Patient Perspectives of the Doctor-at-Home Service

Introduction. Home health care has been established as an effective model for reducing mortality in the elderly. The Doctor-at-Home Service at the Community Health Centers of Burlington (CHCB) has offered home health care to Burlington residents since January 2015. Dr. Karen Sokol, MD, alone provides care to 176 patients at their homes, including at-home palliative care. CHCB hope to expand this program by hiring more providers. Objective. To understand the impact of the Doctor-at-Home Service from the pa- tients’ perspective. Methods. A survey was administered to a cohort of eighteen patients over an 8- week period and addressed topics such as barriers to healthcare, benefits, and costs associated with doctor-at-home programs. A theme analysis on the responses was then conducted to reflect patient opinions. Available summary data describing the pa- tient population was also analyzed. Results. The Doctor- at- Home program serves patients ranging from 26 to 100 years old, with the majority of the patient population comprised of senior citizens. Prior to at home care, patients faced barriers such as lack of transportation, negative past experi- ences, anxiety, and distance from relatives. Four main themes from patient responses were physician-patient relationship, convenience, quality of care, and environment of care. Discussion. Evidence is compelling that there is a desire and need for an exten- sion of the Doctor-at-Home program to reach additional patients. Doctor-at-Home pro- grams could eliminate identified barriers and provide quality care to patients, especially those with specific barriers to access.https://scholarworks.uvm.edu/comphp_gallery/1256/thumbnail.jp

Modeling the Effects of Hyaluronic Acid Degradation on the Regulation of Human Astrocyte Phenotype Using Multicomponent Interpenetrating Polymer Networks (mIPNs)

Hyaluronic acid (HA) is a highly abundant component in the extracellular matrix (ECM) and a fundamental element to the architecture and the physiology of the central nervous system (CNS). Often, HA degradation occurs when an overreactive inflammatory response, derived from tissue trauma or neurodegenerative diseases such as Alzheimer’s, causes the ECM in the CNS to be remodeled. Herein, we studied the effects of HA content as a key regulator of human astrocyte (HAf) reactivity using multicomponent interpenetrating polymer networks (mIPNs) comprised of Collagen I, HA and poly(ethylene glycol) diacrylate. The selected platform facilities the modulation of HA levels independently of matrix rigidity. Total astrocytic processes length, number of endpoints, the expression of the quiescent markers: Aldehyde Dehydrogenase 1 Family Member L1 (ALDH1L1) and Glutamate Aspartate Transporter (GLAST); the reactive markers: Glial Fibrillary Acidic Protein (GFAP) and S100 Calcium-Binding Protein β (S100β); and the inflammatory markers: Inducible Nitric Oxide Synthase (iNOS), Interleukin 1β (IL-1β) and Tumor Necrosis Factor Alpha (TNFα), were assessed. Cumulatively, our results demonstrated that the decrease in HA concentration elicited a reduction in the total length of astrocytic processes and an increase in the expression of HAf reactive and inflammatory markers

Collagen Based Multicomponent Interpenetrating Networks as Promising Scaffolds for 3D Culture of Human Neural Stem Cells, Human Astrocytes, and Human Microglia

This work describes for the first time the fabrication and characterization of multicomponent interpenetrating networks composed of collagen I, hyaluronic acid, and poly(ethylene glycol) diacrylate for the 3D culture of human neural stem cells, astrocytes, and microglia. The chemical composition of the scaffolds can be modulated while maintaining values of complex moduli within the range of the mechanical performance of brain tissue (∼6.9 kPa) and having cell viability exceeding 84%. The developed scaffolds are a promising new family of biomaterials that can potentially serve as 3D in vitro models for studying the physiology and physiopathology of the central nervous system

Comparing Pupil Light Response Modulation between Saccade Planning and Working Memory

The signature of spatial attention effects has been demonstrated through saccade planning and working memory. Although saccade planning and working memory have been commonly linked to attention, the comparison of effects resulting from saccade planning and working memory is less explored. It has recently been shown that spatial attention interacts with local luminance at the attended location. When bright and dark patch stimuli are presented simultaneously in the periphery, thereby producing no change in global luminance, pupil size is nonetheless smaller when the locus of attention overlaps with the bright, compared to the dark patch stimulus (referred to as the local luminance modulation). Here, we used the local luminance modulation to directly compare the effects of saccade planning and spatial working memory. Participants were required to make a saccade towards a visual target location (visual-delay) or a remembered target location (memory-delay) after a variable delay, and the bright and dark patch stimuli were presented during the delay period between target onset and go signal. Greater pupil constriction was observed when the bright patch, compared to the dark patch, was spatially aligned with the target location in both tasks. However, the effects were diminished when there was no contingency implemented between the patch and target locations, particularly in the memory-delay task. Together, our results suggest the involvement of similar, but not identical, attentional mechanisms through saccade planning and working memory, and highlight a promising potential of local pupil luminance responses for probing visuospatial processing

Early neutrophil trajectory following clozapine may predict clozapine response - Results from an observational study using electronic health records

Background: Clozapine has unique effectiveness in treatment-resistant schizophrenia and is known to cause immunological side-effects. A transient spike in neutrophils commonly occurs in the first weeks of clozapine therapy. There is contradictory evidence in the literature as to whether neutrophil changes with clozapine are linked to treatment response. Aims: The current study aims to further examine the neutrophil changes in response to clozapine and explore any association between neutrophil trajectory and treatment response. Methods: A retrospective cohort study of patients undergoing their first treatment with clozapine and continuing for at least 2 years identified 425 patients (69% male/31% female). Neutrophil counts at baseline, 3 weeks and 1 month were obtained predominantly by linkage with data from the clozapine monitoring service. Clinical Global Impression- Severity (CGI-S) was rated from case notes at the time of clozapine initiation and at 2 years. Latent class growth analysis (LCGA) was performed to define distinct trajectories of neutrophil changes during the first month of treatment. Logistic regression was then conducted to investigate for association between the trajectory of neutrophil count changes in month 1 and clinical response at 2 years as well as between baseline neutrophil count and response. Results: Of the original cohort, 397 (93%) patients had useable neutrophil data during the first 6 weeks of clozapine treatment. LCGA revealed significant differences in neutrophil trajectories with a three-class model being the most parsimonious. The classes had similar trajectory profiles but differed primarily on overall neutrophil count: with low, high-normal and high neutrophil classes, comprising 52%, 40% and 8% of the sample respectively. Membership of the high-normal group was associated with significantly increased odds of a positive response to clozapine, as compared to the low neutrophil group [Odds ratio (OR) = 2.10, p-value = 0.002; 95% confidence interval (95% CI) = 1.31–3.36]. Baseline neutrophil count was a predictor of response to clozapine at 2 years, with counts of ≥5 × 109/l significantly associated with positive response (OR = 1.60, p-value = 0.03; 95% CI = 1.03–2.49). Conclusions: Our data are consistent with the hypothesis that patients with low-level inflammation, reflected in a high-normal neutrophil count, are more likely to respond to clozapine, raising the possibility that clozapine exerts its superior efficacy via immune mechanisms.</p

Improved genome editing in human cell lines using the CRISPR method

The Cas9/CRISPR system has become a popular choice for genome editing. In this system, binding of a single guide (sg) RNA to a cognate genomic sequence enables the Cas9 nuclease to induce a double-strand break at that locus. This break is next repaired by an error-prone mechanism, leading to mutation and gene disruption. In this study we describe a range of refinements of the method, including stable cell lines expressing Cas9, and a PCR based protocol for the generation of the sgRNA. We also describe a simple methodology that allows both elimination of Cas9 from cells after gene disruption and re-introduction of the disrupted gene. This advance enables easy assessment of the off target effects associated with gene disruption, as well as phenotype-based structure-function analysis. In our study, we used the Fan1 DNA repair gene as control in these experiments. Cas9/CRISPR-mediated Fan1 disruption occurred at frequencies of around 29%, and resulted in the anticipated spectrum of genotoxin hypersensitivity, which was rescued by re-introduction of Fan1

Baseline anxiety-sensitivity to estradiol fluctuations predicts anxiety symptom response to transdermal estradiol treatment in perimenopausal women - A randomized clinical trial

BACKGROUND: The menopausal transition (perimenopause) is associated with an increased risk of major depression, characterized by anxiety and anhedonia phenotypes. Greater estradiol (E2) variability predicts the development of perimenopausal depression, especially within the context of stressful life events (SLEs). While transdermal E2 (TE2) reduces perimenopausal depressive symptoms, the mechanisms underlying TE2 efficacy and predictors of TE2 treatment response remain unknown. This study aimed at determining relationships between E2 fluctuations, mood symptoms, and physiologic stress-reactivity (cortisol and interleukin-6) and whether differences in mood-sensitivity to E2 fluctuations predict mood responses to TE2 treatment. METHODS: This randomized, double-blind, placebo-controlled trial investigated medically healthy women (46-60 years) in the early or late menopause transition. Baseline E2-sensitivity strength was calculated from eight weekly individual correlations between week-to-week E2 change and index week anxiety (State-Trait Anxiety Inventory) and anhedonia (Snaith-Hamilton Pleasure Scale). Women then received eight weeks of TE2 or transdermal placebo. RESULTS: Analyses included 73 women (active TE2 n = 35). Greater baseline E2 fluctuations predicted greater anhedonia (p = .002), particularly in women with more SLEs. Greater E2 fluctuations also predicted higher cortisol (p = .012) and blunted interleukin-6 (p = .02) stress-responses. Controlling for baseline symptoms, TE2 was associated with lower post-treatment anxiety (p &lt; .001) and anhedonia (p &lt; .001) versus placebo. However, the efficacy of TE2 for anxiety (p = .007) and also for somatic complaints (p = .05) was strongest in women with greater baseline E2 sensitivity strength. CONCLUSIONS: TE2 treatment reduced perimenopausal anxiety and anhedonia. The ability of baseline mood-sensitivity to E2 fluctuations to predict greater TE2 efficacy has implications for individualized treatment of perimenopausal anxiety disorders