Ensuring Safe Prescription Opioid Use, Storage, and Disposal for Adolescents Undergoing Surgery

Principal Investigator: Lorraine Kelley-Quon, MD, MSHS, Assistant Professor School/Dept: Keck School of Medicine

Co-Investigator: Rachel Ceasar, PhD, Assistant Professor

School/Dept: KSOM Department of Population and Public Health Sciences

Co-Investigator: Alvina Rosalies, PhD, Lead Clinical Psychologist & Co-Director of Pain Medicine Rehabilitation Program

School/Dept: Division of Pain Medicine at CHLA

Status: Complete

Funding Amount: $50,000

Abstract:  Background: Unused prescription opioids in the home contribute to diversion, misuse, and abuse in adolescents. With more than 70% of adolescents reporting unused opioids after surgery, families need education regarding safe prescription opioid use, storage, and disposal while surgeons must tailor prescriptions to actual patient use.

Methods: Adolescents 13-20y who recently underwent surgery (n=16) at CHLA and their parents (n=16) will be recruited to 4 focus groups: 2 Spanish-speaking, 2 English-speaking. Focus group interviews will elicit respondents’ experiences and knowledge of prescription opioids. Respondents will also reflect on an educational handout published by the American College of Surgeons. Grounded theory will identify conceptual categories. Focus group feedback will be used to create a new opioid educational brochure. In parallel, a survey of pediatric surgeons (n=20) at CHLA will be conducted. Surgeons will review clinical vignettes and report the number of opioid pills they would prescribe. Surgeon-reported prescribing will be compared to actual prescription opioid use, shared with surgeon respondents, and surgeons will reflect on future changes in prescribing.

Results: Themes centered around concern for prescription opioid misuse, health literacy, and language will likely be incorporated in the updated educational brochure. Surgeons will over-estimate the number of opioid pills used after surgery. Also, when surgeons are presented with actual prescription opioid use, they will prescribe fewer opioid pills for future patients.

Conclusions: The expected outcomes will be (1) an educational intervention tailored to the diverse needs of families with adolescents undergoing surgery and (2) changes in surgeon opioid prescribing patterns based on real-world data.

Phase 1 Dose-Escalation Study of Dihydromyricetin (DHM) to Treat Alcohol-Associated Liver Disease

Principal Investigator: Brian Lee, MD, MAS, Assistant Professor of Medicine

School/Dept: Keck School of Medicine

Co-Investigator: Daryl Davies, PhD, Professor in Clinical Pharmacy

School/Dept: USC Alfred E. Mann School of Pharmacy

Co-Investigator: Norah Terrault, MD, MPH, Professor of Medicine, Chief, Division of GI and Liver

School/Dept: Keck School of Medicine

Co-Investigator: Neil Kaplowitz, MD, Professor of Medicine

School/Dept: Keck School of Medicine

Co-Investigator: Joshua Silva, PhD, Post-Doctorate in Clinical Pharmacy

School/Dept: USC Alfred E. Mann School of Pharmacy

Status: In-progress

Funding Amount: $49,954

Abstract:  Alcohol-associated liver disease (ALD) accounts for half of liver-related mortality, and almost $10 billion dollars in annual healthcare costs in the United States. There are no FDA approved therapies for ALD, and novel therapies are critically needed.

Our team has recently shown pre-clinical evidence that dihydromyricetin (DHM), a bioactive flavonoid from an edible plant (ampelopsis grossedentata), can potentially reduce/prevent ALD through changes in hepatocellular bioenergetics and mitochondrial biogenesis driven by the AMPK/Sirt-1/PGC-1α axis. Further study of DHM in humans is warranted. There have been no controlled human studies published that have assessed the safety, pharmacokinetics, or optimal dosing of DHM in humans, which is necessary for regulatory approval.

The current proposal is a first-in-human Phase 1 open-label, dose-escalation study to assess the

safety, pharmacokinetics, and the maximum tolerated dose of DHM among healthy volunteers and those with alcohol use disorder and mild ALD using a purified form of DHM from a local cGMP compliant source. We will perform a single, escalating dose study, to study the PK of DHM among healthy individuals in Aim 1, and among individuals with alcohol use disorder with non-cirrhotic ALD in Aim 2.

Completion of the two Aims will significantly advance our understanding regarding DHM (currently available as a dietary supplement) and will support an R21 application to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for a phase 2b multidose and efficacy study of DHM as a novel therapeutic agent for ALD.

Examining the Impact of Cannabis Legalization on Maternal Health Disparities

Principal Investigator: Rachel Ceasar, PhD, Assistant Professor of Clinical Population and Public Health SciencesSchool/Dept:                             

Keck School of Medicine

Co-Investigator: Rosalie Liccardo-Pacula, PhD, Elizabeth Garrett Chair in Health Policy, Economics and Law, and Professor

School/Dept: USC Sol Price School of Public Policy

Status: In-progress

Funding Amount: $68,396

Abstract:  Cannabis is the most commonly used substance during pregnancy. Due to a lack of evidence on efficacy and safety, women are advised not to use cannabis in pregnancy. Yet these recommendations are being made in a context in which policies and perceptions about cannabis use are becoming increasingly acceptable. Community perceptions of maternal cannabis use and risk, and its impact on maternal health disparities remain largely unexplored. Yet these data are urgently needed given expanding legalization, incomplete information about the safety of cannabis during pregnancy, and recent increases in prenatal cannabis use. For the proposed IAS pilot study, we posit that expanding legalization and increasing social acceptability and accessibility of cannabis may worsen existing maternal health disparities. This study will examine how maternal health stakeholders and cannabis retailers perceive cannabis use and its impact on maternal health disparities in BIPOC communities in Los Angeles, California, where adult cannabis use is legal. Using semi-structured qualitative interviews with 15 maternal health stakeholders and 15 cannabis retailers in Los Angeles that serve BIPOC communities (N=30), the proposed study will be one of the first to identify community-level perceptions of cannabis risk, social and structural level influences impacting health disparities, and use 2 patterns. This study advances the scope of Dr. Ceasar’s ongoing research on maternal cannabis use perceptions among pregnant Latinx women in Los Angeles. Findings will provide preliminary data for an R01 on assessing the efficacy of an implementation

Understanding E-cigarette Use, Smoking Risk, and Cessation Needs Among Young Adults

Principal Investigator: Denise Tran, PhD, Assistant Professor of Clinical Psychiatry and the Behavioral Sciences

School/Dept: Keck School of Medicine

Co-Investigator: Eric Pedersen, PhD, Associate Professor of Psychiatry and the Behavioral Sciences

School/Dept: Keck School of Medicine

Co-Investigator: Jordan Davis, PhD, Associate Professor

School/Dept: USC Suzanne Dworak-Peck School of Social Work

Status: Complete

Funding Amount: $14,400

Abstract:

This study aims to qualitatively identify factors that are associated with e-cigarette use (i.e., vaping) initiation, frequent (vs. less frequent use), smoking risk, and barriers to quitting vaping among young adults. We also aim to gather feedback about e-cigarette users’ preferences and thoughts about what they believe should be included in a vaping intervention that would garner acceptability and engage young adults in vaping cessation efforts. To accomplish these aims, we propose to conduct focus group discussions among 40 young adults who are between the ages of 18 and 24 and currently vape nicotine. Guided by Social Norms Theory and Theory of Reasoned Action, we also intend to gather information about normative beliefs (i.e., how prevalent and accepting a behavior is among one’s peer group) and outcome expectancies associated with both vaping and cigarette smoking. Among participants who have begun smoking, we also propose to identify any novel factors that may have facilitated their transition from vaping to smoking (Aim 1). Because information about potential barriers and facilitators of vaping cessation for young individuals are relatively novel areas of research, this aim will largely be exploratory (Aim 2). Lastly, to guide future intervention work, we will also identify content that young adult e-cigarette users believe may discourage further vaping and reduce smoking susceptibility; and intervention components that young individuals believe to be most engaging, feasible, and valuable (Aim 3). This work may offer novel insights that are critical to advancing vaping cessation research and practice among youth adults.

Social Disconnection, Addiction, and the Brain Opioid Theory of Social Attachment

Principal Investigator: Nina C. Christie, MPH (c), PhD (c)

School/Dept: KSOM Department of Population and Public Health Sciences, Psychology

Co-Investigator: John R. Monterosso, Associate Professor of Psychology

School/Dept: USC Dornsife College of Letters, Arts, and Sciences

Co-Investigator: Gail M. Lucas, Research Assistant Professor

School/Dept: USC Department of Computer Science

Status: Complete

Funding Amount: $14,596

Abstract:  Background: COVID-19 has highlighted the importance of social connection for well-being.

Substance use is a well-documented coping mechanism for social distress: both therapeutic

interventions and neuroscience research indicate strong links between social disconnection and

addiction. Moreover, given the central role of the endogenous opioid system in social

attachment, it is possible that social pain (e.g., rejection, isolation) is an especially important

factor in opioid dependence and relapse. Consistent with this, relative to alcohol, marijuana and

methamphetamine, the acute subjective experience of opioids include stronger positive social

(but not non-social) emotional experience (see preliminary data). Approach: In Experiment 1

we will investigate the perceived impact of hypothetical emotional events (social and non-social)

on risk of relapse. Participants reporting past drug problems (opioids, alcohol, marijuana and

methamphetamine, 80 in each group) will estimate relapse risk. We hypothesize that perceived

risk of relapse during opioid recovery will be particularly affected by negative social experiences.

In Study 2 (pilot study) we will use functional Magnetic Resonance Imaging (fMRI) to examine

neural response to social and non-social evocative images in a set of individuals in recovery

from opioid or methamphetamine dependence, and a comparison group. We hypothesize that

individuals with a history of chronic opioid use will evidence an exaggerated neural response to

images of social distress, relative to other groups. These preliminary data will support a planned

NIH grant application.

Neural Substrates of Social Reward Deficits in Comorbid Treatment-Resistant Depression and Nicotine

Principal Investigator: Xiao Liu, MA, PhD student

School/Dept: USC Dornsife College of Letters, Arts, and Sciences

Co-Investigator: Assal Habibi, PhD, Associate Professor

School/Dept: USC Dornsife College of Letters, Arts, and Sciences

Co-Investigator: Adam Leventhal, PhD, Professor of Population and Public Health Sciences

School/Dept: USC Institute for Addiction Science

Co-Investigator: John R. Monterosso, Associate Professor of Psychology

School/Dept: USC Dornsife College of Letters, Arts, and Sciences

Co-Investigator: Stephen Read, PhD, Professor of Psychology

School/Dept: USC Dornsife College of Letters, Arts, and Sciences

Status: Complete

Funding Amount: $14,400

Abstract:

Almost one-third of individuals with Major Depression also suffer from a substance use disorder, and comorbidity is associated with greater social and personal impairments. Social functioning deficits have been extensively studied in relation to depression and have been linked to underlying impairments in social reward processing. Therefore, individuals who have Treatment-Resistant Depression (TRD) may be at greater risk of turning to addictive substances such as nicotine to enhance social pleasure and functioning. Anhedonia is the inability to experience pleasure from reward and is a core symptom of both TRD and nicotine withdrawal. However, the specific deficits in reward valuation and salience networks resulting in anhedonia in the social domain has not been extensively studied and is not well understood in comorbid TRD with Nicotine Dependence. Therefore, we propose a multimodal study to address the gap in knowledge on the (1) acute enhancing effects of nicotine and (2) the anhedonic effects of chronic nicotine exposure on neural activity to rewarding social cues in a population of individuals with TRD. We will use both electroencephalogram recording (EEG) and functional magnetic resonance imaging (fMRI) to temporally and spatially dissociate brain activity related to anticipation and consummation of social reward. By illuminating the deficits in social reward processing we hope to provide the basis for novel targeted therapeutic approaches to prevent the cycle of self-medicating and addiction in people suffering from depression.

Mixed Methods Study Evaluating Multi-level Factors Associated With the Treatment of Injection Drug Use Related to Infective Endocarditis (IDU-IE)

Principal Investigator: Sid S. Ganesh, AB, BS, Doctoral Student

School/Dept: Keck School of Medicine

Co-Investigator: Ricky Bluthenthal, PhD, Associate Dean for Social Justice, Professor

School/Dept: KSOM Department of Population and Public Health Sciences

Co-Investigator: Alice Cepeda, PhD, Associate Professor

School/Dept: USC Suzanne Dworak-Peck School of Social Work

Co-Investigator: Todd W. Schneberk, MD, MS, MA, Resident Physician, Emergency Medicine

School/Dept: Los Angeles General Medical Center

Co-Investigator:  Emily Johnson, MD, Resident Physician, Emergency Medicine

School/Dept: Keck School of Medicine

Status: Complete

Funding Amount: $9,000

Abstract:

Injection drug use related infective endocarditis (IDU-IE) is a bacterial infection of the heart valve. If left

untreated/undertreated, IDU-IE results in significant morbidity and mortality (Cahill & Prendergast, 2016). The

number of IDU-IE cases has increased by 238% between 2013-2017 in Pennsylvania and by 440% from

2011-2016 in New Hampshire (de Gijsel et al., 2020). Studies indicate that using ICD-10 codes to identify

IDU-IE patients, data results in uncounts (up to 36%) and misclassifies (56%) as compared to manually

identified patients (Marks et al, 2020) suggesting an urgent need to develop retrospective methods to identify

true positive cases of IDU-IE.

Patient Directed Discharges (PDD), formerly known as Against Medical Advice (AMA) discharges, are

more prevalent among people who use drugs (PWUD) due to lack of initiation of Medication Assisted

Treatment (MAT); PDD leads to poor outcomes for IDU-IE due to lack of treatment completion (Suzuki et al.,

2020 & Nolan et al., 2020). At the same time, the lack of specific guidelines surrounding IDU-IE leaves room

for provider bias to impact treatment standards (Hayden et al., 2020 & An et al., 2020) – and evidence

suggests that this subjectivity allows for consideration of bioethical themes of futility and rationality, serving as

avenues for disparate treatment of PWUD (Hayden et al., 2020). The goal of this study is to identify an

effective way to find IDU-IE patients via their medical records, to examine factors associated with completion of

treatment for IDU-IE, and to qualitatively describe treatment standards for key IE patients.