Tachypnea Seen During Positive Airway Pressure Titration Studies: A Case Series of Four Patients.

ABSTRACT: We report a case series of four patients where tachypnea was observed during positive airway titration studies, double the baseline breathing rate (tachypnea range 46-68 breaths/min). It happened mainly during non-rapid eye movement to rapid eye movement sleep transitions without significant changes in oxygen saturation or signs of autonomic hyperactivity such as an increased heart rate. The increased respiratory rate may be a normal physiological extreme outlier seen during phasic rapid eye movement sleep triggered by high pressure ventilation and it may also indicate underlying ventilatory instability, making patients predisposed to central sleep apnea.

Physico-chemical properties of manufactured nanomaterials - Characterisation and relevant methods. An outlook based on the OECD Testing Programme.

Identifying and characterising nanomaterials require additional information on physico-chemical properties and test methods, compared to chemicals in general. Furthermore, regulatory decisions for chemicals are usually based upon certain toxicological properties, and these effects may not be equivalent to those for nanomaterials. However, regulatory agencies lack an authoritative decision framework for nanomaterials that links the relevance of certain physico-chemical endpoints to toxicological effects. This paper investigates various physico-chemical endpoints and available test methods that could be used to produce such a decision framework for nanomaterials. It presents an overview of regulatory relevance and methods used for testing fifteen proposed physico-chemical properties of eleven nanomaterials in the OECD Working Party on Manufactured Nanomaterials' Testing Programme, complemented with methods from literature, and assesses the methods' adequacy and applications limits. Most endpoints are of regulatory relevance, though the specific parameters depend on the nanomaterial and type of assessment. Size (distribution) is the common characteristic of all nanomaterials and is decisive information for classifying a material as a nanomaterial. Shape is an important particle descriptor. The octanol-water partitioning coefficient is undefined for particulate nanomaterials. Methods, including sample preparation, need to be further standardised, and some new methods are needed. The current work of OECD's Test Guidelines Programme regarding physico-chemical properties is highlighted.

Effectiveness of Benzodiazepine Receptor Agonists in the Treatment of Insomnia: An Examination of Response and Remission Rates.

Study objectives: To examine the real-world effectiveness of benzodiazepine receptor agonists (BzRAs) by quantifying response and remission rates in a clinical sample receiving chronic BzRA treatment for insomnia. Methods: Participants were outpatients (N = 193; 72% female; 55.2 ± 11.1 year) who had an insomnia diagnosis per medical records, and who were taking a therapeutic dose of BzRA for their insomnia. Endpoints were nocturnal sleep disturbance and Insomnia Severity Index (ISI) scores. A reduction meeting the criterion for the minimally important difference in ISI scores (change ≥ 6) constituted "response"; "remission" was inferred when symptoms fell below the clinical cutoff (ISI < 11). Results: Most participants (71%) used BzRAs at least 5 nights per week. Mean ISI scores were significantly lower (t = 22.31; p < .01) while on BzRAs than when untreated, but remained in the clinical range (mean = 11.0; standard deviation = 5.7). Although 76.7% responded to treatment, only 47.7% remitted. The majority (68.9%) of participants had a sleep-onset latency > 30 minutes and/or wake-time after sleep onset > 60 minutes while on BzRAs. After controlling for gender and insomnia severity when untreated, odds of insomnia persistence despite BzRA use were 2 times higher in patients with comorbid medical [odds ratio (OR) = 2.39; 95% confidence interval (CI) = 1.20% to 4.77%; p < .05] and psychiatric disorders (OR = 2.24; 95% CI = 1.21% to 4.13%; p < .05). Conclusions: This is the first study to distinguish between response and remission in insomnia patients taking BzRAs. Findings suggest that while many insomnia patients respond to chronic BzRA treatment, most do not remit. Remission rates are particularly low for comorbid insomnia, the most prevalent phenotype of the disorder.

A multi-stakeholder perspective on the use of alternative test strategies for nanomaterial safety assessment.

There has been a conceptual shift in toxicological studies from describing what happens to explaining how the adverse outcome occurs, thereby enabling a deeper and improved understanding of how biomolecular and mechanistic profiling can inform hazard identification and improve risk assessment. Compared to traditional toxicology methods, which have a heavy reliance on animals, new approaches to generate toxicological data are becoming available for the safety assessment of chemicals, including high-throughput and high-content screening (HTS, HCS). With the emergence of nanotechnology, the exponential increase in the total number of engineered nanomaterials (ENMs) in research, development, and commercialization requires a robust scientific approach to screen ENM safety in humans and the environment rapidly and efficiently. Spurred by the developments in chemical testing, a promising new toxicological paradigm for ENMs is to use alternative test strategies (ATS), which reduce reliance on animal testing through the use of in vitro and in silico methods such as HTS, HCS, and computational modeling. Furthermore, this allows for the comparative analysis of large numbers of ENMs simultaneously and for hazard assessment at various stages of the product development process and overall life cycle. Using carbon nanotubes as a case study, a workshop bringing together national and international leaders from government, industry, and academia was convened at the University of California, Los Angeles, to discuss the utility of ATS for decision-making analyses of ENMs. After lively discussions, a short list of generally shared viewpoints on this topic was generated, including a general view that ATS approaches for ENMs can significantly benefit chemical safety analysis.

Comparative levels of excessive daytime sleepiness in common medical disorders.

INTRODUCTION: Sleep restriction and sleep disorders are common causes of excessive daytime sleepiness (EDS). Medical disorders (MD) can also cause EDS, but previous studies have used non-standardized measures, selected samples, or have examined EDS in singular disorders. This study describes the relative degree of EDS associated with medical disorders to provide comparative data across a range of common medical conditions in a large unselected community-based sample. METHODS: Responses of 2612 individuals (aged 18-65) were assessed after excluding those with suspected sleep disordered breathing, narcolepsy, and shift workers. Participants across a range of medical disorders were evaluated using the Epworth Sleepiness Scale (ESS) and patient reports of nocturnal sleep. RESULTS: Sixty-seven percent of the sample reported a MD. The prevalence of EDS (ESS>or=10) was 31.4% in individuals with MD and increased as a function of a number of MD (0 MD=29.4%, 1 MD=28.4%, 2 MD=31.0%, 3 MD=35.3%, 4 MD=38.4%). Disorders which were independent predictors of EDS were ulcers OR=2.21 (95% CI=1.35-3.61), migraines OR=1.36 (95% CI=1.08-1.72), and depression OR=1.46 (95% CI=1.16-1.83) after controlling for other conditions, age, gender, time in bed, caffeine, smoking and alcohol use. Participants with ulcers had the highest prevalence of sleepiness, 50.0%, as well as the highest level of problems falling asleep (40.8%) and awakenings during the night (62.5%). CONCLUSIONS: Individuals with ulcers, migraines, and depression have independent and clinically significant levels of EDS relative to other common MD.