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DISCOVERY AND VALIDATION OF AGONISTIC ANGIOTENSIN RECEPTOR AUTOANTIBODIES AS BIOMARKERS OF ADVERSE OUTCOMES

Abadir P, Jain A, Powell L, Xue QL, Tian J, Hamilton RG, Bennett D, Finucane T, Walston JD, Fedarko NS.

Drs. Abadir, Fedarko and colleagues have discovered that frail older individuals have markedly higher levels of an autoantibody that activates the angiotensin system. The angiotensin system is a key hormonal system that regulates blood pressure, inflammation, fibrosis and fluid balance. Consistent with the activation of the angiotension system type 1 receptors, the presence of these antibodies is associated with increased blood pressure, inflammatory burden and falls, and with decline in grip strength, walking speed and increased number of falls. For every 1 microgram per milliliter of blood increase in autoantibodies, the researchers observed a decrease in hand grip strength of 5.7 pounds. Additionally, every 1 microgram per milliliter of blood increase in autoantibodies increased the odds of falling by 30 percent.

To examine the effects of autoantibodies levels on ARBs, data from a second patient population of 60 individuals age 70 to 90 in Chicago was utilized to measure autoantibody levels. One half had been treated with ARBs. The investigators observed similar associations between autoantibody levels and decline in grip strength and walking speed in the Chicago population. Furthermore, for every 1 microgram per milliliter increase of autoantibodies, those not receiving ARBs lived 115 days less — approximately shortened life span by 9 percent. Chronic treatment with ARBs attenuated the autoantibodies’ association with decline in grip strength and increased mortality. The use of angiotensin receptor blocking agents (ARBs) in those with higher levels of autoantibodies also correlated with better control of blood pressure, suggesting a possible personalized medicine approach to high blood pressure treatment in older adults. The study was published on November 30, 2016 in the journal, Circulation. Dr. Abadir is a former JHU OAIC RCDC and Pilot awardee; Dr. Xue is the Biostatistics Core Director; Dr. Fedarko is the Pilot Core Leader; and Dr. Walston is JHU OAIC PI.

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Overview
Americans are living longer than ever, and life expectancy is currently at a record high. More than 10,000 baby boomers turn 65 every day, and according to the Eldercare Workforce Alliance, the United States is ill-prepared to meet current and future workforce needs for its aging adult population.

Be a part of the solution to this major problem facing the healthcare landscape with an online master's degree in gerontology or graduate certificate in aging and geriatric practice from the University of Florida College of Medicine.

Practical education is a must in this changing health care job environment. Opportunities continue to become available for qualified individuals in elder care. Gain credentials that will allow you to further your career through our online educational programs.

Benefits of UF’s online gerontology graduate program include:
  • Interactive, asynchronous courses taught by leading doctors and researchers
  • Flexible schedules tailored for working professionals
  • Continually updated curriculum to reflect the latest research
  • No clinical experience requirement
Learn More on University of Florida's College of Medicine website



6TH VITAL SIGN MEASURING MOBILE HEALTH JOIN THE GLOBAL STUDY. IMPROVE THE HEALTH OF THE WORLD.

6th Vital Sign Help us learn how to improve the health of people around the world!
The 6th Vital Sign is a global research study that uses Apple's ResearchKit to measure a vital sign. Vital signs, like blood pressure or temperature, are measurements used by doctors and nurses to see how healthy a person is. Walking speed has been recommended by experts as the next vital sign to be checked. Walking speed can be used to predict changes in people's health and their ability to do day-to-day activities. It can also predict whether they may fall or need to go to the hospital. Right now we do not have a good way to measure walking speed that is the same for everyone, but you can help! Join our global walking speed study today to help us help people all over the world.
Why It Matters

Walking speed, like blood pressure, can help us predict future health events like heart problems. But walking speed may help us predict if someone is at risk for falling or needs help getting back to their usual self.
Learn

Learn how your walking speed compares to others, and what you can do to stay healthy.
Who can Participate?
  • Anyone over the age of 18 with access to an iPhone 5s, 6 or 6 plus
  • Must be a resident of the United States
  • The first version of the app is only in English
Learn More 



Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction
A Randomized Clinical Trial


Dalane W. Kitzman, MD1; Peter Brubaker, PhD2; Timothy Morgan, PhD3; Mark Haykowsky, PhD4; Gregory Hundley, MD1; William E. Kraus, MD5; Joel Eggebeen, MS6; Barbara J. Nicklas, PhD7

Importance More than 80% of patients with heart failure with preserved ejection fraction (HFPEF), the most common form of heart failure among older persons, are overweight or obese. Exercise intolerance is the primary symptom of chronic HFPEF and a major determinant of reduced quality of life (QOL).

Objective To determine whether caloric restriction (diet) or aerobic exercise training (exercise) improves exercise capacity and QOL in obese older patients with HFPEF.

Design, Setting, and Participants
Randomized, attention-controlled, 2 x 2 factorial trial conducted from February 2009 through November 2014 in an urban academic medical center. Of 577 initially screened participants, 100 older obese participants (mean [SD]: age, 67 years [5]; body mass index, 39.3 [5.6]) with chronic, stable HFPEF were enrolled (366 excluded by inclusion and exclusion criteria, 31 for other reasons, and 80 declined participation).




Frailty in Older Adults: A Nationally Representative Profile in the United States

Bandeen-Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, Xue QL, Walston JD, Kasper JD.
Johns Hopkins University Older Americans Independence Center
A large-scale, nationally representative survey of older Americans living at home or in assisted living settings found that 15 percent of these older Americans are frail, a diminished state that makes people more vulnerable to falls, chronic disease and disability, while another 45 percent are considered pre-frail, or at heightened risk of becoming physically diminished. The Johns Hopkins Older Americans Independence Center study found frailty prevalence to increase sharply with age and to be slightly higher among older women than older men. The researchers found striking racial disparities, with blacks and Hispanics more than 50% more likely to be frail than whites, as well as a heightened prevalence of frailty among poorer Americans. The study also found wide regional differences in frailty prevalence and substantially increased prevalence of various adverse health outcomes among the frail. The study appeared in the November 2015 issue of Journals of Gerontology: Medical Sciences. Dr. Karen Bandeen-Roche is JHU OAIC Co-Pi, and Dr. Jeremy Walston is JHU OAIC PI.


Functional Decline in Patients with Cirrhosis Awaiting Liver Transplantation: Results from the Functional Assessment in Liver Transplantation (FrAILT) Study.

Lai JC, Dodge JL, Sen S, Covinsky K, Feng S.
Hepatology. 2015 Oct 30. doi: 10.1002/hep.28316. [Epub ahead of print]
PMID: 26517301 [PubMed - as supplied by publisher]
This study examined the usefulness of geriatric measures of functional status such as the SPPB in assessing clinical status of patients on the liver transplant wait list. Measures such as the SPPB declined while patients were on the wait list, and the amount of decline strongly predicted wait list mortality, independent of measures of liver disease severity such as the MELD. The study supports the use of functional status measures such as the SPPB in monitoring the status of liver transplant candidates. Jennifer Lai is a UCSF OIAC career development scholar and Ken Covinsky is UCSF OAIC PI.


Increase in Disability Prevalence Before Hip Fracture.

Smith AK, Cenzer IS, John Boscardin W, Ritchie CS, Wallhagen ML, Covinsky KE.
J Am Geriatr Soc. 2015 Oct;63(10):2029-35. doi: 10.1111/jgs.13658.
PMID: 26480970 [PubMed - in process]
This study used the Health and Retirement Study to examine changes in functional status in the 2 years preceding hip fracture in older persons. The study showed marked declines in functional status starting about 10 months before hip fracture. The results provide strong evidence that a substantial component of the poor functional outcomes observed in hip fracture patients is explained by factors other than the hip fracture. All authors are UCSF OIAC investigators. First author Alex Smith is a UCSF OAIC career development scholar.


Treatment patterns for older veterans with localized prostate cancer

Hoffman RM, Shi Y, Freedland SJ, Keating NL, Walter LC.
Cancer Epidemiol. 2015 Jul 27. pii: S1877-7821(15)00142-3. doi: 10.1016/j.canep.2015.07.005. [Epub ahead of print]
PMID: 26228494 [PubMed - as supplied by publisher]

This paper demonstrated that rates of over treatment of prostate cancer have fallen over time in the VA health system. Older men with functional impairment and multi morbidity and low risk disease are more likely to have better outcomes with active surveillance than with surgery, radiotherapy, or androgen deprivation. This study showed that use of active surveillance among these patients has steadily increased. Louise Walter (senior author) directs the UCSF OAIC career development core




Pain in Community-Dwelling Older Adults with Dementia: Results from the National Health and Aging Trends Study

Hunt LJ, Covinsky KE, Yaffe K, Stephens CE, Miao Y, Boscardin WJ, Smith AK.
J Am Geriatr Soc. 2015 Jul 22. doi: 10.1111/jgs.13536. [Epub ahead of print]
PMID: 26200445 [PubMed - as supplied by publisher]

This paper showed high rates of untreated pain among older persons with advanced dementia, suggesting that greater attention to pain as a comorbid symptom in dementia could improve quality of life. All authors are affiliated with the UCSF OAIC. Lauren Hunt (first author) is PhD candidate in the UCSF School of Nursing. Alex Smith (senior author) is UCSF OAIC career development advanced scholar.




The relationship of physical performance with HIV disease and mortality

Greene M, Covinsky K, Astemborski J, Piggott DA, Brown T, Leng S, Galai N, Mehta SH, Guralnik J, Patel KV, Kirk GD.
AIDS. 2014 Nov 28;28(18):2711-9. doi: 10.1097/QAD.0000000000000507.
PMID: 25493597 [PubMed - indexed for MEDLINE]

This paper showed that the SPPB, a commonly used measure of function in Geriatrics, predicts mortality in older persons with HIV. UCSF OAIC authors include Meredith Greene (Career Development Scholar) and Ken Covinsky (OAIC PI).




Quantification of biological aging in young adults

Daniel W. Belskya,b,1, Avshalom Caspic,d,e,f, Renate Houtsc , Harvey J. Cohena , David L. Corcorane , Andrea Danesef,g, HonaLee Harringtonc , Salomon Israelh , Morgan E. Levinei , Jonathan D. Schaeferc , Karen Sugdenc , Ben Williamsc , Anatoli I. Yashinb , Richie Poultonj , and Terrie E. Moffittc,d,e,f

A research team led by Duke Pepper Center Scholar Dan Belsky, and Avshalom Caspi, and Terrie Moffitt at Duke University reports that the process of aging is already highly variable among people still in their 20's and 30's. Young people who are aging rapidly are already showing signs of physical and cognitive decline in their 30's.




Time to benefit for colorectal cancer screening: survival meta-analysis of flexible sigmoidoscopy trials

Tang V, Boscardin WJ, Stijacic-Cenzer I, Lee SJ.
BMJ. 2015 Apr 16;350:h1662. doi: 10.1136/bmj.h1662.
PMID: 25881903 [PubMed - in process] Free PMC Article

This paper assessed how estimates of life expectancy can help guide decisions about which older persons are most likely to benefit from screening from colorectal cancer screening. Using survival metaanalysis of trials of flexible sigmoidoscopy, Tang and colleagues showed that an older person needs a life expectancy of at least 10 years in older to experience a significant chance of mortality reduction with colorectal cancer screening. This project supports the need the role of prognostication in making decisions about cancer screening in older persons. The first author, Vickie Tang a Geriatrics Fellow supported by the UCSF OAIC, and the senior author, Sei Lee is RCDC Scholar. Boscardin leads the UCSF OAIC research design and analysis core and Stijacic-Cenzer is an OAIC senior statistician.




Functional Outcomes After Lower Extremity Revascularization in Nursing Home Residents: A National Cohort Study.

Oresanya L, Zhao S, Gan S, Fries BE, Goodney PP, Covinsky KE, Conte MS, Finlayson E.
JAMA Intern Med. 2015 Apr 6. doi: 10.1001/jamainternmed.2015.0486. [Epub ahead of print]
PMID: 25844523 [PubMed - as supplied by publisher]

This study examined outcomes in a national cohort of nursing home patients receiving revascularization. The study showed that walking ability generally did not improve following surgery and 1 year mortality rates were high. The study supports that need for integrating palliative care into the management of nursing home patients receiving revascularization as well as informed decision making in patients and families. Dr Oresanya is a surgical resident at UCSF and Emily Finlayson is a recipient of a pilot grant from the UCSF OAIC.




A Targeted Infection Prevention Intervention in Nursing Home Residents With Indwelling Devices
A Randomized Clinical Trial


Lona Mody, MD; Sarah L. Krein, PhD; Sanjay K. Saint, MD; Lillian C. Min, MD; Ana Montoya, MD; Bonnie Lansing, LPN; Sara E. McNamara, MPH; Kathleen Symons, BA; Jay Fisch, BS; Evonne Koo, MPH; Ruth Anne Rye, BS; Andrzej Galecki, MD, PhD; Mohammed U. Kabeto, MS; James T. Fitzgerald, PhD; Russell N. Olmsted, MPH; Carol A. Kauffman, MD; Suzanne F. Bradley, MD

Funded by an NIA RO1 and supported by the Ann Arbor OAIC Pepper Center, this study evaluates the effectiveness of a multi-component targeted infection-control program (TIP) in preventing infections and antimicrobial resistance. Using a cluster-randomized study design, we tested whether a multi-modal intervention reduces the prevalence of resistant organisms and incident device-related infections in high-risk nursing home residents with indwelling urinary catheters and/or feeding tubes. The study shows that the intervention facilities had a decrease in the overall prevalence of resistant organisms by 23%, a decline in new MRSA acquisitions by 22%, and clinically-defined catheter-associated urinary tract infections.

Lessons learned from the TIP study and catheter-associated urinary tract infections (CAUTI) reductions efforts in acute care are being implemented in over 500 VA and non-VA NHs in all 50 states through a project funded by the Agency for Healthcare Research and Quality (AHRQ). This “AHRQ Safety Program in Long-Term Care: CAUTI� (Saint, Mody: co-PIs) emphasizes a technical component of professional development in catheter utilization, care and maintenance, antimicrobial stewardship, as well as a socio-adaptive component of culture change, team building, and leadership engagement for the reduction of CAUTIs.




Potential overtreatment of diabetes mellitus in older adults with tight glycemic control
Lipska KJ, Ross JS, Miao Y, Shah ND, Lee SJ, Steinman MA.
JAMA Intern Med. 2015 Mar 1;175(3):356-62. doi: 10.1001/jamainternmed.2014.7345.
PMID: 25581565 [PubMed - in process]

Comment: This paper is part of a very active ongoing collaboration between the Yale and UCSF Pepper Center’s focused on Geriatric Diabetes: Specifically targeted towards individualizing treatment based on the patient characteristics such as functional impairment and multi morbidity. The study strongly suggested very high levels of over treatment of glucose in older persons with serious multi morbidity - with over half of patients with serious comorbidity and an A1c of <7% treated with sulfonylureas or insulin - putting them at risk of hypoglycemia, despite choosing wisely guidelines recommending an A1c target of 8.0% in this population.

The lead author, Kasia Lipska is a Yale Pepper Center Scholar, and mentored by Tom Gill - Joe Ross is also a collaborator of the Yale Pepper Center. The senior author, Mike Steinman, directs the research, design and accrual core of the UCSF Pepper Center. YingHui Miao is a statistician in that core, and Sei Lee is a career development scholar in the UCSF Pepper Center

The paper received a very high level of media attention



Functional Impairment and Hospital Readmission in Medicare Seniors
Greysen SR, Stijacic Cenzer I, Auerbach AD, Covinsky KE.
JAMA Intern Med. 2015 Feb 2. doi: 10.1001/jamainternmed.2014.7756. [Epub ahead of print]
PMID: 25642907 [PubMed - as supplied by publisher]

Comment: This paper showed that ADL impairment is a strong predictor of readmission in a nationally representative sample of older persons following hospitalization. In determining which hospitals will be penalized based on high readmission rates, CMS adjusts for comorbidity, but not functional status. This paper showed that the CMS approach is inadequate, as functional impairment remained a strong predictor, even after adjusting for the chronic conditions assessed by CMS. The article and an accompanying editorial by Ashish Jha focused on the need for hospitals to routinely measure and collect functional data on patients

The lead author, Dr. Ryan Greysen, is a career development scholar in the UCSF OAIC. Stijacic Cenzer is a statistician the data, measures, and analysis core, Auerbach is PESC awardee, and Covinsky is center PI



Outcomes after Breast Cancer Surgery among Nursing Home Residents in the US
Emily Finlayson, MD, MS


Functional Assessment in Liver Transplantation
Jennifer Lai, MD American Journal (Paper), 2014


Marco Pahor, MD; Jack M. Guralnik, MD, PHD;Walter T. Ambrosius, PhD; Steven Blair, PED; Denise E. Bonds, MD; Timothy S. Church, MD, PhD, MPH; Mark A. Espeland, PhD; Roger A. Fielding, PhD; Thomas M. Gill, MD; Erik J. Groessl, PhD; Abby C. King, PhD; Stephen B. Kritchevsky, PhD; Todd M. Manini, PhD; MaryM. McDermott, MD; Michael E. Miller, PhD; Anne B. Newman, MD, MPH;WJack Rejeski, PhD; Kaycee M. Sink, MD, MAS; Jeff D. Williamson, MD, MHS; for the LIFE study investigators
Effect of Structured Physical Activity on Prevention of Major Mobility Disability in Older Adults
The LIFE Study Randomized Clinical Trial


Jared M. Dickinson1, Elena Volpi, and Blake B. Rasmussen2
Exercise and Nutrition to Target Protein Synthesis Impairments in Aging Skeletal Muscle


May 24, 2013: Murphy RA, Register TC, Shively CA, Carr JJ, Ge Y, Heilbrun ME, Cummings SR, Koster A, Nevitt MC, Satterfield S, Tylvasky FA, Strotmeyer ES, Newman AB, Simonsick EM, Scherzinger A, Goodpaster BH, Launer LJ, Eiriksdottir G, Sigurdsson S, Sigurdsson G, Gudnason V, Lang TF, Kritchevsky SB, Harris TB. Adipose tissue density, a novel biomarker predicting mortality risk in older adults.

December 11, 2013: Stephen P. Messier, PhD; Shannon L. Mihalko, PhD; Claudine Legault, PhD; Gary D. Miller, PhD; Barbara J. Nicklas, PhD; Paul DeVita, PhD; Daniel P. Beavers, PhD; David J. Hunter, MBBS, PhD; Mary F. Lyles, MD; Felix Eckstein, MD; Jeff D. Williamson, MD; J. Jeffery Carr, MD; Ali Guermazi, MD, PhD; Richard F. Loeser,MD Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults With Knee Osteoarthritis The IDEA Randomized Clinical Trial

July 3, 2012: Haykowsky MJ, Brubaker PH, Stewart KP, Morgan TM, Eggebeen J, Kitzman DW. Effect of Endurance Training on the Determinants of Peak Exercise Oxygen Consumption in Elderly Patients with Stable Compensated Heart Failure and Preserved Ejection Fraction. Journal of the American College of Cardiology 2012

July 3, 2012: Editorial to Haykowsky Paper; 2. Maurer MS, Schulze PC. Exercise Intolerance in Heart Failure with Preserved Ejection Fraction: Shifting Focus from the Heart to Peripheral Skeletal Muscle. Journal of the American College of Cardiology 2012

April 13, 2012: Antibody Levels in Human Cytomegalovirus Infection, Dr. George Wang Johns Hopkins University

December 29, 2011: Aging Is Associated with an Increase in T Cells and Inflammatory Macrophages in Visceral Adipose Tissue, Dr. Raymond Yung University of Michigan

September 22, 2011: NY Times articlereferncing Dr. Steven Fisher of UTMB

August 16, 2011: Switch in Cell's 'Power Plant' Declines with Age, Rejuvenated by Drug (Johns Hopkins University)

May 12, 2011: Losartan Restores Skeletal Muscle Remodeling and Protects Against Disuse Atrophy in Sarcopenia; Tyesha N. Burks, Eva Andres-Mateos, Ruth Marx, Rebeca Mejias, Christel Van Erp, Jessica L. Simmers, Jeremy D. Walston, Christopher W. Ward and Ronald D. Cohn

September 2, 2010: Adverse Events Associated with Testosterone Administration; Shalender Bhasin, Shehzad Basaria, Thomas Travison, Alan Jette, Thomas Storer and others.

August 23, 2010: A Randomized Trial of Tai Chi for Fibromyalgia, Chenchen Wang, MD, MPH, Boston University

May 2010: The Effect of Randomization to Weight Loss on Total Mortality in Older Overweight and Obese Adults: The ADAPT Study; Shea MK, Houston DK, Nicklas BJ, Messier SP, Davis CC, Miller ME, Harris TB, Kitzman DW, Kennedy K, Kritchevsky SB

April 29, 2010: Belief that Intentional Weight Loss is Harmful to Seniors is Unfounded - WAKE FOREST UNIVERSITY Press Release

July 9, 2009: Anti-aging study shows drug gives mice longevity boost even late in life, Richard A. Miller, MD, PhD; Ann Arbor, MI

September 9, 2009: Obesity, intentional weight loss and physical disability in older adults; Rejeski WJ, Marsh AP, Chmelo E, Rejeski JJ.