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1.
J Gen Intern Med ; 37(14): 3529-3534, 2022 11.
Article in English | MEDLINE | ID: mdl-36042072

ABSTRACT

BACKGROUND: The Veterans Affairs (VA) Healthcare System Rural Transitions Nurse Program (TNP) addresses barriers veterans face when transitioning from urban tertiary VA hospitals to home. Previous clinical evaluations of TNP have shown that enrolled veterans were more likely to follow up with their primary care provider within 14 days of discharge and experience a significant reduction in mortality within 30 days compared to propensity-score matched controls. OBJECTIVE: Examine changes from pre- to post-hospitalization in total, inpatient, and outpatient 30-day healthcare utilization costs for TNP enrollees compared to controls. DESIGN: Quantitative analyses modeling the changes in cost via multivariable linear mixed-effects models to determine the association between TNP enrollment and changes in these costs. PARTICIPANTS: Veterans meeting TNP eligibility criteria who were discharged home following an inpatient hospitalization at one of the 11 implementation sites from April 2017 to September 2019. INTERVENTION: The four-step TNP transitional care intervention. MAIN MEASURES: Changes in 30-day total, inpatient, and outpatient healthcare utilization costs were calculated for TNP enrollees and controls. KEY RESULTS: Among 3001 TNP enrollees and 6002 controls, no statistically significant difference in the change in total costs (p = 0.65, 95% CI: (- $675, $350)) was identified. However, on average, the increase in inpatient costs from pre- to post-hospitalization was approximately $549 less for TNP enrollees (p = 0.02, 95% CI: (- $856, - $246)). The average increase in outpatient costs from pre- to post-hospitalization was approximately $421 more for TNP enrollees compared to controls (p = 0.003, 95% CI: ($109, $671)). CONCLUSIONS: Although we found no difference in change in total costs between veterans enrolled in TNP and controls, TNP was associated with a smaller increase in direct inpatient medical costs and a larger increase in direct outpatient medical costs. This suggests a shifting of costs from the inpatient to outpatient setting.


Subject(s)
Veterans , United States/epidemiology , Humans , United States Department of Veterans Affairs , Patient Acceptance of Health Care , Rural Population , Hospitalization
2.
Int J Vasc Med ; 2022: 3786815, 2022.
Article in English | MEDLINE | ID: mdl-35712525

ABSTRACT

Background: Acute limb ischemia (ALI) is associated with significant morbidity and mortality. Novel anticoagulants reduce adverse events among patients with peripheral artery disease, though the potential effect of these therapies is unclear in patients with ALI. The present study thus sought to evaluate the potential clinical benefit of universal application of novel anticoagulants to a high-risk population of patients with ALI. Methods: In this retrospective cohort study, we identified patients diagnosed with ALI in the Veterans Affairs Healthcare System between 2015 and 2016. We then calculated the incidence of adverse cardiovascular events (death/stroke/myocardial infarction/amputation/repeat intervention) as if they were treated with rivaroxaban using published data. Further, we calculated the cost to treat a Veteran diagnosed with one of these outcomes, and the potential savings had patients been universally treated with novel anticoagulants. Results: We identified 286 patients that presented with lower extremity ALI and were not treated with anticoagulation. Potential treatment of these patients with rivaroxaban resulted in significantly fewer adverse events, with an 11.9% reduction in cases at 21 months (95% CI: 5.5-17.8%) and a 13.4% reduction in cases at 47 months (95% CI: 5.6-20.5%). This corresponded to significant decreases in healthcare spending for patients with ALI who were treated with rivaroxaban. Conclusions: Among patients with ALI, treatment with rivaroxaban could result in a significant reduction in adverse cardiovascular events. The reduction in events would in turn lead to significant decreases in healthcare spending for this population.

3.
Sci Rep ; 10(1): 15437, 2020 09 22.
Article in English | MEDLINE | ID: mdl-32963273

ABSTRACT

Photoperiod or the duration of daylight has been implicated as a risk factor in the development of mood disorders. The dopamine and serotonin systems are impacted by photoperiod and are consistently associated with affective disorders. Hence, we evaluated, at multiple stages of postnatal development, the expression of key dopaminergic (TH) and serotonergic (Tph2, SERT, and Pet-1) genes, and midbrain monoamine content in mice raised under control Equinox (LD 12:12), Short winter-like (LD 8:16), or Long summer-like (LD 16:8) photoperiods. Focusing in early adulthood, we evaluated the midbrain levels of these serotonergic genes, and also assayed these gene levels in the dorsal raphe nucleus (DRN) with RNAScope. Mice that developed under Short photoperiods demonstrated elevated midbrain TH expression levels, specifically during perinatal development compared to mice raised under Long photoperiods, and significantly decreased serotonin and dopamine content throughout the course of development. In adulthood, Long photoperiod mice demonstrated decreased midbrain Tph2 and SERT expression levels and reduced Tph2 levels in the DRN compared Short photoperiod mice. Thus, evaluating gene × environment interactions in the dopaminergic and serotonergic systems during multiple stages of development may lead to novel insights into the underlying mechanisms in the development of affective disorders.


Subject(s)
Biogenic Monoamines/metabolism , Dopamine/metabolism , Dorsal Raphe Nucleus/metabolism , Gene Expression Regulation, Developmental , Photoperiod , Serotonin/metabolism , Animals , Dorsal Raphe Nucleus/cytology , Female , Male , Mice , Mice, Inbred C3H , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Tryptophan Hydroxylase/genetics , Tryptophan Hydroxylase/metabolism , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism
4.
Neuropsychopharmacology ; 43(12): 2408-2417, 2018 11.
Article in English | MEDLINE | ID: mdl-29773909

ABSTRACT

Amphetamine abuse is a major public health concern for which there is currently no effective treatment. To develop effective treatments, the mechanisms by which amphetamine produces its abuse-related effects need to be fully understood. It is well known that amphetamine exerts its actions by targeting high-affinity transporters for monoamines, in particular the cocaine-sensitive dopamine transporter. Organic cation transporter 3 (OCT3) has recently been found to play an important role in regulating monoamine signaling. However, whether OCT3 contributes to the actions of amphetamine is unclear. We found that OCT3 is expressed in dopamine neurons. Then, applying a combination of in vivo, ex vivo, and in vitro approaches, we revealed that a substantial component of amphetamine's actions is OCT3-dependent and cocaine insensitive. Our findings support OCT3 as a new player in the actions of amphetamine and encourage investigation of this transporter as a potential new target for the treatment of psychostimulant abuse.


Subject(s)
Amphetamine/pharmacology , Central Nervous System Stimulants/pharmacology , Octamer Transcription Factor-3/biosynthesis , Animals , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , HEK293 Cells , Humans , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic
5.
ACS Chem Neurosci ; 8(5): 1053-1064, 2017 05 17.
Article in English | MEDLINE | ID: mdl-28375615

ABSTRACT

Molecular characterization of neurons across brain regions has revealed new taxonomies for understanding functional diversity even among classically defined neuronal populations. Neuronal diversity has become evident within the brain serotonin (5-HT) system, which is far more complex than previously appreciated. However, until now it has been difficult to define subpopulations of 5-HT neurons based on molecular phenotypes. We demonstrate that the MET receptor tyrosine kinase (MET) is specifically expressed in a subset of 5-HT neurons within the caudal part of the dorsal raphe nuclei (DRC) that is encompassed by the classic B6 serotonin cell group. Mapping from embryonic day 16 through adulthood reveals that MET is expressed almost exclusively in the DRC as a condensed, paired nucleus, with an additional sparse set of MET+ neurons scattered within the median raphe. Retrograde tracing experiments reveal that MET-expressing 5-HT neurons provide substantial serotonergic input to the ventricular/subventricular region that contains forebrain stem cells, but do not innervate the dorsal hippocampus or entorhinal cortex. Conditional anterograde tracing experiments show that 5-HT neurons in the DRC/B6 target additional forebrain structures such as the medial and lateral septum and the ventral hippocampus. Molecular neuroanatomical analysis identifies 14 genes that are enriched in DRC neurons, including 4 neurotransmitter/neuropeptide receptors and 2 potassium channels. These analyses will lead to future studies determining the specific roles that 5-HTMET+ neurons contribute to the broader set of functions regulated by the serotonergic system.


Subject(s)
Dorsal Raphe Nucleus/metabolism , Proto-Oncogene Proteins c-met/metabolism , Serotonergic Neurons/metabolism , Animals , Immunohistochemistry , Mice , Serotonin
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