Influence of Depression on Treatment and Survival: A Population-based Study in Patients with Breast Cancer in Kentucky

This capstone project describes the results of a consultative experience in biostatistics

Changes in Buprenorphine Prescribing during the COVID-19 Pandemic in Kentucky

Buprenorphine is a medication approved by the U.S. Food and Drug Administration (FDA) to treat opioid use disorder (OUD). There were concerns that the COVID-19-related restrictions would interfere with the in-person prescribing of buprenorphine. In response to the COVID-19 public health emergency declaration, the Drug Enforcement Administration (DEA), partnering with the Substance Abuse and Mental Health Services Administration (SAMHSA), adopted policies to relax buprenorphine prescribing regulations [1], authorizing practitioners to prescribe buprenorphine to existing patients via telemedicine (as of Mar 16, 2020) and new patients via telephone without first having an in-person or telemedicine visit (as of Mar 31, 2020)[2]. This study evaluated the significance of the immediate changes in buprenorphine prescribing in Kentucky after the implementation of the new federal policies on buprenorphine prescribing for OUD treatment

Implementation and Sustainment of a Statewide Telemedicine Diabetic Retinopathy Screening Network for Federally Designated Safety-Net Clinics

CONTEXT: Diabetic retinopathy (DR) is the leading cause of incident blindness among working-age adults in the United States. Federally designated safety-net clinics (FDSC) often serve as point-of-contact for patients least likely to receive recommended DR screenings, creating opportunity for targeted interventions to increase screening access and compliance. STUDY DESIGN AND METHODS: With such a goal, we implemented and assessed the longitudinal performance of an FDSC-based telemedicine DR screening (TDRS) network of 22 clinical sites providing nonmydriatic fundus photography with remote interpretation and reporting. Retrospective analysis of patient encounters between February 2014 and January 2019 was performed to assess rates of pathology and referral. A generalized estimating equation logistic regression model was used for subset analysis from audits of pre- and post-implementation screening rates. Finally, patient surveys were conducted and assessed as a measure of intervention acceptability. RESULTS: Of the 13,923 individual telescreening encounters (4327 female, 4220 male, and 5376 unspecified; mean [SD] age, 54.9 [12.5] years) studied, 10,540 were of adequate quality to identify 3532 (33.5%) patients with ocular pathology: 2319 (22.0%) patients had some level of DR with 1604 (15.2%) requiring specialist referral, and 808 (7.7%) patients required referral for other ocular pathologies. The mean screening rate for audited clinics in the year prior to program implementation was 29.9% (641/2147), which increased to 47.7% (1012/2124) in the program’s first year, doubling patients’ odds of being screened (OR 2.2; 95% CI: 1.3–3.7; P = .003). These gains were sustained over four years following implementation (OR 1.9; 95% CI: 1.1–3.1; P = .018) despite varied clinic screening performance (4-year averaged range, 22.9–55.1%). Odds of early detection likewise doubled for patients with consecutive screenings (OR 2.2, 95% CI: 2.0–2.4; P \u3c .001). Finally, surveyed patients preferred TDRS to specialist exams (82.5%; 776/941) and would recommend the service to friends (92.7%; 868/936). CONCLUSION AND RELEVANCE: A statewide, FDSC-centered TDRS network was successfully established and sustained in a medically underserved region of the United States. Our results suggest that large TDRS networks in FDSCs can increase screening access and compliance for otherwise unscreened populations, but outcomes can vary greatly among clinics. Further work to optimize program implementation is needed to maximize this model\u27s impact

Patterns of Buprenorphine Initiation Treatment for Opioid Use Disorder and Association with Opioid-related Overdose Deaths

Oral presentation at the 38th International Society for Pharmacoepidemiolog

Observation of many-body Fock space dynamics in two dimensions

Quantum many-body simulation provides a straightforward way to understand fundamental physics and connect with quantum information applications. However, suffering from exponentially growing Hilbert space size, characterization in terms of few-body probes in real space is often insufficient to tackle challenging problems such as quantum critical behavior and many-body localization (MBL) in higher dimensions. Here, we experimentally employ a new paradigm on a superconducting quantum processor, exploring such elusive questions from a Fock space view: mapping the many-body system onto an unconventional Anderson model on a complex Fock space network of many-body states. By observing the wave packet propagating in Fock space and the emergence of a statistical ergodic ensemble, we reveal a fresh picture for characterizing representative many-body dynamics: thermalization, localization, and scarring. In addition, we observe a quantum critical regime of anomalously enhanced wave packet width and deduce a critical point from the maximum wave packet fluctuations, which lend support for the two-dimensional MBL transition in finite-sized systems. Our work unveils a new perspective of exploring many-body physics in Fock space, demonstrating its practical applications on contentious MBL aspects such as criticality and dimensionality. Moreover, the entire protocol is universal and scalable, paving the way to finally solve a broader range of controversial many-body problems on future larger quantum devices.Comment: 8 pages, 4 figures + supplementary informatio

OPIOID USE DISORDER TREATMENT WITH BUPRENORPHINE: ANALYSIS OF TREATMENT UTILIZATION AND ASSOCIATED OUTCOMES IN KENTUCKY

Opioid use disorder (OUD) is chronic opioid use that results in clinically significant suffering, impairment, or even death. The opioid epidemic in the United States has become a public health and economic crisis, affecting patients\u27 well-being and the nation\u27s overall health and welfare. Eastern Kentucky was among the first regions affected by the opioid crisis, and Kentucky has historically ranked among the top five states for age-adjusted drug overdose mortality rate. There are three medications (buprenorphine, methadone, naltrexone) approved by the U.S. Food and Drug Administration to treat OUD. As a partial opioid agonist, buprenorphine is a safe medication for OUD (MOUD) because of its ceiling effect, in which higher doses do not increase the risk of respiratory depression in the event of an overdose. While buprenorphine treatment, primarily with the transmucosal (TM) buprenorphine formulations, has increased since its approval in 2002, there are still substantial barriers to the availability and access, with most OUD patients never receiving MOUD. The characteristics of early-stage buprenorphine treatment may affect long-term success. Within the first 30 days of treatment, the discontinuation rate is the highest. In the dissertation’s studies, we evaluated the utilization of buprenorphine treatment for OUD and associated opioid-related overdose deaths in Kentucky. The first study, titled “Changes in Transmucosal Buprenorphine Utilization for Opioid Use Disorder Treatment during the COVID-19 Pandemic in Kentucky,” examined the changes in buprenorphine prescribing for OUD treatment following the COVID-19 emergency declaration from 2019 to 2020 in Kentucky, using a segmented regression analysis for an interrupted time series design. The study reported a drop in the TM buprenorphine MOUD utilization in the first weeks of COVID-19 national emergency for both urban and rural residents, followed by gradual increase that may have been facilitated by the relaxed buprenorphine prescribing regulations by federal agencies. The second study, titled Characteristics of buprenorphine initiation treatment for opioid use disorder and association with the incidence of opioid-related overdose deaths, explored the associations between characteristics of buprenorphine treatment within the first 30 days of treatment and the incidence of opioid-related overdose deaths in the following 12-month period. To account for the competing risks of deaths from causes other than opioid-related overdose deaths, we utilized Fine and Gray proportional subdistribution hazard models to evaluate the associations. The findings suggest that higher dosages and greater patient compliance (a higher proportion of days covered in treatment) within the first 30 days of treatment were associated with a decreased incidence of opioid-related overdose deaths. In the context of the rising number of overdose deaths, the results of this dissertation provide information for making data-driven decisions regarding OUD treatment, and it highlights the significance of treatment decisions and patient compliance during the first month of buprenorphine treatment, to inform the design of future studies

Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of RORγt+ Treg cell-mediated immune tolerance in neonates

ABSTRACTGestational diabetes mellitus (GDM) is an increasing public health concern that significantly increases the risk of early childhood allergic diseases. Altered maternal milk glycobiome may strongly affect gut microbiota and enteric-specific Treg cell-mediated development of immune tolerance in GDM infants. In this study, we found that, compared with healthy Chinese mothers, mothers with GDM had significantly lower levels of total and specific human milk oligosaccharides (HMOs) in their colostrum that subsequently increased with extension of lactation. This alteration in HMO profiles significantly delayed colonization of Lactobacillus and Bifidobacterium spp. in their breast-fed infants, resulting in a distinct gut microbial structure and metabolome. Further experiments in GDM mouse models indicated that decreased contents of milk oligosaccharides, mainly 3ʹ-sialyllactose (3ʹ-SL), in GDM maternal mice reduced colonization of bacteria, such as L. reuteri and L. johnsonii, in the neonatal gut, which impeded development of RORγt+ regulatory T (Treg) cell-mediated immune tolerance. Treatment of GDM neonates with 3ʹ-SL, Lactobacillus reuteri (L. reuteri) and L. johnsonii promoted the proliferation of enteric Treg cells and expression of transcription factor RORγt, which may have contributed to compromising ovalbumin (OVA)-induced allergic responses. In vitro experiments showed that 3ʹ-SL, metabolites of L. johnsonii, and lysates of L. reuteri stimulated differentiation of mouse RORγt+ Treg cells through multiple regulatory effects on Toll-like receptor, MAPK, p53, and NOD-like receptor signaling pathways. This study provides new ideas for the development of gut microbiota and immune tolerance in GDM newborns

Bystander preference for naloxone products: a field experiment

Abstract Background Bystander administration of naloxone is a critical strategy to mitigate opioid overdose mortality. To ensure bystanders’ willingness to carry and administer naloxone in response to a suspected overdose, it is critical to select products for community distribution with the highest likelihood of being utilized. This study examines bystanders’ preference for and willingness to administer three naloxone products approved by the FDA for bystander use and identify product features driving preference. Methods The population was a convenience sample of individuals who attended the Kentucky State Fair, August 18–28, 2022, in Louisville, Kentucky. Participants (n = 503) watched a standardized overdose education and naloxone training video, rated their willingness to administer each of three products (i.e., higher-dose nasal spray, lower-dose nasal spray, intramuscular injection), selected a product to take home, and rated factors affecting choice. Results After training, 44.4% chose the higher-dose nasal spray, 30.1% chose the intramuscular injection, and 25.5% chose the lower-dose nasal spray. Factors most influencing choice on a 10-point Likert scale were ease of use (9 [7–10]), naloxone dose (8 [5–10]), and product familiarity (5 [5–9]). Conclusions Bystanders expressed high willingness to administer all studied formulations of naloxone products. Product choice preference varied as a function of product features. As the number and variety of available products continue to increase, continuous evaluation of formulation acceptability, in addition to including individuals with lived experience who are receiving and administering overdose reversal agents, is critical to support adoption and save lives