Clinicaltrials.gov identifier NCT01681121.

Excessive sleepiness (ES), one of the main presenting symptoms of OSA, is estimated to persist in 12% to 65% of individuals receiving CPAP therapy. 1-4 The effect of ES on individuals with OSA includes functional impairment, reduced quality of life, and increased risk for occupational and motor vehicle accidents. 5-9 Solriamfetol (formerly known as JZP-110 and ADX-N05) is a selective dopamine and norepinephrine reuptake inhibitor with robust wake-promoting effects. Its mechanism of action differs from those of amphetamines, modafinil, and armodafinil. 10 Solriamfetol demonstrated significant efficacy relative to placebo for reducing ES and increasing wakefulness in clinical trials of narcolepsy. 11-13 Efficacy for ES in OSA also was demonstrated by solriamfetol in a 12-week randomized, controlled phase III study. 14 This phase III trial evaluated the maintenance of efficacy and safety of solriamfetol administered once daily compared with placebo for the treatment of ES in adults with OSA. Methods Study Design This was a clinical trial from the Treatment of OSA and Narcolepsy Excessive Sleepiness (TONES) phase III program, the TONES 4 study. This phase III, double-blind, placebo-controlled trial was performed from May 2015 to November 2016 in Finland, France, Germany, Sweden, and the United States. An enriched, randomized withdrawal design was used. The study was approved by the appropriate institutional review boards or independent ethics committees (e-Appendix 1) and was conducted in accordance with the amended Declaration of Helsinki; all participants provided written informed consent (ClinicalTrials. gov identifier NCT02348619; EudraCT number 2014-005515-16). FUNDING/SUPPORT: This study was supported by Jazz Pharmaceuticals. In 2014, Jazz Pharmaceuticals acquired a license to develop and commercialize solriamfetol from Aerial Biopharma. Jazz Pharmaceuticals has worldwide development, manufacturing, and commercialization rights to solriamfetol, excluding certain jurisdictions in Asia. SK Biopharmaceuticals, the discoverer of the compound (also known as SKL-N05), maintains rights in 12 Asian markets, including Korea, China and Japan. Editorial assistance in formatting, proofreading, copyediting, and fact-checking was provided by The Curry Rockefeller Group LLC. Jazz Pharmaceuticals provided funding to The Curry Rockefeller Group LLC for writing and editorial support. *Collaborators from the Tones 4 Study Investigators group are listed in the Acknowledgments.

Persons residing at high altitude who develop excessive polycythemia are more hypoxemic than normal high-altitude residents. We investigated the causes of hypoxemia in 20 patients with excessive polycythemia residing at an altitude of 3,100 m. Lung disease evidenced by abnormal spirometric features and results of a respiratory questionnaire was present in 10 of 20 patients and resulted in increased alveolar-arterial difference for PO2 [(A-a)PO2]. The excessive hypoxemia in the patients with normal lungs was not due to increased (A-a)PO2. We measured ventilatory responses to hypoxia and to hypercapnia to determine whether blunting of these responses was a cause of this excessive hypoxemia. We found, however, that chemical drives to breathe, although blunted, were the same in patients with polycythemia as in high-altitude control subjects. However, an abnormal breathing pattern was observed; the polycythemic patients had a smaller tidal volume and a greater ratio of dead space to tidal volume than did the normal subjects. In addition, the polycythemic patients had increased minute ventilation on breathing 100 percent O2, whereas the normal subjects did not. Thus, hypoxic depression of ventilation may have been present. Our findings suggested that blunted chemical drives are not causative in this disease, and that some other cause of hypoxemia must be present.

Study Objectives: Compare treatment efficacy and objective adherence between the NightBalance sleep position treatment (SPT) device and auto-adjusting positive airway pressure (APAP) in patients with exclusive positional obstructive sleep apnea (ePOSA) defined as a supine apnea-hypopnea index (sAHI) ≥ 2 times the nonsupine AHI (nsAHI) and a nsAHI < 10 events/h. Methods: This prospective multicenter randomized crossover trial enrolled treatment naive participants with ePOSA (AHI ≥ 15 events/h and nsAHI < 10 events/h) or (AHI > 10 and < 15 events/h with daytime sleepiness and nsAH < 5 events/h). Polysomnography and objective adherence determination (device data) were performed at the end of each 6-week treatment. Patient device preference was determined at the end of the study. Results: A total of 117 participants were randomized (58 SPT first, 59 APAP first). Of these, 112 started treatment with the second device (adherence cohort) and 110 completed the study (AHI cohort). The AHI on SPT was higher (mean ± standard deviation, 7.29 ± 6.8 versus 3.71 ± 5.1 events/h, P < .001). The mean AHI difference (SPT-APAP) was 3.58 events/h with a one sided 95% confidence interval upper bound of 4.96 events/h (< the prestudy noninferiority margin of 5 events/h). The average nightly adherence (all nights) was greater on SPT (345.3 ± 111.22 versus 286.98 ± 128.9 minutes, P < .0001). Participants found the SPT to be more comfortable and easier to use and 53% reported a preference for SPT assuming both devices were equally effective. Conclusions: Treatment with SPT resulted in non-inferior treatment efficacy and greater adherence compared to APAP in ePOSA suggesting that SPT is an effective treatment for this group.

Pulmonary and systemic hemodynamics and arterial blood gases were measured in anesthetized and mechanically ventilated dogs before and after oral or intravenous administration of ethanol. Increases in mean pulmonary artery pressure and pulmonary vascular resistance occurred. Platelet antiserum-induced thrombocytopenia inhibition of prostaglandin synthesis with meclofenamate, or alpha-adrenergic blockade did not alter the pulmonary pressor response to ethanol. However, the increase in resistance following ethanol was abolished by hyperoxia and potentiated by hypoxia. Thus, it appears that the effect of ethanol is to augment hypoxic pulmonary vasoconstriction, whereas ethanol per se has no independent pulmonary pressor activity.