31 results on '"Jarreta, D."'
Search Results
2. An Evaluation Of Single And Dual Long-Acting Bronchodilator Therapy As Effective Interventions In Maintenance Therapy-Naïve Patients With COPD
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Singh D, D'Urzo AD, Donohue JF, Kerwin EM, Molins E, Chuecos F, Ribera A, and Jarreta D
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copd ,treatment-naïve ,lama ,laba ,Diseases of the respiratory system ,RC705-779 - Abstract
Dave Singh,1 Anthony D D’Urzo,2 James F Donohue,3 Edward M Kerwin,4 Eduard Molins,5 Ferran Chuecos,5 Anna Ribera,5 Diana Jarreta5 1Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 2Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada; 3Division of Pulmonary Diseases and Critical Care Medicine, University of North Carolina Pulmonary Critical Medicine, Chapel Hill, NC, USA; 4Clinical Research Institute, Medford, OR, USA; 5BioPharmaceuticals R&D, AstraZeneca, Barcelona, SpainCorrespondence: Dave SinghMedicines Evaluation Unit, University of Manchester, Manchester University NHS Foundation Trust, Manchester M23 9QZ, UK Tel +44 161 946 4073Fax +44 161 946 1459Email DSingh@meu.org.ukBackground: Ideally, treatment recommendations for maintenance therapy-naïve patients with COPD should be based on studies conducted specifically in this population. We have reviewed evidence from previous studies of pharmacological treatments in maintenance therapy-naïve patients with COPD and performed a new post-hoc analysis of dual bronchodilator treatment in this population, aiming to assess the effectiveness of these interventions.Materials and methods: A literature review identified clinical trials that included analyses of patients with COPD who were maintenance therapy-naïve with long-acting β2-agonists (LABA) or long-acting muscarinic antagonists (LAMA). Additionally, a post-hoc subgroup analysis was conducted for maintenance therapy-naïve patients with COPD in two large phase III, randomized, double-blind, 24-week trials investigating the efficacy of aclidinium bromide/formoterol fumarate (AB/FF) fixed-dose combination versus monotherapy or placebo (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]).Results: Treatment-naïve patients with COPD often represent a population of patients at the earliest stage at which most patients seek treatment. Of nine relevant studies identified, all reported positive findings for efficacy of LABA, LAMA, or LABA/LAMA treatment in maintenance therapy-naïve populations. Improvements were observed in lung function, symptoms, and health status versus monotherapy or placebo. Post-hoc analysis of ACLIFORM and AUGMENT demonstrated that AB/FF was effective in improving lung function in patients who had received no prior maintenance therapy. AB/FF showed improvements in 1 hr post-dose FEV1, trough FEV1, and patient-reported outcomes versus placebo and monotherapies. Combined with reviews of previous studies in maintenance therapy-naïve patients, these findings suggest that earlier intervention with a dual bronchodilator maintenance therapy, such as AB/FF, may provide significantly greater benefits than LAMA or LABA mono-bronchodilator therapy as a first maintenance treatment for COPD.Conclusion: These data show that therapeutic intervention is effective in treatment-naïve patients. Intervention with dual bronchodilator therapy as a first maintenance treatment for COPD may provide greater benefits than LAMA or LABA monotherapy.Keywords: COPD, treatment-naïve, LAMA, LABA
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- 2019
3. AMPLIFY: a randomized, Phase III study evaluating the efficacy and safety of aclidinium/formoterol vs monocomponents and tiotropium in patients with moderate-to-very severe symptomatic COPD
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Sethi S, Kerwin E, Watz H, Ferguson GT, Mroz RM, Segarra R, Molins E, Jarreta D, and Garcia Gil E
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aclidinium bromide ,bronchodilators ,LAMA ,LABA ,24-hour lung function ,Diseases of the respiratory system ,RC705-779 - Abstract
Sanjay Sethi,1 Edward Kerwin,2 Henrik Watz,3 Gary T Ferguson,4 Robert M Mroz,5,6 Rosa Segarra,7 Eduard Molins,7 Diana Jarreta,7 Esther Garcia Gil7 1Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, Buffalo, NY, USA; 2Clinical Research Institute, Medford, OR, USA; 3Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 4Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI, USA; 5Centrum Medycyny Oddechowej, Białystok, Poland; 6Medical University of Białystok, Białystok, Poland; 7AstraZeneca, Barcelona, Spain Background: AMPLIFY assessed the efficacy and safety of aclidinium bromide/formoterol fumarate (AB/FF) vs its monocomponents and tiotropium (TIO) in patients with moderate-to-very severe symptomatic COPD (NCT02796677).Methods: In this 24-week, Phase III, double-dummy, active-controlled study, symptomatic patients (COPD Assessment Test score ≥10) were randomized to twice-daily AB/FF 400/12 µg, AB 400 µg, or FF 12 µg, or once-daily TIO 18 µg. Co-primary endpoints were change from baseline at week 24 in 1-hour morning post-dose FEV1 (AB/FF vs AB) and in pre-dose (trough) FEV1 (AB/FF vs FF). Non-inferiority of AB vs TIO in pre-dose FEV1 was also an objective. Normalized area under the curve (AUC)0–3/3 h FEV1 and nighttime and early morning symptoms were also assessed. A subgroup participated in a 24-hour serial spirometry sub-study.Results: A total of 1,594 patients were randomized; 566 entered the sub-study. At week 24, 1-hour post-dose FEV1 significantly improved with AB/FF vs AB, FF, and TIO (84, 84, and 92 mL; all P
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- 2019
4. Efficacy of aclidinium/formoterol 400/12 µg, analyzed by airflow obstruction severity, age, sex, and exacerbation history: pooled analysis of ACLIFORM and AUGMENT
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D'Urzo AD, Singh D, Donohue JF, Kerwin EM, Ribera A, Molins E, Chuecos F, Jarreta D, and Garcia Gil E
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COPD ,aclidinium ,formoterol ,Diseases of the respiratory system ,RC705-779 - Abstract
Anthony D D’Urzo,1 Dave Singh,2 James F Donohue,3 Edward M Kerwin,4 Anna Ribera,5 Eduard Molins,5 Ferran Chuecos,5 Diana Jarreta,5 Esther Garcia Gil5 1Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada; 2Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester, UK; 3Division of Pulmonary Diseases & Critical Care Medicine, University of North Carolina School of Medicine at Chapel Hill, Chapel Hill, NC, USA; 4Clinical Research Institute of Southern Oregon, Medford, OR, USA; 5AstraZeneca, Barcelona, Spain Background: Aclidinium/formoterol 400/12 µg is a twice-daily maintenance bronchodilator for COPD. This post hoc study evaluated aclidinium/formoterol vs aclidinium 400 µg, formoterol 12 µg, or placebo in patient subgroups. Patients and methods: Data were pooled from two 24-week Phase III clinical trials (ACLIFORM and AUGMENT). Patients (N=3,394) were analyzed by baseline airflow obstruction severity (moderate/severe), age (
- Published
- 2019
5. ACTIVATE: the effect of aclidinium/formoterol on hyperinflation, exercise capacity, and physical activity in patients with COPD
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Watz H, Troosters T, Beeh KM, Garcia-Aymerich J, Paggiaro P, Molins E, Notari M, Zapata A, Jarreta D, and Garcia Gil E
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COPD ,hyperinflation ,aclidinium ,formoterol ,exercise capacity ,physical activity ,Diseases of the respiratory system ,RC705-779 - Abstract
Henrik Watz,1 Thierry Troosters,2 Kai M Beeh,3 Judith Garcia-Aymerich,4–6 Pierluigi Paggiaro,7 Eduard Molins,8 Massimo Notari,9 Antonio Zapata,10 Diana Jarreta,8 Esther Garcia Gil8 1Pulmonary Research Institute at LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany; 2Department of Rehabilitation Sciences, Pulmonary Rehabilitation and Respiratory Division, University Hospital Leuven, KU Leuven, Leuven, Belgium; 3insaf Respiratory Research Institute GmbH, Wiesbaden, Germany; 4Barcelona Institute of Global Health (ISGlobal), Barcelona, Spain; 5Universitat Pompeu Fabra (UPF), Barcelona, Spain; 6CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; 7Department of Surgery, Medicine, Molecular Biology and Critical Care, University of Pisa, Pisa, Italy; 8AstraZeneca PLC, Barcelona, Spain; 9A. Menarini Farmaceutica Internazionale S.R.L., Firenze, Italy; 10Laboratorios Menarini, S.A., Badalona, Spain Abstract: The Phase IV, 8-week, randomized, double-blind, placebo-controlled ACTIVATE study (NCT02424344) evaluated the effect of aclidinium/formoterol (AB/FF) 400/12 µg twice daily on lung hyperinflation, exercise capacity, and physical activity in patients with moderate-to-severe COPD. Patients received AB/FF (n=134) or placebo (n=133) (1:1) via the Genuair™/Pressair® dry powder inhaler for 8 weeks. From Weeks 5 to 8, all patients participated in behavioral intervention (BI; daily messages providing step goals). The primary end point was trough functional residual capacity (FRC) at Week 4. Exercise endurance time and physical activity were assessed at Week 4 (pharmacotherapy only) and at Week 8 (8 weeks of pharmacotherapy plus 4 weeks of BI). Other end points included post-dose FRC, residual volume, and inspiratory capacity (IC) at rest and during exercise. After 4 weeks, trough FRC improved with AB/FF versus placebo but did not reach significance (125 mL; P=0.0690). However, post-dose FRC, residual volume, and IC at rest improved significantly with AB/FF at Week 4 versus placebo (all P
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- 2017
6. Performance Evaluation of High-Chromium White Cast Irons Dual-Reinforced by Niobium Carbides in the Inner Circumference Abrasion Test with Different Abrasive Rock Types
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Demirer, E., primary, Pourasiabi, Hamid, additional, Jarreta, D. D., additional, and Gates, J. D., additional
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- 2022
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7. A randomised, placebo- and active-controlled dose-finding study of aclidinium bromide administered twice a day in COPD patients
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Singh, D., Magnussen, H., Kirsten, A., Mindt, S., Caracta, C., Seoane, B., Jarreta, D., and Garcia Gil, E.
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- 2012
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8. Effect of Plate Rolling Strategy and Nb Microalloying in the HAZ Performance After Welding
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Isasti, N., primary, Ishikawa, N., additional, Izumi, D., additional, Jarreta, D., additional, Martin, D., additional, Rodriguez-Íbabe, J., additional, Stalheim, D., additional, and Uranga, P., additional
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- 2022
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9. Effects of general anaesthetic procedures on mitochondrial function of human skeletal muscle
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Miró, Ò., Barrientos, A., Alonso, J. R., Casademont, J., Jarreta, D., Urbano-Márquez, Á., and Cardellach, F.
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- 1999
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10. Physical activity patterns and clusters in 1001 patients with COPD
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Mesquita, R, Spina, G, Pitta, F, Donaire-Gonzalez, D, Deering, BM, Patel, MS, Mitchell, KE, Alison, J, Van Gestel, AJR, Zogg, S, Gagnon, P, Abascal-Bolado, B, Vagaggini, B, Garcia-Aymerich, J, Jenkins, SC, Romme, EAPM, Kon, SSC, Albert, PS, Waschki, B, Shrikrishna, D, Singh, SJ, Hopkinson, NS, Miedinger, D, Benzo, RP, Maltais, F, Paggiaro, P, McKeough, ZJ, Polkey, MI, Hill, K, Man, WDC, Clarenbach, CF, Hernandes, NA, Savi, D, Wootton, S, Furlanetto, KC, Cindy Ng, LW, Vaes, AW, Jenkins, C, Eastwood, PR, Jarreta, D, Kirsten, A, Brooks, D, Hillman, DR, Sant'Anna, T, Meijer, K, Dürr, S, Rutten, EPA, Kohler, M, Probst, VS, Tal-Singer, R, Gil, EG, Den Brinker, AC, Leuppi, JD, Calverley, PMA, Smeenk, FWJM, Costello, RW, Gramm, M, Goldstein, R, Groenen, MTJ, Magnussen, H, Wouters, EFM, Zuwallack, RL, Amft, O, Watz, H, Spruit, MA, Mesquita, R, Spina, G, Pitta, F, Donaire-Gonzalez, D, Deering, BM, Patel, MS, Mitchell, KE, Alison, J, Van Gestel, AJR, Zogg, S, Gagnon, P, Abascal-Bolado, B, Vagaggini, B, Garcia-Aymerich, J, Jenkins, SC, Romme, EAPM, Kon, SSC, Albert, PS, Waschki, B, Shrikrishna, D, Singh, SJ, Hopkinson, NS, Miedinger, D, Benzo, RP, Maltais, F, Paggiaro, P, McKeough, ZJ, Polkey, MI, Hill, K, Man, WDC, Clarenbach, CF, Hernandes, NA, Savi, D, Wootton, S, Furlanetto, KC, Cindy Ng, LW, Vaes, AW, Jenkins, C, Eastwood, PR, Jarreta, D, Kirsten, A, Brooks, D, Hillman, DR, Sant'Anna, T, Meijer, K, Dürr, S, Rutten, EPA, Kohler, M, Probst, VS, Tal-Singer, R, Gil, EG, Den Brinker, AC, Leuppi, JD, Calverley, PMA, Smeenk, FWJM, Costello, RW, Gramm, M, Goldstein, R, Groenen, MTJ, Magnussen, H, Wouters, EFM, Zuwallack, RL, Amft, O, Watz, H, and Spruit, MA
- Abstract
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV1], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1, worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.
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- 2017
11. Physical activity patterns and clusters in 1001 patients with COPD
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Mesquita, R., Spina, G., Pitta, F., Donaire-Gonzalez, D., Deering, B., Patel, M., Mitchell, K., Alison, J., Van Gestel, A., Zogg, S., Gagnon, P., Abascal-Bolado, B., Vagaggini, B., Garcia-Aymerich, J., Jenkins, Susan, Romme, E., Kon, S., Albert, P., Waschki, B., Shrikrishna, D., Singh, S., Hopkinson, N., Miedinger, D., Benzo, R., Maltais, F., Paggiaro, P., McKeough, Z., Polkey, M., Hill, Kylie, Man, W., Clarenbach, C., Hernandes, N., Savi, D., Wootton, S., Furlanetto, K., Ng, Cindy, Vaes, A., Jenkins, C., Eastwood, P., Jarreta, D., Kirsten, A., Brooks, D., Hillman, D., Sant'Anna, T., Meijer, K., Dürr, S., Rutten, E., Kohler, M., Probst, V., Tal-Singer, R., Gil, E., Den Brinker, A., Leuppi, J., Calverley, P., Smeenk, F., Costello, R., Gramm, M., Goldstein, R., Groenen, M., Magnussen, H., Wouters, E., Zuwallack, R., Amft, O., Watz, H., Spruit, M., Mesquita, R., Spina, G., Pitta, F., Donaire-Gonzalez, D., Deering, B., Patel, M., Mitchell, K., Alison, J., Van Gestel, A., Zogg, S., Gagnon, P., Abascal-Bolado, B., Vagaggini, B., Garcia-Aymerich, J., Jenkins, Susan, Romme, E., Kon, S., Albert, P., Waschki, B., Shrikrishna, D., Singh, S., Hopkinson, N., Miedinger, D., Benzo, R., Maltais, F., Paggiaro, P., McKeough, Z., Polkey, M., Hill, Kylie, Man, W., Clarenbach, C., Hernandes, N., Savi, D., Wootton, S., Furlanetto, K., Ng, Cindy, Vaes, A., Jenkins, C., Eastwood, P., Jarreta, D., Kirsten, A., Brooks, D., Hillman, D., Sant'Anna, T., Meijer, K., Dürr, S., Rutten, E., Kohler, M., Probst, V., Tal-Singer, R., Gil, E., Den Brinker, A., Leuppi, J., Calverley, P., Smeenk, F., Costello, R., Gramm, M., Goldstein, R., Groenen, M., Magnussen, H., Wouters, E., Zuwallack, R., Amft, O., Watz, H., and Spruit, M.
- Abstract
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters (p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.
- Published
- 2017
12. Analysis of nocturnal actigraphic sleep measures in patients with COPD and their association with daytime physical activity
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Spina, G., Spruit, M., Alison, J., Benzo, R., Calverley, P., Clarenbach, C., Costello, R., Donaire-Gonzalez, D., Dürr, S., Garcia-Aymerich, J., van Gestel, A., Gramm, M., Hernandes, N., Hill, Kylie, Hopkinson, N., Jarreta, D., Kohler, M., Kirsten, A., Leuppi, J., Magnussen, H., Maltais, F., Man, W., McKeough, Z., Mesquita, R., Miedinger, D., Pitta, F., Singh, S., Smeenk, F., Tal-Singer, R., Vagaggini, B., Waschki, B., Watz, H., Wouters, E., Zogg, S., den Brinker, A., Spina, G., Spruit, M., Alison, J., Benzo, R., Calverley, P., Clarenbach, C., Costello, R., Donaire-Gonzalez, D., Dürr, S., Garcia-Aymerich, J., van Gestel, A., Gramm, M., Hernandes, N., Hill, Kylie, Hopkinson, N., Jarreta, D., Kohler, M., Kirsten, A., Leuppi, J., Magnussen, H., Maltais, F., Man, W., McKeough, Z., Mesquita, R., Miedinger, D., Pitta, F., Singh, S., Smeenk, F., Tal-Singer, R., Vagaggini, B., Waschki, B., Watz, H., Wouters, E., Zogg, S., and den Brinker, A.
- Abstract
Background: Sleep disturbances are common in patients with chronic obstructive pulmonary disease (COPD) with a considerable negative impact on their quality of life. However, factors associated with measures of sleep in daily life have not been investigated before nor has the association between sleep and the ability to engage in physical activity on a day-to-day basis been studied. Aims: To provide insight into the relationship between actigraphic sleep measures and disease severity, exertional dyspnoea, gender and parts of the week; and to investigate the association between sleep measures and next day physical activity. Methods: Data were analysed from 932 patients with COPD (66% male, 66.4±8.3 years, FEV1% predicted=50.8±20.5). Participants had sleep and physical activity continuously monitored using a multisensor activity monitor for a median of 6 days. Linear mixed effects models were applied to investigate the factors associated with sleep impairment and the association between nocturnal sleep and patients' subsequent daytime physical activity. Results: Actigraphic estimates of sleep impairment were greater in patients with worse airflow limitation and worse exertional dyspnoea. Patients with better sleep measures (ie, non-fragmented sleep, sleeping bouts ≥225 min, sleep efficiency ≥91% and time spent awake after sleep onset <57 min) spent significantly more time in light (<0.01) and moderate-to-vigorous physical activity (<0.01). Conclusions: There is a relationship between measures of sleep in patients with COPD and the amount of activity they undertake during the waking day. Identifying groups with specific sleep characteristics may be useful information when designing physical activity-enhancing interventions.
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- 2017
13. Corrigendum to “A randomised, placebo- and active-controlled dose-finding study of aclidinium bromide administered twice a day in COPD patients” [Pulm Pharmacol Ther 25 (3) (2012) 248–253]
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Singh, D., primary, Magnussen, H., additional, Kirsten, A., additional, Mindt, S., additional, Caracta, C., additional, Seoane, B., additional, Jarreta, D., additional, and Garcia Gil, E., additional
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- 2013
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14. P256 Aclidinium bromide: a Phase IIb, dose-finding study
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Singh, D., primary, Magnussen, H., additional, Kirsten, A., additional, Mindt-Pruefert, S., additional, Caracta, C., additional, Jarreta, D., additional, and Garcia Gil, E., additional
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- 2011
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15. Peak inspiratory flow through the Genuair® inhaler in patients with moderate or severe COPD
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Magnussen, H., primary, Watz, H., additional, Zimmermann, I., additional, Macht, S., additional, Greguletz, R., additional, Falques, M., additional, Jarreta, D., additional, and Garcia Gil, E., additional
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- 2009
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16. Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy
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Jarreta, D, primary
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- 2000
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17. Skeletal muscle mitochondrial function in polymyalgia rheumatica and in giant cell arteritis
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Miro, O., primary, Casademont, J., additional, Jarreta, D., additional, Grau, J. M., additional, Urbano-Marquez, A., additional, and Cardellach, F., additional
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- 1999
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18. Peak inspiratory flow through the Genuair® inhaler in patients with moderate or severe COPD.
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Magnussen, H., Watz, H., Zimmermann, I., Macht, S., Greguletz, R., Falques, M., Jarreta, D., and Garcia Gil, E.
- Abstract
Summary: The Genuair
® inhaler is a new multidose dry powder inhaler for the delivery of aclidinium bromide – a novel, long-acting, muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to assess the inspiratory flow characteristics through Genuair® in patients with moderate or severe COPD. Using a three-period cross-over design, 48 patients were randomised to inhale placebo powder through Genuair® , HandiHaler® A (slow, deep inhalation as per manufacturer''s instructions) or HandiHaler® B (fast, forceful inhalation). Three measurements of peak inspiratory flow (PIF), 10min apart, were recorded for each method of administration. The highest and average PIFs for the three attempts (mean±standard deviation) generated through the Genuair® inhaler were 97.7±15.7 and 92.0±15.4L/min, respectively. Furthermore, 97% of inhalations with the Genuair® inhaler were successful (activation of trigger threshold mechanism) and optimal (PIF≥45L/min). The highest and average PIFs generated through HandiHaler® A and B were significantly lower than with the Genuair® inhaler. In conclusion, patients with moderate or severe COPD were able to generate sufficient inspiratory airflow through the Genuair® inhaler to reliably inhale the full dose and reset the inhaler. [Copyright &y& Elsevier]- Published
- 2009
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19. Absence of mitochondrial dysfunction in polymyalgia rheumatica. Evidence based on a simultaneous molecular and biochemical approach.
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Miró, Òscar, Jarreta, Diana, Casademont, Jordi, Barrientos, Antoni, Rodríguez, Benjamín, Gómez, Montserrat, Nunes, Virginia, Urbano-Márquez, Álvaro, Cardellach, Francesc, Miró, O, Jarreta, D, Casademont, J, Barrientos, A, Rodríguez, B, Gómez, M, Nunes, V, Urbano-Márquez, A, and Cardellach, F
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POLYMYALGIA rheumatica ,MITOCHONDRIA - Abstract
Objective: To investigate the molecular and biochemical profile of skeletal muscle mitochondria of patients with isolated polymyalgia rheumatica (PMR).Patients and Methods: We included patients with a recent diagnosis of PMR and as control healthy individuals submitted to orthopedic surgery. Skeletal muscle was obtained from quadriceps, thus was mitochondria immediately isolated. Long polymerase chain reaction and Southern blot transference were performed to detect deleted mtDNA molecules. Mitochondrial oxidative activity using different substrates and individual enzyme activity of respiratory chain complexes were assessed to search for any biochemical dysfunction.Results: Fifty-one individuals (PMR=25, controls=26) were included. Mean age was 72 (11) years; 45% were females. We found no significant increase of deleted mtDNA molecules in PMR patients compared to controls. Both groups differed neither on oxygen consumption (p=NS for all substrates) nor enzymatic activity (p=NS for all complexes).Conclusions: Skeletal muscle mitochondria are molecularly and biochemically unaffected in PMR. [ABSTRACT FROM AUTHOR]- Published
- 1999
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20. Histological and biochemical assessment of mitochondrial function in dermatomyositis.
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Miró, Ò, Casademont, J, Grau, JM, Jarreta, D, Urbano-Márquez, Á, and Cardellach, F
- Abstract
Objective: Mitochondrial dysfunction in idiopathic inflammatory myopathies (IIM) remains a controversial issue. The aim of the present study was to investigate the correlation between histological abnormalities and the biochemical function of the skeletal muscle mitochondria from patients with dermatomyositis (DM). [ABSTRACT FROM PUBLISHER]
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- 1998
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21. Oxidative damage on lymphocyte membranes is increased in patients suffering from acute carbon monoxide poisoning
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Miro, O., Alonso, J. Ramon, Casademont, J., Jarreta, D., Urbano-Marquez, A., and Cardellach, F.
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- 1999
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22. Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes
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Miró, Alonso, J.R., Jarreta, D., Casademont, J., Urbano, and Cardellach, F.
- Abstract
Mitochondria constitute a source of reactive oxygen species. We tested whether mitochondrial function from human circulating lymphocytes is affected by smoking habit and if this could be associated with an increase in oxidative damage of biological membranes. We prospectively studied 35 smokers and 35 non-smoking healthy individuals matched by age and sex, with a similar physical activity. Individual enzyme activity of complexes II, III and IV of the mitochondrial respiratory chain (MRC) and of glycerol-3-phosphate dehydrogenase activity were measured spectrophotometrically. Intact cell respiration and oxidative rates after addition of pyruvate, succinate and glycerol-3-phosphate were assessed polarographically. Lipid peroxidation of biological membranes was assessed measuring the loss of cis-parinaric acid fluorescence. Results are expressed as means (±SD). Smokers showed a significant decrease in complex IV activity compared with non-smokers (112.8 ± 40.9 versus 146.4 ± 62.5 nmol/min/mg protein, respectively; 23% of inhibition; P = 0.01), while the rest of the complexes of MRC were unaffected. Conversely, oxidative rate with succinate, but not with the other substrates, was enhanced in smokers compared with non-smokers (16.7 ± 10.4 versus 11.4 ± 4.7 nmol oxygen/min/mg protein, respectively; 46% of activation; P = 0.01). Lipid peroxidation of lymphocyte membranes was increased in smokers with respect to non-smokers (3.49 ± 1.27 versus 4.39 ± 1.76 units of fluorescence/mg protein, respectively; 21% of increase; P = 0.03) and this increase correlated positively with succinate oxidation activation (R = 0.34, P = 0.02) and, to a lesser extent, with complex IV inhibition, although it did not reach statistical significance (R = 0.19, P = 0.18). In smokers, the MRC function of lymphocytes is disturbed and correlates with the degree of oxidative damage of membranes. This mitochondrial dysfunction could contribute to increased endogenous production of reactive oxygen species and could play a role in tobacco carcinogenicity.
- Published
- 1999
23. Histological and biochemical assessment of mitochondrial function in dermatomyositis
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Cardellach, F., Miró, Casademont, J., Grau, J., Jarreta, D., and Urbano
- Abstract
Objective: Mitochondrial dysfunction in idiopathic inflammatory myopathies (IIM) remains a controversial issue. The aim of the present study was to investigate the correlation between histological abnormalities and the biochemical function of the skeletal muscle mitochondria from patients with dermatomyositis (DM).Method: We evaluated 10 patients with a new diagnosis of DM and 15 healthy individuals, matched by age and gender. Muscle biopsy was routinely processed for histochemical studies and biochemical analysis of pure mitochondria. The percentages of ragged-red fibres (RRF), cytochrome c oxidase (COX)-negative fibres and succinic dehydrogenase (SDH) hyper-reactive fibres were calculated, oxygen utilization using different substrates was assessed polarographically, and enzymatic activity of individual complexes of the electron transport chain (ETC) and ATPase was measured spectrophotometrically.Results: We found an increased percentage of COX-negative and SDH hyper-reactive fibres in DM patients (0.82 and 1.82%, respectively) compared to controls (0.26 and 0.22%; P <0.05 and P=0.001, respectively); however, oxidation rates of different substrates and enzymatic activities of ETC and ATPase did not differ significantly between both groups.Conclusion: The overall function of ETC from skeletal muscle mitochondria is not affected in DM.
- Published
- 1998
24. ACLIDINIUM BROMIDE: A PHASE IIB, DOSE-FINDING STUDY.
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Singh, D., Magnussen, H., Kirsten, A., Mindt-Pruefert, S., Caracta, C., Jarreta, D., and Gil, E. Garcia
- Subjects
OBSTRUCTIVE lung disease treatment ,TREATMENT effectiveness ,MUSCARINIC antagonists ,DRUG dosage ,CLINICAL trials - Abstract
Introduction and Objectives Aclidinium bromide, a second-generation, long-acting muscarinic antagonist with low systemic activity, is in clinical development for the twice daily maintenance treatment of chronic obstructive pulmonary disease (COPD). This Phase IIb study investigated the dose-response bronchodilation of aclidinium twice daily vs placebo and an active control (formoterol 12 µg twice daily) in patients with moderate to severe COPD. Methods In this double-blind, double-dummy, cross-over study, 79 patients received 7-day treatments of aclidinium 100 µg, 200 µg and 400 µg, formoterol 12 µg and placebo twice daily over five treatment periods separated by a 7-day washout. The primary endpoint was change from baseline in normalised forced expiratory volume in 1 second (FEV
1 ) area under the curve (AUC)0-12 at Day 7. Other efficacy assessments included change frombaseline at Day 7 in normalised FEV1 AUC0-24 and morning pre-dose (trough) and peak FEV1 . Adverse events (AEs) were reported throughout the study. Results Aclidinium provided dose-dependent bronchodilation compared with placebo as assessed by change from baseline in normalised FEV1 AUC0-12 and FEV1 AUC0-24 at Day 7 (Abstract P256 table 1). The bronchodilation provided by aclidinium 400 µg during the first 12 h was comparable to the active control, formoterol 12 µg. Aclidinium improved morning pre-dose trough FEV1 and peak FEV1 after 7 days compared with placebo; the 400 µg dose was most comparable to formoterol 12 µg. Aclidinium was well tolerated; the safety profile of all doses was comparable to that of placebo. Conclusion A dose-dependent bronchodilation was observed with aclidinium twice daily. The bronchodilation provided by the highest dose of aclidinium (400 µg) twice daily was comparable to formoterol 12 µg twice daily. The safety profile of aclidinium was similar to placebo, with no dose-dependent AEs observed. Funding This study was supported by Almirall S.A., Barcelona, Spain, and Forest Laboratories, Inc., New York, USA. [ABSTRACT FROM AUTHOR]- Published
- 2011
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25. The Effect of Aclidinium on Symptoms Including Cough in Chronic Obstructive Pulmonary Disease: A Phase 4, Double-Blind, Placebo-controlled, Parallel-Group Study.
- Author
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Smith JA, McGarvey L, Morice AH, Birring SS, Wedzicha JA, Notari M, Zapata A, Segarra R, Seoane B, and Jarreta D
- Subjects
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Humans, Male, Middle Aged, Placebos, Bronchodilator Agents therapeutic use, Cough drug therapy, Muscarinic Antagonists therapeutic use, Pulmonary Disease, Chronic Obstructive drug therapy, Pulmonary Disease, Chronic Obstructive physiopathology, Tropanes therapeutic use
- Published
- 2019
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26. Physical activity patterns and clusters in 1001 patients with COPD.
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Mesquita R, Spina G, Pitta F, Donaire-Gonzalez D, Deering BM, Patel MS, Mitchell KE, Alison J, van Gestel AJ, Zogg S, Gagnon P, Abascal-Bolado B, Vagaggini B, Garcia-Aymerich J, Jenkins SC, Romme EA, Kon SS, Albert PS, Waschki B, Shrikrishna D, Singh SJ, Hopkinson NS, Miedinger D, Benzo RP, Maltais F, Paggiaro P, McKeough ZJ, Polkey MI, Hill K, Man WD, Clarenbach CF, Hernandes NA, Savi D, Wootton S, Furlanetto KC, Cindy Ng LW, Vaes AW, Jenkins C, Eastwood PR, Jarreta D, Kirsten A, Brooks D, Hillman DR, Sant'Anna T, Meijer K, Dürr S, Rutten EP, Kohler M, Probst VS, Tal-Singer R, Gil EG, den Brinker AC, Leuppi JD, Calverley PM, Smeenk FW, Costello RW, Gramm M, Goldstein R, Groenen MT, Magnussen H, Wouters EF, ZuWallack RL, Amft O, Watz H, and Spruit MA
- Subjects
- Actigraphy, Age Factors, Aged, Agnosia, Body Mass Index, Cluster Analysis, Cross-Sectional Studies, Dyspnea etiology, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Principal Component Analysis, Pulmonary Disease, Chronic Obstructive complications, Sedentary Behavior, Severity of Illness Index, Exercise, Pulmonary Disease, Chronic Obstructive physiopathology
- Abstract
We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV
1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.- Published
- 2017
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27. Analysis of nocturnal actigraphic sleep measures in patients with COPD and their association with daytime physical activity.
- Author
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Spina G, Spruit MA, Alison J, Benzo RP, Calverley PMA, Clarenbach CF, Costello RW, Donaire-Gonzalez D, Dürr S, Garcia-Aymerich J, van Gestel AJR, Gramm M, Hernandes NA, Hill K, Hopkinson NS, Jarreta D, Kohler M, Kirsten AM, Leuppi JD, Magnussen H, Maltais F, Man WD, McKeough ZJ, Mesquita R, Miedinger D, Pitta F, Singh SJ, Smeenk FWJM, Tal-Singer R, Vagaggini B, Waschki B, Watz H, Wouters EFM, Zogg S, and den Brinker AC
- Subjects
- Aged, Cross-Sectional Studies, Female, Follow-Up Studies, Forced Expiratory Volume, Humans, Male, Pulmonary Disease, Chronic Obstructive diagnosis, Quality of Life, Retrospective Studies, Severity of Illness Index, Time Factors, Actigraphy methods, Circadian Rhythm physiology, Exercise physiology, Pulmonary Disease, Chronic Obstructive physiopathology, Sleep physiology
- Abstract
Background: Sleep disturbances are common in patients with chronic obstructive pulmonary disease (COPD) with a considerable negative impact on their quality of life. However, factors associated with measures of sleep in daily life have not been investigated before nor has the association between sleep and the ability to engage in physical activity on a day-to-day basis been studied., Aims: To provide insight into the relationship between actigraphic sleep measures and disease severity, exertional dyspnoea, gender and parts of the week; and to investigate the association between sleep measures and next day physical activity., Methods: Data were analysed from 932 patients with COPD (66% male, 66.4±8.3 years, FEV
1 % predicted=50.8±20.5). Participants had sleep and physical activity continuously monitored using a multisensor activity monitor for a median of 6 days. Linear mixed effects models were applied to investigate the factors associated with sleep impairment and the association between nocturnal sleep and patients' subsequent daytime physical activity., Results: Actigraphic estimates of sleep impairment were greater in patients with worse airflow limitation and worse exertional dyspnoea. Patients with better sleep measures (ie, non-fragmented sleep, sleeping bouts ≥225 min, sleep efficiency ≥91% and time spent awake after sleep onset <57 min) spent significantly more time in light (p<0.01) and moderate-to-vigorous physical activity (p<0.01)., Conclusions: There is a relationship between measures of sleep in patients with COPD and the amount of activity they undertake during the waking day. Identifying groups with specific sleep characteristics may be useful information when designing physical activity-enhancing interventions., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)- Published
- 2017
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28. Effect of aclidinium bromide on cough and sputum symptoms in moderate-to-severe COPD in three phase III trials.
- Author
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McGarvey L, Morice AH, Smith JA, Birring SS, Chuecos F, Seoane B, and Jarreta D
- Abstract
Background: Cough and sputum are troublesome symptoms in chronic obstructive pulmonary disease (COPD) and are associated with adverse outcomes. The efficacy of aclidinium bromide 400 µg twice daily in patients with stable COPD has been established in two phase III studies (ACCORD COPD I and ATTAIN) and a phase IIIb active-comparator study. This analysis evaluated cough-related symptoms across these studies., Method: Patients were randomised to placebo, aclidinium 200 µg or 400 µg twice daily in ACCORD (12 weeks) and ATTAIN (24 weeks), or to placebo, aclidinium 400 µg twice daily or tiotropium 18 µg once daily (6-week active-comparator study). Analysed end points included changes from baseline in Evaluating Respiratory Symptoms (E-RS; formerly known as EXAcerbations of Chronic pulmonary disease Tool), total and cough/sputum scores and frequency/severity of morning and night-time cough and sputum symptoms., Results: Data for 1792 patients were evaluated. E-RS cough/sputum domain scores were significantly reduced with aclidinium 400 µg versus placebo in ATTAIN (-0.7 vs -0.3, respectively; p<0.01) and the active-comparator study (-0.6 vs -0.2, respectively; p<0.01). In the active-comparator study, significantly greater improvements were observed with aclidinium versus placebo for severity of morning cough (-0.19 vs -0.02; p<0.01) and phlegm (-0.19 vs -0.02; p<0.05). In ACCORD, aclidinium reduced night-time cough frequency (-0.36 vs 0.1 for placebo; p<0.001) and severity (-0.24 vs -0.1 for placebo; p<0.05), and frequency of night-time sputum production (-0.37 vs 0.05 for placebo; p<0.001)., Conclusions: Aclidinium 400 µg twice daily improves cough and sputum expectoration versus placebo in stable COPD., Trial Registration Numbers: NCT00891462; NCT01001494; NCT01462929., Competing Interests: LMG has received honoraria and travel support from AstraZeneca. AHM has received honoraria, travel support and unrestricted grant aid from AstraZeneca. JAS is an inventor on a patent owned by the University Hospital South Manchester covering automated detection of cough from sound signals, and the patent is the subject of a license agreement with Vitalograph Ltd. (Buckinghamshire, UK); has received honoraria from Almirall and holds an MRC project grant part-funded by AstraZeneca. SSB received an honorarium for a scientific advisory board from Almirall. FC, BS and DJ are employees of AstraZeneca PLC and former employees of Almirall, Barcelona, Spain.
- Published
- 2016
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29. Aclidinium improves exercise endurance, dyspnea, lung hyperinflation, and physical activity in patients with COPD: a randomized, placebo-controlled, crossover trial.
- Author
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Beeh KM, Watz H, Puente-Maestu L, de Teresa L, Jarreta D, Caracta C, Garcia Gil E, and Magnussen H
- Subjects
- Accelerometry, Aged, Cross-Over Studies, Double-Blind Method, Dyspnea etiology, Female, Forced Expiratory Volume, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive complications, Treatment Outcome, Dyspnea drug therapy, Exercise Tolerance, Motor Activity, Muscarinic Antagonists therapeutic use, Physical Endurance, Pulmonary Disease, Chronic Obstructive drug therapy, Tropanes therapeutic use
- Abstract
Background: This study evaluated the effects of aclidinium bromide, a long-acting muscarinic antagonist indicated for maintenance treatment of chronic obstructive pulmonary disease (COPD), on exercise endurance, dyspnea, lung hyperinflation, and physical activity., Methods: In this randomized, double-blind, crossover study, patients with stable COPD and moderate-to-severe airflow limitation received aclidinium 400 μg twice daily or placebo via Genuair®/Pressair(®a) for 3 weeks (2-week washout between treatment periods). The primary endpoint was change from baseline to Week 3 in endurance time, measured by constant work rate cycle ergometry testing at 75% peak incremental work rate. Changes from baseline in intensity of exertional dyspnea (Borg CR10 Scale®) and trough inspiratory capacity were secondary endpoints. Additional endpoints included changes from baseline in other spirometric, plethysmographic, and physical activity (assessed by objective accelerometer measurement) parameters. Efficacy endpoints were analyzed using an analysis of covariance model., Results: In total, 112 patients were randomized and treated (mean age 60.3 years; mean post-bronchodilator forced expiratory volume in 1 s 1.7 L [56.7% predicted]; mean endurance time 485.7 s). After 3 weeks, endurance time was significantly increased with aclidinium versus placebo (treatment difference 58.5 s; p < 0.05). At Week 3, aclidinium significantly reduced dyspnea intensity at isotime during exercise (treatment difference -0.63; p < 0.05) and improved trough inspiratory capacity (treatment difference 78 mL; p < 0.05) versus placebo. Significant improvements in spirometric, plethysmographic, and some physical activity parameters were observed with aclidinium versus placebo., Conclusions: These results suggest that aclidinium significantly improves exercise endurance, exertional dyspnea, hyperinflation, and physical activity in patients with COPD., Trial Registration: ClinicalTrials.gov identifier: NCT01471171; URL: http://www.clinicaltrials.gov.
- Published
- 2014
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30. Aclidinium bromide improves exercise endurance and lung hyperinflation in patients with moderate to severe COPD.
- Author
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Maltais F, Celli B, Casaburi R, Porszasz J, Jarreta D, Seoane B, and Caracta C
- Subjects
- Exercise Tolerance physiology, Female, Forced Expiratory Volume drug effects, Humans, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive physiopathology, Pulmonary Disease, Chronic Obstructive rehabilitation, Severity of Illness Index, Treatment Outcome, Vital Capacity drug effects, Bronchodilator Agents therapeutic use, Exercise Tolerance drug effects, Pulmonary Disease, Chronic Obstructive drug therapy, Tropanes therapeutic use
- Abstract
Background: Static and dynamic lung hyperinflation are associated with exercise impairment and poor outcomes in COPD patients. Aclidinium bromide is a novel, long-acting inhaled muscarinic antagonist currently in development for COPD treatment., Methods: Patients with moderate to severe COPD (N = 181) were randomized to once-daily aclidinium 200 μg or placebo for 6 weeks. Constant work rate cycling exercises at 75% of peak work rate were performed at baseline, Day 1, Week 3, and Week 6. The primary efficacy measure was change in exercise endurance time (ET) from baseline to Week 6. Secondary outcomes included changes in trough forced expiratory volume in 1 s (FEV(1)), inspiratory capacity (IC), IC/total lung capacity (TLC), and functional residual capacity (FRC) from baseline to Day 1, Week 3, and Week 6. Borg dyspnea scores during exercise, locus of symptom limitation, and safety measures were assessed., Results: Aclidinium significantly improved ET on Day 1 (P = 0.0002), and improvements were sustained through Week 3 (P = 0.0007) and Week 6 (P = 0.0042) vs placebo. Compared with placebo, aclidinium improved trough FEV(1), IC, and IC/TLC at Weeks 3 and 6 (P < 0.05 for all). Exertional dyspnea scores at isotime were reduced on Day 1, Week 3, and Week 6 for aclidinium vs placebo (P < 0.05). Furthermore, the likelihood of stopping exercise due to breathing discomfort was lower in the aclidinium group at study end (P = 0.0208) compared with placebo. No differences in safety outcomes were reported between treatments., Conclusions: Aclidinium significantly increased exercise tolerance, improved airflow obstruction and lung hyperinflation, and was safe and well tolerated. REGISTRATION OF TRIAL: This trial was registered with ClinicalTrials.gov (NCT00500318) under the name "A Study of Exercise Endurance and Lung Hyperinflation in Patients with Moderate to Severe COPD"., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2011
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31. Localization and mobility of coenzyme Q in lipid bilayers and membranes.
- Author
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Lenaz G, Fato R, Di Bernardo S, Jarreta D, Costa A, Genova ML, and Parenti Castelli G
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- Animals, Computer Simulation, Electron Transport, Intracellular Membranes chemistry, Mitochondria chemistry, Models, Molecular, Molecular Conformation, Ubiquinone analogs & derivatives, Intracellular Membranes metabolism, Lipid Bilayers chemistry, Mitochondria metabolism, Ubiquinone chemistry, Ubiquinone metabolism
- Abstract
We have studied the mobility of coenzyme Q (CoQ) in lipid bilayers and mitochondrial membranes in relation to the control of electron transfer activities. A molecular dynamics computer simulation in the vacuum yielded a folded structure for CoQ10, with a length of only 21 A. Using this information we were able to calculate diffusion coefficients in the range of 10(-6) cm2/s in good agreement with those found experimentally by fluorescence quenching of pyrene derivatives. To investigate if CoQ diffusion may represent the rate-limiting step of electron transfer, we reconstituted complexes I and III and assayed the resulting NADH-cytochrome c reductase activity in presence of different CoQ10 levels and at different distances between complexes; the experimental turnovers were higher than the collision frequencies calculated using diffusion coefficients of 10(-9) cm2/s but compatible with values found by us by fluorescence quenching. Since the experimental turnovers are independent of the distance between complexes, we conclude that CoQ diffusion is not rate-limiting for electron transfer.
- Published
- 1999
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