Practice Facilitation and Peer Coaching for Uncontrolled Hypertension Among Black Individuals: A Randomized Clinical Trial

IMPORTANCE: Rural Black participants need effective intervention to achieve better blood pressure (BP) control. OBJECTIVE: Among Black rural adults with persistently uncontrolled hypertension attending primary care clinics, to determine whether peer coaching (PC), practice facilitation (PF), or both (PCPF) are superior to enhanced usual care (EUC) in improving BP control. DESIGN, SETTING, AND PARTICIPANTS: A cluster randomized clinical trial was conducted in 69 rural primary care practices across Alabama and North Carolina between September 23, 2016, and September 26, 2019. The participating practices were randomized to 4 groups: PC plus EUC, PF plus EUC, PCPF plus EUC, and EUC alone. The baseline EUC approach included a laptop for each participating practice with hyperlinks to participant education on hypertension, a binder of practice tips, a poster showing an algorithm for stepped care to improve BP, and 25 home BP monitors. The trial was stopped on February 28, 2021, after final data collection. The study included Black participants with persistently uncontrolled hypertension. Data were analyzed from February 28, 2021, to December 13, 2022. INTERVENTIONS: Practice facilitators helped practices implement at least 4 quality improvement projects designed to improve BP control throughout 1 year. Peer coaches delivered a structured program via telephone on hypertension self-management throughout 1 year. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of participants in each trial group with BP values of less than 140/90 mm Hg at 6 months and 12 months. The secondary outcome was a change in the systolic BP of participants at 6 months and 12 months. RESULTS: A total of 69 practices were randomized, and 1209 participants\u27 data were included in the analysis. The mean (SD) age of participants was 58 (12) years, and 748 (62%) were women. In the intention-to-treat analyses, neither intervention alone nor in combination improved BP control or BP levels more than EUC (at 12 months, PF vs EUC odds ratio [OR], 0.94 [95% CI, 0.58-1.52]; PC vs EUC OR, 1.30 [95% CI, 0.83-2.04]; PCPF vs EUC OR, 1.02 [95% CI, 0.64-1.64]). In preplanned subgroup analyses, participants younger than 60 years in the PC and PCPF groups experienced a significant 5 mm Hg greater reduction in systolic BP than participants younger than 60 years in the EUC group at 12 months. Practicewide BP control estimates in PF groups suggested that BP control improved from 54% to 61%, a finding that was not observed in the trial\u27s participants. CONCLUSIONS AND RELEVANCE: The results of this cluster randomized clinical trial demonstrated that neither PC nor PF demonstrated a superior improvement in overall BP control compared with EUC. However, PC led to a significant reduction in systolic BP among younger adults

Recruitment and retention of primary care practices in the Southeastern Collaboration to Improve Blood Pressure Control

Background: Racial disparities related to hypertension prevalence and control persist, with Black persons continuing to have both high prevalence and suboptimal control. The Black Belt region of the US Southeast is characterized by multiple critical priority populations: rural, low-income, and minority (Black). Methods: In a cluster-randomized, controlled, pragmatic implementation trial, the Southeastern Collaboration to Improve Blood Pressure Control evaluated two multi-component, multi-level functional interventions – peer coaching (PC) and practice facilitation (PF) (separately and combined) – as adjuncts to usual care to improve blood pressure control in the Black Belt. The overall goal was to randomize 80 primary care practices (later reduced to 69 practices) in Alabama and North Carolina to one of four interventions: 1) enhanced usual care (EUC); 2) EUC plus PC; 3) EUC plus PF; or 4) EUC plus both PC and PF. Several measures to facilitate recruitment and retention of practices were employed, including practice readiness assessment. Results: Contact was initiated with 248 practices during the study enrollment period. Of these, 99 declined participation, 39 were ineligible, and 41 were being evaluated for inclusion when the target number of practices was reached. The remaining 69 practices eventually were enrolled, with 18 practices randomized to EUC, 19 to PC, 16 to PF, and 16 to PC plus PF. Only two practices (2.9%) were withdrawn during the study. Several facilitators of and barriers to practice recruitment and retention were identified. Conclusion: Our findings underscore the importance of a structured approach to recruiting primary care practices in a pragmatic implementation trial.ClinicalTrials.gov registration number NCT0286666

Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis

T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets

Resolving medulloblastoma cellular architecture by single-cell genomics

Medulloblastoma is a malignant childhood cerebellar tumour type that comprises distinct molecular subgroups. Whereas genomic characteristics of these subgroups are well defined, the extent to which cellular diversity underlies their divergent biology and clinical behaviour remains largely unexplored. Here we used single-cell transcriptomics to investigate intra- and intertumoral heterogeneity in 25 medulloblastomas spanning all molecular subgroups. WNT, SHH and Group 3 tumours comprised subgroup-specific undifferentiated and differentiated neuronal-like malignant populations, whereas Group 4 tumours consisted exclusively of differentiated neuronal-like neoplastic cells. SHH tumours closely resembled granule neurons of varying differentiation states that correlated with patient age. Group 3 and Group 4 tumours exhibited a developmental trajectory from primitive progenitor-like to more mature neuronal-like cells, the relative proportions of which distinguished these subgroups. Cross-species transcriptomics defined distinct glutamatergic populations as putative cells-of-origin for SHH and Group 4 subtypes. Collectively, these data provide insights into the cellular and developmental states underlying subtype-specific medulloblastoma biology

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4–6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically ‘cold’ tumour microenvironment8. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone—a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma—generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4–6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically ‘cold’ tumour microenvironment8. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone—a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma—generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma