical fiber. We have demonstrated an optical time-of-flight approach to distinguishing the fluorescence output of such arrays, as well as a synthesis of combinatorial libraries that takes advantage of a support of linear morphology to make numerous compounds in a simple manner without information loss in the synthesis. To unite these research areas, we needed an optical fiber cladding material that meets demanding synthetic and optical requirements. We have chosen the Meldal SPOCC polymer support as the best candidate for such a material and report here our initial results with this material.