Why the Indian Health Care Improvement Act Has Failed to Effectively Fund Workforce Development for the Indian Health Service.

The Indian Health Service (IHS) faces severe workforce shortages due to underfunding and underdevelopment of clinical training programs. Unlike other direct federal health care systems that have implemented clinical training paradigms as central parts of their success, the IHS has no formalized process for developing such programs internally or in partnership with academic institutions. While the Indian Health Care Improvement Act (IHCIA) authorizes mechanisms by which the IHS can support overall workforce development, a critical portion of the act (U.S. Code 1616p) intended for developing clinical training programs within the agency remains unfunded. Here, we review the funding challenges of the IHCIA, as well as its authorized and funded workforce development programs that have only partially addressed workforce shortages. We propose that through additional funding to 1616p, the IHS could implement clinical training programs needed to prepare a larger workforce more capable of meeting the needs of American Indian/Alaska Native communities.

Ibrutinib as first-line therapy for mantle cell lymphoma: a multicenter, real-world UK study.

ABSTRACT: During the COVID-19 pandemic, ibrutinib with or without rituximab was approved in England for initial treatment of mantle cell lymphoma (MCL) instead of immunochemotherapy. Because limited data are available in this setting, we conducted an observational cohort study evaluating safety and efficacy. Adults receiving ibrutinib with or without rituximab for untreated MCL were evaluated for treatment toxicity, response, and survival, including outcomes in high-risk MCL (TP53 mutation/deletion/p53 overexpression, blastoid/pleomorphic, or Ki67 ≥ 30%). A total of 149 patients from 43 participating centers were enrolled: 74.1% male, median age 75 years, 75.2% Eastern Cooperative Oncology Group status of 0 to 1, 36.2% high-risk, and 8.9% autologous transplant candidates. All patients received ≥1 cycle ibrutinib (median, 8 cycles), 39.0% with rituximab. Grade ≥3 toxicity occurred in 20.3%, and 33.8% required dose reductions/delays. At 15.6-month median follow-up, 41.6% discontinued ibrutinib, 8.1% due to toxicity. Of 104 response-assessed patients, overall (ORR) and complete response (CR) rates were 71.2% and 20.2%, respectively. ORR was 77.3% (low risk) vs 59.0% (high risk) (P = .05) and 78.7% (ibrutinib-rituximab) vs 64.9% (ibrutinib; P = .13). Median progression-free survival (PFS) was 26.0 months (all patients); 13.7 months (high risk) vs not reached (NR) (low risk; hazard ratio [HR], 2.19; P = .004). Median overall survival was NR (all); 14.8 months (high risk) vs NR (low risk; HR, 2.36; P = .005). Median post-ibrutinib survival was 1.4 months, longer in 41.9% patients receiving subsequent treatment (median, 8.6 vs 0.6 months; HR, 0.36; P = .002). Ibrutinib with or without rituximab was effective and well tolerated as first-line treatment of MCL, including older and transplant-ineligible patients. PFS and OS were significantly inferior in one-third of patients with high-risk disease and those unsuitable for post-ibrutinib treatment, highlighting the need for novel approaches in these groups.

A nationwide analysis of disparities in guideline-concordant care in American Indians and Alaska Natives with stage I non-small cell lung cancer.

Background: Several studies have shown racial disparities in lung cancer care in the United States in the Black and Hispanic populations but not many have included American Indian/Alaska Native (AI/AN) patients. We retrospectively evaluated the factors associated with receipt of guideline-concordant care in AI/AN and non-Hispanic White (NHW) patients with stage I non-small cell lung cancer (NSCLC) and describe the relationship between guideline-concordant care and survival outcomes in these populations. Methods: Using the National Cancer Database, we identified NHW and AI/AN patients diagnosed with stage I NSCLC between 2004 and 2017. We evaluated the utilization of anatomic resection among both NHW and AI/AN and described the variables associated with anatomic resection. We also evaluated 5-year overall survival (OS) by treatment and race. We used the chi-square test, multivariable analysis, and the Kaplan-Meier method for statistical analysis. Results: We identified 196,349 patients. Of these, 195,736 (99.69%) were NHW and 613 (0.31%) were AI/AN. Relative to NHW, AI/AN were more frequently diagnosed at a younger age (40% vs. 28% diagnosed at 18-64 years of age; P<0.001) and more commonly resided in rural areas (14% vs. 5%; P<0.001). In our multivariable analysis adjusting for all patient factors [age at diagnosis, sex, race, residence location, Charlson Comorbidity Index (CCI), tumor stage, lymph node status, and treatment facility], AI/AN patients were less likely to undergo anatomic resection than NHW patients [odds ratio (OR), 0.74; 95% confidence interval (CI): 0.62-0.89]. In our unadjusted survival analysis, AI/AN patients had lower 5-year OS than NHW (58% vs. 56%; P=0.04). When adjusted for surgery this difference was no longer significant. Conclusions: AI/AN patients with stage I NSCLC undergo anatomic resection less frequently than do NHW, with lower 5-year OS than NHW. However, this survival difference is mitigated when AI/AN undergo anatomic resection.

Evaluating Disparities in Colon Cancer Survival in American Indian/Alaskan Native Patients Using the National Cancer Database.

BACKGROUND: Studies demonstrate higher mortality rates from colon cancer in American Indian/Alaskan Native (AI/AN) patients compared to non-Hispanic White (nHW). We aim to identify factors that contribute to survival disparities. METHODS: We used the National Cancer Database to identify AI/AN (n = 2127) and nHW (n = 527,045) patients with stage I-IV colon cancer from 2004 to 2016. Overall survival among stage I-IV colon cancer patients was estimated by Kaplan-Meier analysis; Cox proportional hazard ratios were used to identify independent predictors of survival. RESULTS: AI/AN patients with stage I-III disease had significantly shorter median survival than nHW (73 vs 77 months, respectively; p < 0.001); there were no differences in survival for stage IV. Adjusted analyses demonstrated that AI/AN race was an independent predictor of higher overall mortality compared to nHW (HR 1.19, 95% CI 1.01-1.33, p = 0.002). Importantly, compared to nHW, AI/AN were younger, had more comorbidities, had greater rurality, had more left-sided colon cancers, had higher stage but lower grade tumors, were less frequently treated at an academic facility, were more likely to experience a delay in initiation of chemotherapy, and were less likely to receive adjuvant chemotherapy for stage III disease. We found no differences in sex, receipt of surgery, or adequacy of lymph node dissection. CONCLUSION: We found patient, tumor, and treatment factors that potentially contribute to worse survival rates observed in AI/AN colon cancer patients. Limitations include the heterogeneity of AI/AN patients and the use of overall survival as an endpoint. Additional studies are needed to implement strategies to eliminate disparities.

Disparities in post-mastectomy reconstruction use among American Indian and Alaska Native women.

BACKGROUND: American Indian/Alaska Native (AI/AN) breast cancer patients undergo post-mastectomy reconstruction (PMR) infrequently relative to Non-Hispanic White (NHW) patients. Factors associated with low PMR rates among AI/AN are poorly understood. We sought to describe factors associated with this disparity in surgical care. METHODS: A retrospective cohort study of the National Cancer Database (2004 - 2017) identified AI/AN and NHW women, ages 18 - 64, who underwent mastectomy for stage 0 - III breast cancer. Patient characteristics, annual PMR rates, and factors associated with PMR were described with univariable analysis, the Cochran-Armitage test, and multivariable logistical regression. RESULTS: 414,036 NHW and 1,980 AI/AN met inclusion criteria. Relative to NHW, AI/AN had more comorbidities (20% vs 12% Charlson Comorbidity Index ≥ 1, p < 0.001), had non-private insurance (49% vs 20%, p < 0.001), and underwent unilateral mastectomy more frequently (69% vs 61%, p < 0.001). PMR rates increased over the study period, from 13% to 47% for AI/AN and from 29% to 62% for NHW (p <0.001). AI/AN race was independently associated with decreased likelihood of PMR (OR 0.62, 95% CI 0.56-0.69). Among AI/AN, decreased likelihood of PMR was significantly associated with older age at diagnosis, more remote year of diagnosis, advanced disease (tumor size > 5 cm, positive lymph nodes), unilateral mastectomy, non-private insurance, and lower educational attainment in patient's area of residence. CONCLUSION: PMR rates among AI/AN with stage 0 - III breast cancer have increased, yet remain significantly lower than among NHW. Further research should elicit AI/AN perspectives on PMR, and guide early breast cancer detection and treatment.

Improving Patient Experience Scores Using Simultaneous Interpretation on Family-Centered Rounds.

OBJECTIVES: Patients speaking a primary language other than English face barriers to equitable care, particularly patient-provider communications. There is no gold standard for providing inpatient medical interpretation on family-centered rounds (FCR). We aimed to implement simultaneous, in-person interpretation of FCR for Spanish-speaking families and hypothesized improved satisfaction in care. METHODS: In-person, Spanish Equipment-Assisted Simultaneous Medical Interpretation (EASMI) was implemented in March 2018 on FCR. Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) experience scores on communication domains were analyzed for Spanish and English-speaking families pre- (n = 118) and postimplementation (n = 552). Postimplementation, we conducted medical team surveys (n = 104) and semistructured interviews with Spanish-speaking families (n = 25) to determine satisfaction with interpretation modalities (phone, video, and EASMI). RESULTS: Spanish-speaking families exhibited statistically significant improvements in Child HCAHPS top box scores compared to English-speaking families in multiple communication and informed care-related domains. For example, "How often did your child's doctors explain things to you in a way that was easy to understand?" top box scores improved from 58% to 95% for Spanish-speaking families, compared to 85% to 83% for English speakers, with the differential effect of the intervention showing statistical significance (P = .001). Medical team surveys demonstrated high satisfaction with EASMI. Qualitative themes from interviews and open-ended survey responses emphasized multiple care benefits with EASMI, including a perceived reduction of communication errors and increased family participation. CONCLUSIONS: EASMI was associated with significant improvements in Child HCAHPS scores in communication domains and increased medical team and family members' satisfaction with interpretation. EASMI presents a novel method for equitable FCR for Spanish-speaking families.

Lasting Solutions for Advancement of Women of Color.

Despite efforts to improve parity in the biomedical workforce, gender bias persists related to equitable pay, promotion, speaking opportunities, journal editorial positions, research funding, and leadership positions. This bias becomes more prominent for women of color and women with other intersectional identities who come from underrepresented groups. It is critical to understand the barriers that women face and why the pathway is especially challenging for women of color. In this commentary, the authors cite research related to the effects of institutional gender bias in academic medicine, including research on bias against women of color. As academic leaders who come from underrepresented groups, the authors are aware that traditional approaches to reducing this bias have not worked well, and they instead highlight promising strategies aimed at filling the pathway to leadership with women of color who are qualified and ready to take the helm. They address solutions to ensure the academic pathway is supportive. They also provide several recommendations, including: offering more opportunities for mentorship and sponsorship, improving access to formal leadership programming, modeling successful upstander initiatives, recognizing the growing role of minority-based medical societies, implementing early-career education, increasing journal editorial board representation, and expanding promotion criteria. Appropriate training, education, and partnership with internal and external stakeholders are necessary to advance leadership equity for women of color in academic medicine.

Weaving pathways: talking with our Elders.

While there exists a relative paucity of completed healthcare directives nationally in the USA, even fewer exist within minority populations. This report describes one model for bringing advance care planning and discussions to American Indian and Alaska Native (AIAN) communities. In 2018, Honoring Choices of Minnesota approached the Center of American Indian and Minority Health (CAIMH), housed in the University of Minnesota Medical School, to collaborate on a project to increase healthcare directives in AIAN communities. CAIMH assembled AIAN students, faculty and community members to identify and address barriers to healthcare directive completion and discussions about end-of-life choices. The project team decided upon a two-pronged approach: culturally informed provider training paralleling culturally relevant community engagement. We aimed to empower AIAN to engage with healthcare providers on decisions impacting their care. To further support AIAN patients and their providers, a toolkit was created and will soon be available for dissemination.

Pain and Functional Limitations Among Midlife and Older Canadians: The Role of Discrimination, Race and Sense of Belonging.

OBJECTIVES: We drew on fundamental cause theory and the weathering hypothesis to examine how discrimination influences aging for midlife and older adults in Canada. METHODS: Using nationally representative data, we assessed the associations between discrimination and pain and functional limitations among adults 45 years of age and older. Discrimination was measured using a modified version of the Everyday Discrimination Scale. Chi-square tests were performed to check for baseline differences in the dependent and key predictor variables by race. Logistic regression was used to estimate the associations of discrimination, race, and sense of belonging with pain and functional limitations, net of sociodemographic characteristics and SES. RESULTS: Indigenous respondents showed a clear health disadvantage, with higher rates of pain and functional limitations compared to Whites and Asians. Self-reported discrimination was also higher for Indigenous midlife and older adults than for their White and Asian age counterparts. Discrimination had a direct and robust association with pain (OR 1.56, 95% CI 1.31, 1.87) and functional limitations (OR 1.55, 95% CI 1.29, 1.87). However, race moderated the impact of discrimination on functional limitations for Blacks. Finally, a strong sense of belonging to one's local community was protective against pain and functional limitations for all racial groups. DISCUSSION: Future research needs to further examine the impact of discrimination on Indigenous peoples' aging process. High rates of discrimination coupled with a greater burden of pain means that Indigenous midlife and older adults may require additional and targeted health and social service resources to age successfully.

Nuclear Medicine Advanced Associates: Physician Extenders in Nuclear Medicine-Now Is the Time.

From its inception in 2008 until 2020, the nuclear medicine advanced associate (NMAA) has evolved into a valuable member of the imaging team. Data show that NMAAs perform key services including supervision, interpretation, protocoling of adjunct studies, and management, freeing nuclear medicine physicians to concentrate on more complicated and time-intensive responsibilities. Additionally, the profession has gained ground by becoming recognized by the Nuclear Medicine Technology Certification Board (NMTCB), with the advent of a formal NMAA certification examination and recognition guidelines for institutions interested in establishing NMAA educational programs. Actions are under way for the creation of new NMAA programs with pathways to enhance and expand student recruitment. A special task force has been established by the Society of Nuclear Medicine and Molecular Imaging Advanced Associate Council to raise awareness of the advantages of the physician extender within the practice setting. Practicing NMAAs perform duties that are beyond the scope of nuclear medicine technologists.

Localization of the kinase Ataxia Telangiectasia Mutated to Adenovirus E4 mutant DNA replication centers is important for its inhibitory effect on viral DNA accumulation.

Adenovirus (Ad) type 5 (Ad5) E4 deletion mutants including H5dl1007 (E4-) induce a DNA damage response (DDR) that activates the kinase ataxia-telangiectasia mutated (ATM), which can interfere with efficient viral DNA replication. We find that localization of active phosphorylated ATM (pATM) to E4- viral replication centers (VRCs) is important for its inhibitory effect. ATM is necessary for localization of RNF8 and 53BP1 to E4 mutant VRCs, while recruitment of DDR factors Mre11, Mdc1 and γH2AX is ATM-independent, raising the possibility that ATM may affect viral chromatin at VRCs. We assessed E4- and Ad5 chromatin organization by micrococcal nuclease (MN) digestion. A significant fraction of Ad5 DNA is somewhat resistant to MN digestion, whereas E4- DNA is more susceptible. ATM inhibition increases the fraction of E4- DNA that is resistant to MN digestion. Our results address possible mechanisms through which ATM inhibits E4- DNA replication.

A critical role for donor-derived IL-22 in cutaneous chronic GVHD.

Graft-versus-host disease (GVHD) is the major cause of nonrelapse morbidity and mortality after allogeneic stem cell transplantation (allo-SCT). Prevention and treatment of GVHD remain inadequate and commonly lead to end-organ dysfunction and opportunistic infection. The role of interleukin (IL)-17 and IL-22 in GVHD remains uncertain, due to an apparent lack of lineage fidelity and variable and contextually determined protective and pathogenic effects. We demonstrate that donor T cell-derived IL-22 significantly exacerbates cutaneous chronic GVHD and that IL-22 is produced by highly inflammatory donor CD4+ T cells posttransplantation. IL-22 and IL-17A derive from both independent and overlapping lineages, defined as T helper (Th)22 and IL-22+ Th17 cells. Donor Th22 and IL-22+ Th17 cells share a similar IL-6-dependent developmental pathway, and while Th22 cells arise independently of the IL-22+ Th17 lineage, IL-17 signaling to donor Th22 directly promotes their development in allo-SCT. Importantly, while both IL-22 and IL-17 mediate skin GVHD, Th17-induced chronic GVHD can be attenuated by IL-22 inhibition in preclinical systems. In the clinic, high levels of both IL-17A and IL-22 expression are present in the skin of patients with GVHD after allo-SCT. Together, these data demonstrate a key role for donor-derived IL-22 in patients with chronic skin GVHD and confirm parallel but symbiotic developmental pathways of Th22 and Th17 differentiation.