Year 4. July 14. Science Monday
Our department is a community of remarkable scholars who work tirelessly to support our strategic vision of LEADING in innovation, TRANSFORMING care, and ADVANCING health for all. I invite you to learn from a sample of recently published studies across multiple divisions; they span a wide swath of research questions and approaches that have provided important insights in the past three months. I hope you will agree that our research accomplishments represent important contributions to the health of our communities and that by highlighting these advances, we underscore our commitment to supporting research in our department. Use these and many other examples to tell stories beyond our walls to the broader community and policymakers to educate them of the importance of maintaining public support for research and innovation.
Max Jordan Nguemeni Tiako, MD, MS Finds ER Pain Treatment Gaps for Black Patients Increases Risk of Opioid Misuse
Advancing health for all is a core commitment of the UCLA Department of Medicine (DoM), and we pursue this by advancing health disparities research and policy that promote health equity. A new study led by Max Jordan Nguemeni Tiako, MD, MS, faculty in the UCLA Division of General Internal Medicine and Health Services Research (GIM-HSR) brings to light an important problem and advances potential solutions: Dr. Nguemeni’s team demonstrated that Black emergency room patients who are denied opioid pain medication despite expressing their preference for it are at greater risk of later opioid misuse, and that self-reported satisfaction with pain treatment reduces this risk — even if a patient is not prescribed the medication they wanted.
“Patients' satisfaction with pain care — especially when their preferences aren’t met — can reduce their risk of future opioid misuse, highlighting the importance of feeling heard and respected,” said Dr. Nguemeni, who recently celebrated his one-year anniversary at UCLA. “Clinicians should recognize that undertreating pain or disregarding patient preferences, particularly among Black patients who historically experience discrimination when seeking care, especially pain care, and are often weary of it, may push them toward unofficial channels, increase opioid misuse risk and worsen disparities.”
For Dr. Nguemeni’s study, the results of which were published on June 25 in the Journal of General Internal Medicine, he and a team of co-investigators from the University of Pennsylvania and Brigham & Women’s Hospital sought to answer three questions. First, in situations where it was equally reasonable to prescribe or not prescribe a short course of opioids for acute pain, are patients whose request for opioids is not honored at a higher risk of later opioid misuse three months later? Second, is this more frequently seen among Black patients — whose medication preferences are more often ignored than white patients — and does self-reported satisfaction with pain treatment change the later likelihood of opioid misuse, even if their preference is unmet?
To find out, Dr. Nguemeni and his team used data from a randomized, controlled, multi-center trial of 735 emergency room patients with acute pain who were already enrolled in a study about personalized opioid risk communication. They followed the patients for three months and surveyed them at days 1, 7, 14 and 90 after their visit. After being randomized into one of the study groups, the subjects were asked whether they preferred opioids, NSAIDS, both, or neither for their pain medication, and providers were informed of their preferences.
On the day after their visit, the subjects were asked to rate their satisfaction with the pain medication they received. On day 90, they completed a questionnaire called the “Current Opioid Misuse Measure”, a tool that estimates the risk of opioid misuse. Dr. Nguemeni and his team used this data to examine how race, unmet pain treatment preference, and satisfaction with their care interacted to influence patients’ risk of opioid misuse.
Dr. Nguemeni is already digging deeper into his findings to see if he can figure out what constitutes “satisfaction” with pain care. During our last DoM Research Day, he presented evidence that shared decision-making and trust in providers predict how satisfied patients will be with their pain treatment, even if their preference for opioid pain medication is not honored. He is complementing this work with additional research on administrative claims to see if his findings in the recently published study can be replicated with a much larger sample — a key factor that would help inform policy discussions. While his results are unpublished, they preliminarily suggest that clinicians talking to patients about pain treatment and conveying their desire to get the best outcomes go a long way in helping them feel satisfied, regardless of whether or not they receive the medication they want.
“The takeaway for me, which I find very applicable to every day clinical practice, is that first, it is really crucial to engage in true shared decision-making, especially in pain care,” Dr. Nguemeni said. “Second, engaging with patients in a way that is genuine such that they feel that we care about them can often go a long way, especially for patients who have reasons to be weary of mistreatment or discrimination when they are seeking care.”
Congratulations, Max, on publishing this important study! I look forward to what comes next for your crucial area of research.
Exercise Prevents Aortic Stiffness by Modulating Neuro-Immune Interaction, Jae Min Cho, PhD, and Team Find
Artery stiffness is a key risk factor for high blood pressure, heart failure, and organ damage, but many questions remain about how and why it develops. One major mystery involves the outer layer of the aorta — known as the adventitia — and the nerves and immune cells within it. Now, post-doctoral scholar Jae Min Cho, PhD, along with a team of scientists from Tzung K. Hsiai, MD, PhD's cardiovascular bioengineering lab, and Mark W. Chapleau, PhD, at the University of Iowa, has made progress thanks to a new study in mice that shows how habitual exercise can influence the interactions between nerve and immune cells in the adventitia to reduce aortic stiffening. The team also demonstrated that regular exercise could prevent this interaction and, consequently, aortic stiffness. An article about their work was published on April 30 in Circulation Research.
This is important for patients because aortic stiffness worsens with aging or disease and contributes to cardiovascular conditions like hypertension, especially for patients whose physical limitation may prevent them from regular exercise,” Dr. Cho said. “Understanding the mechanotransduction mechanisms underlying regular exercise and how sympathetic nerve axons interact with the immune cells and fibroblasts can influence aortic stiffness, which may lead to the identification of targeted therapies for our patients who cannot perform physical activity.”
To understand how immune cells and nerve cells interact in the adventitia, the researchers used a combination of pharmacological and surgical methods to denervate sympathetic nerves, depleted circulating macrophages using pharmacological and genetic techniques, and performed an analysis called single-cell RNA sequencing to document the cellular and molecular reprogramming in the adventitia. They tested the effects of exercise using mice given an infusion of angiotensin II, using the voluntary wheel running system.
The experiments showed how exercise reduces the interaction between sympathetic nerves and a specific group of immune cells, macrophages in the aortic adventitia, leading to lower inflammation and communication with the extracellular matrix-producing fibroblasts, which decreases arterial elasticity. The team utilized the well-recognized angiotensin II infusion model to simulate the arterial stiffness. It demonstrated increased sympathetic nerve fibers in the adventitia, causing them to release excess norepinephrine and activate the beta-2 adrenergic receptors on circulating macrophages in the adventitia. Exercise countered the effects of angiotensin II in the mouse models.
“Overall, our results show that exercise prevents aortic stiffness by mitigating the neuro-immune interaction in the aortic adventitia,” Dr. Cho said.
He and the team’s next plan is to study how exercise affects interactions between vasculature and the immune system, focusing on mechanosensitive pathways and spatial transcriptomic profiling to translate their findings into a clinical trial. They feel fortunate to be able to carry out their work in the UCLA Department of Medicine. “The DoM provides a highly collaborative and interdisciplinary environment ideal for this research. It brings together experts in the cardiovascular physiology, immunology, and neuroscience fields that are the central axis of our study of neuroimmune regulation of vascular stiffness,” Dr. Cho added. “The department also offers access to cutting-edge technologies, such as single-cell sequencing, advanced imaging, and animal models, which are critical for our work.”
Congratulations to all on your exciting progress, and these important insights!
Activation of Key Estrogen Receptor Could Fight Metabolic Disease
While a growing body of research has suggested that reduced activity of estradiol — a form of estrogen — is linked to obesity and insulin resistance, it was unclear exactly what the hormone was doing in cells and tissues that was so important to metabolic health, especially in men. A new study led by corresponding author Andrea Hevener, PhD and first author Zhenqi Zhou, PhD, scientists and professors of medicine in the division of endocrinology, offers some answers: Dr. Hevener and her team found that the expression of a gene called Esr1 in the muscle is critical for mitochondrial function and metabolic health in male mice, and that tissue-selective activation of the receptor that the gene encodes, estrogen receptor alpha (ERa), can fight metabolic-related disease in both male and female mice.
A journal article describing the study was published May 5 in Cell Reports Medicine. In it, Dr. Hevener explained how her team used mouse models that either had muscle-specific loss or gain of Esr1 to show that the gene promotes mitochondrial DNA replication and health in a way that is important to metabolic function and insulin action in skeletal muscle. Additionally, genetically altered male and female mice in which human ERa was over-expressed maintained their metabolic health even when they were fed a diet designed to induce metabolic disease. Their mitochondria also adapted better to exercise than control animals.
“Our findings indicate that muscle expression of Esr1 is critical for the maintenance of mitochondrial function and metabolic health in males and that tissue-selective activation of ERα can be leveraged to combat metabolic-related diseases in both sexes,” the researchers wrote in their paper.
To Drs. Hevener and Zhou, the DoM provides a uniquely interdisciplinary environment that facilitates the kind of collaboration required to make discoveries that could have a big impact on patients.
“The DoM offers access to cutting-edge core facilities, robust mentorship, and a culture that encourages cross-disciplinary innovation — all of which are essential for advancing my research goals and for generating impactful findings with clinical relevance,” Dr. Hevener said.
Dr. Hevener’s team included DoM faculty and post-doctoral scholars from the divisions of endocrinology, geriatrics and cardiology. Congratulations to all on an impressive paper!
Adding an Intranasal Drug to Tuberculosis Regimen Speeds Up Cure in Mice, UCLA Researchers Find
Tuberculosis is one of the deadliest infectious diseases but can take as long as six to eight months to cure — a protracted timeline that contributes to the development of permanent organ damage and drug resistance. Scientists in the lab of Marcus A. Horwitz, MD have been working hard to shorten the time it takes to eliminate the disease; back in 2019, they identified a novel oral four-drug regimen that could cut the time to cure tuberculosis in a mouse model by around 85% to just three weeks. Now, they’ve trimmed that time once again to as little as a week and a half by delivering additional doses of two of the drugs intranasally.
“Our results show that combining intranasal treatment with oral therapy can shorten the treatment time required to achieve relapse-free cure in mice,” said Bai-Yu Lee, PhD, a researcher in Dr. Horwitz’s lab and first author of an academic article on the study that published June 11 in the Journal of Infectious Diseases. “Since the results of drug treatment in the mouse model of pulmonary tuberculosis are fairly predictable of the results in humans, we anticipate that combining inhalational and oral routes for administration of anti-tuberculosis drugs will achieve more rapid and effective treatment of tuberculosis in humans.”
The researchers’ short-course regimen consists of the drugs clofazimine, bedaquiline, pyrazinamide and delamanid. Knowing that bypassing the gastrointestinal tract might make their regimen more potent, they selected the strongest two drugs — bedaquiline and delamanid — and suspended them in Infasurf, an FDA-approved intranasal agent used to treat respiratory distress in newborns. To test out the approach, they treated one cohort of a tuberculosis mouse model with the oral regimen and the intranasal additions, and a second one with the original oral-only regimen. For comparison, they treated another group with the standard treatment for tuberculosis. The mice that received the lab’s treatment protocols were split into three groups that were treated for 1.5, 2 or 3 weeks, while the ones on the standard regimen were treated for 3 weeks.
All the mice were held for three months after completing treatment, at which point their lungs were assessed for the presence of the bacterium that causes tuberculosis. They used stringent criteria to define a “cure”: Mice with even one bacterium in their lungs were considered to have relapsed.
For the group that received the lab’s oral-only regimen, mice treated for 1.5 weeks had a 60% relapse rate at three months, compared to an 11% rate for the group that received the combined oral and intranasal treatment. In the mice treated for 2 weeks, none that were treated with either the intranasal-oral or oral-only treatments relapsed; in the group that was treated for 3 weeks, none of the mice that received the intranasal-oral regimen relapsed, and only 10% of the mice that received the oral-only regimen relapsed. In contrast, all of the mice that were on the standard protocol relapsed three months after treatment stopped.
The researchers plan to conduct additional experiments to see whether Infasurf might have influenced the treatment’s efficacy. They also hope to obtain funding to conduct research on their updated regimen in nonhuman primates — and ultimately industry partners who could help develop inhalation platforms for tuberculosis drugs, according to co-author Daniel L. Clemens, MD, PhD.
Dr. Lee sees the UCLA Department of Medicine as one of the world’s best places to conduct research on one of the world’s deadliest diseases.
“The DoM is actively engaged in treating patients with these infectious diseases both in the United States and abroad. Moreover, preclinical animal models must use highly virulent strains of tubercle bacilli to provide accurate information in therapeutic drug studies,” Dr. Lee explained. “The DoM has state-of-the-art Biosafety Level 3 facilities required for work with virulent tubercle bacilli and UCLA is able to provide the biosafety training necessary for our work.”
Congratulations, team, on an outstanding study!
Heart Health Biomarkers Predict Cancer Risk
When one thinks about heart health, cancer may not be the first thing that comes to mind. However, a new study involving DoM faculty members Xinjiang Cai, MD, PhD, Karol E. Watson, MD, PhD and Eric H. Yang, MD suggests that elevated cardiovascular biomarkers are linked to a higher risk of cancer, even in people who have neither heart disease nor cancer.
“From a preventive cardiology standpoint, these findings encourage a reevaluation of mildly elevated baseline cardiac biomarkers in asymptomatic individuals — levels that may have previously been overlooked for cancer association,” said Dr. Cai, who served as first author on a journal article describing the results that published June 16 in JACC: Advances. “While a cardiovascular workup remains essential to assess potential subclinical cardiac disease, our results suggest that clinicians should also consider broader implications, including the possibility of increased cancer risk.”
Given that prevention is a key objective in both cancer and cardiovascular disease, the researchers wondered whether the same biomarkers that are used to detect subclinical heart disease, such as high-sensitivity cardiac troponin (hs-CTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), might also predict cancer risk. To investigate this link, they analyzed data from 6,244 participants in the Multi-Ethnic Study of Atherosclerosis (MESA), which included adults between 45 to 84 years of age who did not have cardiovascular disease at the beginning of the study, which was conducted between 2000 and 2002. MESA investigators measured participants blood levels of hs-cTnT and NT-proBNP.
The study subjects were followed for nearly 18 years. Using rigorous statistical analyses, the researchers showed that even very small increases in hs-cTnT and NT-proBNP strongly predicted those who would develop cancer in the future regardless of their initial health status. High levels of both proteins were linked to a greater chance of developing colon cancer, while higher levels of NT-proBNP alone were associated with a greater risk of lung cancer. The findings held true even after cardiovascular risk factors like smoking, diabetes, high blood pressure and high cholesterol were taken into account.
Armed with these findings, the researchers will next look to both replicate the results in bigger sample sets and to figure out whether cardiovascular disease and cancer might have some biological underpinnings in common.
“Our next steps include validating these findings in additional large, diverse cohort studies. Ultimately, prospective clinical cohorts specifically designed to examine the relationship between baseline cardiac biomarkers and cancer outcomes would provide stronger evidence,” Dr. Cai said. “In parallel, mechanistic studies are needed to better understand the biological pathways underlying this association—particularly the roles of inflammation, oxidative stress, and other shared pathophysiological mechanisms between cardiovascular disease and cancer.”
Dr. Cai believes the study’s success is a result of the intellectual environment, resources and collaborative opportunities provided by the DoM as well as the strength of its interdisciplinary research team, which included scientists from the Lundquist Institute at Harbor-UCLA Medical Center, the University of Washington, Johns Hopkins School of Medicine, Inova Heart and Vascular Institute in addition to UCLA.
“I benefit from outstanding mentorship and strong infrastructure for both basic and translational research in the DoM,” Dr. Cai said. “Importantly, the DoM demonstrates a deep commitment to supporting the career development of early-career physician-scientists like me.”
Kudos to Dr. Cai, Dr. Watson, Dr. Yang and the rest of the team on this intriguing and provocative study!
DoM Quality Cardiology Incentive Program Improves Patient Adherence To Life Saving Medical Therapy Outcomes
Outstanding patient care is our top priority, and the UCLA Department of Medicine Quality team is at the forefront of helping us succeed in our mission. One of the initiatives the team is most excited about is our specialty quality incentive programs, the first of which rolled out to the cardiology division in July 2021. Since then, the UCLA Cardiology Quality Improvement Program (CQIP) has grown to include more than 60 cardiologists across 16 clinics — and, as a new study shows, is demonstrably improving patient outcomes. A publication on the program’s impact was published June 20 in JACC: Advances, becoming one of the first-peer reviewed evaluations of a specialty-specific quality incentive program that demonstrated statistically significant and sustained improvement in guideline-directed medical therapy (GDMT) for cardiovascular disease.
“The study provides evidence that combining financial incentives with accurate data infrastructure and embedded clinical decision support tools can lead to durable improvements in care delivery,” David H. Cho, MD, co-director of the UCLA Cardiology Quality Program, said. “The findings establish CQIP as a potential scalable model across other health care systems and specialties. Our program also shows that quality improvement doesn’t have to feel punitive or burdensome, but can be designed as a practical, constructive tool that helps physicians deliver better care over time”
The program is a pay-for-performance initiative that makes it easier for physicians and patients to adhere to GDMT for cardiovascular disease. Physicians each get their own quality dashboards with monthly scorecards that benchmark them against the entire division. They receive incentives based on achievement of key quality metrics in heart failure, blood pressure control and lipid management, and have access to tools to help them close care gaps in real time without additional administrative work.
The analysis documented in the paper showed that the incentive has led to statistically significant improvements in adherence to therapies for heart failure with reduced ejection fraction and sustained improvements in blood pressure control and the use of statin/PCSK9i use for atherosclerotic cardiovascular disease prevention. It also demonstrated the importance of gaining clinician trust, providing real-time feedback and actionable data in driving change.
“We hope other institutions see this as a potential blueprint for launching their own specialty QI initiatives. Our experience demonstrates that high-impact change is possible when physicians are empowered with accurate data, clear benchmarks, and aligned incentives,” Pooya I. Bookhoor, MD, co-director of the UCLA Cardiology Quality Program, said. “Rewarding physicians for providing high quality care that meaningfully improves patient health without overburdening their workflows can also potentially improve resilience and reduce burnout.”
Similar programs are already underway in the DoM in the divisions of nephrology, hospital medicine and primary care, and the quality team is in the process of expanding them to palliative care, endocrinology, rheumatology and infectious disease.
“This work wouldn’t have been possible without the strong support of our department of medicine and cardiology division leadership, as well as the dedication of our programmers, analysts, and project managers who helped bring the program to life,” Dr. Cho said. “We are very thankful to be a part of a team that brings together clinical expertise, operational support, and technical collaboration to improve our patients’ health.”
Fantastic work, DoM Quality! Thank you for helping us serve our patients better.
DoM Professional Coaching Program Mediates Physician Burnout, Data Shows
I am particularly pleased to share a publication that arose from one of our department’s signature initiatives in the area of faculty wellness. This past Friday, the DoM Office of Wellness published in the Journal of General Internal Medicine the results of a clinical trial to assess the efficacy and feasibility of the DoM Professional Coaching Program, a popular initiative that was first rolled out in 2021 as a pilot program. The study showed that participants experienced as much as a nearly 30% decline in burnout.
“Coaching provides participants the time and space to actively explore what brings them joy and meaning- important aspects in one’s career and personal life that are easily forgotten amongst the stress and challenges we face professionally and personally,” Joshua N. Khalili, MD — the first author on the paper who led the clinical trial, and participant in the pilot — said.
Dr. Khalili’s own experience in the pilot program led him to become leader in its efforts. After his father passed away suddenly, he hoped that professional coaching would guide him to focus on what he valued most in his career and his life.
“It certainly did that,” Dr. Khalili said. “My professional coach, Chantal Veale, helped me explore my goals and passion and work and discover methods to improve my work-life integration."
Given his experience with the program, he immersed himself in the evidence of how professional coaching could help reduce burnout and improve physician well-being. This felt especially urgent given the crisis of physician burnout; almost half of all physicians in the US experience emotional exhaustion, depersonalization and decreased personal accomplishment as a result of feeling overworked and under-supported. This motivated him to lead a clinical trial to study its effects.
The trial included 79 DoM physicians across 13 divisions. Twenty-five of them were randomized into an arm where they received one-on-one coaching, as Dr. Khalili had; 27 were in the small group arm; and 27 were in the delayed-entry control group. Coaching was conducted over six one-hour sessions via Zoom and were scheduled every two to three weeks within a four-month period. Participants completed surveys at baseline, immediately after program, and six months after the intervention that assessed burnout as well as work-life balance, work engagement, self-efficacy, social isolation and provisions.
By the end of the program, the subjects who participated in the small group and one-on-one coaching intervention experienced a 29.6% and 13.4% reduction in burnout, respectively, while the burnout levels of those in the control group increased by 11.1%. There was no significant difference in burnout rates between those in the small group and one-on-one arms, suggesting that both types of interventions were effective.
“While effectively tackling burnout and improving physician well-being requires system-based, structural changes, we found that a brief, six-hours of coaching via Zoom was effective in reducing burnout and resulted in a sustained reduction in burnout over time,” Dr. Khalili said.
The team hopes that other institutions and healthcare organizations will feel empowered to launch their own programs after reading their new publication. He added that while some may have valid concerns about cost, he and the rest of the team involved in the program hope that their study demonstrates that the effectiveness of small group coaching — which cost $400 per participant, about 40% the cost of one-on-one coaching — is well worth the price compared to the cost of burnout, which is estimated to be around $6,000 to $8,000 per physician per year.
Based on the results of the study, DoM leadership has opened up its coaching among DoM faculty. In just the last few months, the DoM Office of Wellness has enrolled more than 20 DoM faculty with small group and one-on-one coaching. They’re working to continue expanding coaching more broadly.
Dr. Khalili was grateful for the support from the department that enabled him to make the study possible.
“I never thought I’d be able to run a clinical trial as a full-time clinician, but the only way that I could was with the help of an entire team,” he said. He credited Sun M. Yoo, MD with having the vision to implement the small group modality to scale up coaching in the DoM, as well John M. Mafi, MD, MPH; Karen A. Miotto, MD; Elizabeth Kyababchyan, MPH; Jesse Sanford; David Elashoff, MD; Jenny Brook; Yetunde Adebambo; Paige-Ashley I. Smith; and Emma Nguyen.
Congratulations to Josh, the trial team and the DoM Office of Wellness on this outstanding study!
I hope you will agree that robust scholarship across all of our missions is alive and well within the DoM and represents an important metric of our strength and leadership.
Dale
P.S.
I was up in San Francisco this weekend to attend the annual meeting of the Endocrine Society. I ran into three of our outstanding endocrine fellows — Diana Torres Pinzon, MD, MPH; Katayoun Khoshbin, MD; and Elyssa Berg, MD, MPH — who were in attendance and giving presentations. As you can see from their badges relative to mine, our fellows are clearly overachievers.
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