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Our faculty are prolific writers and make impressive contributions to the scientific and medical literature. Periodically, I devote my blog to highlight recent publications by our faculty over the preceding three months. While we do not have space to highlight everyone’s research or scholarly commentary, the quality of your exceptional and essential work never ceases to amaze me.

This week, note the breadth of our faculty’s contributions from public policy to fundamental discoveries.

End-of-Life Care Differences Persist Beyond the Treating Physician, Deborah Oyeyemi Walton, MD Finds

Our aging population has ushered in a new need for high-quality end-of-life care, as more people than ever before are living long enough to risk developing dementia. However, research has established that older adults from racial and ethnic backgrounds that have historically experienced systemic oppression receive less dementia care and end-of-life services, raising concerns about equity and access.

Dr. Oyeyemi Walton and her team used Medicare Fee-for- service data from 259,945 deceased beneficiaries with dementia. Among them, 8.3% were Black, 4.4% were Hispanic and 87.3% were white. Gender was split between about 60% female and 40% male. Black and Hispanic patients had lower median household incomes and were more likely to be Medicaid beneficiaries compared to white patients, while fewer Hispanic patients (44.9%) were nursing home residents compared to Black (53.8%) and White (50%) patients.

The team compared the groups across nine end-of-life care and utilization measures. For utilization they evaluated emergency department (ED) visit, hospitalization, intensive care unit visit, mechanical ventilation or cardiopulmonary resuscitation, and feeding tube placement in the last 30 days of life, as well as death in an acute care hospital. They also evaluated hospice use and palliative care counseling in the last 180 days of life, and any billed advance care planning. Black and Hispanic individuals with dementia were more likely than white individuals to have an ED visit, hospitalization or ICU visit in the last 30 days of their life, as well as to receive mechanical ventilation, CPR or feeding tube placement. They were also more likely to die in an acute care hospital and were less likely to receive hospice care.

Interestingly, the team’s findings on advance care planning contrasted with prior findings in the literature. Dr. Oyeyemi Walton and her team found that Black and Hispanic patients were more likely than white patients to have palliative care counseling and billed advance care planning.

“This was surprising to us,” Dr. Oyeyemi Walton said. “I think there's this kind of understanding in the literature that certain groups tend to use more acute care towards the end of life for various reasons, but I think there was also a thought that these groups would also be less likely to have discussions around end-of-life care.”

An explanation for why prior studies had demonstrated different results may lie in how advance care planning was measured. Past researchers have based their analyses on self- and/or proxy reports from caregivers rather than on billing rates, such as in this study.

“It was interesting to find that Black and Hispanic older adults were being billed at similar, if not slightly higher, rates [for advance care planning] than white older adults, but were still having more intensive end-of-life care,” Dr. Oyeyemi Walton said.

The researchers then analyzed whether the disparities they found could be explained by differences between the physicians who cared for the patients. Accounting for physician differences slightly adjusted the magnitude of racial and ethnic differences but did not change the overall findings.

“End‑of‑life care for older adults with dementia continues to differ by race and ethnicity, and these differences do not appear to be primarily driven by which physician a patient sees,” Dr. Oyeyemi Walton said. “These findings align with broader research on social determinants of health."

She noted that the study only included individuals with a regular physician and a claims-based dementia diagnosis. “The differences may be even greater among those who are more marginalized and not captured by our eligibility criteria,” Dr. Oyeyemi Walton said.

Dr. Oyeyemi Walton noted that this study is especially timely in light of Centers for Medicare & Medicaid’s recently-launched the Guiding an Improved Dementia Experience (GUIDE) Model, a national model for dementia care to study how providing evidence-based tools and support for patients and caregivers improves their quality of life. (I would like to note that our work here in the UCLA Department of Medicine (DoM) was crucial to the GUIDE Model’s development, and UCLA Health is among the first health systems to test it!)

“There’s a lot of momentum behind figuring out how to reimburse and support high-quality dementia care,” she said.

Dr. Oyeyemi Walton is grateful to her NCSP advisor and the study’s senior author, Yusuke Tsugawa, MD, MPH, PhD, for his guidance on her work. She has been doing research on cognitive impairment in older adults since medical school and found that his expertise in Medicare data strongly complimented her clinical and research experience. 

“We came together through the NCSP, and our interests really collided,” she said. I am happy that the kind of mentor-mentee collaboration we strive to offer in the DoM can result in important work like this. Well done, Deborah and team!

Banned Words Harm Patients, Nupur Agrawal, MD, MPH and Keith C. Norris, MD, PhD Write in JAMA

Amid the many dramatic changes that U.S. federal health agencies underwent last year was the news of a list of more than 200 “prohibited words” that they could no longer use in external communications — words like “accessibility,” “diversity,” “racism,” “socioeconomic,” “underserved,” “vulnerable populations” and “women.” These words describe core parts of our missions here in the DoM, where we strive to advance health for all — and, as Nupur Agrawal, MD, MPH and Keith C. Norris, MD, PhD explained in a perspective article published Dec. 10 in JAMA, their loss in health communications endanger health advocacy, the well-being of patients and the integrity of medicine.

“We wrote it in a non-partisan way, with a focus on caring for the patients and allowing clinicians and researchers to do the best work they can do,” said Dr. Norris, a professor of medicine in the UCLA Division of General Internal Medicine and Health Services Research (GIMHSR) and executive vice chair of the DoM Office of Community Engagement and Inclusive Excellence (CEIE).

As Dr. Agrawal and Dr. Norris recapped in their article, by banning words, federal officials sought to reflect how the current administration views diversity, equity, inclusion and gender in agencies’ public materials. The implications reached well beyond agency headquarters, particularly for a public institution like ours that relies heavily on federal funding: Those of us who are part of inclusive excellence initiatives remember well the initial efforts to revise our public-facing materials to meet new federal requirements, and faculty and staff who are part of health services research recall the challenge of trying to describe health equity and health disparities research in grant applications without being able to use those very words, or even the words of the populations they sought to study.

Dr. Agrawal and Dr. Norris were motivated to work together on the article based on their own experiences with the fallout of banned words. Dr. Agrawal found that she was struggling to publish her team’s work on her Macy Faculty Scholars grant project in journals that normally readily published health services studies, while nearly every aspect of Dr. Norris’ role as executive vice chair of the DoM Office of CEIE was affected, right down to its original name.

While both of them were willing to make changes in order to advance their work, they wanted to warn the wider medical field of the dangers of this kind of censorship. At the time, no other articles on the potential consequences had been published.

“We all knew what was happening, but nobody had codified that it’s having an impact,” Dr. Norris said. “If we didn’t speak up, someone would be able to say, ‘Well, no one ever complained or talked about it.’” 

The blend of their two perspectives helped lay out the extent of the disruption that banned words have had on our work, from research to training. At a baseline, it distracts us from the most important aspects of what we do as scientists, physicians and educators, they claimed.

“Our efforts have been diverted from caring for patients, educating trainees, and conducting critical health-promoting research to instead scrubbing our websites and revising grants, scholarly writings, and written communications of anything that may upset the government,” Dr. Agrawal and Dr. Norris wrote in their article. “Word censorship coupled with funding cuts have palpably strained an already stressed system plagued with physician shortages and burnout.”

Dr. Agrawal and Dr. Norris noted that language has been central to the immense efforts to establish trust with patients from historically marginalized populations and, as they wrote, to capture nuanced aspects of their complex lives, as well as those of community partners. 

“If we can’t use these words, it impairs our relationship with patients, and for many patients, having trust and confidence in the provider and the health system is crucial for them to get the care they need,” Dr. Norris said. “For many non-dominant groups, the health care system is not seen as a friend — and the language we use has built up confidence.”

But, if that’s taken away, “our concern is that patients may stop coming or stop listening to our recommendations, and that could impact their health outcomes,” Dr. Norris said.

Dr. Norris and Dr. Agrawal included an example in their paper that illustrates how embedded this language is in a physician’s work: One afternoon in the clinic can see a clinician care for a Black man needing the banned word “advocacy” to get his medication covered by insurance, a newborn with weight loss due to issues with the banned word “breastfeeding,” a young person who happens to be best described by the banned word “pregnant woman” needing abortion care following a sexual assault, and a person who is characterized as the banned word “transgender” requiring hormone therapy.

“Words that capture patients’ personal identities are an indispensable part of their medical and social histories that provide invaluable insight and prompt deeper exploration into their unique stories,” Dr. Agrawal and Dr. Norris wrote. “Connecting to people using their words demonstrates respect and opens meaningful dialogue needed socioculturally sensitive, holistic care that people need beyond diagnostics and prescriptions.”

Word bans also add unnecessary friction to educational efforts and collaboration in the workplace. Shared definitions of key words and concepts makes it possible to disseminate knowledge with trainees and colleagues as well as to discuss experiences that do not equally impact everyone.

“We define and use special words to appropriately reframe inaccurate narratives (e.g., highlighting structural and institutional racism and related barriers to lift the false veil of innate inferiority and move from what is wrong with a given group to what happened to them),” Dr. Agrawal and Dr. Norris wrote. “We need banned words like female, gender, sex, and woman to describe half the population when doing research, and we must consider socioeconomic factors to understand financial and systemic implications of interventions.” 

Even those who do not feel that such bans have impacted them or their work must resist such censorship. As Dr. Norris pointed out, if left unchecked, those first 200 words will be just the start.

“How this game works is that if you can ban those words and you don’t get pushback, then great — we have another 200 words we’re going to ban,” he said. “We have to figure out how to navigate these things and where we have a voice.”

It is also imperative to figure out how to take action. The University of California system has so far not complied with federal requirements that challenge its principles and values, even at the risk of losing over $1 billion in funding; as we are all well aware, the government also froze more than half a million dollars in research grants to UCLA. After faculty, system unions and staff sued the administration, a judge blocked the freeze and restored our grants.

From Dr. Norris’ perspective, actions like these are crucial to not only preserving our own futures, but those of the patients who need us most. 

“It’s important that each of us in different spaces, whatever and wherever we can, do what we can do to make sure that we are helping those who need the most help,” Dr. Norris said. “The banning of these words is targeted to disempower those of us who work with those communities.”

When asked if they worried about the professional ramifications of speaking out against word bans, Dr. Norris said he felt that doing so was relatively easy compared to the work of those who paved the way for him.

“I am where I am in life because of what people did before me. They didn’t write an editorial. They marched. They got beat. They got hosed down. Communities bombed. People were lynched,” he said. “I just got to write an editorial. That’s a pretty low bar for me.” 

For Dr. Agrawal, the “risk” never registered. 

“It’s funny, because that’s the perspective a lot of people close to me had — they said, ‘Wow, it’s so brave of you to put yourself out there,’” she recalled. “To me, it didn’t feel like putting myself out there. It’s just what we observe as physicians.”

She added that she sees this part of her work as an extension of her duties as a doctor. “These are the implications for the people we care about, and the most important part of our profession is caring for people,” Dr. Agrawal said.

OBBBA Benefits Pharma, But Not Patients, William B. Feldman, MD, PhD, MPH Writes

U.S. health care policy is evolving rapidly, with major consequences for the health of our patients. Health care policy researcher and pharmaceutical industry expert William B. Feldman, MD, PhD, MPH, an associate professor of medicine in the pulmonary, critical care, sleep medicine and allergy and immunology division, recently co-authored a perspective article that was published Dec. 30 in the Annals of Internal Medicine. There he and his co-authors contend that the One Big Beautiful Bill Act (OBBBA), a wide-ranging piece of legislation signed into law last summer, financially benefits the pharmaceutical industry at the expense of patients by reducing the number of drugs that are subject to Medicare price negotiation and decreasing the numbers of patients covered by Medicaid, which could hurt safety net institutions.

“In my view, we should be strengthening price negotiation under the IRA not watering it down,” Dr. Feldman said.

The IRA previously exempted drugs approved for just one rare disease from Medicare price negotiations, a move designed to incentivize drugmakers to develop treatments for rare conditions with few therapies. The OBBBA expands this — but in a way that helps drugmakers without benefitting patients, according to Dr. Feldman: Orphan drugs that are approved for multiple rare diseases will now be exempt from price negotiation. One example of this is the drug zanubrutinib, an oral BTK inhibitor commercialized by BeiGene as Brukinsa. Zanubrutinib is used to treat seven different types of hematologic malignancies. All of them on their own are rare diseases — but because drugs that treat multiple rare disease are now excluded from Medicare price negotiation under the OBBBA, we will continue paying higher prices for zanubrutinib over longer periods. 

On top of that, the OBBBA also extends the timeline between when drugs for rare diseases can be eligible for Medicare price negotiation. The IRA made it so that negotiated prices could go into effect starting nine years after the approval of small-molecule drugs and 13 years for biologics. Now, the clock for Medicare price negotiation only begins once the first nonrare indication is approved. 

These new limits on Medicare price negotiation for orphan drugs could make them pricier for our healthcare system. They could also promote what is known as “indication-splitting,” a strategy where a pharmaceutical firm chooses to obtain Food and Drug Administration approval for one narrow indication to access additional tax breaks and regulatory protections that they would miss out on if their drug was approved for broader indications. 

“These new limits could result in higher out-of-pocket costs for patients over longer periods of time, leading to reduced areas of access and adverse clinical outcomes,” Dr. Feldman and his co-authors wrote in their article, adding that the Congressional Budget Office estimates that rare disease provisions in the OBBBA will increase health care costs by $9 billion over the next decade.

In addition to reducing drug access for Medicare patients, the OBBBA adds new requirements for coverage, including work requirements and periodic eligibility verification, that will shrink Medicaid coverage. These changes are anticipated to lead to an additional 11.8 million people becoming uninsured by 2034, according to KFF.

In theory, this could reduce pharmaceutical company revenues, because fewer patients will be eligible to receive expensive prescription drugs. However, as Dr. Feldman and his co-authors pointed out, Medicaid only covers one tenth of all prescriptions filled in the U.S., and large statutory rebates on these drugs already limit pharmaceutical company revenue.

Meanwhile, hospitals that are part of the 340B Drug Pricing Program — a Health Resources and Services Administration program designed to help safety net hospital stretch federal resources — have much more to lose: Most hospitals that qualify for this program do so based on their Disproportionate Share Hospital percentage, which is linked to the number of Medicaid-eligible patients they serve. Lower Medicaid enrollment means lower Disproportionate Share Hospital percentages, which could result in fewer hospitals qualifying for the 340B program — and, as a consequence, fewer vulnerable patients getting the drugs they need. One estimate suggests as many as 12% of hospitals could be cut.

While there are some concerns about hospitals appropriately using 340B Drug Pricing Program funds, Dr. Feldman feels there are better ways to address them than reducing program eligibility. 

“I and many others have advocated for reforms aimed at ensuring that the 340B program will continue to meet these core goals,” Dr. Feldman said. “The key is that policies must be targeted — and not impose undue burdens on community health centers and other covered entities that depend on 340B revenue to support safety net care.” Indeed, Dr. Feldman recently discussed potential targeted solutions with lawmakers in testimony before the Senate Health, Education, Labor, and Pensions Committee.

Meanwhile, as the OBBBA undermines hospitals’ ability to care for under-served patients, it delivers pharmaceutical companies a big win in the form of corporate tax breaks. Those savings could be reinvested research and development that benefits patients — but they might go towards larger dividends towards shareholders instead. 

“It’s very hard to know,” Dr. Feldman said. “But we will see.” 

When asked to anticipate how the OBBBA could impact our work and that of our affiliates — particularly Federally Qualified Health Centers — Dr. Feldman did not mince words.

“The OBBBA will harm public health,” he said. “Millions of Americans will lose health insurance, and that will place an increasing strain on health centers across the country.”

Lab of Ira B. Kurtz, MD Identifies Structure and Function of Key Breast Cancer Protein

Faculty all across our department are connecting dots between disciplines to make groundbreaking scientific discoveries. One example of this that I share with you this week is a recent study led by Ira B. Kurtz, MD, a nephrologist who studies ion transport disorders, the structural biology of membrane transport proteins and the biophysics of membrane transport processes in the kidney. The Kurtz lab’s results, which were published Nov. 11 in Nature Communications, unveil the atomic structure, mechanism and function of a transport protein called NBCn1, which recent research has implicated in breast cancer.

To understand its role in breast cancer, the team needed to learn the atomic structure of NBCn1; the ions it transports and how they are coupled; where the ions bind to the protein; and how the protein changes structurally during transport, as well as the implications for the regulation of intracellular and extracellular pH. 

“A major goal was to connect structure to mechanism and function — specifically, how NBCn1 moves ions across the plasma membrane during its transport cycle,” Dr. Kurtz said. First, he and his team used a Nobel Prize-winning technique called cryo-electron microscopy (cryo-EM) to determine the protein’s three-dimensional structure at very high resolution. The cryo-EM process involves rapidly freezing proteins of interest in a thin layer of ice, then imaging them with an electron microscope. The pictures are then combined computationally to reconstruct the protein’s structure.

After they determined NBCn1’s structure, the team moved to computer modeling of how the protein’s structure changes throughout its transport cycle, also known as its conformational state changes. As Dr. Kurtz described it, transporters are dynamic proteins that move through multiple structural states during their transport cycle.

“Computational modeling allows us to connect those structural snapshots and simulate transitions between them, revealing how the protein moves during transport,” he explained. Their work showed that NBCn1 transports 2 sodium ions together with 1 carbonate ion through what is known as an alternating-access mechanism.

“Unlike ion channels, which form a pore through which ions can flow, transporters bind ions on one side of the membrane, close access to that side, and then open to the opposite side to release them,” Dr. Kurtz said. Their modeling also demonstrated what he described as an “elevator-type” movement, in which the part of the protein carrying the bound ions moves vertically relative to the more rigid scaffold of the transporter as it shifts cargo from one side of the plasma membrane to the other.

Their modeling also showed that each transporter can complete 15,000 transport cycles per second. 

“This is extraordinarily fast,” he said, “consistent with a very high-capacity mechanism for influencing intracellular and extracellular pH.” 

The Kurtz lab was surprised by the transporter’s elevator-type movement and by the rate at which it completes transport cycles. Dr. Kurtz noted that it was challenging to capture membrane transporters at high resolution, as their shape changes rapidly. They are also embedded in the lipid environment of the plasma membrane, making it hard to obtain the high-purity sample necessary for cryo-EM. 

“Obtaining high-quality cryo-EM data and then integrating it with computational modeling was essential to interpret how NBCn1 moves through an alternating-access cycle and to relate the structural cryo-EM snapshots to a mechanism relevant to intracellular alkalinization together with extracellular acidification,” Dr. Kurtz said.

The Kurtz lab’s next step is to translate these findings by developing molecules that target a key extracellular region of NBCn1 to block its transport activity. They are working on antibodies against that region and exploring approaches that combine NBCn1 targeting with breast-specific tumor markers to improve tumor selectivity, then plan to test these strategies in the lab and in animal models of breast cancer.

“Membrane proteins are major therapeutic targets,” Dr. Kurtz said. “A large fraction of approved drugs, often estimated at more than half, act on membrane proteins such as receptors, ion channels and transporters.” 

Dr. Kurtz emphasized that cancer pH biology involves both sides of the cell membrane — the alkaline intracellular pH together with the acidic extracellular pH.

“Understanding transporters like NBCn1 helps explain how tumors, including breast cancer, maintain an abnormal reverse pH gradient that favors tumor growth and progression,” he said. 

To Dr. Kurtz, cross-disciplinary research matters because biology does not organize itself by medical specialty. The same molecular mechanisms that are central to the function of one organ can contribute to disease in another.

“Understanding how nature works often requires integrating clinical physiology with molecular and structural mechanisms,” Dr. Kurtz said. He added that ion transport is a good example: transporters and channels are often expressed in more than one organ, so they regulate fundamental processes like pH balance and electrolyte handling in multiple tissues.

Dr. Kurtz believes these results open new paths that offer much to look forward to. 

“The future of this work is exciting because each structural insight removes a layer of mystery,” he said. “That kind of clarity is valuable in itself, but it also gives us a much more rational starting point for designing ways to interfere with the biology that tumors depend on.”

UC President’s Office Highlights Work of Arjun Deb, MD

Last month, in celebration of both heart month and Valentine’s Day, cardiologist Arjun Deb, MD was featured by the University of California Office of the President for his research on a molecule that can help heal heart cells after a heart attack.

This work is much needed and very promising, and I am pleased to see Dr. Deb’s work highlighted as an example of the impactful research conducted within the UC system. Read the full article here.

Dale

P.S. 

Cardinal events mark anniversaries. This one marked my 4^th year of CA regulatory compliance. DMV coming up soon.

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