Treatment failure and hospital readmissions in severe COPD exacerbations treated with azithromycin versus placebo - A post-hoc analysis of the BACE randomized controlled trial

Background: In the BACE trial, a 3-month (3 m) intervention with azithromycin, initiated at the onset of an infectious COPD exacerbation requiring hospitalization, decreased the rate of a first treatment failure (TF); the composite of treatment intensification (TI), step-up in hospital care (SH) and mortality. Objectives: (1) To investigate the intervention's effect on recurrent events, and (2) to identify clinical subgroups most likely to benefit, determined from the incidence rate of TF and hospital readmissions. Methods: Enrolment criteria included the diagnosis of COPD, a smoking history of ≥10 pack-years and ≥ 1 exacerbation in the previous year. Rate ratio (RR) calculations, subgroup analyses and modelling of continuous variables using splines were based on a Poisson regression model, adjusted for exposure time. Results: Azithromycin significantly reduced TF by 24% within 3 m (RR = 0.76, 95%CI:0.59;0.97, p = 0.031) through a 50% reduction in SH (RR = 0.50, 95%CI:0.30;0.81, p = 0.006), which comprised of a 53% reduction in hospital readmissions (RR = 0.47, 95%CI:0.27;0.80; p = 0.007). A significant interaction between the intervention, CRP and blood eosinophil count at hospital admission was found, with azithromycin significantly reducing hospital readmissions in patients with high CRP (> 50 mg/L, RR = 0.18, 95%CI:0.05;0.60, p = 0.005), or low blood eosinophil count (<300cells/μL, RR = 0.33, 95%CI:0.17;0.64, p = 0.001). No differences were observed in treatment response by age, FEV1, CRP or blood eosinophil count in continuous analyses. Conclusions: This post-hoc analysis of the BACE trial shows that azithromycin initiated at the onset of an infectious COPD exacerbation requiring hospitalization reduces the incidence rate of TF within 3 m by preventing hospital readmissions. In patients with high CRP or low blood eosinophil count at admission this treatment effect was more pronounced, suggesting a potential role for these biomarkers in guiding azithromycin therapy. Trial registration: ClinicalTrials.gov number. NCT02135354. © 2019 The Author(s)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

The measurement of DLNO and DLCO: A manufacturer's perspective.

The simultaneous measurement of the lung transfer factor for carbon monoxide (DLCO) and nitric oxide (DLNO) is now available as a powerful method for studying the alveolar-capillary gas exchange. However, application of the DLNO-CO technique in daily settings is still limited by some technical drawbacks. This paper provides a manufacturer's overview of the measuring principles, technical challenges and current available solutions for implementing the DLNO-CO measurement in to a marketed device. This includes the recent developments in technology for NO sensors, latest findings on NO uptake and new statistical methods

Determinants of apnea-hypopnea index variability during home sleep testing

Study objectives The prospective Self-Efficacy Measure for Sleep Apnea study (SEMSAS) is investigating thresholds for health literacy, self-efficacy and precariousness at obstructive sleep apnea (OSA) diagnosis to predict CPAP adherence. This paper describes the study protocol and presents baseline data from the ongoing study. Methods Eligible individuals had confirmed OSA and were referred to a homecare provider for continuous positive airway pressure (CPAP) therapy initiation. Data on patient characteristics and comorbidities were collected, along with baseline evaluations of self-efficacy [15-item Self-Efficacy Measure for Sleep Apnea tool (SEMSA-15)], precariousness [Deprivation in Primary Care Questionnaire (DipCareQ)], and health literacy (Health Literacy Questionnaire). CPAP adherence over 12 months of follow-up will be determined using remote monitoring of CPAP device data. The primary objective is to define an optimal SEMSA-15 score threshold to predict CPAP adherence at 3- and 12-month follow-up. Results Enrollment of 302 participants (71% male, median age 55 years, median body mass index 31.6 kg/m 2 ) is complete. Low self-efficacy (SEMSA-15 score ≤ 2.78) was found in 93/302 participants (31%), and 38 (12.6%) reported precariousness (DipCareQ score &gt; 1); precariousness did not differ significantly between individuals with a SEMSA-15 score ≤ 2.78 versus &gt;2.78. Health literacy was generally good, but was significantly lower in individuals with versus without precariousness, and with low versus high self-efficacy. Conclusion SEMSAS is the first study using multidimensional baseline assessment of self-efficacy, health literacy and precariousness, plus other characteristics, to determine future adherence to CPAP, including CPAP adherence trajectories. Collection of follow-up data is underway

Determinants of unintentional leak during CPAP treatment in obstructive sleep apnea syndrome.

BACKGROUND: Unintentional leakage from the mouth or around the mask may lead to cessation of CPAP treatment; however, the causes of unintentional leaks are poorly understood. The objectives of this study were (1) to identify determining factors of unintentional leakage and (2) to determine the effect of the type of mask (nasal/oronasal) used on unintentional leakage. METHODS: Seventy-four polysomnograms from patients with OSA syndrome treated with auto-CPAP were analyzed (23 women; 56 ± 13 years; BMI, 32.9 kg/m2 (range, 29.0-38.0 kg/m2). Polysomnographic recordings were obtained under auto-CPAP, and mandibular behavior was measured with a magnetic sensor. After sleep and respiratory scoring, polysomnographic signals were computed as mean values over nonoverlapping 10-s intervals. The presence/absence of unintentional leakage was dichotomized for each 10-s interval (yes/no). Univariate and multivariate conditional regression models estimated the risk of unintentional leaks during an interval "T" based on the explanatory variables from the previous interval "T-1." A sensitivity analysis for the type of mask was then conducted. RESULTS: The univariate analysis showed that mandibular lowering (mouth opening), a high level of CPAP, body position (other than supine), and rapid eye movement (REM) sleep increased the risk of unintentional leaks and microarousal decreased it. In the multivariate analysis, the same variables remained independently associated with an increased risk of unintentional leakage. The sensitivity analysis showed that oronasal masks reduced the risk of unintentional leaks in cases of mouth opening and REM sleep. CONCLUSIONS: Mouth opening, CPAP level, sleep position, and REM sleep independently contribute to unintentional leakage. These results provide a strong rationale for the definition of phenotypes and the individual management of leaks during CPAP treatment

Factors Contributing to Unintentional Leak During CPAP Treatment: A Systematic Review.

CPAP is the first-line treatment for moderate to severe OSA syndrome. Up to 25% of patients with OSA syndrome discontinue CPAP treatment due to side effects. Unintentional leakage and its associated annoying consequences are the most frequently reported adverse effects of CPAP. Successive technological improvements have not succeeded in addressing this issue. A systematic review was conducted (1) to assess the impact of different technological advances on unintentional leaks and (2) to determine if any patient characteristics have already been identified as determinants of unintentional leakage. No CPAP modality was superior to another in reducing unintentional leaks and, surprisingly, oronasal masks were associated with higher unintentional leaks. Nasal obstruction, older age, higher BMI, central fat distribution, and male sex might be associated with an increased risk of unintentional leakage. Such leaks remain an important problem. Further studies are needed to improve the understanding of underlying clinical factors so that patients at risk of unintentional leaks may be identified and individualized solutions applied

Deprescribing antihypertensive drugs after starting OSA primary therapy?

International audienc

Les mouvements de la mandibule informent sur l’effet thérapeutique de l’orthèse d’avancée mandibulaire

L’étude des mouvements mandibulaires pendant le sommeil informent de manière précise sur l’évolution des indices d’apnées/hypopnées au cours de la titration de l’orthèse d’avancée mandibulaire dans le traitement du syndrome des apnées obstructives. Ces mouvements mandibulaires peuvent, maintenant, être monitorés nuit après nuit par une nouvelle technologie connectée, qui vérifie la levée de l’effort respiratoire sous l’effet de l’orthèse en avancée

Creating an Optimal Approach for Diagnosing Sleep Apnea

Sleep apnea is nowadays recognized as a treatable chronic disease and awareness of it has increased, leading to an upsurge in demand for diagnostic testing. Conventionally, diagnosis depends on overnight polysomnography in a sleep clinic, which is highly human-resource intensive and ignores the night-to-night variability in classical sleep apnea markers, such as the apnea-hypopnea index. In this review, the authors summarize the main improvements that could be made in the sleep apnea diagnosis strategy; how technological innovations and multi-night home testing could be used to simplify, increase access, and reduce costs of diagnostic testing while avoiding misclassification of severity