In-home evaluation of efficacy and titration of a mandibular advancement device for obstructive sleep apnea

There is increasing evidence that mandibular advancement devices (MADs) can be an effective treatment for some patients with obstructive sleep apnea, a highly prevalent chronic disease. In this study, the objectives were to objectively assess the effectiveness of MAD therapy using a limited channel recorder, and to develop a model for identifying patients who may be appropriate for MAD therapy as the initial treatment option. Thirty patients were prospectively recruited and studied at two independent dentist offices and the participants’ homes. Subjects wore the ARES Unicorder for two nights before insertion of the MAD, and again when the dentist determined that the patient had reached the titration endpoint. Self-reported measures of depression, sleepiness, and quality of life were obtained pre- and posttreatment. The reviewer was blinded to the study status while the physiological signals were being visually inspected. Significant reductions in the apnea/hypopnea index (AHI), hypoxemia measures, and snoring level were observed posttreatment. Twenty-seven of the 30 (90%) patients had a posttreatment AHI (using a 4% desaturation for hypopneas) below a clinical cut-off of 10. All but one patient (97%) exhibited at least a 50% decrease in AHI or had a posttreatment AHI ≤ 10. Significant differences in body mass index, weight, and neck circumference in patients with posttreatment AHIs above and below a clinical cut-off of five were identified. The linear regression used to predict the posttreatment AHI using pretreatment data resulted in an R2 of 0.68. The model correctly predicted two patients who were unable to obtain a posttreatment AHI of 10 or less. This study was designed to demonstrate two models of collaboration between a dental sleep medicine specialist and a sleep medicine physician in the monitoring of a patient treated with a MAD. The outcome data suggest that the limited channel recording system can be used as an alternative to laboratory polysomnography to reduce the cost of MAD treatment, and to improve the quality and consistency of posttreatment patient care

The impact of viral mutations on recognition by SARS-CoV-2 specific T cells.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.This work is supported by the UK Medical Research Council (MRC); Chinese Academy of Medical Sciences(CAMS) Innovation Fund for Medical Sciences (CIFMS), China; National Institute for Health Research (NIHR)Oxford Biomedical Research Centre, and UK Researchand Innovation (UKRI)/NIHR through the UK Coro-navirus Immunology Consortium (UK-CIC). Sequencing of SARS-CoV-2 samples and collation of data wasundertaken by the COG-UK CONSORTIUM. COG-UK is supported by funding from the Medical ResearchCouncil (MRC) part of UK Research & Innovation (UKRI),the National Institute of Health Research (NIHR),and Genome Research Limited, operating as the Wellcome Sanger Institute. T.I.d.S. is supported by a Well-come Trust Intermediate Clinical Fellowship (110058/Z/15/Z). L.T. is supported by the Wellcome Trust(grant number 205228/Z/16/Z) and by theUniversity of Liverpool Centre for Excellence in Infectious DiseaseResearch (CEIDR). S.D. is funded by an NIHR GlobalResearch Professorship (NIHR300791). L.T. and S.C.M.are also supported by the U.S. Food and Drug Administration Medical Countermeasures Initiative contract75F40120C00085 and the National Institute for Health Research Health Protection Research Unit (HPRU) inEmerging and Zoonotic Infections (NIHR200907) at University of Liverpool inpartnership with Public HealthEngland (PHE), in collaboration with Liverpool School of Tropical Medicine and the University of Oxford.L.T. is based at the University of Liverpool. M.D.P. is funded by the NIHR Sheffield Biomedical ResearchCentre (BRC – IS-BRC-1215-20017). ISARIC4C is supported by the MRC (grant no MC_PC_19059). J.C.K.is a Wellcome Investigator (WT204969/Z/16/Z) and supported by NIHR Oxford Biomedical Research Centreand CIFMS. The views expressed are those of the authors and not necessarily those of the NIHR or MRC

Outcome of hospitalization for COVID-19 in patients with interstitial lung disease. An international multicenter study

Rationale: The impact of coronavirus disease (COVID-19) on patients with interstitial lung disease (ILD) has not been established. Objectives: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age-, sex-, and comorbidity-matched population. Methods: An international multicenter audit of patients with a prior diagnosis of ILD admitted to the hospital with COVID-19 between March 1 and May 1, 2020, was undertaken and compared with patients without ILD, obtained from the ISARIC4C (International Severe Acute Respiratory and Emerging Infection Consortium Coronavirus Clinical Characterisation Consortium) cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished idiopathic pulmonary fibrosis from non–idiopathic pulmonary fibrosis ILD and used lung function to determine the greatest risks of death. Measurements and Main Results: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to the hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching, patients with ILD with COVID-19 had significantly poorer survival (hazard ratio [HR], 1.60; confidence interval, 1.17–2.18; P = 0.003) than age-, sex-, and comorbidity-matched controls without ILD. Patients with an FVC of <80% had an increased risk of death versus patients with FVC ≥80% (HR, 1.72; 1.05–2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR, 2.27; 1.39−3.71). Conclusions: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD

Systemic hypertension and obstructive sleep apnoea.

This article is a review of the current evidence that links systemic hypertension with obstructive sleep apnoea. Whilst a causal association has been suspected for some time, the day to day variability of both blood pressure and sleep apnoea severity, and clustering of confounding cardiovascular risk factors in sleep apnoea patients has made this association difficult to prove. There is unassailable evidence that obstructive apnoeas raise blood pressure acutely in both animal models and humans, through a combination of autonomic and state dependent arousal with some mechanical influences, and these rises can be controlled by nasal continuous positive airway pressure. Thus, although repetitive apnoeas alter the blood pressure variability and raise sleeping blood pressure in patients with OSA and sophisticated animal models have demonstrated increases in daytime blood pressure after the onset of OSA in the short term, such effects on diurnal BP have yet to be proven in humans. Recent rigorously designed large epidemiological studies have proven an independent association between OSA and systemic hypertension in both general and sleep clinic populations, with closely matched case control series also reporting raised blood pressure in OSA patients. A direct temporal causal association between the onset of obstructive sleep apnoea and raised blood pressure is expected to be confirmed by longitudinal data from the continuing epidemiological population studies. Finally, several studies on the beneficial effects of nasal continuous positive airway pressure in reducing blood pressure in OSA patients have preliminary results in abstract form, with one published in full

Sleep studies for sleep apnoea.

Sleep studies have grown to encompass a broad range of technologies employed to study and diagnose a variety of sleep disorders. From their inception in neurophysiology laboratories interested in investigating primary disorders of sleep architecture from psychiatric illness, their remit has widened such that their most common role is currently to diagnose secondary sleep disruption from respiratory, cardiovascular or other systemic causes. This review outlines the pathophysiology of obstructive sleep apnoea in particular and how sleep studies have improved our understanding of the complex dynamic changes in blood gas tensions, cardiovascular control and cerebral arousal that occur with these repetitive events. We review the historical development of standard laboratory-based sleep studies and discuss their limitations in staging sleep, reflecting the episodes of increased upper airway resistance that underlie these disorders and their ability to predict individuals' symptoms or response to medical or surgical therapies. We then describe some alternative signals that have been employed to monitor the physiological changes in upper airway resistance and arousal with a discussion of some of the evidence that these 'limited' studies may provide diagnostic information that can guide clinical decision making and may predict the outcome without the need, in some cases, for more complex and costly laboratory-based studies

A randomized controlled trial of adaptive ventilation for Cheyne-Stokes breathing in heart failure.

Heart failure is associated with Cheyne-Stokes breathing, which fragments patients' sleep. Correction of respiratory disturbance may reduce sleep fragmentation and excessive daytime sleepiness. This randomized prospective parallel trial assesses whether nocturnal-assist servoventilation improves daytime sleepiness compared with the control. A total of 30 subjects (29 male) with Cheyne-Stokes breathing (mean apnea-hypopnea index 19.8 [SD 2.6] and stable symptomatic chronic heart failure (New York Heart Association Class II-IV) were treated with 1 month's therapeutic (n = 15) or subtherapeutic adaptive servoventilation. Daytime sleepiness (Osler test) was measured before and after the trial with change in measured sleepiness the primary endpoint. Secondary endpoints included brain natriuretic peptide levels and catecholamine excretion. Active treatment reduced excessive daytime sleepiness; the mean Osler change was +7.9 minutes (SEM 2.9), when compared with the control, the change was -1.0 minutes (SEM, 1.7), and the difference was 8.9 minutes (95% confidence interval, 1.9-15.9 minutes; p = 0.014, unpaired t test). Significant falls occurred in plasma brain natriuretic peptide and urinary metadrenaline excretion. We conclude that adaptive servoventilation produces an improvement in excessive daytime sleepiness in patients with Cheyne-Stokes breathing and chronic heart failure. This study suggests improvements in neurohormonal activation with this treatment

Ambulatory blood pressure after therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised parallel trial.

BACKGROUND: Obstructive sleep apnoea is associated with raised blood pressure. If blood pressure can be reduced by nasal continuous positive airway pressure (nCPAP), such treatment could reduce risk of cardiovascular disease in patients with obstructive sleep apnoea. Our aim was to see whether nCPAP for sleep apnoea reduces blood pressure compared with the most robust control intervention subtherapeutic nCPAP. METHODS: We did a randomised parallel trial to compare change in blood pressure in 118 men with obstructive sleep apnoea (Epworth score &gt; 9, and a &gt; 4% oxygen desaturation index of &gt; 10 per h) who were assigned to either therapeutic (n=59) or subtherapeutic (59) nCPAP (about 1 cm H(2)O pressure) for 1 month. The primary outcome was the change in 24-h mean blood pressure. Secondary outcomes were changes in systolic, diastolic, sleep, and wake blood pressure, and relations between blood pressure changes, baseline blood pressure, and severity of sleep apnoea. FINDINGS: Therapeutic nCPAP reduced mean arterial ambulatory blood pressure by 2.5 mm Hg (SE 0.8), whereas subtherapeutic nCPAP increased blood pressure by 0.8 mm Hg (0.7) (difference -3.3 [95% CI -5.3 to -1.3]; p=0.0013, unpaired t test). This benefit was seen in both systolic and diastolic blood pressure, and during both sleep and wake. The benefit was larger in patients with more severe sleep apnoea than those who had less severe apnoea, but was independent of the baseline blood pressure. The benefit was especially large in patients taking drug treatment for blood pressure. INTERPRETATION: In patients with most severe sleep apnoea, nCPAP reduces blood pressure, providing significant vascular risk benefits, and substantially improving excessive daytime sleepiness and quality of life