A description of sleep behaviour in healthy late pregnancy, and the accuracy of self-reports.

BACKGROUND: The importance of maternal sleep and its contribution to maternal and fetal health during pregnancy is increasingly being recognised. However, the ability to accurately recall sleep practices during pregnancy has been questioned. The aim of this study is to test the accuracy of recall of normal sleep practices in late pregnancy. METHODS: Thirty healthy women between 35 and 38 weeks of gestation underwent level III respiratory polysomnography (PSG) with infrared digital video recordings in their own homes. Data regarding sleep positions, number of times getting out of bed during the night and respiratory measures were collected. A sleep questionnaire was administered the morning after the recorded sleep. Continuous data were assessed using Spearman's Rho and Bland-Altman. Cohen's Kappa was used to assess recall in the categorical variables. RESULTS: Two-thirds of participants went to sleep on their left side. There was good agreement in sleep onset position between video and questionnaire data (Kappa 0.52), however the there was poor agreement on position on wakening (Kappa 0.24). The number of times getting out of bed during the night was accurately recalled (Kappa 0.65). Twenty five out of 30 participants snored as recorded by PSG. Questionnaire data was inaccurate for this measure. Bland-Altman plots demonstrated acceptable agreement between video and questionnaire data for estimated sleep duration, but not the time taken to fall asleep (sleep latency). One participant had mild obstructive sleep apnoea and another probable high upper airways resistance. CONCLUSIONS: Sleep onset position, sleep duration and the number of times getting out of bed during the night were accurately recalled, but sleep latency and sleep position on waking were not. This study identifies the sleep variables that can be accurately obtained by questionnaire and those that cannot.

Recombinant Alpha-1 Antitrypsin-Fc Fusion Protein INBRX-101 in Adults With Alpha-1 Antitrypsin Deficiency: A Phase 1 Study.

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by low alpha-1 antitrypsin (AAT) levels, predisposing individuals to lung disease. The standard of care, plasma-derived AAT (pdAAT), is delivered as weekly infusions to maintain serum AAT concentrations ≥11µM (≈50% of those in healthy individuals). INBRX-101, a recombinant human AAT-Fc fusion protein, was designed to have a longer half-life and achieve higher AAT levels than pdAAT. Methods: In this phase 1 dose-escalation study (N=31), adults with AATD received 1 dose (part 1) or 3 doses (part 2) of 10 (part 1), 40, 80, or 120mg/kg INBRX-101 every 3 weeks (Q3W) via intravenous infusion. The primary endpoint was safety and tolerability. Secondary endpoints were pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of INBRX-101. Results: INBRX-101 was well tolerated. Most treatment-emergent adverse events were grade ≤2. In part 2 (n=18; each dose, n=6), dose-related increases in serum functional AAT (fAAT) were observed; mean fAAT levels remained above the 21 µM target for up to 4 weeks after the final dose in the 120-mg/kg cohort. Antidrug antibodies had no meaningful impact on PK or PD. INBRX-101 was detected in pulmonary epithelial lining fluid (PELF) from all patients assessed (n=11), and PELF fAAT increased after dosing. PK/PD modeling projected steady-state serum fAAT ≥21µM at 120 mg/kg Q3W (average concentration ≈43µM; trough concentration ≈28µM) and Q4W (≈34µM; ≈21µM). Conclusion: The favorable safety profile and ability to maintain serum fAAT levels >21µM with extended-interval dosing, support a phase 2 trial evaluating Q3W and Q4W dosing of INBRX-101.

Effect of tubing condensate on non-invasive positive pressure ventilators tested under simulated clinical conditions.

RATIONALE: Water condensate in the humidifier tubing can affect bi-level ventilation by narrowing tube diameter and increasing airflow resistance. We investigated room temperature and tubing type as ways to reduce condensate and its effect on bi-level triggering and pressure delivery. In this bench study, the aim was to test the hypothesis that a relationship exists between room temperature and tubing condensate. METHODS: Using a patient simulator, a Res-med bi-level device was set to 18/8 cm H(2)O and run for 6 h at room temperatures of 16°C, 18°C and 20°C. The built-in humidifier was set to a low, medium or high setting while using unheated or insulated tubing or replaced with a humidifier using heated tubing. Humidifier output, condensate, mask pressure and triggering delay of the bi-level were measured at 1 and 6 h using an infrared hygrometer, metric weights, Honeywell pressure transducer and TSI pneumotach. RESULTS: When humidity output exceeded 17.5 mg H(2)O/L, inspiratory pressure fell by 2-15 cm H(2)O and triggering was delayed by 0.2-0.9 s. Heating the tubing avoided any such ventilatory effect whereas warmer room temperatures or insulating the tubing were of marginal benefit. CONCLUSIONS: Users of bi-level ventilators need to be aware of this problem and its solution. Bi-level humidifier tubing may need to be heated to ensure correct humidification, pressure delivery and triggering.

Patent foramen ovale closure in the treatment of obstructive sleep apnea.

Obstructive sleep apnea (OSA) and patent foramen ovale (PFO) are common conditions and may coexist. In patients with OSA, increases in right-to-left shunting across a PFO may result in increased burden of hypoxia, although the effect of this is unknown. We report the cases of 3 patients with highly symptomatic OSA and PFO who underwent percutaneous closure with the Coherex FlatStent PFO Closure System. Although PFO closure can be achieved with minimally invasive techniques and low rates of adverse events, its importance in reducing hypoxia in this population is unknown. PFO closure may result in improvement in apneas and symptoms in selected OSA patients and may impact cardiovascular events in this group through hypoxia-mediated or other unrecognized mechanisms.