Clinical Outcomes of Patients Hospitalized with Coronavirus Disease 2019 (COVID-19) in Boston

BackgroundOutcomes of hospitalized patients with COVID-19 have been described in health systems overwhelmed with a surge of cases. However, studies examining outcomes of patients admitted to hospitals not in crisis are lacking.ObjectiveTo describe clinical characteristic and outcomes of all patients with COVID-19 who are admitted to hospitals not in crisis, and factors associated with mortality in this population.DesignA retrospective analysisParticipantsIn total, 470 consecutive patients with COVID-19 requiring hospitalization in one health system in Boston from January 1, 2020 to April 15, 2020.Main MeasuresWe collected clinical outcomes during hospitalization including intensive care unit (ICU) admission, receipt of mechanical ventilation, and vasopressors. We utilized multivariable logistic regression models to examine factors associated with mortality.Key ResultsA total of 470 patients (median age 66 [range 23–98], 54.0% male) were included. The most common comorbidities were diabetes (38.5%, 181/470) and obesity (41.3%, 194/470). On admission, 41.9% (197/470) of patients were febrile and 60.6% (285/470) required supplemental oxygen. During hospitalization, 37.9% (178/470) were admitted to the ICU, 33.6% (158/470) received mechanical ventilation, 29.4% (138/470) received vasopressors, 16.4% (77/470) reported limitations on their desire for life-sustaining therapies such as intubation and cardiopulmonary resuscitation, and 25.1% (118/470) died. Among those admitted to the ICU (N=178), the median number of days on the ventilator was 10 days (IQR 1–29), and 58.4% (104/178) were discharged alive. Older age (OR=1.04, P<0.001), male sex (OR=2.14, P=0.007), higher comorbidities (OR=1.20, P=0.001), higher lactate dehydrogenase on admission (2nd tertile: OR=4.07, P<0.001; 3rd tertile: OR=8.04, P<0.001), and the need for supplemental oxygen on admission (OR=2.17, P=0.014) were all associated with higher mortality.ConclusionsThe majority of hospitalized patients with COVID-19 and those who received mechanical ventilation survived. These data highlight the need to examine public health and system factors that contribute to improved outcomes for this population.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06622-x.     

Operational implications of varying ambient light levels and time-of-day effects on saccadic velocity and pupillary light reflex

Changes in maximal saccadic velocity (SV), initial pupil diameter (IPD), constriction latency (CL) and constriction amplitude (CA) determined by the pupillary light reflex have been found to be sensitive indicators of impairment as a result of drugs, sleepiness, and/or fatigue. Ambient illuminance and time of day are controlled when these indices are applied as repeated measures in fitness-for-duty determinations. The application of oculometrics in unrestricted operational environments, where ambient illuminance and time-of-day testing are not constant, requires understanding of, and potential compensation for, the effects of, and interactions among, these multiple uncontrolled variables. SV, IPD, CL, and CA were evaluated in the morning and evening on two consecutive days following adequate nightly sleep under one baseline ambient illuminance and seven test ambient illuminances. Sixteen healthy volunteers (21-38 years, eight females/eight males) participated. Within and across days, SV was unaffected by decreasing ambient light or time-of-day effects. With the increase of ambient light from 670 to 3300 lx, CL decreased by 1%, while IPD and CA decreased by 17% and 20%, respectively. IPD increased with time of day by 1-10% (IPD was smaller in the morning). The results show that SV and CL are essentially resistant to changes in ambient light and time-of-day effects, simplifying their application in uncontrolled operational environments.     

Role of polymorphic human cytochrome P450 enzymes in estrone oxidation.

Estrogen and its metabolites are believed to play important roles in breast cancer. The influence of genetic polymorphisms in the enzymes responsible for formation and disposition of estrogen on breast cancer risk may shed light on the importance of estrogen metabolites in this disease. However, for such studies to be valid, it is important to correctly identify the enzymes involved in estrogen bioactivation. Therefore, we assessed the human cytochrome P450-dependent oxidation of estrone using substrate concentrations that more closely approximate the maximum expected concentrations in breast tissue. The in vitro metabolism of estrone by recombinant human cytochrome P450 enzymes and human liver microsomes was studied. The formation of estrone metabolites (2-hydroxyestrone, 4-hydroxyestrone, and 16alpha-hydroxyestrone) was monitored by high-performance liquid chromatography. 2-Hydroxyestrone formation was catalyzed predominantly by CYP1A2, CYP1A1, and CYP1B1 enzymes; 4-hydroxyestrone formation was catalyzed predominantly by CYP1B1, CYP1A2, and CYP1A1 enzymes; and 16alpha-hydroxyestrone formation was catalyzed predominantly by CYP2C19, CYP1A1, and CYP3A5. This study confirms the important role of members of the CYP1 family in the 2-hydroxylation and 4-hydroxylation of estrone, but the enzymes identified as responsible for the 16alpha-hydroxylation of estrone are different from those previously identified. The relative importance of these enzymes in vivo would depend on the specific tissue expression of the enzymes. These enzymes are all known to be genetically variant in the human population, and additional studies to assess the role CYP1A2, CYP2C19, and CYP3A5 in breast cancer risk are indicated.     

Caffeine maintains vigilance and improves run times during night operations for Special Forces

PURPOSE: This study examined the effects of caffeine (CAF) on vigilance, marksmanship, and run performance during 27 h of sustained wakefulness in Special Forces personnel. METHODS: There were 31 soldiers (29.8 +/- 5.4 yr, 86.4 +/- 8.6 kg) who were divided into placebo (PLAC, n = 15) and CAF (n = 16) groups. A 6.3-km control run was completed on the morning of Day 1. In the evening of Day 2, soldiers performed a control observation and reconnaissance vigilance task (ORVT) in the field. This 90-min task was repeated twice more between 02:00 and 06:00 on Day 3 during an overnight period of sleep deprivation. Marksmanship was assessed before and after the ORVT. PLAC or 200 mg of CAF gum was administered at 01:45, 03:45, and approximately 06:30 on Day 3. A final 6.3-km run commenced within 30 min of receiving the final dose. RESULTS: ORVT was maintained in CAF at control levels of 77 +/- 13% during the overnight testing. However, values decreased significantly for PLAC from 77 +/- 15% to 54 +/- 29% and 51 +/- 31% during the first and second overnight testing periods, respectively. CAF had no effect on marksmanship but improved 6.3-km run times by 1.2 +/- 1.8 min. Run times slowed for PLAC by 0.9 +/- 0.8 min from approximately 35 min during the control run; the changes in performance were significant between groups. CONCLUSIONS: It was concluded that CAF maintained vigilance and improved running performance during an overnight field operation for Special Forces personnel.     

Visual neglect: occurrence and patterns in pilots in a simulated overnight flight

INTRODUCTION: Visual neglect is the unconscious inability to recognize or acknowledge some visual information in the presence of a structurally intact visual system, and was hypothesized to occur with less than 24 h of continuous wakefulness. Visual perception was evaluated in military pilots during a simulated overnight flight to explore for the possible occurrence of visual neglect. METHODS: There were eight military pilots (male, 31-52 yr of age, mean 37 yr) on flight status who were recruited to perform the primary task of flying a simulated 12.5 h overnight mission after a day of continuous wakefulness and the secondary task of responding to repeated 20 min presentations of single- and double-light stimuli displayed in random sequence at 15 degrees intervals across the cockpit instrument panel. In addition to the visual performance task, simulator shutdowns occurring when the tolerances of the simulator were exceeded were measured and simple reaction time on the psychomotor vigilance task was assessed. Total continuous wakefulness was 26.5 h. RESULTS: Combined performance on the visual perception task showed response omissions increasing at 19 h of continuous wakefulness. Patterns included omissions at all stimulus locations, of primarily peripherally located stimuli, and of one of two simultaneously presented stimuli. Simulator shutdowns began at 21.5 h of continuous wakefulness. Correlation of visual task response omissions with simulator shutdowns was r = 0.95, p < 0.0001. CONCLUSIONS: Significant neglect of visual stimuli occurred in pilots beginning at 19 h of continuous wakefulness in a simulated overnight fixed wing aircraft flight, preceded simulator shutdowns, and correlated at 0.95 with simulator shutdowns.     

Circadian rhythm of serum cortisol after repeated inhalation of the new topical steroid ciclesonide

The new inhalative glucocorticoid ciclesonide which is activated in lung to a more potent metabolite was hypothesized to have low risk for systemic and local side-effects in man. Therefore, a placebo-controlled, randomized, double-blind, four-period, change-over equivalence study in 12 healthy male volunteers (age 21-28 yr, body weight 62-90 kg) was conducted to assess the influence of three dosage regimens (800 microg in the morning, 800 microg in the evening, 400 microg twice daily for 7 d, metered inhalers) on the circadian time serum cortisol rhythm. RESULTS: Serum cortisol showed the typical circadian rhythm. The geometric mean of the 24-h mesor (AUC((0-24 h))/24 h) was 7.22 microg/dl for placebo, 6.75 microg/dl for the 800 microg ciclesonide morning dose, 7.08 microg/dl for the 800 microg evening dose, and 6.75 microg/dl for 400 microg ciclesonide inhaled twice daily. Because there was also no influence on cortisol amplitude and acrophase (time of maximum), the profiles after ciclesonide were equivalent to the placebo control. The small differences were considered not to be of clinical significance. In conclusion, inhaled ciclesonide in daily doses of 800 microg for 7 d is without clinically relevant effects on the hypothalamic-pituitary-adrenal axis independent of the time of administration.     

Carvedilol blockade of rat myocardial alpha1-adrenoceptors

Carvedilol is a combined alpha(1)- and beta-adrenoceptor antagonist. The ability of carvedilol to antagonize functional effects mediated through myocardial alpha(1)-adrenoceptors has never been investigated. We tested the ability of carvedilol to antagonize the inotropic effect mediated by myocardial alpha(1)-adrenoceptors compared to the antagonism of beta-adrenoceptors. Papillary muscles from rat heart left ventricle were mounted in an organ bath and concentration-response experiments for the inotropic effects of separate alpha(1)- and beta-adrenoceptor stimulation were performed in the absence and presence of carvedilol. Carvedilol antagonized myocardial alpha(1)-adrenoceptors with an inhibition constant (K(i)) of 11.0+/-3.0 nmol/l and the functional experiments were supported by radioligand-binding studies. Corresponding functional studies on the response to beta-adrenoceptor stimulation revealed a K(i) of 1.2+/-0.35 nmol/l. Thus, carvedilol antagonizes the myocardial alpha(1)-adrenoceptors with a 9-fold lower potency than the beta-adrenoceptors. Antagonism of myocardial alpha(1)-adrenoceptor evoked effects may contribute to clinical effects of carvedilol.