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The 2003 Dennis W. Jahnigen Career Development Scholars Abstracts
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Jayakrishna Ambati, MD, University of Kentucky
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Novel Mouse Models of Age-Related Macular Degeneration
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Age-related
macular degeneration (AMD) is the leading cause of blindness among
those over 65 in the U.S., Western Europe, and Japan. It affects over
11 million persons in this country alone, and with the aging
population will exact a greater toll. The absence of a faithful
animal model has hampered the study of AMD and the development of
therapeutics. We have discovered two strains of genetically modified
mice that develop many features of AMD as they age. Elderly mice (9 -
24 months) deficient either in the monocyte chemoattractant protein-1
(MCP-1) or CC chemokine receptor-2 (CCR2) genes develop lipofuscin
(autofluorescent lysosomal storage bodies in the retina), drusen
(lipoproteinaceous deposits between the retina & choroid), and
thickened Bruch’s membrane (an extra cellular matrix between
the retina and choroid), the earliest manifestations of AMD in
humans, as well as choroidal neovascularization, the late exudative,
blinding form of AMD. These lesions are ophthalmoscopically,
angiographically, and histopathologically similar to those in
patients with AMD. These pathologies are absent in age-matched wild
type mice and several other knockout strains.
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We
hypothesize that the accumulation of drusen and lipofuscin associated
with senescence is normally cleared by the recruitment of scavenger
macrophages, which is impaired in the absence of MCP-1 or its
receptor CCR2, and that rescue of MCP-1 or CCR2 function can regress
AMD. These hypotheses will be directly tested by (1) characterizing
the temporal development of AMD features in MCP-1 or CCR2 -/- mice
from ages 9 to 24 months by ophthalmoscopy, angiography, and
histopathology, compared to wild type age-matched mice, and (2)
testing whether rescue of MCP-1 or CCR2 function will lead to
regression of AMD in elderly MCP-1 or CCR2 -/- mice. The rescue
strategies will include intraocular injection of an adeno-associated
viral vector coding for MCP-1 in elderly MCP-1 -/- mice, systemic
delivery of MCP-1 via osmotic pumps in elderly MCP-1 -/- mice, or
introduction of CCR2 bearing stem cells capable of differentiating
into macrophages into bone marrow-ablated CCR2 -/- mice.
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These
mice represent the first faithful models of both early and late AMD.
As such they can provide mechanistic insights into the development
AMD and assist in efficacy testing of candidate drugs.
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Opthalmology
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Susan M. Day, MD, Michigan State University
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Development of a Problem-Oriented, Computer-Based Geriatric Curriculum
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For
most people, increasing age leads to degeneration of the
musculoskeletal system. By the year 2020 about 20% or an estimated
60 million people will be over the age of 65. Approximately 80% of
those individuals will have musculoskeletal complaints.
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The
development of a geriatric orthopaedic curriculum and the teaching of
that curriculum are necessary to improve the care of the older
orthopaedic patient with a musculoskeletal complaint. This project
will address both development of the curriculum as well as
instruction. A geriatric orthopaedic curriculum will be put into a
problem-oriented format and presented using a computer based,
self-directed learning module. A problem-oriented curriculum allows
the integration of orthopaedic techniques and concepts with problems
unique to geriatric patients. This computer-based curriculum will be
accessible to all surgeons as part of residency education or
continuing medical education.
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Brooke H. Gurland, MD, Maimonides Medical Center/Mt. Sinai School of Medicine
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Multidisciplinary
Pelvic Floor Evaluation for Women with Lower Tract Dysfunction,
Pelvic Organ Prolapse, and Defecation Disorders
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Pelvic floor disorders such as: urinary and fecal incontinence,
constipation, pelvic organ prolapse (cystocele, enterocele, vaginal
and rectal prolapse), pelvic pain disorders, and sexual dysfunction
diminish the quality of life of the geriatric patient. These
disorders are evaluated by sub -specialists in gynecology, urology,
colorectal surgery and gastroenterology. This represents an
artificial division of the pelvic structures into anterior middle and
posterior compartments. The pelvic floor structures share a common
muscular support and innervations and there is a growing consensus
that a combined approach to evaluating and treating these disorders
is beneficial.
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The purpose of this study is 1. To establish a multidisciplinary approach
to geriatric patients with pelvic floor pathology 2. To perform a
standardized work up evaluating all three compartments 3. To educate
health care professionals and the community to identify patients with
pelvic floor disorders.
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Patient
selection will include geriatric patients presenting with urinary or
fecal incontinence, obstructed defecation, or pelvic floor prolapse.
A detailed history will be taken and pelvic and rectal examination
will be performed. A standardized pelvic floor evaluation will
include urodynamics, anal ultrasound, anal manometry, pudendal nerve
terminal latencies, electromyography and cinedefecography. A
multidisciplinary “pelvic floor team” will meet to review
patient cases and to formulate treatment plans based on the
standardized pelvic floor evaluation. Residents in primary care,
obstetrics and gynecology, and surgery will participate in the
“pelvic floor team” through direct patient evaluation and
multidisciplinary conferences. Patient data will be collected in a
centralized pelvic floor database. Data analysis will allow us to
evaluate the incidence of symptomatic versus occult multi-compartment
pathology and to follow its effect on postoperative success. The
pelvic floor team will educate health care professionals and the
community through seminars and lectures.
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Ultimately,
we hope to improve the recognition and diagnosis of elderly women
with pelvic floor disorders through physician and patient education
and our contributions to the literature. We hope to improve patient
care by standardizing a pelvic floor evaluation prior to proceeding
with surgery.
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General Surgery
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Clifford Y. Ko, MD, MS, MSHS, University of California
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Developing Quality Indicators to Improve the Care in Geriatric Surgery Patients
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This
proposal seeks to develop quality process indicators that will be
used to improve the surgical care of older patients. (“Process”
is defined as the set of activities that goes on between the patient
and practitioners and commonly refers to whether the medically
appropriate decisions are made). Quality process indicators are
measures that signify higher quality care. Moreover, they typically
set a standard that if not performed almost certainly identifies
poor-quality care. While they can be used for evaluative purposes,
our underlying aim is for the quality indicators to be used to
educate surgeons as to what is important for improving the quality of
care, as well as for teaching residents and medical students. Using
validated methods, this study will produce quality indicators that
may be used for improving the pre-, intra-, and post-operative care
of the elderly patient undergoing surgery. We will specifically
address the care revolving around the operative resection of the
colon/rectum.
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This
project is important because it will, for the first time, provide
valid processes of care – specifically for surgeons –
with which surgical care to the elderly may be improved. Also, it is
paving the way for subsequent important studies that could further
change the clinical behavior of surgeons (and consulting
geriatricians) in a significant way. Our preliminary workload
studies have demonstrated that these resections will increase by over
40% in the next twenty years – and will be primarily performed
in the elderly.
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General Surgery
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Laura W. Lee, MD, University of Virginia Health Systems
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The
Effect of a Hip Stretching Program on the Gait of Elderly People Who
Have Had Hip Fractures
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Approximately
340,000 people 65 years old or older are hospitalized for hip
fractures annually in the United States, resulting in significant
residual disability to those who survive the fracture. Studies have
demonstrated that mobility and ambulation are particularly affected,
with limited long-term improvement. People who have had hip
fractures are more likely to be immobile than case matched controls
that have not had hip fractures, but specific impairments causing the
disability are unclear. From previous studies on a related
population, the elderly fallers, reduced hip extension, increased
anterior pelvic tilting, and decreased step length were noted during
walking. The objective of this study is to determine the extent of
dynamic hip extension and related joint motion abnormalities in
subjects who have had a hip fracture, and whether a hip flexor
stretching program will correct the gait abnormalities, leading to a
more efficient gait and improved functional mobility. We propose a
randomized prospective 8-week trial of a supervised hip
flexor-stretching program (with controls undergoing shoulder
stretching) for 70 subjects who have had hip fractures. Gait
parameters, functional mobility, and activities of daily living
measurements will be assessed before and after the stretching
program. This study will offer information about specific gait
impairments in people with hip fractures who are at high risk for
loss of mobility and test an intervention, which may improve gait in
this population.
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Physical Medicine & Rehabilitation
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Stacy Lindau, MD, The University of Chicago
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Sexuality, Intimacy,
and Social Life in Older People with Life-Threatening Illness
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Little
attention has been given to the role or experience of social life,
sexuality and intimacy among elders and even less to those facing
life-threatening illnesses (LTI). Physicians and public health
policy makers lack a scientific base of information for advising
patients and families or for designing programs that might maximize
social and intimate relationships among older people with life
threatening illness. Health researchers know little about the role
of social life and sexual health in well being in later life or in
the context of LTI.
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We
propose a clinic-based longitudinal survey of older
community-residing adults (age 65+) with life-threatening illness,
which aims to understand the relationship between social life,
sexuality and intimacy among older people with LTI in relation to
health outcomes for the individual and the significant other. This
study also aims to explore the strategies used by people with LTI to
navigate, negotiate, and bring closure to social, intimate and sexual
relationships. A comparison sample of younger adults with
comparable diagnostic and symptom criteria will be included to begin
to examine the moderating effect of life stage on the relationships
between LTI, social life, sexuality, and intimacy.
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For
this initial phase of the research, we will study a cohort of people
with lung cancer and their significant others. Lung cancer provides
an excellent initial model of the relationship between
sexuality/intimacy and LTI because it is so prevalent, affects men
and women, affects younger and older people, is not hormonally
mediated, does not directly distort the sex organs, is not generally
grossly disfiguring, and is frequently complicated by pain and
fatigue. Additionally, because of its poor prognosis, studying
people with lung cancer will allow us to follow dyads through the
transition of death.
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Gynecology
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Manish N. Shah, MD, University of Rochester Medical Center
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Prehospital Screening to Prevent Injuries and Illness
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The
goal of this project is to prevent injuries and diseases among older
adults through the development and evaluation of a novel emergency
medical services (EMS)-based screening program to identify
individuals at risk for preventable injuries and diseases.
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The
National Institute on Aging has declared that its challenge is to
maximize the health of older adults by preventing frailty and
disability. However, prevention programs based in physician offices
and local departments of health have had difficulty achieving
targeted results.
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The
EMS system has the unique ability to use a community-wide medical
delivery system that can perform unscheduled in-home evaluations to
uniformly implement prevention programs. Furthermore, because older
adults use EMS services at high rates, EMS can contact a significant
proportion of the older adult population. However, very few
prevention programs have used this unique ability of the EMS system
to implement and evaluate the outcomes of an EMS-based older adult
screening program.
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To
prevent injuries and diseases among older adults, this study
specifically aims to:
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1. Evaluate
the feasibility of an EMS-based primary prevention program that
screens older adults for need of pneumococcal vaccination and for
risk of falling during emergency medical responses in a rural
setting.
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2. Evaluate
the outcome of the EMT-implemented screening and education program
by performing a 30-day telephone follow-up on older adults cared for
by EMTs.
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At
the conclusion of this award, we will determine if an EMT-implemented
primary prevention program for older adults is feasible and results
in interventions. Most importantly, by forming a collaborative
relationship between geriatricians and emergency medicine physicians,
at the conclusion of this award we will have developed a Geriatric
Emergency Medicine “laboratory” through which we can
continue to study health issues faced by older adults.
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Emergency Medicine
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Edward Weaver, MD, MPH, University of Washington
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Sleep Apnea and Perioperative Complications in Geriatric Patients
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Obstructive sleep apnea occurs in 47-81% of adult’s ≥ 60 years old. It
is characterized by recurrent upper airway obstructions during sleep
that result in serious physiologic abnormalities and medical risks,
including a presumed increased risk for serious perioperative
complications. This proposal supports the career development of the
principal investigator to characterize the perioperative risk
associated with sleep apnea in geriatric patients (≥ 60 years),
focusing initially on patients having total hip or knee replacement.
The study hypothesis is that sleep apnea is associated with an
elevated 30-day mortality and with other serious perioperative
complications in these patients. The principal investigator will
examine this association in a retrospective cohort study of 27,779
elderly hip or knee replacement patients from the VA National
Surgical Quality Improvement Program, using multivariate logistic
regression and adjusting for demographic variables. He will further
examine the association in a nested case-control study of the 242
cases of 30-day mortality and 242 age- and gender-matched controls
from the cohort by extracting more detailed data (e.g., sleep apnea
severity and treatment) from the record and again employing
multivariate regression techniques. Future studies will examine the
association of sleep apnea and perioperative complications of other
surgeries and the impact of sleep apnea treatment on reducing
complications.
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Otolaryngology
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Scott T. Wilber, MD, Summa Health System/Northeastern Ohio Universities
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Prediction
of Short-Term Functional Decline and Service Needs in Older ED
Patients
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Injuries
are common reasons for ED visits in older patients; the majority
result from falls. Approximately ¾ of these patients are
discharged from the ED; a significant proportion will experience some
loss of functional independence at 3-month follow up. However, the
injuries themselves or treatments such as splinting may result in an
immediate decline in functional status. There is no instrument
available to identify older patients at high risk for immediate
post-injury functional decline. The care needs for these patients
are unknown, which makes discharge planning difficult for treating
physicians.
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The
study aims are to describe the functional status of older ED patients
with blunt injuries and to determine factors predictive of short-term
functional decline. This project will also describe their care
needs, and develop and pilot an intervention aimed at maintaining
functional independence in these patients.
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Three
hundred patients ≥ 65 years with blunt injuries will be enrolled.
Interviews are derived from validated instruments and include
information on mental status, comorbidities, medication use, social
supports, ADLs, and service use. Current functional abilities will
be assessed using the “Get-up and Go” test and the time
to put on and remove a jacket (from the Physical Performance Test).
All patients will be followed by telephone at one week to assess
changes in ADLs, and repeat doctor visits for functional concerns.
One-third of patients will be followed at 4 weeks by telephone to
assess the trajectory of functional decline and monitor for recovery.
The primary outcome is significant reduction in ADL score at one
week. This information will be used to develop an intervention aimed
at mitigating functional decline in these patients. Pilot testing of
this intervention will lead to a federally funded grant proposal to
evaluate its effectiveness.
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Emergency Medicine
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David Yuh, MD, The Johns Hopkins Hospital
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Assessing
the Efficacy of a Neuroleptic, Benzodiazepine and 5-HT3
Receptor Antagonist Regimen in the Treatment of Postoperative
Delirium in Geriatric Patients After Cardiac Surgery
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Postoperative
delirium and agitation is a neuropsychiatric complication of cardiac
surgery associated with significantly increased morbidity (e.g.,
falls, infections, pressure sores), mortality, prolonged hospital
stays and costs, and increased requirements for post-discharge
institutionalization. There is clear scientific evidence that
geriatric patients suffer from delirium after cardiac surgery more
frequently than younger patients, however, due to the variability in
its presentation as well as the greater medical complexities inherent
in this older patient population, delirium is often overlooked,
misdiagnosed, and mistreated. Currently, neuroleptics and
benzodiazepines comprise treatment for postoperative delirium in the
elderly. Unfortunately, geriatric patients are particularly
susceptible to the untoward side effects of these medications and an
optimal dosing regimen has not yet been developed in an organized
study. Furthermore, there has been promising preliminary evidence
that ondansetron, a serotonin (a neurotransmitter) 5-HT3
receptor antagonist, effectively ameliorates postoperative delirium
in cardiac patients. In this proposal, we seek to develop and apply
reasoned protocols for the treatment of postoperative delirium
incurred after cardiac surgery, specifically for geriatric patient
population, based upon these medications. These protocols will be
based upon substantial clinical experience with combined neuroleptic
and benzodiazepine therapies for delirium accumulated over three
years. They will be applied with careful perioperative
neurocognitive monitoring to assess efficacy. This study would
represent the first treatment protocol of its kind to be applied
specifically to geriatric patients undergoing cardio thoracic
surgery. Optimized treatment of postoperative delirium in the
geriatric patient would most certainly yield positive effects upon
their postoperative courses.
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Thoracic Surgery
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