Monday, April 29, 2024

Kaposi sarcoma discovery could facilitate drug development

UNIVERSITY OF NORTH CAROLINA HEALTH CARE

Dirk Dittmer, PhD — IMAGE:
DIRK DITTMER, PHD, AND COLLEAGUES HAVE DEVELOPED A MODEL OF KAPOSI SARCOMA COULD BE KEY TO THE DEVELOPMENT OF NEW DRUGS TO TREAT THE DISEASE. KAPOSI SARCOMA IS THE MOST COMMON CANCER IN PEOPLE LIVING WITH HIV. “BEFORE THIS, ONLY REPURPOSED DRUGS FROM OTHER CANCERS WERE USED TO TREAT KAPOSI SARCOMA, BUT NOW WE CAN START INVESTIGATING ENTIRELY NEW COMPOUNDS TO HELP TREAT WHAT CAN BE A LETHAL CANCER.”
view more
CREDIT: UNC LINEBERGER COMPREHENSIVE CANCER CENTER

Researchers at UNC Lineberger Comprehensive Cancer Center, after decades of research efforts, have developed a mouse model of Kaposi sarcoma that could be key to the development of new drugs to treat the disease. Kaposi sarcoma is a cancer that is the most common cancer in people living with HIV.

The findings appeared in Cell Host & Microbe.

“This is an important development as we have created the first animal model ever of Kaposi sarcoma. Animal models are essential to move new drugs from the laboratory bench into clinical trials,” said UNC Lineberger’s Dirk Dittmer, PhD, senior corresponding author, co-leader of the UNC Lineberger Virology Research Program and director of the UNC Viral Genomics Core. “Before this, only repurposed drugs from other cancers were used to treat Kaposi sarcoma, but now we can start investigating entirely new compounds to help treat what can be a lethal cancer.”

About 20% of all human cancers arise from viruses or require viral infection as an essential cofactor. The Kaposi sarcoma-associated herpes virus (KSHV) was discovered in 1994 and is associated with Kaposi’s sarcoma as well as B-cell cancers. KSHV-associated diseases affect internal organs and are ultimately fatal. In the U.S., the diseases are found primarily in immunosuppressed people such as those who are HIV-positive or are transplant patients.

Worldwide, an estimated 34,270 cases of Kaposi sarcoma were diagnosed, and 15,086 deaths reported in 2020, with twice as many cases and deaths occurring in men compared to women. Africa accounted for 73% of new cases and 86.6% of the deaths from Kaposi sarcoma worldwide. The disease is endemic, and not HIV-related, in some southern and eastern African countries.

Aside from animal models, one way to study cancer is to look at tumor cells in the lab. But according to Dittmer, Kaposi sarcoma tumor cells are very finicky and dependent on signaling molecules and blood supply, which is why they don’t survive in a laboratory culture dish. Therefore, researchers have been focusing on developing animal models that would mimic, as closely as possible, the disease in humans.

One of the challenges the researchers faced in developing their model was the fact that two types of genes are transcribed into proteins in the Kaposi sarcoma mouse model. Normally when a virus infects a cell, the cell dies as the virus replicates, which is a process called cell lysis; the genes that are needed for the virus to propagate itself are lytic genes. Cancer viruses are different as they enter a quiet state, called latency, where only the genes that help the infected cell survive are expressed. The mouse model the researchers developed is complex as a bit of both types of genes were needed.

Cervical cancer and its related virus, HPV (human papilloma virus), offers a good comparison for the challenge of developing a Kaposi sarcoma mouse model. The KSHV genome is 20 times larger than HPV. HPV has two cancer-causing genes, E6 and E7, so to mimic the disease in animals, researchers only needed to design two mice, one for each gene. KSHV may have as many as 10 cancer-causing genes that all work together so it would be way too difficult to develop that many mice, hence the virtue of their single model, Dittmer noted.

“Another of the key virtues of our new mouse model is that it helps us understand angiogenesis, or new blood vessel formation. Without angiogenesis cancer cells are deprived of oxygen and die,” Dittmer said. “In this mouse model, we can study angiogenesis blocking drugs better than ever before. If new drugs work against Kaposi sarcoma, they will also likely work against lesser-angiogenic tumors, which would be a major plus.”

For next steps, the researchers hope that others will pursue drug and vaccine development based on a new understanding of fundamental aspects of KSHV provided by their mouse model, including possible development of a much-needed primate model for human KSHV and Kaposi sarcoma.

JOURNAL

Cell Host & Microbe

DOI

10.1016/j.chom.2024.03.012

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

The complete Kaposi sarcoma-associated herpesvirus genome induces early-onset, metastatic angiosarcoma in transgenic mice

Study finds school entry requirements linked to increased HPV vaccination rates

ATRIUM HEALTH WAKE FOREST BAPTIST

WINSTON-SALEM, N.C. – April 29, 2024 – A new study from researchers at Wake Forest University School of Medicine shows that school entry requirements are linked to an increase in human papillomavirus (HPV) vaccinations.

The findings appear online in Pediatrics.

HPV is a common sexually transmitted infection, which can cause health problems such as genital warts and certain cancers. To prevent infection, the Centers for Disease Control and Prevention (CDC) recommend that 11- to 12-year-olds receive two doses of the HPV vaccine, given 6 to 12 months apart. However, CDC data from 2022 shows that only 50% of 13-year-olds were up to date on HPV vaccinations.

School-entry requirements, where parents/guardians are required to vaccinate their children against HPV or receive an exemption before beginning a particular grade, are currently only found in Hawaii, Puerto Rico, Rhode Island, Virginia and Washington, D.C.

“There are a variety of state and federal policies designed to address low HPV vaccination rates among adolescents, but there has been little research to determine which policies are most effective,” said Brigid Grabert, Ph.D., J.D., assistant professor of implementation science at Wake Forest University School of Medicine and senior author of the study.

In collaboration with researchers at the University of North Carolina at Chapel Hill and Duke University, Grabert and team systematically reviewed studies from 2009-2022 assessing the association between policies and HPV vaccination coverage among U.S. adolescents. The team identified 36 eligible studies and summarized findings based on policy type such as school-entry requirements, federally funded policies and educational requirements, which require schools or other organizations to distribute information about the benefits of HPV vaccination.

“We found consistent evidence that school-entry requirements work in places that require parents who don’t vaccinate to submit an exemption,” Grabert said. “We also found that school-entry requirements for other vaccines resulted in positive spillover effects for HPV vaccinations.”

Grabert said that federally funded policies related to the Vaccines for Children program and Medicaid were also consistently associated with an increase in HPV vaccinations. However, few studies noted an association between educational requirements and HPV vaccination coverage.

“Policymakers should be aware that HPV-related cancers and disease can be reduced,” Grabert said. “But not all policies are effective. Policymakers should carefully consider the best strategy to increase the administration of HPV vaccines.”

JOURNAL

PEDIATRICS

DOI

10.1542/peds.2023-064692

METHOD OF RESEARCH

Systematic review

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Policy Approaches for Increasing Adolescent HPV Vaccination Coverage: A Systematic Review

COVID-19-induced financial hardships reveal mental health struggles

UNIVERSITY OF SOUTH AUSTRALIA

When COVID-19 caused significant economic disruptions, thousands of people around the world experienced sudden shocks to their financial situation through reduced earnings or job losses.

Now economic researchers at the University of South Australia have examined the mental health effects on people who experienced immediate or expected financial setbacks during the height of the pandemic.

Data gathered from China, Japan and South Korea during the early phases of the pandemic revealed that the severe economic shocks induced by COVID-19 caused significant effects to people’s mental health including anxiety, sleeping troubles, boredom and loneliness.

UniSA’s Associate Professor of Economics Tony Cavoli says the anticipation of future income loss had a more profound impact on people’s mental wellbeing compared to the actual decreases in their income.

“Our research shows that mental health issues are more likely to occur due to anticipated income losses rather than actual losses. It was also interesting to find that although women are generally more likely to experience mental health problems, in many instances in our study we found that men were more likely to experience anxiety than women in response to either actual or expected losses in their income,” he says.

“There are a couple of reasons as to why this might be the case. Firstly, in societies that are perhaps seen as more traditional in terms of household and familial structures, it is possible that males feel greater societal pressure to remain employed. Secondly, those industries for which there was a higher likelihood of experiencing income reductions were more likely to have greater participation by males.”

The initial impacts of COVID-19 lockdowns led to decreased demand, a reduction in hours worked and significant job losses. The Australian Bureau of Statistics predicted the pandemic caused a $47 billion hit to the country’s economy.

Assoc Prof Cavoli says his study presents an important insight into people’s anxieties arising from economic turbulence and uncertainties.

“We have an insight into how people dealt with income shocks during stressful times, and this is a really important opportunity for future policy implications, particularly around the design of government support and other interventions,” he says.

“Responses from governments, for example, early in times of crisis may help individuals manage possibility anxieties arising from economic uncertainties."

For more information:

Akbar Zamanzadeh, Tony Cavoli, Matina Ghasemi, Ladan Rokni, "The effect of actual and expected income shocks on mental wellbeing: Evidence from three East Asian countries during COVID-19," Economics & Human Biology, Volume 53, 2024, 101378, ISSN 1570-677X, https://doi.org/10.1016/j.ehb.2024.101378.

END.

………………………………………………………

Media contact: Melissa Keogh, Communications Officer, UniSA Media
M: +61 403 659 154 E: Melissa.Keogh@unisa.edu.au

Researcher contact: Associate Professor Tony Cavoli, UniSA, E: Tony.Cavoli@unisa.edu.au

JOURNAL

Economics & Human Biology

DOI

10.1016/j.ehb.2024.101378

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The effect of actual and expected income shocks on mental wellbeing: Evidence from three East Asian countries during COVID-19

Study suggests staying current with COVID-19 vaccinations helps combat emerging variants

OHSU is among first to test in a biosafety level 3 laboratory whether vaccine-elicited antibodies block infection of a live virus

Peer-Reviewed Publication

OREGON HEALTH & SCIENCE UNIVERSITY

New research using live SARS-CoV-2 virus reveals an updated vaccine provides a strong immune response against previous strains and emerging variants.

The findings by researchers at Oregon Health & Science University, published in the journal Emerging Infectious Diseases, suggest a clear benefit in receiving updated vaccinations on a regular basis, especially among older people or those with underlying medical conditions.

“The virus is still circulating, it’s continuing to evolve, and it remains dangerous,” said co-senior author Fikadu Tafesse, Ph.D., associate professor of molecular microbiology and immunology in the OHSU School of Medicine. “Sooner or later, there will be another variant that evades the immunity we have already built up. Our study demonstrates that it’s worthwhile to update our immune repertoire.”

As the pandemic has receded from public consciousness, vaccine uptake has waned in the U.S., according to federal data.

The new study is the latest in laboratory research at OHSU testing variants of the SARS-CoV-2 virus. The project relies upon more than 2,000 university employees who have volunteered to have their blood drawn before, during and after vaccination. The research project began early in the pandemic with antibody testing.

In the latest study, researchers isolated blood drawn from 55 people before and after they received an updated vaccine beginning last fall that targets the XBB.1.5 subvariant of the omicron variant of the virus.

They found a strong response in terms of the levels of antibodies generated, and their ability to neutralize the original strain of SARS-CoV-2 plus new variants that have emerged since the novel coronavirus arrived in late 2019. Importantly, the vaccine appeared to generate a strong response against the JN.1 variant that is now circulating broadly worldwide – suggesting regularly updating the vaccine will be useful in confronting emerging variants.

The study marks another milepost in the evolution of the SARS-CoV-2 virus.

“Overall, this work strongly supports use of the updated vaccine,” said co-senior author Marcel Curlin, M.D., associate professor of medicine (infectious diseases) in the OHSU School of Medicine and medical director of OHSU Occupational Health. “In the big picture, COVID-19 is not going away but lining up alongside the other common respiratory illnesses such as flu and RSV, which cause relatively mild disease for most people and a lot of harm to a few.”

In contrast to most other research studies, OHSU is among the first to test the ability of vaccine-elicited antibodies in blood serum to block infection of a live virus in a biosafety level 3 laboratory.

In addition to Tafesse and Curlin, co-authors include Xammy Huu Nguyenla, Mastura Wahedi, Timothy Bates and Mila Trank-Greene of OHSU.

The work was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, award R01AI141549. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

JOURNAL

Emerging Infectious Diseases

DOI

10.3201/eid3006.240051

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Evaluating Humoral Immunity Elicited by XBB.1.5 Monovalent COVID-19 Vaccine

ARTICLE PUBLICATION DATE

26-Apr-2024

Pandemic fatigue and vaccine hesitancy continue to affect global public health, new 23-country study in Nature Medicine reports

Responses from 23,000 people point to need for more locally relevant communication strategies to increase vaccine confidence

CUNY GRADUATE SCHOOL OF PUBLIC HEALTH AND HEALTH POLICY

While it found that global uptake of at least one COVID-19 vaccine dose was robust, a new survey published today in Nature Medicine revealed mixed signals about the current acceptance of vaccines generally, especially COVID-19 boosters. The new survey of 23,000 respondents from 23 countries representing more than 60% of the world’s population is the fourth in series of studies led annually since 2020 by a team from the City University of New York Graduate School of Public Health and Health Policy (CUNY SPH).

“The repercussions of pandemic disruptions in healthcare services, the effects of the inequitable and slow global vaccine distribution, and the prevalence of misinformation and mistrust in health authorities continue to be felt,” says Jeffrey V. Lazarus, Professor of Global Health at CUNY SPH, head of the Health Systems Research Group at Barcelona Institute for Global Health, and coordinator of the study. “They represent major obstacles for health practitioners struggling to meet the urgent need to get people caught up on routine immunizations and ready to face the next pandemic.”

Reported global uptake of at least one COVID-19 vaccine dose rose last year to 87.8%, as compared to 36.9% in 2021 and 70.4% in 2022. However, the intent to get a COVID-19 booster (71.6%) was lower compared to 2022 (87.9%).

“The SARS-CoV-2 virus continues to circulate and mutate,” says Ayman El-Mohandes, senior author and dean of CUNY SPH. “Variant-adapted boosters are available, but public health statistics show that many older people and others who are at higher risk of severe disease and death have not accepted them.”

In addition, documented spillover effects on routine immunization raise the threat of the reemergence of other childhood and adult vaccine-preventable diseases. While just more than three respondents in five (60.8%) said that their experience with COVID-19 made them more willing to get vaccinated against other diseases other than COVID-19, almost a quarter (23.1%) reported greater reluctance to do so.

“While we are concerned about the evident fallout of the pandemic on large numbers of people, we still see a general openness to immunization that we must build on to boost vaccine confidence, including acceptance of new generations of COVID-19 vaccines and boosters,” says El-Mohandes. “We must design targeted messages from trusted communicators to encourage vaccine uptake.”

Survey responses on trust in sources that provide information or guidance on pandemic interventions revealed somewhat higher levels of trust in those close to or well recognized by the individual, although all 11 studied sources averaged less than 7 on a 10-point scale. The most trusted sources were “my doctor or nurse” and the World Health Organization, averaging 6.9 and 6.5, respectively.

The report also noted interesting variations in trusted sources across different countries. For example, “religious leaders” ranked 3.16 in Sweden and 3.19 in Germany but 6.57 in Nigeria and 6.72 in India, whereas “my doctor or nurse” ranked 4.95 in Russia and 7.70 in Kenya.

General trust in health authorities was reported by 65.4% of respondents, while general trust in government was 56.4%. A decrease in trust in science was reported by 13.9%, and 18.7% reported less trust in the pharmaceutical industry compared to prior surveys.

“These findings emphasize that vaccine hesitancy and trust in health and science remain complex challenges, and underscore the need for targeted, culturally sensitive health communication messages and outreach strategies going forward,” Lazarus states.

Lazarus, J.V., White, T.M., Wyka, K. et al. Influence of COVID-19 on trust in routine immunization, health information sources and pandemic preparedness in 23 countries in 2023. Nat Med (2024). https://doi.org/10.1038/s41591-024-02939-2

About CUNY SPH

CUNY SPH is committed to teaching, research, and service that creates a healthier New York City and helps promote equitable, efficient, and evidence-based solutions to pressing health problems facing cities around the world.

JOURNAL

Nature Medicine

DOI

10.1038/s41591-024-02939-2

METHOD OF RESEARCH

Survey

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Influence of COVID-19 on trust in routine immunization, health information sources and pandemic preparedness in 23 countries in 2023

ARTICLE PUBLICATION DATE

29-Apr-2024

COI STATEMENT

Study funding was provided by Moderna, Inc., to the City University of New York (CUNY) Research Foundation. Authors retained full autonomy in the design of the study; the development of the survey instrument; the collection, analysis, and interpretation of data; the presentation of results; and the decision to submit the article for publication. JVL has received speaker fees from Echosens, Gilead Sciences, Moderna, Novo Nordisk, Novovax, Pfizer and ViiV, and grants from Gilead Sciences, GSK, Madrigal Pharmaceuticals, and Roche Diagnostics, outside the submitted work. All other authors declare no competing interests.

Cancer screening rates are significantly lower in US federally qualified health centers

Study finds breast, cervical and colorectal cancer screening substantially lower in clinics serving underrepresented communities compared to overall national and state rates.

UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER

Jane Montealegre, Ph.D. — IMAGE:
JANE MONTEALEGRE, PH.D.
view more
CREDIT: THE UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER

HOUSTON and ALBUQUERQUE, N.M. ― A national study led by researchers at The University of Texas MD Anderson Cancer Center and The University of New Mexico (UNM) Comprehensive Cancer Center found major gaps in breast, cervical and colorectal cancer screening use in Federally Qualified Health Centers (FQHCs) in the U.S., relative to overall screening rates in the country.

The findings, published today in JAMA Internal Medicine, revealed screening use in FQHCs was 45.4% for breast cancer, 51% for cervical cancer and 40.2% for colorectal cancer, compared to cancer screening rates in the general American population of 78.2%, 82.9% and 72.3%, respectively.

“FQHCs provide high-quality primary care to underserved communities in the U.S., which are disproportionately comprised of racial and ethnic minorities, people without health insurance, and those living below the poverty level,” said study author Jane Montealegre, Ph.D., associate professor of Behavioral Science at MD Anderson. “These findings highlight an urgent need to focus on scaling up evidence-based screenings in these populations to mitigate cancer disparities.”

The U.S. Preventive Services Task Force (USPSTF) offers guidance for the general population to get screened for breast, cervical and colorectal cancer based on age and family history. However, screening use remains suboptimal in many marginalized populations. About 30 million people in the U.S. who might not otherwise have access to medical services currently use FQHCs.

The study, led by postdoctoral fellow Trisha Amboree, Ph.D., examined screening information from the Health Center Program Uniform Data System from 1,364 FQHCs between January 1 and December 31, 2020. To understand screening in the general population, researchers evaluated data from the Behavioral Risk Factor Surveillance System, which includes the use of preventive health services for non-institutionalized U.S. adults over the age of 18, during the same time period.

Researchers found cancer screening use in FQHCs varied widely across states. Certain states, such as Maine and New Hampshire, achieved screening rates over 60% and others fell below 35%, including Utah, Wyoming and Alabama. Additionally, the study revealed underscreened populations served by FQHCs in specific states contributed to a large proportion of America’s overall underscreened population. Experts attribute these differences, in part, to the variability of state screening programs and policies around healthcare funding.

“FQHCs face financial constraints and staff turnover while trying to provide care in a fragmented health system. Implementing clinical preventive services such as cancer screenings will require additional support,” said corresponding author Prajakta Adsul, M.B.B.S, Ph.D., assistant professor of Internal Medicine at UNM. “With investments in implementation research in FQHCs, there is potential to mitigate screening-related disparities in medically underserved populations.”

Limitations of the study include self-reporting in the datasets and potential effects from the COVID-19 pandemic.

The research was supported by the National Institutes of Health (R01MD013715, R01CA232888, R01CA256660). A full list of collaborating authors and their disclosures can be found here.

JOURNAL

JAMA Internal Medicine

The aspirin conundrum: navigating negative results, age, aging dynamics and equity

GEORGETOWN UNIVERSITY MEDICAL CENTER

WASHINGTON – A new study examining the role of aspirin in breast cancer treatment reveals critical issues related to health equity and aging that have broad implications for cancer and other disease intervention trials, say researchers from Georgetown University’s Lombardi Comprehensive Cancer Center. They outline their concerns in an editorial accompanying the study’s findings published April 29 in the JAMA (“The Aspirin Conundrum: Navigating Negative Results, Age, Aging Dynamics and Equity”).

The study, called the Alliance trial, was launched after researchers noted that breast cancer survivors taking aspirin as part of another clinical trial for cardiovascular disease lived longer.

To confirm the observation, a phase 3 clinical trial randomly assigned volunteers with nonmetastatic, high-risk breast cancer to receive either 300mg of aspirin or placebo daily. The outcome was a disappointment. The study was suspended at the first interim safety analysis because the results indicated futility – aspirin did not decrease the risk of cancer recurrence or improve survival.

In their editorial examining the trial, the Georgetown researchers, Jeanne Mandelblatt, MD, MPH; Candace Mainor, MD; and Barry Hudson, PhD, raise several important questions about the outcome.

For example, the authors point out that despite efforts to include various groups in the study, certain subgroups, like racial minorities and those with high exposure to systemic racism, may not have been adequately represented.

“Some individuals from these groups may experience chronic life stressors that affect inflammation, accelerate biological aging and contribute to disparities in cancer risk, recurrence and mortality,” they write, noting that these individuals could potentially benefit from aspirin, an anti-inflammatory drug.

Researchers say another issue with this and other trials is how chronological age and biological age might affect implications for a trial’s design and its results.

The results in the Alliance trial “raises the question of whether aspirin's lack of benefit could be partly explained by variations in biological age, including heterogeneity in immune and platelet function, inflammatory responses and host-tumor microenvironment interactions,” they write. “Thus, careful consideration of the intersectionality of aging, cancer and disparities will be critical in designing future oncology and other disease trials to advance health equity.”

Finally, the researchers say clinicians may find it challenging to integrate new findings into routine practice because the results suggest a lack of intervention efficacy along with the many unanswered questions.

Despite the fairly definitive negative result for use of aspirin to improve invasive disease-free survival among breast cancer survivors, the researchers say, “...oncology and primary care providers may still consider discussing with each other and their patients the potential benefits and harms of aspirin used for other reasons.”

###

Mandelblatt was supported in part by the National Institutes of Health at the National Cancer Institute Grants R01CA129769, R35CA197289 and R35CA283926 and National Institutes of Health at the National Institute on Aging Grants R01AG082348, R56AG068086 and R21/R33AG075008. Hudson is supported in part by the National Institutes of Health at the National Cancer Institute Grant R01CA276587.

The funders did not have any role in the writing of this editorial or the decision to submit the editorial for publication.

The authors report the following disclosures:

Mandelblatt is a member of the Alliance Cancer in the Older Adult Committee. She is co-inventor on a pending invention patent application (PCT/US2022/028741) filed by Georgetown University titled “Use of RAGE inhibitors to Treat Cancer-Related Cognitive Decline” and licensed to Cantex Pharmaceuticals. Mandelblatt has waived her rights and will not receive any remuneration, consideration or revenue generated from this license or the patents and patent applications licensed thereunder.

Mainor receives institutional clinical trial funding support from Pfizer and Cantex pharmaceuticals.

Hudson is a co-inventor on a pending invention patent application (PCT/US2022/028741) filed by Georgetown University entitled “Use of RAGE inhibitors to Treat Cancer-Related Cognitive Decline” and licensed to Cantex Pharmaceuticals. Dr Hudson is also a co-inventor on a pending Canadian patent application (CA3118711A1) filed by the University of Miami titled “Method For Treating Breast Cancer and Chronic Diseases.” Development of this latter invention was supported by the Florida Department of Health, Bankhead-Coley Cancer Biomedical Research Program Grant no. 8BC06.

JOURNAL

JAMA

DOI

10.1001/jama.2024.4828

METHOD OF RESEARCH

Commentary/editorial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

The Aspirin Conundrum: Navigating Negative Results, Age, Aging Dynamics and Equity

ARTICLE PUBLICATION DATE

29-Apr-2024

COI STATEMENT

The authors report the following disclosures: Mandelblatt is a member of the Alliance Cancer in the Older Adult Committee. She is co-inventor on a pending invention patent application (PCT/US2022/028741) filed by Georgetown University titled “Use of RAGE inhibitors to Treat Cancer-Related Cognitive Decline” and licensed to Cantex Pharmaceuticals. Mandelblatt has waived her rights and will not receive any remuneration, consideration or revenue generated from this license or the patents and patent applications licensed thereunder. Mainor receives institutional clinical trial funding support from Pfizer and Cantex pharmaceuticals. Hudson is a co-inventor on a pending invention patent application (PCT/US2022/028741) filed by Georgetown University entitled “Use of RAGE inhibitors to Treat Cancer-Related Cognitive Decline” and licensed to Cantex Pharmaceuticals. Dr Hudson is also a co-inventor on a pending Canadian patent application (CA3118711A1) filed by the University of Miami titled “Method For Treating Breast Cancer and Chronic Diseases.” Development of this latter invention was supported by the Florida Department of Health, Bankhead-Coley Cancer Biomedical Research Program Grant no. 8BC06.

Expanding health equity by including nursing home residents in clinical trials

REGENSTRIEF INSTITUTE

INDIANAPOLIS – Clinical trials are constantly being designed and study participants enrolled to determine if medical treatments and therapies are safe and effective. Much has been written about the importance of including diverse populations in these trials.

However, the nearly 1.4 million individuals who live in the 15,600 nursing homes across the U.S. have been largely left out of clinical trials, despite the prevalence of such common conditions as hypertension, depression, diabetes and Alzheimer’s disease in this population.

A commentary by faculty of Regenstrief Institute, Indiana University, UCLA and the universities of North Carolina, Colorado and Massachusetts, published in the Journal of the American Geriatrics Society (JAGS), focuses on the importance of including nursing home residents, a population with significant medical complexity, in clinical trials. The essay highlights the benefits and challenges of conducting research on medical therapies in nursing homes. The authors identify key elements for successful nursing home clinical trials and propose a nursing home clinical trials network, noting that ensuring diversity, equity and inclusion in any trial design is imperative.

“Among the questions we want to ask are: Is this therapy appropriate for a nursing home population? Does it work in a nursing home population but are there issues around implementation? Are there challenges to delivering it in a nursing home setting?” notes corresponding author Kathleen Unroe, M.D., MHA, M.S., a Regenstrief Institute and IU School of Medicine researcher-clinician. “Nursing homes were not built to facilitate research. We as researchers need to fit in. We need to appreciate the realities of providing clinical care in this setting and adjust and adapt our protocols to work within that system.”

Among the topics discussed in the commentary:

The need for clinical trials in nursing homes
Gaps that can be filled with these clinical trials
Challenges conducting these clinical trials
Next steps in conducting clinical trials in nursing homes
A framework for making a nursing home clinical trials network a reality

“It is imperative that we build the science of nursing home care around testing, prevention, diagnosis, and treatment. It is a unique setting that merits more focus given the essential role it plays in the continuum of care for seriously ill adults,” said commentary co-author Susan Hickman, PhD, director of Regenstrief Institute’s Center for Aging Research and a faculty member of IU schools of nursing and medicine.

Citing a missed opportunity, the authors write, “Inclusion of nursing home residents in COVID-19 therapeutics trials might have identified specific issues relating to dosing, administration and monitoring, spurred creation of training materials specifically for nursing home staff, and promoted the development of consistent policies to identify appropriate candidates and deliver treatments promptly, safely, and optimally.”

Dr. Unroe adds, “Nursing home residents should have access to evidence-based therapies. When we choose not to do the hard work to test them in the nursing home setting, we are setting ourselves up for a much more difficult implementation.” She notes that “Conducting trials in the nursing home may generate generalizable knowledge that also would be highly relevant to people who are cared for in assisted living facilities or even the broader geriatric population living at home.”

"Evaluation of medical therapies in the nursing home population: Gaps, challenges, and next steps” is part of a JAGS special collection, "A changing landscape for evaluation of new therapies for older adults and diverse populations: National and international perspectives."

Authors and affiliations:

1Division of General Internal Medicine and Geriatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA

2Indiana University Center for Aging Research, Regenstrief Institute Inc., Indianapolis, Indiana, USA

3Research in Palliative and End-of-Life Communication and Training (RESPECT) Center, Indiana University School of Medicine, Indianapolis, Indiana, USA

4US Department of Veterans Affairs Greater Los Angeles Healthcare System (VAGLAS) Health Services Research and Development Service (HSR&D) Center of Innovation, Los Angeles, California, USA

5David Geffen School of Medicine, University of California, Los Angeles, California, USA

6Anna and Harry Borun Center for Gerontological Research, University of California Division of Geriatrics, Los Angeles, California, USA

7RAND Corporation, Santa Monica, California, USA

8Indiana University School of Nursing, Indianapolis, Indiana, USA

9School of Social Work, University of North Carolina, Chapel Hill, North Carolina, USA

10Cecil G. Sheps Center for Health Services Research, University of North Carolina, Chapel Hill, North Carolina, USA

11Center for Excellence in Assisted Living (CEAL), School of Social Work, University of North Carolina, Chapel Hill, North Carolina, USA

12Division of Geriatric Medicine, University of Colorado School of Medicine Anschutz Campus, Aurora, Colorado, USA

13Denver Veterans Affairs Medical Center, Aurora, Colorado, USA

14Division of Geriatric Medicine, UMass Chan Medical School, Worcester, Massachusetts, USA

Kathleen T. Unroe, M.D., MHA, M.S.

In addition to being a research scientist with the Indiana University Center for Aging Research at Regenstrief Institute, Kathleen Unroe, M.D., MHA, M.S., is an associate professor of medicine at Indiana University School of Medicine and a practicing geriatrician. Dr. Unroe is the founder and an executive officer of Probari, a healthcare start-up supporting nursing home care.

Susan Hickman, PhD

In addition to serving as director and a research scientist with the Indiana University Center for Aging Research at Regenstrief Institute, Susan Hickman, PhD, is a professor at Indiana University School of Nursing, a professor of medicine and the Cornelius and Yvonne Pettinga Professor of Aging Research at Indiana University School of Medicine and co-director of the IU Indianapolis Research in Palliative and End-of-Life Communicating and Training (RESPECT) Signature Center.

JOURNAL

Journal of the American Geriatrics Society

DOI

10.1111/jgs.18829

ARTICLE TITLE

Evaluation of medical therapies in the nursing home population: Gaps, challenges, and next steps

Becker to study Channel Island deer mouse

GEORGE MASON UNIVERSITY

Becker To Study Channel Island Deer Mouse

Madeleine Becker, a Mason doctoral student studying with Cody Edwards, Senior Associate Dean for Faculty and Academic Affairs, College of Science; Executive Director, Smithsonian-Mason School of Conservation (SMSC), Associate Provost for a Sustainable Earth, Office of the Provost, is set to receive funding for the study: “Controlling for time: disentangling evolutionary and conservation genomics questions using ‘time series museomics’ in the California Channel Island deer mouse.”

Becker will investigate evolutionary and conservation genomics in insular Peromyscus populations to uncover general patterns in isolated wild mammal populations while parsing the influences of founder effects, biogeography, lineage, and recent change.

By sequencing genome-wide loci from samples spanning 120 years across the eight California Channel Islands, Becker will take a time-series museomics approach to disentangling signatures of island colonization, inter-island migration, and historically documented bottlenecks.

Additionally, Becker will compare current population-level metrics of inbreeding and mutational load between islands and mainland mice as well as through time. By taking this unconventional approach in a well-studied mammal abundant in museum collections and the wild, she aims to extend the utility of islands as natural laboratories to test common genetic monitoring techniques and better understand baseline patterns of microevolution in isolation. This research will be valuable both in: 1) its evaluation of the success of conservation interventions implemented on the California Channel Islands specifically, and 2) by serving as an important reference point for ex situ conservation efforts hoping to replicate these measures or otherwise mitigate the harmful effects of genetic isolation and bottlenecks in threatened species.

Becker will receive $6,000 as part of an Ecological, Evolutionary, and Conservation Genomics Research Award from the American Genetics Association for this research. Funding will begin in May 2024 and will end in late April 2025.

###