Point-of-Care Ultrasound-Guided Arthrocentesis of a Pediatric Septic Ankle.

ABSTRACT: Septic arthritis is one potential cause of pediatric joint effusion and pain that may lead to significant morbidity. We present a case where point-of-care ultrasound was used to identify and aspirate a joint effusion in a pediatric patient with septic arthritis of the ankle, facilitating timely diagnosis and care. We review the technique for arthrocentesis of the ankle and literature on point-of-care ultrasound in the diagnosis of pediatric septic arthritis.

Patient and social factors related to nebulizer use in COPD patients at the transition of care: a qualitative study.

BACKGROUND: Transition from hospital to home is a vulnerable period for patients with COPD exacerbations, with a high risk for readmission and mortality. Twenty percent of patients with an initial hospitalization for a COPD exacerbation are readmitted to a hospital within 30 days, costing the health care system over $15 billion annually. While nebulizer therapy directed at some high-risk COPD patients may improve the transition from hospital to home, patient and social factors are likely to contribute to difficulties with their use. Current literature describing the COPD patient's experience with utilizing nebulizer therapy, particularly during care transitions, is limited. Therefore, the objective of this study was to explore underlying COPD patient and social factors contributing to practical difficulties with nebulizer use at the care transition from hospital to home. METHODS: This was a qualitative study conducted between September 2020 and June 2022. Patients were included if they were ≥ 40 years old, had a current diagnosis of COPD, had an inpatient admission at a hospital, and were discharged directly to home with nebulizer therapy. Semi-structured, one-on-one interviews with patients were conducted covering a broad range of patient and social factors and their relationships with nebulizer use and readmission. Interviews were recorded and transcribed verbatim. A thematic analysis was performed using a mixed inductive and deductive approach. RESULTS: Twenty-one interviews were conducted, and subjects had a mean age of 64 ± 8.4 years, 62% were female, and 76% were White. The predominant interview themes were health care system interactions and medication management. The interviews highlighted that discharge counseling methods and depth of counseling from hospitals were inconsistent and were not always patient-friendly. They also suggested that patients could appropriately identify, set up, and utilize their nebulizer treatment without difficulties, but additional patient education is required for nebulizer clean up and maintenance. CONCLUSIONS: Our interviews suggest that there is room for improvement within the health care system for providing consistent, effective discharge counseling. Also, COPD patients discharged from a hospital on nebulizer therapy can access and understand their treatment but require additional education for nebulizer clean up and maintenance.

Clinical and economic effectiveness of a pharmacy and primary care collaborative transition of care program.

BACKGROUND: Primary care pharmacists are uniquely positioned to improve care quality by intervening within care transitions in the postdischarge period. However, additional evidence is required to demonstrate that pharmacist-led interventions can reduce health care utilization in a cost-effective manner. The study's objective was to evaluate the clinical and economic effectiveness of a pharmacy-led transition of care (TOC) program within a primary care setting. METHODS: This cluster randomized trial was conducted between 2019 and 2021 and included three primary care practices. Eligible patients were ≥18 years of age and at high risk of readmission. The multifaceted pharmacy intervention included medication reconciliation, comprehensive medication review, and patient and provider follow-up. The primary composite endpoint included hospital readmissions and emergency department (ED) visits within 30 days of discharge. Differences in outcomes were modeled using a generalized estimated equations approach and outcomes were assumed to be distributed as a Poisson random variable. A cost-benefit analysis was embedded within the study and estimated economic outcomes from a provider group/health system perspective. Cost measures included: net benefit, benefit to cost ratio (BCR), and return on investment (ROI). RESULTS: Of 300 eligible patients, 36 were in the intervention group and 264 in the control group. The intervention significantly reduced the primary composite outcome of all-cause readmissions and ED visits within 30 days (adjusted incidence rate ratio [aIRR], 0.54; 95% CI, 0.44-0.66; P < 0.001). There were significant reductions in both 30-day all-cause readmissions (aIRR, 0.64; 95% CI, 0.60-0.67; P < 0.001) and ED visits (aIRR, 0.25; 95% CI, 0.20, 0.31; P < 0.001) between groups. The net benefit of the intervention was $9,078, with a BCR of 2.11 and a ROI of 111%. Sensitivity analyses were robust to changes in economic inputs. CONCLUSION: This care transition program had positive clinical and economic benefits, providing further support for the essential role pharmacists demonstrate in providing TOC services.

IL-6-GP130 signaling protects human hepatocytes against lipid droplet accumulation in humanized liver models.

Liver steatosis is an increasing health issue with few therapeutic options, partly because of a paucity of experimental models. In humanized liver rodent models, abnormal lipid accumulation in transplanted human hepatocytes occurs spontaneously. Here, we demonstrate that this abnormality is associated with compromised interleukin-6 (IL-6)-glycoprotein 130 (GP130) signaling in human hepatocytes because of incompatibility between host rodent IL-6 and human IL-6 receptor (IL-6R) on donor hepatocytes. Restoration of hepatic IL-6-GP130 signaling, through ectopic expression of rodent IL-6R, constitutive activation of GP130 in human hepatocytes, or humanization of an Il6 allele in recipient mice, substantially reduced hepatosteatosis. Notably, providing human Kupffer cells via hematopoietic stem cell engraftment in humanized liver mice also corrected the abnormality. Our observations suggest an important role of IL-6-GP130 pathway in regulating lipid accumulation in hepatocytes and not only provide a method to improve humanized liver models but also suggest therapeutic potential for manipulating GP130 signaling in human liver steatosis.

Generic versus disease-specific adverse event reporting: a comparison of the NSQIP and SAVES databases for the identification of acute care adverse events in adult spine surgery.

OBJECTIVE: The accurate identification and reporting of adverse events (AEs) is crucial for quality improvement. A myriad of AE systems are utilized. There is a lack of understanding of the differences between prospective versus retrospective, disease-specific versus generic, and point-of-care versus chart-abstracted systems. The objective of this study was to compare the benefits and limitations between the prospective, disease-specific, point-of-care Spine Adverse Events Severity System (SAVES) and the retrospective, generic, and chart-abstracted National Surgical Quality Improvement Program (NSQIP) for the identification and reporting of AEs in adult patients undergoing spinal surgery. METHODS: The authors conducted an observational ambidirectional cohort study of adult patients undergoing spine surgery other than for trauma between 2011 and 2019 in a quaternary spine center. Patients were identified using Current Procedural Terminology codes in the NSQIP database and matched using unique medical record numbers to their corresponding record in SAVES. The incidence of AEs and per-patient AEs as recorded in NSQIP and SAVES was the primary outcome of interest. Comparable AEs were identified by matching NSQIP AEs to equivalent ones in SAVES. Chi-square tests were used to test for significant differences in the incidence of overall and comparable AEs between the databases. RESULTS: There were 2198 patients identified in NSQIP, of whom 2033 also had complete records in SAVES. SAVES identified 5342 individual AEs in 1484 patients (73%) compared with 1291 individual AEs in 807 patients (39.7%) with the NSQIP database (p < 0.001). SAVES identified 250 intraoperative and 422 postoperative spine-specific AEs that NSQIP did not record. NSQIP captured a greater number of AEs beyond 30 days, including prolonged length of stay > 30 days, unplanned readmission, unplanned reoperation, and death later than 30 days after surgery compared with SAVES. CONCLUSIONS: SAVES captures a greater incidence of peri- and intraoperative spine-specific AEs than NSQIP, while NSQIP identifies a greater number of AEs beyond 30 days. While a prospective, disease-specific, point-of-care AE system such as SAVES is specific for guiding quality improvement in spine surgery, it incurs greater time and financial costs. Conversely, a retrospective, generic, and chart-abstracted system such as NSQIP provides equivocal cross-institutional comparability with reduced time and financial costs. Specific contextual and aim-specific needs should guide the choice and implementation of an AE system.

A Bispecific METxMET Antibody-Drug Conjugate with Cleavable Linker Is Processed in Recycling and Late Endosomes.

Most antibody-drug conjugates (ADC) approved for the treatment of cancer contain protease-cleavable linkers. ADCs that traffic to lysosomes traverse highly acidic late endosomes, while ADCs that recycle to the plasma membrane traffic through mildly acidic sorting and recycling endosomes. Although endosomes have been proposed to process cleavable ADCs, the precise identity of the relevant compartments and their relative contributions to ADC processing remain undefined. Here we show that a METxMET biparatopic antibody internalizes into sorting endosomes, rapidly traffics to recycling endosomes, and slowly reaches late endosomes. In agreement with the current model of ADC trafficking, late endosomes are the primary processing site of MET, EGFR, and prolactin receptor ADCs. Interestingly, recycling endosomes contribute up to 35% processing of the MET and EGFR ADCs in different cancer cells, mediated by cathepsin-L, which localizes to this compartment. Taken together, our findings provide insight into the relationship between transendosomal trafficking and ADC processing and suggest that receptors that traffic through recycling endosomes might be suitable targets for cleavable ADCs.

Integrating community health workers within a pharmacy to address health-related social needs.

BACKGROUND: Community pharmacies in the United States are beginning to serve as patient care service destinations addressing both clinical and health-related social needs (HRSN). Although there is support for integrating social determinant of health (SDoH) activities into community pharmacy practice, the literature remains sparse on optimal pharmacy roles and practice models. OBJECTIVE: To assess the feasibility of a community pharmacy HRSN screening and referral program adapted from a community health worker (CHW) model and evaluate participant perceptions and attitudes toward the program. METHODS: This feasibility study was conducted from January 2022 to April 2022 at an independent pharmacy in Buffalo, NY. Collaborative relationships were developed with 3 community-based organizations including one experienced in implementing CHW programs. An HRSN screening and referral intervention was developed and implemented applying a CHW practice model. Pharmacy staff screened subjects for social needs and referred to an embedded CHW, who assessed and referred subjects to community resources with as-needed follow-up. Post intervention, subjects completed a survey regarding their program experience. Descriptive statistics were used to report demographics, screening form, and survey responses. RESULTS: Eighty-six subjects completed screening and 21 (24.4%) an intervention and referral. Most participants utilized Medicaid (57%) and lived within a ZIP Code associated with the lowest estimated quartile for median household income (66%). Eighty-seven social needs were identified among the intervention subjects, with neighborhood and built environment (31%) and economic stability challenges (30%) being the most common SDoH domains. The CHW spent an average of 33 minutes per patient from initial case review through follow-up. All respondents had a positive perception of the program, and the majority agreed that community pharmacies should help patients with their social needs (70%). CONCLUSIONS: This feasibility study demonstrated that embedding a CHW into a community pharmacy setting can successfully address HRSN and that participants have a positive perception toward these activities.

Preclinical Study of a Biparatopic METxMET Antibody-Drug Conjugate, REGN5093-M114, Overcomes MET-driven Acquired Resistance to EGFR TKIs in EGFR-mutant NSCLC.

PURPOSE: MET amplification is a frequent mechanism of resistance to EGFR tyrosine kinase inhibitors (TKI) in patients with EGFR-mutated non-small cell lung cancer (NSCLC), and combined treatment with EGFR TKIs and MET TKIs has been explored as a strategy to overcome resistance. However, durable response is invariably limited by the emergence of acquired resistance. Here, we investigated the preclinical activity of REGN5093-M114, a novel antibody-drug conjugate targeting MET in MET-driven patient-derived models. EXPERIMENTAL DESIGN: Patient-derived organoids, patient-derived cells, or ATCC cell lines were used to investigate the in vitro/in vivo activity of REGN5093-M114. RESULTS: REGN5093-M114 exhibited significant antitumor efficacy compared with MET TKI or unconjugated METxMET biparatopic antibody (REGN5093). Regardless of MET gene copy number, MET-overexpressed TKI-naïve EGFR-mutant NSCLC cells responded to REGN5093-M114 treatment. Cell surface MET expression had the most predictive power in determining the efficacy of REGN5093-M114. REGN5093-M114 potently reduced tumor growth of EGFR-mutant NSCLC with PTEN loss or MET Y1230C mutation after progression on prior osimertinib and savolitinib treatment. CONCLUSIONS: Altogether, REGN5093-M114 is a promising candidate to overcome the challenges facing functional MET pathway blockade.

A taxonomy for community pharmacy patient care services reported in Pharmacist eCare Plans.

BACKGROUND: Pharmacies belonging to the Community Pharmacy Enhanced Service Networks (CPESN) are transforming their practices with support of the Flip the Pharmacy initiative. These pharmacies are submitting eCare plans that describe care that they have provided to patients. OBJECTIVES: The objectives of this study were (1) To develop a taxonomy for services reported by community pharmacies participating in year 1 of the Flip the Pharmacy initiative and (2) to illustrate the use of the taxonomy for hypertension-related services. METHODS: A retrospective observational study design was used. The analyzed data were extracted from eCare plans submitted by participating pharmacies during the first year of the Flip the Pharmacy initiative (October 1, 2019-September 30, 2020). Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) codes submitted for encounter reason and for procedures were sorted into categories based on similarity of terminology in the SNOMED-CT code labels. All SNOMED-CT codes in the encounter reasons that had blood pressure or hypertension in their labels were mapped to taxonomy categories. Descriptive statistics were calculated for all variables. RESULTS: A total of 368,297 eCare plans reporting 1,049,061 SNOMED-CT procedures were submitted for 133,210 patients by 526 pharmacies. Seven categories of community pharmacy patient care services were identified: medication synchronization, medication review, monitoring, immunizations, patient education, adherence, and recommendations. Over half of the encounter reasons (63.5%) and procedures (56.2%) were for medication synchronization. Both medication review and monitoring accounted for about 10% of the encounters, and medication review made up over 30% of procedures. A total of 18,307 encounters were related to hypertension. Of these, monitoring was the most frequent, with 11,285 encounters (61.6%) encounters, followed by patient education, with 5173 encounters (28.3%). CONCLUSION: CPESN pharmacies are delivering a wide range of patient care services. This taxonomy provides a concise way to organize and report services being delivered by community pharmacies.

Assessing Community Pharmacists' Perception on Readiness to Initiate Point-of-Care Testing for SARS-CoV-2 in New York State During the Pandemic.

Introduction: Pursuant to the COVID-19 pandemic, an executive order issued by the New York State (NYS) governor allowed pharmacists to act as laboratory directors for a limited-service laboratory (LSL) to order and perform Food and Drug Administration (FDA) and Emergency Use Authorization (EUA) Clinical Laboratory Improvement Amendment (CLIA)-waived COVID-19 point-of-care testing (POCT). Objectives: To (i) assess the status of NYS community pharmacists with POCT in the early stages of the COVID-19 pandemic, (ii) assess the readiness and willingness of community pharmacists to incorporate COVID-19 POCT into their workflow during a pandemic, and (iii) assess community pharmacists' perception of the barrier to initiating COVID-19 POCT. Methods: This is a prospective cross-sectional study conducted from February 4 to February 21, 2021. An electronic survey consisting of 66 Likert-type questions, select all that apply, and fill-in-style questions were emailed to 250 Community Pharmacy Enhanced Service Network (CPESN) NY pharmacies, with a follow-up email sent halfway into the data collection period. The data were analyzed using descriptive statistics. Results: The result indicated that most participants (median = 5) demonstrated readiness and willingness to offer COVID-19 testing. Barriers to COVID-19 POCT were identified: impact on pharmacy workflow (59%), lack of payment mechanism (55%) and lack of sufficient training (21%). Most participants expressed interest in continuing POCT beyond the pandemic (86.1%). Conclusion: Community pharmacists in NYS reported willingness to initiate COVID-19 POCT. Addressing the identified barriers, such as workflow disruption and reimbursement challenges, will enable pharmacies to be better prepared to provide patient care, including POCT.

Implementation and evaluation of social determinants of health practice models within community pharmacy.

BACKGROUND: While community pharmacies are an ideal setting for social needs screening and referral programs, information on social risk assessment within pharmacy practice is limited. OBJECTIVES: Our primary objective was to describe 2 social determinant of health (SDOH) practice models implemented within community pharmacies. The secondary objective was to evaluate implementation practices utilizing the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. PRACTICE DESCRIPTION: Two pharmacy groups participated in a 3-month study, one in New York (9 pharmacies) and another in Missouri (1 pharmacy). The New York pharmacies implemented an SDOH specialist practice model, in which pharmacy staff members facilitate the program. The Missouri pharmacy implemented a community health worker (CHW) model by cross training their technicians. Each pharmacy developed their program using the Community Pharmacy Enhanced Services Network Care Model. PRACTICE INNOVATION: Both programs expanded the technician role to take on additional responsibilities. The SDOH specialist model partnered with a local independent practice association to create a social needs referral program using a technology platform for closed-loop communication. All workflow steps of the self-contained CHW program were completed within the pharmacy, placing additional responsibility on the CHW and pharmacy staff. EVALUATION METHODS: RE-AIM framework dimensions of Reach, Effectiveness, and Adoption. RESULTS: Social challenges were identified in 49 of 76 (65%) generated SDOH screenings. The most prevalent social needs reported were affordability of daily needs (33%) and health care system navigation (15%). While most pharmacy staff indicated that workflow steps were clearly defined, assessments and referral tools were identified as potential gaps. While approximately 50% of pharmacy staff were comfortable with their assigned roles and in addressing SDOH challenges, physical and mental health concerns required additional education for intervention. CONCLUSION: The successful implementation of community pharmacy SDOH programs connected patients with local resources. Community pharmacies are ideally positioned to expand their public health footprint through SDOH interactions that consequently improve patient care.

Deriving Large-Scale Coastal Bathymetry from Sentinel-2 Images Using an HIGH-Performance Cluster: A Case Study Covering North Africa's Coastal Zone.

Coasts are areas of vitality because they host numerous activities worldwide. Despite their major importance, the knowledge of the main characteristics of the majority of coastal areas (e.g., coastal bathymetry) is still very limited. This is mainly due to the scarcity and lack of accurate measurements or observations, and the sparsity of coastal waters. Moreover, the high cost of performing observations with conventional methods does not allow expansion of the monitoring chain in different coastal areas. In this study, we suggest that the advent of remote sensing data (e.g., Sentinel 2A/B) and high performance computing could open a new perspective to overcome the lack of coastal observations. Indeed, previous research has shown that it is possible to derive large-scale coastal bathymetry from S-2 images. The large S-2 coverage, however, leads to a high computational cost when post-processing the images. Thus, we develop a methodology implemented on a High-Performance cluster (HPC) to derive the bathymetry from S-2 over the globe. In this paper, we describe the conceptualization and implementation of this methodology. Moreover, we will give a general overview of the generated bathymetry map for NA compared with the reference GEBCO global bathymetric product. Finally, we will highlight some hotspots by looking closely to their outputs.

Socio-demographic and -economic factors associated with 30-day readmission for conditions targeted by the hospital readmissions reduction program: a population-based study.

BACKGROUND: Early hospital readmissions remain common in patients with conditions targeted by the CMS Hospital Readmission Reduction Program (HRRP). There is still no consensus on whether readmission measures should be adjusted based on social factors, and there are few population studies within the U.S. examining how social characteristics influence readmissions for HRRP-targeted conditions. The objective of this study was to determine if specific socio-demographic and -economic factors are associated with 30-day readmissions in HRRP-targeted conditions: acute exacerbation of chronic obstructive pulmonary disease, pneumonia, acute myocardial infarction, and heart failure. METHODS: The Nationwide Readmissions Database was used to identify patients admitted with HRRP-targeted conditions between January 1, 2010 and September 30, 2015. Stroke was included as a control condition because it is not included in the HRRP. Multivariate models were used to assess the relationship between three social and economic characteristics (gender, urban/rural hospital designation, and estimated median household income within the patient's zip code) and 30-day readmission rates using a hierarchical two-level logistic model. Age-adjusted models were used to assess relationship differences between Medicare vs. non-Medicare populations. RESULTS: There were 19,253,997 weighted index hospital admissions for all diagnoses and 3,613,488 30-day readmissions between 2010 and 2015. Patients in the lowest income quartile (≤$37,999) had an increased odds of 30-day readmission across all conditions (P < 0.0001). Female gender and rural hospital designation were associated with a decreased odds of 30-day readmission for most targeted conditions (P < 0.05). Similar findings were also seen in patients ≥65 years old. CONCLUSIONS: Socio-demographic and -economic factors are associated with 30-day readmission rates and should be incorporated into tools or interventions to improve discharge planning and mitigate against readmission.

A Biparatopic Antibody-Drug Conjugate to Treat MET-Expressing Cancers, Including Those that Are Unresponsive to MET Pathway Blockade.

Lung cancers harboring mesenchymal-to-epithelial transition factor (MET) genetic alterations, such as exon 14 skipping mutations or high-level gene amplification, respond well to MET-selective tyrosine kinase inhibitors (TKI). However, these agents benefit a relatively small group of patients (4%-5% of lung cancers), and acquired resistance limits response durability. An antibody-drug conjugate (ADC) targeting MET might enable effective treatment of MET-overexpressing tumors (approximately 25% of lung cancers) that do not respond to MET targeted therapies. Using a protease-cleavable linker, we conjugated a biparatopic METxMET antibody to a maytansinoid payload to generate a MET ADC (METxMET-M114). METxMET-M114 promotes substantial and durable tumor regression in xenografts with moderate to high MET expression, including models that exhibit innate or acquired resistance to MET blockers. Positron emission tomography (PET) studies show that tumor uptake of radiolabeled METxMET antibody correlates with MET expression levels and METxMET-M114 efficacy. In a cynomolgus monkey toxicology study, METxMET-M114 was well tolerated at a dose that provides circulating drug concentrations that are sufficient for maximal antitumor activity in mouse models. Our findings suggest that METxMET-M114, which takes advantage of the unique trafficking properties of our METxMET antibody, is a promising candidate for the treatment of MET-overexpressing tumors, with the potential to address some of the limitations faced by the MET function blockers currently in clinical use.

Addressing social determinants of health in community pharmacy: Innovative opportunities and practice models.

Social determinants of health (SDoH) account for up to 90% of health outcomes, whereas medical care accounts for only 10%-15%; despite this disparity, only 24% of hospitals and 16% of physician practices screen for the 5 social needs. Community-embedded and highly accessible, pharmacies are uniquely positioned to connect individuals to local community and social resources and thereby address SDoH. In this article, we explore novel community pharmacy practice models that address SDoH, provide real-world examples of these models, and discuss pathways for reimbursement and sustainability. A number of innovative community pharmacy practice models that focus on social issues are currently being explored. These include integrating community health workers (CHWs) or SDoH specialists, wherein CHWs are frontline public health workers who can effectively bridge the health care system and their community, whereas SDoH specialists are pharmacy team members trained with substantial SDoH knowledge and how to use it to connect pharmacy patients to community resources. Three community pharmacy networks have implemented pilot programs using either a CHW or SDoH specialist model. An essential component for program success in all cases has been partnership development and increased interdependence between the pharmacies, local community organizations, and the public health sector. New payment models and financial incentives will be necessary to expand and sustain these programs. A potential Approach may be the use of Z codes, a subset of ICD-10-CM codes specific to assessing SDoH. Although opportunities are developing for community pharmacies to play a major role in sustainably addressing SDoH, additional work is needed before there is a widespread acceptance of pharmacies becoming service referral destinations for patients with social needs. Evaluation of these models on a wider scale will be necessary to fully evaluate their effectiveness, costs, and implementation within different community pharmacy settings.

Readmissions and costs among younger and older adults for targeted conditions during the enactment of the hospital readmission reduction program.

BACKGROUND: The Hospital Readmissions Reduction Program (HRRP) was introduced to reduce readmission rates among Medicare beneficiaries, however little is known about readmissions and costs for HRRP-targeted conditions in younger populations. The primary objective of this study was to examine readmission trends and costs for targeted conditions during policy implementation among younger and older adults in the U.S. METHODS: We analyzed the Nationwide Readmission Database from January 2010 to September 2015 in younger (18-64 years) and older (≥65 years) patients with acute myocardial infarction (AMI), heart failure (HF), pneumonia, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Pre- and post-HRRP periods were defined based on implementation of the policy for each condition. Readmission rates were evaluated using an interrupted time series with difference-in-difference analyses and hospital cost differences between early and late readmissions (≤30 vs. > 30 days) were evaluated using generalized linear models. RESULTS: Overall, this study included 16,884,612 hospitalizations with 3,337,266 readmissions among all age groups and 5,977,177 hospitalizations with 1,104,940 readmissions in those aged 18-64 years. Readmission rates decreased in all conditions. In the HRRP announcement period, readmissions declined significantly for those aged 40-64 years for AMI (p < 0.0001) and HF (p = 0.003). Readmissions decreased significantly in the post-HRRP period for those aged 40-64 years at a slower rate for AMI (p = 0.003) and HF (p = 0.05). Readmission rates among younger patients (18-64 years) varied within all four targeted conditions in HRRP announcement and post-HRRP periods. Adjusted models showed a significantly higher readmission cost in those readmitted within 30 days among younger and older populations for AMI (p < 0.0001), HF (p < 0.0001), pneumonia (p < 0.0001), and AECOPD (p < 0.0001). CONCLUSION: Readmissions for targeted conditions decreased in the U.S. during the enactment of the HRRP policy and younger age groups (< 65 years) not targeted by the policy saw a mixed effect. Healthcare expenditures in younger and older populations were significantly higher for early readmissions with all targeted conditions. Further research is necessary evaluating total healthcare utilization including emergency department visits, observation units, and hospital readmissions in order to better understand the extent of the HRRP on U.S. healthcare.

Monomeric/dimeric forms of Fgf15/FGF19 show differential activity in hepatocyte proliferation and metabolic function.

Human Fibroblast Growth Factor 19 (FGF19) and mouse ortholog Fgf15 play similar roles in liver regeneration and metabolism via the activation of Fgfr4/b-klotho (Klb). Monomeric FGF19 and dimeric Fgf15 are both necessary for liver regeneration and proper bile acid (BA) metabolism. FGF19 elicits stronger effects than Fgf15 on glucose and fatty acid metabolism and only FGF19 induces hepatocellular carcinoma (HCC). However, inhibiting FGF19/FGFR4 signaling in HCC patients is associated with toxicity due to elevated BA levels. Here, we examine the structure/function relationship in Fgf15/FGF19 to better understand the molecular basis for their distinct functions. We demonstrate that FGF19 is a more effective activator of Fgfr4 and of downstream signaling (Erk, Plcg1) than Fgf15. Furthermore, we use site-directed mutagenesis to show that the presence or absence of an unpaired cysteine in Fgf15/19 modulates ligand structure and determines the ability of these molecules to induce hepatocyte proliferation, with monomers being more potent activators. Consistent with these findings, an engineered dimeric variant of FGF19 is less effective than wild-type FGF19 at inducing liver growth in cooperation with the Wnt-enhancer RSPO3. In contrast to effects on proliferation, monomeric and dimeric ligands equally inhibited the expression of Cyp7a1, the enzyme catalyzing the rate limiting step in BA production. Thus, structure and function of Fgf15/FGF19 are intricately linked, explaining why FGF19, but not Fgf15, induces liver tumorigenesis. Our data provide insight into FGF19/FGFR4 signaling and may inform strategies to target this pathway while limiting on-target toxicity due to dysregulation of BA production or induction of hepatocyte proliferation.

Impact of Community Pharmacist Interventions With Managed Care to Improve Medication Adherence.

BACKGROUND: Nonadherence to medications is a concern due to adverse outcomes and higher costs of care. The Centers for Medicare and Medicaid Services has made adherence a key measurement for Star ratings. OBJECTIVE: To evaluate the impact of a collaborative pilot program between a third-party payer, local pharmacy organization, and academic institution focusing on improving medication adherence with community pharmacies. METHODS: Twenty-five community pharmacies implemented adherence-based interventions in patients ≥65 years old, who were Medicare Advantage Plan members, taking targeted medications (statins, oral diabetic medications, angiotensin-converting enzyme inhibitors [ACE-Is] and angiotensin receptor blockers [ARBs]). Outcome measures were (1) pharmacy intervention completion rate, (2) type of adherence interventions, (3) change in the proportion of days covered (PDC) following pharmacist intervention based on adherence group, and (4) nonadherence barriers. RESULTS: A total of 1263 interventions met the eligibility criteria, and common interventions included explaining the benefit of the medication (n = 453, 35.9%) and provider follow-up (n = 109, 8.6%). Among nonadherent subjects who became adherent, the mean PDC increased by 14% (74%-88%, P < .0001), with a 12% decrease in mean PDC score in the nonadherent who remained nonadherent group (71%-58%, P < .0001). Common patient barriers for nonadherence were forgetfulness (n = 451, 35.7%) and denial (n = 84, 6.7%). System and therapeutic barriers included complexity (n = 155, 12.3%) and adverse side effects (n = 42, 3.3%). CONCLUSION: This collaborative effort successfully implemented a community pharmacist-led adherence intervention in 25 independent pharmacies. Our findings highlight increased interactions with patients and in some cases improved adherence measures. Future research must include implementation outcomes in order to effectively implement these interventions in the community pharmacy setting.

Community Pharmacists' Perceptions of Patient Care Services within an Enhanced Service Network.

BACKGROUND: Pharmacists are positioned as an accessible source of patient care services (PCS). Despite the adversity community pharmacies continue to face, the expanding opportunity of offering PCS continues to be a pathway forward. OBJECTIVE: To identify community pharmacists' perceptions to deliver PCS within an enhanced service network. METHODS: One-on-one semi-structured phone interviews were conducted as part of a mixed-methods approach. Interview transcripts were analyzed using a consensus codebook to draft thematic findings. Participants were recruited from an electronic survey targeting community pharmacists from the New York chapters of the Community Pharmacy Enhanced Services Network (CPESN). RESULTS: Twelve pharmacists were interviewed with four main themes identified. The majority of study participants were pharmacy owners (92%) devoting an average of 15 h/week to PCS and 8 h/week addressing social barriers. The main themes identified include: (1) perceptions of pharmacy profession, (2) reimbursement models and sustainability of PCS, (3) provision of patient care services, and (4) how PCS address social determinants of health. CONCLUSIONS: Offering PCS opportunities for patients is a direction many community pharmacists have embraced and are working to succeed. Ongoing research is needed focusing on community pharmacists' self-perceptions of the clinical impact and role they hold in an evolving healthcare system.

Potentially Inappropriate Medications Are Associated with Increased Healthcare Utilization and Costs.

BACKGROUND/OBJECTIVES: To examine the prevalence of potentially inappropriate medication (PIM) prescribing and its association with healthcare utilization and related expenditures utilizing nationally representative data from the United States. DESIGN: Retrospective cohort study. SETTING: The 2011-2015 Medical Expenditure Panel Survey (MEPS). PARTICIPANTS: Community-dwelling sample of U.S. adults aged 65 and older during the first round of each MEPS cycle. MEASUREMENTS: A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to estimate the prevalence of PIM prescribing over the study period. Negative binomial models were assembled to examine associations between PIM exposure and healthcare utilization including hospitalizations, emergency department (ED) visits, and outpatient provider visits. Generalized linear models with the log link function and gamma distribution were used to analyze associations between PIM exposure and healthcare expenditures. Sensitivity analyses were conducted utilizing inverse probability treatment weighting using propensity scores for being prescribed a PIM. RESULTS: The period prevalence of PIM prescribing over the 5-year sample was 34.4%. PIM prescribing was positively associated with hospitalizations (adjusted incidence rate ratio [aIRR] = 1.17; 95 confidence interval [CI] = 1.08-1.26; P < .001), ED visits (aIRR = 1.26; 95% CI = 1.17-1.35; P < .001), and outpatient provider visits (aIRR = 1.18; 95% CI = 1.14-1.21; P < .001). PIM exposure was associated with higher marginal costs within outpatient visits ($116; 95% CI = $105-$243; P < .001), prescription medications ($128; 95% CI = $72-$199; P < .001), and total healthcare expenditures ($458; 95% CI = $295-$664; P < .001). Similar results were found in our propensity score analyses. CONCLUSION: PIMs continue to be prescribed at a high rate among older adults in the United States. Our results suggest that receipt of PIMs is associated with higher rates of healthcare utilization and increased costs across the healthcare continuum. Further work is needed to implement evidence-based deprescribing interventions that may in turn reduce unnecessary healthcare utilization.