Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4ß7-Blocking Therapy in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response. METHODS: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4ß7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell variable, diversity, and joining sequencing; serum proteomics; and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response. RESULTS: Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4+ memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4ß1, potentially making these cells less susceptible to direct targeting by vedolizumab. CONCLUSIONS: These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.

Educational Debt and Income Among Pharmacists and Other Health Professionals.

OBJECTIVE: Given the substantial increases in student educational loan debt in recent years, the objective was to assess trends in educational debt-to-income ratios for graduates of pharmacy, medicine, dentistry, optometry, and veterinary medicine programs in the United States in the 2017-2022 period. METHODS: A retrospective analysis of 2017-2022 data for educational debt and income for select health professions was conducted. Annual income data were collected from the American Community Survey, and educational debt data were collected from health professions organizations. Educational debt-to-income ratios for each health profession were calculated, as was the mean change per year in debt-to-income ratio. RESULTS: With the exception of medicine, educational debt consistently exceeded income across the selected health professions in the 2017-2022 period. Debt-to-income ratios of pharmacists and the remaining health professionals decreased on average per year between 2017 and 2022. Physicians had the lowest debt-to-income ratios and dentists had the highest debt-to-income ratios in the study period. CONCLUSION: Debt-to-income ratios fell below the 2017 levels for the health professions of interest, suggesting that average growth in income outpaced that of debt for the study period. Regardless, debt remains high and may influence health care professionals' postgraduate training and career decisions, and in turn affect access to health care. Therefore, a call to action is proposed to address educational debt burden. Several strategies are suggested, including federal policy changes, implementing tuition reductions or minimal increases, facilitating financial aid options, and reducing underlying costs of health professions programs.

Analysis of 10-year income trends for pharmacists and other select health professionals.

PURPOSE: To evaluate income trends among pharmacists and other select health professions (dentists, nurse practitioners, registered nurses, and physicians) in the US for the 10-year period of 2012 to 2021, with special attention given to the first 2 years of the COVID-19 pandemic (2020 and 2021). METHODS: A retrospective analysis was conducted of 2012 to 2021 income data for select health professions, collected from the American Community Survey. Univariate time series analysis was conducted using exponential smoothing to examine income patterns over the 10-year study period and forecast income for the next 5-year period (2022 to 2026) for each health profession. Additionally, time series regression models were constructed for each health profession. Descriptive statistics (mean percent change in income and SD) were calculated for each health profession for the prepandemic era (2012 to 2019) and the first 2 years of the pandemic (2020 and 2021). RESULTS: Goodness-of-fit statistics for each forecast model indicate highly accurate forecasts. The model for each health profession indicates a significant positive trajectory in income (P < 0.001), although pharmacists are projected to have a lower rate of income growth among the 5 health professions for the next 5-year period, 2022 to 2026. During the first 2 years of the pandemic, pharmacists had the lowest mean percent change in income (mean, 2.0%; SD, 2.0%) among the 5 health professions. CONCLUSION: Growth in pharmacist income is projected to lag behind that in other health professions in the near future. Individual-, organization-, and profession-level strategies may facilitate opportunities for income growth among pharmacists.

Effects of Medicare Part D medication therapy management on racial/ethnic disparities in adherence to antidementia medications among patients with Alzheimer's disease and related dementias: An observational study.

Background: Evidence is sparse on the effects of Medicare medication therapy management (MTM) on racial/ethnic disparities in medication adherence among patients with Alzheimer's disease and related dementias. Objectives: This study examined the Medicare MTM program's effects on racial/ethnic disparities in the adherence to antidementia medications among patients with Alzheimer's disease and related dementias. Methods: This is a retrospective analysis of 100% of 2010-2017 Medicare Parts A, B, and D data linked to Area Health Resources Files. The study outcome was nonadherence to antidementia medications, and intervention was defined as new MTM enrollment in 2017. Propensity score matching was conducted to create intervention and comparison groups with comparable characteristics. A difference-in-differences model was employed with logistic regression, including interaction terms of dummy variables for the intervention group and racial/ethnic minorities. Results: Unadjusted comparisons revealed that Black, Hispanic, and Asian/Pacific Islander patients were more likely to be nonadherent than non-Hispanic White (White) patients in 2016. Differences in odds of nonadherence between Black and White patients among the intervention group were lower in 2017 than in 2016 by 27% (odds ratios [OR]: 0.73, 95% confidence interval [CI]: 0.65-0.82). A similar lowering was seen between Hispanic and White patients by 26% (OR: 0.74, 95% CI: 0.63-0.87). MTM enrollment was associated with reduced disparities in nonadherence for Black-White patients of 33% (OR: 0.67, 95% CI: 0.57-0.78) and Hispanic-White patients of 19% (OR: 0.81, 95% CI: 0.67-0.99). Discussion: The Medicare MTM program was associated with lower disparities in adherence to antidementia medications between Black and White patients, and between Hispanic and White patients in the population with Alzheimer's disease and related dementias. Conclusions: Expanding the MTM program may particularly benefit racial/ethnic minorities in Alzheimer's disease and related dementia care.

Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration.

Age-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.

Patient reported goals for medications for opioid use disorder: A theory of proximal goal attainment.

Background: There exist substantial patient barriers to accessing medications for opioid use disorder (MOUD), including travel distance, stigma, and availability of MOUD providers. Yet, despite these barriers, there exists a subset of patients who possess the requisite motivation to seek and remain adherent to treatment. Objective: To explore patient-derived goals in MOUD treatment-adherent patients. Methods: This study used in-depth interviews with patients receiving methadone who were enrolled in opioid treatment programs (OTPs) across Tennessee. Participants were recruited from 12 different OTPs to participate in telephonic semi-structured interviews to a point of saturation. Participants had to be adherent to treatment, in treatment for 6 months or greater, and English speaking. Analysis occurred inductively using a constructivist approach to Grounded Theory. Results: In total, 17 patient interviews were conducted in the spring of 2021. Participants described goal setting across three general stages of treatment: (1) addressing acute physical and emotional needs upon treatment entry, (2) development of supportive structure and routine to develop healthy skills facilitated by treatment team, and (3) identifying and pursuing future-focused goals not directly linked to treatment. A Proximal Goals in MOUD Framework is introduced. Conclusion: In this qualitative study on patient reported goals in MOUD it was found that goals are transitory and relative to the stage of treatment. Further research is needed to better understand goal evolution over the course of treatment and its impact on treatment retention.

Integration of Trauma-informed Care Into the Doctor of Pharmacy Curriculum.

Trauma-informed care (TIC) is a framework based on understanding and responding to individuals' experiences of psychological trauma (defined as harmful circumstances that have a lasting impact on emotional well-being), as well as fostering their sense of safety and empowerment. Health profession degree programs are increasingly integrating TIC training into their curricula. Although literature is scarce regarding TIC education in academic pharmacy, student pharmacists will likely encounter patients, co-workers, and peers who have experienced psychological trauma. Students may also have experienced psychological trauma themselves. Therefore, student pharmacists would benefit from TIC learning, and pharmacy educators should consider implementing trauma-informed education. This commentary defines the TIC framework, explores its benefits, and considers an approach to implementing the TIC framework in pharmacy education with little disruption to existing curricula.

Racial and ethnic disparities in the enrolment of medicare medication therapy management programs.

Objectives: Racial/ethnic disparities have been found in prior literature examining enrolment in Medicare medication therapy management programs. However, those studies were based on various eligibility scenarios because enrolment data were unavailable. This study tested for potential disparities in enrolment using actual MTM enrolment data. Methods: Medicare Parts A&B claims, Medication Therapy Management Data Files, and the Area Health Resources File from 2013 to 2014 and 2016 to 2017 were analysed in this retrospective analysis. An adjusted logistic regression compared odds of enrolment between racial/ethnic minorities and non-Hispanic Whites (Whites) in the total sample and subpopulations with diabetes, hypertension, or hyperlipidaemia. Trends in disparities were analysed by including interaction terms in regressions between dummy variables for race/ethnic minority groups and period 2016-2017. Key Findings: Disparities in MTM enrolment were detected between Blacks and Whites with diabetes in 2013-2014 (Odds Ratio = 0.78, 95% Confidence Interval = 0.75-0.81). This disparity improved from 2013-2014 to 2016-2017 for Blacks (Odds Ratio=1.08, 95% Confidence Interval = 1.04-1.11) but persisted in 2016-2017 (Odds Ratio = 0.84, 95% Confidence Interval = 0.81-0.87). A disparity was identified between Blacks and Whites with hypertension in 2013-2014 (Odds Ratio = 0.92, 95% Confidence Interval = 0.89-0.95) but not in 2016-2017. Enrolment for all groups, however, declined between periods. For example, in the total sample, the odds of enrolment declined from 2013-2014 to 2016-2017 by 22% (Odds Ratio=0.78, 95% Confidence Interval=0.75-0.81). Conclusions: Racial disparities in MTM enrolment were found between Blacks and Whites among Medicare beneficiaries with diabetes in both periods and among individuals with hypertension in 2013-2014. As overall enrolment fell between periods, concerns about program enrolment remain.

Solving racial/ethnic disparities associated with Medicare Part D Star Ratings.

OBJECTIVE: Medicare Part D Star Ratings are instrumental in shaping healthcare quality improvement efforts. However, the calculation metrics for medication performance measures for this program have been associated with racial/ethnic disparities. In this study, we aimed to explore whether an alternative program, named Star Plus by us that included all medication performance measures developed by Pharmacy Quality Alliance and applicable to our study population, would reduce such disparities among Medicare beneficiaries with diabetes, hypertension, and/or hyperlipidemia. METHOD: We conducted an analysis of a 10% random sample of Medicare A/B/D claims linked to the Area Health Resources File. Multivariate logistic regressions with minority dummy variables were used to examine racial/ethnic disparities in measure calculations of Star Ratings and Star Plus, respectively. RESULTS: Adjusted results indicated that relative to non-Hispanic Whites (Whites), racial/ethnic minorities had significantly lower odds of being included in the Star Ratings measure calculations: the odds ratios (ORs) for Blacks, Hispanics, Asians, and Others were 0.68 (95% confidence interval [CI] = 0.66-0.71), 0.73 (CI = 0.69-0.78), 0.88 (CI = 0.82-0.93), and 0.92 (CI = 0.88-0.97), respectively. In contrast, every beneficiary in the sample was included in Star Plus. Further, racial/ethnic minorities had significantly higher increase in the odds of being included in measure calculation in Star Plus than Star Ratings. The ORs for Blacks, Hispanics, Asians, and Others were 1.47 (CI = 1.41-1.52), 1.37 (CI = 1.29-1.45), 1.14 (CI = 1.07-1.22), and 1.09 (CI = 1.03-1.14), respectively. CONCLUSIONS: Our study demonstrated that racial/ethnic disparities may be eliminated by including additional medication performance measures to Star Ratings.

Community-Centered Patient Journey Map in Opioid Use Disorder: A Tool to Address Compassion Fatigue among Community Pharmacists.

Community pharmacists have become increasingly exposed to opioid use disorders in recent decades. However, both pharmacist training and traditional practice environments have not been adequate to prepare the pharmacist for both the patient care needs and regulatory barriers of patients experiencing opioid use disorders (OUD). As a result, there is a need to increase pharmacists' awareness of both the overall patient experience as they navigate their OUD and the role of the community pharmacy as a touchpoint within that experience. To this end, a Community-Centered Patient Journey in Drug Addiction Treatment journey map was developed with expert insights, clinical experience, and in-depth interviews (conducted in spring of 2021) with 16 participants enrolled in licensed opioid treatment programs in Tennessee. Patients, policymakers, clinicians, and academic researchers were involved in the map development. Lived experiences of key informants were captured via in-depth interviews. A consensus decision-making approach was used throughout the patient journey map development process. The final patient journey map illustrates a non-linear pathway, describes the central role of the patient's community, and emphasizes three major "pain points" within the system (access, adherence, and affordability). Future research should investigate the impact of such a journey map on pharmacy personnel's knowledge, attitudes, and behaviors.

Daratumumab for the treatment of refractory ANCA-associated vasculitis.

Objective Treatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells.Methods We treated two patients with severe life-threatening AAV with renal and pulmonary manifestation despite induction therapy with rituximab and cyclophosphamide with four to eight doses of 1800 mg daratumumab. We followed clinical and immunological responses.Results The first patient with myeloperoxidase-ANCA-positive microscopic polyangiitis had resolution of pneumonitis and pleuritis and stabilisation of kidney function after daratumumab. The second patient with proteinase 3-ANCA-positive granulomatosis with polyangiitis, diffuse alveolar haemorrhage necessitating extracorporeal membrane oxygenation (ECMO) and acute kidney failure, requiring kidney replacement therapy, was weaned off ECMO, mechanical ventilation and dialysis and discharged home after daratumumab. Clinical improvement was paralleled by a strong reduction in serum ANCA levels as well as total IgG, indicating depletion of plasma cells. Apart from the depletion of CD38+ natural killer cells, blood leucocyte levels were not notably influenced by daratumumab. Only mild adverse events, such as hypogammaglobulinaemia and an upper respiratory tract infection occurred.Conclusion Daratumumab was safe and effective in inducing remission in two patients with severe treatment-refractory AAV, warranting prospective clinical trials to establish safety and efficacy.

Racial and ethnic disparities in Medicare Part D medication therapy management services utilization.

Background: The Medicare Part D medication therapy management (MTM) program has positive effects on medication and health service utilization. However, little is known about its utilization, much less so about the use among racial and ethnic minorities. Objective: To examine MTM service utilization among older Medicare beneficiaries and to identify any racial and ethnic disparity patterns. Methods: A retrospective cross-sectional analysis of 2017 Medicare administrative data, linked to the Area Health Resources Files. Fourteen outcomes related to MTM service nature, initiation, quantity, and delivery were examined using logistic, negative binomial, and Cox proportional hazards regression models. Results: Racial and ethnic disparities were found with varying patterns across outcomes. For example, compared with White patients, the odds of opting out of MTM were 8% higher for Black patients (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.03-1.14), 57% higher for Hispanic patients (OR = 1.57, 95% CI = 1.42-1.72), and 57% higher for Asian patients (OR = 1.57, 95% CI = 1.33-1.85). The odds of continuing MTM from the previous years were 12% lower for Black patients (OR = 0.88, 95% CI = 0.86-0.90) and 3% lower for other patients (OR = 0.97, 95% CI = 0.95-0.99). In addition, the probability of being offered a comprehensive medication review (CMR) after MTM enrollment was 9% lower for Hispanic patients (hazard ratio [HR] = 0.91, 95% CI = 0.85-0.97), 9% lower for Asian patients (HR = 0.91, 95% CI = 0.87-0.94), and 3% lower for other patients (HR = 0.97, 95% CI = 0.95-0.99). Hispanic and Asian patients were more likely to have someone other than themselves receive a CMR. Conclusions: Racial and ethnic disparities in MTM service utilization were identified. Although the disparities in specific utilization outcomes vary across racial/ethnic groups, it is evident that these disparities exist and may result in vulnerable communities not fully benefiting from the MTM services. Causes of the disparities should be explored to inform future reform of the Medicare Part D MTM program.

Cost-Effectiveness of Medication Therapy Management Program Across Racial and Ethnic Groups Among Medicare Beneficiaries.

OBJECTIVES: Equity and effectiveness of the medication therapy management (MTM) program in Medicare has been a policy focus since its inception. The objective of this study was to evaluate the cost-effectiveness of the Medicare MTM program in improving medication utilization quality across racial and ethnic groups. METHODS: This study analyzed 2017 Medicare data linked to the Area Health Recourses File. A propensity score was used to match MTM enrollees and nonenrollees, and an incremental cost-effectiveness ratio between the 2 groups was calculated. Effectiveness was measured as the proportion of appropriate medication utilization based on medication utilization measures developed by Pharmacy Quality Alliance. Net monetary benefits were compared across racial and ethnic groups at various societal willingness-to-pay (WTP) thresholds. The 95% confidence intervals were obtained by nonparametric bootstrapping. RESULTS: MTM dominated non-MTM among the total sample (N = 699 992), as MTM enrollees had lower healthcare costs ($31 135.89 vs $32 696.69) and higher proportions of appropriate medication utilization (87.47% vs 85.31%) than nonenrollees. MTM enrollees had both lower medication costs ($10 681.21 vs $11 003.08) and medical costs ($20 454.68 vs $21 693.61) compared with nonenrollees. The cost-effectiveness of MTM was higher among Black patients than White patients across the WTP thresholds. For instance, at a WTP of $3006 per percentage point increase in effectiveness, the net monetary benefit for Black patients was greater than White patients by $2334.57 (95% confidence interval $1606.53-$3028.85). CONCLUSIONS: MTM is cost-effective in improving medication utilization quality among Medicare beneficiaries and can potentially reduce disparities between Black and White patients. Expansion of the current MTM program could maximize these benefits.

Structural and functional distinctions of co-resident microglia and monocyte-derived macrophages after retinal degeneration.

BACKGROUND: Both resident microglia and invading peripheral immune cells can respond to injury and degeneration in the central nervous system. However, after dead and dying neurons have been cleared and homeostasis is re-established, it is unknown whether resident immune cells fully resume normal functions and to what degree the peripheral immune cells take up residence. METHODS: Using flow cytometry, in vivo retinal imaging, immunohistochemistry, and single-cell mRNA sequencing, we assess resident microglia and monocyte-derived macrophages in the retina during and after the loss of photoreceptors in the Arr1-/- mouse model of inducible degeneration. RESULTS: We find that photoreceptor loss results in a small, sustained increase in mononuclear phagocytes and, after degeneration wanes, these cells re-establish a spatial mosaic reminiscent of healthy retinas. Transcriptomic analysis revealed the population remained unusually heterogeneous, with several subpopulations expressing gene patterns consistent with mildly activated phenotypes. Roughly a third of "new resident" cells expressed markers traditionally associated with both microglial and monocytic lineages, making their etiology ambiguous. Using an inducible Cre-based fluorescent lineage tracing paradigm to confirm the origins of new resident immune cells, we found approximately equal numbers of microglia and monocyte-derived macrophages after degeneration had subsided. In vivo retinal imaging and immunohistochemical analysis showed that both subpopulations remained functionally responsive to sites of local damage, though on average the monocyte-derived cells had less morphological complexity, expressed higher levels of MHCII, and had less migratory activity than the native resident population. CONCLUSIONS: Monocytic cells that infiltrate the retina during degeneration differentiate into monocyte-derived macrophages that can remain in the retina long-term. These monocyte-derived macrophages adopt ramified morphologies and microglia-like gene expression. However, they remain distinguishable in morphology and gene expression from resident microglia and appear to differ functionally, showing less responsiveness to subsequent retinal injuries. These findings support the idea that persistent changes in the local immune population that occur in response to cell loss in aging and progressive retinal diseases may include the establishment of subpopulations of bone marrow-derived cells whose ability to respond to subsequent insults wanes over time.

A Qualitative Systematic Review of Access to Substance Use Disorder Care in the United States Criminal Justice System.

BACKGROUND: The majority of patients with a substance use disorder (SUD) in the United States do not receive evidence-based treatment. Research has also demonstrated challenges to accessing SUD care in the US criminal justice system. We conducted a systematic review of access to SUD care in the US criminal justice system. METHODS: We searched for comprehensive qualitative studies in multiple databases through April 2021, and two researchers reviewed 6858 studies using pre-selected inclusion criteria. Once eligibility was determined, themes were extracted from the data. This review provides a thematic overview of the US qualitative studies to inform future research-based interventions. This review was conducted in compliance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). RESULTS: There were 6858 unique abstract results identified for review, and seven qualitative studies met the inclusion criteria. Two themes were identified from these results: (1) managing withdrawal from medication-assisted treatment, and (2) facilitators and barriers to treatment programs in the criminal justice system. CONCLUSIONS: Qualitative research evaluating access to SUD care in the US criminal justice system varied, with some interventions reported not rooted in evidence-based medicine. An opportunity may exist to develop best practices to ensure evidence-based treatment for SUDs is delivered to patients who need it in the US criminal justice system.