Age-Specific All-Cause Mortality Disparities by Race and Ethnicity During the COVID-19 Pandemic (preprint)

BACKGROUND. The end of the public health emergency provides an opportunity to fully describe disparities during the Covid-19 pandemic. METHODS. In this retrospective cohort analysis of US deaths during the Covid-19 public health emergency (March 2020-April 2023), all-cause excess mortality and years of potential life lost (YPLL) were calculated by race or ethnicity overall and by age groups (ages <25 years, 25-64 years, [≥]65 years). Temporal correlations with Covid-19-specific mortality were measured. RESULTS. >1.38 million all-cause excess deaths and ~23 million corresponding YPLL occurred during the pandemic. Had the rate of excess mortality observed among the White population been observed among the total population, >252,300 (18%) fewer excess deaths, and >5,192,000 fewer (22%) YPLL would have occurred. The highest excess mortality rates were among the American Indian/Alaska Native (AI/AN, 822 per 100,000; ~405,700 YPLL) and the Black (549 per 100,000; ~4,289,200 YPLL) populations. The highest relative increase in mortality was observed in the AI/AN population (1.34; 95% CI 1.31-1.37), followed by Hispanic (1.31; 95% CI 1.27-1.34), Native Hawaiian or Other Pacific Islander (1.24; 95% CI 1.21-1.27), Asian (1.20; 95% CI 1.18-1.20), Black (1.20; 95% CI 1.18-1.22) and White (1.12; 95% CI 1.09-1.15) populations. Greater disparities occurred among children and adults <65 years. CONCLUSIONS. Excess mortality occurred in all groups during the Covid-19 pandemic, with disparities by race and ethnicity, especially in younger and middle-aged populations. >252,000 and 5.2 million fewer YPLL would have been observed had increases in mortality among the total population been similar to the White population.

Effects of a social norm-based handwashing intervention including handwashing stations, and a handwashing station-only intervention on handwashing with soap in urban Côte d'Ivoire: a cluster randomised controlled trial.

BACKGROUND: Diarrhoeal diseases are an important cause of mortality in children younger than 5 years in sub-Saharan Africa. We aimed to evaluate the effect of three handwashing interventions on handwashing with soap (HWWS) after toilet use. METHODS: In this cluster randomised trial in Abidjan, Côte d'Ivoire, we randomly assigned communal housing compounds (1:1:1) to receive one of three interventions: a theory of normative social behaviour (TNSB) intervention, including provision of handwashing stations; handwashing stations only; and no intervention. The TNSB intervention was designed to shift the outcome expectation associated with HWWS from health to riddance of faeces-related disgust, and to increase the perceived descriptive norm and perceived handwashing publicness. Participants and fieldworkers were masked to the study objectives. The primary outcome was HWWS after toilet use, assessed at 1 month and 5 months follow-ups. Analysis was by intention to treat. This trial is registered at the Pan African Clinical Trial Registry, PACTR201501000892239. FINDINGS: Between April 10 and May 22, 2014, we identified 92 eligible compounds, of which 75 compounds were included. Follow-up data on HWWS were available for 23 compounds for the TNSB group, 25 compounds for the handwashing station-only group, and 25 compounds for the control group. The study ended in April, 2017. Compared with a frequency of 5% (29 of 604 occasions) in the control group, HWWS after toilet use increased to 9% (49 of 557 occasions; adjusted risk ratio 1·89, 95% CI 1·16-3·08) in the handwashing station-only group, and 24% (143 of 588 occasions; 4·82, 3·06-7·59) in the TNSB group, at the 1-month follow-up. The intervention effect was only sustained in the TNSB group (98 [22%] of 450 compounds; 2·68, 1·65-4·34). INTERPRETATION: A social norm-based handwashing intervention combined with disgust-inducing messages, with provision of handwashing stations, was effective at increasing HWWS after toilet use. The provision of handwashing stations alone had little effect. Future studies should investigate whether the same approach, when delivered via mass media, can have a similar effect to the face-to-face delivery used in this study. FUNDING: None.

Pilot Implementation of Psychoeducational Workshops on Behavior Management and Stress Management for Parents and Teachers

The COVID-19 pandemic created compounding stressors for school-aged children, parents, and teachers and underscored the urgent need to widely implement evidence-based programs for promoting youth mental and behavioral health. In two community-engaged studies, we piloted psychoeducational workshops that taught behavior management and stress management strategies to parents and teachers. The research team partnered with a northern California school district to develop and implement these psychoeducational workshops. In study 1, parents (N = 165) participated in a series of workshops on behavior management. Parents perceived the strategies covered in each workshop to be acceptable, appropriate, and feasible and were able to accurately describe behavior management strategies following each workshop. In study 2, teachers (N = 113) participated in workshops on behavior management and stress management. Teachers perceived the strategies covered in each workshop to be acceptable, appropriate, and feasible and were able to accurately describe the strategies following each workshop. Findings suggest that psychoeducational workshops may be a promising avenue for promoting youth mental and behavioral health. Lessons learned from conducting this community-engaged research are discussed, as well as future directions for widely implementing psychoeducational workshops for parents and teachers.

Increased Hair Cortisol Levels are Associated With a Shift Towards Exploitative Decision-Making in Health Care Workers in the COVID-19 Pandemic

Background: During the COVID-19 pandemic, healthcare workers (HCWs) were required to make flexible decisions in a rapidly changing environment under significant stress. Linking subjective and physiological markers of stress to quantitative measures of decision-making is critical for understanding the resilience of healthcare workers during the pandemic. The aim of this study was to utilize an explore-exploit computational psychiatry paradigm to measure the effects of COVID-19 related stress on decision-making flexibility. Methods: We utilized biomarker and survey data to query chronic stress;123 participants completed the survey and 54 hair samples were collected. Cortisol was measured with LC/MS/MS. We evaluated explore/exploit behavior with a resting three-arm bandit task, and 66 completed the task. Results: Eighty-seven met criteria for COVID-19 related PTSD, however, we found no significant correlation between hair cortisol and symptoms measures. In contrast, we found that participants with higher hair cortisol exhibited greater exploitation (Pearsons’ r=-0.36, p=0.046). Additionally, explore-state reward-dependent switching behavior, a state-specific measure of learning from reward, significantly decreased with increasing cortisol (r=-0.49, p=0.007). Further, in a basic 3-parameter reinforcement learning model, the learning rate alpha inversely correlated with cortisol (r =-0.467, p=0.007). Conclusions: Computational model-derived decision-making variables demonstrated a robust correlation with hair cortisol concentrations. Without this task, biomarker data may appear independent of chronic stress. This study highlights the importance of quantitative behavioral tasks and physiological signals to understanding the interaction of mood and cognition with stress. Supported By: This work was supported by the University of Minnesota Office of Academic and Clinical Affairs COVID-19 Rapid Response Grant. Research in this publication was also supported in part by the Office Of The Director, National Institutes of Health under Award Number P51OD011106 to the Wisconsin National Primate Research Center, University of Wisconsin-Madison. This research was conducted in part (as applicable) at a facility constructed with support from Research Facilities Improvement Program grant numbers RR15459-01 and RR020141-01. Keywords: Cognitive Flexibility, Hair Cortisol, COVID-19 Pandemic, Computational Psychiatry

Determinants of turnaround time in a rapid genome sequencing program

Previous studies of genome sequencing (GS) in critically ill childrenhave made use of either modified hardware or working procedureswhich would be difficult, if not impossible, to integrate into existingclinical workflows1. Our lab’s transition from exome sequencing (ES) to GS offered an opportunity to implement in-house rapid genomesequencing (rGS) in critically ill children in a manner which couldintegrate with existing clinical workflows. We conducted a feasibilityand implementation pilot by offering rGS to child-parent triosconcurrently undergoing clinical rapid ES (rES) via a reference lab.The purpose of this study was to identify and address operationalbarriers to implementation of a rGS program capable of communicatinga preliminary result within 7 days of consent. We consideredthis time span to be more reflective of clinical realities than lab-quotedturnaround times (TAT) which typically start at sample receipt andthus do not account for challenges in sample acquisition and pre-testcounseling in a critical care setting, nor the impact of shipping times.Here we present data on TAT and lessons learned from the first 27subjects enrolled.Using rapid cycle improvement methodologies, we identified fourdistinct but inter-related workflows requiring optimization:1. Pre-analytic: patient identification through acquisition ofsamples2. Wet-lab: extraction through sequencing3. Bioinformatics: secondary and tertiary analysis as well as rapididentification of causal variants4. Return of resultsFigure 1 summarizes TAT across cases, demonstrating the markedimprovements in TAT with our programmatic approach to improvement.We used our first 9 cases to determine a baseline TAT for theentire process and to delineate the 4 main workflows (above). Atbaseline, excluding cases delayed by COVID-19 restrictions, mean TATwas 17.12 days (3 sequential deviant range: 7.05–27.19 days).Following deployment of our programmatic approach to rGS, meanTAT fell to 6.19 days (3 sequential deviant range: 0.51–11.87 days).Table 1 summarizes the observations and insights, by workflow, whichimpacted upon TAT and/or implementation. The single biggest impacton TAT was optimization of bioinformatics by removing all manualsteps between starting sequencing and producing human interpretable,filtered, annotated output of high-priority variants for interpretation.The second biggest source of improvement was optimization ofthe sequencing itself as well as prioritizing sample processing for andaccess to sequencing runs. While variant ranking is helpful in identifying causal variants, in 9/10 cases with a diagnostic findingthe causal variant(s)were obvious to the study teamwithin minutes ofviewing the annotated variant list, regardless of variant rank. (Figure Presented) As time required for sequencing and analytic workflows fell, therelative contribution of other workflows to overall TAT shifted and itbecame more obvious that early identification and utilization of thisapproach is very important in lowering overall time to diagnosis(Figure 2). In 6/10 cases with a diagnostic finding, the initial approachof the clinical team was NOT rES (and thus patients were not eligiblefor rGS on a research basis). Had rGS been the initial diagnosticmodality chosen, a diagnosis could have been reached in a median 12days sooner (range 2–28 days). There were also several cases wheresequencing was delayed when one or both parents did not present tothe lab to provide a blood sample in a timely manner. Optimization ofsequencing or analytic workflows cannot meaningfully improveoutcomes either of these situations.Our findings suggest some important considerations for institutionsdeveloping or seeking to improve rapid sequencing programs for acuteand critically ill children: (Table Presented) • Optimization of computational resource utilization and phenotypecuration saves more time than improved variant filtering orprioritization.• Obtaining samples from parents is non-trivial.• Even trained geneticists may fail to recognize appropriatecandidates for rGS.

“Indonesian government's public communication management during a pandemic”

The COVID-19 pandemic has triggered a health emergency as a vaccine for it has not been found yet requiring the government to seriously manage it. Therefore, the government needs to effectively implement non-pharmaceutical measures. One of the measures to suppress the spread of the virus is public communication. The government's public communication in dealing with COVID-19 has faced problems resulted in low public discipline and awareness thus far. This study used a quantitative approach with descriptive statistics analysis. The analysis does not generalize the result but it can explain the characteristics of the sample to formulate the meaning of the result. The findings show that the public communication management of the government of Indonesia has not been effective because the dissemination of public information is diverse and inconsistent. This is because the government gives freedom to various media to provide information to the public, which creates a gap in the management of COVID-19 in Indonesia and results in low public discipline and awareness (mean value 2,97). Therefore, it is difficult for the government to deal with and manage health emergencies caused by the COVID-19 pandemic. Research has shown that the government must provide the public with consistent and valid information (mean value 3,51), monitor and supervise mass and electronic media, and use social media and online media to provide valid information from the government and disseminate positive and educative information to the public (mean value 4,06). © Achmad Herman, 2021

Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome Due to COVID-19: A Cohort Study and Analysis of Physiology.

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19. METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning. RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2: FiO2) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every 8 patients treated. Replicating results and scaling the intervention are important, but prone positioning may represent an additional therapeutic option in patients with ARDS due to COVID-19.

Prone Positioning in Moderate to Severe Acute Respiratory Distress Syndrome due to COVID-19: A Cohort Study and Analysis of Physiology (preprint)

BACKGROUND: Coronavirus disease 2019 (COVID-19) can lead to acute respiratory distress syndrome (ARDS) but it is unknown whether prone positioning improves outcomes in mechanically ventilated patients with moderate to severe ARDS due to COVID-19.METHODS: A cohort study at a New York City hospital at the peak of the early pandemic in the United States, under crisis conditions. The aim was to determine the benefit of prone positioning in mechanically ventilated patients with ARDS due to COVID-19. The primary outcome was in-hospital death. Secondary outcomes included changes in physiologic parameters. Fine-Gray competing risks models with stabilized inverse probability treatment weighting (sIPTW) were used to determine the effect of prone positioning on outcomes. In addition, linear mixed effects models (LMM) were used to assess changes in physiology with prone positioning.RESULTS: Out of 335 participants who were intubated and mechanically ventilated, 62 underwent prone positioning, 199 met prone positioning criteria and served as controls and 74 were excluded. The intervention and control groups were similar at baseline. In multivariate-adjusted competing risks models with sIPTW, prone positioning was significantly associated with reduced mortality (SHR 0.61, 95% CI 0.46-0.80, P < 0.005). Using LMM to evaluate the impact of positioning maneuvers on physiological parameters, the oxygenation-saturation index was significantly improved during days 1-3 (P < 0.01) whereas oxygenation-saturation index (OSI), oxygenation-index (OI) and arterial oxygen partial pressure to fractional inspired oxygen (PaO2:FiO2) were significantly improved during days 4-7 (P < 0.05 for all). CONCLUSIONS: Prone positioning in patients with moderate to severe ARDS due to COVID-19 is associated with reduced mortality and improved physiologic parameters. One in-hospital death could be averted for every eight patients treated. Replicating results and scaling the intervention are important, but prone positioning may represented an additional therapeutic option in patients with ARDS due to COVID-19.