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For nearly 2 decades, the Community Health Status Indicators tool reliably supplied communities with standardized, local health data and the capacity for peer-community comparisons. At the same time, it created a large community of users who shared learning in addressing local health needs. The tool survived a transition from the Health Resources and Services Administration to the Centers for Disease Control and Prevention before being shuttered in 2017. While new community data tools have come online, nothing has replaced Community Health Status Indicators, and many stakeholders continue to clamor for something new that will enable local health needs assessments, peer comparisons, and creation of a community of solutions. The National Committee on Vital and Health Statistics heard from many stakeholders that they still need a replacement data source. (Am J Public Health. 2021;111(10):1865–1873. https://doi.org/10.2105/AJPH.2021.306437 )

The physician gender wage gap may be due, in part, to productivity-based compensation models that undervalue female practice patterns.To determine how primary care physician (PCP) compensation by gender differs when applying existing productivity-based and alternative compensation models.Microsimulation.2016 to 2019 national clinical registry of 1222 primary care practices.Male and female PCPs matched on specialty, years since medical school graduation, practice site, and sessions worked.Net annual, full-time-equivalent compensation for male versus female PCPs, under productivity-based fee-for-service, panel size-based capitation without or with risk adjustment, and hybrid payment models. Microsimulation inputs included patient and visit characteristics and overhead expenses.Among 1435 matched male (Panel attribution based on office visits.The gender wage gap varied by compensation model, with capitation risk-adjusted for patient age and sex resulting in a smaller gap. Future models might better align with primary care effort and outcomes.None.

Supplemental Figures 1-5 with figure legends embedded.

Castration-resistant prostate cancer can be treated with the antiandrogen enzalutamide, but responses and duration of response are variable. To identify genes that support enzalutamide resistance, we performed a short hairpin RNA (shRNA) screen in the bone-homing, castration-resistant prostate cancer cell line, C4-2B. We identified 11 genes (TFAP2C, CAD, SPDEF, EIF6, GABRG2, CDC37, PSMD12, COL5A2, AR, MAP3K11, and ACAT1) whose loss resulted in decreased cell survival in response to enzalutamide. To validate our screen, we performed transient knockdowns in C4-2B and 22Rv1 cells and evaluated cell survival in response to enzalutamide. Through these studies, we validated three genes (ACAT1, MAP3K11, and PSMD12) as supporters of enzalutamide resistance in vitro. Although ACAT1 expression is lower in metastatic castration-resistant prostate cancer samples versus primary prostate cancer samples, knockdown of ACAT1 was sufficient to reduce cell survival in C4-2B and 22Rv1 cells. MAP3K11 expression increases with Gleason grade, and the highest expression is observed in metastatic castration-resistant disease. Knockdown of MAP3K11 reduced cell survival, and pharmacologic inhibition of MAP3K11 with CEP-1347 in combination with enzalutamide resulted in a dramatic increase in cell death. This was associated with decreased phosphorylation of AR-Serine650, which is required for maximal AR activation. Finally, although PSMD12 expression did not change during disease progression, knockdown of PSMD12 resulted in decreased AR and AR splice variant expression, likely contributing to the C4-2B and 22Rv1 decrease in cell survival. Our study has therefore identified at least three new supporters of enzalutamide resistance in castration-resistant prostate cancer cells in vitro.

Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cells. Inhibition of KDR catalytic activity blocks tumor neoangiogenesis, reduces vascular permeability, and, in animal models, inhibits tumor growth and metastasis. Using a gene expression profiling strategy in rat tumor models, we identified a set of six genes that are selectively overexpressed in tumor endothelial cells relative to tumor cells and whose pattern of expression correlates with the rate of tumor endothelial cell proliferation. In addition to being potential targets for antiangiogenesis tumor therapy, the expression patterns of these genes or their protein products may aid the development of pharmacodynamic assays for small molecule inhibitors of the KDR kinase in human tumors.

Supplementary Table S1 from Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling

The graduate medical education (GME) system is heavily subsidized by the public in return for producing physicians who meet society's needs. Under the terms of this implicit social contract, decisions about how this funding is allocated are deferred to the individual training sites. Institutions receiving public funding face potential conflicts of interest, which have at times prioritized institutional purposes and needs over societal needs, highlighting that there is little public accountability for how such funding is used. The cost and institutional burden of assessing many fundamental GME outcomes, such as specialty, geographic physician distribution, training-imprinted cost behaviors, and populations served, could be mitigated as data sources and methods for assessing GME outcomes and guiding training improvement already exist. This new capacity to assess system-level outcomes could help institutions and policymakers strategically address the greatest public needs. Measurement of educational outcomes can also be used to guide training improvement at every level of the educational system (i.e., the individual trainee, individual teaching institution, and collective GME system levels). There are good examples of institutions, states, and training consortia that are already assessing and using GME outcomes in these ways. The ultimate outcome could be a GME system that better meets the needs of society and better honors what is now only an implicit social contract.

SummaryDrugs of abuse increase extracellular concentrations of dopamine in the nucleus accumbens (NAc), resulting in transcriptional alterations that drive long-lasting cellular and behavioral adaptations. While decades of research have focused on the transcriptional mechanisms by which drugs of abuse influence neuronal physiology and function, few studies have comprehensively defined NAc cell type heterogeneity in transcriptional responses to drugs of abuse. Here, we used single nucleus RNA-seq (snRNA-seq) to characterize the transcriptome of over 39,000 NAc cells from male and female adult Sprague-Dawley rats following acute or repeated cocaine experience. This dataset identified 16 transcriptionally distinct cell populations, including two populations of medium spiny neurons (MSNs) that express the Drd1 dopamine receptor (D1-MSNs). Critically, while both populations expressed classic marker genes of D1-MSNs, only one population exhibited a robust transcriptional response to cocaine. Validation of population-selective transcripts using RNA in situ hybridization revealed distinct spatial compartmentalization of these D1-MSN populations within the NAc. Finally, analysis of published NAc snRNA-seq datasets from non-human primates and humans demonstrated conservation of MSN subtypes across rat and higher order mammals, and further highlighted cell type-specific transcriptional differences across the NAc and broader striatum. These results highlight the utility in using snRNA-seq to characterize both cell type heterogeneity and cell type-specific responses to cocaine and provides a useful resource for cross-species comparisons of NAc cell composition.

Background: Electronic health records (EHRs) have been connected to excessive workload and physician burnout. Little is known about variation in physician experience with different EHRs, however. Objective: To analyze variation in reported usability and satisfaction across EHRs. Design: Internet-based survey available between December 2021 and October 2022 integrated into American Board of Family Medicine (ABFM) certification process. Participants: ABFM-certified family physicians who use an EHR with at least 50 total responding physicians. Measurements: Self-reported experience of EHR usability and satisfaction. Key Results: We analyzed the responses of 3358 physicians who used one of nine EHRs. Epic, athenahealth, and Practice Fusion were rated significantly higher across six measures of usability. Overall, between 10 and 30% reported being very satisfied with their EHR, and another 32 to 40% report being somewhat satisfied. Physicians who use athenahealth or Epic were most likely to be very satisfied, while physicians using Allscripts, Cerner, or Greenway were the least likely to be very satisfied. EHR-specific factors were the greatest overall influence on variation in satisfaction: they explained 48% of variation in the probability of being very satisfied with Epic, 46% with eClinical Works, 14% with athenahealth, and 49% with Cerner. Conclusions: Meaningful differences exist in physician-reported usability and overall satisfaction with EHRs, largely explained by EHR-specific factors. User-centric design and implementation, and robust ongoing evaluation are needed to reduce physician burden and ensure excellent experience with EHRs.

Will stakeholder theory continue to transform how we think about business and society? On the occasion of this journal’s 60th anniversary, this review article examines the journal’s role in shaping stakeholder theory to date and suggests that it still has transformative potential. We conducted a bibliometric analysis of co-citations in the literature from 1984 to 2020. Reporting these results, we examine the field’s evolving structure. Contextualized theoretically as an accomplishment of institutional work—the creation of a meaningful and innovative field ideology—this structure is remarkable for how it integrates ethical and behavioral arguments, invites engagement from adjacent domains, and arrives at important insights for business and society. We advance a research agenda consistent with this larger institutional project.

This study evaluated the utility and performance of the LACE index and HOSPITAL score with consideration of the type of diagnoses and assessed the accuracy of these models for predicting readmission risks in patient cohorts from 2 large academic medical centers. Admissions to 2 hospitals from 2011 to 2015, derived from the Vizient Clinical Data Base and regional health information exchange, were included in this study (291 886 encounters). Models were assessed using Bayesian information criterion and area under the receiver operating characteristic curve. They were compared in CMS diagnosis-based cohorts and in 2 non-CMS cancer diagnosis-based cohorts. Overall, both models for readmission risk performed well, with LACE performing slightly better (area under the receiver operating characteristic curve 0.73 versus 0.69; P ≤ 0.001). HOSPITAL consistently outperformed LACE among 4 CMS target diagnoses, lung cancer, and colon cancer. Both LACE and HOSPITAL predict readmission risks well in the overall population, but performance varies by salient, diagnosis-based risk factors.

BACKGROUND The Centers for Medicare and Medicaid Services proposed that the Transforming Clinical Practice Initiative (TCPI) would improve health outcomes for patients, reduce utilization of institutional services, and generate significant savings for payers by the end of September 2019. OBJECTIVE The objective of this study was to investigate whether participation in TCPI's Practice Transformation Networks (PTNs) was associated with improved cost and utilization outcomes for Medicare patients of family medicine-based practices in the first 2 years, that is, 2016-2017, of the Initiative. STUDY DESIGN A quasi-experimental design with a longitudinal cohort of family medicine-based practices and a propensity-matched comparison sample. SUBJECTS A total of 761 PTN practices and 3451 non-PTN practices. MEASURES To measure practice-level patient outcomes, we attributed patients to practice based on the plurality of office visits. We obtained Medicare claims from 2011 to 2017 to assess PTN participation effects for Medicare Part A and B costs, hospital admission, and emergency department visit rates using a Difference-in-Differences design, adjusting for baseline characteristics. RESULTS The differences in Medicare Part A and B costs (-1.71%, P=0.25), annual rates of hospitalization (-0.59%, P=0.12) and emergency department visit (-0.29%, P=0.46) were not significantly lower among PTN practices (N=761) than among propensity score-matched non-PTN practices (N=3541). CONCLUSIONS TCPI's transforming efforts, such as the outcomes examined in the study, might need a longer time frame to manifest and require evaluation after the full 4-year participation period. The indistinguishable effect of PTN participation may also be attributed to the fact that non-PTN practices might have participated in other initiatives that changed their care and curbed health care utilization and costs consequently.

Background The risk of severe COVID-19 varies significantly among persons of similar age and is higher in males. Age-independent, sex-biased differences in susceptibility to severe COVID-19 may be ascribable to deficits in a sexually dimorphic protective attribute that we termed immunologic resilience (IR). Objective To examine whether deficits in IR that antedate or are induced by SARS-CoV-2 infection independently predict COVID-19 mortality. Methods IR levels were quantified with two novel metrics: immune health grades (IHG-I [best] to IHG-IV) to gauge CD8+ and CD4+ T-cell count equilibrium, and blood gene expression signatures. IR metrics were examined in a prospective COVID-19 cohort (n=522); primary outcome was 30-day mortality. Associations of IR metrics with outcomes in non-COVID-19 cohorts (n=13,461) provided the framework for linking pre-COVID-19 IR status to IR during COVID-19, as well as to clinical outcomes. Results IHG-I, tracking high-grade equilibrium between CD8+ and CD4+ T-cell counts, was the most common grade (73%) among healthy adults, particularly in females. SARS-CoV-2 infection associated with underrepresentation of IHG-I (21%) vs. overrepresentation (77%) of IHG-II or IHG-IV, especially in males vs. females (P Conclusion Preservation of immunocompetence with controlled inflammation during antigenic challenges is a hallmark of IR and associates with longevity and AIDS resistance. Independent of age, a male-biased proclivity to degrade IR before and/or during SARS-CoV-2 infection predisposes to severe COVID-19. Clinical implications Biomarkers tracking immunologic resilience may have broad prognostic utility, as they associated with longevity, as well as resistance to a progressive disease course during SARS-CoV-2, influenza, or HIV infection.

Aims Knee arthroplasty surgery is a highly effective treatment for arthritis and disorders of the knee. There are a wide variety of implant brands and types of knee arthroplasty available to surgeons. As a result of a number of highly publicized failures, arthroplasty surgery is highly regulated in the UK and many other countries through national registries, introduced to monitor implant performance, surgeons, and hospitals. With time, the options available within many brand portfolios have grown, with alternative tibial or femoral components, tibial insert materials, or shapes and patella resurfacings. In this study we have investigated the effect of the expansion of implant brand portfolios and where there may be a lack of transparency around a brand name. We also aimed to establish the potential numbers of compatible implant construct combinations. Methods Hypothetical implant brand portfolios were proposed, and the number of compatible implant construct combinations was calculated. Results A simple knee portfolio with cemented cruciate-retaining (CR) and posterior-stabilized (PS) components, with and without a patella, has four combinations. If there are two options available for each component, the numbers double for each option, resulting in 32 combinations. The effect of adding a third option multiplies the number by 1.3. Introducing compatible uncemented options, with the effect of hybrids, multiplies the number by 4. An implant portfolio with two femoral components (both in CR and PS), with two insert options and a patella, all in cemented and uncemented versions leads to 192 possible compatible implant construct combinations. There are implant brands available to surgeons with many more than two options. Conclusion This study demonstrates that the addition of multiple variants within a knee brand portfolio leads to a large number (many hundreds) of compatible implant construct combinations. Revision rates of implant combinations are not currently reviewed at this level of granularity, leading to the risk of camouflage of true outcomes. Cite this article: Bone Joint J 2021;103-B(10):1555–1560.

A National Academies of Sciences, Engineering, and Medicine committee developed a plan to implement high-quality primary care. One of the 5 key objectives was designing information technology that serves the patient, family, and interprofessional care team. The committee defined high-quality primary care as the provision of whole person, integrated, accessible, and equitable healthcare by interprofessional teams who are accountable for addressing most of an individual’s health across settings and through sustained relationships. The committee recommended 2 essential actions for digital health. The first action is developing the next phase of digital health certification standards that support relationship-based, continuous, person-centered care; simplify user experience; ensure equitable access; and hold vendors accountable. Second, the committee recommended adopting a comprehensive aggregate patient data system usable by any certified digital health tool. This article reviews primary care’s digital health needs and describes successful digital health for primary care.

A 2021 article, "Now is our time to act: Why academic medicine must embrace community collaboration as its fourth mission," by Association of American Medical Colleges (AAMC) authors, including AAMC president and CEO Dr. David J. Skorton, offers 2 aims that are highly related: community collaboration and health equity. The AAMC's call to prioritize community collaboration and health equity as pillars of the academic medicine mission echo earlier work on community-oriented primary care (COPC) and an even more robust model that builds on COPC, community-engaged health care (CEHC). COPC is a tested, systematic approach to health care by which a health clinic or system collaborates with a community to reshape priorities and services based on assessed health needs and determinants of health. COPC affirms health inequities' socioeconomic and political roots, emphasizing health care as a relationship, not a transaction or commodity. Communities where COPC is implemented often see reductions in health inequities, especially those related to socioeconomic, structural, and environmental factors. COPC was the foundation on which community health centers were built, and early models had demonstrable effects on community health and engagement. Several academic health centers build on COPC to achieve community-engaged health care (CEHC). In CEHC, primary care remains critical, but more of the academic health center's functions are pulled into community engagement and trust building. Thus, the AAMC has described and embraced a care and training model for which there are good, longitudinal examples among medical schools and teaching hospitals. Spreading CEHC and aligning the Community Health Needs Assessment requirements of academic health centers with the fourth mission could go a long way to improving equity, building trust, and repairing the social contract for health care.

d-Glucosaminate-6-phosphate ammonia-lyase (DGL) catalyzes the conversion of d-glucosaminate-6-phosphate to 2-keto-3-deoxyglutarate-6-phosphate, with stereospecific protonation of C-3 of the product. The crystal structure of DGL showed that His-163 could serve as the proton donor. H163A mutant DGL is fully active in the steady-state reaction, and the pre-steady-state kinetics are very similar to those of wild-type DGL. However, H163A DGL accumulates a transient intermediate with λ