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  • 1.
    Franklin, Karl A.
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Haglund, Bengt
    Axelsson, Susanna
    Holmlund, Thorbjörn
    Rehnqvist, Nina
    Rosen, Måns
    Frequency of serious complications after surgery for snoring and sleep apnea2011In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 131, no 3, p. 298-302Article in journal (Refereed)
    Abstract [en]

    Conclusion: No case of death related to surgery in the form of uvulopalatopharyngoplasty, uvulopalatoplasty or nasal surgery for snoring or sleep apnea has been recorded in Sweden among 4876 patients treated between 1997 and 2005. Severe complications of surgery in the peri-and postoperative period, especially in the form of bleedings and infections, were most common after uvulopalatopharyngoplasty, occurring in 3.7%. Objective: To investigate the frequency of serious complications, including death, of surgery for treatment of snoring and sleep apnea. Methods: All Swedish adults who were treated surgically because of snoring or sleep apnea from January 1997 to December 2005 were identified in the National Patient Register. Mortality and serious complications within 30 days from surgery were obtained from the National Cause of Death Register and the National Patient Register. Results: A total of 4876 patients were treated surgically. Uvulopalatopharyngoplasty was performed in 3572 patients, uvulopalatoplasty in 929 patients, and nasal surgery in 375 patients. None of the surgically treated patients died in the peri-and postoperative period. Severe complications, mainly bleedings and infections, were recorded in 37.1 per 1000 patients treated with uvulopalatopharyngoplasty, in 5.6 per 1000 patients after uvulopalatoplasty, and in 8.8 per 1000 patients after nasal surgery.

  • 2.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Evaluation of surgical methods for sleep apnea and snoring2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Snoring and obstructive sleep apnea (OSA) are both common disorders with a number of negative health effects. The safety and efficacy of treating snoring and OSA surgically have been questioned and there has been a lack of studies in the field. Aims: 1) To investigate the frequency of serious complications, including death, after surgery for the treatment of snoring and sleep apnea; 2) to evaluate the effect on daytime sleepiness after radiofrequency surgery of the soft palate in snoring men with mild or no OSA; 3) to evaluate the effect of tonsillectomy on sleep apnea in adults with OSA and tonsillar hypertrophy; 4) to investigate the morphology and cytoarchitecture of muscle fibers in human soft palatal muscles with immunohistochemical and morphological techniques. Methods and results: In paper 1, a retrospective database study. All Swedish adults who were treated surgically because of snoring or OSA from January 1997 to December 2005 were identified in the National Patient Register. None of the surgically treated patients died in the peri- and postoperative period. Severe complications were recorded in 37.1 of 1,000 patients treated with uvulopalatopharyngoplasty (UPPP), in 5.6 of 1,000 patients after uvulopalatoplasty (UPP) and in 8.8 of 1,000 patients after nasal surgery. In paper 2, the study was designed as a randomized, controlled trial. 35 snoring men with mild or no OSA were randomized to either radiofrequency or sham surgery of the soft palate. Radiofrequency surgery was not found to be effective since there was no significant difference between the two groups in relation to the Epworth Sleepiness Scale (ESS) or apnea-hypopnea index (AHI) at follow-up. Paper 3 was a prospective study, including 28 patients with an AHI of >10 and with large tonsils. In these patients, tonsillectomy was an effective treatment for OSA; the mean AHI was reduced from 40 units/h to 7 units/h (p<0.001), and the mean ESS was reduced from 10.1 to 6.0 (p<0.001) at the six-month follow-up after surgery. Minor and moderate swallowing dysfunction was found in seven of eight patients investigated before surgery and the swallowing function improved in 5 of them after surgery, while no one deteriorated. In paper 4, we investigated the morphology and cytoarchitecture in normal soft palate muscles. Human limb muscles were used as reference. The findings showed that the soft palate muscle fibers have a cytoskeletal architecture and cellmembrane complex that differs from that of the limb muscles. Conclusions No case of death related to surgery was found among 4,876 patients treated with UPPP, UPP or nasal surgery for snoring or OSA in Sweden between 1997 and 2005. Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring or apnea frequency in snoring men with mild or no OSA. Tonsillectomy can be an effective treatment for OSA in adults with large tonsils. A subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

  • 3.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindqvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Larsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sahlin, C.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tonsillectomy in adults with obstructive sleep apnea2016In: Journal of Sleep Research, ISSN 0962-1105, E-ISSN 1365-2869, Vol. 25, p. 161-161Article in journal (Other academic)
  • 4.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Lindqvist, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Larsson, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Sahlin-Ingridsson, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Tonsillectomy in adults with obstructive sleep apnea2016In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 126, no 12, p. 2859-2862Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis To study whether tonsillectomy is effective on obstructive sleep apnea (OSA) in adults with large tonsils. Study Design A multicenter prospective interventional study. Methods The study comprised 28 patients with OSA, an apnea-hypopnea index of > 10, large tonsils (Friedman tonsil size 3 and 4), and age 18 to 59 years. They were derived from 41 consecutive males and females with large tonsils referred for a suspicion of sleep apnea to the ear, nose, and throat departments in Umea, Skelleftea, and Sunderbyn in northern Sweden. The primary outcome was the apnea-hypopnea index, measured with polygraphic sleep apnea recordings 6 months after surgery. Secondary outcomes included daytime sleepiness, as measured with the Epworth Sleepiness Scale, and swallowing function, using video-fluoroscopy. Results The apnea-hypopnea index was reduced from a mean of 40 units per hour (95% confidence interval [CI] 28-51) to seven units per hour (95% CI 3-11), P < 0.001, at the 6-month follow-up after surgery. The apnea-hypopnea index was reduced in all patients and 18 (64%) were cured. The Epworth Sleepiness Scale was reduced from a mean of 11 (95% CI 8-13) to 6.0 (95% CI 4-7), P < 0.001. A swallowing dysfunction was found in seven of eight investigated patients before surgery. Of those, swallowing function improved in five patients after surgery, whereas no one deteriorated. Conclusion Tonsillectomy may be effective treatment for adult patients with OSA and large tonsils. Tonsillectomy may be suggested for adults with OSA and large tonsils. Level of Evidence 4.

  • 5.
    Holmlund, Thorbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Effects of Radiofrequency versus Sham Surgery of the Soft Palate on Daytime Sleepiness2014In: The Laryngoscope, ISSN 0023-852X, E-ISSN 1531-4995, Vol. 124, no 10, p. 2422-2426Article in journal (Refereed)
    Abstract [en]

    Objectives/Hypothesis: To evaluate the effect of radiofrequency surgery of the soft palate on daytime sleepiness in snoring men with mild or no sleep apnea Study design: Randomized controlled trial Methods: Thirty-five men were recruited from consecutive patients referred to the Ear, Nose and Throat Clinic due to snoring and complaints of daytime sleepiness. The inclusion criteria were an apnea-hypopnea index of ≤ 15, male gender and age 18-65 years. Patients were randomized to either radiofrequency or sham surgery of the soft palate. All but one chose and received the option of three treatments. All patients participated in a follow-up including an overnight sleep apnea recording and questionnaires 12 months after the last treatment. The primary outcome was daytime sleepiness measured with the Epworth Sleepiness Scale (ESS) and other questionnaires. Secondary outcomes were effects on the apnea-hypopnea index and subjective snoring. Results: Thirty-two of 35 patients, 19 of 20 in the radiofrequency surgery group and 13 of 15 in the sham surgery group, completed the study. No differences between the two groups in relation to the ESS or apnea-hypopnea index were found at follow-up. Conclusion: Radiofrequency surgery of the soft palate has no effect on daytime sleepiness, snoring or apnea frequency in snoring men with mild or no sleep apnea, one year after surgery.

  • 6.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Unique expression of cytoskeletal proteins in human soft palate muscles2016In: Journal of Anatomy, ISSN 0021-8782, E-ISSN 1469-7580, Vol. 228, no 3, p. 487-494Article in journal (Refereed)
    Abstract [en]

    The human oropharyngeal muscles have a unique anatomy with diverse and intricate functions. To investigate if this specialization is also reflected in the cytoarchitecture of muscle fibers, intermediate filament proteins and the dystrophin-associated protein complex have been analyzed in two human palate muscles, musculus uvula (UV) and musculus palatopharyngeus (PP), with immunohistochenmical and morphological techniques. Human limb muscles were used as reference. The findings show that the soft palate muscle fibers have a cytoskeletal architecture that differs from the limb muscles. While all limb muscles showed immunoreaction for a panel of antibodies directed against different domains of cytoskeletal proteins desmin and dystrophin, a subpopulation of palate muscle fibers lacked or had a faint immunoreaction for desmin (UV 11.7% and PP 9.8%) and the C-terminal of the dystrophin molecule (UV 4.2% and PP 6.4%). The vast majority of these fibers expressed slow contractile protein myosin heavy chain I. Furthermore, an unusual staining pattern was also observed in these fibers for β-dystroglycan, caveolin-3 and neuronal nitric oxide synthase nNOS, which are all membrane-linking proteins associated with the dystrophin C-terminus. While the immunoreaction for nNOS was generally weak or absent, β-dystroglycan and caveolin-3 showed a stronger immunostaining. The absence or a low expression of cytoskeletal proteins otherwise considered ubiquitous and important for integration and contraction of muscle cells indicate a unique cytoarchitecture designed to meet the intricate demands of the upper airway muscles. It can be concluded that a subgroup of muscle fibers in the human soft palate appears to have special biomechanical properties, and their unique cytoarchitecture must be taken into account while assessing function and pathology in oropharyngeal muscles.

  • 7.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Jaghagen, Eva Levring
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Neurotrophic factor BDNF is upregulated in soft palate muscles of snorers and sleep apnea patients2019In: Laryngoscope Investigative Otolaryngology, ISSN 2378-8038, Vol. 4, no 1, p. 174-180Article in journal (Refereed)
    Abstract [en]

    Objectives: Neuromuscular injuries are suggested to contribute to upper airway collapse and swallowing dysfunction in patients with sleep apnea. Neurotrophins, a family of proteins involved in survival, development, and function of neurons, are reported to be upregulated in limb muscle fibers in response to overload and nerve damage. We aimed to investigate the expression of two important neurotrophins, brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), in muscle fibers of uvula from snorers and sleep apnea patients and to compare these findings with pharyngeal function.

    Methods: Uvula muscle biopsies from 22 patients and 10 controls were analyzed for BDNF, NGF, and cytoskeletal protein desmin using immunohistochemistry. Pharyngeal swallowing function was assessed using videoradiography.

    Results: BDNF, but not NGF, was significantly upregulated in a subpopulation of muscle fibers in snoring and sleep apnea patients. Two major immunoreaction patterns for BDNF were observed; a fine grainy point like BDNF staining was displayed in muscle fibers of both patients and controls (41 +/- 23 vs. 25 +/- 17%, respectively, P = .06), while an abnormal upregulated intense-dotted or disorganized reaction was mainly observed in patients (8 +/- 8 vs. 2 +/- 2%, P = .02). The latter fibers, which often displayed an abnormal immunoreaction for desmin, were more frequent in patients with than without swallowing dysfunction (10 +/- 8 vs. 3 +/- 3%, P = .05).

    Conclusion: BDNF is upregulated in the upper airway muscles of snorers and sleep apnea patients, and especially in patients with swallowing dysfunction. Upregulation of BDNF is suggested to be a response to denervation, reinnervation, and repair of injured muscle fibers. Our findings propose that damaged upper airway muscles might heal following treatment for snoring and sleep apnea.

  • 8.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Upregulated expression of brain-derived neurotrophic factor in soft palate muscles of snorers and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 9.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin abnormalities in upper airway muscles of snorers and patients with sleep apnea2019In: Respiratory Research, ISSN 1465-993X, Vol. 20, article id 31Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of obstruction and swallowing dysfunction in snores and sleep apnea patients remains unclear. Neuropathy and to some extent myopathy have been suggested as contributing causes. Recently we reported an absence and an abnormal isoform of two cytoskeletal proteins, desmin, and dystrophin, in upper airway muscles of healthy humans. These cytoskeletal proteins are considered vital for muscle function. We aimed to investigate for muscle cytoskeletal abnormalities in upper airways and its association with swallowing dysfunction and severity of sleep apnea. Cytoskeletal proteins desmin and dystrophin were morphologically evaluated in the uvula muscle of 22 patients undergoing soft palate surgery due to snoring and sleep apnea and in 10 healthy controls. The muscles were analysed with immunohistochemical methods, and swallowing function was assessed using videoradiography. Desmin displayed a disorganized pattern in 21 +/- 13% of the muscle fibres in patients, while these fibers were not present in controls. Muscle fibres lacking desmin were present in both patients and controls, but the proportion was higher in patients (25 +/- 12% vs. 14 +/- 7%, p = 0.009). The overall desmin abnormalities were significantly more frequent in patients than in controls (46 +/- 18% vs. 14 +/- 7%, p < 0.001). In patients, the C-terminus of the dystrophin molecule was absent in 19 +/- 18% of the desmin-abnormal muscle fibres. Patients with swallowing dysfunction had 55 +/- 10% desmin-abnormal muscle fibres vs. 22 +/- 6% in patients without swallowing dysfunction, p = 0.002. Cytoskeletal abnormalities in soft palate muscles most likely contribute to pharyngeal dysfunction in snorers and sleep apnea patients. Plausible causes for the presence of these abnormalities is traumatic snoring vibrations, tissue stretch or muscle overload.

  • 10.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Franklin, Karl
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Desmin and dystrophin myopathy in the upper airway of snoring and obstructive sleep apnea patientsManuscript (preprint) (Other academic)
  • 11.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann Cell Degeneration in Nerves of Upper Airway Relates to Pharyngeal Dysfunction in Snorers and Patients With Sleep Apnea2018In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 154, no 5, p. 1091-1098Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The pathophysiologic mechanism of nocturnal obstruction and swallowing dysfunction commonly occurring in patients with sleep apnea is unclear. The goal of this study was to investigate whether nerve injuries in the upper airways of snorers and patients with sleep apnea are associated with pharyngeal dysfunction and severity of sleep apnea.

    METHODS: Twenty-two patients undergoing palatal surgery due to snoring and sleep apnea were investigated for a swallowing dysfunction by using videoradiography. Twelve healthy nonsnoring subjects were included as control subjects. Tissue samples from the soft palate at the base of the uvula were obtained in all patients and control subjects. Nerves and muscle were analyzed with immunohistochemical and morphologic methods, and the findings were correlated with swallowing function and degree of sleep apnea.

    RESULTS: In the soft palate of patients, nerve fascicles exhibited a significantly lower density of axons (5.4 vs 17.9 x 10(-3) axons/mu m(2); P = .02), a smaller percentage area occupied by Schwann cells (17.5% vs 45.2%; P = .001) and a larger number of circular shaped Schwann cells lacking central axons (43.0% vs 12.7%; P < 0.001) compared with control subjects. The low density of axons was significantly related to degree of swallowing dysfunction (r = 0.5; P = .03) and apnea-hypopnea index > 5 (P = .03). Regenerating axons were frequently observed in patients compared with control subjects (11.3 +/- 4.2% vs 4.8 +/- 2.4%; P = .02).

    CONCLUSIONS: Axon degeneration in preterminal nerves of the soft palate is associated with pharyngeal dysfunction in snorers and patients with sleep apnea. The most likely cause for the nerve injuries is traumatic snoring vibrations and tissue stretch, leading to swallowing dysfunction and increased risk for upper airway obstruction during sleep.

  • 12.
    Shah, Farhan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Laboratory of Muscle Biology, IMB, Umeå University.
    Holmlund, Thorbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Levring Jäghagen, Eva
    Umeå University, Faculty of Medicine, Department of Odontology.
    Berggren, Diana
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Otorhinolaryngology.
    Franklin, Karl A.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Forsgren, Sture
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Axon and Schwann cell degeneration in nerves of upper airway relates to pharyngeal dysfunction in snorers and sleep apnea patientsManuscript (preprint) (Other academic)
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