Noninvasive Ventilation for Preoxygenation during Emergency Intubation.

BACKGROUND: Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. METHODS: In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. RESULTS: Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). CONCLUSIONS: Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials. METHODS: A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models. RESULTS: Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time. CONCLUSIONS: Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

Association between monoclonal antibody therapy, vaccination, and longer-term symptom resolution after acute COVID-19.

Effective therapies for reducing post-acute sequelae of COVID-19 (PASC) symptoms are lacking. Evaluate the association between monoclonal antibody (mAb) treatment or COVID-19 vaccination with symptom recovery in COVID-19 participants. The longitudinal survey-based cohort study was conducted from April 2021 to January 2022 across a multihospital Colorado health system. Adults ≥18 years with a positive SARS-CoV-2 test were included. Primary exposures were mAb treatment and COVID-19 vaccination. The primary outcome was time to symptom resolution after SARS-CoV-2 positive test date. The secondary outcome was hospitalization within 28 days of a positive SARS-CoV-2 test. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. Analysis included 1612 participants, 539 mAb treated, and 486 with ≥2 vaccinations. Time to symptom resolution was similar between mAb treated versus untreated patients (adjusted hazard ratio (aHR): 0.90, 95% CI: 0.77-1.04). Time to symptom resolution was shorter for patients who received ≥2 vaccinations compared to those unvaccinated (aHR: 1.56, 95% CI: 1.31-1.88). 28-day hospitalization risk was lower for patients receiving mAb therapy (adjusted odds ratio [aOR]: 0.31, 95% CI: 0.19-0.50) and ≥2 vaccinations (aOR: 0.33, 95% CI: 0.20-0.55), compared with untreated or unvaccinated status. COVID-19 vaccination, but not mAb therapy, was associated with a shorter time to symptom resolution. Both were associated with lower 28-day hospitalization.

Neuroethics and neurolaw in forensic neuropsychiatry: A guide for clinicians.

As neuroscience technologies develop, ethical and legal questions arise regarding their use and societal impact. Neuroethics and neurolaw are growing interdisciplinary fields that address these questions. This review article presents the research agenda of both areas, examines the use and admissibility of neuroscience in expert testimony and legal settings, and discusses ethical issues related to forensic neuropsychiatrists claiming expertise in neuroscience, formulating medical opinions based on neuroscience, and considering its relevance to criminal responsibility. Forensic neuropsychiatrists should be aware of emerging neuroscientific evidence, its utility and limits in rendering diagnoses and explaining behavior, and, before seeking such evidence for legal purposes, its availability and admissibility. When testifying in matters involving neuroscientific evidence, ensuring truthfulness and balance, having sufficient and validated knowledge (including openness with confirming and disconfirming evidence), understanding standards of practice, and drawing relevant and appropriate conclusions remain important.

Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial.

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates. Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo. Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation. Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days. Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL. Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen. Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

Patient Perceptions of Illness Causes and Treatment Preferences for Obsessive-Compulsive Disorder: A Mixed-Methods Study.

Obsessive-compulsive disorder (OCD) is a condition with high patient morbidity and mortality. Research shows that eliciting patient explanations about illness causes and treatment preferences promotes cross-cultural work and engagement in health services. These topics are in the Cultural Formulation Interview (CFI), a semi-structured interview first published in DSM-5 that applies anthropological approaches within mental health services to promote person-centered care. This study focuses on the New York City site of an international multi-site study that used qualitative-quantitative mixed methods to: (1) analyze CFI transcripts with 55 adults with OCD to explore perceived illness causes and treatment preferences, and (2) explore whether past treatment experiences are related to perceptions about causes of current symptoms. The most commonly named causes were circumstantial stressors (n = 16), genetics (n = 12), personal psychological traits (n = 9), an interaction between circumstantial stressors and participants' brains (n = 6), and a non-specific brain problem (n = 6). The most common treatment preferences were psychotherapy (n = 42), anything (n = 4), nothing (n = 4), and medications (n = 2). Those with a prior medication history had twice the odds of reporting a biological cause, though this was not a statistically significant difference. Our findings suggest that providers should ask patients about illness causes and treatment preferences to guide treatment choice.

Epigenetics may characterize asymptomatic COVID-19 infection.

RT-PCR is the foremost clinical test for diagnosis of COVID-19. Unfortunately, PCR-based testing has limitations and may not result in a positive test early in the course of infection before symptoms develop. Enveloped RNA viruses, such as coronaviruses, alter peripheral blood methylation and DNA methylation signatures may characterize asymptomatic versus symptomatic infection. We used Illumina's Infinium MethylationEPIC BeadChip array to profile peripheral blood samples from 164 patients who tested positive for SARS-CoV-2 by RT-PCR, of whom 8 had no symptoms. Epigenome-wide association analysis identified 10 methylation sites associated with infection and a quantile-quantile plot showed little inflation. These preliminary results suggest that differences in methylation patterns may distinguish asymptomatic from symptomatic infection.

Evaluating Primary Endpoints for COVID-19 Therapeutic Trials to Assess Recovery.

Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.

The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19.

BACKGROUND: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. OBJECTIVE: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. DESIGN: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. SETTING: 114 centers in 10 countries. PARTICIPANTS: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. MEASUREMENTS: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. RESULTS: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. LIMITATIONS: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. CONCLUSION: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients. PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

The Evolving Culture Concept in Psychiatric Cultural Formulation: Implications for Anthropological Theory and Psychiatric Practice.

For thirty years, psychiatrists and anthropologists have collaborated to improve the validity of psychiatric diagnosis. This collaboration has produced the DSM-IV Outline for Cultural Formulation (OCF) and the DSM-5 Cultural Formulation Interview (CFI). Nonetheless, some anthropologists have critiqued the concept of culture in DSM-5 as too focused on patient meanings and not on clinician practices. This article traces the evolution of the culture concept from DSM-IV through DSM-5-TR by analyzing publications from the American Psychiatric Association on the OCF and CFI alongside scholarship in psychiatry and anthropology. DSM-IV relied on a culture concept of coherent ethnic communities sharing coherent cultures, primarily for minoritized ethnoracial individuals in the United States. Changing demographics and newer immigration patterns around the world deminoritized the culture concept for DSM-5. After George Floyd's death and demands for social justice, the culture concept in DSM-5-TR emphasized social structures. The article proposes an intersubjective model of culture through which patients and clinicians work through similarities and differences. It recommends a revised formulation that attends to clinician practices such as communicating, diagnosing, recommending treatments, and documenting, beyond collecting patient meanings. It also raises the question of whether an intersubjective model of culture prompts reconsiderations of culture-related text in other sections of the DSM. The social sciences can redirect attention to the clinician's culture of biomedicine to close patient health disparities.

Patient identity narratives through the cultural formulation interview in a New York City outpatient clinic.

Anthropologists have critiqued cultural competence programs in medical settings while introducing mental health clinicians to social theories on culture for practice. We explore how patients articulated narratives about themselves and how clinicians responded to such narratives through an intervention known as the Cultural Formulation Interview that anthropologists have helped develop. We conducted over 500 hours of fieldwork from 2014 to 2019 at an outpatient clinic in New York, analyzing multiple data (participant observation, medical records, patient-clinician sessions, and individual debriefing interviews) in a trial joining clinical and ethnographic methods. Our study enrolled 45 patients and six clinicians, yielding 117 patient-clinician appointments and 98 debriefing interviews. Most patients differed in how they presented their identities through demographic forms and discussed them in sessions with their clinicians. Two-thirds of the patients drew connections between their personal identities and experiences of mental illness. These results reveal why cultural identities should not be taken for granted in clinical settings.

Real-World Evidence of the Neutralizing Monoclonal Antibody Sotrovimab for Preventing Hospitalization and Mortality in COVID-19 Outpatients.

BACKGROUND: It is not known whether sotrovimab, a neutralizing monoclonal antibody (mAb) treatment authorized for early symptomatic coronavirus disease 2019 (COVID-19) patients, is also effective in preventing the progression of severe disease and mortality following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant infection. METHODS: In an observational cohort study of nonhospitalized adult patients with SARS-CoV-2 infection, 1 October 2021-11 December 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data, we used propensity matching to select 3 patients not receiving mAbs for each patient who received outpatient sotrovimab treatment. The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. RESULTS: Of 10 036 patients with SARS-CoV-2 infection, 522 receiving sotrovimab were matched to 1563 not receiving mAbs. Compared to mAb-untreated patients, sotrovimab treatment was associated with a 63% decrease in the odds of all-cause hospitalization (raw rate 2.1% vs 5.7%; adjusted odds ratio [aOR], 0.37; 95% confidence interval [CI], .19-.66) and an 89% decrease in the odds of all-cause 28-day mortality (raw rate 0% vs 1.0%; aOR, 0.11; 95% CI, .0-.79), and may reduce respiratory disease severity among those hospitalized. CONCLUSIONS: Real-world evidence demonstrated sotrovimab effectiveness in reducing hospitalization and all-cause 28-day mortality among COVID-19 outpatients during the Delta variant phase.

Association between treatment failure and hospitalization after receipt of neutralizing monoclonal antibody treatment for COVID-19 outpatients.

BACKGROUND: Neutralizing monoclonal antibodies (mAbs) are highly effective in reducing hospitalization and mortality among early symptomatic COVID-19 patients in clinical trials and real-world data. While resistance to some mAbs has since emerged among new variants, characteristics associated with treatment failure of mAbs remain unknown. METHODS: This multicenter, observational cohort study included patients with COVID-19 who received mAb treatment between November 20, 2020, and December 9, 2021. We utilized electronic health records from a statewide health system plus state-level vaccine and mortality data. The primary outcome was mAb treatment failure, defined as hospitalization or death within 28 days of a positive SARS-CoV-2 test. RESULTS: COVID-19 mAb was administered to 7406 patients. Hospitalization within 28 days of positive SARS-CoV-2 test occurred in 258 (3.5%) of all patients who received mAb treatment. Ten patients (0.1%) died within 28 days, and all but one were hospitalized prior to death. Characteristics associated with treatment failure included having two or more comorbidities excluding obesity and immunocompromised status (adjusted odds ratio [OR] 3.71, 95% confidence interval [CI] 2.52-5.56), lack of SARS-CoV-2 vaccination (OR 2.73, 95% CI 2.01-3.77), non-Hispanic black race/ethnicity (OR 2.21, 95% CI 1.20-3.82), obesity (OR 1.79, 95% CI 1.36-2.34), one comorbidity (OR 1.68, 95% CI 1.11-2.57), age ≥ 65 years (OR 1.62, 95% CI 1.13-2.35), and male sex (OR 1.56, 95% CI 1.21-2.02). Immunocompromised status (none, mild, or moderate/severe), pandemic phase, and type of mAb received were not associated with treatment failure (all p > 0.05). CONCLUSIONS: Comorbidities, lack of prior SARS-CoV-2 vaccination, non-Hispanic black race/ethnicity, obesity, age ≥ 65 years, and male sex are associated with treatment failure of mAbs.

Person-Centered Cultural Assessment Can Improve Child Mental Health Service Engagement and Outcomes.

OBJECTIVE: Disparities in child mental health service engagement suggest traditional evidence-based practices do not properly consider cultural and contextual factors relevant for marginalized families. We propose a person-centered approach to improve the cultural responsiveness of services. Preliminary research supports broadening standard assessments to include a person-centered evaluation of patient cultural factors, however, controlled studies have not been conducted in the context of children's mental health care. METHODS: Participants included families (N = 89; 89% racial/ethnic minority) receiving services for child externalizing problems. Prior to intake, caregivers were randomized to receive either Assessment as Usual (AAU) or AAU augmented with the Cultural Formulation Interview (CFI+AAU), a brief caregiver assessment of cultural factors affecting their child's problems and family help-seeking. RESULTS: Implementation data showed strong provider fidelity and clinical utility. Following assessments, CFI+AAU caregivers (relative to AAU caregivers) reported feeling better understood by their provider, and providers reported better understanding CFI+AAU families' values. Caregiver satisfaction was rated highly overall, yet providers reported being more satisfied with the assessment when the CFI was incorporated. Engagement outcomes found CFI+AAU families were significantly more likely than AAU families to subsequently complete the first phase of treatment. Further, among families receiving services in Spanish, CFI+AAU, relative to AAU, was associated with significantly higher treatment attendance, homework completion, and treatment response. CONCLUSIONS: The results underscore the utility of incorporating a brief cultural assessment in pretreatment assessments. To improve the cultural responsiveness of services, efforts may do well to promote the uptake of person-centered approaches such as cultural assessment into usual care. Registered at clinicaltrials.gov (NCT03499600).

If You Don't Ask, They Don't Tell: The Cultural Formulation Interview and Patient Perceptions of the Clinical Relationship.

SYNOPSIS: More than half of participating patients expressed mistrust or ambivalence toward clinicians related to differences in cultural background using the Cultural Formulation Interview, which can help enhance communication and trust and help clinicians to anticipate treatment barriers.

Reporting Grantee Demographics for Diversity, Equity, and Inclusion in Neuroscience.

Professional neuroscience organizations have recently pledged their commitments to diversity, equity, and inclusion in examining institutional discrimination; to raise questions about how to train underrepresented scientists; and to recruit underrepresented subjects for a more equitable scientific enterprise in the 21st century. Studies have illuminated racial disparities in funding, likely because of implicit bias in the review process and differential access to resources. We propose that one concrete way to monitor and redress these disparities is to collect and publicize data on grantees by gender, race, ethnicity, and location from neuroscience funding agencies. Beyond remedying historical disadvantages, disseminating funding more equitably across recipients would be an empirical solution that can improve the very quality of neuroscience.

Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines-Selecting Compounds for Clinical Evaluation in Coronavirus Disease 2019 Clinical Trials.

Given the urgent need for coronavirus disease 2019 therapeutics, early in the pandemic the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership rapidly designed a unique therapeutic agent intake and assessment process for candidate treatments of coronavirus disease 2019. These treatments included antivirals, immune modulators, severe acute respiratory syndrome coronavirus 2 neutralizing antibodies, and organ-supportive treatments at both the preclinical and clinical stages of development. The ACTIV Therapeutics-Clinical Working Group Agent Prioritization subgroup established a uniform data collection process required to perform an assessment of any agent type using review criteria that were identified and differentially weighted for each agent class. The ACTIV Therapeutics-Clinical Working Group evaluated over 750 therapeutic agents with potential application for coronavirus disease 2019 and prioritized promising candidates for testing within the master protocols conducted by ACTIV. In addition, promising agents among preclinical candidates were selected by ACTIV to be matched with laboratories that could assist in executing rigorous preclinical studies. Between April 14, 2020, and May 31, 2021, the Agent Prioritization subgroup advanced 20 agents into the Accelerating Coronavirus Disease 2019 Therapeutic Interventions and Vaccines master protocols and matched 25 agents with laboratories to assist with preclinical testing.

Identifying Clinical Research Priorities in Adult Pulmonary and Critical Care. NHLBI Working Group Report.

Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the NHLBI. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have yielded improvements in supportive care, which have translated into improved patient outcomes. Novel therapeutics have largely failed to translate from promising preclinical findings into improved patient outcomes in late-phase clinical trials. Recent advances in personalized medicine, "big data," causal inference using observational data, novel clinical trial designs, preclinical disease modeling, and understanding of recovery from acute illness promise to transform the methods of pulmonary and critical care clinical research. To assess the current state of, research priorities for, and future directions in adult pulmonary and critical care research, the NHLBI assembled a multidisciplinary working group of investigators. This working group identified recommendations for future research, including 1) focusing on understanding the clinical, physiological, and biological underpinnings of heterogeneity in syndromes, diseases, and treatment response with the goal of developing targeted, personalized interventions; 2) optimizing preclinical models by incorporating comorbidities, cointerventions, and organ support; 3) developing and applying novel clinical trial designs; and 4) advancing mechanistic understanding of injury and recovery to develop and test interventions targeted at achieving long-term improvements in the lives of patients and families. Specific areas of research are highlighted as especially promising for making advances in pneumonia, acute hypoxemic respiratory failure, and acute respiratory distress syndrome.

Patient and clinician communication practices during the DSM-5 cultural formulation interview field trial.

Cultural psychiatrists and medical anthropologists have collaborated to help clinicians screen for culture-related issues in patient explanatory models of illness and to enhance the clinical processes of engagement, diagnosis, and treatment planning. This effort prioritises patient perspectives on suffering and healing to counter the trend of symptom-based interviews which assume biologically determined models of mental disorders. The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) includes the Cultural Formulation Interview (CFI), a semi-structured questionnaire for eliciting patient explanatory models. This paper analyses specific linguistic meanings and practices that could account for patient perceptions of improved rapport with clinicians, clinician perceptions of improving information gathering, and cultural models of health and illness during the DSM-5 field trial piloting the CFI. Twenty-seven audiotapes were analysed through the Roter Interaction Analysis System (RIAS), a standardised method for examining medical interviews based on ethnographic studies of small-group communication. After an introduction with procedural and reassurance statements to orient communication, the CFI's open-ended questions elicited patients' opinions on interpersonal, environmental, and biomedical information. Clinicians made facilitation and activation statements for patients to speak more and informed patients about what to expect. Patients constructed cultural models of illness that weaved interpersonal, environmental, and biomedical information. Clinicians and patients made rapport-building statements to each other. A RIAS-derived patient-centred score indicates that CFI sessions addressed patient concerns. Our work offers a way to analyse the discursive construction of culture in health settings and patient-centredness through detailed examinations of linguistic meanings and practices.