Background Sleep deprivation and fatigue are common subjective complaints among astronauts. We conducted the first large-scale evaluation of objectively-estimated sleep of astronauts on both short- and long-duration spaceflight missions. Methods Allnon-Russian crewmembers assigned to space shuttle flights with inflight experiments from July 2001 until July 2011 or ISS Expeditions from 2006 –2011 were eligible to participate. We objectively assessed, via wrist actigraphy and daily logs, sleep-wake timing of 64 astronauts on 80 Space Shuttle missions, encompassing 26 Space Transportation System flights (1,063 inflight days), and 21 astronauts on the International Space Station (ISS) (3,248 inflight days) and, for each astronaut, during two Earth-based data-collection intervals prior to and one following spaceflight (4,013 ground-based days). Findings Astronauts attempted and obtained significantly less actigraphically-estimated sleep per night on space shuttle missions (7·35 ± 0·47 and 5·96 ± 0·56 hours, respectively), in the 11-days before spaceflight (7·35 ± 0·51 and 6·04 ± 0·72 hours, respectively) and even three months before spaceflight (7·40 ± 0·59 and 6·29 ± 0·67 hours, respectively) than they did upon their return to Earth (8·01 ± 0·78 and 6·74 ± 0·91 hours, respectively) (p < 0·0001 for each) Astronauts on ISS missions also obtained significantly less sleep three months prior (6.41 ± 0.65), in the 11 days prior (5.86 ± 0.94) and during spaceflight (6.09 ± 0.67 hours), as compared to the first week post-mission (6.95 ± 1.04 hours; p < 0·0001). Seventy-eight percent (61/78) of shuttle mission-crewmembers reported taking a dose of sleep-promoting medications on 52% of nights (500/963) and 2 doses on 17% of nights during flight (87/500); 75% of ISS crewmembers (12/16) reported using sleep-promoting medications. Interpretation Sleep deficiency in astronauts was prevalent not only during space shuttle and ISS missions, but also throughout a 3-month pre-flight training interval. Despite chronic sleep curtailment, sleeping pill use was pervasive during spaceflight. As chronic sleep loss produces performance decrements, these findings highlight the need for development of effective counter measures to promote sleep. Funding The study was supported by NASA cooperative agreement NCC 9–119. Drs. Czeisler and Barger received support from the NSBRI (HFP01601).

Sleep deficiency and the use of sleep-promoting medication are prevalent during spaceflight. Operations frequently dictate work during the biological night and sleep during the biological day, which contribute to circadian misalignment. We investigated whether circadian misalignment was associated with adverse sleep outcomes before (preflight) and during spaceflight missions aboard the International Space Station (ISS). Actigraphy and photometry data for 21 astronauts were collected over 3,248 days of long-duration spaceflight on the ISS and 11 days prior to launch (n=231 days). Sleep logs, collected one out of every 3 weeks in flight and daily on Earth, were used to determine medication use and subjective ratings of sleep quality. Actigraphy and photometry data were processed using Circadian Performance Simulation Software to calculate the estimated endogenous circadian temperature minimum. Sleep episodes were classified as aligned or misaligned relative to the estimated endogenous circadian temperature minimum. Mixed-effects regression models accounting for repeated measures were computed by data collection interval (preflight, flight) and circadian alignment status. The estimated endogenous circadian temperature minimum occurred outside sleep episodes on 13% of sleep episodes during preflight and on 19% of sleep episodes during spaceflight. The mean sleep duration in low-Earth orbit on the ISS was 6.4±1.2 h during aligned and 5.4±1.4 h (P<0.01) during misaligned sleep episodes. During aligned sleep episodes, astronauts rated their sleep quality as significantly better than during misaligned sleep episodes (66.8±17.7 vs. 60.2±21.0, P<0.01). Sleep-promoting medication use was significantly higher during misaligned (24%) compared with aligned (11%) sleep episodes (P<0.01). Use of any medication was significantly higher on days when sleep episodes were misaligned (63%) compared with when sleep episodes were aligned (49%; P<0.01). Circadian misalignment is associated with sleep deficiency and increased medication use during spaceflight. These findings suggest that there is an immediate need to deploy and assess effective countermeasures to minimize circadian misalignment and consequent adverse sleep outcomes both before and during spaceflight.

The basic goal of this research is to determine the best combination of light wavelengths for use as a lighting countermeasure for circadian and sleep disruption during space exploration, as well as for individuals living on Earth. Action spectra employing monochromatic light and selected monochromatic wavelength comparisons have shown that short‐wavelength visible light in the blue‐appearing portion of the spectrum is most potent for neuroendocrine, circadian, and neurobehavioral regulation. The studies presented here tested the hypothesis that broad spectrum, polychromatic fluorescent light enriched in the short‐wavelength portion of the visible spectrum is more potent for pineal melatonin suppression in healthy men and women. A total of 24 subjects were tested across three separate experiments. Each experiment used a within‐subjects study design that tested eight volunteers to establish the full‐range fluence–response relationship between corneal light irradiance and nocturnal plasma melatonin suppression. Each experiment tested one of the three types of fluorescent lamps that differed in their relative emission of light in the short‐wavelength end of the visible spectrum between 400 and 500 nm. A hazard analysis, based on national and international eye safety criteria, determined that all light exposures used in this study were safe. Each fluence–response curve demonstrated that increasing corneal irradiances of light evoked progressively increasing suppression of nocturnal melatonin. Comparison of these fluence–response curves supports the hypothesis that polychromatic fluorescent light is more potent for melatonin regulation when enriched in the short‐wavelength spectrum.

Introduction During the early months of the COVID-19 pandemic, mortality associated with the disease declined in the United States. The standard of care for pharmacological interventions evolved during this period as new and repurposed treatments were used alone and in combination. Though these medications have been studied individually, data are limited regarding the relative impact of different medication combinations. The objectives of this study were to evaluate the association of COVID-19-related mortality and observed medication combinations and to determine whether changes in medication-related practice patterns and measured patient characteristics, alone, explain the decline in mortality seen early in the COVID-19 pandemic. Methods A retrospective cohort study was conducted at a multi-hospital healthcare system exploring the association of mortality and combinations of remdesivir, corticosteroids, anticoagulants, tocilizumab, and hydroxychloroquine. Multivariable logistic regression was used to identify predictors of mortality for both the overall population and the population stratified by intensive care and non-intensive care unit admissions. A separate model was created to control for the change in unmeasured variables over time. Results For all patients, four treatment combinations were associated with lower mortality: Anticoagulation Only (OR 0.24, p < 0.0001), Anticoagulation and Remdesivir (OR 0.25, p = 0.0031), Anticoagulation and Corticosteroids (OR 0.53, p = 0.0263), and Anticoagulation, Corticosteroids and Remdesivir (OR 0.42, p = 0.026). For non-intensive care unit patients, the same combinations were significantly associated with lower mortality. For patients admitted to the intensive care unit, Anticoagulation Only was the sole treatment category associated with decreased mortality. When adjusted for demographics, clinical characteristics, and all treatment combinations there was an absolute decrease in the mortality rate by 2.5% between early and late periods of the study. However, when including an additional control for changes in unmeasured variables overtime, the absolute mortality rate decreased by 5.4%. Conclusions This study found that anticoagulation was the most significant treatment for the reduction of COVID-related mortality. Anticoagulation Only was the sole treatment category associated with a significant decrease in mortality for both intensive care and non-intensive care patients. Treatment combinations that additionally included corticosteroids and/or remdesivir were also associated with decreased mortality, though only in the non-intensive care stratum. Further, we found that factors other than measured changes in demographics, clinical characteristics or pharmacological interventions accounted for an additional decrease in the COVID-19-related mortality rate over time.

Mobile electrocardiograms (ECGs) (mECGs) using smartphone applications are an emerging technology. In the coronavirus disease 2019 (COVID-19) era, minimizing patient contact has gained increasing importance. Additionally, increased QT/corrected QT (QTc) monitoring has concurrently been required. The KardiaMobile 6L ECG device, cleared by the United States Food and Drug Administration (FDA) for recording ECGs, along with the KardiaStation tablet application is a platform (AliveCor, Mountain View, CA, USA) that addresses these two issues. A team of residents, fellows, hospitalists, and cardiologists identified inpatients in need of QT/QTc interval monitoring to pilot the adoption of a system composed of a KardiaMobile 6L ECG device with the accompanying KardiaStation tablet application. Concurrent standard ECGs provided validation. Adoption and performance issues were recorded. Four patients agreed to participate in QT/QTc interval monitoring, three of whom were positive for severe acute respiratory syndrome coronavirus 2 viral infection. After basic instructions were given to the patients and their clinical nurses, all patients recorded mECGs successfully. Patients were able to record their own mECG tracings at least once without any assistance. The 12-lead ECGs and mECGs each showed the correct rhythm, and the measured QTc intervals on each modality were consistently acceptable (< 500 ms). Contactless ECGs were successfully uploaded to KardiaStation for QT/QTc interval measurement and archiving. In this study, we showed that an FDA-cleared product, KardiaMobile 6L, has the ability to provide high-quality contactless ECGs for reliable QT/QTc interval measurements. Hospitalized patients were able to perform recordings when requested after receiving simple instructions at the time of first use. This technology has applications during the COVID-19 pandemic and beyond.

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COVID-19 has disproportionately affected low-income communities and people of color. Previous studies demonstrated that race/ethnicity and socioeconomic status (SES) are not independently correlated with COVID-19 mortality. The purpose of our study is to determine the effect of race/ethnicity and SES on COVID-19 30-day mortality in a diverse, Philadelphian population. This is a retrospective cohort study in a single-center tertiary care hospital in Philadelphia, PA. The study includes adult patients hospitalized with polymerase-chain-reaction-confirmed COVID-19 between March 1, 2020 and June 6, 2020. The primary outcome was a composite of COVID-19 death or hospice discharge within 30 days of discharge. The secondary outcome was intensive care unit (ICU) admission. The study included 426 patients: 16.7% died, 3.3% were discharged to hospice, and 20.0% were admitted to the ICU. Using multivariable analysis, race/ethnicity was not associated with the primary nor secondary outcome. In Model 4, age greater than 75 (odds ratio [OR]: 11.01; 95% confidence interval [CI]: 1.96-61.97) and renal disease (OR: 2.78; 95% CI: 1.31-5.90) were associated with higher odds of the composite primary outcome.Living in a "very-low-income area" (OR: 0.29; 95% CI: 0.12-0.71) and body mass index (BMI) 30-35 (OR: 0.24; 95% CI: 0.08-0.69) were associated with lower odds of the primary outcome. When controlling for demographics, SES, and comorbidities, race/ethnicity was not independently associated with the composite primary outcome. Very-low SES, as extrapolated from census-tract-level income data, was associated with lower odds of the composite primary outcome.

International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD‐10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. Objective: Compare COVID‐19 cohort manual‐chart‐review and ICD‐10‐based comorbidity data; characterize the accuracy of different methods of extracting ICD‐10‐code‐based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. Design: Retrospective cross‐sectional study. Measurements: ICD‐10‐based‐data performance characteristics relative to manual‐chart‐review. Results: Discharge billing diagnoses had a sensitivity of 0.82 (95% confidence interval [CI]: 0.79–0.85; comorbidity range: 0.35–0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69–0.76; range: 0.44–0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63–0.71; range: 0.47–0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54–0.63; range: 0.30–0.68)and past medical history table had a sensitivity of 0.48 (95% CI: 0.43–0.53; range: 0.30–0.56). Conclusions and Relevance: ICD‐10‐based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual‐chart‐review.