Bias in team decision-making for advanced heart failure therapies: model application.

Bias in advanced heart failure therapy allocation results in inequitable outcomes for minoritized populations. The purpose of this study was to examine how bias is introduced during group decision-making with an interprofessional team using Breathett's Model of Heart Failure Decision-Making. This was a secondary qualitative descriptive analysis from a study focused on bias in advanced heart failure therapy allocation. Team meetings were recorded and transcribed from four heart failure centers. Breathett's Model was applied both deductively and inductively to transcripts (n = 12). Bias was identified during discussions about patient characteristics, clinical fragility, and prior clinical decision-making. Some patients were labeled as "good citizens" or as adherent/non-adherent while others benefited from strong advocacy from interprofessional team members. Social determinants of health also impacted therapy allocation. Interprofessional collaboration with advanced heart failure therapy allocation may be enhanced with the inclusion of patient advocates and limit of clinical decision-making using subjective data.

Diversity in connexin biology.

Over 35 years ago the cell biology community was introduced to connexins as the subunit employed to assemble semicrystalline clusters of intercellular channels that had been well described morphologically as gap junctions. The decade that followed would see knowledge of the unexpectedly large 21-member human connexin family grow to reflect unique and overlapping expression patterns in all organ systems. While connexin biology initially focused on their role in constructing highly regulated intercellular channels, this was destined to change as discoveries revealed that connexin hemichannels at the cell surface had novel roles in many cell types, especially when considering connexin pathologies. Acceptance of connexins as having bifunctional channel properties was initially met with some resistance, which has given way in recent years to the premise that connexins have multifunctional properties. Depending on the connexin isoform and cell of origin, connexins have wide-ranging half-lives that vary from a couple of hours to the life expectancy of the cell. Diversity in connexin channel characteristics and molecular properties were further revealed by X-ray crystallography and single-particle cryo-EM. New avenues have seen connexins or connexin fragments playing roles in cell adhesion, tunneling nanotubes, extracellular vesicles, mitochondrial membranes, transcription regulation, and in other emerging cellular functions. These discoveries were largely linked to Cx43, which is prominent in most human organs. Here, we will review the evolution of knowledge on connexin expression in human adults and more recent evidence linking connexins to a highly diverse array of cellular functions.

A novel approach for assessing bias during team-based clinical decision-making.

Many clinical processes include multidisciplinary group decision-making, yet few methods exist to evaluate the presence of implicit bias during this collective process. Implicit bias negatively impacts the equitable delivery of evidence-based interventions and ultimately patient outcomes. Since implicit bias can be difficult to assess, novel approaches are required to detect and analyze this elusive phenomenon. In this paper, we describe how the de Groot Critically Reflective Diagnoses Protocol (DCRDP) can be used as a data analysis tool to evaluate group dynamics as an essential foundation for exploring how interactions can bias collective clinical decision-making. The DCRDP includes 6 distinct criteria: challenging groupthink, critical opinion sharing, research utilization, openness to mistakes, asking and giving feedback, and experimentation. Based on the strength and frequency of codes in the form of exemplar quotes, each criterion was given a numerical score of 1-4 with 1 representing teams that are interactive, reflective, higher functioning, and more equitable. When applied as a coding scheme to transcripts of recorded decision-making meetings, the DCRDP was revealed as a practical tool for examining group decision-making bias. It can be adapted to a variety of clinical, educational, and other professional settings as an impetus for recognizing the presence of team-based bias, engaging in reflexivity, informing the design and testing of implementation strategies, and monitoring long-term outcomes to promote more equitable decision-making processes in healthcare.

Pilot test of a multicomponent implementation strategy for equity in advanced heart failure allocation.

Advanced heart failure (AHF) therapy allocation is vulnerable to bias related to subjective assessments and poor group dynamics. Our objective was to determine whether an implementation strategy for AHF team members could feasibly contribute to organizational and culture change supporting equity in AHF allocation. Using a pretest-posttest design, the strategy included an 8-week multicomponent training on bias reduction, standardized numerical social assessments, and enhanced group dynamics at an AHF center. Evaluations of organizational and cultural changes included pretest-posttest AHF team member surveys, transcripts of AHF meetings to assess group dynamics using a standardized scoring system, and posttest interviews guided by a framework for implementing a complex strategy. Results were analyzed with qualitative descriptive methods and Brunner-Munzel tests for relative effect (RE, RE >0.5 signals posttest improvement). The majority of survey metrics revealed potential benefit with RE >0.5. REs were >0.5 for 5 of 6 group dynamics metrics. Themes for implementation included (1) promoting equitable distribution of scarce resources, (2) requiring a change in team members' time investment to correct bias and change the meeting structure, (3) slowing and then accelerating the allocation process, and (4) adaptable beyond AHF and reinforceable with semi-annual trainings. An implementation strategy for AHF equity demonstrated the feasibility for organizational and culture changes.

Modeling Heart Diseases on a Chip: Advantages and Future Opportunities.

Heart disease is a significant burden on global health care systems and is a leading cause of death each year. To improve our understanding of heart disease, high quality disease models are needed. These will facilitate the discovery and development of new treatments for heart disease. Traditionally, researchers have relied on 2D monolayer systems or animal models of heart disease to elucidate pathophysiology and drug responses. Heart-on-a-chip (HOC) technology is an emerging field where cardiomyocytes among other cell types in the heart can be used to generate functional, beating cardiac microtissues that recapitulate many features of the human heart. HOC models are showing great promise as disease modeling platforms and are poised to serve as important tools in the drug development pipeline. By leveraging advances in human pluripotent stem cell-derived cardiomyocyte biology and microfabrication technology, diseased HOCs are highly tuneable and can be generated via different approaches such as: using cells with defined genetic backgrounds (patient-derived cells), adding small molecules, modifying the cells' environment, altering cell ratio/composition of microtissues, among others. HOCs have been used to faithfully model aspects of arrhythmia, fibrosis, infection, cardiomyopathies, and ischemia, to name a few. In this review, we highlight recent advances in disease modeling using HOC systems, describing instances where these models outperformed other models in terms of reproducing disease phenotypes and/or led to drug development.

Group Dynamics and Allocation of Advanced Heart Failure Therapies-Heart Transplants and Ventricular Assist Devices-By Gender, Racial, and Ethnic Group.

Background US regulatory framework for advanced heart failure therapies (AHFT), ventricular assist devices, and heart transplants, delegate eligibility decisions to multidisciplinary groups at the center level. The subjective nature of decision-making is at risk for racial, ethnic, and gender bias. We sought to determine how group dynamics impact allocation decision-making by patient gender, racial, and ethnic group. Methods and Results We performed a mixed-methods study among 4 AHFT centers. For ≈ 1 month, AHFT meetings were audio recorded. Meeting transcripts were evaluated for group function scores using de Groot Critically Reflective Diagnoses protocol (metrics: challenging groupthink, critical opinion sharing, openness to mistakes, asking/giving feedback, and experimentation; scoring: 1 to 4 [high to low quality]). The relationship between summed group function scores and AHFT allocation was assessed via hierarchical logistic regression with patients nested within meetings nested within centers, and interaction effects of group function score with gender and race, adjusting for patient age and comorbidities. Among 87 patients (24% women, 66% White race) evaluated for AHFT, 57% of women, 38% of men, 44% of White race, and 40% of patients of color were allocated to AHFT. The interaction between group function score and allocation by patient gender was statistically significant (P=0.035); as group function scores improved, the probability of AHFT allocation increased for women and decreased for men, a pattern that was similar irrespective of racial and ethnic groups. Conclusions Women evaluated for AHFT were more likely to receive AHFT when group decision-making processes were of higher quality. Further investigation is needed to promote routine high-quality group decision-making and reduce known disparities in AHFT allocation.

Race and Gender-Based Perceptions of Older Septuagenarian Adults.

Objectives: Older adults face racism, sexism, and ageism. As the U.S. population ages, it is important to understand how the current population views older adults. Methods: Participants recruited through Amazon's Mechanical Turk provided perceptions of older Black and White models' photographs. Using mixed-effect models, we assessed interactions between race and gender of participants and models. Results: Among Participants of Color and White participants (n = 712, 70% non-Hispanic White, 70% women, mean 37.81 years), Black models were perceived as more attractive, less threatening, and sadder than White models, but differences were greater for White participants (race-by-race interaction: attractive p = 0.003, threatening p = 0.009, sad p = 0.016). Each gender perceived their respective gender as more attractive (gender-by-gender interaction p < 0.0001). Male and female participants perceived male models as happier than female models, but differences were greater for male participants (p = 0.026). Irrespective of participant age group, women were perceived as more threatening (p = 0.012). Other perceptions were not significant. Discussion: Participants had few biases toward older Black and White models, while gender biases favored men.

Hearing Loss After Radiation and Chemotherapy for CNS and Head-and-Neck Tumors in Children.

PURPOSE: Hearing loss (HL) is a serious secondary effect of treatment for CNS and head-and-neck tumors in children. The goal of this study was to evaluate incidence and risk factors for HL in patients with multiple ototoxic exposures. PATIENTS AND METHODS: We evaluated 340 ears from 171 patients with CNS or head-and-neck tumors treated with radiation, with or without chemotherapy, who had longitudinal audiologic evaluation. International Society of Pediatric Oncology-Boston grades were assigned to 2,420 hearing assessments. Multivariable weighted ordinal logistic regression was fitted to evaluate the effect of clinicopathologic features on HL. RESULTS: Mean cochlea dose (odds ratio [OR] 1.04 per Gy, P < .001), time since radiotherapy (RT; OR 1.21 per year, P < .001), cisplatin dose (OR 1.48 per 100 mg/m2, P < .001), and carboplatin dose (OR 1.41 per 1,000 mg/m2, P = .002) were associated with increasing International Society of Pediatric Oncology-Boston grade of HL. There was no synergistic effect of RT and cisplatin (interaction term, P = .53) or RT and carboplatin (interaction term, P = .85). Cumulative incidence of high-frequency HL (> 4 kHz) was 50% or greater at 5 years after RT if mean cochlea dose was > 30 Gy, while incidence of HL across all frequencies continued to increase beyond 5 years after RT. CONCLUSION: Children treated with radiation and chemotherapy experience a high incidence of HL over time, with associations found between more severe HL and cisplatin or carboplatin dose as well as mean cochlea dose. Mean cochlea dose of ≤ 30 Gy is proposed as a goal to reduce the risk of HL; a lower threshold (20-25 Gy) may be considered in patients receiving platinum chemotherapy to reduce cumulative HL burden.

Association of Gender and Race With Allocation of Advanced Heart Failure Therapies.

Importance: Racial bias is associated with the allocation of advanced heart failure therapies, heart transplants, and ventricular assist devices. It is unknown whether gender and racial biases are associated with the allocation of advanced therapies among women. Objective: To determine whether the intersection of patient gender and race is associated with the decision-making of clinicians during the allocation of advanced heart failure therapies. Design, Setting, and Participants: In this qualitative study, 46 US clinicians attending a conference for an international heart transplant organization in April 2019 were interviewed on the allocation of advanced heart failure therapies. Participants were randomized to examine clinical vignettes that varied 1:1 by patient race (African American to white) and 20:3 by gender (women to men) to purposefully target vignettes of women patients to compare with a prior study of vignettes of men patients. Participants were interviewed about their decision-making process using the think-aloud technique and provided supplemental surveys. Interviews were analyzed using grounded theory methodology, and surveys were analyzed with Wilcoxon tests. Exposure: Randomization to clinical vignettes. Main Outcomes and Measures: Thematic differences in allocation of advanced therapies by patient race and gender. Results: Among 46 participants (24 [52%] women, 20 [43%] racial minority), participants were randomized to the vignette of a white woman (20 participants [43%]), an African American woman (20 participants [43%]), a white man (3 participants [7%]), and an African American man (3 participants [7%]). Allocation differences centered on 5 themes. First, clinicians critiqued the appearance of the women more harshly than the men as part of their overall impressions. Second, the African American man was perceived as experiencing more severe illness than individuals from other racial and gender groups. Third, there was more concern regarding appropriateness of prior care of the African American woman compared with the white woman. Fourth, there were greater concerns about adequacy of social support for the women than for the men. Children were perceived as liabilities for women, particularly the African American woman. Family dynamics and finances were perceived to be greater concerns for the African American woman than for individuals in the other vignettes; spouses were deemed inadequate support for women. Last, participants recommended ventricular assist devices over transplantation for all racial and gender groups. Surveys revealed no statistically significant differences in allocation recommendations for African American and white women patients. Conclusions and Relevance: This national study of health care professionals randomized to clinical vignettes that varied only by gender and race found evidence of gender and race bias in the decision-making process for offering advanced therapies for heart failure, particularly for African American women patients, who were judged more harshly by appearance and adequacy of social support. There was no associated between patient gender and race and final recommendations for allocation of advanced therapies. However, it is possible that bias may contribute to delayed allocation and ultimately inequity in the allocation of advanced therapies in a clinical setting.

Minimizing General Anesthetic Use in Pediatric Radiation Therapy.

PURPOSE: At our institution, a multifaceted approach is used to reduce general anesthetic (GA) use for children receiving photon radiation therapy (RT) as standard-of-care treatment. The purpose of this study was to evaluate the effectiveness of our methods. METHODS AND MATERIALS: Patients treated as part of the pediatric radiation therapy program from 2010 to 2018 were retrospectively reviewed. GA use was defined as need for intravenous propofol or inhaled gaseous anesthetic for at least 1 simulation or RT session. Methods to reduce GA use included presence of a dedicated pediatric nurse for procedural preparation, audiovisual distraction (television during RT), and 2-way audio communication with caregivers. RESULTS: There were 779 unique patients who received RT over 14 163 fractions of radiation. GA utilization was 90% in those under age 3, 28% in those age 3 to 6, 1% in those age 7 to 11, and <1% in those ≥12 years of age. Four years of age is a cutoff age at which the majority of patients switch from needing GA (56.6% for those aged 3) to not needing GA (29.8% for those aged 4). Younger age, use of total body irradiation, and craniospinal irradiation were independently associated with requiring GA. CONCLUSIONS: Using methods designed to reduce GA use, most children aged 4 years or older were able receive RT awake. Our GA rates compare favorably to other literature reports; thus, pediatric RT centers should consider adopting specific interventions to reduce GA use.

Patient and caregiver engagement in research: factors that influence co-enrollment in research.

BACKGROUND: Recruitment of pediatric participants in studies is difficult due to the vulnerability of this population and the scarcity of certain conditions. Co-enrolling in multiple studies is a strategy that may help overcome this problem. Although anecdotal evidence suggests that co-enrollment may increase patient and caregiver burden, few studies have been conducted from the patient perspective. The objective of this quality improvement project was to elicit patient and caregiver opinions on co-enrolling in multiple research studies. METHODS: Patients and caregivers attending the rheumatology clinic at The Hospital for Sick Children were invited to participate in a semi-structured interview or focus group session. Participants were asked to respond to ten prompts, organized into five categories: experience in clinical research, multiple studies, study selection, study timing and other comments. Sessions were recorded, transcribed and analyzed using NVivo 10 to identify common themes. RESULTS: Overall, eighteen caregivers and two patients were included in the study. Participants felt that the level of study involvement, rather than the number of studies, was the biggest factor affecting their decision to participate. Another factor commonly identified was the competing demands of participants' work and family life. Participants indicated that they generally preferred to be informed about all study opportunities and liked to receive this information prior to their appointments. Once informed, they preferred to be approached by the research team while they were waiting for their appointment. CONCLUSION: Patients and caregivers are open to the concept of co-enrolling in multiple research studies. There are multiple factors which influence decisions to co-enroll in studies including the demands of the study and personal limitations. These findings will help guide the design and practices of future research.

Re-irradiation for children with recurrent medulloblastoma in Toronto, Canada: a 20-year experience.

PURPOSE: Children with recurrent medulloblastoma have a poor prognosis. Re-irradiation is an option for some patients, but has not been well-studied in the era of molecular characterization for pediatric medulloblastoma. METHODS: This was a retrospective cohort study of 14 children age 18 years and younger at initial diagnosis with recurrent medulloblastoma, who received two or more courses of radiation therapy (RT). Molecular subgrouping was performed using nanoString and was available for nine patients. The primary study endpoint was overall survival. RESULTS: Re-irradiation (RT2) was directed at the supratentorial brain in six patients, infratentorial brain in one patient, and spine in seven patients. In addition, six patients received stem cell transplant as part of salvage therapy. Median OS for all patients was 12.4 months. One patient with recurrent Wnt-activated medulloblastoma remains alive with 154 months' survival; median survival was not reached for four patients with Group 4 disease, while three with Shh-activated disease had median survival of 2.2 months. A single patient with Group 3 disease died 4.3 months after RT2. Patients treated with RT2 to the spine for diffuse disease had poorer OS (p = 0.02), as compared to focal RT2 for intracranial recurrence. Distant failure, outside RT2 volumes, was the predominant pattern of recurrence after RT2. CONCLUSIONS: Re-irradiation for recurrent pediatric medulloblastoma can offer some patients disease control, particularly those with focally recurrent disease in the brain. Prospective studies are needed to confirm subgroups of patients who may benefit most from RT2.

Repeat irradiation for children with supratentorial high-grade glioma.

BACKGROUND: There are very few studies about the role of repeat irradiation (RT2) for children with recurrent supratentorial high-grade glioma (HGG). It was the aim of this study to assess the effectiveness and safety of RT2 in this population. PROCEDURE: This was a retrospective cohort study of 40 children age 18 years and under with recurrent supratentorial HGG who had received at least one course of RT. In-field reirradiation volumes included focal or whole brain RT, with doses ranging from 30 to 54 Gy. The primary endpoint was overall survival (OS) from the first day of RT2. RESULTS: Fourteen patients underwent RT2. The median survival of these patients was 6.5 months. Patients with ≥12 months elapsed time between RT1 and RT2 experienced longer OS than patients who had < 12 months (P = 0.009). There was no difference in OS between patients with or without germline mutations (e.g., Lynch, Li-Fraumeni, or constitutional mismatch-repair deficiency, P = 0.20). Ten patients received RT2 that overlapped with RT1 volumes for locally recurrent disease. Of this group, 80% experienced clinical benefit from in-field RT2, defined as clinical/radiologic response or stable disease. Ninety-three percent completed the prescribed course of RT2, with one patient developing grade 3 radiation necrosis four months after RT2. When compared with 26 patients who were not offered reirradiation, those selected for RT2 had improved median survival from the time of first disease progression (9.4 vs 3.8 months, P = 0.005). CONCLUSIONS: Reirradiation for children with recurrent supratentorial HGG is a safe, effective treatment that provides short-term disease control.

P3a from white noise.

P3a and P3b event-related brain potentials (ERPs) were elicited with an auditory three-stimulus (target, distracter, and standard) discrimination task in which subjects responded only to the target. Distracter stimuli consisted of white noise or novel sounds with stimulus characteristics perceptually matched. Target/standard discrimination difficulty was manipulated by varying target/standard pitch differences to produce relatively easy, medium, and hard tasks. Error rate and response time increased with increases in task difficulty. P3a was larger for the white noise compared to novel sounds, maximum over the central/parietal recording sites, and did not differ in size across difficulty levels. P3b was unaffected by distracter type, decreased as task difficulty increased, and maximum over the parietal recording sites. The findings indicate that P3a from white noise is robust and should be useful for applied studies as it removes stimulus novelty variability. Theoretical perspectives are discussed.