Pharmacists Colocated With Primary Care Physicians: Understanding Delivery of Interprofessional Primary Care.

BACKGROUND: While evidence supports interprofessional primary care models that include pharmacists, the extent to which pharmacists are working in primary care and the factors associated with colocation is unknown. OBJECTIVES: This study aimed to analyze the physical colocation of pharmacists with primary care providers (PCPs) and examine predictors associated with colocation. RESEARCH DESIGN: This is a retrospective cross-sectional study of pharmacists and PCPs with individual National Provider Identifiers in the National Plan and Provider Enumeration System's database. Pharmacist and PCP practice addresses of the health care professionals were geocoded, and distances less than 0.1 miles were considered physically colocated. SUBJECTS: In all, 502,373 physicians and 221,534 pharmacists were included. RESULTS: When excluding hospital-based pharmacists, 1 in 10 (11%) pharmacists were colocated with a PCP. Pharmacists in urban settings were more likely to be colocated than those in rural areas (OR=1.32, CI: 1.26-1.38). Counties with the highest proportion of licensed pharmacists per 100,000 people in the county had higher colocation (OR=1.38, CI: 1.32-1.45). Colocation was significantly higher in states with an expanded scope of practice (OR 1.37, CI: 1.32-1.42) and those that have expanded Medicaid (OR 1.07, CI: 1.03-1.11). Colocated pharmacists more commonly worked in larger physician practices. CONCLUSION: Although including pharmacists on primary care teams improves clinical outcomes, reduces health care costs, and enhances patient and provider experience, colocation appears to be unevenly dispersed across the United States, with lower rates in rural areas. As the integration of pharmacists in primary care continues to expand, knowing the prevalence and facilitators of growth will be helpful to policymakers, researchers, and clinical administrators.

Responding to One Rural Community's Primary Care Needs: Investing in Workforce and Broad Community Stakeholder Engagement.

Lack of access to high-quality primary care has been shown to contribute to urban-rural health disparities. We describe a model in which an academic health system made targeted primary care investments to address rural health disparities while building the health workforce to ensure sustainability.

The Distribution of Additional Residency Slots to Rural and Underserved Areas.

This study analyzes data from the Centers for Medicare & Medicaid Services to identify whether new residency training slots went to rural and underserved areas with the greatest need.

Post-Hospital Discharge Care: A Retrospective Cohort Study Exploring the Value of Pharmacist-Enhanced Care and Describing Medication-Related Problems.

BACKGROUND Medication-related problems occur at high rates during care transitions. Evidence suggests that pharmacists are well-suited to identify and resolve medication-related problems during hospital admission and at discharge. Additional evidence is needed to understand the impact of face-to-face pharmacist visits in primary care after discharge. The purpose of the study was to describe medication-related problems found during face-to-face pharmacist visits in a medical home after hospital discharge.METHODS A retrospective cohort study was conducted within an academic primary care center staffed by family medicine trained physicians that evaluated patients who attended a hospital follow-up visit with pharmacist-enhanced care (N = 86) versus usual care (N = 86). The primary objective was to describe medication-related problems identified by pharmacists using a modified individualized Medication Assessment and Planning tool for patients receiving pharmacist-enhanced care. Secondary analyses were also conducted to compare 30-day and 60-day hospital readmission and emergency department visit rates in those exposed to pharmacist-enhanced care versus those who were not.RESULTS At baseline, the mean hospitalizations in the prior year were 1.1 ± 1.7 (pharmacist-enhanced care) and 0.76 ± 1.2 (usual care), indicating a low initial readmission risk. Of patients receiving pharmacist-enhanced care, 97.7% were found to have at least 1 medication-related problem, with an average of 4.36 medication-related problems per patient. The 30-day readmission rate was lower, but not significantly different between groups (8.1% for pharmacist-enhanced care versus 12.8% for usual care; adjusted odds ratio (OR), 0.47; 95% confidence interval (CI), 0.16-1.36).LIMITATIONS Limitations include the retrospective cohort study design and small sample size. Medication-related problems were identified and collected prospectively during pharmacist visits.CONCLUSION Medication-related problems are ubiquitous after hospital discharge. Larger prospective studies will be needed to understand the potential value of pharmacist-enhanced care during hospital follow-up visits on readmission rates in low-risk patient populations receiving care within a primary care medical home.

Identification of risk factors for inappropriate and suboptimal initiation of direct oral anticoagulants.

Direct Oral Anticoagulants (DOACs) require specific dosing and monitoring to ensure safe and appropriate use. The purpose of this evaluation was to identify patient- and process-related factors that correlate with increased risk of inappropriate prescribing of DOACs. A retrospective chart review was conducted in three outpatient clinics within an academic medical center to identify patients started on DOAC therapy and evaluate the appropriateness of DOAC initiation. Data collected included patient demographics, DOAC medication initiated, dose, indication, baseline laboratory values, concomitant medications, type and specialty of prescriber, and initiation setting. Appropriateness of initial dose was assessed and data were analyzed in order to identify factors correlating with inappropriate use. One-hundred sixty-seven patients initiated on a DOAC were identified. Most patients were prescribed anticoagulation for atrial fibrillation (74.9 %) and most commonly prescribed rivaroxaban (62.9 %). An inappropriate dose was prescribed in 24 (14.4 %) patients. Female patients and patients over 75 years were more likely to be prescribed an inappropriate initial dose. Baseline evaluation of blood counts and organ function were often not performed: hemoglobin values had not been drawn within the month prior to initiation in 28.7 % of patients, serum creatinine in 22.8 %, alanine transaminase in 52.1 %, and total bilirubin in 64.1 %. Lack of baseline labs was more pronounced in patients initiated on a DOAC in the outpatient setting. Dosing and baseline lab collection for DOAC initiation were suboptimal in all settings analyzed. Targeted interventions are needed to ensure the safe and appropriate use of DOAC therapy.

Heparin-Calibrated Chromogenic Anti-Xa Activity Measurements in Patients Receiving Rivaroxaban: Can This Test Be Used to Quantify Drug Level?

BACKGROUND: Determination of plasma rivaroxaban concentration may be necessary in certain clinical situations. Rivaroxaban concentration can be accurately and rapidly determined using a chromogenic anti-activated factor X (factor Xa) assay with specific drug calibrator material. However, there are currently no Food and Drug Administration (FDA)-approved rivaroxaban calibrators available in the United States. OBJECTIVE: To determine whether FDA-approved commercial kits for measuring heparin anti-factor Xa activity can be used to assess rivaroxaban concentrations when calibrated for unfractionated heparin or low-molecular-weight heparins. METHODS: Trough and peak samples were taken from 30 patients taking rivaroxaban as part of their routine care for atrial fibrillation or venous thromboembolism. The samples were tested using 3 different FDA-approved commercial kits for measuring heparin anti-factor Xa activity. RESULTS: There was acceptable correlation between rivaroxaban levels and heparin anti-factor Xa activity using Berichrom and COAMATIC heparin kits. The STA liquid heparin method was the most sensitive to presence of rivaroxaban. CONCLUSION: This study demonstrates a strong correlation, but variability between kits, for assessing rivaroxaban concentrations using heparin anti-factor Xa assays. The extent of the heparin calibration curve significantly limits the measurable rivaroxaban range, and this application may be useful only for trough samples. The STA liquid heparin, being exquisitely sensitive to rivaroxaban, may be suitable for ruling out presence of the drug. The routine use of heparin-calibrated anti-factor Xa assays to quantify rivaroxaban is not advocated, and when applied, it must be used with caution and limitations clearly understood.

Implementing Evidence-Based Guidelines: The Role of Ambulatory Care Pharmacists.

Pharmacists strive to align patients' medication regimens with evidence-based guidelines through medication therapy management and through the utilization of protocols based on best practices for chronic disease management. Ambulatory care pharmacists also assist in implementing guidelines through developing evidence-based algorithms and processes, educating providers and staff, and participating in population management.

Academic Medicine and Rural Health System Partnerships: Enhancing Education While Advancing Physician Workforce Priorities.

ABSTRACT: A worsening shortage of rural physicians paralleling increasing health disparities demands attention. Past and ongoing efforts to address this shortage have had positive effects and can inform new strategies to achieve even greater impact. Interventions have included the development of regional medical school campuses and rural-focused tracks to recruit medical students from rural areas, expansion of rural-based graduate medical education (GME) programs and tracks, and use of institutional and individual financial incentives for rural-based training and/or practice. National policy has also taken aim at this challenge with provisions aimed at expanding rural GME in the Medicare, Medicaid, and State Children's Health Insurance Program Balanced Budget Refinement Act of 1999 and the Consolidated Appropriations Act of 2021. Additionally, several states have funded growth in GME, and supportive pathways for Medicare reimbursement and for Veterans Administration funding have been implemented. The authors recommend a new strategy for bolstering the rural physician workforce, focused on using academic-rural partnerships to incorporate rural rotations as a routine part of GME. They explain how the current health care landscape supports this approach and outline additional steps toward implementation. Centralized data collection and analysis are noted as essential to guide future efforts.

Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.

G6PC2 encodes a glucose-6-phosphatase (G6Pase) catalytic subunit, primarily expressed in pancreatic islet ß cells, which modulates the sensitivity of insulin secretion to glucose and thereby regulates fasting blood glucose (FBG). Mutational analyses were conducted to validate an AlphaFold2 (AF2)-predicted structure of human G6PC2 in conjunction with a novel method to solubilize and purify human G6PC2 from a heterologous expression system. These analyses show that residues forming a predicted intramolecular disulfide bond are essential for G6PC2 expression and that residues forming part of a type 2 phosphatidic acid phosphatase (PAP2) motif are critical for enzyme activity. Additional mutagenesis shows that residues forming a predicted substrate cavity modulate enzyme activity and substrate specificity and residues forming a putative cholesterol recognition amino acid consensus (CRAC) motif influence protein expression or enzyme activity. This CRAC motif begins at residue 219, the site of a common G6PC2 non-synonymous single-nucleotide polymorphism (SNP), rs492594 (Val219Leu), though the functional impact of this SNP is disputed. In microsomal membrane preparations, the L219 variant has greater activity than the V219 variant, but this difference disappears when G6PC2 is purified in detergent micelles. We hypothesize that this was due to a differential association of the two variants with cholesterol. This concept was supported by the observation that the addition of cholesteryl hemi-succinate to the purified enzymes decreased the Vmax of the V219 and L219 variants ∼8-fold and ∼3 fold, respectively. We anticipate that these observations should support the rational development of G6PC2 inhibitors designed to lower FBG.

Ten-Year Outcomes: Community Health Center/Academic Medicine Partnership for Rural Family Medicine Training.

BACKGROUND AND OBJECTIVES: The widening gap between urban and rural health outcomes is exacerbated by physician shortages that disproportionately affect rural communities. Rural residencies are an effective mechanism to increase physician placement in rural and medically underserved areas yet are limited in number due to funding. Community health center/academic medicine partnerships (CHAMPs) can serve as a collaborative framework for expansion of academic primary care residencies outside of traditional funding models. This report describes 10-year outcomes of a rural training pathway developed as part of a CHAMP collaboration. METHODS: Using data from internal registries and public sources, our retrospective study examined demographic and postgraduation practice characteristics for rural pathway graduates. We identified the rates of postgraduation placement in rural (Federal Office of Rural Health Policy grant-eligible) and federally designated Medically Underserved Areas/Populations (MUA/Ps). We assessed current placement for graduates >3 years from program completion. RESULTS: Over a 10-year period, 25 trainees graduated from the two residency expansion sites. Immediately postgraduation, 84% (21) were in primary care Health Professional Shortage Areas (HPSAs), 80% (20) in MUA/Ps, and 60% (15) in rural locations. Sixteen graduates were >3 years from program completion, including 69% (11) in primary care HPSAs, 69% (11) in MUA/Ps, and 50% (5) in rural locations. CONCLUSIONS: This CHAMP collaboration supported development of a rural pathway that embedded family medicine residents in community health centers and effectively increased placement in rural and MUA/Ps. This report adds to national research on rural workforce development, highlighting the role of academic-community partnerships in expanding rural residency training outside of traditional funding models.

Recruitment of Residents to Rural Programs: Early Outcomes From Cohort 1 of the Rural Residency Planning and Development Grants Program.

Background To address rural physician workforce shortages, the Health Resources and Services Administration funded multiple Rural Residency Planning and Development (RRPD) awards, beginning in 2019, to develop rural residency programs in needed specialties. Objective To describe early resident recruitment outcomes of the RRPD grants program. Methods A cross-sectional survey of program directors or administrators of these 25 new rural residency training programs across the United States was administered at RRPD award conclusion in 2022. We performed descriptive analyses of applicant and Match data, including applications and interviews per resident position, positions filled in the main Match vs the Supplemental Offer and Acceptance Program (SOAP), and recruitment of residents from the program's state. Results The 25 Cohort 1 RRPD programs ranged from 2 to 8 residents per year. Most programs (16 of 25, 64.0%) were rural expansion tracks of an urban program. Most programs were sufficiently developed to participate in the 2022 (N=17) or 2023 (N=20) Match; we report on 13 of 17 (76.5%) programs for 2022 and 14 of 20 (70.0%) programs for 2023. Programs completed a median of 14.8 interviews per position. Most positions were filled in the Match (43 of 58, 74.1% in 2022; 45 of 58, 77.6% in 2023); most others were filled in the SOAP. On average, 34.4% of enrolled residents were from the same state as the program (range 0-78.6%). Conclusions The early resident recruitment outcomes of the RRPD model for developing new physician training in rural communities had sufficient recruitment success to support program continuation.

Lessons Learned From State-Based Efforts to Leverage Medicaid Funds for Graduate Medical Education.

PURPOSE: Total Medicaid funds invested in graduate medical education (GME) increased from $3.78 billion in 2009 to $7.39 billion in 2022. States have flexibility in designing Medicaid GME payments to address population health needs. This study assessed states' impetus for using Medicaid funds for GME, structure of state Medicaid payments, composition and charge of advisory bodies that guide these investments, and degree of transparency and accountability to track whether Medicaid GME investments achieved desired workforce outcomes. METHOD: Structured interviews were conducted in 2015 to 2016 and 2020 to 2021 with subject matter experts representing 10 states. Interview transcripts were analyzed and coded in 6 thematic areas: impetus for using Medicaid funds, the structure of state Medicaid payments, the composition of advisory bodies, the degree of transparency of Medicaid investments, accountability of Medicaid investments, and challenges and changes. RESULTS: States used Medicaid GME funding to address maldistribution of physicians by geography, setting, and specialty, respond to population growth and undergraduate medical education expansion, offset potential loss of teaching health center program funds, and launch new programs and sustain existing ones. States leveraged Medicaid funding by modifying state plan amendments and redesigning funding formulas to meet specific health workforce needs. Many states had advisory bodies to educate legislators, reach consensus on workforce needs, recommend how to disburse funds, and navigate competing stakeholder interests. States identified a need for improved data and analytic systems to understand workforce needs and monitor the outcomes of GME investments. Determining which accountability measures to use and implementing metrics were challenges. CONCLUSIONS: States have much to learn from each other about strategies to best leverage Medicaid funds to develop and sustain residency programs to meet population health needs. Learning collaboratives should be developed to provide a forum for states to share best practices and strategies for overcoming challenges.

Integrative analysis of pathogenic variants in glucose-6-phosphatase based on an AlphaFold2 model.

Mediating the terminal reaction of gluconeogenesis and glycogenolysis, the integral membrane protein glucose-6-phosphate catalytic subunit 1 (G6PC1) regulates hepatic glucose production by catalyzing hydrolysis of glucose-6-phosphate (G6P) within the lumen of the endoplasmic reticulum. Consistent with its vital contribution to glucose homeostasis, inactivating mutations in G6PC1 causes glycogen storage disease (GSD) type 1a characterized by hepatomegaly and severe hypoglycemia. Despite its physiological importance, the structural basis of G6P binding to G6PC1 and the molecular disruptions induced by missense mutations within the active site that give rise to GSD type 1a are unknown. In this study, we determine the atomic interactions governing G6P binding as well as explore the perturbations imposed by disease-linked missense variants by subjecting an AlphaFold2 G6PC1 structural model to molecular dynamics simulations and in silico predictions of thermodynamic stability validated with robust in vitro and in situ biochemical assays. We identify a collection of side chains, including conserved residues from the signature phosphatidic acid phosphatase motif, that contribute to a hydrogen bonding and van der Waals network stabilizing G6P in the active site. The introduction of GSD type 1a mutations modified the thermodynamic landscape, altered side chain packing and substrate-binding interactions, and induced trapping of catalytic intermediates. Our results, which corroborate the high quality of the AF2 model as a guide for experimental design and to interpret outcomes, not only confirm the active-site structural organization but also identify previously unobserved mechanistic contributions of catalytic and noncatalytic side chains.

Biochemical and metabolic characterization of a G6PC2 inhibitor.

Three glucose-6-phosphatase catalytic subunits, that hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate, have been identified, designated G6PC1-3, but only G6PC1 and G6PC2 have been implicated in the regulation of fasting blood glucose (FBG). Elevated FBG has been associated with multiple adverse clinical outcomes, including increased risk for type 2 diabetes and various cancers. Therefore, G6PC1 and G6PC2 inhibitors that lower FBG may be of prophylactic value for the prevention of multiple conditions. The studies described here characterize a G6PC2 inhibitor, designated VU0945627, previously identified as Compound 3. We show that VU0945627 preferentially inhibits human G6PC2 versus human G6PC1 but activates human G6PC3. VU0945627 is a mixed G6PC2 inhibitor, increasing the Km but reducing the Vmax for G6P hydrolysis. PyRx virtual docking to an AlphaFold2-derived G6PC2 structural model suggests VU0945627 binds two sites in human G6PC2. Mutation of residues in these sites reduces the inhibitory effect of VU0945627. VU0945627 does not inhibit mouse G6PC2 despite its 84% sequence identity with human G6PC2. Mutagenesis studies suggest this lack of inhibition of mouse G6PC2 is due, in part, to a change in residue 318 from histidine in human G6PC2 to proline in mouse G6PC2. Surprisingly, VU0945627 still inhibited glucose cycling in the mouse islet-derived ßTC-3 cell line. Studies using intact mouse liver microsomes and PyRx docking suggest that this observation can be explained by an ability of VU0945627 to also inhibit the G6P transporter SLC37A4. These data will inform future computational modeling studies designed to identify G6PC isoform-specific inhibitors.

Characteristics of Hospitals by Graduate Medical Education Expense Category: Implications for Rural Residency Program Expansion.

PURPOSE: To describe how the characteristics of the hospitals and communities they serve vary across the 4 hospital graduate medical education (GME) expense categories (according to Section 131 of the Consolidated Appropriations Act of 2021) and identify the rurally located never claimer hospitals that are most similar to teaching hospitals, signaling that they might be good candidates for new rural GME programs. METHOD: Hospital categories and characteristics were gathered from the March 2022 Medicare Cost Reports; 2022 County Health Rankings & Roadmaps data were used for community characteristics. Each acute hospital was classified into 1 of the following 4 mutually exclusive hospital categories: category A, category B, established teaching hospital (ETH), and never claimer. Multinomial logistic regressions were conducted to estimate the adjusted associations of hospital characteristics with hospital categories and to identify the never claimer hospitals in rural locations that have characteristics similar to teaching hospitals (category A, category B, and ETHs). RESULTS: Out of 3,590 hospitals, 2,075 (57.8%) were never claimer hospitals. After adjusting for multiple characteristics, rural hospitals had a similar probability of being in each hospital category as that of urban hospitals. Never claimer hospitals served an older population and were located in communities with more uninsured adults and children and less availability of primary care physicians, dentists, and mental health professionals. CONCLUSIONS: This study demonstrated that most hospitals in every category, but especially teaching hospitals (i.e., category A hospitals, category B hospitals, and ETHs), were concentrated in urban areas. Larger hospitals (measured by net patient revenue) were more likely to report GME expenses (i.e., be a category A hospital, a category B hospital, or an ETH). The study suggests that there are roughly 145 rural never claimer hospitals that might be strong candidates for initiating new residency programs.

Postgraduate education to expand access to dental care: A roadmap to community dental program development.

Evidence indicates an increasing shortage of dentists in communities across the United States with potentially significant implications for oral health, as well as overall health and well-being. One strategy to increase access to dental care in rural and underserved communities is community-based postgraduate dental training. However, developing new dental programs requires navigating complex accreditation, financial and community governance, among other, barriers. The Roadmap for Teaching Health Center Dental Program Development presents a framework that guides institutions through the successive steps of developing new postgraduate training programs from identification of need to ultimate maintenance and sustainability. The tool assists programs in anticipating and understanding requirements, reducing time, expense, and uncertainty. While the framework was developed for community-based programs, the steps are applicable to postgraduate programs sponsored by academic institutions as well.

G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.

In the endoplasmic reticulum (ER) lumen, glucose-6-phosphatase catalytic subunit 1 and 2 (G6PC1; G6PC2) hydrolyze glucose-6-phosphate (G6P) to glucose and inorganic phosphate whereas hexose-6-phosphate dehydrogenase (H6PD) hydrolyzes G6P to 6-phosphogluconate (6PG) in a reaction that generates NADPH. 11ß-hydroxysteroid dehydrogenase type 1 (HSD11B1) utilizes this NADPH to convert inactive cortisone to cortisol. HSD11B1 inhibitors improve insulin sensitivity whereas G6PC inhibitors are predicted to lower fasting blood glucose (FBG). This study investigated whether G6PC1 and G6PC2 influence G6P flux through H6PD and vice versa. Using a novel transcriptional assay that utilizes separate fusion genes to quantitate glucocorticoid and glucose signaling, we show that overexpression of H6PD and HSD11B1 in the islet-derived 832/13 cell line activated glucocorticoid-stimulated fusion gene expression. Overexpression of HSD11B1 blunted glucose-stimulated fusion gene expression independently of altered G6P flux. While overexpression of G6PC1 and G6PC2 blunted glucose-stimulated fusion gene expression, it had minimal effect on glucocorticoid-stimulated fusion gene expression. In the liver-derived HepG2 cell line, overexpression of H6PD and HSD11B1 activated glucocorticoid-stimulated fusion gene expression but overexpression of G6PC1 and G6PC2 had no effect. In rodents, HSD11B1 converts 11-dehydrocorticosterone (11-DHC) to corticosterone. Studies in wild-type and G6pc2 knockout mice treated with 11-DHC for 5 weeks reveal metabolic changes unaffected by the absence of G6PC2. These data suggest that HSD11B1 activity is not significantly affected by the presence or absence of G6PC1 or G6PC2. As such, G6PC1 and G6PC2 inhibitors are predicted to have beneficial effects by reducing FBG without causing a deleterious increase in glucocorticoid signaling.

Bolstering the rural physician workforce in underserved communities: Are Rural Residency Planning and Development Programs finding the sweet spot?

PURPOSE: The purpose of this study is to describe the characteristics of Rural Residency Planning and Development (RRPD) Programs, compare the characteristics of counties with and without RRPD programs, and identify rural places where future RRPD programs could be developed. METHODS: The study sample comprised 67 rural sites training residents in 40 counties in 24 US states. Descriptive statistics were used to describe RRPD programs and logistic regression to predict the probability of a county being an RRPD site as a function of population, primary care physicians (PCP) per 10,000 population, and the social vulnerability index (SVI) compared to a control sample of nonmetro counties without RRPD sites. FINDINGS: Most RRPD grantees (78%) were family medicine programs affiliated with medical schools (97%). RRPD counties were more populous (P<.01), had a higher population density (P<.05), and a higher percent of the non-White or Hispanic population (P = .05) compared to non-RRPD counties. Both higher population (P<.001) and PCP ratio (P = .046) were strong predictors, while SVI (P = .07) was a weak predictor of being an RRPD county. CONCLUSIONS: RRPD sites appear to represent a "sweet spot" of rural counties that have the population and physician supply to support a training program but also are relatively more socially vulnerable with high-need populations. Additional counties fitting this "sweet spot" could be targeted for funding to address health disparities and health workforce maldistribution.