Additive value of lung ultrasound to clinical parameters for prognosticating COVID-19.

The inclusion of LUS with simple, point-of-care clinical parameters have potential to improve COVID-19 prognostication above that from standard clinical care delivery. https://bit.ly/3InePYK.

The efficacy of intranasal leptin for opioid-induced respiratory depression depends on sex and obesity state.

Introduction: Opioid-induced respiratory depression (OIRD) is the primary cause of death associated with opioids and individuals with obesity are particularly susceptible due to comorbid obstructive sleep apnea (OSA). Repeated exposure to opioids, as in the case of pain management, results in diminished therapeutic effect and/or the need for higher doses to maintain the same effect. With limited means to address the negative impact of repeated exposure it is critical to develop drugs that prevent deaths induced by opioids without reducing beneficial analgesia. Methods: We hypothesized that OIRD as a result of chronic opioid use can be attenuated by administration of IN leptin while also maintaining analgesia in both lean mice and mice with diet-induced obesity (DIO) of both sexes. To test this hypothesis, an opioid tolerance protocol was developed and a model of OIRD in mice chronically receiving morphine and tolerant to morphine analgesia was established. Subsequently, breathing was recorded by barometric plethysmography in four experimental groups: obese male, obese female, lean male, and lean female following acute administration of IN leptin. Respiratory data were complemented with measures of arterial blood gas. Operant behavioral assays were used to determine the impact of IN leptin on the analgesic efficacy of morphine. Results: Acute administration of IN leptin significantly attenuated OIRD in DIO male mice decreasing the apnea index by 58.9% and apnea time by 60.1%. In lean mice leptin was ineffective. Blood gas measures confirmed the effectiveness of IN leptin for preventing respiratory acidosis in DIO male mice. However, IN leptin was not effective in lean mice of both sexes and appeared to exacerbate acid-base disturbances in DIO female mice. Additionally, morphine caused a complete loss of temperature aversion which was not reduced by intranasal leptin indicating IN leptin does not decrease morphine analgesia. Discussion: IN leptin effectively treated OIRD in morphine-tolerant DIO male mice without impacting analgesia. In contrast, IN leptin had no effect in lean mice of either sex or DIO female mice. The arterial blood gas data were consistent with ventilatory findings showing that IN leptin reversed morphine-induced respiratory acidosis only in DIO male mice but not in other mouse groups. Finally, a hypercapnic sensitivity study revealed that IN leptin rescued minute ventilation under hypercapnic conditions only in DIO male mice, which suggests that differential responses to IN leptin are attributable to different leptin sensitivities depending on sex and the obesity status.

Point-of-Care Lung Ultrasound Predicts Severe Disease and Death Due to COVID-19: A Prospective Cohort Study.

The clinical utility of point-of-care lung ultrasound (LUS) among hospitalized patients with COVID-19 is unclear. DESIGN: Prospective cohort study. SETTING: A large tertiary care center in Maryland, between April 2020 and September 2021. PATIENTS: Hospitalized adults (≥ 18 yr old) with positive severe acute respiratory syndrome coronavirus 2 reverse transcriptase-polymerase chain reaction results. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were scanned using a standardized protocol including 12 lung zones and followed to determine clinical outcomes until hospital discharge and vital status at 28 days. Ultrasounds were independently reviewed for lung and pleural line artifacts and abnormalities, and the mean LUS Score (mLUSS) (ranging from 0 to 3) across lung zones was determined. The primary outcome was time to ICU-level care, defined as high-flow oxygen, noninvasive, or invasive mechanical ventilation, within 28 days of the initial ultrasound. Cox proportional hazards regression models adjusted for age and sex were fit for mLUSS and each ultrasound covariate. A total of 264 participants were enrolled in the study; the median age was 61 years and 114 participants (43.2%) were female. The median mLUSS was 1.0 (interquartile range, 0.5-1.3). Following enrollment, 27 participants (10.0%) went on to require ICU-level care, and 14 (5.3%) subsequently died by 28 days. Each increase in mLUSS at enrollment was associated with disease progression to ICU-level care (adjusted hazard ratio [aHR], 3.61; 95% CI, 1.27-10.2) and 28-day mortality (aHR, 3.10; 95% CI, 1.29-7.50). Pleural line abnormalities were independently associated with disease progression to death (aHR, 20.93; CI, 3.33-131.30). CONCLUSIONS: Participants with a mLUSS greater than or equal to 1 or pleural line changes on LUS had an increased likelihood of subsequent requirement of high-flow oxygen or greater. LUS is a promising tool for assessing risk of COVID-19 progression at the bedside.

A comparison of automated and manual sleep staging and respiratory event recognition in a portable sleep diagnostic device with in-lab sleep study.

STUDY OBJECTIVES: The objectives were to develop and validate an algorithm for editing WatchPAT scoring and assess the accuracy in an unselected clinical population as well as age and sex substrata. METHODS: Two hundred sixty-two participants were enrolled to undergo WatchPAT simultaneously with in-lab polysomnography (PSG) recordings for developing (n = 30), optimizing (n = 62), and validating (n = 170) an algorithm to review and edit respiratory events and sleep architecture of WatchPAT recordings, which was based on visual inspection of WatchPAT signals. Apnea-hypopnea index (AHI) and sleep indices were compared with PSG-derived and automated WatchPAT indices. RESULTS: Although estimation of total sleep time (TST) was comparable between automated and manual algorithm, estimation of rapid eye movement (REM) sleep time was markedly improved with manual editing from 0.48, 23.0 min (-43.9 to 89.8) to 0.64, 18.3 min (-32.6 to 69.1) (correlation with PSG, mean difference [reference range] from PSG, respectively). Manual scoring also improved correlation and agreement with PSG AHI from 0.65, 2.5 events/h (-24.0 to 28.9) to 0.81, -4.5 events/h (-22.5 to 13.6) as well as concordance for categorical agreement of sleep-disordered breathing severity and concordance for detecting severe REM-related sleep-disordered breathing. Interscorer reliabilities were excellent for TST and AHI, while good for REM sleep time. The automated algorithm performed better in younger than in older patients, while performed similarly between men and women with respect to concordance statistics. The manual algorithm markedly improved concordances more in older patients and women than in their counterparts. CONCLUSIONS: Our manual editing algorithm improves correlation and agreement with PSG-derived sleep and breathing indices. Sex and age influence the accuracy of automated analysis and the performance of manual editing on AHI concordance.