Do Employees From Less-Healthy Communities Use More Care and Cost More? Seeking to Establish a Business Case for Investment in Community Health.

INTRODUCTION: Few studies have examined the impact of community health on employers. We explored whether employed adults and their adult dependents living in less-healthy communities in the greater Philadelphia region used more care and incurred higher costs to employers than employees from healthier communities. METHODS: We used a multi-employer database to identify adult employees and dependents with continuous employment and mapped them to 31 zip code regions. We calculated community health scores at the regional level, by using metrics similar to the Robert Wood Johnson Foundation (RWJF) County Health Rankings but with local data. We used descriptive analyses and multilevel linear modeling to explore relationships between community health and 3 outcome variables: emergency department (ED) use, hospital use, and paid claims. Business leaders reviewed findings and offered insights on preparedness to invest in community health improvement. RESULTS: Poorer community health was associated with high use of ED services, after controlling for age and sex. After including a summary measure of racial composition at the zip code region level, the relationship between community health and ED use became nonsignificant. No significant relationships between community health and hospitalizations or paid claims were identified. Business leaders expressed interest in further understanding health needs of communities where their employees live. CONCLUSION: The health of communities in which adult employees and dependents live was associated with ED use, but similar relationships were not seen for hospitalizations or paid claims. This finding suggests a need for more primary care access. Despite limited quantitative evidence, business leaders expressed interest in guidance on investing in community health improvement

Identifying disability level in multiple sclerosis patients in a U.S.-based health plan claims database.

AIMS: In clinical trials, disability progression in multiple sclerosis (MS) is measured by the Kurtzke expanded disability status scale (EDSS), which is not captured in routine clinical care in the U.S. This study developed a claims-based disability score (CDS) based on the EDSS for assigning MS disability level in a U.S. claims database. METHODS: This retrospective cohort study of patients with MS in the U.S., utilized adjudicated health plan claims data linked to electronic medical records (EMRs) data. Patients were identified between 1 January 2012 and 31 December 2016 and indexed on the first date of MS diagnosis. The CDS was developed to assign disability level at baseline using claims and ambulatory EMR records observed over the 1-year baseline period. All-cause healthcare costs were assessed by baseline disability level to validate the CDS. RESULTS: In total, 45,687 patients were identified in claims (full sample) and 1,599 linked to EMR (core sample). Over half of patients in both samples were classified with mild disability at baseline. Adjusted healthcare costs in patients with moderate and severe disability were 15% (p CONCLUSIONS: The CDS is the first claims-based measure of MS disability utilizing data from EMR. This novel measure advances the opportunity to examine outcomes by disability accumulation in the absence of standard markers of disease progression. Although formal validation of the CDS was not possible due to lack of available EDSS in the EMR, the economic burden results align with prior publications and show that healthcare costs increase with increasing disability. Future validation studies of the CDS are warranted

Pacific Portraits: The People Behind the Scenes at Pacific University (Volume One)

When a dormitory toilet is clogged, who’s the guy charged with fixing it? Who assures that benefits and work-study monies are paid and accounted for on time? And who is tasked with ensuring Luau goes off without a hitch or that students from Saudi Arabia know how to navigate the cultural idiosyncrasies of an American university? Meet the people who work behind the scenes at Pacific University—the community of staff and faculty—as captured by Pacific’s own creative writing and photography students. Their jobs and lives are varied, but their dedication to ensuring a dynamic educational experience in all its varieties is common between them. This book strives to capture and share their stories through the creative efforts of the students their work serves.https://commons.pacificu.edu/beetree/1001/thumbnail.jp

Real-World Treatment Patterns among Patients with Alopecia Areata in the USA: A Retrospective Claims Analysis

Alopecia areata is an autoimmune disorder characterized by hair loss, for which there are few treatment options. This claims-based study characterized recent real-world treatment patterns among patients in the USA with alopecia areata, including the subtypes alopecia totalis and alopecia universalis, in the first year after diagnosis of an episode of alopecia areata. Approximately 5% of all patients (adults (age ≥ 18 years), n = 7,703; adolescents (age 12–17 years), n = 595) had alopecia totalis or alopecia universalis. Corticosteroids were the most common first-line (1L) and second-line (2L) treatments. The mean time from diagnosis of alopecia areata to initiation of 1L treatment was 2.2 days for adults and 2.6 days for adolescents; mean 1L duration was 76.9 and 64.3 days, respectively. For adults (57.5%) and adolescents (59.7%) with 2L therapy, the mean time from 1L discontinuation to 2L initiation was 57.2 and 53.6 days, respectively; the mean duration of 2L treatment was 55.5 and 50.1 days, respectively. More patients with vs without alopecia totalis or alopecia universalis initiated 2L therapy (adults: 71.9% vs 56.8%; adolescents: 71.4% vs 58.9%). The proportion of days covered during the first year post-diagnosis was 36.7% (adults) and 34.1% (adolescents). These results highlight the substantial disease burden of alopecia areata and a need for more effective treatments

Anti-ganglioside antibody internalization attenuates motor nerve terminal injury in a mouse model of acute motor axonal neuropathy

In the Guillain-Barré syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor nerve terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement-mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse nerve terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barré syndrome subforms and their chronic counterparts

Periplasmic Transit and Disulfide Bond Formation of the Autotransported Shigella Protein IcsA

The Shigella outer membrane protein IcsA belongs to the family of type V secreted (autotransported) virulence factors. Members of this family mediate their own translocation across the bacterial outer membrane: the carboxy-terminal β domain forms a β barrel channel in the outer membrane through which the amino-terminal α domain passes. IcsA, which is localized at one pole of the bacterium, mediates actin assembly by Shigella, which is essential for bacterial intracellular movement and intercellular dissemination. Here, we characterize the transit of IcsA across the periplasm during its secretion. We show that an insertion in the dsbB gene, whose gene product mediates disulfide bond formation of many periplasmic intermediates, does not affect the surface expression or unipolar targeting of IcsA. However, IcsA forms one disulfide bond in the periplasm in a DsbA/DsbB-dependent fashion. Furthermore, cellular fractionation studies reveal that IcsA has a transient soluble periplasmic intermediate. Our data also suggest that IcsA is folded in a proteinase K-resistant state in the periplasm. From these data, we propose a novel model for the secretion of IcsA that may be applicable to other autotransported proteins

The GPCR–Gαs–PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure

Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs-DREADD to activate CD8-restricted Gαs signaling and show that a Gαs-PKA signaling axis promotes CD8+ T cell dysfunction and immunotherapy failure. These data indicate that Gαs-GPCRs are druggable immune checkpoints that might be targeted to enhance the response to ICB immunotherapies

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale