A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study.

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

A Dual-Center Cohort Study on The Association Between Early Deep Sedation and Clinical Outcomes in Mechanically Ventilated Patients During the COVID-19 Pandemic: the COVID-SED Study.

Background : Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. Study Design and Methods : Dual-center, retrospective cohort study conducted over six months (March - August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Riker Sedation-Agitation Scale of 1 - 3. To examine impact of early sedation depth on hospital mortality (primary outcome) we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. Results : 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation ( p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65 - 7.17; p <0.01). These results were stable in the subgroup of patients with COVID-19. Conclusions : The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach. Clinical Trial Registration : Not applicable.

Social workers' determination of when children's access or potential access to loaded firearms constitutes child neglect.

BACKGROUND: Pediatric firearm-related deaths and injuries are a serious societal problem. Our study's objective was to determine social workers' assessment of child neglect with respect to access or potential access to a loaded firearm. METHODS: Study invitations were delivered by e-mail to National Association of Social Workers members designating their practice as "Child/Family Welfare" (N = 4933) in October/November, 2015. Demographics, attitudes regarding child access prevention (CAP) laws, and the ages (4-14 years) at which social workers deemed several scenarios as child neglect were determined. Descriptive (frequencies) and bivariate (chi square) analyses were performed. RESULTS: 485 of 4933 social workers completed the survey (9.8%). Of these, most agreed or strongly agreed (≥92%) there should be laws in place requiring firearms to be stored so unwanted access cannot be obtained by a child, even up to 15 years of age. In a scenario where a child had potential access to a loaded firearm, but never gained access, the presence of a CAP law pertinent to the child in the scenario increased the likelihood respondents would find the situation child neglect for all ages (p < 0.0001 for each age comparison). Moreover, 10.3% felt they could not deem the situation child neglect without the presence of a CAP law, no matter the age of the child. In a scenario where a child gained access to a loaded firearm, the vast majority found this to be child neglect (82-99%, with the percentage varying by the age of the child involved), regardless of the presence or absence of a CAP law and/or an injury being sustained. In addition, when a CAP law was in place, social workers were more likely to find neglect if the child had sustained a firearm-related injury as well (p values ranged from 0.016-0.0081 for age comparisons). CONCLUSIONS: The vast majority of child/family welfare social workers surveyed found it to be child neglect when youth accessed or had potential access to a loaded, unsecured firearm. Results of the study provide support for the passage of universal CAP laws to help protect children equally across states and ensure the safe storage of firearms in homes.

High Enrichment [13 C]-Labeling of Plants Grown Hydroponically from Seed to Seed in a Controlled 13 C-Carbon Dioxide Atmosphere Enclosure.

In vivo isotopic labeling empowers proteomic and metabolomic analyses to resolve relationships between the molecular composition, environment, and phenotype of an organism. Carbon-13 is particularly useful for plant labeling as it can be introduced via 13 CO2 gas and readily assimilated into plant metabolic systems through natural carbon fixation. While short-term labeling experiments can be performed within a simple sealed enclosure, long-term growth in an isolated environment raises many challenges beyond nutrient availability and buildup of metabolic waste. Viable growth conditions must be maintained by means that do not compromise the integrity of the carbon-13 enrichment. To address these issues, an automated growth chamber equipped with countermeasures to neutralize stresses and ensure high isotopic enrichment throughout the life cycle of the plant has been developed. The following describes this growth chamber and its use in an example 130-day growth of ten soybean plants to full maturity, achieving 100% carbon-13 enrichment of new seed tissue. © 2018 by John Wiley & Sons, Inc.

Metabolic Patterns in Spirodela polyrhiza Revealed by 15N Stable Isotope Labeling of Amino Acids in Photoautotrophic, Heterotrophic, and Mixotrophic Growth Conditions.

In this study we describe a [15N] stable isotopic labeling study of amino acids in Spirodela polyrhiza (common duckweed) grown under three different light and carbon input conditions which represent unique potential metabolic modes. Plants were grown with a light cycle, either with supplemental sucrose (mixotrophic) or without supplemental sucrose (photoautotrophic) and in the dark with supplemental sucrose (heterotrophic). Labeling patterns, pool sizes (both metabolically active and inactive), and kinetics/turnover rates were estimated for 17 of the proteinogenic amino acids. Estimation of these parameters followed several overall trends. First, most amino acids showed plateaus in labeling patterns of <100% [15N]-labeling, indicating the possibility of a large proportion of amino acids residing in metabolically inactive metabolite pools. Second, total pool sizes appear largest in the dark (heterotrophic) condition, whereas active pool sizes appeared to be largest in the light with sucrose (mixotrophic) growth condition. In contrast turnover measurements based on pool size were highest overall in the light with sucrose experiment, with the exception of leucine/isoleucine, lysine, and arginine, which all showed higher turnover in the dark. K-means clustering analysis also revealed more rapid turnover in the light treatments with many amino acids clustering in lower-turnover groups. Emerging insights from other research were also supported, such as the prevalence of alternate pathways for serine metabolism in non-photosynthetic cells. These data provide extensive novel information on amino acid pool size and kinetics in S. polyrhiza and can serve as groundwork for future metabolic studies.

Child welfare professionals' determination of when children's access or potential access to loaded firearms constitutes child neglect.

BACKGROUND: Pediatric deaths and injuries from access to firearms are a significant public health problem. No studies have examined how experts determine child neglect regarding firearm access in the home. Our study objectives were to identify factors that influenced pediatric experts' finding of firearm-related child neglect and to assess their attitudes toward child access prevention (CAP) laws. METHODS: A survey was distributed to the American Academy of Pediatrics Section on Child Abuse and Neglect members. Demographics, attitudes regarding CAP laws, and ages (up to 14 years old) at which experts deemed several scenarios as child neglect were determined. Scenarios tested potential versus actual loaded firearm access, presence or absence of a CAP law, and injury versus no injury when the firearm was accessed. RESULTS: One hundred ninety-three surveys were completed. Experts agreed (>95%) that CAP laws were important, even for children up to age 15 years. Although a high percentage considered potential access to a loaded firearm as child neglect, a CAP law significantly increased the percentage for each age. In addition, higher percentages of respondents from states with CAP laws than those without deemed potential access as child neglect for 12- and 14-year-olds. In contrast, if the child had accessed a loaded firearm, there were no significant differences in the high percentages that deemed the scenario as child neglect under any conditions, including with and without a CAP law. CONCLUSIONS: Although almost all child neglect experts considered potential and actual access to loaded firearms as child neglect, CAP laws increased the percentage for cases of potential access. Universal CAP laws may help ensure that determinations of child neglect are more consistent across states. The deterrent effect of potential child neglect findings may increase the number of parents securing firearms in ways that prevent child access and reduce firearm-related deaths and injuries. LEVEL OF EVIDENCE: Epidemiologic study, level III.