Factors Associated with COVID-19 Vaccination Uptake in Great Plains American Indian Communities.

With the development of the COVID-19 vaccine in late 2020, the importance of understanding the drivers of vaccine acceptance and vaccine hesitancy is important for the health of American Indian and Alaska Native communities. We conducted a cross-sectional, anonymous survey in October 2021 using established quantitative methods of virtual surveys to reach tribal members living on three reservations in the Great Plains (N = 679). We conducted multivariate analyses using logistic regression to assess the association between independent variables and COVID-19 vaccination status after adjusting for confounding. Respondents were more likely to have received a COVID-19 vaccine if they were older, had a full-time job, had previously received a flu vaccination, reported a higher level of trust in the health care system, had increased access to vaccinations, were able to isolate, or if they held a desire to keep their family safe. This study is one of the first to offer insights into the associations and possible determinants of COVID-19 vaccine uptake among American Indians in the Great Plains and was completed as part of the National Institutes of Health Rapid Acceleration of Diagnostics of Underserved Populations consortium. We identified a set of demographic, socioeconomic, and motivational factors that are associated with COVID-19 vaccination uptake among Great Plains American Indians and Alaska Natives. It is possible that future vaccine uptake may be enhanced through economic development, strengthening health care operations and care quality, and focusing vaccination messaging on family and community impact.

Amygdalar activity measured using FDG-PET/CT at head and neck cancer staging independently predicts survival.

IMPORTANCE: The mechanisms underlying the association between chronic stress and higher mortality among individuals with cancer remain incompletely understood. OBJECTIVE: To test the hypotheses that among individuals with active head and neck cancer, that higher stress-associated neural activity (ie. metabolic amygdalar activity [AmygA]) at cancer staging associates with survival. DESIGN: Retrospective cohort study. SETTING: Academic Medical Center (Massachusetts General Hospital, Boston). PARTICIPANTS: 240 patients with head and neck cancer (HNCA) who underwent 18F-FDG-PET/CT imaging as part of initial cancer staging. MEASUREMENTS: 18F-FDG uptake in the amygdala was determined by placing circular regions of interest in the right and left amygdalae and measuring the mean tracer accumulation (i.e., standardized uptake value [SUV]) in each region of interest. Amygdalar uptake was corrected for background cerebral activity (mean temporal lobe SUV). RESULTS: Among individuals with HNCA (age 59±13 years; 30% female), 67 died over a median follow-up period of 3 years (IQR: 1.7-5.1). AmygA associated with heightened bone marrow activity, leukocytosis, and C-reactive protein (P<0.05 each). In adjusted and unadjusted analyses, AmygA associated with subsequent mortality (HR [95% CI]: 1.35, [1.07-1.70], P = 0.009); the association persisted in stratified subset analyses restricted to patients with advanced cancer stage (P<0.001). Individuals within the highest tertile of AmygA experienced a 2-fold higher mortality rate compared to others (P = 0.01). The median progression-free survival was 25 months in patients with higher AmygA (upper tertile) as compared with 36.5 months in other individuals (HR for progression or death [95%CI], 1.83 [1.24-2.68], P = 0.001). CONCLUSIONS AND RELEVANCE: AmygA, quantified on routine 18F-FDG-PET/CT images obtained at cancer staging, independently and robustly predicts mortality and cancer progression among patients with HNCA. Future studies should test whether strategies that attenuate AmygA (or its downstream biological consequences) may improve cancer survival.

Great Plains American Indians' Perspectives on Patient and Family Needs Throughout the Cancer Journey.

PURPOSE: To explore the perspectives on patient and family needs during cancer treatment and survivorship of American Indian (AI) cancer survivors, caregivers, Tribal leaders, and healers. PARTICIPANTS & SETTING: 36 AI cancer survivors from three reservations in the Great Plains region. METHODOLOGIC APPROACH: A community-based participatory research design was employed. Postcolonial Indigenous research techniques of talking circles and semistructured interviews were used to gather qualitative data. Data were analyzed using content analysis to identify themes. FINDINGS: The overarching theme of accompaniment was identified. The following themes were intertwined with this theme: (a) the need for home health care, with the subthemes of family support and symptom management; and (b) patient and family education. IMPLICATIONS FOR NURSING: To provide high-quality cancer care to AI patients in their home communities, oncology clinicians should collaborate with local care providers, relevant organizations, and the Indian Health Service to identify and develop essential services. Future efforts must emphasize culturally responsive interventions in which Tribal community health workers serve as navigators to accompany patients and families during treatment and in survivorship.

Small-scale genetic structure of coral populations in Palau based on whole mitochondrial genomes: Implications for future coral resilience.

The ability of local populations to adapt to future climate conditions is facilitated by a balance between short range dispersal allowing local buildup of adaptively beneficial alleles, and longer dispersal moving these alleles throughout the species range. Reef building corals have relatively low dispersal larvae, but most population genetic studies show differentiation only over 100s of km. Here, we report full mitochondrial genome sequences from 284 tabletop corals (Acropora hyacinthus) from 39 patch reefs in Palau, and show two signals of genetic structure across reef scales from 1 to 55 km. First, divergent mitochondrial DNA haplotypes exist in different proportions from reef to reef, causing PhiST values of 0.02 (p = 0.02). Second, closely related sequences of mitochondrial Haplogroups are more likely to be co-located on the same reefs than expected by chance alone. We also compared these sequences to prior data on 155 colonies from American Samoa. In these comparisons, many Haplogroups in Palau were disproportionately represented or absent in American Samoa, and inter-regional PhiST = 0.259. However, we saw three instances of identical mitochondrial genomes between locations. Together, these data sets suggest two features of coral dispersal revealed by occurrence patterns in highly similar mitochondrial genomes. First, the Palau-American Samoa data suggest that long distance dispersal in corals is rare, as expected, but that it is common enough to deliver identical mitochondrial genomes across the Pacific. Second, higher than expected co-occurrence of Haplogroups on the same Palau reefs suggests greater retention of coral larvae on local reefs than predicted by many current oceanographic models of larval movement. Increased attention to local scales of coral genetic structure, dispersal, and selection may help increase the accuracy of models of future adaptation of corals and of assisted migration as a reef resilience intervention.

How Should Health Professions Educators and Organizations Desegregate Teaching and Learning Environments?

Motivating health equity requires taking deliberate steps toward desegregating health care, especially in academic health centers. One step should incorporate rigorous measurement and assessment of patients' access to health services and ongoing collection and review of patients' health outcomes data. Another step should develop, fund, incorporate and administer initiatives with community members that address social determinants of community and individual health, including academic health centers' inpatient and outpatient service delivery sites, insurance programs, and federal policy. Academic health centers must also be accountable for monitoring initiatives' successes and failures over short- and long-term trajectories and for modifying initiatives' methods as needed to achieve equity in access to health services and health outcomes.

COVID-19 Testing Factors Among Great Plains American Indians.

BACKGROUND: COVID-19 created unparalleled challenges for vulnerable communities, especially among American Indians and Alaska Natives. An effective COVID-19 response requires a tribally driven effort to understand the perspectives of Tribal members on testing and to ensure that delivery strategies are grounded in the cultural values, traditions, and experiences of the Tribes. METHODS: We conducted a cross-sectional, anonymous survey in October 2021 using established methods to reach Tribal members residing in three Reservations in the Great Plains (N = 679). Multivariate analyses were conducted using logistic regression to assess the association between independent variables and COVID-19 testing uptake after adjusting for confounding. RESULTS: After multivariate adjustment, a respondent's employment status, ability to isolate if diagnosed with COVID-19, and endorsing that COVID-19 testing is only needed if one has symptoms were significantly correlated with having been previously tested for COVID-19. Participants without a full-time job were about half as likely to have been tested for COVID-19 compared to those with full-time jobs. Participants who reported not being able to isolate if they tested positive for COVID-19 and participants who did not think testing was needed if asymptomatic were also half as likely to be tested. CONCLUSIONS: Ensuring that everyone has the ability to isolate, that people who are not working have easy access to testing, and that everyone understands the value of testing after exposure are key steps to maximizing testing uptake. Efforts will only be successful if there is continued investment in programs that provide free testing access for everyone on Reservations.

Association of Self-reported Primary Care Physician Tolerance for Uncertainty With Variations in Resource Use and Patient Experience.

Importance: Inappropriate variations in clinical practice are a known cause of poor quality and safety, with variations often associated with nonclinical factors, such as individual differences in cognitive processing. The differential response of physicians to uncertainty may explain some of the variations in resource use and patient experience. Objective: To examine the association of physician tolerance for uncertainty with variations in resource use and patient experience. Design, Setting, and Participants: This survey study linked physician survey data (May to June 2019), patient experience survey data (January 2016 to December 2019), and billing data (January 2019 to December 2019) among primary care physicians (PCPs) at Massachusetts General Hospital with at least 10 visits in 2019. The statistical analysis was performed in 2021. Main Outcomes and Measures: The analysis examined associations of PCP tolerance for uncertainty with the tendency to order diagnostic tests, the frequency of outpatient visits, hospital admissions, emergency department visits, and patient experience data (focused on physician communication and overall rating). A 2-stage hierarchical framework was used to account for clustering of patients under PCPs. Binary outcomes were modeled using a hierarchical logistic model, and count outcomes were modeled using hierarchical Poisson or negative binomial models. The analysis was adjusted for patient demographic variables (age, sex, and race and ethnicity), socioeconomic factors (payer and neighborhood income), and clinical comorbidities. Results: Of 217 included physicians, 137 (63.1%) were women, and 174 (80.2%) were adult PCPs. A total of 62 physicians (28.6%) reported low tolerance, 59 (27.2%) reported medium tolerance, and 96 (44.2%) reported high tolerance for uncertainty. Physicians with a low tolerance for uncertainty were less likely to order complete blood cell counts (odds ratio [OR], 0.66; 95% CI, 0.50-0.88), thyroid tests (OR, 0.67; 95% CI, 0.52-0.88), a basic metabolic profile (OR, 0.78; 95% CI, 0.60-1.00), and liver function tests (OR, 0.72; 95% CI, 0.53-0.99) than physicians with a high tolerance for uncertainty. Physicians who reported higher tolerance for uncertainty were more likely to receive higher patient experience scores for listening to patients carefully (OR, 0.65; 95% CI, 0.50-0.83) and higher overall ratings (OR, 0.80; 95% CI, 0.66-0.98) than physicians with medium tolerance. Conversely, no association was found between physician tolerance for uncertainty and patient outpatient visits, hospital admissions, or emergency department visits. Conclusions and Relevance: In clinical practice, identifying and effectively managing inappropriate variations and improving patient experience have proven to be difficult, despite increased attention to these issues. This study supports the hypothesis that physicians' tolerance for uncertainty is associated with differences in resource use and patient experience. Whether enhancing physicians' tolerance for uncertainty could help reduce unwarranted practice variations, improve quality and patient safety, and improve patient's experience remains to be established.

Breast cancer polygenic risk scores are associated with short-term risk of poor prognosis breast cancer.

PURPOSE: Polygenic risk scores (PRS) for breast cancer may help guide screening decisions. However, few studies have examined whether PRS are associated with risk of short-term or poor prognosis breast cancers. The study purpose was to evaluate the association of the 313 SNP breast cancer PRS with 2-year risk of poor prognosis breast cancer. METHODS: We evaluated the association of breast cancer PRS with breast cancer overall, ER + and ER- breast cancer, and poor prognosis breast cancer diagnosed within 2 years of a negative mammogram among a cohort of 3657 women using logistic regression adjusted for age, breast density, race/ethnicity, year of screening, and genetic ancestry principal components. Breast cancers were considered poor prognosis if they were metastatic, positive lymph nodes, ER/PR + HER2- and > 2 cm, ER/PR/HER2-, or HER2 + and > 1 cm. RESULTS: Of the 308 breast cancers, 137 (44%) were poor prognosis. The overall breast cancer PRS was significantly associated with breast cancer diagnosis within 2 years (OR 1.39, 95% CI 1.23-1.57, p < 0.001). The breast cancer PRS was also associated specifically with diagnosis of poor prognosis disease (OR 1.24, 95% CI 1.03-1.49, p = 0.018), but was more strongly associated with good prognosis cancer (OR 1.52 95% CI 1.29-1.80 p = 3.60 × 10-7) The ER + PRS was significantly associated with ER/PR + breast cancer (OR 1.41, 95% CI 1.24-1.61, p < 0.001) and the ER- PRS was significantly associated with ER- breast cancer (OR 1.48, 95% CI 1.08-2.02, p = 0.015). CONCLUSION: Breast cancer PRS was independently and significantly associated with diagnosis of both breast cancer overall and poor prognosis breast cancer within 2 years of a negative mammogram, suggesting PRS may help guide decisions about screening intervals and supplemental screening.

Persistence of phenotypic responses to short-term heat stress in the tabletop coral Acropora hyacinthus.

Widespread mapping of coral thermal resilience is essential for developing effective management strategies and requires replicable and rapid multi-location assays of heat resistance and recovery. One- or two-day short-term heat stress experiments have been previously employed to assess heat resistance, followed by single assays of bleaching condition. We tested the reliability of short-term heat stress resistance, and linked resistance and recovery assays, by monitoring the phenotypic response of fragments from 101 Acropora hyacinthus colonies located in Palau (Micronesia) to short-term heat stress. Following short-term heat stress, bleaching and mortality were recorded after 16 hours, daily for seven days, and after one and two months of recovery. To follow corals over time, we utilized a qualitative, non-destructive visual bleaching score metric that correlated with standard symbiont retention assays. The bleaching state of coral fragments 16 hours post-heat stress was highly indicative of their state over the next 7 days, suggesting that symbiont population sizes within corals may quickly stabilize post-heat stress. Bleaching 16 hours post-heat stress predicted likelihood of mortality over the subsequent 3-5 days, after which there was little additional mortality. Together, bleaching and mortality suggested that rapid assays of the phenotypic response following short-term heat stress were good metrics of the total heat treatment effect. Additionally, our data confirm geographic patterns of intraspecific variation in Palau and show that bleaching severity among colonies was highly correlated with mortality over the first week post-stress. We found high survival (98%) and visible recovery (100%) two months after heat stress among coral fragments that survived the first week post-stress. These findings help simplify rapid, widespread surveys of heat sensitivity in Acropora hyacinthus by showing that standardized short-term experiments can be confidently assayed after 16 hours, and that bleaching sensitivity may be linked to subsequent survival using experimental assessments.

Proteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19.

BACKGROUND: The high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID-19 severity in epidemiologic studies. Cardiometabolic protein biomarkers, therefore, may provide predictive insight regarding which patients are most susceptible to severe illness from COVID-19. METHODS: In plasma samples collected from 343 patients hospitalized with COVID-19 during the first wave of the pandemic, we measured 92 circulating protein biomarkers previously implicated in cardiometabolic disease. We performed proteomic analysis and developed predictive models for severe outcomes. We then used these models to predict the outcomes of out-of-sample patients hospitalized with COVID-19 later in the surge (N = 194). RESULTS: We identified a set of seven protein biomarkers predictive of admission to the intensive care unit and/or death (ICU/death) within 28 days of presentation to care. Two of the biomarkers, ADAMTS13 and VEGFD, were associated with a lower risk of ICU/death. The remaining biomarkers, ACE2, IL-1RA, IL6, KIM1, and CTSL1, were associated with higher risk. When used to predict the outcomes of the future, out-of-sample patients, the predictive models built with these protein biomarkers outperformed all models built from standard clinical data, including known COVID-19 risk factors. CONCLUSIONS: These findings suggest that proteomic profiling can inform the early clinical impression of a patient's likelihood of developing severe COVID-19 outcomes and, ultimately, accelerate the recognition and treatment of high-risk patients.

Proteomic analysis of cardiometabolic biomarkers and predictive modeling of severe outcomes in patients hospitalized with COVID-19.

Background: The high heterogeneity in the symptoms and severity of COVID-19 makes it challenging to identify high-risk patients early in the disease. Cardiometabolic comorbidities have shown strong associations with COVID-19 severity in epidemiologic studies. Cardiometabolic protein biomarkers, therefore, may provide predictive insight regarding which patients are most susceptible to severe illness from COVID-19. Methods: In plasma samples collected from 343 patients hospitalized with COVID-19 during the first wave of the pandemic, we measured 92 circulating protein biomarkers previously implicated in cardiometabolic disease. We performed proteomic analysis and developed predictive models for severe outcomes. We then used these models to predict the outcomes of out-of-sample patients hospitalized with COVID-19 later in the surge (N=194). Results: We identified a set of seven biomarkers predictive of admission to the intensive care unit and/or death (ICU/death) within 28 days of presentation to care. Two of the biomarkers, ADAMTS13 and VEGFD, were associated with a lower risk of ICU/death. The remaining biomarkers, ACE2, IL-1RA, IL6, KIM1, and CTSL1, were associated with higher risk. When used to predict the outcomes of the future, out-of-sample patients, the predictive models built with these biomarkers outperformed all models built from standard clinical data, including known COVID-19 risk factors. Conclusions: These findings suggest that proteomic profiling can inform the early clinical impression of a patient’s likelihood of developing severe COVID-19 outcomes and, ultimately, accelerate the recognition and treatment of high-risk patients.

"Calling the Spirit Back:" Spiritual Needs Among Great Plains American Indians.

CONTEXT: American Indians (AIs) are disproportionately affected by serious illness such as cancer. Colonization, cultural genocide, and trauma have adversely affected AIs' ability to attain health and well-being, and in many cases led to the loss of the right to practice traditional ceremonies and rituals. Still many AIs describe well-being as being rooted in spirituality. OBJECTIVES: The purpose of this project was to learn about the perspectives of AI cancer survivors, caregivers, and Tribal leaders and healers specific to spirituality while on the cancer journey. METHODS: Qualitative interviews and Indigenous talking circle methodologies were used to explore AIs cancer survivors, caregivers, and Tribal leaders and healers' perspectives on spirituality while on the cancer journey. A data analysis team consisting of AI and non-AI members analyzed the narrative data. RESULTS: Qualitative analysis of interviews and talking circles revealed 4 major themes related to spirituality: the chasm of colonialism, coexistence of Traditional and Christian religions, calling the Spirit back, and prayer as sacred energy. CONCLUSION: It is critical that clinicians caring for AIs with serious illness seek to understand their patients' spiritual beliefs about disease treatment and death and work with them and their families to support quality of life throughout their illness journey. In addition, clinicians must recognize the systemic racism inherent in our healthcare systems, and dismantle cultural clashes and bias for all patients, particularly AIs, who have long suffered from poorer health outcomes.

Factors Influencing Palliative Care Access and Delivery for Great Plains American Indians.

CONTEXT: Despite the known importance of culturally tailored palliative care (PC), American Indian people (AIs) in the Great Plains lack access to such services. While clinicians caring for AIs in the Great Plains have long acknowledged major barriers to serious illness care, there is a paucity of literature describing specific factors influencing PC access and delivery for AI patients living on reservation land. OBJECTIVES: This study aimed to explore factors influencing PC access and delivery on reservation land in the Great Plains to inform the development culturally tailored PC services for AIs. METHODS: Three authors recorded and transcribed interviews with 21 specialty and 17 primary clinicians. A data analysis team of seven authors analyzed transcripts using conventional content analysis. The analysis team met over Zoom to engage in code negotiation, classify codes, and develop themes. RESULTS: Qualitative analysis of interview data revealed four themes encompassing factors influencing palliative care delivery and access for Great Plains American Indians: health care system operations (e.g., hospice and home health availability, fragmented services), geography (e.g., weather, travel distances), workforce elements (e.g., care continuity, inadequate staffing, cultural familiarity), and historical trauma and racism. CONCLUSION: Our findings emphasize the importance of addressing the time and cost of travel for seriously ill patients, increasing home health and hospice availability on reservations, and improving trust in the medical system. Strengthening the AI medical workforce, increasing funding for the Indian Health Service, and transitioning the governance of reservation health care to Tribal entities may improve the trustworthiness of the medical system.

Association of Socioeconomic Status and Infarct Volume With Functional Outcome in Patients With Ischemic Stroke.

Importance: Long-term disability after stroke is associated with socioeconomic status (SES). However, the reasons for such disparities in outcomes remain unclear. Objective: To assess whether lower SES is associated with larger admission infarct volume and whether initial infarct volume accounts for the association between SES and long-term disability. Design, Setting, and Participants: This cohort study was conducted in a prospective, consecutive population (n = 1256) presenting with acute ischemic stroke who underwent magnetic resonance imaging (MRI) within 24 hours of admission. Patients were recruited in Massachusetts General Hospital, Boston, from May 31, 2009, to December 31, 2011. Data were analyzed from May 1, 2019, until June 30, 2020. Main Outcomes and Measures: Initial stroke severity (within 24 hours of presentation) was determined using clinical (National Institutes of Health Stroke Scale [NIHSS]) and imaging (infarct volume by diffusion-weighted MRI) measures. Stroke etiologic subtypes were determined using the Causative Classification of Ischemic Stroke algorithm. Long-term stroke disability was measured using the modified Rankin Scale. Socioeconomic status was estimated using zip code-derived median household income and census block group-derived area deprivation index (ADI). Regression and mediation analyses were performed. Results: A total of 1098 patients had imaging and SES data available (mean [SD] age, 68.1 [15.7] years; 607 men [55.3%]). Income was inversely associated with initial infarct volume (standardized ß, -0.074 [95% CI, -0.127 to -0.020]; P = .007), initial NIHSS (standardized ß, -0.113 [95% CI, -0.171 to -0.054]; P < .001), and long-term disability (standardized ß, -0.092 [95% CI, -0.149 to -0.035]; P = .001), which remained significant after multivariable adjustments. Initial stroke severity accounted for 64% of the association between SES and long-term disability (standardized ß, -0.063 [95% CI, -0.095 to -0.029]; P < .05). Findings were similar when SES was alternatively assessed using ADI. Conclusions and Relevance: The findings of this cohort study suggest that lower SES is associated with larger infarct volumes on presentation. These SES-associated differences in initial stroke severity accounted for most of the subsequent disparities in long-term disability in this study. These findings shift the culpability for SES-associated disparities in poststroke disability from poststroke factors to those that precede presentation.

Attitudes and Actions Related to Racism: the Anti-RaCism (ARC) Survey Study.

BACKGROUND: Racism negatively impacts health and well-being. Members of the medical community must intervene to address racism. OBJECTIVE: To assess whether attitudes about the impact of racism on health or society are associated with intervening around racism. DESIGN: Cross-sectional survey of a large department of medicine in an urban academic setting. PARTICIPANTS: Interns, residents, fellows, and faculty. MAIN MEASURES: The primary outcome was the likelihood of intervening around an observed racist encounter or a racist policy. Predictor variables included age, gender identity, race/ethnicity, and attitudes about racism. KEY RESULTS: Although the majority of the 948 respondents endorsed the impact of racism on health and other societal effects, levels of endorsement were lower among older individuals, or those reporting male gender identity or selecting other race. Higher endorsement of the impact of racism on health was associated with increased odds of speaking up about a racist encounter or racist policy, with odds ratios from 1.18 to 1.30 across scenarios. Likelihood of speaking up about racism did not differ by racial or ethnic group, but older individuals were generally more likely to speak up and individuals between 20 and 29 years of age were more likely to speak with someone other than leadership or the source of a racist encounter. CONCLUSIONS: Awareness of the effects of racism on health is associated with increased likelihood of intervening when a racist encounter is observed or a racist policy is noted. Including information on the impact of racism on health and creating safe spaces to discuss racism may increase the likelihood of bystander intervention in anti-racism strategies.

Utilizing the Consolidated Framework for Implementation Research to Explore Palliative Care Program Implementation for American Indian and Alaska Natives throughout the United States.

Background: A significant shortage of palliative care (PC) services exists for American Indian and Alaska Native people (AI/ANs) across the United States. Using an implementation science framework, we interviewed key individuals associated with AI/AN-focused PC programs to explore what is needed to develop and sustain such programs. Objectives: To identify facilitators of implementation and barriers to sustainability associated with the development of PC programs designed for AI/ANs across the United States. Methods: We interviewed 12 key individuals responsible for the implementation of AI/AN-focused PC services. The Consolidated Framework for Implementation Research (CFIR) guided data coding and interpretation of themes. Results: We identified nine themes that map to CFIR constructs. Facilitators of implementation include high tension for change and respecting cultural values. Barriers to program sustainability include a lack of administrative leadership support. Discussion: AI/AN-focused PC programs should be congruent with community needs. PC program developers should focus on sustainability well before initial implementation.