Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.

Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP): study protocol for a multicenter, randomized, adaptive allocation clinical trial to identify the optimal duration of induced hypothermia for neuroprotection in comatose, adult survivors of after out-of-hospital cardiac arrest.

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).

Traumatic Brain Injury and Risk of Schizophrenia and Other Non-mood Psychotic Disorders: Findings From a Large Inpatient Database in the United States.

BACKGROUND: Traumatic brain injury (TBI) is linked with an increased risk of schizophrenia and other non-mood psychotic disorders (psychotic disorders), but the prevalence and contributing factors of these psychiatric conditions post-TBI remain unclear. This study explores this link to identify key risk factors in TBI patients. METHODS: We used the 2017 National Inpatient Sample dataset. Patients with a history of TBI (n = 26 187) were identified and matched 1:1 by age and gender to controls without TBI (n = 26 187). We compared clinical and demographic characteristics between groups. The association between TBI and psychotic disorders was explored using the logistic regression analysis, and results were presented as Odds ratio (OR) and 95% confidence interval (CI). RESULTS: Psychotic disorders were significantly more prevalent in TBI patients (10.9%) vs controls (4.7%) (P < .001). Adjusted odds of psychotic disorders were 2.2 times higher for TBI patients (95% CI 2.05-2.43, P < .001). Male TBI patients had higher psychotic disorders prevalence than females (11.9% vs 8.4%). Younger age, bipolar disorder, anxiety disorders, substance abuse, personality disorders, and intellectual disability are associated with an increased risk of psychotic disorders in men. CONCLUSION: Our study found that hospitalized TBI patients had 2.2 times higher odds of Schizophrenia non-mood psychotic disorder, indicating an association. This highlights the need for early screening of psychotic disorders and intervention in TBI patients, calling for more research.

Three Lessons Learned About Power and Improving Recruitment of Underrepresented Populations in Clinical Trials.

This Open Forum is relevant for investigators who conduct research with historically understudied and marginalized populations. The authors introduce a U.S. Department of Veterans Affairs clinical trial that experienced challenges with recruitment of African American or Black veterans and was terminated for not achieving its recruitment goals. The role of power dynamics in clinical research is discussed, specifically how unequal distributions of power may create recruitment challenges. The authors summarize three lessons learned and offer recommendations for sharing power equitably between investigators and potential participants. By recounting these experiences, the authors seek to promote culturally sensitive, veteran-centered approaches to recruitment in future clinical trials.

Duty Hours on Surgery Clerkship: From Compliance Nightmare to Leadership and Professional Development Opportunity.

OBJECTIVE: To evaluate the impact of an innovative leadership development initiative in the core surgery clerkship that addressed duty hours compliance and time-off requests. DESIGN: A combination of deductive and inductive analysis of medical student reflections written after rotating on Acute Care Surgery over 2 academic years (2019-2020 and 2020-2021) was performed. Reflections were part of criteria to receive honors and a prompt was given to discuss their experience in creating their own call schedules. We utilized a combined deductive and inductive process to identify predominant themes within the reflections. Once established, we quantitatively identified frequency and density of themes cited, along with qualitative analysis to determine barriers and lessons learned. SETTING: Dell Seton Medical Center, Dell Medical School at The University of Texas at Austin, a tertiary academic facility. PARTICIPANTS: There were 96 students who rotated on Acute Care Surgery during the study period, 64 (66.7%) of whom completed the reflection piece. RESULTS: We identified 10 predominant themes through the combined deductive and inductive processes. Barriers were cited by most students (n = 58, 91%), with communication being the most commonly discussed theme when cited with a mean 1.96 references per student. Learned leadership skills included: communication, independence, teamwork, negotiating skills, reflection of best practices by residents, and realizing the importance of duty hours. CONCLUSIONS: Transferring duty hour scheduling responsibilities to medical students resulted in multiple professional development opportunities while decreasing administrative burden and improving adherence to duty hour requirements. This approach requires further validation, but may be considered at other institutions seeking to improve the leadership and communication skills of its students, while improving adherence to duty hour restrictions.

Enhancing study recruitment through implementation of an opt-out, cold contact process with consideration for autonomy, beneficence and justice.

The potential utilization of a cold-contact approach to research recruitment, where members of the research team are unknown to the patient, has grown with the expanded use of electronic health records (EHRs) and affiliated patient portals. Institutions that permit this strategy vary in their implementation and management of it but tend to lean towards more conservative approaches. This process paper describes the Medical University of South Carolina's transition to an opt-out model of "cold-contact" recruitment (known as patient outreach recruitment or POR), wherein patients can be contacted so long as they do not express an unwillingness to receive such communication. The work highlights the benefits of this model by explaining how it, in many ways, supports and protects autonomy, beneficence, and justice for patients. The paper then describes the process of standing up the recruitment strategy, communicating the change to patients and the community, and documenting study team contact and patient research preference. Data supporting increased access to potentially eligible patients of greater diversity as well as initial researcher feedback on perceived success of POR is also shared. The paper ends with a discussion of next steps to enhance the POR process via more detailed data collection and reengagement with community stakeholders.

The use of current knowledge and non-invasive testing modalities for predicting at-risk non-alcoholic steatohepatitis and assessing fibrosis.

There is ongoing recognition of the burden of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), with fibrosis being the most important histological feature that is associated with progression to cirrhosis and the occurrence of major adverse liver outcomes. Liver biopsy is the gold standard applied to detect NASH and determine the stage of fibrosis, but its use is limited. There is a need for non-invasive testing (NIT) techniques to identify patients considered at-risk NASH (NASH with NAFLD activity score > 4 and ≥ F2 fibrosis). For NAFLD-associated fibrosis, several wet (serological) and dry (imaging) NITs are available and demonstrate a high negative predictive value (NPV) for excluding those with advanced hepatic fibrosis. However, identifying at-risk NASH is more challenging; there is little guidance on how to use available NITs for these purposes, and these NITs are not specifically designed to identify at-risk NASH patients. This review discusses the need for NITs in NAFLD and NASH and provides data to support the use of NITs, focusing on newer methods to non-invasively identify at-risk NASH patients. This review concludes with an algorithm that serves as an example of how NITs can be integrated into care pathways of patients with suspected NAFLD and potential NASH. This algorithm can be used for staging, risk stratification and the effective transition of patients who may benefit from specialty care.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Racial Disparities in Breast Cancer Presentation and Diagnosis in COVID-Era Central Texas.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the diagnosis of breast cancer (BC). With a large Hispanic/Latinx population, early revocation of mask mandates, and lower vaccination rate than many other states, this study explores the relationship between COVID-19 and the presentation and diagnosis of BC patients in the unique socio-politico-economic context of Central Texas. METHODS: This study is a retrospective review of the Seton Medical Center Austin tumor registry for BC patients from March 1, 2019 to March 2, 2021. We compared demographics, insurance status, clinical and pathologic stage, and time from diagnosis to intervention between "pre-COVID" (March 1, 2019- March 1, 2020) and "post-COVID" (March 2, 2020-March 2, 2021). We utilized descriptive, univariate, and multivariable logistic regression statistics. RESULTS: There were 781 patients diagnosed with BC, with 113 fewer post-COVID compared to pre-COVID. The proportion of Black patients diagnosed with BC decreased post-COVID compared with pre-COVID (10.1%-4.5%, P = 0.002). When adjusting for other factors, uninsured and underinsured patients had increased odds of presenting with late-stage BC (odds ratio:5.40, P < 0.001). There was also an association between presenting with stage 2 or greater BC and delayed time-to-intervention. CONCLUSIONS: Although fewer women overall were diagnosed with BC post-COVID, the return to baseline diagnoses has yet to be seen. We identified a pandemic-related decrease in BC diagnoses in Black women and increased odds of late-stage cancer among uninsured patients, suggesting a disparate relationship between COVID-19 and health care access and affordability. Outreach and screening efforts should address strategies to engage Black and uninsured patients.

Parents' and children's intolerance of uncertainty and their reactions to COVID-19: A story of remarkable similarity.

The COVID-19 viral outbreak is a one in 100 year public health crisis. In addition to the stunning morbidity and mortality rates related to infection, multiple psychiatric sequelae erupted. Unfortunately, children and adolescents are neither immune to infection nor to the emotional consequences associated with the pandemic. Not surprisingly, the field's understanding of the psychological consequences of the viral outbreak are nascent. Consequently, this study examines the relationship between parents' and children's intolerance of uncertainty (IU) and their reactions to COVID-19. Seventy-three parents and 62 children participated in the on-line survey utilizing innovative measures of IU and COVID-19- related thoughts/behaviors. The results revealed remarkable similarities in parents' and children's responses. Parents' and children's reports of the impact of COVID on their lives were highly correlated (r = .53, df = 60, p < .001). Parents' perceptions of children's COVID-19 thoughts and behaviors were strongly aligned with the youths' self-report of their COVID reactions (r = .69, df = 60, p < .001) as well as the appraisal of the virus' impact on their lives (r = .-.42, df = 60, p < .001). Finally, children's reports of their COVID-19 related thoughts and behaviors were significantly linked to their IU (r = .60, df = 60, p < .001). Methodological limitations notwithstanding, the study's findings provide compelling implications for the conceptualization, assessment, and treatment of emotional distress in the peri- and post-pandemic periods.

Modeling HCV elimination recovery following the COVID-19 pandemic in the United States: Pathways to regain progress.

BACKGROUND: As of 2019, the United States (US) was not on track to achieve targets for elimination, due to increasing incidence and treatment barriers. In 2020, the COVID-19 pandemic disrupted HCV services globally and in the US. As healthcare services normalize, there is an urgent need to reassess progress and evaluate scenarios that restore a pathway toward HCV elimination. METHODS: We updated a validated Markov model to estimate HCV-related morbidity and mortality in the US. Five scenarios were developed to bookend possible HCV outcomes in the wake of the pandemic. These included 1) return to pre-COVID-19 treatment forecasts; 2) achieve elimination targets through treatment and harm reduction; 3) long-term treatment disruptions; 4/5) achieve elimination targets through increased treatment without increased harm reduction, starting in either 2022 or 2025. FINDINGS: From 2014-2019, more than 1.2 million patients were treated for HCV in the US. Elimination targets in 2030 could be achieved in the US by treating an additional 3.2-3.3 million patients from 2020 to 2030, or by preventing new infections through expanded harm reduction programs and treating up to 2.7 million patients. Intervention scenarios could prevent over 30,000 HCC cases and over 29,000 liver-related deaths. INTERPRETATION: The US has made strides toward HCV elimination, but gains could be lost in the wake of the pandemic. However, it is still possible to avert nearly 30,000 deaths through increased harm reduction and increased treatment rates. This requires a coordinated effort from the entire HCV community.

Systematic review of quantitative studies assessing the relationship between environment and mental health in rural areas.

OBJECTIVE: Physical and natural environments might strongly influence mental health and well-being. Many studies have examined this relationship in urban environments, with fewer focused on rural settings. The aim of this systematic review was to synthesise quantitative evidence for the relationship between environmental factors (drought, climate and extreme weather events, land use/environmental degradation, green space/vegetation, engagement in natural resource management activities) and mental health or well-being in rural areas. DESIGN: Following a systematic search of three databases (PsycINFO, MEDLINE and Web of Science), 4368 articles were identified, of which 28 met eligibility criteria for inclusion in the review. RESULTS: Poorer mental health and well-being was typically found to have an association with extreme climate or weather events and environmental degradation. The observed relationships were largely assessed at area-wide or community levels. CONCLUSIONS: Studies examining the relationship between the environmental condition of land and mental health at an individual level, particularly within farms, are lacking. Addressing this gap in research requires interdisciplinary expertise and diverse methodology. Few studies examined the effects of natural resource management practices/principles or biodiversity on mental health. While there is evidence that extreme climate or weather events have a negative impact on mental health in rural areas, there remain considerable gaps in our knowledge of how rural environments influence mental health and well-being.

The Effect of Academic Nurse Leaders' Toxic Behaviors.

BACKGROUND: A growing nursing faculty shortage, despite recruitment and retention efforts, is negatively affecting the nursing shortage. This study explored the relationships between academic nurse leaders' (ANL) toxic behaviors, job satisfaction, and anticipated turnover, and identified specific behaviors that affect faculty members' intent to stay. METHOD: A descriptive, correlational, mixed-methods study was conducted using a convenience sample of nursing faculty (N = 58). Participants completed the Toxic Leadership Scale, the Anticipated Turnover Scale, and the Minnesota Satisfaction Questionnaire Short-Form and also answered two open-ended questions. RESULTS: Moderate negative correlations between toxic leadership and intrinsic satisfaction, extrinsic factors, and general satisfaction were revealed, as well as specific behaviors causing faculty to want to leave. CONCLUSION: Increased awareness about the nature and influence of ANL toxic behaviors is needed to effectively address toxic behaviors and promote ANL accountability. Results indicate faculty are more satisfied in their role when ANL demonstrated open, honest, and transparent communication. [J Nurs Educ. 2022;61(2):88-92.].

Crafting Community-Based Participatory Research Stroke Interventions.

Stroke exerts a tremendous burden on individuals, families, communities, and health systems globally. Even more troublesome are the striking disparities faced across diverse populations. These disparities are further exacerbated by the COVID-19 pandemic. Despite efforts to advance stroke research, substantial gaps remain in understanding factors that contribute to stroke disparities, including the Social Determinants of Health. Strategically designed studies and tailored interventions are needed to bridge the inequities high-risk populations face and to meet their specific needs. Community-based participatory research offers an approach to equitably partner with community members to understand and work collaboratively to address community-specific health priorities. In this focused update, we highlight the main processes of community-based participatory research studies and share exemplars from our team's work in stroke research and from the literature. As we continue to face an increasing prevalence of stroke, compounded by the COVID-19 pandemic and ongoing implications of the Social Determinants of Health, partnering with communities to address community-driven health priorities can inform interventions targeted to overcome the disparities faced by certain populations.

Legal Admissibility of the Competence Assessment for Standing Trial for Defendants with Mental Retardation (CAST-MR).

The Competence Assessment for Standing Trial for Defendants with Mental Retardation (CAST-MR) was developed to assess competence to stand trial in defendants with Intellectual Disability. Although it remains the only validated instrument for this population, previous research has suggested it is rarely used by forensic examiners, a finding our survey of legal cases confirms. Initial validation studies provided some support for the instrument's reliability and validity. However, in both these and subsequent studies, there were significant limitations with respect to the size and representativeness of study samples, and therefore the associated interpretation of scores, such that questions remain as to whether the tool adequately assesses competence to stand trial in this population. In this paper, we review the research on the CAST-MR, discuss the strengths and limitations of the instrument, and debate its legal admissibility.

Characteristics and outcomes for defendants charged with misdemeanors referred for court-ordered competency evaluations.

Recent research has suggested nationwide increases in the rates of referral for competence to stand trial (CST) evaluations across the United States. Many of these evaluations are for defendants charged only with misdemeanor offenses and for whom diversion programs are most appropriate. The present study was designed to analyze the characteristics of, and re-arrest outcomes for, defendants charged with misdemeanors ordered to undergo CST evaluations in a large metropolitan area. Overall, there was a high base rate of incompetent to stand trial (IST) opinions (over 70% of defendants) in this sample, with the greatest impairments in rational understanding and ability to assist counsel. Defendants opined IST were more likely to have a psychotic disorder, a history of psychiatric hospitalization, and greater abnormalities in thought content relative to their competent counterparts. Of concern, defendants opined IST, and especially those referred for crisis evaluations upon dismissal of the charges, were significantly more likely to be re-arrested than their counterparts. These data support the criminalization hypothesis, suggesting that criminal justice involvement for this subset of defendants inappropriately reflects psychiatric instability, supporting the need for more options for inpatient and outpatient treatment to effectively intervene in this process. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Measuring what matters: identifying assessments that reflect learning on the core surgical clerkship.

Purpose: There are various assessments used during the core surgical clerkship (CSC), each of which may be influenced by factors external to the CSC or have inherent biases from an equity lens. In particular, the National Board of Medical Examiners' Clinical Subject Exams ("Shelf") is used heavily and may not reflect clerkship curriculum or clinical learning. Methods: This is a retrospective review of medical student characteristics and assessments during the CSC from July 2017-June 2021. Assessment methods included: subjective Clinical Performance Assessments (CPA), Shelf, Objective Structured Clinical Examinations, and a short-answer in-house examination (IHE) culminating in a Final Grade (FG) of Honors/Pass/Fail. A Shelf score threshold for Honors was added in academic years 2020-2021. Descriptive, univariate, and multivariable logistic and linear regression statistics were utilized. Results: We reviewed records of 192 students. Of these, 107 (55.7%) were female, median age was 24 [IQR: 23-26] years, and most were White/Caucasian (N = 106, 55.2%). Univariate analysis showed the number of Exceeds Expectations obtained on CPA to be influenced by surgical subspecialty taken (p = 0.013) and academic year (p < 0.001). Shelf was influenced by students' race (p = 0.009), timing of CSC before or after Internal Medicine (67.9 ± 7.3 vs 72.9 ± 7.1, p < 0.001), and Term taken (increasing from 66.0 ± 8.7 to 73.4 ± 7.5, p < 0.001). IHE scores did not have any external associations. After adjustment with multivariable logistic and linear regressions, CPA and IHE did not have external associations, but higher scores were obtained on Shelf exam in Terms 3, 5, and 6 (by 4.62 [95% CI 0.86-8.37], 4.92 [95% CI 0.53-9.31], and 7.56 [95% CI 2.81-12.31] points, respectively. Odds of FG honors were lower when Shelf threshold was implemented (OR 0.17 [95% CI 0.06-0.50]), and increased as students got older (OR 1.14 [95% CI 1.01-1.30]) or on specific subspecialties, such as vascular surgery (OR 7.06 [95% CI 1.21-41.26]). Conclusions: The Shelf is substantially influenced by temporal associations across Terms and timing in relation to other clerkships, such as Internal Medicine. An IHE reflective of a clerkship's specified curriculum may be a more equitable summative assessment of the learning that occurs from the CSC curriculum, with fewer biases or influences external to the CSC. Supplementary Information: The online version contains supplementary material available at 10.1007/s44186-022-00047-8.