Category: US Department of Health

Source: US Department of Health and Human Services – 2

News Release

Wednesday, September 27, 2023

New diagnoses of six major cancer types in the United States fell abruptly in early 2020, coinciding with the start of the COVID-19 pandemic, according to findings from part 2 of the latest Annual Report to the Nation on the Status of Cancer. The volume of pathology reports also declined sharply in early 2020, suggesting that fewer cancer screenings and other cancer-related procedures were performed during that time. Taken together, the findings suggest that many cancers were not being diagnosed in a timely manner during the early part of the COVID-19 pandemic, likely due to interruptions in medical care.

“These missed opportunities for early cancer detection are alarming, particularly for those vulnerable populations that continue to face significant barriers in accessing cancer care,” said Monica M. Bertagnolli, M.D., director of the National Cancer Institute (NCI). “This report highlights the urgency in helping all Americans get back on track with their cancer care so that we can avoid unnecessary deaths and complications from cancer. That’s exactly why expanding cancer screening access and awareness is a key priority of the Biden-Harris administration’s Cancer Moonshot.”

This study is the largest to date using population-based data from central cancer registries to assess the impact of the COVID-19 pandemic on cancer incidence (new diagnoses of cancer) in the United States. The report appeared September 27, 2023, in Cancer.

The Annual Report to the Nation on the Status of Cancer is a collaborative effort among NCI, part of the National Institutes of Health; the Centers for Disease Control and Prevention (CDC); the American Cancer Society; and the North American Association of Central Cancer Registries to provide information about cancer occurrence and trends in the United States. Part 1 of the latest report, which focused on national cancer statistics, was released in October 2022.

Part 2 of the latest report focuses on changes in cancer diagnoses in the United States during the first year of the COVID-19 pandemic. The authors suggest that these changes were due in part to interruptions in medical care. In particular, early 2020 saw a decline in cancer screenings. In addition, diagnoses made as a result of early symptoms or in the course of routine medical visits may have been delayed when people held off on seeing their doctors.  

The authors analyzed cancer incidence data for 2015 to 2020 using data from select population-based cancer registries that participate in CDC’s National Program of Cancer Registries or NCI’s Surveillance, Epidemiology, and End Results (SEER) Program.

The authors compared the number of newly diagnosed cases of cancer in 2020 with what was expected based on previous years. They looked at female breast, lung, and colorectal cancers, which are often diagnosed through screening tests or other forms of early detection that may have been disrupted by the pandemic; thyroid and prostate cancers, which are often diagnosed incidentally; and pancreatic cancer, which is usually diagnosed when the patient presents with symptoms. The authors also compared the volume of electronic pathology reports sent to central cancer registries in 2020 with the volume sent in 2019.

From March to May 2020, new cases of all six cancer types fell sharply. By July 2020, however, diagnoses of all cancer types except prostate cancer had returned to pre-pandemic levels, with little difference between observed and expected numbers during the second half of the year.

Over the same period in early 2020, the volume of electronic pathology reports also declined steeply before returning to pre-pandemic levels. Because these reports are transmitted automatically to cancer registries, the findings suggest that the decline in new cancer diagnoses was not due to delays in reporting caused by pandemic disruptions but rather to missed screenings and delays in other cancer-related procedures.

The authors also looked at declines in new cancer cases by cancer stage at diagnosis, sex, age, and population group. For each cancer type in the study, new cases of early-stage cancers fell more sharply than new cases of advanced cancers. The declines were greatest for the cancers typically diagnosed through screening (female breast, lung, and colorectal cancer). For example, 7,147 cases of early-stage colorectal cancer were expected to be diagnosed in 2020, but only 5,983 cases were diagnosed—meaning that potentially more than 16% of early-stage colorectal cancer cases weren’t caught.

“We are deeply concerned about the implications of delayed diagnosis, which is typically associated with more aggressive disease and worse outcomes,” said Karen E. Knudsen, M.B.A., Ph.D., chief executive officer of the American Cancer Society. “It is imperative to ensure that we make up for lost ground on finding cancers early, and thereby maximize opportunities for effective treatment and survival.”

However, missed screenings only partly explain the observed declines in new cancer cases. Fewer in-person medical visits likely also contributed to the underdiagnoses, particularly for diseases such as thyroid cancer, which is often caught incidentally during other medical procedures.

Asian or Pacific Islander populations had greater declines in new cases of all cancer types, except for pancreatic cancer, compared with White, Black, and American Indian or Alaska Native populations. Another notable population group difference was a greater decline in prostate cancer diagnoses among White people than Black people.

The authors acknowledged that the data comprise information reported to a subset of cancer registries, which may not be representative of the entire U.S. population. Nor does it include in-depth analyses on cancer diagnoses in Hispanic populations, which will be incorporated at a later point.

Nevertheless, the findings suggest that there were missed opportunities for early cancer detection during the pandemic. Other studies have suggested that delays in cancer detection may lead to long-term consequences, such as shorter survival and greater number of deaths. The authors noted that efforts to get people back on track with screening should focus on removing barriers to preventive care visits and reducing disparities in early detection.

As part of the reignited Cancer Moonshot, the President and First Lady announced a call to action on cancer screening to jump-start progress on the nearly 10 million screenings in the United States that were missed as a result of the pandemic. To date, the Cancer Moonshot has accelerated innovations in cancer prevention, detection, and treatment and has expanded access to cancer screening across all 50 states, territories, and Tribal organizations, including through $200 million invested from CDC. The Biden-Harris administration continues to prioritize closing the screening gap so Americans can catch cancer early, when outcomes are best, and encourage Americans to get recommended screenings.

“We recommend everyone get back into routine health care, including cancer screening,” said Lisa C. Richardson, M.D., M.P.H., director of CDC’s Division of Cancer Prevention and Control. “It’s also important to make sure children, adolescents, and adults are up to date on vaccines to prevent infections with viruses—like hepatitis B virus and human papillomavirus—that can lead to cancer.” 

Meanwhile, research is ongoing to gain additional insights into the impacts of the pandemic on cancer trends.

“This study is a reminder that a decline in cancer incidence may not always reflect progress in the fight against cancer,” said Betsy A. Kohler, M.P.H., North American Association of Central Cancer Registries executive director. “We are currently conducting more in-depth analysis of the full 2020 data to further understand the implications of the pandemic on cancer outcomes.”

For more about the report, see: https://seer.cancer.gov/report_to_nation.

About the American Cancer Society (ACS): The American Cancer Society is a leading cancer-fighting organization with a vision to end cancer as we know it, for everyone. For more than 100 years, we have been improving the lives of people with cancer and their families as the only organization combating cancer through advocacy, research, and patient support. We are committed to ensuring everyone has an opportunity to prevent, detect, treat, and survive cancer. To learn more, visit cancer.org or call our 24/7 helpline at 1-800-227-2345. Connect with us on Facebook, Twitter, and Instagram.

About the Centers for Disease Control and Prevention (CDC): CDC works 24/7 protecting America’s health, safety, and security. Whether diseases start at home or abroad, are curable or preventable, chronic or acute, or from human activity or deliberate attack, CDC responds to America’s most pressing health threats. CDC is headquartered in Atlanta and has experts located throughout the United States and the world. 

About the North American Association of Central Cancer Registries (NAACCR): The North American Association of Central Cancer Registries, Inc., is a professional organization that develops and promotes uniform data standards for cancer registration; provides education and training; certifies population-based registries; aggregates and publishes data from central cancer registries; and promotes the use of cancer surveillance data and systems for cancer control and epidemiologic research, public health programs, and patient care to reduce the burden of cancer in North America. For more, see naaccr.org.

About the National Cancer Institute (NCI): NCI leads the National Cancer Program and NIH’s efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website at cancer.gov or call NCI’s contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237). 

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

Media Advisory

Wednesday, September 27, 2023

NIH-funded study identifies managing maternal stress as a possible way to lessen impacts of prenatal infection on infant socioemotional and cognitive development.

What

For mothers who experience high stress during their pregnancy, prenatal COVID-19 infection may be associated with an increased risk for impaired attention and delayed socioemotional and cognitive functioning in their infants, according to a small study funded by the National Institute of Mental Health, part of the National Institutes of Health. The findings highlight maternal stress as a modifiable target to potentially reduce negative outcomes from prenatal COVID-19 infection and the possible protective benefits to expectant mothers of getting vaccinated for COVID-19 during their pregnancy.

The study, which appears in Pediatric Research, was led by Denise Werchan, Ph.D., Moriah Thomason, Ph.D., and Natalie Brito, Ph.D., at New York University, New York. It included 167 mothers and their infants—50 who reported COVID-19 symptoms or a positive COVID-19 test during their pregnancy and 117 who did not report having COVID-19 while pregnant. The researchers enrolled families between March 2020 and January 2023, with most enrolled between March and August 2020.

Mothers reported on depression, anxiety, and post-traumatic stress symptoms and physical complaints during their pregnancy, which were then averaged into an overall score of prenatal psychosocial stress. Infant development at 6 months was assessed using a behavioral task and self-report measure, in which researchers remotely led families through a visual eye gaze task to measure infant attention and mothers filled out a survey of infant self-regulation. When infants were 12 months old, 99 participating mothers completed surveys to identify possible delays in their child’s socioemotional and cognitive development.

Independently, prenatal stress and COVID-19 infection were not related to infant outcomes at either age. In pregnancies without COVID-19, no association was found between prenatal stress and infant attention at 6 months. However, in pregnancies positive for COVID-19, higher prenatal stress was associated with poorer infant attention. In turn, infants with poorer attention at 6 months were more likely to show possible delays in socioemotional functioning and cognition at 12 months.

The researchers are continuing follow this cohort of children into later ages to examine if the impact of maternal stress on their neurobehavioral development persists, as reflected by parental report, biospecimens, behavioral assessment, and neuroimaging.

Who

Julia Zehr, Ph.D., chief of the Developmental Mechanisms and Trajectories of Psychopathology Branch in the NIMH Division of Translational Research, is available for comment.

Article:

Werchan, D. M., Hendrix, C. L., Hume, A. M., Zhang, M., Thomason, M. E., & Brito, N. H. (2023). Effects of prenatal psychosocial stress and COVID-19 infection on infant attention and socioemotional development. Pediatric Research. https://www.nature.com/articles/s41390-023-02807-8

About the National Institute of Mental Health (NIMH): The mission of NIMH is to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. For more information, visit the NIMH website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

News Release

Tuesday, September 26, 2023

Designation, new research program and update to NIH mission are actions to ensure inclusion of people with disabilities.

Today, Eliseo J. Pérez-Stable, M.D., director of the National Institute on Minority Health and Health Disparities (NIMHD), designated people with disabilities as a population with health disparities for research supported by the National Institutes of Health. The decision was made in consultation with Robert Otto Valdez, Ph.D., the director of the Agency for Healthcare Research and Quality, after careful consideration of a report delivered by an NIMHD advisory council, input from the disability community and a review of the science and evidence. A report issued in December 2022 by the Advisory Committee to the (NIH) Director (ACD), informed by the work of the Subgroup on Individuals with Disabilities, explored similar issues faced by people with disabilities. The designation is one of several steps NIH is taking to address health disparities faced by people with disabilities and ensure their representation in NIH research.

“This designation recognizes the importance and need for research advances to improve our understanding of the complexities leading to disparate health outcomes and multilevel interventions,” said Dr. Pérez-Stable. “Toward this effort, NIMHD and other NIH institutes launched a new research program to better understand the health disparities faced by people with disabilities who are also part of other populations designated as having health disparities.”

NIMHD is the lead NIH institute on monitoring minority health and health disparities research. Designated populations experience significant disparities in their rates of illness, morbidity, mortality and survival, driven by social disadvantage, compared to the health status of the general population. A health disparity designation helps to encourage research specific to the health issues and unmet health needs of these populations. Other NIH-designated populations with health disparities include racial and ethnic minority groups, people with lower socioeconomic status, underserved rural communities and sexual and gender minority groups.

“Access to quality health care is a basic human right. It is unacceptable that in 2023, every person in the United States of America does not have that access,” said HHS Secretary Xavier Becerra. “Research to understand the barriers and unmet needs faced by people with disabilities, and to develop effective interventions to address them, is needed. This designation will help to improve access to healthcare and health outcomes for all people.” 

People with disabilities often experience a wide and varying range of health conditions leading to poorer health and shorter lifespan. In addition, discrimination, inequality and exclusionary structural practices, programs and policies inhibit access to timely and comprehensive health care, which further results in poorer health outcomes. People with disabilities who also belong to one or more other populations with health disparities fare even worse.

Today, NIH also issued a notice of funding opportunity calling for research applications focused on novel and innovative approaches and interventions that address the intersecting impact of disability, race and ethnicity, and socioeconomic status on healthcare access and health outcomes.

“To the disability community, we hear you and thank you for sharing your lived experiences with NIH,” said Acting NIH Director Lawrence A. Tabak, D.D.S., Ph.D. “This designation marks an important step in an agency-wide effort to advance health equity for people with disabilities which also includes updating the NIH mission statement to accurately reflect our goal of turning scientific discoveries into better health for all, including people with disabilities.”

NIH recently issued a Request for Information (RFI) inviting feedback on a proposed update to the NIH mission statement following the recommendations by the ACD informed by the work of the Subgroup on Individuals with Disabilities. The ACD issued a report in December 2022 that included the recommendation to update the NIH mission statement, particularly the phrase “reduce […] disability.” NIH leadership and subject matter experts evaluated the current mission statement and proposed a revised mission statement. The RFI is open through Nov. 24, 2023.

“The Administration for Community Living commends NIH for taking these critical steps to begin addressing the significant and longstanding health disparities experienced by people with disabilities,” said Alison Barkoff, who leads ACL and serves as the advisor to the HHS Secretary on disability policy. “Today’s decision complements other important actions HHS has taken to advance equity for disabled people, including the proposed update to the regulations prohibiting disability discrimination by recipients of HHS funding.” 

About the Agency for Healthcare Research and Quality (AHRQ): AHRQ is the lead Federal agency charged with improving the safety and quality of healthcare for all Americans. AHRQ develops the knowledge, tools, and data needed to improve the healthcare system and help consumers, healthcare professionals, and policymakers make informed health decisions. For more information about AHRQ, visit https://www.ahrq.gov.

National Institute on Minority Health and Health Disparities (NIMHD): NIMHD leads scientific research to improve minority health and reduce health disparities by conducting and supporting research; planning, reviewing, coordinating, and evaluating all minority health and health disparities research at NIH; promoting and supporting the training of a diverse research workforce; translating and disseminating research information; and fostering collaborations and partnerships. For more information about NIMHD, visit https://www.nimhd.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

News Release

Friday, September 22, 2023

Part of NIH’s STRIVE consortium, the therapeutic may prevent overactive immune systems from causing severe symptoms.

A clinical trial has launched to test whether early intensive immune modulation for hospitalized COVID-19 patients with relatively mild illness is beneficial. The placebo-controlled study, part of the global clinical trials consortium known as Strategies and Treatments for Respiratory Infections and Viral Emergencies (STRIVE), will enroll approximately 1,500 people at research sites around the world. It is supported by the National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) in partnership with NIH’s National Center for Advancing Translational Sciences (NCATS).

Immune modulators—treatments for modifying the immune system to better respond to disease or illness—are lifesaving for certain hospitalized COVID-19 patients. However, the optimal timing for administering the medicines to achieve the best outcomes has not been defined.

“The evidence is clear that immune modulation can be beneficial for severely ill COVID-19 patients,” said NIAID Acting Director Hugh Auchincloss, M.D. “Patients with milder cases of COVID-19 are often administered one immune modulator, and a second treatment is added only if the patient becomes severely ill. It is possible that adding a second therapeutic earlier in the patient’s treatment could prevent progression to severe illness and improve recovery. This clinical study aims to answer that question.”

The drug being used to test the strategy of early intensification of immune modulation, abatacept (or Orencia), is manufactured by Bristol Myers Squibb, Princeton, New Jersey. It was first approved by the U.S. Food and Drug Administration in 2005 as a treatment for rheumatoid arthritis in adults and subsequently has been approved to treat other forms of arthritis in adults and children. Researchers think it may also be useful as an immune modulator for COVID-19 by tamping down over-active immune responses.

Abatacept works by binding to and blocking molecules that normally activate T cells, a key part of the immune system. Other immune cells may also be affected by the drug. For patients taking abatacept, the immune system may be less likely to “overreact” when fighting an infection such as COVID-19. Symptoms from an unregulated immune response to COVID-19 can include severe respiratory distress, which can be fatal.

Participants may enroll in the current trial if they are receiving supplemental low-flow oxygen upon being hospitalized for COVID-19 infection at one of the participating study sites. In addition to the local standard of care (which varies by site but must include an immune modulator drug), participants will be randomized to immediately receive either a single intravenous infusion of abatacept with dosage dependent on the patient’s weight, or a placebo infusion. Neither the investigators nor the participants will know who is receiving early immunomodulator intensification and who is not.

Throughout the trial, patient safety will be monitored. Study investigators will closely track participants’ progress over the course of 60 days and will note when they are well enough to be discharged from the hospital and return home. These data, together with the patients’ status at 60 days, will help the study team to understand whether patients benefit from early immune modulator intensification.

Through the STRIVE platform, multiple therapeutic interventions for respiratory infections may be tested at once across a global network of study sites. More than 270 international sites plan to participate in this program, which enables continuous enrollment as COVID-19 surges in different parts of the world. The platform is designed to rapidly test new interventions to combat outbreaks of any respiratory disease, including pathogen X. STRIVE began its first trial, a test of the antiviral S-217622, in February 2023.

For more information about the trial, please visit ClinicalTrials.gov and search identifier NCT05822583.

STRIVE emerged from the NIH ACTIV public-private-partnership initiated in April 2020. The purpose of ACTIV was to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines for COVID-19. STRIVE builds on the efforts of prior ACTIV master protocols that evaluated various therapeutics for people hospitalized with COVID-19. STRIVE is composed of global clinical trial experts from several medical specialties including infectious diseases, pulmonology, intensive care, and emergency medicine. Trial leadership includes Protocol co-chairs Christina Barkauskas, M.D., Duke University, Durham, N.C.; Jane O’Halloran, M.D., Ph.D., Washington University in St. Louis; Nnakelu Eriobu, M.D., Institute of Human Virology in Nigeria; and Tom Murray, Ph.D., from the University of Minnesota in Minneapolis.

NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

News Release

Wednesday, September 20, 2023

First-of-its-kind study points to uric acid as a promising treatment for further investigation.

Researchers have identified uric acid as a potential therapy to enhance recovery from acute ischemic stroke using a new method for conducting preclinical animal research. In the study, researchers from the National Institutes of Health’s Stroke Preclinical Assessment Network (SPAN) rigorously tested the effectiveness of six novel therapies in reducing ischemic brain injury in rodents using strategies normally reserved for clinical studies in humans. The results suggest that uric acid warrants further investigation in additional studies, and potentially human clinical trials. The study was published in Science Translational Medicine.

Ischemic stroke, a leading cause of disability and death in the United States, occurs when a blood clot or other blockage in an artery cuts off blood supply to the brain. Current treatments are aimed at removing the clot by dissolving it with blood-thinners, surgically removing it from the blood vessel, or a combination of both.

Although these treatments help patients recover, scientists are seeking a therapy that could protect the brain from damage, known as a cerebroprotectant, that occurs before or during the restoration of blood flow. While previous preclinical studies in animals have identified numerous promising therapies, they failed to translate to human stroke patients in subsequent clinical trials. Many findings also did not replicate in other laboratories.

“We were faced with a critical need to redesign the entire preclinical approach,” said Francesca Bosetti, Ph.D., Pharm.D., program director at NINDS. “SPAN successfully applied well known clinical research practices to a preclinical trial—randomization, pre-determined sample sizes, treatment masking, blinded analysis, and efforts to make results reproducible in other laboratories.”

In the current study, six candidate therapies were selected based on prior research showing evidence that they could potentially treat stroke. Animals were randomly assigned to treatment and researchers from six different labs tested one of the therapies or a placebo. The efficacy of each treatment was assessed by giving animals a series of behavioral tests. After collecting these data, researchers used a new statistical method to evaluate the therapies at four points in the testing process. They also measured MRI brain scans of lesion volumes. Based on the test results, treatments that failed to show sufficient efficacy were dropped.

In addition to incorporating scientific rigor into preclinical testing, researchers used animal models that resembled typical stroke patients. The study included young mice and rats, aging mice, mice with diet-induced obesity or hyperglycemia, and rats with spontaneous hypertension, with equal numbers of males and females.

“SPAN gives us a head start in screening lots of stroke therapies, and rapidly and efficiently finding drugs that have a higher likelihood of working in human clinical trials,” said Patrick D. Lyden, M.D., professor of physiology and neuroscience at the Zilkha Neurogenetic Institute and professor in the Department of Neurology at the USC Keck School of Medicine, Los Angeles, and principal investigator of the SPAN coordinating center.

Uric acid was the only candidate that passed the efficacy boundary through all phases of analysis. The other interventions, which included four drugs approved by the U.S. Food and Drug Administration to treat other conditions and remote ischemic conditioning, an experimental medical procedure, were dropped after the second or third evaluation.

Uric acid has previously been tested in stroke patients, but not in combination with the clot removal treatment modeled by the study, suggesting that the drug could do well in future trials. However, investigators recommend further testing in animal models before clinical trials in humans.

In the next research phase, which began earlier this year, the SPAN network will expand to include more testing sites and evaluate five additional cerebroprotective interventions.

“SPAN is a collaborative effort by many labs to document reproducible effects in animal models of stroke that mimic treatments in patients,” said Walter J. Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS), which funds SPAN. “We now have a feasible preclinical research method to help identify therapies with a higher chance of success in clinical trials.”

SPAN is composed of a coordinating center at the University of Southern California, Los Angeles, and six research laboratories at Johns Hopkins University, Baltimore; Massachusetts General Hospital, Boston, Yale University, New Haven, Connecticut; the Medical College of Georgia at Augusta University; the University of Iowa, Iowa City; and the University of Texas Health Science Center at Houston.

The study was supported in part by the NINDS (U24NS113452, U01NS113356, U01NS113443, U01NS113445, U01NS113388, U01NS113451,U01NS113444, R01NS099455, R01NS112511, R01NS110378, R01NS117565, R01NS102583, R01NS109910), the National Heart Lung and Blood Institute (R35HL139926), National Center for Advancing Translational Sciences (UL1TR001881), and the National Institute of Biomedical Imaging and Bioengineering (P41EB015922). Author Ryan P. Cabeen is supported in part the Chan Zuckerberg Initiative. Aging mice were provided by the National Institute of Aging’s aged rodent colonies.

NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

News Release

Wednesday, September 20, 2023

New deep brain stimulation device coupled with powerful AI may improve therapy for treatment-resistant depression.

Using a novel deep brain stimulation (DBS) device capable of recording brain signals, researchers have identified a pattern of brain activity or “biomarker” related to clinical signs of recovery from treatment-resistant depression. The findings from this small study are an important step towards using brain data to understand a patient’s response to DBS treatment. The study was published in Nature and supported by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies^® Initiative, or The BRAIN Initiative^®.

Although the approach is still experimental, clinical research shows that DBS can be used safely and effectively to treat cases of depression in which symptoms have not improved with antidepressant medications, referred to as treatment-resistant depression. People receiving DBS undergo surgery to have a thin metal electrode implanted into specific brain areas to deliver electrical impulses that modulate brain activity. How exactly DBS improves symptoms in people with depression is not well-understood, which has made it difficult for researchers to objectively track patients’ response to treatment and adjust as needed.

The small study enrolled 10 adults with treatment-resistant depression, all of whom underwent DBS therapy for six months. Each participant received the same stimulation dose to begin and then stimulation levels were increased once or twice. Later, researchers used artificial intelligence (AI) tools to analyze collected brain data from six patients and observed a common brain activity signature or biomarker that correlated with patients self-reporting feeling symptoms of depression or stable as they recovered. In one patient, researchers identified the biomarker and were retrospectively able to predict that a patient would fall back into a major depressive episode four weeks before clinical interviews showed they were at risk of a relapse occurring.

“This study demonstrates how new technology and a data-driven approach can refine DBS therapy for severe depression, which can be debilitating,” said John Ngai, Ph.D., director of the BRAIN Initiative. “It’s this type of collaborative work made possible by the BRAIN Initiative that moves promising therapies closer to clinical use.”

In the study, patients received DBS targeting the subcallosal cingulate cortex (SCC), a brain region that regulates emotional behavior and is involved in feelings of sadness. DBS of the SCC is an emerging therapy that can provide stable, long-term relief from depressive symptoms for years. However, using DBS to treat depression remains challenging because each patient’s path to stable recovery looks different. Clinicians also must rely on subjective self-reports from patient interviews and psychiatric rating scales to track symptoms, which can fluctuate over time. This makes it hard to distinguish between normal mood variations and more serious situations requiring a tweak in stimulation. In addition, changes in symptoms in response to DBS can take weeks or months to occur, making it difficult to tell how well the therapy is working.

“This biomarker suggests that brain signals can be used to help understand a patient’s response to DBS treatment and adjust the treatment accordingly,” said Joshua A. Gordon, M.D., Ph.D., director of NIH’s National Institute of Mental Health. “The findings mark a major advance in translating a therapy into practice.”

The patients in the study responded well to DBS therapy; after six months, 90% showed a significant improvement in depression symptoms, and 70% were in remission or no longer depressed. This high response rate was a unique opportunity to look back and examine how each patient’s brain responded differently to the stimulation during treatment.

Christopher Rozell, Ph.D., Julian T. Hightower Chair and professor of electrical and computer engineering at Georgia Tech in Atlanta, and his colleagues used a technique called explainable artificial intelligence to understand these subtle changes in brain activity. The algorithm used brain data to distinguish between depressive versus stable recovery states and was able to explain what activity changes in the brain were the main drivers of this transition. Importantly, the biomarker also distinguished between normal day-to-day transient mood changes and sustained worsening symptoms. This algorithm could provide clinicians with an early warning signal that a patient is moving toward a highly depressive state and requires a DBS adjustment and extra clinical care.

“Nine out of 10 patients in the study got better, providing a perfect opportunity to use a novel technology to track the trajectory of their recovery,” said Helen Mayberg, M.D., director of the Nash Family Center for Advanced Circuit Therapeutics at Icahn Mount Sinai in New York City and co-senior author of the study. “Our goal is to identify an objective, neurological signal to help clinicians decide when, or when not, to make a DBS adjustment.”

“We showed that by using a scalable procedure with single electrodes in the same brain region and informed clinical management, we can get people better,” said Dr. Rozell, co-senior author of the study. “This study also gives us an amazing scientific platform to understand the variation between patients, which is key to treating complex psychiatric disorders like treatment-resistant depression.”

Next, the team analyzed data from MRI brain scans collected from patients before surgery. The results revealed structural and functional abnormalities in the specific brain network targeted by the DBS therapy. More severe white matter deficits were related to longer recovery times.

Researchers also used AI tools to analyze changes in facial expression extracted from videos of participant interviews. In a clinical setting, a patient’s facial expression can reflect the severity of their depression symptoms, a change that psychiatrists likely pick up on in routine clinical evaluations. They found patterns in individual patient expressions that coincided with their transition from illness to stable recovery. This could serve as an additional tool and new behavioral marker to track recovery in DBS therapy. More research is needed to determine whether the video analysis can reliably predict current and future disease states.

Both the observed facial expression changes and anatomical deficits correlated with cognitive states captured by the biomarker, supporting the use of this biomarker in managing DBS therapy for depression.

The research team, including Drs. Mayberg and Rozell, and Patricio Riva-Posse, M.D., at Emory University School of Medicine in Atlanta, is now confirming their findings in a second cohort of patients at Mount Sinai. Future studies will continue to explore the antidepressant effects of DBS by using a next-generation device to study the neural basis of moment-to-moment changes in mood.

According to the research team, this study represents a significant advance in early stage DBS therapy for various mental disorders, including severe depression, obsessive-compulsive disorder, post-traumatic stress disorder, binge eating disorder, and substance use disorder. Other DBS studies have identified brain biomarkers for chronic pain, but using brain data to successfully treat patients is still under development.

The study was supported by the NIH BRAIN Initiative (UH3NS103550), the National Science Foundation, the Hope for Depression Research Foundation, and the Julian T. Hightower Chair at Georgia Tech.

The NIH BRAIN Initiative is managed by 10 Institutes and Centers whose missions and current research portfolios complement the goals of The BRAIN Initiative^®: National Center for Complementary and Integrative Health, National Eye Institute, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute of Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Drug Abuse, National Institute on Deafness and other Communication Disorders, National Institute of Mental Health, and National Institute of Neurological Disorders and Stroke.

NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

Source: US Department of Health and Human Services – 2

News Release

Monday, September 18, 2023

NIH-funded study suggests need to reevaluate opioid addiction treatment recommendations in the era of fentanyl.

Individuals with opioid use disorder who were prescribed a lower buprenorphine dose were 20% more likely to discontinue treatment than those on a higher dose, according to a study of patients prescribed buprenorphine in Rhode Island from 2016 to 2020, as fentanyl became widely available. The study, published today in JAMA Network Open, was supported by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and conducted by researchers at Brown University, Providence, Rhode Island; NIDA and the Rhode Island Department of Health.

Among patients newly initiating buprenorphine treatment for opioid use disorder, 59% of those prescribed the target daily dose of 16 milligrams recommended by the U.S. Food and Drug Administration and 53% of those prescribed the higher 24 mg daily dose discontinued treatment within 180 days. A statistical analysis that allowed for multivariable comparison of these two dose groups showed patients prescribed the recommended dose (16 mg) were significantly more likely to discontinue treatment over 180 days compared to those prescribed 24 mg.

Medications for opioid use disorder such as buprenorphine can safely and effectively support reduction in opioid use and overdose as well as recovery by decreasing opioid cravings and easing withdrawal symptoms. These findings build upon accumulating evidence of the safety and efficacy of higher doses of buprenorphine. Studies have shown that more than 16 mg of buprenorphine is safe and well tolerated in people with opioid use disorder in emergency department and outpatient treatment settings.

“Effective treatment can save lives, but our proven treatments for opioid use disorders must evolve to match the challenges posed by the fentanyl crisis,” said NIDA Director, Nora Volkow, M.D. “If science continues to demonstrate that a higher dosage of buprenorphine increases treatment retention, we must reevaluate clinical guidelines to optimize treatment and help people achieve recovery.”

In 2021, of nearly 107,000 overdose deaths reported, more than 70,000 were primarily due to fentanyl, a synthetic opioid that is approximately 50 times stronger than heroin. The ubiquity of fentanyl in the drug supply and resulting overdose death rate increase have raised questions about whether existing dosing guidelines for buprenorphine should be modified to better address the unique challenges posed by such a potent opioid. Currently, labeling approved by the FDA states that maintenance doses should range from 4 mg to 24 mg, with a recommended target dose of 16 mg per day for most patients. Recommended doses for treatment can also vary widely depending on the individual’s needs and response to the medication.

In this study, researchers retrospectively examined data from a statewide population of 6,499 Rhode Island residents initiating buprenorphine as part of treatment for opioid use disorder from 2016 to 2020, a period of fentanyl emergence and predominance. The goal was to estimate the association between patients’ daily buprenorphine dose and retention in treatment over 180 days, a time frame which aligns with the minimum treatment period considered by the U.S. Centers for Medicare and Medicaid Services to measure treatment continuity for opioid use disorder.

Most patients were aged 25 to 44 years, were male, and had private or Medicaid insurance. At initiation of buprenorphine treatment, approximately 21% (1,343 patients) were prescribed 8 mg, 50% (3,264 patients) 16 mg, and 10% (668 patients) 24 mg. Those prescribed more than 24 mg were unable to be analyzed due to the small number (0.2%, or 15 patients) prescribed such doses during the study period.

Patients prescribed a 24 mg dose of buprenorphine were retained in treatment for a longer period than those prescribed the recommended target maintenance dose of 16 mg. A statistical analysis showed the latter group was 20% more likely to discontinue treatment than those prescribed 24 mg.

“The current recommended target dose of buprenorphine was derived from studies conducted prior to the widespread availability of fentanyl. Now, we’re seeing people with higher levels of tolerance to and dependence on opioids, and our findings suggest that a higher buprenorphine dose – up to 24 mg – may help improve treatment retention for these individuals,” said Rachel Wightman, M.D., Associate Professor of Emergency Medicine and Epidemiology at Alpert Medical School of Brown University and one of the principal investigators of the study. “We have a responsibility to set patients up for success.”

To continue this research, scientists aim to conduct a prospective randomized clinical trial to assess the impact of daily buprenorphine doses up to 24 mg in improving treatment retention and reducing the risk of overdose and death. Within this trial, the researchers will also investigate the role of other factors that may be associated with treatment retention, including clinician prescribing practices, as well as patient socio-demographics and life circumstances. Findings from this trial could ultimately help inform updates to opioid use disorder treatment standards.

For more information on substance and mental health treatment programs in your area, call the free and confidential National Helpline 1-800-662-HELP (4357) or visit www.FindTreatment.gov. 

About the National Institute on Drug Abuse (NIDA): NIDA is a component of the National Institutes of Health, U.S. Department of Health and Human Services. NIDA supports most of the world’s research on the health aspects of drug use and addiction. The Institute carries out a large variety of programs to inform policy, improve practice, and advance addiction science. For more information about NIDA and its programs, visit https://www.nida.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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Source: US Department of Health and Human Services – 2

News Release

Monday, September 18, 2023

NIH study reviews 25 years of data and finds AI/ML can detect common hormone disorder.

Artificial intelligence (AI) and machine learning (ML) can effectively detect and diagnose Polycystic Ovary Syndrome (PCOS), which is the most common hormone disorder among women, typically between ages 15 and 45, according to a new study by the National Institutes of Health. Researchers systematically reviewed published scientific studies that used AI/ML to analyze data to diagnose and classify PCOS and found that AI/ML based programs were able to successfully detect PCOS.

“Given the large burden of under- and mis-diagnosed PCOS in the community and its potentially serious outcomes, we wanted to identify the utility of AI/ML in the identification of patients that may be at risk for PCOS,” said Janet Hall, M.D., senior investigator and endocrinologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and a study co-author. “The effectiveness of AI and machine learning in detecting PCOS was even more impressive than we had thought.”

PCOS occurs when the ovaries do not work properly, and in many cases, is accompanied by elevated levels of testosterone. The disorder can cause irregular periods, acne, extra facial hair, or hair loss from the head. Women with PCOS are often at an increased risk for developing type 2 diabetes, as well as sleep, psychological, cardiovascular, and other reproductive disorders such as uterine cancer and infertility.

“PCOS can be challenging to diagnose given its overlap with other conditions,” said Skand Shekhar, M.D., senior author of the study and assistant research physician and endocrinologist at the NIEHS. “These data reflect the untapped potential of incorporating AI/ML in electronic health records and other clinical settings to improve the diagnosis and care of women with PCOS.”

Study authors suggested integrating large population-based studies with electronic health datasets and analyzing common laboratory tests to identify sensitive diagnostic biomarkers that can facilitate the diagnosis of PCOS.

Diagnosis is based on widely accepted standardized criteria that have evolved over the years, but typically includes clinical features (e.g., acne, excess hair growth, and irregular periods) accompanied by laboratory (e.g., high blood testosterone) and radiological findings (e.g., multiple small cysts and increased ovarian volume on ovarian ultrasound). However, because some of the features of PCOS can co-occur with other disorders such as obesity, diabetes, and cardiometabolic disorders, it frequently goes unrecognized.

AI refers to the use of computer-based systems or tools to mimic human intelligence and to help make decisions or predictions. ML is a subdivision of AI focused on learning from previous events and applying this knowledge to future decision-making. AI can process massive amounts of distinct data, such as that derived from electronic health records, making it an ideal aid in the diagnosis of difficult to diagnose disorders like PCOS. 

The researchers conducted a systematic review of all peer-reviewed studies published on this topic for the past 25 years (1997-2022) that used  AI/ML to detect PCOS. With the help of an experienced NIH librarian, the researchers identified potentially eligible studies. In total, they screened 135 studies and included 31 in this paper. All studies were observational and assessed the use of AI/ML technologies on patient diagnosis. Ultrasound images were included in about  half the studies. The average age of the participants in the studies was 29.

Among the 10 studies that used standardized diagnostic criteria to diagnose PCOS, the accuracy of detection ranged from 80-90%.

“Across a range of diagnostic and classification modalities, there was an extremely high performance of AI/ML in detecting PCOS, which is the most important takeaway of our study,” said Shekhar. 

The authors note that AI/ML based programs have the potential to significantly enhance our capability to identify women with PCOS early, with associated cost savings and a reduced burden of PCOS on patients and on the health system.

Follow-up studies with robust validation and testing practices will allow for the smooth integration of AI/ML for chronic health conditions.    

Several NIEHS clinical studies focus on understanding and detecting PCOS. Learn more at https://joinastudy.niehs.nih.gov.

Grants. This work was supported by the Intramural Research Program of the NIH/National Institute of Environmental Health Sciences (ZIDES102465 and ZIDES103323).

About the National Institute of Environmental Health Sciences (NIEHS): NIEHS supports research to understand the effects of the environment on human health and is part of the National Institutes of Health. For more information on NIEHS or environmental health topics, visit https://www.niehs.nih.gov or subscribe to a news list.

About the National Institutes of Health (NIH): NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH…Turning Discovery Into Health^®

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