Prescribing and Acceptance of Medications for Opioid Use Disorder in VA Primary Care: Veteran and Provider Perspectives.

BACKGROUND: Medications to treat opioid use disorder (MOUD) such as buprenorphine/naloxone can effectively treat OUD and reduce opioid-related mortality, but they remain underutilized, especially in non-substance use disorder settings such as primary care (PC). OBJECTIVE: To uncover the factors that can facilitate successful prescribing of MOUD and uptake/acceptance of MOUD by patients in PC settings in the Veterans Health Administration. DESIGN: Semi-structured qualitative telephone interviews with 77 providers (e.g., primary care providers, hospitalists, nurses, addiction psychiatrists) and 22 Veteran patients with experience taking MOUD. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach. KEY RESULTS: Providers and patients shared their general perceptions and experiences with MOUD, including high satisfaction with buprenorphine/naloxone with few side effects and caveats, although some patients reported drawbacks to methadone. Both providers and patients supported the idea of prescribing MOUD in PC settings to prioritize patient comfort and convenience. Providers described individual-level barriers (e.g., time, stigma, perceptions of difficulty level), structural-level barriers (e.g., pharmacy not having medications ready, space for inductions), and organizational-level barriers (e.g., inadequate staff support, lack of nursing protocols) to PC providers prescribing MOUD. Facilitators centered on education and knowledge enhancement, workflow and practice support, patient engagement and patient-provider communication, and leadership and organizational support. The most common barrier faced by patients to starting MOUD was apprehensions about pain, while facilitators focused on personal motivation, encouragement from others, education about MOUD, and optimally timed provider communication strategies. CONCLUSIONS: These findings can help improve provider-, clinic-, and system-level supports for MOUD prescribing across multiple settings, as well as foster communication strategies that can increase patient acceptance of MOUD. They also point to how interprofessional collaboration across service lines and leadership support can facilitate MOUD prescribing among non-addiction providers.

Comparing Quality, Costs, and Outcomes of VA and Community Primary Care for Patients with Diabetes.

BACKGROUND: The Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act expanded access to independent community providers outside the Veterans Health Administration (VA). Little is known how quality, costs, and outcomes of primary care received in the community compare to that of the VA. OBJECTIVE: To compare quality, costs, and outcomes of community and VA-provided primary care for patients with diabetes over a 12-month episode. DESIGN: A cross-sectional study using VA administrative data and community care claims. Adjusted analyses were conducted using inverse probability weighted regression adjustment to balance patient characteristics. PARTICIPANTS: Veterans with diabetes receiving primary care in the VA or community. MAIN MEASURES: Quality measures included receipt of hemoglobin A1C tests, eye exams, microalbumin urine tests, and flu shots. Outcomes were measured by hospitalizations for an ambulatory care sensitive condition (ACSC). Costs were measured for VA and community outpatient care, inpatient care, and prescription drugs. KEY RESULTS: There were 652,648 VA patients and 3650 community care patients. VA patients were less likely to be White, had shorter mean drive time to VA primary care, and were less likely to be rural than community care patients. In adjusted analyses, community care patients had significantly lower probability of receiving a hemoglobin A1C test, eye exam, microalbumin urine test, and flu shot compared to the VA group. There was no difference in probability of an ACSC hospitalization. Community care patients had higher mean total costs ($1741 [95% CI, $431, $3052]), driven by higher inpatient and prescription drug costs but lower emergency care costs than VA patients. CONCLUSION: Patients receiving community primary care had worse diabetes quality and higher costs than patients receiving VA primary care. There was no difference in health outcomes. Care provided by an integrated delivery system may have advantages in quality and value.

Impact of Referring High-Risk Patients to Intensive Outpatient Primary Care Services: A Propensity Score-Matched Analysis.

BACKGROUND: Many healthcare systems have implemented intensive outpatient primary care programs with the hopes of reducing healthcare costs. OBJECTIVE: The Veterans Health Administration (VHA) piloted primary care intensive management (PIM) for patients at high risk for hospitalization or death, or "high-risk." We evaluated whether a referral model would decrease high-risk patient costs. DESIGN: Retrospective cohort study using a quasi-experimental design comparing 456 high-risk patients referred to PIM from October 2017 to September 2018 to 415 high-risk patients matched on propensity score. PARTICIPANTS: Veterans in the top 10th percentile of risk for 90-day hospitalization or death and recent hospitalization or emergency department (ED) visit. INTERVENTION: PIM consisted of interdisciplinary teams that performed comprehensive assessments, intensive case management, and care coordination services. MAIN OUTCOMES AND MEASURES: Change in VHA and non-VHA outpatient utilization, inpatient admissions, and costs 12 months pre- and post-index date. KEY RESULTS: Of the 456 patients referred to PIM, 301 (66%) enrolled. High-risk patients referred to PIM had a marginal reduction in ED visits (- 0.7; [95% CI - 1.50 to 0.08]; p = 0.08) compared to propensity-matched high-risk patients; overall outpatient costs were similar. High-risk patients referred to PIM had similar number of medical/surgical hospitalizations (- 0.2; [95% CI, - 0.6 to 0.16]; p = 0.2), significant increases in length of stay (6.36; [CI, - 0.01 to 12.72]; p = 0.05), and higher inpatient costs ($22,628, [CI, $3587 to $41,669]; p = 0.02) than those not referred to PIM. CONCLUSIONS AND RELEVANCE: VHA intensive outpatient primary care was associated with higher costs. Referral to intensive case management programs targets the most complex patients and may lead to increased utilization and costs, particularly in an integrated healthcare setting with robust patient-centered medical homes. TRIAL REGISTRATION: PIM 2.0: Patient Aligned Care Team (PACT) Intensive Management (PIM) Project (PIM2). NCT04521816. https://clinicaltrials.gov/study/NCT04521816.

Longitudinal sex-specific impacts of high-fat diet on dopaminergic dysregulation and behavior from periadolescence to late adulthood.

OBJECTIVES: Obesity is recognized for its adverse impact on brain health and related behaviors; however, the specific longitudinal effects of a high-fat diet (HFD) from juvenile stages of development through late adulthood remain poorly understood, particularly sex-specific outcomes. This study aimed to determine how prolonged exposure to HFD, commencing during periadolescence, would differentially predispose male and female mice to an elevated risk of dopaminergic dysregulation and associated behavioral deficits. METHODS: One-month-old C57BL/6J male and female mice were subjected to either a control diet or an HFD for 5 and 9 months. Muscle strength, motor skills, sensorimotor integration, and anxiety-like behaviors were assessed at the end of the 5th and 8th months. Key dopaminergic molecules, including dopamine (DA), dopamine receptor D2 (DRD2), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2), were quantified at the end of the 5th or 9th months. RESULTS: Behaviorally, male mice exposed to HFD exhibited more pronounced alterations in sensorimotor integration, anxiety-like behavior, and muscle strength after the 5th month of dietary exposure. In contrast, female mice displayed most behavioral differences after the 8th month of HFD exposure. Physiologically, there were notable sex-specific variations in the dopaminergic pathway response to HFD. Male mice exposed to HFD exhibited elevated tissue levels of VMAT2 and DRD2, whereas female mice showed reduced levels of DRD2 and DAT compared to control groups. DISCUSSION: These findings indicate a general trend of altered time course susceptibility in male mice to chronic HFD consumption compared to their female counterparts, with male mice impacted earlier than females.

Lipid membrane mimetics and oligomerization tune functional properties of proteorhodopsin.

The functional properties of proteorhodopsin (PR) have been found to be strongly modulated by oligomeric distributions and lipid membrane mimetics. This study aims to distinguish and explain their effects by investigating how oligomer formation impacts PR's function of proton transport in lipid-based membrane mimetic environments. We find that PR forms stable hexamers and pentamers in both E. coli membranes and synthetic liposomes. Compared with the monomers, the photocycle kinetics of PR oligomers is ∼2 and ∼4.5 times slower for transitions between the K and M and the M and N photointermediates, respectively, indicating that oligomerization significantly slows PR's rate of proton transport in liposomes. In contrast, the apparent pKa of the key proton acceptor residue D97 (pKaD97) of liposome-embedded PR persists at 6.2-6.6, regardless of cross-protomer modulation of D97, suggesting that the liposome environment helps maintain PR's functional activity at neutral pH. By comparison, when extracted directly from E. coli membranes into styrene-maleic acid lipid particles, the pKaD97 of monomer-enriched E50Q PR drastically increases to 8.9, implying that there is a very low active PR population at neutral pH to engage in PR's photocycle. These findings demonstrate that oligomerization impacts PR's photocycle kinetics, while lipid-based membrane mimetics strongly affect PR's active population via different mechanisms.

High fat diet reveals sex-specific fecal and liver metabolic alterations in C57BL/6J obese mice.

Obesity is a major health concern that poses significant risks for many other diseases, including diabetes, cardiovascular disease, and cancer. Prevalence of these diseases varies by biological sex. This study utilizes a mouse (C57BL/6J) model of obesity to analyze liver and fecal metabolic profiles at various time points of dietary exposure: 5, 9, and 12 months in control or high fat diet (HFD)-exposed mice. Our study discovered that the female HFD group has a more discernable perturbation and set of significant changes in metabolic profiles than the male HFD group. In the female mice, HFD fecal metabolites including pyruvate, aspartate, and glutamate were lower than control diet-exposed mice after both 9th and 12th month exposure time points, while lactate and alanine were significantly downregulated only at the 12th month. Perturbations of liver metabolic profiles were observed in both male and female HFD groups, compared to controls at the 12th month. Overall, the female HFD group showed higher lactate and glutathione levels compared to controls, while the male HFD group showed higher levels of glutamine and taurine compared to controls. These metabolite-based findings in both fecal and liver samples for a diet-induced effect of obesity may help guide future pioneering discoveries relating to the analysis and prevention of obesity in people, especially for females.

Crisaborole efficacy in murine models of skin inflammation and Staphylococcus aureus infection.

Phosphodiesterase 4 (PDE4) is highly expressed in keratinocytes and immune cells and promotes pro-inflammatory responses upon activation. The activity of PDE4 has been attributed to various inflammatory conditions, leading to the development and approval of PDE4 inhibitors as host-directed therapeutics in humans. For example, the topical PDE4 inhibitor, crisaborole, is approved for the treatment of mild-to-moderate atopic dermatitis and has shown efficacy in patients with psoriasis. However, the role of crisaborole in regulating the immunopathogenesis of inflammatory skin diseases and infection is not entirely known. Therefore, we evaluated the effects of crisaborole in multiple mouse models, including psoriasis-like dermatitis, AD-like skin inflammation with and without filaggrin mutations, and Staphylococcus aureus skin infection. We discovered that crisaborole dampens myeloid cells and itch in the skin during psoriasis-like dermatitis. Furthermore, crisaborole was effective in reducing skin inflammation in the context of filaggrin deficiency. Importantly, crisaborole reduced S. aureus skin colonization during AD-like skin inflammation. However, crisaborole was not efficacious in treating S. aureus skin infections, even as adjunctive therapy to antibiotics. Taken together, we found that crisaborole reduced itch during psoriasis-like dermatitis and decreased S. aureus skin colonization upon AD-like skin inflammation, which act as additional mechanisms by which crisaborole dampens the immunopathogenesis in mouse models of inflammatory skin diseases. Further examination is warranted to translate these preclinical findings to human disease.

Types of Engagement Strategies to Engage High-Risk Patients in VA.

BACKGROUND: Many healthcare systems seek to improve care for complex high-risk patients, but engaging such patients to actively participate in their healthcare can be challenging. OBJECTIVE: To identify and describe types of patient engagement strategies reported as successfully deployed by providers/teams and experienced by patients in a Veterans Health Administration (VA) intensive primary care (IPC) pilot program. METHODS: We conducted semi-structured qualitative telephone interviews with 29 VA IPC staff (e.g., physicians, nurses, psychologists) and 51 patients who had at least four IPC team encounters. Interviews were recorded, transcribed, and analyzed thematically using a combination a priori/inductive approach. RESULTS: The engagement strategies successfully deployed by the IPC providers/teams could be considered either more "facilitative," i.e., facilitated by and dependent on staff actions, or more "self-sustaining," i.e., taught to patients, thus cultivating their ongoing patient self-care. Facilitative strategies revolved around enhancing patient access and coordination of care, trust-building, and addressing social determinants of health. Self-sustaining strategies were oriented around patient empowerment and education, caregiver and/or community support, and boundaries and responsibilities. When patients described their experiences with the "facilitative" strategies, many discussed positive proximal outcomes (e.g., increased access to healthcare providers). Self-sustaining strategies led to positive (self-reported) longer-term clinical outcomes, such as behavior change. CONCLUSION: We identified two categories of strategies for successfully engaging complex, high-risk patients: facilitative and self-sustaining. Intensive primary care program leaders may consider thoughtfully building "self-sustaining" engagement strategies into program development. Future research can confirm their effectiveness in improving health outcomes.

Caring for high-need patients.

OBJECTIVE: We aimed to explore the construct of "high need" and identify common need domains among high-need patients, their care professionals, and healthcare organizations; and to describe the interventions that health care systems use to address these needs, including exploring the potential unintended consequences of interventions. METHODS: We conducted a modified Delphi panel informed by an environmental scan. Expert stakeholders included patients, interdisciplinary healthcare practitioners (physicians, social workers, peer navigators), implementation scientists, and policy makers. The environmental scan used a rapid literature review and semi-structured interviews with key informants who provide healthcare for high-need patients. We convened a day-long virtual panel meeting, preceded and followed by online surveys to establish consensus. RESULTS: The environmental scan identified 46 systematic reviews on high-need patients, 19 empirical studies documenting needs, 14 intervention taxonomies, and 9 studies providing construct validity for the concept "high need." Panelists explored the construct and terminology and established that individual patients' needs are unique, but areas of commonality exist across all high-need patients. Panelists agreed on 11 domains describing patient (e.g., social circumstances), 5 care professional (e.g., communication), and 8 organizational (e.g., staffing arrangements) needs. Panelists developed a taxonomy of interventions with 15 categories (e.g., care navigation, care coordination, identification and monitoring) directed at patients, care professionals, or the organization. The project identified potentially unintended consequences of interventions for high-need patients, including high costs incurred for patients, increased time and effort for care professionals, and identification of needs without resources to respond appropriately. CONCLUSIONS: Care for high-need patients requires a thoughtful approach; differentiating need domains provides multiple entry points for interventions directed at patients, care professionals, and organizations. Implementation efforts should consider outlined intended and unintended downstream effects on patients, care professionals, and organizations.

Quality Indicators for High-Need Patients: a Systematic Review.

BACKGROUND: Healthcare systems are increasingly implementing programs for high-need patients, who often have multiple chronic conditions and complex social situations. Little, however, is known about quality indicators that might guide healthcare organizations and providers in improving care for high-need patients. We sought to conduct a systematic review to identify potential quality indicators for high-need patients. METHODS: This systematic review (CRD42020215917) searched PubMed, CINAHL, and EMBASE; guideline clearing houses ECRI and GIN; and Google scholar. We included publications suggesting, evaluating, and utilizing indicators to assess quality of care for high-need patients. Critical appraisal of the indicators addressed the development process, endorsement and adoption, and characteristics, such as feasibility. We standardized indicators by patient population subgroups to facilitate comparisons across different indicator groups. RESULTS: The search identified 6964 citations. Of these, 1382 publications were obtained as full text, and 53 studies met inclusion criteria. We identified over 1700 quality indicators across studies. Quality indicator characteristics varied widely. The scope of the selected indicators ranged from detailed criterion (e.g., "annual eye exam") to very broad categories (e.g., "care coordination"). Some publications suggested disease condition-specific indicators (e.g., diabetes), some used condition-independent criteria (e.g., "documentation of the medication list in the medical record available to all care agencies"), and some publications used a mixture of indicator types. DISCUSSION: We identified and evaluated existing quality indicators for a complex, heterogeneous patient group. Although some quality indicators were not disease-specific, we found very few that accounted for social determinants of health and behavioral factors. More research is needed to develop quality indicators that address patient risk factors.

The Effectiveness of a Specialized Primary Care Medical Home for Patients with Serious Mental Illness.

BACKGROUND: There are unmet primary care needs among people with serious mental illness that might be improved with integrated care and medical care management. Many healthcare organizations have attempted to address this problem, but few interventions have been rigorously studied and found to be effective. OBJECTIVE: Study the implementation and effectiveness of a novel, specialized primary care medical home designed to improve the healthcare of patients with serious mental illness. DESIGN, SETTING, AND PARTICIPANTS: Clustered controlled trial for a median of 401 days. One Veterans Health Administration medical center was assigned to intervention and two were assigned to usual care (control). Thirty-nine clinicians and managers were included in the study, as well as 331 patients who met eligibility criteria. INTERVENTION: A specialized medical home with systematic patient engagement, proactive nurse panel management, a collaborative care psychiatrist, and a primary care physician providing care that included psychiatric treatment. MAIN MEASURES: Quality of care, chronic illness care and care experience, symptoms, and quality of life. KEY RESULTS: Sixty-five intervention patients (40%) moved all psychiatric care to the primary care team. No adverse events were attributable to the intervention. Compared with control, intervention patients had greater improvement over time in appropriate screening for body mass index, lipids, and glucose (χ2 = 6.9, 14.3, and 3.9; P's < .05); greater improvement in all domains of chronic illness care (activation, decision support, goal-setting, counseling, coordination) and care experience (doctor-patient interaction, shared decision-making, care coordination, access; F for each 10-24, P's < .05); and greater improvement in mental health-related quality of life (F = 3.9, P = .05) and psychotic symptoms (F = 3.9, P = .05). CONCLUSION: A primary care medical home for serious mental illness can be feasible to implement, safe, and more effective than usual care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01668355.

What Is the Return on Investment of Caring for Complex High-need, High-cost Patients?

Randomized controlled trials to improve care for complex, high-need, high-cost patients have not consistently demonstrated a relative decrease in acute care utilization or cost savings. However, the Veterans Health Administration (VHA) has been able to glean lessons from these trials and generate realistic expectations for success. Lessons include the following: (1) combining population management tools (e.g., risk scores) and clinician judgment is more effective than either alone to identify the patients best suited for intensive management; (2) treatment adherence and engagement may contribute more to preventable emergency department visits and hospitalizations than care coordination; and (3) efforts should focus on assessing for and treating those risk factors that are most amenable to intervention. Because it is unlikely that cost savings can fund add-on intensive management programs, the VHA Office of Primary Care plans to incorporate those intensive management practices that are feasible into existing patient-centered medical homes as a high reliability organization.

What Do Patient-Centered Medical Home (PCMH) Teams Need to Improve Care for Primary Care Patients with Complex Needs?

BACKGROUND: Intensive primary care (IPC) programs for patients with complex needs do not generate cost savings in most settings. Strengthening existing patient-centered medical homes (PCMH) to address the needs of these patients in primary care is a potential high-value alternative. OBJECTIVES: Explore PCMH team functioning and characteristics that may impact their ability to perform IPC tasks; identify the IPC components that could be incorporated into PCMH teams' workflow; and identify additional resources, trainings, and staff needed to better manage patients with complex needs in primary care. METHODS: We interviewed 44 primary care leaders, PCMH team members (providers, nurses, social workers), and IPC program leaders at 5 VA IPC sites and analyzed a priori themes using a matrix analysis approach. RESULTS: Higher-functioning PCMH teams were described as already performing most IPC tasks, including panel management and care coordination. All sites reported that PCMH teams had the knowledge and skills to perform IPC tasks, but not with the same intensity as specialized IPC teams. Home visits/assessments and co-attending appointments were perceived as not feasible to perform. Key stakeholders identified 6 categories of supports and capabilities that PCMH teams would need to better manage complex patients, with care coordination/management and fully staffed teams as the most frequently mentioned. Many thought that PCMH teams could make better use of existing VA and non-VA resources, but might need training in identifying and using those resources. CONCLUSIONS: PCMH teams can potentially offer certain clinic-based services associated with IPC programs, but tasks that are time intensive or require physical absence from clinic might require collaboration with community service providers and better use of internal and external healthcare system resources. Future studies should explore the feasibility of PCMH adoption of IPC tasks and the impact on patient outcomes.

Outcomes that Matter: High-Needs Patients' and Primary Care Leaders' Perspectives on an Intensive Primary Care Pilot.

BACKGROUND: Quantitative evaluations of the effectiveness of intensive primary care (IPC) programs for high-needs patients have yielded mixed results for improving healthcare utilization, cost, and mortality. However, IPC programs may provide other value. OBJECTIVE: To understand the perspectives of high-needs patients and primary care facility leaders on the effects of a Veterans Affairs (VA) IPC program on patients. DESIGN: A total of 66 semi-structured telephone interviews with high-needs VA patients and primary care facility leaders were conducted as part of the IPC program evaluation. PARTICIPANTS: High-needs patients (n = 51) and primary care facility leaders (n = 15) at 5 VA pilot sites. APPROACH: We used content analysis to examine interview transcripts for both a priori and emergent themes about perceived IPC program effects. KEY RESULTS: Patients enrolled in VA IPCs reported improvements in their experience of VA care (e.g., patient-provider relationship, access to their team). Both patients and leaders reported improvements in patient motivation to engage with self-care and with their IPC team, and behaviors, especially diet, exercise, and medication management. Patients also perceived improvements in health and described receiving assistance with social needs. Despite this, patients and leaders also outlined patient health characteristics and contextual factors (e.g., chronic health conditions, housing insecurity) that may have limited the effectiveness of the program on healthcare cost and utilization. CONCLUSIONS: Patients and primary care facility leaders report benefits for high-needs patients from IPC interventions that translated into perceived improvements in healthcare, health behaviors, and physical and mental health status. Most program evaluations focus on cost and utilization, which may be less amenable to change given this cohort's numerous comorbid health conditions and complex social circumstances. Future IPC program evaluations should additionally examine IPC's effects on quality of care, patient satisfaction, quality of life, and patient health behaviors other than utilization (e.g., engagement, self-efficacy).

Increasing Access to Medications for Opioid Use Disorder and Complementary and Integrative Health Services in Primary Care.

OBJECTIVES: Evidence-based therapies for opioid use disorder (OUD) and chronic pain, such as medications for OUD (MOUD) and complementary and integrative health (CIH; e.g., acupuncture and meditation) therapies, exist. However, their adoption has been slow, particularly in primary care, due to numerous implementation challenges. We sought to expand the use of MOUD and CIH within primary care by using an evidence-based quality improvement (EBQI) implementation strategy. METHODS: We used EBQI to engage two facilities in the Veterans Health Administration (VHA) from June 2018 to September 2019. EBQI included multilevel stakeholder engagement, with external facilitators providing technical support, practice facilitation, and routine data feedback. We established a quality improvement (QI) team at each facility with diverse stakeholders (e.g., primary care, addiction, pain, nursing, pharmacy). We met monthly with regional stakeholders to address implementation barriers. We also convened an advisory board to ensure alignment with national priorities. RESULTS: Pre-implementation interviews indicated facility-level and provider-level barriers to prescribing buprenorphine, including strong primary care provider resistance. Both facilities developed action plans. They both conducted educational meetings (e.g., Grand Rounds, MOUD waiver trainings). Facility A also offered clinical preceptorships for newly trained primary care prescribers. Facility B used mass media and mailings to educate patients about MOUD and CIH options and dashboards to identify potential candidates for MOUD. After 15 months, both facilities increased their OUD treatment rates to the ≥ 90th percentile of VHA medical centers nationally. Exit interviews indicated an attitudinal shift in MOUD delivery in primary care. Stakeholders valued the EBQI process, particularly cross-site collaboration. IMPLICATIONS: Despite initial implementation barriers, we effectively engaged stakeholders using EBQI strategies. Local QI teams used an assortment of QI interventions and developed tools to catapult their facilities to among the highest performers in VHA OUD treatment. IMPACTS: EBQI is an effective strategy to partner with stakeholders to implement MOUD and CIH therapies.

Biosynthesis of redox-active metabolites in response to iron deficiency in plants.

Iron is an essential but poorly bioavailable nutrient because of its low solubility, especially in alkaline soils. Here, we describe the discovery of a previously undescribed redox-active catecholic metabolite, termed sideretin, which derives from the coumarin fraxetin and is the primary molecule exuded by Arabidopsis thaliana roots in response to iron deficiency. We identified two enzymes that complete the biosynthetic pathway of fraxetin and sideretin. Chemical characterization of fraxetin and sideretin, and biological assays with pathway mutants, suggest that these coumarins are critical for iron nutrition in A. thaliana. Further, we show that sideretin production also occurs in eudicot species only distantly related to A. thaliana. Untargeted metabolomics of the root exudates of various eudicots revealed production of structurally diverse redox-active molecules in response to iron deficiency. Our results indicate that secretion of small-molecule reductants by roots may be a widespread and previously underappreciated component of reduction-based iron uptake.

High-Need Patients' Goals and Goal Progress in a Veterans Affairs Intensive Outpatient Care Program.

BACKGROUND: Healthcare systems nationwide are implementing intensive outpatient care programs to optimize care for high-need patients; however, little is known about these patients' personal goals and factors associated with goal progress. OBJECTIVE: To describe high-need patients' goals, and to identify factors associated with their goal progress DESIGN: Retrospective cohort study PARTICIPANTS: A total of 113 high-need patients participated in a single-site Veterans Affairs intensive outpatient care program. MAIN MEASURES: Two independent reviewers examined patients' goals recorded in the electronic health record, categorized each goal into one of three domains (medical, behavioral, or social), and determined whether patients attained goal progress during program participation. Logistic regression was used to determine factors associated with goal progress. RESULTS: The majority (n = 72, 64%) of the 113 patients attained goal progress. Among the 100 (88%) patients with at least one identified goal, 58 set goal(s) in the medical domain; 60 in the behavioral domain; and 52 in the social domain. Within each respective domain, 41 (71%) attained medical goal progress; 34 (57%) attained behavioral goal progress; and 32 (62%) attained social goal progress. Patients with mental health condition(s) (aOR 0.3; 95% CI 0.1-0.9; p = 0.03) and those living alone (aOR 0.4; 95% CI 0.1-1.0; p = 0.05) were less likely to attain goal progress. Those with mental health condition(s) and those who were living alone were least likely to attain goal progress (interaction aOR 0.1 compared to those with neither characteristic; 95% CI 0.0-0.7; p = 0.02). CONCLUSIONS: Among high-need patients participating in an intensive outpatient care program, patient goals were fairly evenly distributed across medical, behavioral, and social domains. Notably, individuals living alone with mental health conditions were least likely to attain progress. Future care coordination interventions might incorporate strategies to address this gap, e.g., broader integration of behavioral and social service components.

Effects of Intensive Primary Care on High-Need Patient Experiences: Survey Findings from a Veterans Affairs Randomized Quality Improvement Trial.

BACKGROUND: Intensive primary care programs aim to coordinate care for patients with medical, behavioral, and social complexity, but little is known about their impact on patient experience when implemented in a medical home. OBJECTIVE: Determine how augmenting the VA's medical home (Patient Aligned Care Team, PACT) with a PACT-Intensive Management (PIM) program influences patient experiences with care coordination, access, provider relationships, and satisfaction. DESIGN: Cross-sectional analysis of patient survey data from a five-site randomized quality improvement study. PARTICIPANTS: Two thousand five hundred sixty-six Veterans with hospitalization risk scores ≥ 90th percentile and recent acute care. INTERVENTION: PIM offered patients intensive care coordination, including home visits, accompaniment to specialists, acute care follow-up, and case management from a team staffed by primary care providers, social workers, psychologists, nurses, and/or other support staff. MAIN MEASURES: Patient-reported experiences with care coordination (e.g., health goal assessment, test and appointment follow-up, Patient Assessment of Chronic Illness Care (PACIC)), access to healthcare services, provider relationships, and satisfaction. KEY RESULTS: Seven hundred fifty-nine PIM and 768 PACT patients responded to the survey (response rate 60%). Patients randomized to PIM were more likely than those in PACT to report that they were asked about their health goals (AOR = 1.26; P = 0.046) and that they have a VA provider whom they trust (AOR = 1.35; P = 0.005). PIM patients also had higher mean (SD) PACIC scores compared with PACT patients (2.91 (1.31) vs. 2.75 (1.25), respectively; P = 0.022) and were more likely to report 10 out of 10 on satisfaction with primary care (AOR = 1.25; P = 0.048). However, other effects on coordination, access, and satisfaction did not achieve statistical significance. CONCLUSIONS: Augmenting VA's patient-centered medical home with intensive primary care had a modestly positive influence on high-risk patients' experiences with care coordination and provider relationships, but did not have a significant impact on most patient-reported access and satisfaction measures.

Chromodomain-mediated oligomerization of HP1 suggests a nucleosome-bridging mechanism for heterochromatin assembly.

HP1 proteins are central to the assembly and spread of heterochromatin containing histone H3K9 methylation. The chromodomain (CD) of HP1 proteins specifically recognizes the methyl mark on H3 peptides, but the same extent of specificity is not observed within chromatin. The chromoshadow domain of HP1 proteins promotes homodimerization, but this alone cannot explain heterochromatin spread. Using the S. pombe HP1 protein, Swi6, we show that recognition of H3K9-methylated chromatin in vitro relies on an interface between two CDs. This interaction causes Swi6 to tetramerize on a nucleosome, generating two vacant CD sticky ends. On nucleosomal arrays, methyl mark recognition is highly sensitive to internucleosomal distance, suggesting that the CD sticky ends bridge nearby methylated nucleosomes. Strengthening the CD-CD interaction enhances silencing and heterochromatin spread in vivo. Our findings suggest that recognition of methylated nucleosomes and HP1 spread on chromatin are structurally coupled and imply that methylation and nucleosome arrangement synergistically regulate HP1 function.

Impact of Primary Care Intensive Management on High-Risk Veterans' Costs and Utilization: A Randomized Quality Improvement Trial.

Background: Primary care models that offer comprehensive, accessible care to all patients may provide insufficient resources to meet the needs of patients with complex conditions who have the greatest risk for hospitalization. Objective: To assess whether augmenting usual primary care with team-based intensive management lowers utilization and costs for high-risk patients. Design: Randomized quality improvement trial. (ClinicalTrials.gov: NCT03100526). Setting: 5 U.S. Department of Veterans Affairs (VA) medical centers. Patients: Primary care patients at high risk for hospitalization who had a recent acute care episode. Intervention: Locally tailored intensive management programs providing care coordination, goals assessment, health coaching, medication reconciliation, and home visits through an interdisciplinary team, including a physician or nurse practitioner, a nurse, and psychosocial experts. Measurements: Utilization and costs (including intensive management program expenses) 12 months before and after randomization. Results: 2210 patients were randomly assigned, 1105 to intensive management and 1105 to usual care. Patients had a mean age of 63 years and an average of 7 chronic conditions; 90% were men. Of the patients assigned to intensive management, 487 (44%) received intensive outpatient care (that is, ≥3 encounters in person or by telephone) and 204 (18%) received limited intervention. From the pre- to postrandomization periods, mean inpatient costs decreased more for the intensive management than the usual care group (-$2164 [95% CI, -$7916 to $3587]). Outpatient costs increased more for the intensive management than the usual care group ($2636 [CI, $524 to $4748]), driven by greater use of primary care, home care, telephone care, and telehealth. Mean total costs were similar in the 2 groups before and after randomization. Limitations: Sites took up to several months to contact eligible patients, limiting the time between treatment and outcome assessment. Only VA costs were assessed. Conclusion: High-risk patients with access to an intensive management program received more outpatient care with no increase in total costs. Primary Funding Source: Veterans Health Administration Primary Care Services.