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JAMA Otolaryngology-- Head & Neck... Jun 2023Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).
IMPORTANCE
Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).
OBJECTIVE
To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023.
INTERVENTION
Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively.
MAIN OUTCOMES AND MEASURES
Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale).
RESULTS
Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02263859.
Topics: Humans; Female; Middle Aged; Male; Hypoglossal Nerve; Quality of Life; Sleepiness; Sleep Apnea, Obstructive; Sleep Apnea Syndromes
PubMed: 37022679
DOI: 10.1001/jamaoto.2023.0161 -
Neurology Mar 2023Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the...
BACKGROUND AND OBJECTIVES
Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD).
METHODS
We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD.
RESULTS
We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD ( ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance.
DISCUSSION
Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.
Topics: Humans; Neuromyelitis Optica; Multiple Sclerosis; Immunoglobulin G; Retrospective Studies; Sleepiness; Aquaporin 4; Myelin-Oligodendrocyte Glycoprotein; Recurrence; Autoantibodies
PubMed: 36690455
DOI: 10.1212/WNL.0000000000206820 -
Sleep Jun 2022To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial.
METHODS
Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments.
RESULTS
In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105). For the three coprimary endpoints and Epworth Sleepiness Scale, all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). For ON-SXB 9 g versus placebo, increase in mean sleep latency was 10.8 versus 4.7 min (Least squares mean difference, LSMD [95% CI], 6.13 [3.52 to 8.75]), 72.0% versus 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76 to 11.23]), change in mean weekly number of cataplexy attacks was -11.5 versus -4.9 (LSMD [95% CI], -6.65 [-9.32 to -3.98]), and change in Epworth Sleepiness Scale was -6.5 and -2.7 (LSMD [95% CI], -6.52 [-5.47 to -2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis.
CONCLUSIONS
ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT02720744, https://clinicaltrials.gov/ct2/show/NCT02720744.
Topics: Cataplexy; Double-Blind Method; Humans; Narcolepsy; Sleepiness; Sodium Oxybate; Treatment Outcome; Wakefulness
PubMed: 34358324
DOI: 10.1093/sleep/zsab200 -
The Journal of Clinical Psychiatry Oct 2022Determine if sublingual dexmedetomidine, a selective α adrenergic receptor agonist, reduces symptoms of acute agitation associated with schizophrenia or... (Randomized Controlled Trial)
Randomized Controlled Trial
Determine if sublingual dexmedetomidine, a selective α adrenergic receptor agonist, reduces symptoms of acute agitation associated with schizophrenia or schizoaffective disorder. This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults diagnosed with schizophrenia or schizoaffective disorder per the , Fifth Edition () criteria. The study was conducted at 15 US sites between January 23, 2020, and May 8, 2020. Participants were randomized to sublingual dexmedetomidine 180 μg, 120 μg, or matching placebo. The primary efficacy endpoint was mean change from baseline in the Positive and Negative Syndrome Scale-Excited Component (PEC) total score at 2 hours postdose. Altogether, 380 participants (mean age 45.6 years, 63.4% identifying as male, 77.9% identifying as Black or African American) were randomized; 380 (100%) self-administered study medication, and 372 (97.9%) completed the study. The mean PEC total score at baseline (17.6) indicated mild to moderate agitation. At 2 hours postdose, the least squares mean changes (SE) from baseline were -10.3 (0.4) for sublingual dexmedetomidine 180 μg, -8.5 (0.4) for 120 μg, and -4.8 (0.4) for placebo. Least squares mean differences (97.5% confidence intervals) in the sublingual dexmedetomidine groups were -5.5 (-6.7 to -4.3) for 180 μg and -3.7 (-4.9 to -2.5) for 120 μg (both < .001 vs placebo). The most commonly encountered adverse events with dexmedetomidine (incidence ≥ 5% and ≥ 2× rate observed with placebo) were somnolence, dry mouth, and hypotension for the 120 μg dose, and somnolence, dizziness, orthostatic hypotension, and oral hypoesthesia for the 180 μg dose. Treatment with sublingual dexmedetomidine 180 μg or 120 μg was more efficacious than placebo in reducing acute agitation associated with schizophrenia as measured by PEC scores at 2 hours postdose. ClinicalTrials.gov identifier: NCT04268303.
Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Antipsychotic Agents; Dexmedetomidine; Double-Blind Method; Humans; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Sleepiness; Treatment Outcome
PubMed: 36198061
DOI: 10.4088/JCP.22m14447 -
JAMA Sep 2020Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.
IMPORTANCE
Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated.
OBJECTIVE
To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018.
INTERVENTIONS
Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51).
MAIN OUTCOMES AND MEASURES
Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS.
RESULTS
Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood).
CONCLUSIONS AND RELEVANCE
In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.
Topics: Adult; Blood Pressure; Continuous Positive Airway Pressure; Female; Humans; Male; Middle Aged; Oxygen; Palate, Soft; Polysomnography; Self Report; Severity of Illness Index; Sleep Apnea, Obstructive; Sleep Latency; Sleepiness; Tongue
PubMed: 32886102
DOI: 10.1001/jama.2020.14265 -
Epilepsy Research Aug 2019Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which... (Clinical Trial)
Clinical Trial
BACKGROUND
Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.
METHODS
Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2-10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25-50 mg/kg/day. Patient visits were every 2-4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks.
RESULTS
Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0-10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1-146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%).
CONCLUSIONS
Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.
Topics: Adolescent; Adult; Anticonvulsants; Cannabidiol; Child; Child, Preschool; Diarrhea; Drug Resistant Epilepsy; Duration of Therapy; Epilepsies, Myoclonic; Female; Humans; Infant; Lennox Gastaut Syndrome; Male; Middle Aged; Sleepiness; Treatment Outcome; Young Adult
PubMed: 31022635
DOI: 10.1016/j.eplepsyres.2019.03.015 -
Journal of Global Health Dec 2023Unhealthy lifestyle and diet may contribute to the development of cardiovascular disease (CVD), but limited evidence exists regarding the association between sleep...
Interplay of sleep patterns and oxidative balance score on total cardiovascular disease risk: Insights from the National Health and Nutrition Examination Survey 2005-2018.
BACKGROUND
Unhealthy lifestyle and diet may contribute to the development of cardiovascular disease (CVD), but limited evidence exists regarding the association between sleep patterns, oxidative stress-related exposures to diet and lifestyle, and CVD risk.
METHODS
We analysed data from 10 212 adults in the National Health and Nutrition Examination Survey (NHANES) database (2005-2018). Self-report questionnaires were used to collect data on sleep duration, sleepiness, and trouble sleeping, classified into three categories: healthy, intermediate, and poor sleep patterns. Healthy sleep was defined as sleeping seven to nine hours per night with no self-reported sleepiness or trouble sleeping, while intermediate and poor sleep patterns indicated one and two to three sleep problems, respectively. The oxidative balance score (OBS) was calculated based on twenty oxidative stress-related exposures to dietary and lifestyle factors, with a higher score indicating greater antioxidant exposure. Survey-based multivariable-adjusted regression analysis was conducted to examine the association of sleep patterns or OBS alone and combined with the total and specific CVD risk.
RESULTS
Participants with poor sleep patterns had a higher likelihood of developing CVD (odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.26-2.45, P < 0.05), while an inverse association was found between OBS and CVD risk (quartile (Q) 4 vs Q1: OR = 0.67; 95% CI = 0.47-0.94, P = 0.02, P for trend <0.05). There was an interaction between sleep patterns and OBS (P for interaction = 0.03). Participants with unhealthy (intermediate and poor) sleep patterns and pro-oxidant OBS (Q1 and Q2) were significantly associated with increased risk of total CVD (OR = 2.31; 95% CI = 1.42-3.74, P < 0.05), as well as angina and congestive heart failure, but not coronary heart disease (CHD). Stratified analysis showed that among individuals without hyperlipidaemia, participants with both unhealthy sleep patterns and pro-oxidant OBS exhibited a higher risk of CHD compared to those with healthy sleep patterns and antioxidative OBS.
CONCLUSIONS
Unhealthy sleep patterns and reduced oxidative balance are positively associated with an increased risk of overall and specific CVD. Interventions that target healthy sleep habits and antioxidant-rich diets and lifestyles may be important for reducing the risk of CVD.
Topics: Adult; Humans; Nutrition Surveys; Cardiovascular Diseases; Antioxidants; Reactive Oxygen Species; Risk Factors; Sleepiness; Oxidative Stress; Sleep
PubMed: 38085249
DOI: 10.7189/jogh.14.04170 -
Drugs & Aging Oct 2022The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults').
METHODS
Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness.
RESULTS
At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour.
CONCLUSIONS
In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg. Older patients particularly require this dose to improve daytime functioning. Older patients are not at an increased risk of adverse events or residual effects the next morning after night-time administration of daridorexant, even at 50 mg. The dose of daridorexant does not need to be decreased for older patients.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov (NCT03545191) [first posted: 4 June, 4 2018], https://clinicaltrials.gov/ct2/show/NCT03545191 .
Topics: Aged; Double-Blind Method; Humans; Imidazoles; Lipopolysaccharides; Orexin Receptor Antagonists; Pyrrolidines; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome
PubMed: 36098936
DOI: 10.1007/s40266-022-00977-4 -
American Journal of Respiratory and... Sep 2022Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Here, in this analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; : = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) ( < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; = 0.6). The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.
Topics: Adult; Aged; Continuous Positive Airway Pressure; Coronary Artery Disease; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Prospective Studies; Sleep Apnea, Obstructive; Sleepiness; Treatment Outcome
PubMed: 35579605
DOI: 10.1164/rccm.202111-2608OC -
Sleep Advances : a Journal of the Sleep... 2023Drowsiness associated with sleep loss and circadian misalignment is a risk factor for accidents and human error. The percentage of time that the eyes are more than 80%... (Review)
Review
Drowsiness associated with sleep loss and circadian misalignment is a risk factor for accidents and human error. The percentage of time that the eyes are more than 80% closed (PERCLOS) is one of the most validated indices used for the passive detection of drowsiness, which is increased with sleep deprivation, after partial sleep restriction, at nighttime, and by other drowsiness manipulations during vigilance tests, simulated driving, and on-road driving. However, some cases have been reported wherein PERCLOS was not affected by drowsiness manipulations, such as in moderate drowsiness conditions, in older adults, and during aviation-related tasks. Additionally, although PERCLOS is one of the most sensitive indices for detecting drowsiness-related performance impairments during the psychomotor vigilance test or behavioral maintenance of wakefulness test, no single index is currently available as an optimal marker for detecting drowsiness during driving or other real-world situations. Based on the current published evidence, this narrative review suggests that future studies should focus on: (1) standardization to minimize differences in the definition of PERCLOS between studies; (2) extensive validation using a single device that utilizes PERCLOS-based technology; (3) development and validation of technologies that integrate PERCLOS with other behavioral and/or physiological indices, because PERCLOS alone may not be sufficiently sensitive for detecting drowsiness caused by factors other than falling asleep, such as inattention or distraction; and (4) further validation studies and field trials targeting sleep disorders and trials in real-world environments. Through such studies, PERCLOS-based technology may contribute to preventing drowsiness-related accidents and human error.
PubMed: 37193281
DOI: 10.1093/sleepadvances/zpad006