The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Bradley A Edwards - One of the best experts on this subject based on the ideXlab platform.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Background and objectiveUpper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.MethodsTherapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.ResultsResponders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.ConclusionTherapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • the combination of supplemental oxygen and a hypnotic markedly improves obstructive sleep apnea in patients with a mild to moderate upper airway collapsibility
    Sleep, 2016
    Co-Authors: Danny J. Eckert, Robert L. Owens, Bradley A Edwards, Scott A Sands, Shane A Landry, David P. White
    Abstract:

    Author(s): Edwards, Bradley A; Sands, Scott A; Owens, Robert L; Eckert, Danny J; Landry, Shane; White, David P; Malhotra, Atul; Wellman, Andrew | Abstract: STUDY OBJECTIVES:Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA. Therefore, our aim was to determine how the combination of oxygen and Eszopiclone alters the phenotypic traits and OSA severity and to assess the baseline phenotypic characteristics of responders/nonresponders to combination therapy. METHODS:In a single-blinded randomized crossover study, 20 OSA patients received combination therapy (3 mg Eszopiclone and 40% oxygen) versus placebo/sham air, with 1 w between conditions. Under each condition, we assessed the effects on OSA severity (clinical polysomnography) and the phenotypic traits causing OSA using CPAP manipulations (research polysomnography). RESULTS:Combination therapy reduced the apnea-hypopnea index (51.9 ± 6.2 vs. 29.5 ± 5.3 events/h; P l 0.001), lowered both the ventilation associated with arousal (5.7 ± 0.3 vs. 5.2 ± 0.3 L/min; P = 0.05) and loop gain (3.3 ± 0.5 vs. 2.2 ± 0.3; P = 0.025). Responders to therapy (apnea-hypopnea index reduced by g 50% to below 15 events/h; n = 9/20) had less severe OSA (P = 0.001), a less collapsible upper airway (P = 0.01) and greater upper airway muscle effectiveness (P = 0.002). CONCLUSIONS:The combination of lowering loop gain and raising the arousal threshold is an effective therapy in patients whose anatomy is not severely compromised. Our work demonstrates that combining therapies that target multiple traits can resolve OSA in selected individuals. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT01633827.

Thomas Roth - One of the best experts on this subject based on the ideXlab platform.

  • a 12 week randomized double blind placebo controlled study evaluating the effect of Eszopiclone 2 mg on sleep wake function in older adults with primary and comorbid insomnia
    Sleep, 2010
    Co-Authors: Sonia Ancoliisrael, Kendyl Schaefer, Robert Rubens, Andrew D. Krystal, Amy Wilson, Raymond Claus, Vaughn W Mccall, Thomas Roth
    Abstract:

    Background: Longer-term pharmacologic studies for insomnia in older individuals are sparse. Objective: To evaluate the efficacy and safety of 12 weeks of nightly Eszopiclone in elderly outpatients with insomnia. Methods: Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) ≤ 6 h, and wake time after sleep onset (WASO) ≥ 45 min. Participants were randomized to 12 weeks of Eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, well-being, ability to function) were assessed. AEs were monitored. Results: Subjects treated with 2 mg Eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for Eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, Eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for Eszopiclone (P-values ≤ 0.01), indicating no rebound. The most common AEs (≥ 5%) were headache (Eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%). Conclusion: In this Phase IV trial of older adults with insomnia, Eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated. Clinical Trial Information: A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=Eszopiclone&rank=24.

  • nightly treatment of primary insomnia with Eszopiclone for six months effect on sleep quality of life and work limitations
    Sleep, 2007
    Co-Authors: Andrew D. Krystal, Kendyl Schaefer, Thomas Wessel, Judy Caron, David A. Amato, James M. Roach, Robert Rubens, Gene Wallenstein, Thomas Roth
    Abstract:

    Study Objectives: To evaluate 6 months' Eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations.

  • Eszopiclone in patients with insomnia during perimenopause and early postmenopause a randomized controlled trial
    Obstetrics & Gynecology, 2006
    Co-Authors: Claudio N Soares, Judy Caron, Thomas Roth, Robert Rubens, Hadine Joffe, Lee S Cohen
    Abstract:

    OBJECTIVE:To evaluate Eszopiclone 3 mg for treatment of insomnia in perimenopausal and early postmenopausal women, as well as the impact of insomnia treatment on mood, menopause-related symptoms, and quality of life.METHODS:This was a double-blind, placebo-controlled study with 410 women (aged 40–60

  • Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder.
    Biological Psychiatry, 2006
    Co-Authors: Maurizio Fava, Thomas Wessel, Judy Caron, David A. Amato, W. Vaughn Mccall, Robert Rubens, Andrew D. Krystal, Thomas Roth
    Abstract:

    Background Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding Eszopiclone to fluoxetine. Methods Patients who met DSM-IV criteria for both MDD and insomnia ( n = 545) received morning fluoxetine and were randomized to nightly Eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S). Results Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p p = .01) with progressive improvement at Week 8 ( p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 ( p p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates. Conclusions In this study, Eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.

  • an evaluation of the efficacy and safety of Eszopiclone over 12 months in patients with chronic primary insomnia
    Sleep Medicine, 2005
    Co-Authors: Thomas Roth, Thomas Wessel, James K Walsh, Andrew D. Krystal, Timothy Roehrs
    Abstract:

    Abstract Background and purpose A double-blind placebo-controlled study of Eszopiclone found significant, sustained improvement in sleep and daytime function. The 6-month open-label extension phase is described herein. Patients and methods Adults (21–64) with primary insomnia who reported sleep duration 30 min/night were included. Patient-reported endpoints included sleep and daytime function. Safety and compliance were assessed at monthly clinic visits. The final double-blind month was used as the baseline for efficacy analyses of the open-label period. Results Patients who were initially randomized to double-blind placebo and then switched to open-label Eszopiclone ( n =111) significantly reported the following: (1) decreased sleep latency, wake time after sleep onset, and number of awakenings; (2) increased total sleep time and sleep quality; and (3) improved ratings of daytime ability to function, alertness and sense of physical well-being compared to baseline ( P ≤0.0001 all monthly endpoints). There was no evidence of tolerance on any measure in either group. These subjects ( n =360) sustained the double-blind treatment gains for all sleep and daytime parameters, with further significant improvement in a number of measures. Eszopiclone was well tolerated in both groups; unpleasant taste was the only undesirable effect reported by >5% of patients. Conclusions The significant improvements in sleep and daytime function were evident in those switched from double-blind placebo to 6 months of open-label Eszopiclone therapy and were sustained during the 6 months of open-label treatment for those receiving prior double-blind Eszopiclone. During 12 months of nightly treatment, Eszopiclone 3 mg was well tolerated; tolerance was not observed.

Atul Malhotra - One of the best experts on this subject based on the ideXlab platform.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Background and objectiveUpper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.MethodsTherapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.ResultsResponders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.ConclusionTherapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • Eszopiclone increases the respiratory arousal threshold and lowers the apnoea hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold
    Clinical Science, 2011
    Co-Authors: Danny J. Eckert, Robert L. Owens, Geoffrey B. Kehlmann, Andrew Wellman, Shilpa Rahangdale, David P. White, Susie Yimyeh, Atul Malhotra
    Abstract:

    Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, Eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that Eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to −15 cmH2O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO2 (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of Eszopiclone or placebo immediately prior to each study. Compared with placebo, Eszopiclone significantly increased the arousal threshold [−14.0 (−19.9 to −10.9) compared with −18.0 (−22.2 to −15.1) cmH2O; P < 0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25 ± 6 compared with 14 ± 4 events/h of sleep; P < 0.01). In conclusion, Eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.

David P. White - One of the best experts on this subject based on the ideXlab platform.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Upper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.Therapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.Responders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.Therapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • response to a combination of oxygen and a hypnotic as treatment for obstructive sleep apnoea is predicted by a patient s therapeutic cpap requirement
    Respirology, 2017
    Co-Authors: Shane A Landry, Andrew Wellman, David P. White, Atul Malhotra, Bradley A Edwards, Scott A Sands, Simon A Joosten, Garun S Hamilton
    Abstract:

    Author(s): Landry, Shane A; Joosten, Simon A; Sands, Scott A; White, David P; Malhotra, Atul; Wellman, Andrew; Hamilton, Garun S; Edwards, Bradley A | Abstract: Background and objectiveUpper airway collapsibility predicts the response to several non-continuous positive airway pressure (CPAP) interventions for obstructive sleep apnoea (OSA). Measures of upper airway collapsibility cannot be easily performed in a clinical context; however, a patient's therapeutic CPAP requirement may serve as a surrogate measure of collapsibility. The present work aimed to compare the predictive use of CPAP level with detailed physiological measures of collapsibility.MethodsTherapeutic CPAP levels and gold-standard pharyngeal collapsibility measures (passive pharyngeal critical closing pressure (Pcrit ) and ventilation at CPAP level of 0 cmH2 O (Vpassive )) were retrospectively analysed from a randomized controlled trial (n = 20) comparing the combination of oxygen and Eszopiclone (treatment) versus placebo/air control. Responders (9/20) to treatment were defined as those who exhibited a 50% reduction in apnoea/hypopnoea index (AHI) plus an AHIl15 events/h on-therapy.ResultsResponders to treatment had a lower therapeutic CPAP requirement compared with non-responders (6.6 (5.4-8.1) cmH2 O vs 8.9 (8.4-10.4) cmH2 O, P = 0.007), consistent with their reduced collapsibility (lower Pcrit , P = 0.017, higher Vpassive P = 0.025). Therapeutic CPAP level provided the highest predictive accuracy for differentiating responders from non-responders (area under the curve (AUC) = 0.86 ± 0.9, 95% CI: 0.68-1.00, P = 0.007). However, both Pcrit (AUC = 0.83 ± 0.11, 95% CI: 0.62-1.00, P = 0.017) and Vpassive (AUC = 0.77 ± 0.12, 95% CI: 0.53-1.00, P = 0.44) performed well, and the difference in AUC for these three metrics was not statistically different. A therapeutic CPAP level ≤8 cmH2 O provided 78% sensitivity and 82% specificity (positive predictive value = 78%, negative predictive value = 82%) for predicting a response to these therapies.ConclusionTherapeutic CPAP requirement, as a surrogate measure of pharyngeal collapsibility, predicts the response to non-anatomical therapy (oxygen and Eszopiclone) for OSA.

  • the combination of supplemental oxygen and a hypnotic markedly improves obstructive sleep apnea in patients with a mild to moderate upper airway collapsibility
    Sleep, 2016
    Co-Authors: Danny J. Eckert, Robert L. Owens, Bradley A Edwards, Scott A Sands, Shane A Landry, David P. White
    Abstract:

    Author(s): Edwards, Bradley A; Sands, Scott A; Owens, Robert L; Eckert, Danny J; Landry, Shane; White, David P; Malhotra, Atul; Wellman, Andrew | Abstract: STUDY OBJECTIVES:Obstructive sleep apnea (OSA) results from the interaction of several physiological traits; specifically a compromised upper airway anatomy and muscle function, and two key non-anatomical deficits: elevated loop gain and a low arousal threshold. Although continuous positive airway pressure (CPAP) is an efficacious treatment, it is often poorly tolerated. An alternative approach could involve administering therapies targeting the non-anatomic causes. However, therapies (oxygen or hypnotics) targeting these traits in isolation typically improve, but rarely resolve OSA. Therefore, our aim was to determine how the combination of oxygen and Eszopiclone alters the phenotypic traits and OSA severity and to assess the baseline phenotypic characteristics of responders/nonresponders to combination therapy. METHODS:In a single-blinded randomized crossover study, 20 OSA patients received combination therapy (3 mg Eszopiclone and 40% oxygen) versus placebo/sham air, with 1 w between conditions. Under each condition, we assessed the effects on OSA severity (clinical polysomnography) and the phenotypic traits causing OSA using CPAP manipulations (research polysomnography). RESULTS:Combination therapy reduced the apnea-hypopnea index (51.9 ± 6.2 vs. 29.5 ± 5.3 events/h; P l 0.001), lowered both the ventilation associated with arousal (5.7 ± 0.3 vs. 5.2 ± 0.3 L/min; P = 0.05) and loop gain (3.3 ± 0.5 vs. 2.2 ± 0.3; P = 0.025). Responders to therapy (apnea-hypopnea index reduced by g 50% to below 15 events/h; n = 9/20) had less severe OSA (P = 0.001), a less collapsible upper airway (P = 0.01) and greater upper airway muscle effectiveness (P = 0.002). CONCLUSIONS:The combination of lowering loop gain and raising the arousal threshold is an effective therapy in patients whose anatomy is not severely compromised. Our work demonstrates that combining therapies that target multiple traits can resolve OSA in selected individuals. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, ID: NCT01633827.

  • Eszopiclone increases the respiratory arousal threshold and lowers the apnoea hypopnoea index in obstructive sleep apnoea patients with a low arousal threshold
    Clinical Science, 2011
    Co-Authors: Danny J. Eckert, Robert L. Owens, Geoffrey B. Kehlmann, Andrew Wellman, Shilpa Rahangdale, David P. White, Susie Yimyeh, Atul Malhotra
    Abstract:

    Recent insights into sleep apnoea pathogenesis reveal that a low respiratory arousal threshold (awaken easily) is important for many patients. As most patients experience stable breathing periods mediated by upper-airway dilator muscle activation via accumulation of respiratory stimuli, premature awakening may prevent respiratory stimuli build up as well as the resulting stabilization of sleep and breathing. The aim of the present physiological study was to determine the effects of a non-benzodiazepine sedative, Eszopiclone, on the arousal threshold and the AHI (apnoea/hypopnoea index) in obstructive sleep apnoea patients. We hypothesized that Eszopiclone would increase the arousal threshold and lower the AHI in patients with a low arousal threshold (0 to −15 cmH2O). Following a baseline overnight polysomnogram with an epiglottic pressure catheter to quantify the arousal threshold, 17 obstructive sleep apnoea patients, without major hypoxaemia [nadir SaO2 (arterial blood oxygen saturation) >70%], returned on two additional nights and received 3 mg of Eszopiclone or placebo immediately prior to each study. Compared with placebo, Eszopiclone significantly increased the arousal threshold [−14.0 (−19.9 to −10.9) compared with −18.0 (−22.2 to −15.1) cmH2O; P < 0.01], and sleep duration, improved sleep quality and lowered the AHI without respiratory event prolongation or worsening hypoxaemia. Among the eight patients identified as having a low arousal threshold, reductions in the AHI occurred invariably and were most pronounced (25 ± 6 compared with 14 ± 4 events/h of sleep; P < 0.01). In conclusion, Eszopiclone increases the arousal threshold and lowers the AHI in obstructive sleep apnoea patients that do not have marked overnight hypoxaemia. The greatest reductions in the AHI occurred in those with a low arousal threshold. The results of this single night physiological study suggest that certain sedatives may be of therapeutic benefit for a definable subgroup of patients. However, additional treatment strategies are probably required to achieve elimination of apnoea.

Andrew D. Krystal - One of the best experts on this subject based on the ideXlab platform.

  • Eszopiclone treatment for insomnia effect size comparisons in patients with primary insomnia and insomnia with medical and psychiatric comorbidity
    The Primary Care Companion To The Journal of Clinical Psychiatry, 2012
    Co-Authors: Andrew D. Krystal, Holly Huang, Maurizio Fava, Vaughn W Mccall, Hadine Joffe, Claudio N Soares, Todd Grinell, Jacqueline Zummo, William Spalding, Randall Marshall
    Abstract:

    Objective: The purpose of this post hoc analysis was to compare the treatment effect size of Eszopiclone 3 mg for insomnia in patients with a diagnosis of primary insomnia and in several of the psychiatric and medical conditions that are most commonly comorbid with insomnia. Method: Data were analyzed from 5 large, multicenter, randomized, double-blind, placebo-controlled studies of adult outpatients of at least 1 month duration published between 2006 and 2009. Diary-derived indices of sleep and daytime functioning and the Insomnia Severity Index were compared for patients with primary insomnia (DSM-IV-TR criteria, n = 828) and for those with insomnia comorbid with major depressive disorder (MDD, DSM-IV-TR criteria, n = 545), generalized anxiety disorder (GAD, DSM-IV-TR criteria, n = 595), perimenopause/postmenopause (Stages of Reproductive Aging Workshop criteria, n = 410), and rheumatoid arthritis (American College of Rheumatology criteria, n = 153). Cohen d effect sizes were calculated for each individual study as the between-treatment difference score divided by the pooled standard deviation. Results: Effect sizes ranged from 0.40 to 0.69 (small–medium) as early as week 1 and were maintained at 0.26–0.63 at week 4 for sleep latency, wake time after sleep onset, and total sleep time. Sleep latency and total sleep time effect sizes increased from week 1 to week 4 in the primary insomnia group. At week 4, effect sizes on all 3 parameters and the Insomnia Severity Index tended to be highest for the primary insomnia patients and tended to be lowest for patients with comorbid GAD and MDD. The effect sizes for daytime functioning were small for all insomnia patient groups. Conclusions: Eszopiclone 3 mg is an effective treatment for insomnia across 5 clinically diverse patient populations; however, magnitude of effect is mediated by underlying comorbidity and their treatments, with largest measures of effect seen in primary insomnia and lowest in MDD and GAD. These consistent results, and the fact that clinical trials were conducted in patients being treated as appropriate for their comorbid clinical conditions, support the results’ real-world generalizability and utility to clinical practice.

  • a 12 week randomized double blind placebo controlled study evaluating the effect of Eszopiclone 2 mg on sleep wake function in older adults with primary and comorbid insomnia
    Sleep, 2010
    Co-Authors: Sonia Ancoliisrael, Kendyl Schaefer, Robert Rubens, Andrew D. Krystal, Amy Wilson, Raymond Claus, Vaughn W Mccall, Thomas Roth
    Abstract:

    Background: Longer-term pharmacologic studies for insomnia in older individuals are sparse. Objective: To evaluate the efficacy and safety of 12 weeks of nightly Eszopiclone in elderly outpatients with insomnia. Methods: Participants (65-85 years) met DSM-IV-TR criteria for insomnia with total sleep times (TST) ≤ 6 h, and wake time after sleep onset (WASO) ≥ 45 min. Participants were randomized to 12 weeks of Eszopiclone 2 mg (n = 194) or placebo (n = 194), followed by a 2-week single-blind placebo run-out. Subject-reported measures of sleep (sTST, sleep latency [sSL], sWASO) and daytime function (alertness, concentration, well-being, ability to function) were assessed. AEs were monitored. Results: Subjects treated with 2 mg Eszopiclone slept longer at night on average and at every individual time point compared to baseline than placebo subjects, as measured by TST over the 12-week double-blind period (P < 0.0001). Mean sTST over the double-blind period for Eszopiclone-treated subjects was 360.08 min compared to 297.86 min at baseline, a mean change of 63.24 min. Over the double-blind period, Eszopiclone-treated subjects also experienced a significantly greater improvement in sSL compared to placebo, with a mean decrease of 24.62 min versus a mean decrease of 19.92 min, respectively (P = 0.0014). Eszopiclone subjects also experienced a significantly greater decrease in WASO (mean decrease of 36.4 min) compared to placebo subjects (decrease of 14.8 min) (P < 0.0001). Post-discontinuation, sleep parameters were statistically improved versus baseline for Eszopiclone (P-values ≤ 0.01), indicating no rebound. The most common AEs (≥ 5%) were headache (Eszopiclone 13.9%, placebo 12.4%), unpleasant taste (12.4%, 1.5%), and nasopharyngitis (5.7%, 6.2%). Conclusion: In this Phase IV trial of older adults with insomnia, Eszopiclone significantly improved patient-reported sleep and daytime function relative to placebo. Improvements occurred within the first week and were maintained for 3 months, with no evidence of rebound insomnia following discontinuation. The 12 weeks of treatment were well tolerated. Clinical Trial Information: A Long-Term Safety and Efficacy Study of Eszopiclone in Elderly Subjects With Primary Chronic Insomnia; Registration #NCT00386334; URL - http://www.clinicaltrials.gov/ct2/show/NCT00386334?term=Eszopiclone&rank=24.

  • nightly treatment of primary insomnia with Eszopiclone for six months effect on sleep quality of life and work limitations
    Sleep, 2007
    Co-Authors: Andrew D. Krystal, Kendyl Schaefer, Thomas Wessel, Judy Caron, David A. Amato, James M. Roach, Robert Rubens, Gene Wallenstein, Thomas Roth
    Abstract:

    Study Objectives: To evaluate 6 months' Eszopiclone treatment upon patient-reported sleep, fatigue and sleepiness, insomnia severity, quality of life, and work limitations.

  • Eszopiclone co-administered with fluoxetine in patients with insomnia coexisting with major depressive disorder.
    Biological Psychiatry, 2006
    Co-Authors: Maurizio Fava, Thomas Wessel, Judy Caron, David A. Amato, W. Vaughn Mccall, Robert Rubens, Andrew D. Krystal, Thomas Roth
    Abstract:

    Background Insomnia and major depressive disorder (MDD) can coexist. This study evaluated the effect of adding Eszopiclone to fluoxetine. Methods Patients who met DSM-IV criteria for both MDD and insomnia ( n = 545) received morning fluoxetine and were randomized to nightly Eszopiclone 3 mg (ESZ+FLX) or placebo (PBO+FLX) for 8 weeks. Subjective sleep and daytime function were assessed weekly. Depression was assessed with the 17-item Hamilton Rating Scale for Depression (HAM-D-17) and the Clinical Global Impression Improvement (CGI-I) and Severity items (CGI-S). Results Patients in the ESZ+FLX group had significantly decreased sleep latency, wake time after sleep onset (WASO), increased total sleep time (TST), sleep quality, and depth of sleep at all double-blind time points (all p p = .01) with progressive improvement at Week 8 ( p = .002); significantly improved CGI-I and CGI-S scores at all time points beyond Week 1 ( p p = .009) and remitters (42% vs. 33%; p = .03) at Week 8. Treatment was well tolerated, with similar adverse event and dropout rates. Conclusions In this study, Eszopiclone/fluoxetine co-therapy was relatively well tolerated and associated with rapid, substantial, and sustained sleep improvement, a faster onset of antidepressant response on the basis of CGI, and a greater magnitude of the antidepressant effect.

  • an evaluation of the efficacy and safety of Eszopiclone over 12 months in patients with chronic primary insomnia
    Sleep Medicine, 2005
    Co-Authors: Thomas Roth, Thomas Wessel, James K Walsh, Andrew D. Krystal, Timothy Roehrs
    Abstract:

    Abstract Background and purpose A double-blind placebo-controlled study of Eszopiclone found significant, sustained improvement in sleep and daytime function. The 6-month open-label extension phase is described herein. Patients and methods Adults (21–64) with primary insomnia who reported sleep duration 30 min/night were included. Patient-reported endpoints included sleep and daytime function. Safety and compliance were assessed at monthly clinic visits. The final double-blind month was used as the baseline for efficacy analyses of the open-label period. Results Patients who were initially randomized to double-blind placebo and then switched to open-label Eszopiclone ( n =111) significantly reported the following: (1) decreased sleep latency, wake time after sleep onset, and number of awakenings; (2) increased total sleep time and sleep quality; and (3) improved ratings of daytime ability to function, alertness and sense of physical well-being compared to baseline ( P ≤0.0001 all monthly endpoints). There was no evidence of tolerance on any measure in either group. These subjects ( n =360) sustained the double-blind treatment gains for all sleep and daytime parameters, with further significant improvement in a number of measures. Eszopiclone was well tolerated in both groups; unpleasant taste was the only undesirable effect reported by >5% of patients. Conclusions The significant improvements in sleep and daytime function were evident in those switched from double-blind placebo to 6 months of open-label Eszopiclone therapy and were sustained during the 6 months of open-label treatment for those receiving prior double-blind Eszopiclone. During 12 months of nightly treatment, Eszopiclone 3 mg was well tolerated; tolerance was not observed.