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Wael Barsoum, MD, The Cleveland Clinic, Cleveland, OH

Dr. Barsoum is an Assistant Professor of Surgery at the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University. He also serves as the Vice Chairman and Staff Surgeon in the Department of Orthopaedic Surgery at the Cleveland Clinic in Cleveland, Ohio. As a joint replacement specialist Dr. Barsoum has worked extensively with the aging population, conducting research in the field of musculoskeletal disease among the elderly. Prior to receiving the Jahnigen Award, Dr. Barsoum had helped to create a registry of patients undergoing total knee or hip arthroplasty (TKA or THA) at the Cleveland Clinic. His Jahnigen project will advance the resources of this registry to include additional perioperative variables testing the hypothesis that age and body mass index are associated with higher risk and lower health-related quality of life in geriatric patients undergoing hip or knee arthroplasty. This project will help refine our understanding of associated risk factors and co-morbities.

Age and Body Mass Index as Preoperative Predictors of Outcomes in the Geriatric Population after Total Joint Arthoplasty

ABSTRACT:
By 2030, 70 million people will be age 65 or older. Degenerative joint disease is one of the most common conditions affecting this population, and joint arthroplasty is a highly successful option in treating this disease. While good outcomes are most common in arthroplasty, as many as 10% of patients experience a decrease in health-related quality of life (HRQOL) at 1 year after surgery. This decline is often related to progression of disease in other joints, but is also related to postoperative complications and worsening of other pre-existing medical conditions. We expect that these limitations can be prevented or limited through more targeted proactive perioperative management of at risk populations. However, our existing literature is relatively silent with respect to the causes and magnitude of these limitations, predictive factors, and means of proactive management.

Within the geriatric population, both advancing age and body mass index (BMI) are implicated in adverse outcomes of arthroplasty, though others contest this finding. To investigate age, BMI and other variables on surgical outcome and HRQOL, we have established a registry of all patients undergoing total knee or hip arthroplasty (TKA or THA) at the CC. Preliminary results have confirmed that increased BMI and age correlate with lower preoperative SF-36 scores and less incremental improvement following arthroplasty procedures, as well as a higher rate of corrective surgeries.

This proposal will advance the resources of this registry to include additional perioperative variables to test the hypothesis that age and BMI are associated with higher risk and lower HRQOL in geriatric patients undergoing TKA or THA and refine our understanding of associated risk factors and co-morbities, and means for stratification. A prospective cohort of 300 consecutive patients undergoing primary TKA or THA will be followed for 1 year, documenting surgical complications, co-morbidities, and HRQOL measured by SF-12 scores.
Orthopaedic Surgery

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Brian J. Blyth, MD, University of Rochester, Rochester, NY
Dr. Blyth is a Senior Instructor in the Department of Emergency Medicine at the University of Rochester Medical Center, Emergency Physician at Strong Memorial Hospital, as well as an Associate Attending Physician at Highland Hospital, both in Rochester, NY. As an Emergency Medicine doctor, Dr. Blyth treats elderly patients suffering from various stages of dementia, for which there is a shortage of treatment options. This, paired with his interest in basic neuroscience investigation, has led Dr. Blyth to devote his research to understanding the molecular basis of Alzheimer's disease (AD). The Jahnigen Career Development Award will continue to support his exploration into AD, focusing on hypoxia inducible factor 1 (HIF-1) as it relates to a transgenic model of AD.

Pharmacologic Stabilization of HIF-1 for the Treatment of Alzheimer's Disease

Abstract:
Alzheimer's disease (AD) is the most common cause of dementia in the elderly. By 2050, it is estimated that 13.2 million will be affected with this disease unless new therapies are developed. AD is characterized by accumulation of extracellular Aß Plaques and intra-neuronal neurofibrillary tangles (NFT's) within the brain leading to extensive synaptic dysfunction, neuronal death and progressive dementia. Oxidative stress resulting from accumulated Aß peptide is believed to be a primary cause of the synaptic dysfunction and also the neuronal death occurring in AD. The pattern of neuronal death is heterogeneous with certain subpopulations of neurons surviving longer than others. Recent in vitro work demonstrates that neuronal cells resistant to Aß toxicity are protected from death via regulation of glucose metabolism by hypoxia inducible factor 1 (HIF-1). Stable HIF-1 in the resistant cells resulted in enhanced uptake and utilization of glucose for energy production and defense against oxidative stress. We hypothesize that in vitro HIF-1 mediated neuroprotection from Aß toxicity will manifest in vivo in a transgenic mouse model of AD. Further, we hypothesize that HIF-1 mediated neuroprotection will protect animals from the behavioral effects of Aß mediated neuronal injury. HIF-1 is constitutively expressed but rapidly degraded under most conditions via a group of prolyl hydroxylases. Inhibition of prolyl hydroxylases allows stable HIF-1 to form and transactivate its target genes. We propose to use the propyl hydroxylase inhibitor dimethyloxalylglycine (DMOG), to accomplish the following specific aims:

1. Demonstrate that HIF-1 medicated neuroprotection occurs in a transgenic model of AD.
2. Demonstrate that transgenic mice receiving DMOG, a HIF-1 stabilizing drug, will have improved behavioral outcomes when compared with sham-treated transgenic animals.

Successful demonstration of synaptoprotection, neuroprotection, or behavioral preservation will compel consideration of an investigational drug process leading to hopefully a Phase I trial in patients.
Emergency Medicine

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Jeffrey Caterino, MD, The Ohio State University, Columbus, Ohio
Dr. Caterino is an Assistant Professor in the Departments of Emergency Medicine and Internal Medicine at the Ohio State University, Columbus, OH, where he also serves as the Director of the Emergency Department Undergraduate Research Associate Program. His interests in geriatric care developed during his combined Emergency/Internal Medicine residency. He is seeking to improve care in the Emergency Department itself and at the interface between the ED and inpatient or outpatient follow-up care. Dr. Caterino's particular interest lies in the management of infections in the elderly, a theme he has been exploring for the larger part of his career. He continues his devotion to geriatric medicine through his Jahnigen-funded study, which aims to improve the quality of care received by elders in the emergency department by creating a decision rule which can more accurately risk assess the severity of infection in elderly patients.

Predictors of Clinical Course in Infected ED Elders

Abstract:
Elderly emergency department (ED) patients with severe infection are often seriously ill, but may have a non-specific clinical presentation. Failure to rapidly and accurately identify serious infection has significant adverse effects on morbidity and mortality. In assessing elders with infection, previous ED studies have generally failed to emphasize or consider geriatric specific factors such as functional status (the ability to perform activities of daily living). This is particularly important as over l5 million elders visit U.S. EDs yearly. As a result there are no proven outcome prediction models for the infected elderly ED patient, limiting emergency physician's ability to diagnose and treat these patients.

We will enroll ED patients aged> 65 admitted with systemic infection in a prospective, observational cohort trial with emphasis on functional status measures. Our overall objectives are: (1) to identify the relationship between functional status and complicated clinical course (defined as in-hospital mortality, need for ICU-level care within 48 hours, or worsening in sepsis criteria within 48 hours) and (2) to develop a clinical decision rule to predict complicated clinical course in infected ED elders.

We will first determine the relationship between the Older Americans Resources and Services functional status score and complicated clinical course. Then, we will identify Independent predictors using logistic regression and CART analysis. The ultimate goal is to create and validate a decision rule which can more accurately risk asses infected elderly ED patients.

The results will improve care of ED elders by identifying those most likely to require aggressive intervention. This project will place emphasis on geriatric-specific factors, such as functional status, to improve the accuracy of the predictive models. It will be accompanied by a training program including course work towards an MPH degree and masters-level courses in gerontology aiming to develop the PI as an independently funded Geriatric Emergency Medicine researcher.
Emergency Medicine

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Joshua Dunaief, MD, PhD, F.M. Kirby Center for Molecular Ophthalmology, Philadelphia, PA
Dr. Dunaief is an Assistant Professor of Ophthalmology at the University Of Pennsylvania School Of Medicine. His love of ophthalmology was instilled in him by his father, an ophthalmologist. While an undergraduate at Harvard, Dr. Dunaief decided to devote most of his time doing biomedical research studying aging. He has spent most of his professional career in studying the most common cause of blindness in the elderly, age-related macular degeneration (AMD). Through treating patients with AMD, he has become devoted to understanding aging mechanisms. As a Jahnigen Scholar, he will continue his work studying AMD, expanding on his findings of elevated iron levels in patients with the disease. The goal of his study is to test whether dietary iron limitation in mice can reduce iron stores in the retina, brain and liver and extend longevity.

The effect of dietary iron restriction on longevity and retinal aging in mice

Abstract
Iron is an essential element for metabolic processes, but is also a potent generator of oxidative damage if improperly handled. Iron accumulates in many tissues with age because it is absorbed through the diet but it is not excreted. Iron levels are elevated in the brains of patients with Alzheimer's and Parkinson's diseases and in the retinas of patients with age-related macular degeneration (AMD) , suggesting that iron induced oxidative damage may contribute to these diseases. Consistent with this idea, hereditary diseases affecting iron transport cause iron accumulation in the brain and retina resulting in neurodegeneration. Since oxidative damage is implicated as a cause of aging, it is also possible that iron contributes to age-associated degeneration in a number of organs. This hypothesis is supported by studies manipulating the diet of fruit flies. Flies accumulating less iron lived longer than flies on a normal diet, and flies fed a high iron diet lived shorter. Similarly, mice given a lifespan-extending calorie restricted diet accumulated less iron in tissues. In the current proposal, we will test the hypothesis that iron limitation in the diet will extend the lifespan of the mouse and protect against age-associated neurodegeneration in the retina. A strain of inbred mice will be fed low or normal iron diets to test the effect on lifespan and retinal morphology. If a low iron diet increases mouse lifespan, following clinical trials, this may lead to a simple dietary modification in humans that could promote healthy aging and perhaps even lead to moderate lifespan extension.
Ophthalmology

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Misop Han, MD, James Buchanan Brady Urological Institute at Johns Hopkins, Baltimore, MD
Dr. Han is an Assistant Professor of Urology at the Johns Hopkins School of Medicine. During his urology residency at Johns Hopkins, he became interested in prostate cancer treatment outcomes analysis. Prostate cancer affects nearly 1 in 6 men in America. He will study the prostate cancer-specific mortality rate in elderly men, evaluating the co-morbidity status of these men at the time of surgery, and, comparing the expected and actual life expectancy of these men. The goal of this study is for patients to make rational decisions in their treatment course for prostate cancer.

Competing Mortality Risks of Men Undergoing Radical Prostatectomy for Prostate Cancer

Abstract
Prostate cancer is the most common non-dermatologic malignancy and is the third leading cause of cancer death in men in the United States. Early stage prostate cancer is potentially cured by surgery or radiation therapy, whereas advanced disease usually carries a poor prognosis. Given the natural history and progression of prostate cancer, early detection and treatment are critical.
Considering the rapidly expanding elderly population and increasing incidence of prostate cancer with advancing age, the optimal treatment algorithm for prostate cancer in elderly men is urgently needed.

I plan to utilize a large radical prostatectomy database at Johns Hopkins Hospital to (1) determine the prostate cancer-specific mortality rate in elderly Men, (2) evaluate the co-morbidity status of elderly men at the time of surgery, and (3) compare the expected and actual life expectancy of elderly men. In the process, I plan to apply statistical methodology to generate improved practical guidelines for prostate cancer treatment in elderly men that will result in a reduction in the psychological morbidity and financial costs of non-beneficial treatment and potentially reduce over-treatment by identifying a subpopulation of men with aggressive prostate cancer who will benefit most from primary therapy such as surgery or radiation. Estimating the patient's life expectancy accurately by carefully considering the patient's co-morbidities and known factors for prostate cancer aggressiveness will allow a rational decision making for prostate cancer treatment in elderly men.
Urology

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Bradley Katz, MD, PhD, John A Moran Eye Center, Salt Lake City, UT
Dr. Katz is an Assistant Professor in the Department of Ophthalmology at the University of Utah in Salt Lake City. He holds prominent committee positions in the North American Neuro-Ophthalmology Society and at his home institution, the University of Utah. As a physician, Dr. Katz's goal is to combine his interests in patient care and research. Treating patients with giant cell arteritis (GCA), a well-known but little understood disease which affects older patients, Dr. Katz became committed to improving the lives and outcomes for these patients through more rapid diagnosis and better treatments. The Jahnigen Scholar award will support his research into GCA. The goals of his project are to identify areas of the human genome associated with GCA, to establish a GCA tissue bank for temporal arteries at the University of Utah, and to use proteomics to identify and validate GCA biomarkers.

Proteomics and Genomics of Giant Cell Arthritis

Abstract
Objectives: To identify areas of the human genome associated with giant cell arteritis (GCA) by conducting linkage studies of pedigrees indemnified by the Utah Population Database (UPDB). To establish a GCA tissue bank for temporal arteries at the University of Utah. To use proteomics to identify and validate GCA biomarkers.
Significance: GCA is exclusively a disease of the elderly and affects up to 44.7 patients per 100,000 population. Many of those affected suffer serious ophthalmic or neurologic deficits, including loss of vision in one or both eyes and stroke. In addition, most patients treated for GCA suffer complications as a result of treatment with immunosuppressive drugs. An understanding of the genetic, immunologic, and environmental factors that are involved in the pathophysiology of GCA would greatly improve our ability to diagnose GCA, to treat GCA, and to minimize complications of treatment.
Methods: We have already identified 8 pedigrees of GCA including one pedigree with 7 affected members. We are linking our database with data on more than100 other GCA patients from the only other major tertiary care center in Utah. Single tandem repeat (STR) markers will be used to conduct genome-wide scans. Once linkage is found, standard molecular biology techniques will be used to identify genes associated with GCA. Neuroophthalmologists and rheumatologists at 20 institutions will be recruited to contribute to the tissue bank. Investigators will enroll any patient suspected of having GCA in who superficial temporal artery biopsy (STAB) is clinically indicated. Biopsy and blood specimens will be banked at the University of Utah until sufficient tissue has been obtained to begin proteomic studies. Proteomic studies will be employed to identify disease biomarkers. Genomics and proteomics will yield information about the pathophysiology of GCA, suggest treatments for GCA, and assist physicians in minimizing the side effects of treatment.
Ophthalmology

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Adam Klausner, MD, VCU Health System, Richmond, VA
Dr. Klausner is an Assistant Professor of Urology at Virginia Commonwealth University and an Assistant Professor of Urological Research in the University of Virginia Health System. During his urological residency, he became interested in the developing field surrounding incontinence and voiding dysfunction, conditions which primarily affect older adults. Recognizing the rapidly growing geriatric population, Dr. Klausner is committed to improving treatment quality and options for older adults through his research. He will investigate Normal Pressure Hydrocephalus (NPH), a chronic neurologic condition which affects geriatric patients and is associated with incontinence. Successful completion of this proposal will improve management of geriatric patients with NPH and provide a stepping stone for additional collaborative research.

An Investigation of Urinary Incontinence in Geriatric Patients with Normal Pressure Hydrocephalus

Abstract
Normal Pressure Hydrocephalus (NPH) is a chronic neurologic condition in which ventricular enlargement is associated with the triad of gait disturbances, dementia, and incontinence. Patients present in the 6th to 8th decades of life with gradual onset and progressive worsening of symptoms. The mainstay of treatment remains ventriculoperitoneal (VP) shunting of the cerebrospinal fluid (CSF). Currently, very little is known about the type, severity, and quality-of-life impact of the incontinence associated with this geriatric condition. Therefore, a comprehensive investigation of urinary incontinence in patients with NPH is required to improve understanding and optimize strategies for effective treatment.

The aims of this proposal are 1) to establish a correlation between the degree of incontinence, ventricular size, and intracranial pressure in the setting of NPH by administration of validated symptom scores, voiding diaries, pad tests, and urodynamic evaluations; 2) to determine if treatment of NPH by VP shunting or lumbar drainage results in improvement in objective measures of urinary incontinence; 3) to collect and store CSF and urine for quantification of Nerve Growth Factor levels and other neurochemical products that may contribute to urinary incontinence at the level of the sacral spinal cord, detrusor muscle, or urothelium.

Access to a large volume NPH referral clinic staffed by Dr. Anthony Marmaru, a leading expert, and my training and experience as a neuro-urologist, will facilitate the achievement of these research goals. The condition of NPH is also unique because it represents a reversible neurologic disease in which measures of urinary incontinence can be tested prior to and after definitive treatment. Furthermore, NPH is a condition that offers the opportunity to examine CSF for basic science studies to investigate mechanisms of urinary incontinence. Successful completion of this proposal will improve management of geriatric patients with NPH and provide a stepping stone for additional collaborative research.
Urology

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Simon Law, MD, PharmD, Jules Stein Eye Institute, Los Angeles, CA
Dr. Law is an Associate Professor of Ophthalmology and a high-volume glaucoma specialist at the Jules Stein Eye Institute at UCLA. He is also the Chief of the Section of Ophthalmology Surgical Services and responsible for supervising the glaucoma clinic at the Department of Veteran Affairs Healthcare Center in West Los Angeles. He has already pioneered research in the glaucoma-like optic nerve changes and macular degeneration, which he will continue to explore under the Jahnigen program. He will continue to work to clarify the clinical relationship between optic neuropathy such as glaucoma and age-related macular degeneration.

Optic disc appearance in advanced age-related macular degeneration

Abstract
Worldwide, age-related macular degeneration (AMD) and glaucoma are the two leading causes of irreversible blindness. Prevalence of blindness secondary to these two diseases increases dramatically with the age of the population. At least one prospective study, the Visual Impairment Project (VIP) in Australia, found that the presence of AMD is associated with a greater risk of developing glaucoma. In addition, a histopathological evaluation showed that there is a significant reduction in the number of ganglionic neurons in eyes with advanced AMD. However, research on the relationship between these two diseases is limited. As a result, it is often difficult to establish an early diagnosis of glaucoma in patients with advanced stages of AMD is often difficult. We previously reported in a retrospective review comparing the optic nerve between the two eyes of a patient with asymmetric involvement of advanced stages of AMD that eyes with larger area of macular damage had a greater amount of thinning of the neural rim and were more glaucoma-like. However, the retrospective design of the study may have unavoidable selection bias that some of the patients might indeed have glaucoma and the optic nerve changes might occur before or after the development of the advanced AMD changes.

Because of the limited research in the relationship of these two leading causes of blindness in the elderly, we believe it is necessary to further evaluate the optic nerve and retinal fiber layer changes in eyes with AMD in a prospective longitudinal fashion. The purpose of the study proposed is three-fold: (1) characterize the feature of the optic nerve and retinal nerve fiber layer in eyes with AMD, (2) understand the relationship of the presence and absence of AMD and the extent of AMD with the appearance of the optic nerve and retinal nerve fiber layer, and (3) longitudinally compare the appearance of the optic nerve with respect to the progression of AMD.

Subjects with AMD without other ocular diseases and a control group of subjects without ocular disease will be invited to enroll in the study. The macular and the optic nerve of the subjects will be photographed for clinical evaluation. Digital optic nerve and retinal nerve fiber imaging technology will be used to analyze the optic nerve contour and the retinal nerve fiber layer thickness. The structural appearance of the optic nerve in eyes with AMD will be characterized by comparing with the control group. The relationship between the presence (and extent) or absence of macular degeneration and appearance of the optic nerve will be analyzed. In the longitudinal monitoring of subjects, periodic macular and optic nerve photographs and digital images of the optic nerve and retinal nerve fiber layer will be analyzed to detect the effects of macular changes on the structure of the optic nerve and retinal nerve fiber layer.
Ophthalmology

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Jayant Pinto, MD, The University of Chicago, Chicago, IL
Dr. Pinto is an Assistant Professor in the Section of Otolaryngology-Head and Neck Surgery at the University of Chicago's Pritzker School of Medicine. He was drawn to the specialty of otolaryngology primarily because of the breadth of clinical problems, impact on a wide range of the population, and central focus on the essentials in life (hearing, smell, speech, swallowing, breathing) which are critical as people age. While treating patients, Dr. Pinto was struck by the need to understand the biology of sensory disorders to develop better diagnosis, improved treatment, and ultimately, preventative strategies. To help improve the quality of life for older adults, he is embarking on a study targeting the genetic basis of olfactory decline, including the relationship of olfaction to other neurodegenerative disorders, sensory deficits, and cognitive impairments in the elderly. The goal of this work is to understand what factors predispose elderly individuals to lose olfactory function, and ultimately, to develop therapies to alleviate or prevent this important sensory deficit.

Age-Related Olfactory Decline: The Role of Genetic Factors

Abstract
Olfactory dysfunction is an important public health problem in the US, with approximately 14 million elderly Americans having chronic olfactory problems. Because olfaction declines with age, the clinical impact is likely to increase as our population ages. Furthermore, the relationship of olfaction to other neurodegenerative disorders, sensory deficits, and cognitive impairments in the elderly, its relationship to other special senses, and the importance of olfaction in evolution emphasize the importance of further investigation in this field.

Studies of olfactory physiology in humans have been limited by access to tissue, potential influences of environmental factors, and the complexity of the neurosensory physiology. Therefore, we took a novel approach to investigating olfaction in humans. We performed a genome-wide screen for loci influencing susceptibility to age-related olfactory loss (presbyosmia) in the Hutterites, a founder population that practices a communal lifestyle. Using interviews and objective testing, we identified subjects with olfactory loss. A genome screen for loci underlying susceptibility to presbyosmia was performed. The most significant evidence for linkage with presbyosmia extended over a 49 cM region on chromosome 4q (P = 0.0013). These results represent the first genome-wide screen for a chemosensory phenotype in humans and also offer the strongest data to date on the effects of genetic variation on age-related olfactory dysfunction.

In this application, I propose to identify the gene on chromosome 4q that causes olfactory dysfunction in the Hutterites by positional cloning. We will first narrow our region of interest through high density single nucleotide polymorphism (SNP) genotyping and then examine SNPs in candidate genes to assess evidence for association. I also propose to validate our screening instrument. This approach will provide insight into the pathophysiology of olfactory dysfunction and, ultimately, may lead to improved diagnostic and therapeutic modalities for this important disease.
Otolaryngology

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Taylor Riall, MD, University of Texas Medical Branch at Galveston, Galveston, TX
Dr. Riall graduated from the Johns Hopkins University School of Medicine in 1996. She subsequently trained in General Surgery, also at Johns Hopkins, from June 1996 through July 2005. During her last year, she served in an instructor-level faculty fellowship position in which she studied advanced surgical techniques in the field of pancreaticobiliary surgery. She is currently an Assistant Professor in the Department of Surgery at the University of Texas Medical Branch in Galveston, TX, where she practices pancreaticobiliary and general surgery. Since her arrival at UTMB, Dr. Riall has been enrolled in the Graduate School of Biomedical Sciences where she is pursuing a Ph.D. in the Clinical Science Graduate Program's Health Services Research Track. Her research has focused on surgical outcomes in the elderly population with pancreatic cancer. The goal of her proposal is to improve survival in geriatric patients with pancreatic cancer by identifying barriers to surgical resection, providing algorithms for pancreatic surgical risk in the elderly and optimizing surgical resection rates at high-volume centers.

Pancreatic cancer in the elderly: Population-based outcomes following surgical resection

Abstract
Pancreatic cancer primarily occurs in the elderly population, with a mean age of presentation of approximately 70 years. Pancreatic cancer remains the fourth leading cause of cancer deaths on the U.S. Currently, approximately 30-40% of patients present with locoregional disease amenable to surgical resection and surgical resection offers the only hope for a cure.

With the increase in the average lifespan of Americans and the aging of the baby boom generation, increasing number of surgeons are asked to evaluate elderly patients for major pancreatic resection. Pancreatic resection at high-volume centers ( >10 cases per year) can be performed safely with mortality rates of less than 5% and morbidity rates of 25-40%, leading to the recommendation that pancreatic surgery be regionalized to such centers. Data from single-institution studies have demonstrated slightly increased but acceptable mortality and morbidity rates in elderly patients (> 70 or 80 years of age) undergoing pancreatic resection.

Despite these data, in preliminary analysis of the SEER data, patients 65-74 years were less likely to undergo surgical resection for pancreatic cancer than younger patients with the same disease stage. To date, no population-based studies have evaluated the surgical outcomes and indication for pancreatic resection in the elderly population. We plan to use the SEER-Medicare linked data to: 1) evaluated outcomes following pancreatic resection for elderly (>65 years) pancreatic cancer patients, 2) determine the factors that influence surgical outcomes in elderly patients and develop guidelines to assist in choosing appropriate elderly candidates, and 3) evaluated the extent of regionalization of care of elderly patients to high-volume centers over the last decade. The goal of this proposal is to improve survival in geriatric patients with pancreatic cancer by identifying barriers to surgical resection, providing algorithms for pancreatic surgical risk ion the elderly, optimizing surgical resection rates at high-volume centers.
General Surgery

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Dorry Segev, MD, Johns Hopkins Hospital, Baltimore, MD
Dr. Segev is an Assistant Professor of Surgery in the Department of Transplant Surgery at Johns Hopkins University School of Medicine. Dr. Segev saw that the fastest growing population with renal failure is the elderly, and that there is discordance between elderly patients who develop renal failure and those who are listed for transplantation. The hypothesis of his study is that the inability to quantify the complexities of physiology and multi-morbidity specific to elderly patients causes risk prediction in this population to be subjective, overly restrictive, and naively based on models designed for younger patients. His goals are to better identify elderly patients who are appropriate for transplantation, to study barriers to access through a multi-level approach, and to develop a model to help guide the choices of elderly patients.

Kidney Transplantation in Elderly Patients with Renal Failure

Abstract
Based on analysis of national data from the USRDS (United States Renal Data System) and UNOS (United Network for Organ Sharing), we discovered that very few patients over 65 with renal failure were considered for kidney transplantation. This is surprising since elderly patients potentially derive a survival advantage for organs donated by older donors (known as ECD, or expanded criteria donors); in fact, many organs from older donors are turned down by younger patients and as a result are often not used.

We hypothesize that the inability to quantify the complexities of physiology and multi-morbidity specific to elderly patients causes risk prediction in this population to be subjective, overly restrictive, and naively based on models designed for younger patients. The goals of our study are:

1. To better identify elderly patients who are appropriate for transplantation. By analyzing data from USRDS and OPTN, we will identify risk factors specific to elderly patients. A multi-order interaction term analysis will be performed to account for the complex morbidities of this patient group as well as the potential interplay between donor factors and recipient physiology.
2. To study barriers to access through a multi-level approach. Through survey and focus group methodology, we will assess potential barriers to transplantation for elderly patients. A geriatrics focus group will lead queries at other levels, include patient attitudes, patient and family financial means and logistical barriers, provider (primary care and nephrologist) attitudes, and support from community networks such as dialysis centers and long-term care facilities.
3. To develop a model to help guide the choices of elderly patients with ESRD. A stochastic Markov decision process model specific to elderly patients will be designed. For each possible combination of factors, the Markov model will help the patient decide between remaining on dialysis, waiting for an SCD kidney, or accepting an ECD kidney.

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Thomas Wheeler II, MD, University of Alabama at Birmingham , Birmingham, AL
Dr. Wheeler is an Assistant Professor in the Division of Women's Pelvic Medicine & Reconstructive Surgery at the University of Alabama at Birmingham, and a scholar for the Southeast Center for Excellence in Geriatric Medicine. During his Female Pelvic Medicine and Reconstructive Pelvic Surgery Fellowship, he studied and treated pelvic floor disorders. Dr. Wheeler's goal is to improve the patient's quality of life while minimizing risks to patients' functional status by non-surgical and surgical interventions. His current project focuses on changes in Life Space after conservative management of urinary incontinence. Findings of his project could be used to help counsel older women with decreased mobility and incontinence that non-surgical treatment of UI could help increase the range of their usual activities.

Life Space Assessment in Older Women Undergoing Non-surgical Treatment for Urinary Incontinence

Abstract
Urinary incontinence (UI) is a common pelvic floor disorder which may affect up to 50% of women. Even though a third of women will undergo surgery for pelvic floor disorders during their lifetime, non-surgical primary treatments are extremely important, especially for older women, because surgery poses a greater threat to functional status. Therefore, the impact of nonsurgical treatments on UI is an important research area. Since mobility is a gauge of functional status, its impact on UI has been investigated and a strong correlation exists between impaired mobility and incontinence. The impact of treatment of UI on mobility needs further study.

A new measure for mobility is the Life Space Assessment (LSA). The LSA is unique in that it measures what a patient actually does and is not just an estimate of what a patient can do, as found with traditional mobility measures. LSA is a conceptual model of actual mobility as a series of concentric rings radiating from the room where a person sleeps, out through their home and town, to an unlimited space away. LSA was validated at UAB, and further study has underscored the impact of other factors on LSA besides physical functioning. One of which would be UI.

The proposed research project will primarily measure for improvements in LSA in community dwelling older women (>70 years old) desiring non-surgical treatment of UI. The study will also assess for correlations between improvement on LSA with participant perceived improvement in UI and improvement on LSA with improvement on validated measures of UI. Further, the impact of baseline comorbidities on improvement in LSA will be investigated. Findings could be used to help counsel older women with decreased mobility and incontinence that non-surgical treatment of UI could help increase the range of their usual activities.
Gynecology

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