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BackgroundInformation about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited.ObjectiveTo measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19.DesignThree retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir.SettingVeterans Health Administration (VHA).ParticipantsNonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022.InterventionNirmatrelvir-ritonavir or molnupiravir pharmacotherapy.MeasurementsIncidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days.ResultsEighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants.LimitationThe date of COVID-19 symptom onset for most veterans was unknown.ConclusionNirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals.Primary funding sourceU.S. Department of Veterans Affairs.

Recent research has found substantial gaps in knowledge surrounding concussion assessment and management in various groups of Canadian healthcare professionals, including medical students, physiotherapists, chiropractic students, and family medicine physicians. The purpose of this project was to explore concussion knowledge in a sample of athletic therapy students and to use these findings to make practical pedagogical recommendations to improve concussion education. A sequential explanatory mixed-methods approach (initial questionnaire, student interviews, clinical educator interviews) was used to investigate the research question. The findings showed a large gap between theoretical knowledge and practical abilities to assess and manage concussions. Additionally, students felt less prepared to assist throughout the entire continuum of concussion care (from initial recognition to return-to-play). Based on these findings, educators should consider innovative pedagogical strategies that focus on true competence development in concussion assessment and management while bridging the gap between foundational theory and practical application/skill development.

The goal of this work was to explore ways, within an existing engineering curriculum, to address the culture of disengagement by challenging the dominant engineering mindset. We conducted Collaborative Action Research to explore the implementation of Transformative Learning pedagogies in a Human-Centered Design context to understand how students make meaning of engineering contexts that involve unique sociotechnical considerations. Findings suggest that introducing students to such contexts allows them to use other points of view which can challenge the dominant engineering mindset and promote openness to the social nature of engineering, resulting in a more informed understanding of the nature of engineering overall. Furthermore, adopting Transformative Learning Theory as a framework for understanding and interpreting how the points of view students utilize can address the culture of disengagement by challenging the dominant engineering mindset. A framework connecting students' points of view to their understanding of the nature of engineering is provided.

This perspective paper seeks to lay out an efficient approach for health care providers, researchers, and other stakeholders involved in interventions aimed at improving care coordination to partner in locating and using applicable care coordination theory. The objective is to learn from relevant theory-based literature about fit between intervention options and coordination needs, thereby bringing insights from theory to enhance intervention design, implementation, and troubleshooting. To take this idea from an abstract notion to tangible application, our workgroup on models and measures from the Veterans Health Administration (VA) State of the Art (SOTA) conference on care coordination first summarizes our distillation of care coordination theoretical frameworks (models) into three common conceptual domains-context of an intervention, locus in which an intervention is applied, and specific design features of the intervention. Then we apply these three conceptual domains to four cases of care coordination interventions ("use cases") chosen to represent various scopes and stages of interventions to improve care coordination for veterans. Taken together, these examples make theory more accessible and practical by demonstrating how it can be applied to specific cases. Drawing from theory offers one method to anticipate which intervention options match a particular coordination situation.

Public and patient involvement (PPI) has been identified as an increasingly desired and, often, required component of trial methodology–leading to higher quality, more accessible and relevant clinical research, alongside increased recruitment, funding success and insight into research impact. However, despite the great variety of frameworks and checklists available for assessing PPI, most are limited with respect to important features (e.g. applicable in specific contexts only, fail to clarify what should be assessed and reported, lack the necessary comprehensiveness or are biased in favour of researcher reporting). Thus, the current research aimed to address such limitations through the development of a new checklist, the EPPIIC, through review, thematic analysis and 'meta-evaluation' in conjunction with PPI engagement. Upon completion of the EPPIIC, three thematic 'sub-scales' emerged: (1) Policy & Practice, (2) Participatory Culture and (3) Influence & Impact. All findings are presented and discussed in light of theory and research. Notably, findings recommend EPPIIC as a useful means of assessing PPI in future trials. [ABSTRACT FROM AUTHOR]

Objective: The epidemiology of COVID-19 has substantially changed since its emergence given the availability of effective vaccines, circulation of different viral variants, and re-infections. We aimed to develop models to predict 30-day COVID-19 hospitalization and death in the Omicron era for contemporary clinical and research applications. Methods: We used comprehensive electronic health records from a national cohort of patients in the Veterans Health Administration (VHA) who tested positive for SARS-CoV-2 between March 1, 2022, and March 31, 2023. Full models incorporated 84 predictors, including demographics, comorbidities, and receipt of COVID-19 vaccinations and anti-SARS-CoV-2 treatments. Parsimonious models included 19 predictors. We created models for 30-day hospitalization or death, 30-day hospitalization, and 30-day all-cause mortality. We used the Super Learner ensemble machine learning algorithm to fit prediction models. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), Brier scores, and calibration intercepts and slopes in a 20% holdout dataset. Results: Models were trained and tested on 198,174 patients, of whom 8% were hospitalized or died within 30 days of testing positive. AUCs for the full models ranged from 0.80 (hospitalization) to 0.91 (death). Brier scores were close to 0, with the lowest error in the mortality model (Brier score: 0.01). All three models were well calibrated with calibration intercepts <0.23 and slopes <1.05. Parsimonious models performed comparably to full models. Conclusions: We developed prediction models that accurately estimate COVID-19 hospitalization and mortality risk following emergence of the Omicron variant and in the setting of COVID-19 vaccinations and antiviral treatments. These models may be used for risk stratification to inform COVID-19 treatment and to identify high-risk patients for inclusion in clinical trials. [ABSTRACT FROM AUTHOR]

Omaveloxolone is a nuclear factor (erythroid‐derived 2)‐like 2 activator approved in the United States and the European Union for the treatment of patients with Friedreich ataxia aged ≥16 years, with a recommended dosage of 150 mg orally once daily on an empty stomach. The effect of the US Food and Drug Administration (FDA) high‐fat breakfast on the pharmacokinetic profile of omaveloxolone observed in study 408‐C‐1703 (NCT03664453) deviated from the usual linear correlation between fed/fasted maximum plasma concentration (Cmax) and area under the concentration–time curve (AUC) ratios reported for various oral drugs across 323 food effect studies. Here, physiologically based biopharmaceutics modeling (PBBM) was implemented to predict and explain the effect of the FDA high‐fat breakfast on a 150‐mg dose of omaveloxolone. The model was developed and validated based on dissolution and pharmacokinetic data available across dose‐ranging, food effect, and drug–drug interaction clinical studies. PBBM predictions support clinical observations of the unique effect of a high‐fat meal on omaveloxolone pharmacokinetic profile, in which the Cmax increased by 350% with only a 15% increase in the AUC. Key parameters influencing omaveloxolone pharmacokinetics in the fasted state based on a parameter sensitivity analysis included bile salt solubilization, CYP3A4 activity, drug substance particle size distribution, and permeability. Mechanistically, in vivo omaveloxolone absorption was solubility and dissolution rate limited. However, in the fed state, higher bile salt solubilization led to more rapid dissolution with predominant absorption in the upper gastrointestinal tract, resulting in increased susceptibility to first‐pass gut extraction; this accounts for the lack of correlation between Cmax and AUC for omaveloxolone. [ABSTRACT FROM AUTHOR]

Omaveloxolone (SKYCLARYS®) is approved for the treatment of Friedreich ataxia (FA) in patients aged ≥16 years in the United States and European Union (EU). The recommended dosage is 150 mg administered orally once daily as three 50‐mg capsules. However, some patients with FA may have oropharyngeal dysphagia or difficulty swallowing whole capsules; therefore, alternate method(s) of administration are needed. A Phase 1 clinical study in 32 healthy volunteers evaluated the relative bioavailability, safety, and tolerability of a single dose of omaveloxolone when capsule contents were sprinkled on and mixed in applesauce compared to when taken as intact capsules. Palatability when sprinkled on and mixed in applesauce was assessed with a questionnaire. After a single 150‐mg dose, the peak and overall exposures of omaveloxolone were similar irrespective of administration method, with the 90% CIs of the geometric least squares mean ratio (%) for maximum plasma concentration (Cmax), AUC0‐t, and AUC0‐∞ within the 80% to 125% reference intervals. Omaveloxolone was absorbed more slowly as intact capsules (median tmax, 10 h) compared with sprinkled capsule contents over applesauce (median tmax, 6 h). With chronic daily administration of omaveloxolone to treat FA, the 4‐h difference in tmax is not considered clinically relevant. Sprinkled omaveloxolone capsule contents on applesauce were well tolerated, with acceptable palatability and no serious adverse events. Given the similar systemic exposure when capsules were swallowed whole, sprinkling omaveloxolone capsule contents on and mixing in applesauce is a feasible alternative method of administering omaveloxolone and has been included in both the United States and EU prescribing information. [ABSTRACT FROM AUTHOR]

Place-based branding strategies are important marketing tools for both regions and firms and take advantage of consumers' embrace of the local in response to globalisation. Craft-brewing is a particularly salient user of these strategies and provides ample data. We use a dataset of breweries, their marketing language and their consumer ratings to study the effectiveness of place-based branding. We use named entity recognition to count references to geography, and measure how these references impact ratings. We find a strong, positive link between the number of place-based labels and a brewery's rating, suggesting consumers are receptive to placed-based branding. [ABSTRACT FROM AUTHOR]

Many Veterans receive Department of Veterans Affairs (VA)-purchased care from non-VA facilities but little is known about factors that Veterans consider for this choice. Between May 2020 and August 2021, we surveyed VA-purchased care-eligible VA patients about barriers and facilitators to choosing where to receive care. We examined the association between travel time to their VA facility and their choice of VA-purchased care (VA-paid health care received in non-VA settings) versus VA facility and whether this association was modified by distrust. We received 1,662 responses and 692 (42%) chose a VA facility. Eighty percent reported quality care was in their top three factors that influenced their decision. Respondents with the highest distrust and who lived >1 hr from the nearest VA facility had the lowest predicted probability (PP) of choosing VA (PP 15%; 95% confidence interval: 10%–20%). Veterans value quality of care. VA and other health care systems should consider patient-centered ways to improve and publicize quality and reduce distrust. [ABSTRACT FROM AUTHOR]

Computational thinking requires high cognitive load as students work to manage multiple tasks in their problem-solving environment. Through research in K-2 classrooms on computational thinking, we noticed that students lack the representational fluency needed to move from one form to another--such as moving from physical to more abstract representations. Therefore, the following research question was studied: How do second-grade students use and translate among representations to solve computational thinking tasks using the robot mouse game? To address this, we employed a task-based interview approach with three second-grade students who were engaged in four computational thinking tasks using the Code and Go Robot Mouse Coding Activity Set developed by Learning Resources. Through four clinical tasks involving the robot mouse, students solved puzzles set up to force them to make particular representational translations. Each translation involved a level of cognitive complexity the students needed to manage to successfully complete the task. We found that students translated between many different representations using concrete representations to ease translations, language as a scaffold between translations, and embodied movements as representations or to assist with translation. Furthermore, the levels of representational maturity showed by the students varied with the difficulty of the task, and the spatial orientation was particularly difficult for them. These results provide important insights into how learners may develop their ability to engage with abstract representations that will be part of future practices associated with activities in science, mathematics, engineering, and computational thinking.