Evaluation of Tricyclic Antidepressant Deprescribing in the Treatment of Diabetic Peripheral Neuropathy within Federally Qualified Health Centers.

BACKGROUND: Tricyclic antidepressants (TCAs) are a treatment option for diabetic peripheral neuropathy (DPN). Existing evidence demonstrates the prolonged use of TCA therapy increases the risk of cognitive decline and dementia, likely due to the anticholinergic effects of these medications. The anticholinergic activity is thought to contribute significantly to the observed increase in cognitive decline and dementia risks associated with long-term TCA use. There is little information available to describe the usage patterns of TCAs in DPN, particularly within underserved populations who receive care at Federally Qualified Health Centers (FQHCs). OBJECTIVES: The objective of this study was to characterize: 1) prescribing patterns of TCAs as a treatment for DPN and 2) evidence of deprescribing attempts in a FQHC population. METHODS: A retrospective chart review of electronic medical record (EMR) data for patients at two different FQHCs was performed. A convenience sample of 100 adults ≥ 18 years of age was stratified into two age groups, 18-55 years, and 55+ years. All patients had a diagnosis of Type 1 or Type 2 diabetes mellitus and had been prescribed TCAs in the previous four years and had a visit with a primary care provider (PCP) in the past 12 months. RESULTS: The study population was comprised of 100 individuals. Seventy-four of 100 were persistent users of TCAs at the time of data collection, and the mean duration of utilization was 54.8 months. In total, 104 TCAs were prescribed across 100 individual patients. Of all 104 prescribed TCAs, 66 (63%) were prescribed at a rate that exceeded thresholds associated with a higher risk of dementia. Black older adults prescribed TCAs were more likely to exceed this dose threshold. CONCLUSION: 65% of patients used TCAs with a strength, frequency, and duration that exceeded risk thresholds for dementia in an older adult population. Interventions preventing use of or deprescribing TCAs in patients with DPN should be conducted for the potential benefits of preventing or delaying cognitive impairment and promoting equitable care.

The influence of saccades on yaw gaze stabilization in fly flight.

In a way analogous to human vision, the fruit fly D. melanogaster and many other flying insects generate smooth and saccadic movements to stabilize and shift their gaze in flight, respectively. It has been hypothesized that this combination of continuous and discrete movements benefits both flight stability and performance, particularly at high frequencies or speeds. Here we develop a hybrid control system model to explore the effects of saccades on the yaw stabilization reflex of D. melanogaster. Inspired from experimental data, the model includes a first order plant, a Proportional-Integral (PI) continuous controller, and a saccadic reset system that fires based on the integrated error of the continuous controller. We explore the gain, delay and switching threshold parameter space to quantify the optimum regions for yaw stability and performance. We show that the addition of saccades to a continuous controller provides benefits to both stability and performance across a range of frequencies. Our model suggests that Drosophila operates near its optimal switching threshold for its experimental gain set. We also show that based on experimental data, D. melanogaster operates in a region that trades off performance and stability. This trade-off increases flight robustness to compensate for internal perturbations such as wing damage.

Pharmacist-led hormonal contraceptive prescribing service in a Federally Qualified Health Center: Initial implementation outcomes.

BACKGROUND: The United States has a higher rate of unintended pregnancy than many other developed countries, and Indiana's unintended pregnancy rate is above the national average. Unintended pregnancy rates are highest among low-income women. Federally Qualified Health Centers (FQHC) provide care for the underserved and uninsured patient population. OBJECTIVE: To determine the acceptability, adoption, appropriateness, and feasibility of a pharmacist-led hormonal contraception prescribing service within a FQHC through a collaborative drug therapy management protocol. METHODS: An explanatory mixed methods analysis included surveys followed by semistructured interviews. A survey was created and distributed to all patients who received the service and all providers (physicians and nurse practitioners) employed at the FQHC during service implementation. Semistructured interviews were conducted with a subset of patients and providers. RESULTS: A total of 11 patients and 8 providers completed the survey between January 1, 2022 and June 10, 2022. Of these participants, 4 patients and 4 providers completed an interview between May 1, 2022 and June 30, 2022. Both patients and providers perceived the service as acceptable and appropriate, and providers perceived implementation of the service within clinic as feasible. Ten patients received a prescription from the pharmacist; 1 patient was referred to a provider as the pharmacist was unable to prescribe the medication requested. CONCLUSION: Implementation of pharmacist prescribed hormonal contraception was perceived as acceptable, appropriate, and feasible by patients and providers. Pharmacists are perceived by patients and providers as an additional resource for hormonal contraception prescribing within a FQHC due to their clinical knowledge, efficiency, and attention paid to patients' concerns.

Wind Dispersal of Natural and Biomimetic Maple Samaras.

Maple trees (genus Acer) accomplish the task of distributing objects to a wide area by producing seeds, known as samaras, which are carried by the wind as they autorotate and slowly descend to the ground. With the goal of supporting engineering applications, such as gathering environmental data over a broad area, we developed 3D-printed artificial samaras. Here, we compare the behavior of both natural and artificial samaras in both still-air laboratory experiments and wind dispersal experiments in the field. We show that the artificial samaras are able to replicate (within one standard deviation) the behavior of natural samaras in a lab setting. We further use the notion of windage to compare dispersal behavior, and show that the natural samara has the highest mean windage, corresponding to the longest flights during both high wind and low wind experimental trials. This study demonstrated a bioinspired design for the dispersed deployment of sensors and provides a better understanding of wind-dispersal of both natural and artificial samaras.

Provider and health care team member insights for implementing a transitions of care clinic in a federally qualified health center.

OBJECTIVES: To identify medical professionals' specific insights to implementing a transitions of care (TOC) clinic in a federally qualified health center (FQHC). DESIGN: The investigators conducted focus groups during the structured 1-hour provider meetings that take place at each clinic. Each meeting was split into two 30-minute group sessions that consisted of licensed providers and of other health care team members. During the focus groups, investigators explored past experiences of care provided to patients recently discharged from hospitalizations, and the perceived benefits, barriers, and workflow for a TOC clinic. Questions used were based on the consolidated framework for implementation research (CFIR). Transcriptions were coded with the use of qualitative research data analysis software by 2 investigators independently. Initial codes were based on the CFIR constructs to identify themes in responses while remaining adaptable for any themes or discussion that the participants found important. SETTING AND PARTICIPANTS: Participants were selected via purposive sampling within FQHCs of northwest Indiana. Participants included physicians, nurse practitioners, team care nurses, pharmacists, and behavioral health consultants. RESULTS: A total of 40 participants took part in 8 focus groups. Major themes identified were inaccessibility to patient information, apprehension about implementation, lack of familiarity with transitions of care service, and FQHC patient-centered factors. Aspects of each of the 5 CFIR constructs are discussed. CONCLUSION: Participants provided numerous factors that may affect the success of this patient care intervention in an FQHC. Proper external communication with other health care providers, comprehensive assessment of patient access to necessary resources, and collaboration at the site are the most crucial factors. Many FQHCs work with scarce resources and high patient volumes; being able to develop appropriate processes for a patient care service as encompassing and important as a TOC will affect both patient and provider experience in primary care.

Operative time and cost variability for functional endoscopic sinus surgery.

BACKGROUND: Understanding the variation in costs of endoscopic sinus surgery (ESS) is critical to defining value. Current published costs of ESS have not identified potential sources of variation. Our objective was to analyze ESS costs to identify sources of variance that could guide value-improving decisions. METHODS: ESS cases (n = 1739) performed between 2008 and 2016 were identified from a database of 22 rural to tertiary facilities. Cost and time data were extracted from the database. Medical records were reviewed to confirm procedures. Three bilateral groupings were examined (n = 895 cases from 13 facilities): (1) full ESS (all sinuses); (2) intermediate ESS (total ethmoid, maxillary); and (3) anterior ESS (anterior ethmoid, maxillary). Cost and operative time were analyzed using multivariable gamma regression. RESULTS: Median costs for full, intermediate, and anterior ESS were $4281, $3716, and $2549 U.S. dollars (p < 0.001). Median durations were 87, 60, and 58 minutes (p < 0.001). Among patients with no additional procedures, those with full ESS had operative duration, total cost, and supply costs that were 1.37 (95% confidence interval [CI], 1.17 to 1.61), 1.52 (95% CI, 1.32 to 1.75), and 2.40 (95% CI, 1.76 to 3.25) times greater than anterior ESS, respectively (all p < 0.001). Intermediate ESS duration at community urban facilities was 1.87 (95% CI, 1.74 to 2.02) times that of community rural facilities (p < 0.001). CONCLUSION: Duration of surgery, extent of surgery, and location of surgery are sources of significant variation in the cost of ESS. These findings will assist healthcare policy makers, hospitals, and surgeons in optimizing the value of ESS.

A synthetic glycosaminoglycan reduces sinonasal inflammation in a murine model of chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is characterized by sustained mucosal inflammation, impaired mucociliary clearance, loss of cilia and epithelial barrier breakdown, and tissue remodeling. Certain glycosaminoglycans inhibit various inflammatory mediators, suppress bacterial growth, and provide important functions in mucosal tissue repair and mucociliary clearance. Herein, we evaluated the effects of a synthetic glycosaminoglycan, GM-1111, on the clinical signs and inflammatory tissue changes associated with CRS in mice. CRS was generated by repeated intranasal applications of Aspergillus fumigatus (A. fumigatus) extracts over 4 weeks. Mice were then intranasally administered GM-1111 (600 µg per dose, 5 times a week) or vehicle (phosphate buffered saline, PBS) for an additional 4 weeks while still being given A. fumigatus extracts to maintain a chronic inflammatory environment with acute exacerbations. Clinical signs indicative of sinonasal inflammation were recorded throughout the study. After 9 weeks, whole blood and sinonasal tissues were harvested for hematological, histological, and biochemical examination. The clinical signs, white blood cell counts, tissue markers of sinonasal inflammation, and histological changes caused by A. fumigatus extract administration were compared to the healthy (PBS vehicle) and GM-1111-treated groups (n = 12 per treatment group). Compared to vehicle-treated animals, animals treated with GM-1111 demonstrated significant reductions in clinical signs (p<0.05), degenerative tissue changes, goblet cell hyperplasia, inflammatory cell infiltration (p<0.01), innate immunity- (tlr2, tlr4, myd88, il1b, tnfa, il6, and il12) and adaptive immunity-associated (ccl11, ccl24, ccl5, il4, il5, and il13) cytokine gene expression (p<0.05 to p<0.0001) in sinonasal tissues, and serum IgE levels (p<0.01). Our data suggest that GM-1111 significantly reduces local and systemic effects of CRS-associated sinonasal inflammation.

Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic Rhinosinusitis.

Background Calgranulin C (S100A12) is an innate immune peptide at the air-mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity. Methods A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12. Results S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05). Conclusions S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.

LL-37 causes cell death of human nasal epithelial cells, which is inhibited with a synthetic glycosaminoglycan.

LL-37 is an immune peptide that regulates innate and adaptive immune responses in the upper airways. Elevated levels of LL-37 have been linked to cell death and inflammatory diseases, such as chronic rhinosinusitis (CRS). Glycosaminoglycans (GAGs) are polysaccharides that are found on respiratory epithelial cells and serve important roles in mucosal surface repair. Recent findings suggest that a synthetic glycosaminoglycan (GM-0111) can protect against LL-37-induced sinonasal mucosal inflammation and cell death in a murine model of acute RS. Herein, we elucidated the mechanisms by which LL-37 causes sinonasal inflammation and how GM-0111 can prevent these mechanisms. When challenged with LL-37, human nasal epithelial cells (HNEpCs) and mouse macrophages (J774.2) demonstrated increased release of adenosine triphosphate (ATP) and interleukin (IL)-6 and -8, as well as cell death and lysis. These cellular responses were all blocked dose-dependently by pre-treatment with GM-0111. We identified that LL-37-induced cell death is associated with caspase-1 and -8 activation, but not activation of caspase-3/7. These responses were again blocked by GM-0111. Our data suggest that LL-37 causes cellular death of HNEpCs and macrophages through the pro-inflammatory necrotic and/or pyroptotic pathways rather than apoptosis, and that a GM-0111 is capable of inhibiting these pro-inflammatory cellular events.