One Mission, One Goal: Veterans Health

About NCIRE

We are a scientific community of clinicians and researchers and we partner with the University of California, San Francisco (UCSF) and the San Francisco VA Health Care System (SFVAHCS) to bring the power of modern medicine to the health of our nation’s Veterans.

Congratulations to Barbara Bensing, PhD and Paul Sullam, MD for their recently published studies!

NCIRE-supported investigator Barbara Bensing, PhD co-authored the following published studies:

Molecular recognition of sialoglycans by streptococcal Siglec-like adhesins: toward the shape of specific inhibitors

Publication: RSC Chemical Biology, Oct 18, 2021

https://pubmed.ncbi.nlm.nih.gov/34977577/

O-linked α2,3 sialylation defines stem cell populations in breast cancer

Publication: Science Advances, January 7, 2022

https://pubmed.ncbi.nlm.nih.gov/34995107/

Paul Sullam, MD, a fellow NCIRE-supported investigator, joined his colleague Dr. Bensing to co-author the following studies:

Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis

Publication: Glycobiology, August 25, 2021

https://pubmed.ncbi.nlm.nih.gov/34459483/

Origins of glycan selectivity in streptococcal Siglec-like adhesins suggest mechanisms of receptor adaptation.

Publication: Nature Communications, May 18, 2022

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Glycemic treatment deintensification practices in nursing home residents with type 2 diabetes

Nursing home (NH) residents with diabetes represent a large, growing population at high-risk for adverse events from glucose-lowering medications (GLMs). Studies in community dwelling older adults have shown that glycemic overtreatment is common and can cause significant harms. Recent studies have documented increased risk of mortality, severe hypoglycemia, cognitive impairment, and falls as potential negative consequences of overtreatment.

Approximately 1.3 million adults resided in an NH in 2016; an estimated 25%–34% of these NH residents have diabetes. Yet, despite the large and growing numbers of NH residents with diabetes, little is known about GLM prescribing and deprescribing practices in this population.

To dive into this mystery, NCIRE-supported investigators Sei Lee, MD, Michael Steinman, MD, and their colleagues conducted a cohort study from January 1, 2013, to December 31, 2019, among Veterans Affairs (VA) NH residents. Participants were VA NH residents age ≥65 with type 2 diabetes with a NH length of stay (LOS) ≥ 30 days and an HbA1c result during their NH stay. The study defined overtreatment as HbA1c <6.5 with any insulin use, and potential overtreatment as HbA1c <7.5 with any insulin use or HbA1c <6.5 on any glucose-lowering medication (GLM) other than metformin alone. The primary outcome was continued glycemic overtreatment without deintensification 14 days after HbA1c.

Sliding scale insulin use in a national cohort study of nursing home residents with type 2 diabetes

NCIRE scientist Sei Lee, MD co-published a study that sought to determine the prevalence of sliding scale insulin (SSI) use and identify factors associated with stopping SSI or transitioning to another short-acting insulin regimen, in light of health guidelines that discourage SSI use after the first week of a nursing home (NH) admission.

The observational study gathered data from October 1, 2013, to June 30, 2017, of non-hospice Veterans Affairs NH residents with type 2 diabetes and an NH admission over 1 week and compared the weekly prevalence of SSI versus two other short-acting insulin regimens – fixed dose insulin (FDI) or correction dose insulin (CDI, defined as variable SSI given alongside fixed doses of insulin) – from week 2 to week 12 of admission.

Among those on SSI in week 2, the study examined factors associated with stopping SSI or transitioning to other regimens by week 5. Factors included demographics (e.g., age, sex, race/ethnicity), frailty-related factors (e.g., comorbidities, cognitive impairment, functional impairment), and diabetes-related factors (e.g., HbA1c, long-acting insulin use, hyperglycemia, and hypoglycemia).

In week 2, 21% of the cohort was on SSI, 8% was on FDI, and 7% was on CDI. SSI was the most common regimen in frail subgroups (e.g., 18% of our cohort with moderate–severe cognitive impairment was on SSI vs 5% on FDI and 4% on CDI). SSI prevalence decreased steadily from 21% to 16% at week 12 (p for linear trend <0.001), mostly through stopping SSI. Diabetes-related factors (e.g., hyperglycemia) were more strongly associated with continuing SSI or transitioning to a non-SSI short-acting insulin regimen than frailty-related factors.

The study was published in the Journal of the American Geriatrics Society.

Association of Race and Ethnicity with Incidence of Dementia Among Older Adults

The racial and ethnic diversity of the U.S., including among patients receiving their care at the Veterans Health Administration (VHA), is increasing. Dementia is a significant public health challenge and may have greater incidence among older adults from underrepresented racial and ethnic minority groups.

Studies examining racial and ethnic disparities in dementia incidence in the U.S. have consistently reported higher rates of dementia for Black adults. Hispanic older adults are less well studied, but also have greater dementia incidence than White older adults. Much less is known about dementia incidence for American Indian or Alaska Native or for Asian individuals.

NCIRE Board Director Kristine Yaffe, MD, and fellow NCIRE-supported investigators John Boscardin, PhD, and Deborah Barnes, PhD, MPH co-published a study that sought to answer: Is there a difference in incidence of dementia by race and ethnicity among enrollees in the U.S. VHA?

This retrospective cohort study sampled 1,869,090 older adults receiving care at VHA medical centers, the largest integrated health care system in the US. Differences in incidence rates by geographical region across the US were also examined. The sample group were aged 55 years or older and with data evaluated from October 1, 1999, to September 30, 2019 (the date of final follow-up).

The study found that among older adults who received care at VHA medical centers, there were significant differences in dementia incidence based on race and ethnicity. Further research is needed to understand the mechanisms responsible for these differences.

The study was published in the JAMA Network.

Surrogate Decision Makers Need Better Preparation for Their Role: Advice from Experienced Surrogates

Surrogate decision makers are required to make difficult end-of-life decisions with little preparation. Little is known about what surrogates may need to adequately prepare for their role, and few resources exist to prepare them.

NCIRE-supported scientists Deborah Barnes, PhD and Rebecca Sudore, MD, with a team of investigators, explored experiences and advice from surrogates about how best to prepare for the surrogate role. Using a semi-structured focus group model, the study recruited 69 participants through convenience sampling in San Francisco area hospitals, cancer support groups, and community centers for 13 focus groups. Surrogates were included if they were 18 years of age or older and reported having made medical decisions for others.

Experienced surrogate decision makers emphasized the importance of advance care planning (ACP) and advised that surrogates need their own preparation to initiate ACP conversations, learn patients' values, advocate for patients, and make informed surrogate decisions. Future interventions should address these preparation topics to ease surrogate burden and decrease disparities in surrogate decision making.

The study was published in the Journal of Palliative Medicine.

Life expectancy for community-dwelling persons with dementia and severe disability

For people with dementia or a severe disability having a clear understanding of their prognosis can help them, their care partners, and clinicians anticipate and plan for future social, financial, functional, and clinical needs.

While prior work around life expectancy and needs of persons with dementia have focused on either overall life expectancy at the time of diagnosis or on end-of-life estimates in nursing home settings, there have been no studies examining life expectancy in community-dwelling persons with dementia, even though the majority of care partners and persons with dementia want to remain at home.

In a first of its kind study, NCIRE Board Director Kristine Yaffe, MD, and fellow NCIRE-supported investigator John Boscardin, PhD, and their colleagues found that among the 842 community-dwelling persons with dementia and severe disability evaluated, the median life expectancy is 1.7 years; one quarter died within 7 months.

The paper was published in the Journal of the American Geriatrics Society.

https://agsjournals.onlinelibrary.wiley.com/doi/10.1111/jgs.17767

Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality

The relationship between vitamin D status and COVID-19-related clinical outcomes is controversial. Prior studies have been conducted in smaller, single-site, or homogeneous populations limiting adjustments for social determinants of health (race/ethnicity and poverty) common to both vitamin D deficiency and COVID-19 outcomes.

NCIRE Board Director Carl Grunfeld, MD, PhD, and fellow NCIRE-supported investigators, Karen Seal, MD and Daniel Bikle, MD, PhD, co-authored a study that evaluates the dose-response relationship between continuous 25(OH)D and risk for COVID-19-related hospitalization and mortality after adjusting for covariates associated with both vitamin D deficiency and COVID-19 outcomes.

The retrospective cohort study investigated 4,599 Veteran patients receiving care in U.S. Department of Veteran Affairs health care facilities with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test and a blood 25(OH)D test between February 20, 2020, and November 8, 2020, followed for up to 60 days.

https://pubmed.ncbi.nlm.nih.gov/34981368/#:~:text=After%20adjusting%20for%20all%20covariates,%25%2C%20p%3D0.009)%20and

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Screening and enrollment of underrepresented ethnocultural and educational populations in the Alzheimer's Disease Neuroimaging Initiative (ADNI)

According to the Alzheimer’s Association, older Black Americans are about twice as likely to have Alzheimer’s or other dementias as whites; older Hispanics are one-and-a-half times as likely to have these disorders as whites. By 2030, nearly 40 percent of all Americans living with Alzheimer’s will be Black or Latino, according to UsAgainstAlzheimer’s, an organization founded in 2010 to diversify Alzheimer’s research.

With this is mind, NCIRE-supported Investigator Michael Weiner, MD and his cohorts conducted an analysis of the ethnocultural and socioeconomic composition of Alzheimer's Disease Neuroimaging Initiative (ADNI) participants to assess the generalizability of ADNI data to diverse populations.

ADNI, which began in 2004 under Weiner’s leadership, is the most extensive Alzheimer’s observational study globally and considered by many to be the gold standard for clinical trials for the disease. The study has attracted more than 2,000 subjects since 2004 at 60 sites across the U.S. and Canada.

In the analysis, ADNI data collected between October 2004 and November 2020 were used to determine ethnocultural and educational composition of the sample and differences in the following metrics: screening, screen fails, enrollment, biomarkers.

Of the 3739 screened individuals, 11 percent identified as being from ethnoculturally underrepresented populations (e.g., Black, Latinx) and 16 percent had less than 12 years of education. Of the 2286 enrolled participants, 11 percent identified as ethnoculturally underrepresented individuals and 15 percent had less than 12 years of education. This participation is considerably lower than US Census data for adults 60+ (ethnoculturally underrepresented populations: 25 percent; less than 12 years of education: 4 percent). Individuals with less than 12 years of education failed screening at a higher rate.

Thomas Neylan, MD, 2021 Robert S. Laufer Memorial Award recipient

The International Society for Traumatic Stress Studies honored NCIRE-supported Investigator Thomas Neylan, MD with its 2021 Robert S. Laufer Memorial Award.

This award is given to an individual or group who has made an outstanding contribution to research in the field of traumatic stress. Robert S. Laufer, PhD, was a sociologist who made early and important contributions to the field of traumatic stress and PTSD through his research on the effects of war experiences on Vietnam combat veterans. Laufer was Professor of Sociology at Brooklyn College of the City University of New York and an author of the groundbreaking study of returning veterans, entitled Legacies of Vietnam: Comparative Adjustment of Veterans and Their Peers, published in 1981, with Arthur Egendorf, Ellen Frey-Wouters, and others.

Laufer and colleagues expanded the concept of combat exposure to include multiple dimensions. In particular, he focused on witnessing or participating in abusive violence, an important new focus for a guerilla war where there were no front lines, and where enemy combatants and civilians were often difficult to distinguish. He found that abusive violence followed from more extreme exposure to combat, and was associated with distinctive psychological and behavioral outcomes, including different aspects of PTSD. Laufer died prematurely of cancer in 1989 at the age of 47. This award is made in his memory.

A rare case of axillary keratoacanthoma arising in hidradenitis suppurativa

Keratoacanthoma (KA), a cutaneous, often spontaneously regressing tumor characteristically presenting as an umbilicated nodule with a central keratin plug, occurs most frequently in lightly pigmented individuals with sun damage. NCIRE-supported Investigator Maria Wei, MD, PhD co-published a study that reports an unusual case of KA with a large pedunculated morphology, diagnosed in an African American man, that arose in hidradenitis suppurativa (HS), a relapsing inflammatory skin disease affecting hair follicles in intertriginous areas.

Daniel Mathalon, PhD honored with Lifetime Achievement Award

NCIRE-supported Investigator Daniel Mathalon, PhD was one of five psychological and brain sciences alumni honored by the University of Indiana at its Department of Psychological and Brain Sciences’ 2021 Alumni Recognition Day back in October 2021.

Dr. Mathalon received the department’s Lifetime Achievement Award for his prestigious work in the field of psychiatry.

The department, in the IU Bloomington College of Arts and Sciences, has acknowledged outstanding graduates of its bachelor’s and Ph.D. programs with a series of awards since 2013, the year of the department’s 125th anniversary.

Dr. Mathalon is the Deputy Vice Chair for Research at the San Francisco VA Health Care System, and professor with the Department of Psychiatry and Behavioral Sciences, Weill Institute for Neurosciences at University of California, San Francisco.

Deep learning for Alzheimer's disease: Mapping large-scale histological tau protein for neuroimaging biomarker validation

Definite diagnosis of Alzheimer’s disease is now determined at autopsy when the abnormal spread in the brain of proteins – including “tau” – are evident. But researchers at the UCSF Center for Intelligent Imaging (ci2), including NCIRE-supported Investigator Duygu Tosun-Turgut, PhD, suggest that “in vivo tau PET imaging” may be a game changer by visualizing tau deposition in living people.

Their study in the March issue of NeuroImage (https://www.sciencedirect.com/science/article/pii/S1053811921010570 ) opens avenues for thorough and systematic validation of new neuroimaging tracers and expediting their approval for clinical use.

"This work outlines an end-to-end deep learning-powered pipeline to facilitate dense quantification of whole-brain tau inclusions observed at autopsy in perfect alignment with in vivo neuroimaging, which will allow directly linking imaging measures to ground-truth neuropathological inclusions at autopsy," said Dr. Tosun.

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