Citations

Abstract Introduction Growing evidence suggests that there are sleep health disparities in the United States that disadvantage communities of color, and other socioeconomically marginalized groups in medical and mental health settings. Research in public policy indicates several points of intervention for increasing engagement with treatment services in communities of color at the primary care level, including individual beliefs about mental health/health issues, and perceptions of various points of treatment engagement, as well as community factors (e.g., neighbors and church; Davey & Watson, 2007). Accordingly, the current study implemented a community-level virtual intervention that targeted beliefs about sleep and perceptions of behavioral sleep treatment with the aim to increase willingness to engage with treatment at the primary care level. Methods We conducted 12 semi-structured qualitative focus groups with 35 individuals from communities of color about their awareness, perception of, and access to behavioral sleep treatment in healthcare settings. Transcripts were coded using the Rapid and Rigorous Qualitative Data Analysis method for themes relevant to the guiding question, 'What are people/persons of color experiences and perspectives of sleep, and specific areas of improvement to increase people/persons of color groups' utilization of behavioral sleep services?'. Results After a brief period of education (range = 15-20 minutes) about cognitive-behavioral therapy for insomnia (CBTi), participants perceived behavioral sleep treatment as a favorable option both over and in conjunction with pharmacological options. Medical mistrust was mentioned as the most significant barrier in each focus group, with participants highlighting that increased attention to collaborative care and comprehensive education about treatment options at the primary care level would be helpful for reducing mistrust. Pre- and post-group survey analysis indicated a significant increase in participants’ willingness to use primary care as an entry point to access/utilization of behavioral sleep treatment (pre-group willingness = 54.84%, post-group willingness = 91.42%, p<.001). Conclusion Findings suggest that intervention at the community level can be powerful for increasing the willingness of communities of color to engage in treatment at the primary care level. It is paramount that future research continues to examine ways to increase engagement with behavioral sleep treatment to help reduce sleep health disparities. Support (if any)

Background Despite its approval for acute ischemic stroke >25 years ago, intravenous thrombolysis (IVT) remains underused, with inequities by age, sex, race, ethnicity, and geography. Little is known about IVT rates by insurance status. Methods and Results We assessed temporal trends from 2002 to 2015 in IVT for acute ischemic stroke in the Nationwide Inpatient Sample using adjusted, survey ‐ weighted logistic regression. We calculated odds ratios for IVT for each category in 2002 to 2008 (period 1) and 2009 to 2015 (period 2). IVT use for acute ischemic stroke increased from 1.0% in 2002 to 6.8% in 2015 (adjusted annual relative ratio, 1.15). Individuals aged ≥85 years had the most pronounced increase during 2002 to 2015 (adjusted annual relative ratio, 1.18) but were less likely to receive IVT compared with 18‐ to 44‐year‐olds in period 1 (adjusted odds ratio [aOR], 0.23) and period 2 (aOR, 0.36). Women were less likely than men to receive IVT, but the disparity narrowed over time (period 1: aOR, 0.81; period 2: aOR, 0.94). Inequities in IVT resolved for Hispanic individuals in period 2 (aOR, 0.96) but not for Black individuals (period 2: aOR, 0.81). The disparity in IVT for Medicare patients, compared with privately insured patients, lessened over time (period 1: aOR, 0.59; period 2: aOR, 0.75). Patients treated in rural hospitals remained less likely to receive IVT than in urban hospitals; a more dramatic increase in urbanity widened the inequity (period 2, urban nonteaching versus rural: aOR, 2.58, period 2, urban teaching versus rural: aOR, 3.90). Conclusions IVT for acute ischemic stroke increased among adults. Despite some encouraging trends, the remaining disparities highlight the need for intensified efforts at addressing inequities.

Peripartum cardiomyopathy (PPCM) is an idiopathic form of pregnancy-induced heart failure associated with preeclampsia. Circulating factors in late pregnancy are thought to contribute to both diseases, suggesting a common underlying pathophysiological process. However, what drives this process remains unclear. Using serum proteomics, we identified the senescence-associated secretory phenotype (SASP), a marker of cellular senescence associated with biological aging, as the most highly up-regulated pathway in young women with PPCM or preeclampsia. Placentas from women with preeclampsia displayed multiple markers of amplified senescence and tissue aging, as well as overall increased gene expression of 28 circulating proteins that contributed to SASP pathway enrichment in serum samples from patients with preeclampsia or PPCM. The most highly expressed placental SASP factor, activin A, was associated with cardiac dysfunction or heart failure severity in women with preeclampsia or PPCM. In a murine model of PPCM induced by cardiomyocyte-specific deletion of the gene encoding peroxisome proliferator–activated receptor γ coactivator-1α, inhibiting activin A signaling in the early postpartum period with a monoclonal antibody to the activin type II receptor improved heart function. In addition, attenuating placental senescence with the senolytic compound fisetin in late pregnancy improved cardiac function in these animals. These findings link senescence biology to cardiac dysfunction in pregnancy and help to elucidate the pathogenesis underlying cardiovascular diseases of pregnancy.

Summary Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai–Dorfman–Destombes disease (RDD) and Erdheim–Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy‐proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty‐seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non‐V600‐BRAF, RAF1 and a BICD2‐BRAF fusion. A repeated‐measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19–137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03–0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.

Abstract Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2–7.6). Median progression-free survival was 6.9 months (95% CI, 5.7–7.4) and median overall survival was 15.9 months (95% CI, 11.8–18.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3–4 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance. Significance: Adagrasib plus cetuximab demonstrates promising clinical activity and tolerable safety in heavily pretreated patients with unresectable or metastatic KRASG12C-mutated colorectal cancer. These data support a potential new standard of care and highlight the significance of testing and identification of KRASG12C mutations in patients with colorectal cancer. This article is featured in Selected Articles from This Issue, p. 897 See co-corresponding author Rona Yaeger discuss this research article, published simultaneously at the AACR Annual Meeting 2024: https://vimeo.com/932606282/f27a6e46f4

ObjectivesTo evaluate the effect of Alzheimer's disease (AD) ‐related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).MethodsData from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4‐R‐Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD‐positive (CBS/PSP‐AD) and AD‐negative (CBS/PSP‐noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p‐tau, t‐tau, and amyloid‐beta, and plasma ptau‐217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole‐brain gray matter volume and functional networks connectivity were compared across groups.ResultsData were analyzed from 87 CBS/PSP‐noAD and 23 CBS/PSP‐AD, 18 AD, and 30 healthy controls. CBS/PSP‐noAD showed worse performance in comparison to CBS/PSP‐AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP‐AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP‐noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP‐AD compared with CBS/PSP‐no AD and controls. The thalamic network connectivity was most affected in CBS/PSP‐noAD.InterpretationAD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co‐pathology. ANN NEUROL 2024;96:99–109

Objectives: To assess clinicians’ prescribing practices for anticoagulation in older adults with atrial fibrillation or atrial flutter (AF/F) and determine factors common among those without anticoagulation. Methods: We performed a community-based retrospective cohort study of adults aged 65 years and older with a history of nonvalvular AF/F to determine the rate of oral anticoagulation utilization. We also assessed for associations between anticoagulation use and comorbid conditions and common geriatric syndromes. Results: A total of 3832 patients with a diagnosis of nonvalvular AF/F were included (mean [SD] age, 79.9 [8.4] years), 2693 (70.3%) of whom were receiving anticoagulation (51.7%, a vitamin K antagonist; 48.1%, a direct-acting oral anticoagulant). Patients with higher Elderly Risk Assessment index (ERA) scores, a surrogate for health vulnerability, received anticoagulation less often than patients with lower scores. The percentage of patients with a history of falling was higher among those who did not receive anticoagulation than among those who did (44.4% vs 32.8%; P < .001). Similarly, a diagnosis of dementia was more common in the no-anticoagulation group than the anticoagulation group (18.5% vs 12.7%; P < .001). Conclusions: A substantial proportion of older adults with AF/F do not receive anticoagulation. Those without anticoagulation had higher risk of health deterioration based on higher ERA scores and had a higher incidence of dementia and fall history. This suggests that the presence of geriatric syndromes may influence the decision to withhold anticoagulation.

Background: Residency is a time of personal and professional growth. Resident assessment and feedback are an integral part of that process. However, assessment may be influenced by various types of bias, including gender bias. Women are less likely than men to be identified by their professional titles in many settings. The use of professional titles for residents in written assessments is unknown and may be a marker of bias. Objective: To assess for differences and trends regarding the use of professional and personal titles in formal resident assessments related to gender-based resident–faculty pairs. Methods: Electronic assessments of postgraduate year 1 (PGY1) internal medicine residents from the 2019–2020 academic year were used. Professional title use was analyzed, as it relates to resident–faculty gendered dyads, among other variables. The primary outcome of professional title usage was split into a binary variable by professional versus other titles and analyzed using logistic regression and random-effects model. Results: We analyzed 1,363 unique electronic assessments (37.8% from female faculty). Female residents were more likely to be addressed by a professional title than their male colleagues (odds ratio [OR], 1.7; confidence interval [CI], 1.2–2.4; p = 0.02). We found no difference in professional title usage based on resident–faculty gendered dyads. After adjusting for repeated faculty and resident encounters with random-effects model, secondary analysis found no significant difference in evaluation of word count between gendered dyads. Conclusions: The analysis found no significant difference in professional title usage based on resident–faculty dyads. In our analysis, female residents were significantly more likely to have their professional title used on assessments than male residents.