November 2016 | Volume 1 | Issue 2
Greer Memorial Hospital, Greer, SC (part of Greenville Health System)
“Joint” Effort, Top Result
Orthopaedics at Patewood Ranks Among Nation’s Best
Make no bones about it—GHS’ Patewood Memorial Hospital has been recognized as a top hospital in
orthopaedics by U.S. News & World Report!
Patewood Memorial Hospital is #19 in the nation for 2016-17—the only hospital in South Carolina to be ranked in
orthopaedics. Patewood also was named High Performing in hip replacement.
In addition, GHS’ Greenville Memorial Hospital was named High Performing in three areas: heart failure, colon
cancer surgery and chronic obstructive pulmonary disease.
These achievements would not be possible without all members of our healthcare team—doctors, nurses,
allied health professionals, support staff and volunteers—combining their joint efforts to deliver high-quality
care. Thanks to their skill and dedication, GHS continues its patient-focused mission to heal compassionately and
improve constantly.
Learn more at ghs.org/usnews.
ghs.org
16-0720
November 2016
Volume 1 | Issue 2
The peer-reviewed journal of Greenville Health System
Vision: To transform health care through the publication of relevant, innovative, and
multidisciplinary scholarship concerning advancements in clinical, academic, and
translational research
Editor-in-Chief: William D. Bolton, MD
Managing Editor: Ally Hale, BA
Associate Editors: A. Michael Devane, MD; Haytham H. Dimashkieh, MD; Jeffrey W. Elder, MD;
Timothy P. McHenry, MD; Naveen N. Parti, MD; Jeremy A. Warren, MD
Editorial Board: Robert W. Allen, PhD; Irfan M. Asif, MD; Jagannadha R. Avasarla, MD, PhD;
Molly Benedum, MD; Susan Bethel, MSN, RN, NE-BC; Parampal Bhullar, MD; Matthew D.
Bitner, MD, MEd, FACEP; Eric S. Bour, MD, MBA, FACS, FASMBS; John S. Bruch, MD, FACE;
Christopher Campen, PharmD, BCOP; Joni Canter, MBA, ATC; Christopher G. Carsten III, MD;
Anna L. Cass, PhD, MPH; India Chandler, MD; Catherine M. Chang, MD; F. Tich Changamire,
MD, ScD, MBA; Patricia L. Cheek, MD; John D. Cull, MD; Patrick J. Culumovic, MD; James R.
Davis, MD; Lauren D. Demosthenes, MD; Kacey Y. Eichelberger, MD; M. Carmela Epright,
PhD; J. Alex Ewing, MS; Sarah R. Farris, MD; Lawrence D. Fredendall, PhD; Sagar S. Gandhi,
MD; Bruce H. Gray, DO; John B. Hartman II, DMin; Steven B. Holsten Jr, MD, FACS; William
W. Hope, MD, FACS; Matthew F. Hudson, PhD; Sandip Jain, MD; Esther M. Johnstone, DNP,
MSN, RN, CNOR; Lindsay H. Jones, CRNA; J. William Kelly, MD; Laura H. Leduc, MD; Bruce
A. Lessey, MD, PhD; Tina Lindsey, CCP Perfusion; Ervin L. Lowther, MD; Charles G. Marguet,
MD; Nancy Markle, RN; Brian P. McKinley, MD, FACS; Paul B. Miller, MD; Ryan Miller, Sr
Embryologist; Benjie B. Mills, MD; S. John Millon, MD; Ivaylo I. Mitsiev, MD; John S. Morris,
MD; Phillip Moschella, MD, PhD; Bryce A. Nelson, MD; M. Jason Palmer, MD; Puraj Patel,
DO; Nirav T. Patil, MBBS, MPH; Sarah B. Payne-Poff, MD; Larry E. Puls, MD; Krista Ramirez,
PharmD, BCPS; Vinayak S. Rohan, MD; Robert A. Saul, MD; Kerry K. Sease, MD; Rhett M.
Shirley, MD; Dane E. Smith, MD; John A. Spratt, MD; Antine E. Stenbit, MD, PhD; Michael
Stewart, MD; Jeremy Stuart, PhD, MPH; Laurie M. Theriot Roley, MD; Steven D. Trocha,
MD; Adam B. Tyson, MD; Diana Vargas Vives, MD; Thomas L. Wheeler, MD; Michael W.
Wiederman, PhD; Christopher C. Wright, MD; Yuliya Yurko, MD
Editorial Services: Jeanine Halva-Neubauer, MA; Travis Crump, BS
Produced By: GHS Creative Services
Greenville Health System Proceedings (GHS Proceedings) is a peer-reviewed medical journal that represents the top
academic and clinical research activities happening at GHS and throughout the world. GHS Proceedings is published
twice a year (spring and fall) and is a primarily online journal constructed of original research, review articles, case
reports, editorials, book reviews, and more. GHS Proceedings’ mission is to provide high-quality publications on
healthcare innovation and delivery (university.GHS.org/Proceedings).
To receive upcoming issues by email, contact Ally Hale at [email protected].
GHS Proc. November 2016; 1 (2)
87
Table of Contents
Viewpoint
89 OPINION Monoclonal Antibodies, BloodBrain Barrier and Disability in Multiple
Sclerosis: Time for Combination Therapies
by Jagannadha Avasarala
92 TEACHABLE MOMENT Do I Really Need
to Stop Taking Estrogen? by Chelsea W.
Fox, Bruce A. Lessey, and Paul B. Miller
94 VALUE VIGNETTE Choosing High-Value
Care in Suspected Lower Extremity Deep
Vein Thrombosis by Moon Won and Steven
Connelly
Special Article
97 Perceptions of and Preferences for a Mobile
Health Clinic for Underserved Populations
by Melinda Gillispie, Catherine Mobley,
Lynette M. Gibson, and Arelis Moore de
Peralta
Original Research
105 The Gynecology and Obstetrics
Fundamentals of Residency Internship
Training (GO FOR IT) Trial by Francis S.
Nuthalapaty, H. Lee Higdon III, David A.
Forstein, Sarah E. Smith, Julie Z. DeCesare,
Claudette J. Shephard, Robert V. Higgins,
Chadburn H. Ray, Ashlyn H. Savage, Nikki
B. Zite, Spencer G. Kuper, and Brian C. Brost
113 Blood Loss and Transfusions After
Pericardial Closure Using a Porcine-Derived
Extracellular Matrix by Timothy G. Johnson,
William W. Hope, Howard F. Marks, and
Peter N. Kane
117 Impact of Methicillin-Resistant
Staphylococcus aureus (MRSA)
Decolonization Protocol on Colonization
and Infection Rates in a Level III Neonatal
Intensive Care Unit by Myah Griffin, Nirav
T. Patil, and Robin N. LaCroix
121 Does Comprehensive Dementia Education
Impact Self-Efficacy Among Family
Caregivers in the Community? by Xi Pan,
Melissa Bailey, Meghan Socko, and Lisa
Naylor
126 Insurance Status of Deceased Organ
Donors by John D. Cull, Tara L. Spivey,
Samuel Kingsley, David A. Ansell, Kimberly
Joseph, and Edie Y. Chan
Case Studies
130 Catastrophic Upper Gastrointestinal Bleed
in Roux-en-Y Gastric Bypass Patients From
Ulcer Erosion Into the Splenic Artery:
Details of Rapid Surgical Management by
Andrew J. Jones, Nathaniel Walsh, Aaron
Bolduc, Sean Lee, and Brian Lane
133 Dexmedetomidine-Induced Adrenal Crisis
in an Infant by Jeremy M. Loberger, Robert
S. Seigler, and Michael G. Avant
136 Radiographic Evidence of Diffuse Large
B-cell Lymphoma Presenting as Carpal
Tunnel Syndrome by Anthony J. Horton and
Jeffrey R. Wienke
140 Management of Brujeria, a Culture-Bound
Syndrome by Joseph T. Mingoia and Taral
R. Sharma
143 Levamisole-Induced Necrosis Syndrome
Associated With Cocaine Use by Richard
O’Neal and Sheena Henry
All statements and opinions expressed in GHS Proceedings are those of the authors and not necessarily those of
Greenville Health System, its board, or any of its affiliates.
Guidelines for authors are available at university.ghs.org/proceedings/authors. Completed manuscripts may be
submitted online (university.ghs.org/proceedings/submit) or by mail (POSTMASTER: GHS Proceedings, Greenville
Health System, 3rd Floor Support Tower, 701 Grove Rd, Greenville, SC 29605)
Copyright © 2016 Greenville Health System. All rights reserved.
88
GHS Proc. November 2016; 1 (2)
Opinion
Monoclonal Antibodies, Blood-Brain Barrier and Disability
in Multiple Sclerosis: Time for Combination Therapies
Jagannadha Avasarala, MD, PhD
From the Department of Medicine, Division of Neurology at Greenville Health System, Greenville,
SC (J.A.), and University of South Carolina School of Medicine Greenville, Greenville, SC (J.A.)
Abstract
The treatment of multiple sclerosis (MS) continues to evolve. However, even with the introduction
of B-cell–depleting monoclonal antibodies (MAbs), disability progression continues unabated since
B-cell therapies with MAbs do not address disease that lurks in the brain. The principal reason
MAbs cannot enter the brain is because of their considerable size—limitations in size prevent MAbs
from crossing the blood-brain barrier (BBB). To counter this problem, combining drugs that cross
the BBB, such as siponimod, cyclophosphamide, or laquinimod with peripherally acting MAbs, could
be one option. The concept of combining a small molecule with MAbs is novel from a pharmacologic perspective and follows disease pathophysiology. In this brief report, a fundamentally new idea
based on combination therapies designed to address pathology within and outside of the brain/
cord is presented. Limitations to such strategies include scant knowledge of the effects of small
molecules in suppressing disease in the brain/cord, but it has been 23 years since the first MS drug
was approved by the Food and Drug Administration; not a single drug, thus far, halts disability or the
inevitable march of disease progression. It is time for scientists and clinicians to consider a different
approach in MS therapeutics.
R
apid strides have been made in the treatment of multiple sclerosis (MS) since the
Food and Drug Administration (FDA)
approved the first drug for use in 1993. Despite
these advances, treatment options for worsening
disease characterized by accumulating disability
on expanded disability status scores (EDSS) or
cognitive decline are disappointing and unsuccessful. These outcomes are particularly worrisome for African American (AA) patients who
have worse EDSS scores and gait abnormalities
at diagnosis, and they likely have more primary
progressive MS (PPMS) variants.1
The reason for the relentless progression of disability in relapsing-remitting MS (RRMS) across
all racial and ethnic backgrounds that eventually transitions into secondary progressive MS
(SPMS) is probably linked to the poor penetration
of the blood-brain barrier (BBB) by drugs used in
MS therapies in general and monoclonal anti-
GHS Proc. November 2016; 1 (2): 89-91
bodies (MAbs) in particular. Currently, 3 MAbs
have been approved for MS therapy: natalizumab,
alemtuzumab, and daclizumab.
Radiologic stability in patients with MS requires
that no new T1-gadolinium–enhanced lesions or
expanding/new T2 lesions appear in the brain or
spinal cord, a cornerstone of NEDA (no evidence
of disease activity) concept in MS. If MAbs are
being considered for therapy in the face of worsening disability, it can be a challenge since they
do not penetrate the BBB.
Unlike nearly all other blood vessels in the body,
the endothelial cells of the BBB are held together by
tight junctions, and for a drug to enter the central
nervous system (CNS), it must take the transcellular route. The tight junctions, coupled with numerous efflux transporters and metabolizing enzymes,
constitute a barrier to the movement of both molecules and cells from the bloodstream into the CNS.
89
The BBB plays a role in MS treatment at multiple levels, and MAbs that have been listed herein
cannot cross the BBB owing to their large size/
molar mass or molecular size. The molar mass
or the mass of one mole (6.02 x 10^23 molecules,
Avogadro’s number) of the most commonly used
MAbs in neuroimmunology, including those that
are non-FDA approved are natalizumab (146 kDa),
rituximab (143 kDa), alemtuzumab (145 kDa),
ocrelizumab (148 kDa), and daclizumab (142 kDa),
respectively. These data are critical since BBB penetration is inversely related to the square root of the
molecular weight (or molar mass) of a substance2;
typically, few molecules >0.5 kDa cross the BBB.
If drugs are to act in the brain, CSF concentrations must be at least as high as in serum. As an
example, the poor BBB penetration of IV rituximab became apparent in treatment of CNS
lymphoma that produced concentrations that
were 1000-fold less in CSF than seen in serum.6
Additionally, poor BBB penetration of IV rituximab was revealed in a study of 15 patients with
MS that followed IgG levels, IgG index, and oligoclonal band numbers in CSF and noted that
they were not consistently altered at 24 weeks;
however, B and T cells in the CSF compartment
were reduced although the mechanism remains
unclear.7
There is minimal or no evidence that any of the
MAbs impact neurodegeneration in a clinically
relevant manner over the long course of MS,
which is worrisome, particularly if MAbs are used
as the sole therapeutic regimen. Additionally, the
lipophilic or hydrophilic nature of molecules or
size may not be the only limiting factors for drugs
to cross the BBB.3
The treatment landscape for MS continues to
evolve. Impressive phase III data for ocrelizumab
in clinical trials, OPERA I and OPERA II for
RRMS, and ORATORIO for PPMS, have been
reported, particularly for disability scores. In the
latter study, 24% reduced risk of clinical disability
compared to placebo. The drug also reduced the
time required to walk 25 feet by 29%, the volume
of chronic inflammatory brain lesions by 3.4%,
and the rate of brain volume loss by 17.5% compared to placebo. It is unclear how the beneficial
effects on disability and MRI data on the brain
occurred, given the size of the molecule and its
poor penetration of the BBB, but certainly does
not appear to be related to the phenomenon of
“regression to the mean.”
As patients transition into SPMS from RRMS, factors that drive the process include autoreactive T
cells that cross the BBB and participate in demyelination, axonal transection, gliosis, and subsequent
axonal degeneration4; the cascading neuroinflammation and neurodegeneration that follows continues unabated as the BBB forms an impregnable
barrier to drugs. Additionally, memory B cells and
plasma cells, central to humoral immunity, are
found in lesions and cerebrospinal fluid (CSF) of
patients with MS behind a protected BBB.
Ectopic lymphoid follicles located in the meninges
probably drive the pathology of MS and have been
shown to house B cells and plasma cells,5 indicating that B cells migrate to the brain and can be
sustained locally within the CNS. Plasma cells do
not carry CD20 cell surface molecules and are not
affected by anti-CD20 MAbs. Although apparently restricted to late disease phases, the development of lymphoid tissue-like structures in brains
of patients with MS suggests a pathophysiological
role of B cells in MS that is possibly perpetual,
eventually being one of the many contributors
leading to SPMS.
The progressive phase of MS is an autoimmune
disorder characterized by an intrathecal compartmentalization of inflammation resisting
immunosuppressive treatments. The presence of
lymphoid follicle-like structures in the meninges of some MS patients indicates that B cells
can mature and perpetuate a compartmentalized
humoral immune response.
90
Some illustrative examples of drugs—and this
report makes no attempt to list all the possible
combinations that can cross the BBB—are cyclophosphamide (CYC), an alkylating agent that
penetrates the BBB, and CNS parenchyma, which
has been shown to decrease pro-inflammatory T
helper Th1 cytokine interferon-gamma and interleukin-12 in MS. It also increases the secretion of
the anti-inflammatory Th2 cytokines IL-4 and
IL-10 in CSF and peripheral blood.8 It suppresses
cell-mediated and humoral immunity through its
actions of T and B cells.9 Cyclophosphamide may
be useful in advanced disease but has not been
studied in a randomized clinical trial setting. It is
perhaps time to revive an old drug.
Second, laquinimod, an investigational CNS-active immunomodulator and a small molecule, can
diffuse freely across the BBB without any active
transport, but cardiotoxicity at higher doses (1.2
mg/day) halted its progress in clinical trials and
is clearly a limitation.10 Can it be used at lower
doses that do not produce cardiotoxicity and yet
be beneficial when combined with MAbs? That is
a question only clinical trials can address.
GHS Proc. November 2016; 1 (2): 89-91
MONOCLONAL THERAPIES IN MULTIPLE SCLEROSIS
Last, sphingosine-1-phosphate (S1P) receptors
blockers cross the BBB but fingolimod failed in
the PPMS study.10 However, the new S1P blocker
such as siponimod has a relatively short half-life
compared to fingolimod. It has fewer cardiac side
effects and comes with BBB penetration capabilities. A phase III trial of siponimod in SPMS is
ongoing. Could drugs such as CYC, fingolimod, or
laquinimod be the future of MS therapies in combination with MAbs? Some other strategies that
have been tried in oncology, for example, include
the use of nanoparticles, immunoliposomes, peptide vectors, and design of influx transporters and
could perhaps serve as model strategies for MS
therapies moving forward.
The premise of this report lies in the fact that strategies to treat MS ought to begin early, before B-cell
follicles have had time to develop. To address disease within the CNS, molecules that cross the BBB
are critical. Alternatively, the best responsiveness
to MAbs could perhaps be found in strategies that
destroy encephalitogenic B-cell populations in
the periphery at the clinically isolated syndrome
(CIS) stage and not as second-line drugs.
The idea of combination therapy in MS is not
new. Many studies have explored concepts such
as safety, tolerability, and efficacy of several combination regimens but are underpowered and/or
poorly designed. The key to success is to combine
agents that have been shown to penetrate BBB
with drugs that work effectively and show robust
efficacy outside of the CNS, such as MAbs. For
proof-of-concept studies, combination trials need
to identify patients with worsening disability
scores on EDSS, and selection of appropriate target population is key. Enrollment of failed RRMS
patients on a standard drug based on NEDA criteria and whose EDSS is worsening perhaps forms
the most eligible patient cohort to initiate combination therapy trials.
A seminal study analyzed immunological, histochemical, and morphometric data on post-mortem brain tissue samples from 29 SPMS and 7
primary progressive PPMS cases.11 B-cell follicles were detected in the meninges in 41.1% of
the SPMS cases but not in PPMS cases, suggesting that the diseases are fundamentally different
and treatment ought to begin at the RRMS or CIS
stage of the disease. This strategy could be particularly useful for the AA patients with MS.
Correspondence
Address to:
Jagannadha Avasarala,
MD, PhD, Greenville
Health System,
Neuroscience
Associates, 200
Patewood Dr,
Greenville, SC 29615
([email protected])
We will never know if combining a small molecule with MAbs at disease onset could work if
we do not use scientific reasoning to address the
disease mechanisms both inside and outside of
the CNS. It must also be recognized that SPMS
cases with follicles demonstrate younger age at
onset, irreversible disability, death, and more pronounced demyelination, microglia activation, and
loss of neurites in the cerebral cortex.11 Without
addressing such fundamental pathological phenomena residing in a compartmentalized “zone,”
MS therapies will continue to scratch the surface
in treating worsening disability status in patients
and fail summarily.
References
1. Naismith RT, Trinkaus K, Cross AH. Phenotype
and prognosis in African-Americans with multiple
sclerosis: a retrospective chart review. Mult Scler.
2006;12:775-81.
2. Banks WA. Characteristics of compounds that cross
the blood-brain barrier. BMC Neurol. 2009;9:S3.
3. Cheng Z, Zhang J, Liu H, Li Y, Zhao Y, Yang E. Central nervous system penetration for small molecule
therapeutic agents does not increase in multiple sclerosis and Alzheimer’s disease-related animal models
despite reported blood-brain barrier disruption. Drug
Metab Dispos. 2010;38:1355-61.
4. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk
S, Bö L. Axonal transection in the lesions of multiple
sclerosis. N Engl J Med. 1998;338:278-85.
5. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E,
Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol.
2004;14:164-74.
6. Rubenstein JL, Combs D, Rosenberg J, et al. Ritux-
GHS Proc. November 2016; 1 (2): 89-91
imab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101:466-8.
7. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons
JA. Rituximab reduces B and T cells in cerebrospinal
fluid of multiple sclerosis patients. J Neuroimmunol.
2006;180:63-70.
8. Smith DR, Balashov KE, Hafler DA, Khoury SJ,
Weiner HL. Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: increased interleukin-4 production and
associated eosinophilia. Ann Neurol. 1997;42:313-8.
9. Brück W, Wegner C. Insight into the mechanism of
laquinimod action. J Neurol Sci. 2011;306:173-9.
10. Lublin F, Miller DH, Freedman MS, et al. Oral fingolimod in primary progressive multiple sclerosis
(INFORMS): a phase 3, randomized, double-blind,
placebo-controlled trial. Lancet. 2016;387:1075-84.
11. Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell
follicles in secondary progressive multiple sclerosis
associate with early onset of disease and severe cortical pathology. Brain. 2007:130:1089-104.
91
Teachable Moment
Do I Really Need to Stop Taking Estrogen?
Chelsea W. Fox, MD; Bruce A. Lessey, MD, PhD; and Paul B. Miller, MD
From the Department of OB/GYN, Greenville Health System, Greenville, SC (C.W.F., B.A.L., P.B.M.),
and University of South Carolina School of Medicine Greenville, Greenville, SC (B.A.L., P.B.M.)
Story From the Front Line
D.H. is a healthy 58-year-old woman who went
through menopause at 54, with the onset of hot
flashes, vaginal dryness, forgetfulness, and frequent nighttime awakenings. She was offered
hormone replacement for symptomatic relief
shortly after the onset of menopause and because
she has a uterus was put on combined conjugated
equine estrogen (CEE) and medroxyprogesterone acetate. She has a total cholesterol of 212, a
high-density lipoprotein of 43, and a family history of heart disease in a maternal aunt. She has
also been treated long term with cabergoline for
a prolactin-secreting pituitary adenoma, which
is currently well controlled.
During the past year, she saw her internist who
strongly recommended that she discontinue
estrogen treatment secondary to concern for
increased cardiovascular disease (CVD) risk. She
was prescribed an herbal supplement and told to
exercise more often. She is happily married and
notes new onset of vaginal dryness, dyspareunia,
and return of hot flashes and sleep disturbances
since she recently discontinued her hormone
replacement therapy (HRT). When seen for her
refills for medications for her adenoma, she asked
her reproductive endocrinologist, “Do I really
need to stop taking estrogen?”
Teachable Moment
Myocardial infarction (MI) is the greatest risk
for death in postmenopausal North American
women.1 Data from over 30 observational studies have strongly suggested that estrogen is protective against heart disease.2 For example, the
Nurse’s Health Study showed that ever users and
current users had 0.5 (95% CI, 0.3–0.8, P = .007)
and 0.3 (95% CI, 0.2–0.6, P = .001) relative risks
(RR), respectively, for coronary disease compared
to never users of menopausal hormonal therapy
92
(HT).3 However, the Women’s Health Initiative (WHI), a large randomized controlled trial
(RCT) aimed to address the effect of HT on CVD,
breast cancer, and osteoporosis, discontinued the
estrogen plus progestin arm because of lack of
any demonstrable cardioprotective effect, excessive breast cancers (RR 1.26; 95% CI, 1.0–1.6), and
an increased risk in the Global Index of Harm.4
The impact of these results was profound, with
many women discontinuing their HT. However,
when CEE was analyzed alone, the adverse effect
on breast cancer virtually went away with a RR
of 0.77 (95% CI, 0.6–1.0), but still there was a
slight increased risk for all CVD (RR 1.12; 95%
CI, 1.0–1.2).4
In retrospect, the WHI was not designed to
answer the question of whether estrogen can prevent heart attacks in newly menopausal women
without heart disease. It enrolled older women
(average age of 63) who were more likely to have
advanced stages of atherosclerosis, supporting
conclusions from the Heart and Estrogen/progestin Replacement Study (HERS) study, which suggested that HRT in women with known coronary
artery disease might be at increased risk, at least
in the first year of treatment.5,6
With the passage of time since the landmark
WHI study, there have been further re-analyses
that suggested younger women on estrogen benefit disproportionately compared to older women.7
A 13-year follow-up of the WHI showed the group
of women ages 50–59 at randomization who
received CEEs had a 40% lower risk of MI than
those who received placebo, whereas no effect
was seen in women who were ages 60 or older at
randomization.8 Furthermore, subsequent analyses from the WHI have shown the absolute risk
of adverse effects (measured by the global index
including stroke, pulmonary embolism, colorectal cancer, endometrial cancer, hip fracture, and
GHS Proc. November 2016; 1 (2): 92-93
DO I REALLY NEED TO STOP TAKING ESTROGEN?
death) is much lower for younger women than for
older women on HRT (12 excess cases per 10 000
women annually for ages 50–59 years compared
to 38 for ages 70–79 years).8
In a smaller, more recent RCT, the Danish Osteoporosis Prevention Study,9 women were randomized to estrogen and norethisterone acetate
or placebo if they had a uterus, and 2 mg oral
estradiol or placebo if they did not. Over 16 years
of follow-up, there was a reduction in CVD endpoints with an RR of 0.61 (95% CI, 0.4–0.9). These
studies support a “critical window” hypothesis,
suggesting women receive the greatest cardiovascular benefit from HRT when started immediately at the onset of menopause.
The recently published ELITE (Early versus Late
Intervention Trial with Estradiol) trial was specifically designed to test this hormone-timing
hypothesis.10 This RCT stratified postmenopausal women into either early postmenopausal
(<6 years) or late postmenopausal (≥10 years)
groups and randomized them to receive oral
estradiol (with vaginal progesterone if they had
a uterus) or placebo. The primary outcome was
the rate of change in carotid-artery intima-media thickness (CIMT) assessed by ultrasound
every 6 months. After 5 years of intervention,
the rate of CIMT progression in the early-postmenopausal group was significantly lower in
the estradiol group than in the placebo group
(absolute difference 0.0034 mm/year, P = .008),
whereas the rate of CIMT progression in the
late-postmenopausal group was similar in the
estradiol and placebo groups (difference 0.0012
mm/year, P = .29).
The Global Consensus Statement on Menopausal
Hormone Therapy, endorsed by the American
Society for Reproductive Medicine and the North
American Menopause Society, states menopausal
hormone therapy (MHT) is the most effective
treatment for vasomotor symptoms associated
with menopause, particularly for women less
than 60 years of age or within 10 years of menopause.11 Furthermore, randomized clinical trials
and observational data have provided evidence
that MHT may actually decrease coronary heart
disease and all-cause mortality when initiated in
women less than 60 years of age and within 10
years of menopause.11
Correspondence
Address to:
Chelsea Fox, MD,
Greenville Health
System, Department
of OB/GYN, 890 W
Faris Rd, Suite 470,
Greenville, SC 29605
([email protected])
MHT should be considered as a safe option for
symptomatic, healthy, early-menopausal patients,
such as D.H., who should have the right to be
involved in decisions about discontinuation of
their HT regimens. Given the prevalence of heart
disease in North America, if estrogen is a beneficial prevention tool, it deserves further research
and dialogue between healthcare providers and
their patients.
References
1. Cummings SR, Black DM, Rubin SM. Lifetime risks
of hip, Colles’, or vertebral fracture and coronary
heart disease among white postmenopausal women.
Arch Intern Med. 1989;149:2445-8.
2. Barrett-Connor E, Grady D. Hormone replacement
therapy, heart disease, and other considerations.
Annu Rev Public Health. 1998;19:55-72.
3. Stampfer MJ, Willett WC, Colditz GA, Rosner B,
Speizer FE, Hennekens CH. A prospective study of
postmenopausal estrogen therapy and coronary
heart disease. N Engl J Med. 1985;313:1044-9.
4. Anderson GL, Limacher M, Assaf AR, et al. Effects
of conjugated equine estrogen in postmenopausal
women with hysterectomy: the Women’s Health
Initiative randomized controlled trial. JAMA.
2004;291:1701-12.
5. Hulley S, Grady D, Bush T, Furberg C, Herrington
D, Riggs B, Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart
and Estrogen/progestin Replacement Study (HERS)
Research Group. JAMA. 1998;280:605-13.
GHS Proc. November 2016; 1 (2): 92-93
6. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus
progestin and the risk of coronary heart disease. N
Engl J Med. 2003;349:523-34.
7. Harman SM. Menopausal hormone treatment cardiovascular disease: another look at an unresolved
conundrum. Fertil Steril. 2014;101:887-97.
8. Manson JE, Chlebowski RT, Stefanick ML, et al.
Menopausal hormone therapy and health outcomes
during the intervention and extended poststopping
phases of the Women’s Health Initiative randomizaed trials. JAMA. 2013;310:1353-68.
9. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Effect
of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. BMJ. 2012;345:e6409.
10. Hodis HN, Mack WJ, Henderson VW, et al. Vascular
effects of early versus late postmenopausal treatment
with estradiol. N Engl J Med. 2016;374:1221-31.
11.Villiers TJ, Gass ML, Haines, CJ, Hall JE, Lobo
RA, Pierroz DD, Rees M. Global consensus statement on menopausal hormone therapy. Climacteric.
2013;16:203-4.
93
Value Vignette
Choosing High-Value Care in Suspected Lower Extremity
Deep Vein Thrombosis
Moon Won, DO, and Steven Connelly, MD
From the Department of Medicine, Greenville Health System, Greenville, SC (M.W., S.C.)
Clinical Scenario
Treatment Options
A 70-year-old man with a past medical history
significant for combined heart failure, chronic
kidney disease stage 3a, type 2 diabetes mellitus,
and prostate cancer (status postprostatectomy
in 1996 and radiation in 2012) presented from a
nursing home for altered mental status (AMS).
Altered mental status was initially thought to
be secondary to polypharmacy in the setting of
new medication administration of Norco and
Benadryl the night prior to presentation. At baseline, the patient ambulated independently and
required no oxygen supplementation.
Option A: Obtain BLE venous duplex with compression for worsening BLE symptoms to rule
out an acute deep vein thrombosis (DVT). BLE
venous duplex with compression for DVT was
negative. Respiratory status and BLE symptoms
improved with diuretics.
Upon exam, vital signs were stable except for
requiring 2 liters of oxygen supplementation via
nasal cannula to keep oxygen saturation >90%.
Bilateral lower extremity (BLE) pitting edema
(3+) to the knees and tightness were noted with
mild tenderness to palpation bilaterally and
without erythema. Bibasilar breath sounds were
diminished. Cardiac exam was normal. Weight
was 76 kg with a baseline weight of 72 kg. Initial
abnormal labs included an elevated creatinine
of 3.1 mg/dL, venous lactic acid of 4.2 mmol/L,
brain natriuretic peptide of 1450 pg/mL, chest
X-ray with cardiomegaly, and chronic bilateral
pleural effusions.
Home medications furosemide and metolazone
were initially held due to the elevated creatinine
and lactic acidosis.
The patient’s AMS improved on day 2; his respiratory status, however, worsened and required 4
liters of oxygen supplementation. Bilateral lower
extremity edema, tightness, and tenderness were
noted to be worse. Home dose of furosemide and
metolazone was restarted.
94
Option B: Obtain Well’s score: -2. Negative for
active cancer, recent paralysis, paresis, or immobilization of lower extremities, recently bedridden, recent major surgery, localized tenderness
along the distribution of the deep venous system,
entire leg swollen, calf swelling of 1 lower extremity at least 3 cm larger than the other side, pitting
edema confined to the symptomatic leg, previous
DVT. Positive for an alternative diagnosis being
more likely (decompensated heart failure). Low
pretest probability for a lower extremity DVT;
therefore, obtain a D-dimer: 0.15 mcg/mL (negative). Since the pretest probability is low and
D-dimer negative, we can conclude that there
is no DVT without obtaining a lower extremity
venous duplex with compression study. Respiratory status and BLE symptoms improved with
diuretics.
Discussion Questions
1. What is the initial approach to a patient with
signs or symptoms of lower extremity DVT
(ie, unilateral or bilateral lower extremity
edema and/or erythema and/or pain)?
a.Obtain lower extremity venous duplex
with compression study
b. Obtain a D-dimer
c.Obtain pretest probability by using the
Well’s score
GHS Proc. November 2016; 1 (2): 94-96
CHOOSING HIGH-VALUE CARE IN SUSPECTED DVT
Answer: Using the Well’s score for DVT to determine the pretest probability is the most important initial step. In patients with a low or moderate pretest probability (Well’s score of -2 to 2), a
highly sensitive D-dimer test should be the initial
test rather than a venous duplex with compression. In patients with a high pretest probability
(Well’s score of ≥3), a venous duplex with compression should be the initial test.
2. What is the value of D-dimer in diagnosing a
lower extremity DVT?
a. Highly specific test to rule in a DVT
b. Highly sensitive test to rule out a DVT
c. Highly specific and sensitive test to rule in
and rule out a DVT
Answer: D-dimer is a highly sensitive test to rule
out a DVT but lacks specificity. There are multiple
D-dimer assays available. According to Di Nisio
et al, enzyme-linked immunofluorescence assay
(ELFA), microplate enzyme-linked immunosorbent assay (ELISA), and quantitative latex assay
had the highest sensitivities for DVTs with 97%,
95%, and 96% but had specificities of 42%, 47%,
and 48%, respectively.1 A value <500 ng/mL or
<0.5 mcg/mL fibrinogen equivalent units (FEU)
has been frequently studied, but the cutoff value
can vary by institution.2,3 D-dimer value <0.42
mcg/mL FEU is considered a negative value at
Greenville Health System (GHS).
Costs*
Option A: $508 for BLE venous duplex with
compression
Option B: $27 for D-dimer
Costs were obtained from heathcarebluebook.
com.4 These costs are estimates and represent the
amount typically paid by an insurance company.
*
Teaching Moment
The most frequently utilized initial diagnostic tool for a suspected acute lower extremity
DVT at GHS is a venous duplex with compression. This approach is time consuming and very
costly with a low positive yield. The diagnostic
pathway recommended by American College of
Chest Physicians (ACCP) and similarly by the
National Institute for Health and Care Excellence
(NICE) presents a cost-effective, safe, and easyto-use guideline for clinicians to diagnose lower
extremity DVT.5,6
GHS Proc. November 2016; 1 (2): 94-96
In patients who present with signs or symptoms
of lower extremity DVT (ie, most commonly,
unilateral or bilateral lower extremity edema
and/or erythema and/or tenderness), the initial
diagnostic test should be guided by the clinical
assessment of pretest probability by utilizing the
Well’s score for DVT. In patients with a low or
moderate pretest probability (Well’s score of -2
to 2), a highly sensitive D-dimer test should be
the initial test rather than a venous duplex with
compression. In patients with a high pretest probability (Well’s score of ≥3), a venous duplex with
compression should be the initial test.5-7
D-dimer is a sensitive test but lacks specificity
for the diagnosis of DVT and is, therefore, only
useful when negative (ie, D-dimer value <0.42
mcg/mL FEU at GHS). A negative D-dimer level
in conjunction with a low-to-moderate clinical probability of DVT is useful and cost-effective in excluding DVT without the need for an
ultrasound examination.7,8 D-dimer values may
be falsely elevated as a result of multiple factors:
Most notably, the patient’s age (>60) and renal
dysfunction were associated with false-positive
D-dimer levels in 57% and 44% of venous thromboembolism-negative patients, respectively.3,9
Other factors that can lead to a falsely elevated
D-dimer include recent surgery, trauma, pregnancy, and cancer.
There are multiple D-dimer assays available;
at GHS, D-dimer is measured via the quantitative latex assay in mcg/mL FEU. According to
Di-Nisio et al, ELFA, ELISA, and quantitative
latex assay had the highest sensitivities for DVTs
with 96%, 95%, and 93%, respectively.1 Another
study by Bates et al showed that in patients with
low-to-moderate pretest probability of DVT,
a quantitative latex D-dimer assay reliably
excluded DVTs.10
Intervention and Result
We performed a retrospective review of all
patients diagnosed with lower extremity pain,
edema, or swelling who had a unilateral or bilateral lower extremity venous duplex with compression performed during their hospitalization
at GHS’ Greenville Memorial Hospital between
October 2014 and September 2015. The aim was
to evaluate clinicians’ approach to patients with
possible lower extremity DVTs and determine
what measures could have been applied to provide
a safe and most cost-effective work-up. Patients in
the outpatient setting, surgical patients, pediat-
95
Correspondence
Address to:
Moon Won, DO,
Greenville Health
System, Department
of Medicine, 5th Floor
Support Tower, 701
Grove Rd, Greenville,
SC 29605
([email protected])
ric patients, patients with suspected pulmonary
embolism, and patients with suspected upper
extremity DVT were excluded.
Depending on the clinical assessment of pretest probability by utilizing the Well’s score for
DVT, patients were categorized into groups of
low, moderate, or high risk for a lower extremity
DVT. Out of 68 total patients, 59 patients were
categorized into the low-to-moderate risk group.
Fifty-seven out of those 59 patients had a negative
venous duplex with compression study. Ten out
of the total 68 patients had undergone a D-dimer.
Out of those 10 patients, 4 patients who were part
of the low-to-moderate risk group had a negative
D-dimer and had a negative venous duplex with
compression study.
If all 59 patients in the low-to-moderate risk
group had a D-dimer level drawn initially (as
recommended by ACCP and per NICE guideline) instead of a venous duplex with compression study, a total of $25 506 could have been
saved. During the same time frame, GHS (inpatient only) as a whole had a total of 218 venous
duplex with compression studies (unilateral
and bilateral) of the lower extremities ordered.
Extrapolating the data from the study to the
entire GHS, a potential total of $78 262 could
have been saved.
Proposal: In patients who present with a suspected lower extremity DVT (unilateral or bilateral lower extremity edema and/or erythema and/
or tenderness), the initial diagnostic test should
be guided by the clinical assessment of pretest
probability by utilizing the Well’s score for DVT.
In patients with a low or moderate pretest probability (Well’s score of -2 to 2), a D-dimer test
should be the initial test rather than a venous
duplex with compression study. If the D-dimer
is negative (<0.42 mcg/mL), no further testing
is recommended. If D-dimer is elevated above
0.42 mcg/mL, a venous duplex with compression
study is recommended and, depending on those
results, treatment can be started.
In patients with a high pretest probability (Well’s
score of ≥3), a venous duplex with compression
study should be the initial test. If positive, treatment can be started.
References
1. Di Nisio M, Squizzato A, Rutjes AW, Büller HR,
Zwinderman AH, Bossuyt PM. Diagnostic accuracy
of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost.
2007;5:296-304.
2. Bounameaux H, de Moerloose P, Perrier A, Reber G.
Plasma measurement of D-dimer as diagnostic aid in
suspected venous thromboembolism: an overview.
Thromb Haemost. 1994:71:1-6.
3. Mayo Clinic: Mayo Medical Laboratories. D-Dimer, plasma. http://www.mayomedicallaboratories.
com/test-catalog/Clinical+and+Interpretive/9290.
Accessed July 3, 2016.
4.Healthcare Bluebook. https://healthcarebluebook.
com/page _ProcedureDetails.aspx?dataset=md & i d = 4 4 4 & g =A r m% 2 0 o r % 2 0 L e g % 2 0 U l t r a sound%20(Duplex)&directsearch=true.
Accessed
January 10, 2016.
5. Bates SM, Jaeschke R, Stevens SM, et al. Diagnosis
of DVT: antithrombotic therapy and prevention of
thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.
Chest. 2012;141(2 Suppl):e351S-e418S.
96
6. National Institute for Health and Care Excellence
(NICE). Venous thromboembolic diseases: diagnosis,
management and thrombophilia testing. http://www.
nice.org.uk/guidance/cg144/chapter/Recommendations#diagnosis-2. Published June 2012. Updated
November 2015. Accessed January 10, 2016.
7. Society for Vascular Medicine. Deep vein thrombosis.
http://mydeepveinthrombosis.com/addressing-thepatient-with-suspected-dvt/. Accessed July 3, 2016.
8.Bauer KA. UpToDate. Approach to the diagnosis and therapy of lower extremity deep vein
thrombosis.
http://www.uptodate.com/contents/
approach-to-the-diagnosis-and-therapy-of-lower-extremity-deep-vein-thrombosis?source=search_
resu lt&search=diagnosis+of+dv t&selectedTitle=1~150. Updated July 15, 2014. Accessed January
10, 2016.
9. Pulivarthi S, Gurram MK. Effectiveness of d-dimer
as a screening test for venous thromboembolism: an
update. N Am J Med Sci. 2014;6:491-9.
10. Bates SM, Kearon C, Crowther M, et al. A diagnostic
strategy involving a quantitative latex D-dimer assay
reliably excludes deep venous thrombosis. Ann Intern
Med. 2003;138:787-94.
GHS Proc. November 2016; 1 (2): 94-96
Special Article
Perceptions of and Preferences for a Mobile Health Clinic
for Underserved Populations
Melinda Gillispie, MSN, RN; Catherine Mobley, PhD; Lynette M. Gibson, PhD, RN; and Arelis
Moore de Peralta, MD, PhD, MPH, MEd
From the Department of Community Relations, Greenville Health System, Greenville, SC (M.G.);
Department of Sociology and Anthropology, Clemson University, Clemson, SC (C.M.); Mary Black
School of Nursing, University of South Carolina Upstate, Spartanburg, SC (L.M.G.); and Department
of Youth, Family, and Community Studies, Clemson University, Clemson, SC (A.M.P.)
Abstract
Background: Research has established that members of particular demographic groups are inordinately burdened by differential healthcare access. Mobile health clinics (MHCs) are emerging
across health systems to improve access to care of marginalized populations. This study explored
the perceptions and concerns of community residents living in underserved neighborhoods toward
MHC services.
Methods: This study used a qualitative descriptive design with 5 focus group meetings. Purposive
sampling was used to recruit ethnically diverse, English- and Spanish-speaking men and women
ages 20–67 residing in 5 underserved neighborhoods in Greenville County, SC.
Results: Participants (N = 35) felt positive about obtaining personalized health care through an MHC
unit. MHCs were viewed as convenient, situated in a central location in the community. Participants
described positive qualities of MHCs, including cleanliness, attractiveness, convenience, comfort,
consistency, compassion, and safety. Participants suggested the MHC should provide basic emergency “triage” care and transport to the hospital if necessary, and act as a conduit for offering health
education and access to affordable prescriptions. Participants’ preferences for days of service varied; however, consistency of service and placement in a safe community area were more important.
Conclusions: Findings demonstrated that it is important for health systems to ascertain the level of
acceptance and readiness among residents in underserved communities for an MHC; this assessment should take place prior to launching the MHC. Delivering health care through an MHC involves
more than providing tangible healthcare services to community residents. Consistent, respectful,
and high-quality care should be the foundation of MHC development and ongoing implementation.
R
esearch has established that members of particular demographic groups are inordinately
burdened by differential healthcare access
resulting from their race, ethnicity, social class,
and geographic isolation.1,2 Given predictions that
our society will become even more diverse in the
next several decades, these health disparities will
likely continue to be a challenge. To address differential healthcare access, many healthcare systems
have introduced mobile health clinics (MHCs) to
their mix of service delivery options. MHCs are
GHS Proc. November 2016; 1 (2): 97-104
defined as “transportable healthcare units that
enable the provision of community-based care
off-site from institutions and healthcare agencies to underserved populations that may otherwise be hard to reach.”3 That is, MHCs aspire to
reach the more vulnerable populations that would
otherwise have inadequate access to high-quality health care. Many MHCs often operate as an
extension of larger healthcare systems to which
patients are referred if they need additional services not addressed by a particular MHC.
97
MHCs have become increasingly common in the
past decade; estimates indicate that 2000 such
facilities provide services to 6.5 million people
each year.4 MHCs provide a variety of preventive
and primary care services, depending on available resources and on the particular community being served. Services include treatment of
acute conditions (eg, common cold, minor injury
care, etc.) and chronic conditions (eg, diabetes,
hypertension, etc.); lab and diagnostic services;
cancer screenings; specialty clinics; dental care;
ophthalmology services; medication and prescription assistance; and health education. Over
the past several years, MHCs have transitioned
from addressing episodic, urgent healthcare
needs to providing ongoing care to individuals
with chronic conditions, a trend that is likely to
increase in the future.5
In fall 2015, the Department of Community Relations at Greenville Health System (GHS) funded
and initiated a community assessment to determine residents’ attitudes and perceived needs
pertaining to MHCs. This endeavor contributes
to GHS’ efforts to expand access to health care via
an MHC in Greenville County, SC. The research
effort reported here consisted of 5 focus groups
conducted in 5 underserved neighborhoods in
Greenville County. The study results provide a
starting point for the design, development, and
delivery of MHC services to communities across
the county.
Methods
The focus group methodology was used to ascertain residents’ general opinions about and preferences for an MHC. A hallmark of this methodology, which distinguishes it from the frequent,
but inaccurate, label of “group interview,” is
its encouragement of interaction among group
members to elicit richer qualitative data about
the topic under discussion.6 The dynamic nature
of focus groups often brings information to the
surface that would not otherwise emerge through
other methods of research. The open-ended
structure of focus groups allows researchers to
learn what people feel about a particular issue,
as well as how and why.7 In that respect, focus
groups have several advantages over other forms
of research, such as surveys, which generally collect individual responses to closed-ended questions that often do not allow for elaboration.
Sample Selection and Participant
Recruitment
The GHS Institutional Review Board approved
this study in October 2015. Purposive sam98
pling was then used to select ethnically diverse,
English- and Spanish-speaking women and men
ages 20–67 who resided in 1 of 5 underserved
neighborhoods in Greenville County, SC, at the
time of the study. The 5 underserved neighborhoods were chosen based on areas of high risk and
need for healthcare services and were selected as
pilot sites for initial MHC delivery.
Participants were recruited through community
centers, churches, community outreach representatives, community-based service provider
liaisons, and GHS neighborhood health partners. Three days prior to the focus groups, study
researchers contacted participants to remind
them about the study. At the conclusion of each
focus group, participants were provided with a
$25 gas card. All individuals who volunteered to
participate and who were scheduled for one of the
focus groups ultimately participated in the study.
The demographic characteristics of the focus
group participants are summarized in Table 1.
Focus Group Delivery
The focus groups were held December 2015 at
locations convenient to the participants, including community centers and churches. Each
focus group had a main moderator, who led
the focus group, and the principal investigator
who took field notes throughout. Before starting any study-related procedures, participants
were issued the informed consent. Each page of
the informed consent was verbally read to them
to ensure participants had a full understanding
of the study. All participants provided written
informed consent and completed a brief demographic questionnaire, providing information
about background characteristics, current health
status, and primary source of health care. Eleven
questions were asked in the 5 focus groups. All 5
focus groups were audio recorded.
Data Analysis
The data analysis proceeded in several stages.
First, a professional transcriber transcribed
each focus group interview; each transcript was
then verified for accuracy. The Spanish-speaking transcripts were transcribed to English by a
GHS certified Language Services employee. One
study investigator (C.M.) then engaged in more
in-depth analysis, first reading each transcript
in detail and writing initial analytic notes on
emerging insights that guided the subsequent
coding and analysis. The final transcripts were
then uploaded into the qualitative software package ATLAS.ti (Version 1.0.49), an analytical tool
that aided in the initial categorization and codGHS Proc. November 2016; 1 (2): 97-104
PERCEPTIONS/PREFERENCES FOR A MOBILE HEALTH CLINIC
ing of the data. Subsequent data analysis incorporated both deductive and inductive coding.
The deductive analysis reported in this paper
involved a more directed approach, guided by the
interview protocol. Variables were coded according to the questions asked during the focus group.
This coding was done to ensure that the primary
research questions were addressed across all 5
focus groups. Then, using an iterative approach,
these pre-existing codes were compared with the
new codes and themes that emerged in the second
stage of inductive analysis. (NOTE: Actual quotes
from the focus group respondents appear in italics below.)
Results
Initial Perceptions of the MHC Model of
Healthcare Delivery
The first main focus group question (“What is
the first thing that comes to mind when you hear
‘mobile health clinic’? What images come to
mind?”) served as an “ice-breaker” and allowed
the researchers to learn about the participants’
general understanding of the MHC concept.
Their responses provided a starting point for
contextualizing participants’ more specific views
about MHC service delivery.
A few participants were somewhat familiar with
the concept of mobile healthcare delivery or had
experience with similar healthcare offerings in
the community. Some shared their perceptions
about what an MHC looks like, comparing it to
a local bloodmobile unit, a car that has a camper,
a big bus that can care for people, a tour bus, and
something mobile, that keeps moving, here and
there, from one neighborhood to the next. Participants were aware that an MHC is not equivalent
to a hospital and is not an operating room. However, they envisioned that the MHC facility would
have the basic equipment necessary for offering
general health care to the community. The MHC
is viewed as a doctor’s office on wheels that comes
with medicines, vaccinations for the kids, for people, for everybody.
Participants were aware that MHCs offer affordable health care for those who cannot generally
pay to see a doctor through the traditional healthcare system; they perceived that an MHC would be
less expensive than a hospital. Participants felt that
this model of healthcare delivery is thus valuable to
those in need of low-cost health care, especially for
those who don’t have insurance and cannot afford
to take [their children] to the doctor every time they
got a scratch. Such a facility offers easy access for
the people who really need it, if they come and take
GHS Proc. November 2016; 1 (2): 97-104
Table 1
Demographic characteristics of focus group participants.
Characteristic
N
35
Gender, no. (%)
Female
28 (80.0)
Race/Ethnicity, no. (%)
African American/Black
Caucasian/White
Latino/Hispanic
24 (70.6)
2 (5.9)
8 (23.5)
Age, years (mean = 44.8), no. (%)
20–29
7 (20.1)
30–39
8 (22.8)
40–49
6 (17.1)
50–59
5 (14.2)
60–69
9 (25.7)
Education, no. (%)
Junior HS or less (1st-8th grade)
3 (9.1)
Some high school
6 (18.2)
Graduated high school or earned GED
9 (27.3)
Some college/technical school, no degree
10 (30.3)
2-year college degree
4 (12.1)
4-year college degree
1 (3.0)
Employment, no. (%)
Working full-time
5 (14.3)
Working part-time
8 (22.9)
Self-employed
1 (2.9)
A homemaker
6 (17.1)
Out of work for more than a year
2 (5.7)
Out of work for less than a year
1 (2.9)
Retired
2 (5.7)
Unable to work
10 (28.6)
Income, no. (%)
Less than $10 000
16 (47.1)
$10 000–$19 999
9 (26.5)
$20 000–$29 999
2 (5.9)
$30 000–$39 999
3 (8.8)
$80 000–$89 999
2 (5.9)
Choose not to answer
2 (5.9)
Note: Not every focus group respondent answered every item on the
questionnaire.
99
advantage of it. The health care offered through an
MHC was equated to a well-known local clinic for
low-income residents, in terms of affordability and
access. Participants indicated that an MHC would
also offer services to vulnerable populations, such
as the elderly and homeless.
MHCs were viewed as convenient, situated in a
central location in the community, thus offering
quick and easy access to health care. As a model
of mobile sufficient care, MHCs are important
because some people ... may need some [non-emergency] help. And by the bus being in the community, they may be able to get there quicker and
to receive the help they need at that time. This
point is especially important for individuals
lacking transportation and for those whose busy
and complex schedules make it difficult to visit
healthcare professionals in other locations. Thus,
participants envisioned that an MHC would have
a predictable schedule: I imagine that the doctors
come on a certain day, certain time, to a place that
is conditioned to give care. Patients would thus be
able to get an appointment to go there at a certain
time and get out fast.
Related to convenience, accessibility (local health)
was an additional key characteristic. This more
specific factor refers to the ease of seeing a particular doctor. As one participant indicated, the
presence of the MHC would be much like having a workplace nurse that offers “on-the-spot”
diagnosis at places of employment. In the words
of one participant, the nurse could say “you need
to be seen right now. You need to go to the emergency room.” [As a result, at an MHC], at least you
could be told the seriousness of your situation, if it
is serious. Thus, the MHC is also where residents
can get emergency treatment, especially if they
cannot see their regular doctor and the MHC
happens to be in the community at the time that
they need such care.
Prior Experiences With the MHC Model of
Healthcare Delivery
To learn more about participants’ views on
MHCs, participants were asked to describe their
prior experiences with this model of healthcare
delivery. Several participants indicated they had
visited a local bloodmobile unit and remarked on
several positive qualities of this facility, including cleanliness (You wouldn’t be afraid that you
would catch something or be contaminated by;
It’s obviously very clean); attractiveness (It’s very
visible and showy; You can’t miss it); convenience
(You don’t have to have an appointment); comfort
(It’s not like it’s small in there); safety; and the
100
well-qualified staff who know what they’re doing.
Because the local bloodmobile unit has a substantial and known presence in the community, residents seem to trust the care it offers.
Some individuals reported they that had visited
a mobile dental health clinic in the community.
Another participant visited a mobile health facility offered by a local hospital at a local church.
In this instance, the participant described receiving mammograms and other women-centered
services through this healthcare modality. This
participant was impressed with the convenience,
the quality of services provided, and the friendly
and attentive staff: I arrived and they provided
me with a great service, because they are very nice
people, the ones there. Then, I had some tests done
and it was fast. I don’t have a reason to lie to you.
They didn’t take a long time. I even went, “Wow,
this is faster than the hospital.” Another participant, who volunteered at the MHC sponsored by
a local hospital, described the facility as beautiful,
state-of-the-art and the staff as wonderful, very
friendly, and very much oriented to outreach. She
said that she couldn’t imagine someone hesitating
to want to have any kind of health care on that bus.
Nearly all of the participants in one focus group
indicated they did not have prior experience with
an MHC. Similarly, participants in another focus
group indicated that they had no prior experiences with MHCs. However, when prompted,
they said they were familiar with the local bloodmobile unit.
When asked about their initial perceptions of
MHCs, several participants provided examples of
health care offered through other kinds of entities,
such as stand-alone facilities and a logistic transport service. Although not directly comparable
to MHCs, the responses offer insights into the
characteristics that should be considered when
offering MHC services. One participant reported
having a negative experience with a dental clinic
offered through a community-based health clinic
offering medical services to community members
at no cost. She said she waited in line for a long
time for this first-come, first-served service; due
to the long wait, though, she ultimately had to be
rescheduled for the next day.
Perceptions of MHC Delivery in Participants’
Own Neighborhoods
After providing information about their initial perceptions and prior experiences with the
MHC model of health care, participants were
asked several more specific questions: “What do
you think about health services provided on a
GHS Proc. November 2016; 1 (2): 97-104
PERCEPTIONS/PREFERENCES FOR A MOBILE HEALTH CLINIC
bus by the hospital system that would drive into
your neighborhood?” and “How do you feel about
using a mobile health bus in your neighborhood
for healthcare needs?” These questions aimed
to gather information about how participants
would feel about an MHC unit coming to their
own neighborhood versus obtaining health care
through more traditional avenues. In this respect,
then, these questions encouraged participants to
imagine what it would be like, in more specific
terms, if an MHC came into their community. As
indicated below, participants provided more personalized examples and a greater variety of opinions in their responses to these questions.
Overall, participants felt very positive about the
prospect of an MHC coming to their own neighborhood, saying it would be fantastic, great, wonderful, nice, and beneficial to everyone, full circle.
As one participant said, I would love it! That’s all
I’ve got to say. I would love it. Another participant
indicated she would feel comfortable and grateful,
especially given that she faces language barriers
when obtaining health care through a hospital.
Participants felt they could gain access to a variety of services through MHCs and thus expressed
that an MHC would be valuable to children,
teens, elderly, and the disabled alike. In the words
of one participant: I have to take my son to the
doctor when he has a problem … and make sure
he’s fine. But then in the long run, I don’t worry
about myself. I just make sure my child is OK.
Another participant recognized that the MHC
would be an asset for those people who won’t
or can’t get out and that would otherwise not get
treatment, perhaps because they are not able to,
cannot afford it, or resist going to the doctor.
For example, one participant indicated that she
often cancels her regular doctor’s appointments: I
say, “I’ve got a doctor’s appointment. I don’t want
to go.”… [then] I might call and cancel and then
go the next time. However, she indicated that if
the MHC came to her neighborhood, she would
take advantage of its services. Another participant corrected the assumption that an MHC only
benefits very poor community residents, saying
that it would benefit a lot of people with different
incomes, different background[s]. She continued
by saying a lot of people always think it’s just about
somebody who does not work or [is] just poor or
homebound … but it really helps people like me.
I’m working class and … self-employed. So, health
care for me would be very, very expensive. So stuff
like this really helps.
The easily accessible health care available through
an MHC is very important to participants who
GHS Proc. November 2016; 1 (2): 97-104
feel that the MHC would likely curb visits to the
emergency room. Also, participants perceived
that they would not have to wait as long to see a
doctor at an MHC as they would at a hospital or
at a regular doctor’s office. In the words of one
participant: It would be just as good or valuable
to you as being seen in a doctor’s office, where you
may wait 2 hours and then see a nurse practitioner.
Another participant noted that many people feel
like they have to wait for a long time when they
see a regular doctor, and they don’t have time
to go, or don’t want to go, so a lot of people get
neglected by not going. Thus, convenient scheduling is another important characteristic of a neighborhood-based MHC: Maybe they will give you an
appointment … You can go home and come back
at the time they gave you, and this makes it more
accessible.
Although participants felt positive about the
MHC coming to their neighborhoods, some noted
that patients who access health care through an
MHC may be stigmatized by their fellow community members, most probably because the MHC
itself would have such a visible presence in the
community (eg, community residents may see
others waiting in line for MHC services): I think
some people would be ashamed to use it because
[of the perception that it’s] for homeless people, or
people who can’t afford to get in. Such individuals
may be embarrassed to use an MHC due to their
strong sense of pride.
Others indicated that such stereotypes would not
prevent them from seeking health care through
an MHC: It’s [about] my health, and if it can help
me, I don’t care what’s going on or what’s being said
… I will take care of myself. Another indicated he
wouldn’t care what people think. I’d be glad to use
it. Another participant felt that some community members would have mixed thoughts about
the MHC given that it would be a new entity in
the community: There’s going to be a segment of
the population that will receive it very well, and I
think there will be some people that will be hesitant
to think it’s a good thing. But that’s just different
mindsets and different generations … [and] the
way they deal with anything new. It takes time for
them to accept.
Preferences Regarding Types of Services
Offered Through the MHC
Participants offered a variety of suggestions for the
services that could be offered through the MHC,
ranging from basic “wound care” to comprehensive total care … anything that does not require
surgery. They indicated that an MHC could treat
101
both acute conditions (such as the flu) to more
chronic conditions (such as asthma). At the same
time, participants were realistic in their expectations, recognizing that there are certain things you
can’t take care of on a bus or a mobile clinic.
Across all 5 focus groups, the most commonly
requested service was for basic preventive care
and a general check-up. As such, participants
envisioned that the MHC would offer physical
exams, during which the patient could receive a
series of lab services and tests, such as blood pressure checks, cholesterol tests, pregnancy tests,
and diabetes tests. They would like to receive
wound care, plus treatment for fever, colds, and
strep throat along with flu shots and X-rays. A
few participants specified a need for basic ophthalmic and dental care (eg, checkups, dentures,
etc.). They also felt it was important that the MHC
have the ability to fill and refill prescriptions and
that such prescriptions should be affordable: We
know that we need some type of medicine, and
then if we don’t have insurance, we have to pay out
of pocket for that medicine and things like that.
Most medicines I get from the emergency room,
my prescription is $50 and above, and … I [don’t]
always have the money to pay for it. Easy access
to prescriptions was especially important in one
of the communities where many residents do not
have transportation and where there is no drugstore in the community.
In terms of more specialized care, several participants requested a variety of oncology services,
including basic cancer screening, mammograms,
and colonoscopies. Several women expressed a
desire for OB/GYN care and pediatric services on
the MHC. Participants hope that the MHC can
offer specialized services for men. As one participant indicated, the work for men here is so arduous, so hard. Another participant stated that the
men don’t eat well and they work too much, a lot
of physical effort.
Participants envisioned that the MHC would be
able to offer basic emergency “triage” care and
then transport patients to the hospital, if necessary. Similarly, they felt it was important that
the MHC staff be able to refer patients to other
doctors for further care, if necessary, and to send
us to the appropriate doctor that we need. Because
sometimes we don’t know if it is a nutritionist, a
psychologist, neurologist, psychiatrist … We don’t
know. In cases where a patient would need to be
referred to another facility, participants requested
that the MHC staff advise them about affordable
alternatives for the additional health care. As a
102
participant noted: I don’t have health insurance.
[Every year], I go to a private doctor’s office … he
orders labs [tests and] sends me to a lab. That lab
has an agreement with the doctor’s office, and they
give a big discount to that doctor so I can have my
labs done there. She would like similar arrangements to be available through the MHC.
Some participants see the MHC as a conduit for
offering health education to residents; a participant suggested that patients could benefit from
nutrition education, dietary services, and advice
about exercise. In the words of another participant: Doctors give you a lot of stuff, but they don’t
tell you why. They don’t say, “You know, if you eat
more of this, you can stop taking this pill.” … They
tell you to diet, but you know, [there are] all kind of
diets out there that are bad for your health.
Beyond obtaining general healthcare services,
participants would also like to be able to access
information about other services available in the
community, to have the opportunity to talk to a
social worker, to be able to see a doctor who could
diagnose both physical and emotional causes
(eg, stress) of illness, and to receive advice about
payment plans. Several participants hoped the
MHC would also offer a few “extras,” including
bathrooms, blankets (to keep people warm while
they wait), toys, and a waiting room (both for the
participants who may be visiting the MHC and
their children). The facility should also be handicapped accessible, prioritize persons with disabilities, and have bilingual staff on hand.
Preferences Regarding the Schedule of
MHC Services
Participants had a variety of opinions about the
preferred days and hours of MHC services, ranging from twice a week to once a month. Although
most preferred that the MHC visit at least once a
week, they also recognized this option could be
difficult. But even once a month would be preferable and would be better than nothing at all,
because this is really needed; twice-a-month visits would be ideal. As one participant remarked,
however, consistency of service was even more
important than actual frequency. Such consistency would be a way for the MHC staff to show
they cared about the community.
Regarding the preferred days of the week for MHC
services, several participants preferred weekend
hours; participants indicated that both Saturday
and Sunday would be convenient for community
members. However, it would be nearly impossible
for many residents to attend on Saturday due to
GHS Proc. November 2016; 1 (2): 97-104
PERCEPTIONS/PREFERENCES FOR A MOBILE HEALTH CLINIC
childcare duties; thus, they preferred visiting the
MHC during the week, when their children are
in school. In addition, several female participants
indicated that Saturday and Sunday hours would
be ideal for the men in the community as it is very
difficult for them to attend the MHC during the
week (without taking unpaid leave from work).
Preferences Regarding the Location of
the MHC
Regarding the ideal location for the MHC, participants offered suggestions based on their
geographic locations. For example, participants
in one focus group suggested the MHC rotate
around a particular community so more residents could avail themselves of the clinic’s services. The suggestion was also made to locate
the MHC at a church so that healthcare services
could be offered on the van and in the church,
if necessary. Wherever the MHC is eventually
located, several participants indicated that the
MHC must be located in a safe area of the community: And I think people probably would trust,
would feel safe going to an area where the churches
are versus the outskirts of the community that are
maybe perhaps not perceived as safe.
Limitations
As the study relied on a small, purposefully
selected sample, the focus group results should
not be generalized to the population within each
of the 5 communities included in the study or to
Greenville in general. Rather, the findings of the
focus groups represent both the opinions of the
particular individuals who participated, as well
as additional opinions and viewpoints that may
have taken form as a result of participating in the
focus group.8
It is also possible that individuals who participated
in the focus groups may have already been predisposed, one way or another, toward the concept
of MHCs, and thus began the focus group with a
strong bias about MHCs. However, that does not
seem to be the case with this study as only a few
participants had prior knowledge about or experience with MHCs. Although the focus group
format capitalizes on a social context that encourages participants to reflect on one another’s ideas,
it may also limit the information any one participant can share, inhibit the expression of minority
opinions, or limit the participation of individuals
who are not particularly confident or articulate.
Some individuals may not have expressed their
full opinions because of concerns about the confidentiality of what they say in a group setting such
GHS Proc. November 2016; 1 (2): 97-104
as the focus group. It is also possible that some of
the rich data and cultural nuances may have been
lost when the Spanish focus group’s comments
were translated into English.
Discussion
Our study used the focus group methodology to
more effectively capture the variety of opinions
about MHCs in Greenville County. The 5 focus
groups provide important insights into residents’
opinions about MHC healthcare delivery. Importantly, all 5 focus groups included community
residents who are generally disenfranchised from
the traditional healthcare system (ie, by virtue of
social class, race/ethnicity, geographic isolation,
etc.) and thus often do not have the opportunity to
express their opinions regarding healthcare delivery. We believe that the focus group methodology
holds promise for assessing future community
health needs and community interest in health
programs and should be considered in the design
of any future community health assessments.
In all 5 Greenville groups, the most commonly
requested service was for basic preventive care
and a general check-up; health education was suggested as a way to provide this preventive care.
Other researchers agree that services needed
include health promotion and disease prevention3,9,10 instead of focusing on curative services.3 Based on the results of the focus groups,
it is recommended that the MHC provide health
promotion and preventive services and consider providing health education. Additionally,
although there were differing opinions about the
frequency of MHC visits to communities, participants across all 5 focus groups indicated that
consistency and predictability were also important. This finding reinforces Campos and Olmstead-Rose’s research that emphasized the need
for an ongoing provider-patient relationship in
the context of MHC services.5
Across all 5 focus groups, participants generally
felt very positive about the possibility of obtaining personalized health care through an MHC
unit that would visit their own neighborhoods.
Participants prefer MHCs to be convenient, situated in a central location in the community,
thus offering quick and easy access to health care,
and valuable to those who need low-cost health
care. Other research studies report that MHCs,
more than being geographically convenient, are
perceived as offering services that are acceptable,
user-friendly, and accommodating to vulnerable
populations.3,5,9,10
103
Abbreviations and
Acronyms
MHC = mobile
health clinic; GHS =
Greenville Health
System
Correspondence
Address to:
Melinda Gillispie,
MSN, RN, Greenville
Health System,
Department of
Community Relations,
300 E McBee Ave,
Suite 200, Greenville,
SC 29601
([email protected])
Conclusion
This MHC presents an exciting opportunity for
GHS to provide health care to underserved and
vulnerable populations in Greenville County.
Overall, participants had somewhat limited
experiences with obtaining general health care
through an MHC, although several reported
familiarity with the MHC model (similar to
that provided through the local bloodmobile
unit) and others reported receiving specialized
care through MHC-type facilities. Those who
reported receiving such services through these
facilities felt positive about the experience. Participants stressed the importance of the MHC
to offer services with kindness and respect in a
clean, safe, and confidential environment.
It is critical for healthcare providers and health
systems to understand the needs of underserved
communities prior to the launch of healthcare
delivery projects and to ascertain the level of
community readiness and acceptability. Across
all 5 focus groups, participants had favorable
opinions about the possibility of obtaining personalized health care through an MHC unit that
would visit their own neighborhoods.
Participants desire sustainability and consistency
of mobile health delivery services. Participants
are especially interested in receiving preventive
health care through the MHC, including health
education. Thus, health systems may want to
consider providing primary health care at the
beginning of the MHC delivery initiatives and
then consider additional services and programs
as they learn more about the community. This
process will allow health systems to better meet
community members’ primary healthcare needs
and to develop an MHC that reflects the unique
character of each community.
Using focus groups for community needs assessment is a powerful method for determining attitudes and perceived needs because information
comes to the surface that would not otherwise
emerge through other methods of research. In
this study, the researchers, using focus group
methodology, were able to successfully conduct
a community assessment which determined that
groups of residents in underserved communities
expressed a desire and readiness for the MHC.
Their enthusiasm was exhibited by their questions regarding the MHC start date.
References
1. Smith SL, Tessaro IA. Cultural perspectives on diabetes in an Appalachian population. Am J Health
Behav. 2005;29:291-301.
2. Schell R, Tudiver F. Barriers to cancer screening by
rural Appalachian primary care providers. J Rural
Health. 2004;20:368-73.
3. Guruge SH. Immigrant women’s experiences of
receiving care in a mobile health clinic. J Adv Nurs.
2010;66:350-9.
4. Song ZC. Mobile clinic in Massachusetts associated
with cost savings from lowering blood pressure and
emergency department use. Health Aff. 2013;32:36-44.
5. Campos MM, Olmstead-Rose L. Mobile health clinics: Increasing access to care in Central and East
Contra Costa County. Prepared for East and Central
County Health Access Action Team. 2012. http://
www.johnmuirhealth.com/content/dam/jmh/Docu-
104
ments/Community/ Mobile_Health_Clinics-Increasing_Access_to_Care.pdf. Accessed June 15, 2016.
6. Morgan DL. Focus Groups as Qualitative Research.
2nd Edition. London: Sage; 1997.
7.Kitzinger J. Introducing focus groups. BMJ.
1995;311:299-302.
8. Smithson J. Using and analyzing focus groups:
limitations and possibilities. Int J Soc Res Meth.
2000;3:103-19.
9. Abbasi S, Mohajer H, Samouei R. Investigation of
mobile clinics and their challenges. Int J Health Syst
Disaster Manage. 2016;4:1-6.
10.Gibson BA, Gosh D, Morano J, Altice FL. Accessibility and utilization patterns of a mobile medical
clinic among vulnerable populations. Health Place.
2014;28:153-66.
GHS Proc. November 2016; 1 (2): 97-104
Original Research
The Gynecology and Obstetrics Fundamentals of
Residency Internship Training (GO FOR IT) Trial
Francis S. Nuthalapaty, MD; H. Lee Higdon III, PhD; David A. Forstein, DO; Sarah E. Smith, MD;
Julie Z. DeCesare, MD; Claudette J. Shephard, MD; Robert V. Higgins, MD; Chadburn H. Ray, MD;
Ashlyn H. Savage, MD; Nikki B. Zite, MD, MPH; Spencer G. Kuper, MD; and Brian C. Brost, MD
From the Greenville Health System/University of South Carolina School of Medicine Greenville,
Greenville, SC (F.S.N., H.L.H., D.A.F.); East Carolina University Brody School of Medicine, Greenville,
NC (S.E.S); Florida State University College of Medicine Program, Pensacola, Fla (J.Z.D.); University
of Tennessee Health Science Center, Memphis, Tenn (C.J.S.); Carolinas Medical Center, Charlotte,
NC (R.V.H.); Georgia Regents University, Augusta, Ga (C.H.R.); Medical University of South Carolina, Charleston, SC (A.H.S.); University of Tennessee Medical Center at Knoxville, Knoxville, Tenn
(N.B.Z.); University of Alabama at Birmingham, Birmingham, Ala (S.G.K.); Wake Forest School of
Medicine, Winston-Salem, NC (B.C.B.)
Abstract
Background: Boot Camps, condensed format courses that emphasize procedural skills and medical
knowledge, are a common, but unproven approach to helping prepare fourth-year medical students
(M4) for residency.
Methods: This multicenter quasi-experimental static group educational study involved M4 students
from 8 ACGME accredited residency programs. Participants were assigned to either the intervention (GO FOR IT) or control groups based on availability to attend a training course in April 2013.
Course activities included lectures and simulation-based procedural skills practice. End-of-study
competency assessments were conducted June 15–July 2, 2013. The primary study outcome was
the composite score of 13 assessments, including objective-structured clinical exams, technical
skills performance checklists, and knowledge assessments.
Results: Thirty-two of 42 (76%) possible students enrolled in the study, of which 11 were assigned to
the GO FOR IT group and 21 to the control group. The median composite end-of-study assessment
score was 73% in the GO FOR IT group as compared to 41% in the control group (P < .001).
Conclusions: Participation in an intensive 2-week postresidency-match M4 elective resulted in significantly greater scores in the assessment of clinical and procedural skills and medical knowledge
as compared to the usual activities students pursue at the conclusion of medical school.
A
lthough the science and practice of medicine evolves daily, the basic model of
the 4-year medical school curriculum
in the United States has seen little change since
the Flexner Report.1 The transition from medical
school to residency has become an increasingly
difficult one for today’s medical graduates. Of primary concern is the fourth year of medical school
(M4), which has been described as a year lacking
GHS Proc. November 2016; 1 (2): 105-112
direction and missing an opportunity to better
train students to transition into their internship
year.2 Numerous general surgery residency programs have addressed the perceived laxity of the
M4 year with a “boot camp” for senior M4 students entering a surgical specialty.3-6 Participants
have described these camps as the most beneficial
portion of medical school in preparation for their
internship year, reporting an increase in their
105
Table 1
Medical knowledge learning outcomes and associated teaching methods.
Learning Topics
Teaching
Method(s)*
Gynecology
Evaluation and management of abnormal first-trimester
pregnancy, including ectopic
DL
Pathophysiology, evaluation and management of
reproductive tract malignancies
DL
Evaluation of acute pelvic and lower abdominal pain
CBL
Pathophysiology and evaluation of abnormal uterine
bleeding
DL, CBT
Indications and alternatives for hysterectomy
W
Obstetrics
Physiologic adaptations of pregnancy and the puerperium
CBL
Evaluation and management of third-trimester bleeding
CBL
Pathophysiology and management of preterm labor
CBL
Electronic fetal heart rate interpretation
CBT
Indication and interpretation of antenatal fetal testing
DL, CBT
Conduct of postpartum care, including breastfeeding
and contraception
W
Pathophysiology and management of gestational
hypertensive disorders
CBL
Management of diabetes mellitus during pregnancy
CBL
Management of common antepartum complications
CBL
Management of spontaneous abortion
CBL
Counseling for aneuploidy screening
CBL
Evaluation and management of postpartum hemorrhage
CBL
Pathophysiology and management of postpartum fever
CBT
Office practice
Content and conduct of routine well-woman care
Evaluation and management of urinary tract, vaginal,
vulvar, and sexually transmitted infections
DL
DL, CBT
Contraceptive methods, indications, contraindications,
and complications
DL
Evaluation and screening of breast disease
W
Options and counseling for undesired pregnancy
W
Evaluation and management of the abnormal Pap smear
DL, CBT
*Key for teaching methods: DL = didactic lecture; CBT = computerbased training module; W = live webinar. All topics were presented in
a 30-minute learning session. Self-directed CBTs were optional and of
variable length.
106
self-confidence about being a surgical intern, an
enhanced self-perceived dexterity, surgical skills,
and ability to safely manage patients.6-8
Limitations of these preliminary investigations
are their narrow focus on skills sets necessary
for a general surgery residency and their reliance
on learner self-assessment as a primary outcome,
which do not provide objective evidence to support whether such interventions truly impact the
competency of M4 students preparing for an OB/
GYN (Obstetrics and Gynecology) internship.
The objective of this study was to determine the
impact of participation in an intensive 10-day
postresidency-match M4 elective, compared
to usual activities, on clinical, procedural, and
knowledge competencies assessed at the time of
matriculation into an OB/GYN internship.
Methods
The Gynecology and Obstetrics Fundamentals
of Residency Internship Training (GO FOR IT)
Trial was a multicenter educational study involving 8 Accreditation Council for Graduate Medical Education (ACGME) OB/GYN residency programs in the southeastern United States.
Study conduct was separated into 5 sequential
phases. Phase 1 (collaborative and curriculum),
from October 2011 to September 2012, involved
formation of the GO FOR IT trial collaborative
and determination of the curricular content and
assessments. All ACGME-accredited OB/GYN
residency programs within a 300-mile radius of
the primary study center (PSC) were identified and
their program directors contacted to assess interest in joining the study collaborative. Of 23 possible programs, 8 joined the collaborative. This study
was approved by the Institutional Review Board
of Greenville Health System (IRB#Pro00014309),
which served as the PSC and Data Coordination
Center (DCC). Each site also obtained study protocol approval. All site principal investigators (PI)
participated in mandatory web-based and in-person training on study procedures.
Twenty-four medical knowledge (Table 1) and
12 clinical/procedural learning outcomes (Table
2) were selected from the report of the Association of Professors of Gynecology and Obstetrics/
Council on Resident Education for Obstetrics and
Gynecology Joint Task Force on Milestone One.9
De novo assessments were designed for each of
the 12 clinical/procedural learning outcomes. Site
PIs developed a performance checklist and standardized simulation scenario (if needed). Each
assessment tool was then submitted for review to
2 other site PIs to ensure content validity. A list
GHS Proc. November 2016; 1 (2): 105-112
GO FOR IT TRIAL
of the learning outcomes, associated teaching/
learning tools, and assessments was compiled
into a website for on-demand use.10
Phase 2 (recruitment and enrollment) began
in October 2012 and involved site PIs presenting information about the study to M4 students
during their residency interview. Enrollment
commenced on Match Day 2013. Eligible subjects
were those who participated in the 2013 National
Residency Matching Program and matched into
one of the collaborative centers. Additionally,
subjects had to be available to relocate to the
PSC/DCC from April 15−26, 2013. Participants
who were unavailable or unwilling to complete
the end-of-study competency assessments were
excluded from the study. All M4 students who
matched into one of the collaborative programs
were sent electronic and hard copy documents,
which included a formal invitation to participate
in the study, the study brochure, and consent
form. All potential participants were then contacted by phone to complete the consent process.
Phase 3 (assignment) of the study consisted of a
study group assignment contingency plan due
to the uncertainty of student availability. Not
enough students were available to relocate to
accomplish the randomization scheme, so the
contingency plan was activated resulting in a
quasi-experimental static group design.11-13 Educational research differs from clinical research
in both design and nomenclature. Quasi-experimental studies are analogous to observational
studies of clinical research.13 A PubMed search
of “quasi-experimental design” reveals well over
Table 2
Technical learning outcomes and associated teaching and assessment methods.
Learning Outcomes
Teaching
Method(s)*
Assessment Method*
Clinical/Procedural skill
Comprehensive women’s health history
CBT
Standardized patient OSCE with 55-item performance checklist
completed by proctor via direct observation
Breast and pelvic exam
TT, CBT
Standardized patient OSCE with 37-item performance checklist
completed by proctor via direct observation
Two-handed knot-tying
TT
Bench model with visual inspection of completed knot by proctor
Intrapartum cervical assessment
TT
Soft cervical models within blinding chamber (5 items) with
assessment of both dilation and effacement
Normal vaginal delivery
2nd-degree vaginal laceration repair
TT, SS
Simulation scenario using pelvic delivery model; proctor serves
as standardized patient and completes 23-item procedural
checklist immediately following completion of scenario
TT
Bench model with 12-item procedural checklist completed by
proctor via direct observation
Intrauterine device insertion
TT, CBT
Bench model with 12-item procedural checklist completed by
proctor via direct observation
Endometrial biopsy
TT, CBT
Bench model with 12-item procedural checklist completed by
proctor via direct observation
Vaginal wet-prep interpretation
CBT
6-item computer-based assessment
Technical knowledge
Surgical instrument name and principal
use
HO, CBT
30-item computer-based assessment with high-resolution
photographs
Surgical suture, blade, and needle types
HO, CBT
18-item assessment with sutures, blades, and needles identified
by direct visual inspection
*Key for teaching and assessment methods: CBT = computer-based training module; TT = task trainer; SS = simulation scenario;
HO = hands-on use; OSCE = Objective Structured Clinical Exam. Individual skills learning sessions were 30 minutes in length and
offered varying frequencies dependent on learner needs. All skills learning sessions totaled 50 hours. Self-directed CBTs were
optional and of variable length.
GHS Proc. November 2016; 1 (2): 105-112
107
4500 peer-reviewed publications utilizing this
study method.14
Phase 4 (intervention) commenced April 6, 2013.
All subjects completed a baseline demographics
questionnaire and a self-assessment of perceived
competency in knowledge and procedural skills.
Subjects assigned to the intervention group relocated to the PSC/DCC from April 15–26, 2013.
The first day of curriculum exposure for the GO
FOR IT group included a half-day baseline skills
assessment followed by an individual debrief session. Each of the subsequent 8 days followed a
template of three 0.5 hour didactic sessions and
then 6 hours of simulation-based procedural
skills practice. A novel technique for longitudinal
simulation-based training developed by one of
the investigators (B.C.B.), the Procedural Repetition Involving Montessori-type Experience and
Rehearsal (PRIMER) Method (Fig. 1), was utilized.
The last day of the GO FOR IT course included an
Figure 1
Procedural repetition involving Montessori-type experience rehearsal
(PRIMER).
Step 1: Itemize procedural task into individual skill components
Step 2: Stratify skill components into complex and simple
Complex Skill 1
Simple Skill 1
No—stay with Skill 1
Proficient?
Yes—add Skill 1 to
Skill 2
No—stay with Skill 1
Proficient?
Yes—add Skill 1 to
Skill 2
Complex Skill 2
Simple Skill 2
No—stay with Skill 2
Proficient?
Yes—add Skills 1 and
2 to Skill 3
No—stay with Skill 2
Proficient?
Yes—add Skills 1 and
2 to Skill 3
Complex Skill 3
Simple Skill 3
No—stay with Skill 3
Proficient?
Yes—advance to
Integrated Task
No—stay with Skill 3
Proficient?
Yes—advance to
Integrated Task
Step 4: Perform the integrated
procedural task independently.
Practice deficient skills as needed and
then repeat the entire procedural task.
108
LARGE GROUP PRACTICE
SMALL GROUP PRACTICE
Step 3: Practice individual skill components
individual debrief session followed by a final skills
assessment. During the intervention phase, there
was no contact with the subjects in the control
group, except to schedule activities for Phase 5.
Phase 5 (assessment) spanned June 15–July 2, 2013.
All subjects were required to schedule and complete
the National Board of Medical Examiners (NBME)
OB/GYN Subject Exam at a commercial testing
center (Prometric, www.prometric.com). All subjects were also required to report to 1 of 5 collaborative centers to participate in the standardized endof-study assessments. This assessment included
Objective Structured Clinical Exam (OSCE) stations, technical skills procedural checklist stations,
and technical knowledge stations (Table 2). The
assessments were grouped into 7 stations, each 15
minutes in length and video recorded.
The primary outcome for the study was the
median composite score of all end-of-study
assessments (excluding the NBME subject exam).
Secondary outcomes included the individual
OSCE and procedural checklist scores and the
NBME subject exam percentile score. All OSCE
procedural checklist stations were scored immediately at the testing center by the site PI. All other
stations were scored post hoc at the DCC either
by video review or grading of the answer form.
All scoring forms were returned to the DCC and
the data entered into Research Electronic Data
Capture15 and then exported to SPSS (IBM Inc.,
Armonk, NY) for analysis.
The sample size calculation for this study was
based on a traditional two-group superiority
testing approach. The primary outcome was estimated to be 80% in the GO FOR IT group and 64%
in the control group with a standard deviation of
15%. The alpha was set at .05 with a desired power
of 80%. Using a two-tailed test, the resultant sample size calculation was 15 subjects per group. The
statistical plan for secondary outcomes utilized
a similar testing approach with the alpha set at
.05. The statistical analysis was blinded and based
on an intention-to-treat principle. Due to group
size, statistical testing required a non-parametric
approach. Results are reported as median percentages with the 25th and 75th percentiles. The
Wilcoxon rank sum test and Fisher’s exact test
were used to analyze continuous and categorical
variables, respectively. A P value < .05 was considered statistically significant.
GHS Proc. November 2016; 1 (2): 105-112
GO FOR IT TRIAL
Results
On March 15, 2013, 42 M4 students matched into
the 8 study collaborative residency programs.
Eleven students met all study criteria and were
placed into the GO FOR IT group; 21 students
met all criteria except the ability to relocate to the
PSC and were thus placed into the control group.
Ten students declined to participate (Fig. 2). Ultimately, 32/42 (76%) of potential students participated in the trial. There were 4 instances of protocol deviation following group assignment. Three
subjects in the control group failed to complete
the baseline questionnaire and 1 subject in the
control group chose not to complete the NBME
OB/GYN Subject Exam.
There were no differences between the GO FOR IT
group and control group in regard to age, United
States Medical Licensing Examination results, or
time spent in OB/GYN clinical activities in the
M3 year, but the control group did report more
weeks spent in OB/GYN clinical activities in the
M4 year (Table 3). The control group had a higher
median self-rated competency score in twohanded knot-tying and normal vaginal delivery,
as compared to the GO FOR IT group, but all
other self-rated competency scores were similar
between groups (Table 3).
The median composite end-of-study assessment
score was 73% (68%, 77%) in the GO FOR IT
group as compared to 41% (35%, 45%) in the control group (P < .001). Similarly, the GO FOR IT
group scored significantly higher than the control group on 10 of 13 end-of study competency
assessments (Table 4).
There are several key implications of this study.
First, while the curriculum addressed medical
knowledge and procedural skills competencies,
the findings suggest that the curricular format
had the greatest impact on procedural skills. This
finding may be a result of participants having less
procedural competency at baseline as compared
to medical knowledge and thus more to gain
through the procedural training. Alternatively,
either the scope or approach used in addressing
the knowledge competencies in this curriculum
was not effective. Second, it is important to note
that the effect on the procedural competency was
sustained over 8–10 weeks between training and
final testing. This finding suggests offering such
training at the end of the M4 year is an alternative
to delaying such training until residency. Finally,
our study demonstrates how reliance on student
self-perceived competency can be misleading,
and a primary limitation of prior studies.
Several characteristics of this study enhance the
strength of its findings. First, the multicenter
design ensured a heterogeneous study population. Participants came from 18 medical schools,
had a variety of clinical experiences in OB/GYN,
and a breadth of academic performance on stan-
Figure 2
Flow diagram of study participants. Participant recruitment and group
assignment outcomes.
42
Matched into
OB/GYN at GO
FOR IT Trial
Collaborative
Centers
Discussion
In July 2014, the ACGME implemented Milestones for the Obstetrics and Gynecology specialty, which defined an explicit set of competency-based developmental outcomes that can
be demonstrated progressively by residents and
fellows from the beginning of their education
through graduation to the unsupervised practice
of their specialties.16 This study provides objective
evidence regarding the extent to which a short,
intensive course of knowledge and skills training
prior to medical school graduation can impact
clinical competency at the very beginning of the
Milestones continuum.
GHS Proc. November 2016; 1 (2): 105-112
9
2
Available to
participate in
either study
group
Willing to
participate
with school
permission
11
Assigned to and
analyzed in GO
FOR IT group
21
10
Available to
participate in
control group
only
Declined
participation
21
Assigned to
and analyzed in
control group
109
Table 3
Baseline educational
characteristics of
study participants.
Characteristic
GO FOR IT
Control
11
18
26 (25,27)
26 (25, 26)
.60
10 (90.9)
18 (100)
.38
1 (9.1)
0 (0)
Step 1
222 (206,237)
223 (212,228)
.64
Step 2 clinical knowledge
246 (227,259)
238 (233,249)
.34
Pass
11 (100)
17 (100)
1.00
Fail
0 (0)
0 (0)
M3 Year
6 (6,8)
6 (6,9)
.66
M4 Year
4 (4,8)
8 (8,12)
<.01
Jul-Sep 2012
5 (45.4)
4 (22.2)
.31
Oct-Nov 2012
3 (27.3)
10 (55.6)
Jan-May 2013
3 (27.3)
4 (22.2)
Jan-Feb 2013
3 (27.3)
3 (16.7)
Mar 2013
6 (54.5)
6 (33.3)
Apr-May 2013
2 (18.2)
9 (50.0)
N
Age (year)
P Value
Year of medical school graduation
2013
Prior to 2013
USMLE scores
Step 2 clinical skills
Time spent in OB/GYN clinical activities (weeks)
Month of final OB/GYN clinical experience
Month of final M4 clinical experience
.23
Self-rated baseline clinical skills/procedural competency*
Comprehensive women’s health history
4 (3,4)
4 (3,4)
.68
Breast exam
4 (3,4)
4 (3,4)
.62
Pelvic exam
3 (3,4)
3 (3,4)
.20
Two-handed knot-tying
3 (2,3)
3 (3,4)
.01
Intrapartum cervical assessment
2 (2,3)
2 (2,3)
.34
Normal vaginal delivery
2 (2,2)
2.5 (2,3)
<.01
2nd-degree vaginal laceration repair
1 (1,2)
2 (1,2)
.36
2.5 (2,3)
3 (3,3)
.26
Intrauterine device insertion
2 (2,3)
2 (1,2)
.96
Endometrial biopsy
2 (0,2)
2 (1,2)
.44
Vaginal wet-prep interpretation
3 (2,4)
3 (3,4)
.24
Electronic fetal heart rate interpretation
All data reported as either frequency (percent) or median (25th, 75th percentile).*Median scores based
on a 4-point Likert-type scale with scale anchors and values as follows: 1 = I am unable to perform the
entire procedure under supervision; 2 = I am able to perform the procedure under supervision; 3 = I
usually do not require supervision but maybe need help occasionally; 4 = I am competent to perform the
procedure unsupervised (I can deal with complications).
110
GHS Proc. November 2016; 1 (2): 105-112
GO FOR IT TRIAL
dardized assessments (Table 3). Second, the 32
participants, representing 2.5% of the total number of students matching into OB/GYN in 2013,17
provided ample power for identifying statistically
significant differences between groups. Finally,
the inclusion of multiple forms of objective competency assessments strengthens the validity and
generalizability of the findings.
Conversely, limitations of this study should be
noted. First, we were unable to utilize a randomized study design due to recruitment limitations.
The quasi-experimental educational study design
is analogous to a prospective cohort clinical
study design, with the same concerns regarding
unequal distribution of confounders between
groups.11 The similarity in the baseline character-
Table 4
End-of-study clinical skills/procedural skills/knowledge competency outcomes.
GO FOR IT
Control
11
21
73 (68,77)
41 (35,45)
<.001
Comprehensive women’s health history (49 tasks)
76 (69,86)
63 (53,69)
<.01
Breast/Pelvic physical exam (37 tasks)
78 (70,86)
62 (54,68)
<.01
11 (100)
21 (100)
1.0
Dilation (5 tasks)
60 (40,60)
20 (20,20)
<.01
Effacement (5 tasks)
60 (60,80)
20 (10,40)
<.01
Composite of dilation & effacement (10 tasks)
60 (50,70)
30 (20,30)
<.01
Normal vaginal delivery (23 tasks)
65 (52,78)
35 (26,48)
<.01
2nd-degree vaginal laceration repair (12 tasks)
92 (83,100)
50 (42,58)
<.01
IUD insertion (12 tasks)
67 (50,75)
33 (33,50)
<.01
Endometrial biopsy (7 tasks)
57 (43,71)
57 (43,71)
.66
58 (40,89)
49 (29,75)
.41
Name (31 tasks)
87 (77,97)
26 (16,29)
<.01
Primary function (31 tasks)
61 (55,71)
32 (23,39)
<.01
Composite of name and function (62 tasks)
74 (66,79)
29 (23,32)
<.01
57 (43,71)
29 (14,43)
<.01
Surgical blade identification (3 tasks)
100 (33,100)
33 (0,50)
<.01
Surgical needle identification (8 tasks)
75 (62,75)
0 (0,0)
<.01
N
Composite outcome score
P Value
Clinical skills OSCE1
Technical skills stations
2
Two-handed square knot (%)
Intrapartum cervical assessment
Medical/Technical knowledge assessments
NBME Obstetrics & Gynecology Subject Exam3
Surgical instrument identification
Suture identification (7 tasks)
1
Objective Structured Clinical Exam (OSCE) results reported as median percentage of checklist items (ie, tasks) rated as “well done.”
2
Technical skill procedural checklist results reported as median percentage of checklist items (ie, tasks) rated as “complete” for each
subject.
3
National Board of Medical Examiners (NBME) results reported as median overall-year percentiles for each subject.
GHS Proc. November 2016; 1 (2): 105-112
111
Abbreviations and
Acronyms
M4 = fourth year of
medical school;
OB/GYN = obstetrics
and gynecology;
GO FOR IT =
Gynecology
and Obstetrics
Fundamentals of
Residency Internship
Training; ACGME =
Accreditation
Council for Graduate
Medical Education;
PSC = primary
study center; DCC =
Data Coordination
Center; PI = principal
investigator;
PRIMER = Procedural
Repetition Involving
Montessori-type
Experience and
Rehearsal; NBME =
National Board of
Medical Examiners;
OSCE = Objective
Structured Clinical
Exam
Correspondence
Address to:
Francis S. Nuthalapaty,
MD, Greenville Health
System, Department
of OB/GYN, 890 W
Faris Rd, Suite 470,
Greenville, SC 29605
([email protected])
istics between groups (Table 3), however, suggests
that potential confounders were actually biased
in favor of the control group, with greater clinical experience in OB/GYN self-perceived competency, in several areas. Second, the study design
is susceptible to exposure bias resulting from the
GO FOR IT group having greater knowledge of
the assessment scheme through exposure to the
training models. Third, scoring of most procedural stations was unblinded. Fourth, all of the
procedural checklists developed for the assessments were unweighted, diminishing the value
of highly critical steps more closely related to
patient outcome.18 Fifth, we failed to reach the
desired number of participants in the GO FOR IT
Conclusion
The results of this study suggest that OB/GYN
educators should implement intensive residency
preparation courses near the end of the M4
year to prepare students to enter residency with
appropriate skills and knowledge. The curriculum developed for the GO FOR IT Trial is now an
integral component of the M4 curriculum at the
University of South Carolina School of Medicine
Greenville.
References
1. Whitcomb ME. Medical education reform: is it time
for a modern flexner report? Acad Med. 2007;82:1-2.
2. Walling A, Merando A. The fourth year of medical education: a literature review. Acad Med.
2010;85:1698-704.
3. Naylor RA, Hollett LA, Castevllvi AJ, Valentine RJ,
Scott DJ. Preparing medical students to enter surgery
residencies. Am J Surg. 2010;199:105-9.
4. Boehler ML, Rogers DA, Schwind CJ, Fortune J,
Ketchum J, Dunnington G. A senior elective designed
to prepare medical students for surgical residency.
Am J Surg. 2004; 187:695-7.
5. Klingensmith ME, Brunt LM. Focused surgical skills
training for senior medical students and interns. Surg
Clin Am. 2010;90:505-18.
6. Peyre SE, Peyre CG, Sullivan ME, Towfigh S. A surgical skills elective can improve student confidence
prior to internship. J Surg Res. 2006;133:11-5.
7. Esterl RM, Henzi DL, Cohn SM. Senior medical student “Boot Camp”: can result in increased self-confidence before starting internships. Curr Surg.
2006;63:264-8.
8. Laack TA, Newman JS, Goyal DG, Torsher LC. A
1-week simulated internship course helps prepare
medical students for transition to residency. Simul
Healthc. 2010;5:127-32.
9. Milestone Project. Joint Task Force on Preparation
for Residency. Association of Professors of Gynecology and Obstetrics and the Council for Residency
Education in Obstetrics and Gynecology. https://
www.apgo.org/education/536-milestone-project.
html. Accessed July 23, 2015.
112
group as assessed by power calculation. Finally,
as with all simulation-based assessments, there is
an unknown transference to actual clinical performance and outcomes.18
10.Gynecology and Obstetrics Fundamentals of Residency (GOFORIT) Trial. http://www.goforitcourse.
com. Accessed July 23, 2015.
11. Nuthalapaty FS, Casey PM, Cullimore AJ, Dugoff L,
et al. To the point: a primer on medical education
research. Am J Obstet Gynecol. 2012;207:9-13.
12.Creswell JW. Educational Research: Planning, Conducting, and Evaluating Quantitative and Qualitative
Research. 5th ed. Upper Saddle River, NJ: Pearson
Education, Inc; 2015.
13.Campbell DT, Stanley JC. Experimental and Quasi-experimental Designs for Research. Belmont, CA:
Wadsworth; 1963.
14.Pubmed.gov.
http://www.ncbi.nlm.nih.gov/pubmed/?term=quasi-experimental+design. Accessed
December 16, 2015.
15.Harris PA, Taylor R, Thielke R, Payne J, et al.
Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for
providing translational research informatics support. J Biomed Inform. 2009;42:377-81.
16.Milestones FAQ. Accreditation Council for Graduate Medical Education. https://www.acgme.org/acgmeweb/Portals/0/MilestonesFAQ.pdf. Updated in
September 2015. Accessed May 1, 2016.
17.Results and Data: 2015 Main Residency Match.
National Resident Matching Program. http://www.
nrmp.org. Accessed July 23, 2015.
18.Lineberry M, Walwanis M, Reni J. Comparative
research on training simulators in emergency medicine: a methodological review. Simul Healthc.
2013;8:253-61.
GHS Proc. November 2016; 1 (2): 105-112
Original Research
Blood Loss and Transfusions After Pericardial Closure
Using a Porcine-Derived Extracellular Matrix
Timothy G. Johnson, MD; William W. Hope, MD; Howard F. Marks; and Peter N. Kane, MD
From the Department of General Surgery, New Hanover Regional Medical Center, Wilmington, NC
(T.G.J., W.W.H.), and Department of Cardiothoracic Surgery, New Hanover Regional Medical Center, Wilmington, NC (H.F.M., P.N.K.)
Abstract
Background: At the onset of an open heart surgical procedure, the pericardium is opened to facilitate access to the heart and great vessels and was historically left open at the conclusion of the case to theoretically prevent iatrogenic cardiac tamponade. Studies from the 1970s showed that closing the pericardium
was safe and potentially beneficial during repeat mediastinal entry. We evaluated the effect of closing the
pericardium with a porcine-derived extracellular matrix (ECM) patch on postoperative blood loss and
blood transfusion requirements.
Methods: We retrospectively reviewed consecutive open heart procedures by a single surgeon at a single
center over 18 months who closed with patch closure of the pericardium or closed primarily. Mediastinal
and chest tube outputs were used as surrogates for postoperative blood loss. Perioperative blood transfusions were tracked.
Results: We found no significant difference in postoperative blood loss from the mediastinal and chest
tubes (P > .05), no difference in the timing of mediastinal and chest tube removal, and no difference in
need for urgent reoperations between the 2 groups. We identified a statistically significant difference in
postoperative blood transfusion requirements. Patients with patch closure of the pericardium required
fewer transfusions per patient than patients with their pericardium closed primarily (P = .0002).
Conclusions: Closing the pericardium with CorMatrix ECM did not decrease the amount of postoperative
blood loss but resulted in fewer blood transfusions per patient. Limitations to this study included a selection bias that favored the use of patch closure for younger patients, potentially confounding our results.
D
uring open heart surgery, access to the
heart and great vessels is obtained through
a longitudinal incision in the anterior pericardium. Traditionally, at the conclusion of the
case, the pericardium was left open, as closing
the pericardium raised concern about cardiac
tamponade and early graft failure. Reoperation
in patients whose pericardium was left open was
often difficult and occasionally harmful, as adhesions had formed between the heart and the posterior mediastinum. These reoperative findings led
to early attempts to close the pericardium primarily to minimize adhesions.
Early studies on pericardial closure and its hemodynamic and clinical effects began in the late 1970s
and showed that closure of the pericardium was safe
and also decreased adhesions.1-2 Since these early
studies, numerous others have evaluated the effects
GHS Proc. November 2016; 1 (2): 113-116
and different types of pericardial closure. Each of
these studies showed early but transient alterations
to cardiac hemodynamics3-8 and preservation of
distance between heart and sternum.3
In cases where the pericardium cannot be closed,
synthetic and biosynthetic pericardial substitutes have been described to bridge the natural
pericardial closure. Several options are available;
however, data related to these products and their
improvement in outcomes are lacking and their
use is debated. The purpose of this project was to
evaluate the outcomes of using a decellularized
extracellular matrix (CorMatrix ECM , CorMatrix, Roswell, Ga, USA) for pericardial closure in
patients undergoing cardiac bypass and to compare them with patients who did not undergo pericardial closure.
®
®
113
Methods
Following Institutional Review Board approval, we
retrospectively reviewed consecutive open heart
surgery cases from June 1, 2012, through December 21, 2013, performed by a single surgeon at our
medical center. Data were obtained from our electronic medical records and from a prospectively
collected database. Exclusion criteria included
intra- and perioperative deaths and patients who
left the operating room on ECMO (extracorporeal
membrane oxygenation). The decision to use the
extracellular matrix for closure of the pericardium
was left to the discretion of the primary surgeon.
Primary endpoints were postoperative blood loss
and postoperative blood transfusions in units of
packed red blood cells transfused. Amount of chest
tube and mediastinal tube output was used as a
surrogate for postoperative blood loss. Secondary
Table 1
Patient demographics in patch closed and primary closure groups.
Characteristic
N
Patch
Closed
Primary
Closure
143
162
Gender, no. (%)
0.1273
Female
33 (23.1)
50 (30.9)
Male
110 (76.9)
112 (69.1)
60.0 ± 9.1
69.9 ± 11.7
Age, years (mean ± SD)
P Value
<.0001
Figure 1
Chest tube (CT), mediastinal tube (Medi), and total outputs were not
significantly different between the study groups (P = .0631, P = .7654,
and P = .1594).
Output Volume (cc)
1600
1400
1200
1000
800
600
400
200
0
114
CT Output
Medi Output
Patch Closed
Primary Closure
Total Output
endpoints included date of mediastinal and chest
tube removal and number of re-explorations. Basic
demographic data included age and gender of the
patients. Descriptive statistics were generated using
t-test, Fisher’s exact, and Χ² test of independence,
with a P < .05 considered significant.
Results
During the 18-month study, 316 open heart procedures were performed. Eleven patients were
excluded due to 4 patient deaths and 7 patients on
ECMO. Of the 305 patients remaining in the study,
143 had their pericardium closed with CorMatrix ECM, and 162 patients had their pericardium
closed primarily. There was no difference in patient
gender between the 2 groups, but the closed pericardium group was significantly younger than the
group primarily closed (Table 1).
Fluid output was recorded until the tube was
removed or through postoperative day 3, and total
perioperative tube output was compared. There was
no significant difference in chest tube, mediastinal
tube, and total tube output between the 2 groups
(Fig. 1).
There was no significant difference between groups
with regard to the timing of chest tube and mediastinal tube removal (Fig. 2) or in the rate or re-exploration for bleeding between the 2 groups (P > .05).
We found a statistically significant difference in
units of blood transfused between the patch closed
and the primarily closed groups (0.4 units vs. 0.9
units, P < .05) (Fig. 3).
Discussion
Closure of the pericardium at the conclusion of
open heart surgery has been proven to be safe and
effective, causing little ill effects on hemodynamics while minimizing postoperative adhesions to
the posterior sternum.1-8 The primary advantage
of closing the pericardium is decreased adhesions
encountered during repeat median sternotomy.
Though the rate of repeat median sternotomy has
increased in the past due to willingness to perform
cardiac revascularization on older patients,9-11
improved long-term patency of bypass grafts with
vein and left internal mammary artery is extending the time between the first and subsequent cardiac revascularization procedures, causing a plateau in this rate.11 Subsequently, most patients who
undergo a median sternotomy do not benefit from
the primary advantage of a postoperative closed
pericardium.
In our practice, we routinely try to close the pericardium if possible. In cases where pericardial closure may not be feasible due to pericardial contracGHS Proc. November 2016; 1 (2): 113-116
BLEEDING SEQUELAE OF CLOSED PERICARDIUM
tion, cardiac enlargement, and lack of conduit in
re-do operations, alternative means of closure are
now available. There are several options to assist in
pericardial closure, including autogenous tissue,
such as a rotational pericardial flap12 or a pericardial fat pad,13 and synthetic or biosynthetic pericardial substitutes.
These substitutes include PTFE (polytetrafluoroethylene, GORE-TEX [W. L. Gore & Associates,
Inc., Flagstaff, Ariz, USA]), glutaraldehyde-treated
xenografts, bioresorbable polymer films such as a
barrier film containing polylactic acid and polyethylene glycol (REPEL-CV , Sythemed Inc.,
Iselin, NJ, USA), and decellularized extracellular matrix such as CorMatrix ECM.14 CorMatrix
ECM is produced from porcine small intestinal
submucosa that is decellularized, leaving the complex extracellular matrix intact. CorMatrix ECM
supports tissue repair, remodeling into functional
pericardial tissue, and avoiding premature breakdown and calcification when used to close the pericardium.15,16 An explanted CorMatrix ECM patch
used for a pericardial closure that was removed 5
years after the procedure showed that it had been
almost fully recellularized, well integrated, and
densely vascularized, similar to differentiated connective tissue.16
®
®
Overall, there is a paucity of data examining the
potential benefits of closing the pericardium with
CorMatrix ECM. However, CorMatrix ECM has
been shown to decrease the rate of postoperative atrial fibrillation in one retrospective study,
though no randomized trial exists.17 Our report
evaluates the use of CorMatrix ECM to close the
pericardium, specifically evaluating whether we
could find a secondary benefit beyond decreased
reoperative adhesions to potentially offset the cost
of the product used to close the pericardium. We
focused our attention on blood loss and transfusion requirements, knowing that blood transfusion
after cardiac surgery is a risk factor for increased
length of stay if more than 3 units of blood were
transfused18 and shorter length of stay could
potentially offset the material cost of the patch.
We successfully showed a decreased transfusion
need in patients who underwent patch closure of
their pericardium, but likely not enough to offset
the cost or affect length of stay. This decrease in
transfusion requirement is difficult to explain as
the blood loss and chest tube outputs were not different. One explanation is that although our cardiovascular intensive care unit and program, like
many, has protocols and triggers for blood transfusion based on hemoglobin/hematocrit levels,
there is also some subjectivity. In our unit, blood
transfusions are based on certain triggers but also
GHS Proc. November 2016; 1 (2): 113-116
Figure 2
Postoperative days of mediastinal tube and chest tube removal were not
significant between the study groups (P = .258 and P =.419, respectively).
Day of Mediastinal Tube Removal
Patients Removed
70%
60%
50%
40%
30%
20%
10%
0%
Day 0
Day 1
Day 2
Day 3
Day of Chest Tube Removal
Patients Removed
50%
40%
30%
20%
10%
0%
Day 0
Day 1
Patch Closed
Day 2
Day 3
Day 4
Primary Closure
Figure 3
Patients who underwent patch closure received significantly fewer units of
blood than patients in the primary closure group (P = .0002).
Units Transferred
0.9
0.8
0.86
0.7
0.6
0.5
0.4
0.3
0.38
0.2
0.1
0.0
Patch Closed
Primary Closure
115
Abbreviations and
Accroynms
ECM = extracellular
matrix; ECMO =
extracorporeal
membane oxygenation
Correspondence
Address to:
Peter N. Kane,
MD, Department
of Cardiothoracic
Surgery, New Hanover
Regional Medical
Center, 2131 S 17th
St, PO Box 9025,
Wilmington, NC
28401 (4peterkane@
gmail.com)
depend on the hemodynamic and overall clinical
picture of the patient; as a result, variability can
arise, which likely explains the significant difference that likely has no major clinical bearing.
Determining the clinical significance of this variability requires further study.
There are several limitations of our study inherent
in a retrospective review. There was a significant
difference in the group undergoing closure using
the extracellular matrix compared with the group
primarily closed, which could have altered the
results. This is likely from surgeon bias and using
this technique preferentially in younger patients, as
the likelihood for reoperation is potentially higher
due to a presumed longer life span. Furthermore,
the decision about how to close the pericardium
was made by the surgeon at the completion of the
case based on many factors, introducing another
selection bias.
We also did not evaluate the long-term outcomes of
these patients or whether any had undergone reoperation. Previous literature, however, has supported
decreased adhesions with closure of the pericardium even with pericardial substitutes.1-3,13,14,16
There was no difference in re-exploration requirements, which can be considered a corollary finding to the studies that showed no major hemodynamic differences between groups as previously
mentioned. We also found no difference in the
amount of chest and mediastinal tube output, as
well as the time to removal of each tube. At the
onset of our study, we hypothesized that compartmentalization of the mediastinum created
by closing the pericardium may lead to less blood
loss, either by physiologically tolerated compression not causing tamponade, or perhaps prevention of cytokines released from the fresh operative field contacting the cardiac tissue and causing
coagulopathy.
Conclusion
In conclusion, the use of a porcine-derived extracellular matrix patch to close the pericardium after
open heart surgery resulted in no significant differences in chest tube output or time to removal of
tubes or the reoperative rate for bleeding compared
with primary closure. There was a significant difference in transfusion requirements in the CorMatrix ECM pericardial closure group, although this
difference is likely not clinically significant and
requires further study. Future randomized studies
using pericardial closure techniques are needed
to determine the true benefits of this procedure.
Furthermore, a thorough analysis of risk factors
that places a patient at increased risk of requiring
a repeat median sternotomy may allow cardiothoracic surgeons to selectively close the pericardium
of these patients.
References
1. Cunningham JN Jr, Spencer FC, Zeff R,
Williams CD, Cukingnan R, Mullin M.
Influence of primary closure of the pericardium after open-heart surgery on the
frequency of tamponade, postcardiotomy
syndrome, and pulmonary complications. J
Thorac Cardiovasc Surg. 1975;70:119-25.
2. Nandi P, Leung JS, Cheung KL. Closure of
pericardium after open heart surgery. A
way to prevent postoperative cardiac tamponade. Br Heart J. 1976;38:1319-23.
3. Rao V, Komeda M, Weisel RD, Cohen G,
Borger MA, David TE. Should the pericardium be closed routinely after heart operations? Ann Thorac Surg. 1999;67:484-8.
4. Daughters GT, Frist WH, Alderman EL,
Derby GC, Ingels NB Jr, Miller DC. Effects
of the pericardium on left ventricular diastolic filling and systolic performance early
after cardiac operation. J Thorac Cardiovasc
Surg. 1992;104:1084-91.
5. Hunter S, Smith GH, Angelini GD. Adverse
hemodynamic effects of pericardial closure
soon after open heart operation. Ann Thorac Surg. 1992;53:425-9.
6. Izzat MB, Anderson M, Wilde P, Wiseheart
JD, Bryan AJ, Angelini GD. Hemodynamic
116
effects and echocardiographic consequences
of tension-free pericardial closure after heart
valve surgery. J Heart Valve Dis. 1994;3:295-9.
7. Jarvinen A, Peltola K, Rasanen J, Heikkila J.
Immediate hemodynamic effects of pericardial closure after openheart surgery. Scand J
Thorac Cardiovasc Surg. 1987;21:131-4.
8. Damen J, Bolten DT. Acute hemodynamic
effects of pericardial closure in man. Acta
Anaesthesiol Scand. 1989;33:207-9.
9. van Eck FM, Noyez L, Verheugt FW, Brouwer RM. Changing profile of patients
undergoing redo-coronary artery surgery.
Eur J Cardiothorac Surg. 2002;21:205-11.
10. Trehan N, Mishra YK, Malhotra R, Sharma
KK, Mehta Y, Shrivastava S. Off-pump redo
coronary artery bypass grafting. Ann Thorac Surg. 2000;70:1026-9.
11. Yau Tm, Borger MA, Weisel RD, Ivanov J.
The changing pattern of reoperatice coronary surgery: trends in 1230 consecutive
reoperations. J Thorac Cardiovasc Surg.
2000;120:156-63.
12. Karger F, Aazami MH. Rotational pericardial flap: an alternative tension-free technique for pericardial closure. J Thorac Cardiovasc Surg. 2007;137:510-11.
13.Singh T, Ross D, Thomson D. Closure of
pericardium using pericardial fat in primary cardiac operations. Internet J Thoracic
Cardiovasc Surg. 2007;12. http://ispub.com/
IJTCVS/12/2/9843. Accessed April 1, 2015.
14. Boyd WD, Tyberg JV, Cox JL. A review of
the current status of pericardial closure following cardiac surgery. Expert Rev Cardiovasc Ther. 2012;10:1109-18.
15.CorMatrix ECM Bioscaffold. 2013. http://
cormatrix.com. Accessed April 1, 2015.
16. Stelly M, Stelly TC. Histology of cormatrix
bioscaffold 5 years after pericardial closure.
Ann Thorac Surg. 2013;96:e127-9.
17.Boyd WD, Johnson WE 3rd, Sultan PK,
Deering TF, Matheny RG. Pericardial
reconstruction using an extracellular
matrix implant correlates with reduced risk
of postoperative atrial fibrillation in coronary artery bypass surgery patients. Heart
Surg Forum. 2010;13:e311-6.
18. Galas FR, Almeida JP, Fukushima JT, et al.
Blood transfusion in cardiac surgery is a
risk factor for increased hospital length of
stay in adult patients. J Cardiothorac Surg.
2013;8:54.
GHS Proc. November 2016; 1 (2): 113-116
Original Research
Impact of Methicillin-Resistant Staphylococcus aureus
(MRSA) Decolonization Protocol on Colonization and
Infection Rates in a Level III Neonatal Intensive Care Unit
Myah Griffin, MD; Nirav T. Patil, MBBS, MPH; and Robin N. LaCroix, MD
From the University of South Carolina School of Medicine Greenville, Greenville, SC (M.G.); Department of Quality Management, Greenville Health System, Greenville, SC (N.T.P.); and Department of
Pediatrics, Division of Pediatric Infectious Disease, Greenville Health System, Greenville, SC (R.N.L.)
Abstract
Background: In recent decades, the US has seen a substantial increase in Methicillin-resistant Staphylococcus aureus (MRSA) infections and outbreaks in neonatal intensive care units (NICU). In an
effort to eliminate MRSA infections and potential outbreaks, in 2005 we implemented a MRSA
Decolonization Protocol in our Level III NICU. The protocol primarily consisted of 4 pieces: 1) contact precautions, 2) Hibiclens® bath, 3) mupirocin ointment to the nares, and 4) continued surface
surveillance cultures. The purpose of this 10-year study was to determine the impact our NICU
Decolonization Protocol had on the rates of MRSA colonization and infection.
Methods: All neonates born between January 2002 and December 2012 (N = 8283) admitted to our
Level III NICU were identified. Patients were subsequently divided into 2 groups based on date of
protocol implementation: Group 1 consisted of neonates born preprotocol (January 2002–December 2004) and Group 2 of neonates born postprotocol (January 2005–December 2012). Frequency
of MRSA colonization and infection were our primary endpoints.
Results: Group 1 included 2139 infants, of whom 96 developed MRSA colonization (n = 87) and/
or infection (n = 9). Group 2 had 6144 infants; 178 developed MRSA colonization (n = 167) and/or
infection (n = 11). The frequency of MRSA colonization (Group 1: 4.1% vs. Group 2: 2.7%; P = .002)
and infection (0.4% vs. 0.2%; P = .05) was significantly lower in Group 2.
Conclusions: The proportion of neonates with MRSA colonization and/or infection in our Level III
NICU was significantly reduced following implementation of a decolonization protocol.
M
ethicillin-resistant Staphylococcus aureus
(MRSA) is a common bacterium that has
become endemic to hospitals. Infants in
neonatal intensive care units (NICU) represent
a particularly at-risk population. Factors such as
young gestational age, low birth weight, need for
surgical procedures, and utilization of devices,
such as mechanical ventilation, have been shown
to predispose infants to MRSA colonization and
infection.1-3
A large number of humans (30%–70%) are carriers of Staphylococcus aureus.4 Neonates are often
exposed shortly following birth via the environGHS Proc. November 2016; 1 (2): 117-120
ment and/or their parent’s or healthcare worker’s
skin.5-7 Between 1995 and 2004, NICUs in the US
experienced a 300% increase in MRSA infections.8
Around 2001 and 2002, we also noticed an amplified rate of MRSA colonization and infection.
In an effort to eliminate subsequent infections
and potential MRSA outbreaks, we implemented
a MRSA Decolonization Protocol in our Level III
NICU. This protocol was first applied in January
2005 and primarily consisted of 4 pieces: 1) contact precautions, 2) Hibiclens bath, 3) mupirocin
ointment to the nares, and 4) continued surface
surveillance cultures. Hand hygiene is also an
®
117
area of emphasis, as staff members are required
to perform hand hygiene before and after caring
for and/or handling infants. In addition, both
staff and parents are required to wear gloves and
gowns while in the patient’s room if they have a
positive culture for MRSA.
MRSA infection is associated with significant
morbidity in infants, as it can result in subsequent
infections; these include, but are not limited to,
skin infections, conjunctivitis, blood stream
infections, surgical site infections, pneumonia,
meningitis, and respiratory tract infections.9,10
NICUs throughout the country have sought to
reduce MRSA infections and outbreaks; however, as of 2005, optimal management strategies
remained unclear. The purpose of this study was
to determine the impact of a NICU MRSA Decolonization Protocol on neonatal rates of MRSA
colonization and infection.
Methods
Following approval from the Greenville Health
System Institutional Review Board, we identified all neonates born between January 2002 and
December 2012 (N = 8283) admitted to the Level
III NICU at Greenville Memorial Medical Center
(GMMC), a large, tertiary care academic health
center. These patients were subsequently divided
into 2 groups based on date of protocol implementation: Group 1 consisted of neonates born
preprotocol (January 2001–December 2004) and
Group 2 of neonates born postprotocol (January
2005–December 2012). Neonates colonized or
infected with MRSA (n = 274) were then identified by retrospective chart review. Infants transferred from an outside institution or another
floor at GMMC with a MRSA-positive culture
upon admission were excluded from this study
(n = 15).
Data collection included gender, birth weight,
gestational age, mode of delivery, placement of
PICC (peripherally inserted central catheter)
line, presence of necrotizing enterocolitis (NEC)
or other infections, surgery, and MRSA strain.
Primary endpoints were incidence of MRSA
colonization and infection. MRSA colonization
was defined as having a MRSA-positive culture
of the anterior nares and/or skin surface. MRSA
infection was defined as having a MRSA-positive
culture from blood, wound(s), tracheal aspirate,
urine, or cerebrospinal fluid.
Surveillance cultures were collected 1–2 times
per week on all infants in the NICU who were
not under contact precautions for MRSA. Naso-
118
pharyngeal, axillary, and perianal areas were
swabbed with 3 individual cotton swabs and
placed inside a single vial with sterile saline solution. During Group 1’s study period (prior to
2005), all vials were centrifuged and transferred
to sheep blood plates in the GMMC laboratory;
this process took between 4 and 5 days to produce
a positive culture. Starting in 2005 (Group 2), the
laboratory began using Chrome Agar in place of
sheep blood plates; this change enabled growth
observation at approximately 24 hours. MRSA
strains were further characterized using pulsedfield gel electrophoresis.11
®
The MRSA Decolonization Protocol included
a physician’s order for MRSA isolation, contact
precautions, a Hibiclens bath, mupirocin (Bactroban ) to nares 2 times per day for 5 days, and
continued surface surveillance cultures until
Infection Prevention approved removal from isolation. Standard policy in the NICU required all
staff members to follow contact precautions and
to perform hand hygiene before and after caring
for and/or handling infants. Additional measures
required parents to wear gloves and gowns when
in the room with their infant if they had a positive
culture for MRSA.
™
Patients included in the analysis were not colonized or infected upon admission to the NICU.
Bivariate analysis was performed to compare
infant characteristics between study groups.
Categorical variables were compared using Chisquare test. Continuous variables were compared
using student’s t-test. Data are presented as frequency and percentage for categorical variables
or mean ± standard deviation for continuous
variables. P values < .05 were considered indicative of statistical significance. All statistical
analyses were completed using SAS Enterprise
Guide 7.1 software (Statistical Analysis System,
Cary, NC).
Results
During the study period, 8283 neonates were
admitted to the NICU at GMMC and met the
inclusion criteria. From these, 2139 were born
preprotocol (Group 1), of whom 96 developed
MRSA colonization (n = 87) and/or infection
(n = 9). From the 6144 infants born postprotocol
(Group 2), 178 developed MRSA colonization (n =
167) and/or infection (n = 11). All 20 patients who
were infected with MRSA were infected prior to
identification of colonization. The frequency of
MRSA colonization (Group 1: 4.1% vs. Group 2:
2.7%; P = .002) was significantly lower in Group
GHS Proc. November 2016; 1 (2): 117-120
IMPACT OF MRSA DECOLONIZATION PROTOCOL IN NICU
2; frequency of MRSA infection was also lower
in Group 2, although only marginally significant
(0.4% vs. 0.2%; P = .05) (Table 1).
sures to decrease or eliminate bacterial bioburden appear to decrease the risk of progression to
infection.
Patient demographics and risk factors are
described in Table 2. Neonates born preprotocol
and postprotocol were comparable with regard to
gender, birth weight, gestational age, PICC line
placement, mechanical ventilation, and days to
colonization. Mode of delivery and need for surgery were significantly different between groups,
with a higher proportion of neonates in Group 1
born by C-section (77.1% vs. 65.2%, P = .04) and a
higher proportion of infants in Group 2 requiring
surgery (49.0% vs. 70.0%, P < .01).
Conclusion
From the 274 colonized infants, 179 (65%) had
strain typing data available. From these, 14 unrelated MRSA strains were identified, of which
community-associated MRSA USA300 was most
common (n = 28), followed by hospital-associated
MRSA USA800 (n = 22). One MRSA infection
progressed to sepsis and ultimately necrotizing
pneumonia and resulted in death; this was the
only mortality in the study. MRSA strain VIIc
was the causative organism in this mortality—
this was the only infant colonized with this particular strain.
Discussion
MRSA colonization is a risk factor for progression to infection.2 This study demonstrates that
efforts to decolonize neonates can statistically
impact rates of infection. This study is the first
to describe the benefit of decolonization in a vulnerable group of infants. There were no adverse
events associated with the use of the topical chlorohexidine and mupirocin.
Infections in neonates are associated with
increased cost, prolonged length of stay, exposure
to additional antibiotics, and increased invasive
procedures such as central venous access, lumbar puncture, and even surgical interventions.12,13
Additionally, new literature reports invasive
blood stream infections lead to increased risk of
poor neurodevelopmental outcomes in preterm
infants.14,15
Efforts to prevent colonization with MRSA
should be first line. By using active surveillance to
identify infants who become colonized early and
adherence to expanded contact precautions that
include family members, in addition to healthcare workers, the decrease in transmission of
MRSA in the NICU setting can be accomplished.
However, if colonization occurs, additional mea-
GHS Proc. November 2016; 1 (2): 117-120
This study demonstrates that measures of active
surveillance for early recognition of colonization
and isolation combined with implementation of a
NICU MRSA decolonization protocol can reduce
colonization and infection rates, and the associated morbidities attributable to infection.
Table 1
MRSA status preprotocol and postprotocol.
Preprotocol
Postprotocol
2139
6144
Infection, no. (%)
9 (0.42%)
11 (0.18%)
.05
Colonization, no. (%)
87 (4.07)
167 (2.72)
.002
Total: infected or colonized,
no. (%)
96 (4.49)
178 (2.90)
<.001
N
P Value
Table 2
Patient demographics and risk factors.
Preprotocol
Postprotocol
96
178
Female, no. (%)
48 (50.0)
86 (48.3)
.79
Pre-term delivery, no. (%)
92 (95.8)
175 (98.3)
.21
<36 weeks
86 (89.6)
156 (87.6)
.63
<32 weeks
61 (63.5)
96 (53.9)
.12
74 (77.1)
116 (65.2)
.04
1.52 ± 0.88
1.65 ± 0.83
.23
83 (86.4)
148 (83.1)
.47
20.4 ± 20.8
23.2 ± 29.9
.37
Mechanical ventilation,
no. (%)
21 (21.9)
24 (13.5)
.07
PICC line, no. (%)
66 (68.7)
114 (64.0)
.43
Surgery, no. (%)
47 (49.0)
123 (70.0)
<.01
N
P Value
Gestational age, no. (%)
Mode of delivery, no. (%)
C-section
Birth weight (kg), mean ± SD
Low birth weight (<2.5kg)
Days to colonization,
mean ± SD
SD, standard deviation; PICC, peripherally inserted central catheter
119
Abbreviations and
Acronyms
MRSA =
methicillin-resistant
Staphylococcus
aureus; NICU =
neonatal intensive
care unit; GMMC =
Greenville Memorial
Medical Center
Correspondence
Address to:
Robin LaCroix, MD,
Greenville Health
System, Department
of Pediatrics,
Infectious Disease,
200 Patewood Dr,
Suite A200,
Greenville, SC 29615
([email protected])
References
1. Carey AJ, Duchon J, Della-Latta P, et al. The epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in a neonatal intensive
care unit, 2000–2007. J Perinatol. 2010;30:135-9.
2. Huang YC, Chou YH, Su LH, et al. Methicillin-resistant Staphylococcus aureus colonization and
its association with infection among infants hospitalized in neonatal intensive care units. Pediatrics. 2006;118:469-74.
3. Sakaki H, Nishioka M, Kanda K, et al. An investigation of the risk factors for infection with methicillin-resistant Staphylococcus aureus among patients
in a neonatal intensive care unit. Am J Infect Control. 2009;37:580-6.
4. Cimolai N. Staphylococcus aureus outbreaks among
newborns: new frontiers in an old dilemma. Am J
Perinatology. 2003;20:125-36.
5. Geva A, Wright SB, Baldini LM, et al. Spread of
methicillin-resistant Staphylococcus aureus in a
large tertiary NICU: network analysis. Pediatrics.
2011;128:e1173-80.
6. Seybold U, Halvosa JS, White N, et al. Emergence of
and risk factors for methicillin-resistant Staphylococcus aureus of community origin in intensive care
nurseries. Pediatrics. 2008;122:1039-46.
7. Shiojima T, Ohki Y, Nako Y, et al. Immediate control
of a methicillin-resistant Staphylococcus aureus outbreak in a neonatal intensive care unit. J Infect Chemotherapy. 2003;9:243-7.
8. Lessa FC, Edwards JR, Fridkin SK, Tenover FC, Horan
TC, Gorwitz RJ. Trends in incidence of late-onset
methicillin-resistant Staphylococcus aureus infec-
120
tion in neonatal intensive care units: data from the
National Nosocomial Infections Surveillance System, 1995–2004. Pediatr Infect Dis J. 2009;28:577-81.
9. Lessa FC, Edwards JR, Fridkin SK, et al. Trends in
incidence of late-onset methicillin-resistant Staphylococcus aureus infection in neonatal intensive care
units: data from the National Nosocomial Infections
Surveillance System, 1995–2004. Pediatr Infect Dis J.
2009;28:577-81.
10.Carey AJ, Saiman L, Polin RA. Hospital-acquired
infections in the NICU: epidemiology for the new
millennium. Clin Perinatol. 2008;35:223-49.
11. Diederen B, van Duijn I, van Belkum A, et al. Performance of CHROMagar MRSA medium for detection
of methicillin-resistant Staphylococcus aureus. J Clin
Microbiol. 2005;43:1925-7.
12. Schultz ED, Tanaka DT, Goldbert RN, et al. Methicillin-resistant Staphylococcus aureus colonization in
the neonatal intensive care unit increases total hospital costs. Infect Control Hosp Epidemiol. 2009;30:3835.
13.Nelson MU, Gallagher PG. Methicillin-resistant
Staphylococcus aureus in the neonatal intensive care
unit. Semin Perinatol. 2012;36:424-30.
14. Alshaikh B, Yusuf K, Sauve R. Neurodevelopmental
outcomes of very low birth weight infants with neonatal sepsis: systematic review and meta-analysis. J
Perinatol. 2013;33:558-64.
15. Neill S, Haithcock S, Smith PB, et al. Sustained reduction in bloodstream infections in infants at a large
tertiary care neonatal intensive care unit. Adv Neonatal Care. 2016;16:52-9.
GHS Proc. November 2016; 1 (2): 117-120
Original Research
Does Comprehensive Dementia Education Impact SelfEfficacy Among Family Caregivers in the Community?
Xi Pan, PhD; Melissa Bailey, DO, MPH; Meghan Socko, LMSW; and Lisa Naylor, NP
From the Department of Public Health Sciences, Clemson University, Clemson, SC (X.P.), and Division
of Geriatrics, Center for Success in Aging, Greenville Health System, Greenville, SC (M.B., M.S., L.N.)
Abstract
Background: This pilot study assessed the impact of a 6-week comprehensive, multisession, professionally guided, and in-person caregiver educational program on self-efficacy among dementia
family caregivers in Upstate South Carolina (SC).
Methods: Self-efficacy among 28 family dementia caregivers was analyzed using data collected in
2015 with repeated-measure of linear regression (ANOVA).
Results: Results show that caregiver self-efficacy in managing dementia symptoms and the utilization of social support services are significantly improved after the training.
Conclusions: Findings of the study imply that caregiver education is beneficial in reducing caregiver
burnout and optimizing caregiver needs for dementia caregiving. This finding is helpful to develop
family-centered interventions that should be considered as a part of routine dementia treatment
protocol in Upstate SC.
A
lzheimer’s disease and related dementia (ADRD) poses increasing challenges
for public health and requires substantial
resources for dementia care in the United States
(US).1 In 2015, more than 15 million Americans
provided unpaid care (informal care) to their loved
ones with ADRD, and 85% of the caregivers were
family members.2 Family caregivers are burdened
with the complexity of providing assistance in
basic and instrumental activities of daily living.3,4
Many caregivers lack dementia education and are
unprepared for the demands that the disease places
on their time, resources, and health.5 Furthermore,
compared to non-dementia caregivers, dementia
caregivers tend to become more socially isolated
from their peers and others in the community.3
The demands and emotional strains associated
with dementia caregiving reduce caregivers’ physical and psychological well-being and leave them
vulnerable to depression.6
Self-efficacy plays a key role in the relationship
between dementia caregiving and depression
among caregivers.7 Self-efficacy refers to an individual’s belief/assessment of his or her ability to
GHS Proc. November 2016; 1 (2): 121-125
successfully perform daily management of dementia by learning specific behaviors or tasks relevant
to the disease.7,8 Higher levels of self-efficacy predict higher capability of accomplishing dementia
care management and enduring the disease-related
challenges, whereas lower levels of self-efficacy predict higher levels of stress and depression.9,10
Social support and resources are important for
providing emotional support to caregivers and
enhancing their self-efficacy, which can encourage them to access information and education that
may aid in the caregiving journey.3 The majority
of existing dementia education programs in the
US are offered online, emphasize dementia symptom management without fostering the benefits of
social support, and are not facilitated by healthcare professionals. Many of these programs are
challenging for dementia caregivers, particularly
older caregivers, who have limited or no access to
the internet and are not computer savvy.3 What
appears to be lacking is the availability of face-toface, comprehensive educational programs that
focus on multiple aspects of dementia—from basic
education to the challenges that may arise in the
121
caregiving process, including safety concerns and
expectations at each stage of the disease process.
Empirically derived interventions that match the
needs and preferences of caregivers in specific
communities are underdeveloped.11 Existing literature on interventions that effectively improve key
outcomes for family caregivers is limited.
family caregivers in Upstate SC (Greenville-Spartanburg-Anderson) participating in the Caregiver
ABCs program. It was hypothesized that the comprehensive education would have a positive effect
on family caregiver self-efficacy in managing
dementia symptoms and increase caregiver use of
social support resources.
The objective of this study was to evaluate Caregiver ABCs program, a comprehensive caregiver
education, created by the Center for Success in
Aging at Greenville Health System (GHS) in
Greenville, South Carolina (SC). The focus of the
study was assessment of self-efficacy among the
Methods
Table 1
Characteristics of caregiver participants in Caregiver ABCs program.
Characteristic
N
28
Age, years (mean ± SD)
62 ± 6
Gender, no. (%)
Female
21 (75.0)
Race, no. (%)
Caucasian
African American
27 (96.4)
1 (3.6)
Education, no. (%)
Less than 8th grade
0 (0.0)
Some high school
0 (0.0)
High school graduate
3 (10.7)
Some college
9 (32.1)
College graduate
14 (50.0)
Graduate school
2 (7.1)
Marital status, no. (%)
Single or never married
Married
1 (3.6)
23 (82.1)
Living with a partner
0 (0.0)
Divorced or separated
3 (10.7)
Widowed
1 (3.6)
Relationship to care recipients, no. (%)
Spouse or partner
5 (17.9)
Adult child
19 (67.9)
Other family member
4 (14.2)
Friend
0 (0.0)
Living with care recipients, no. (%)
Yes
122
14 (50.0)
Intervention
The Caregiver ABCs program is a 6-week comprehensive educational series consisting of 6 classes: 1)
Alzheimer’s, Aging, and Assessment, 2) Behaviors,
Beliefs, and the Baggage We Bring, 3) Communication, Caring, and Coping, 4) Driving, Dangers, and
Drugs, 5) Elder Law, and 6) Expectations, Emergencies, and Enjoyment. The aims of the program were
to enhance the caregivers’ knowledge in dementia
caregiving and to learn to reduce caregiver stress.
Each class lasts 120 minutes and is taught by nurse
practitioners and a licensed social worker, who
regularly provide health care to individuals with
ADRD in an outpatient setting at GHS. The class
series is repeated 3 times annually.
Sample
Our study population included family caregivers
of people with diagnoses of ADRD who registered
for the Caregiver ABCs program between January 2015 and October 2015 from Upstate SC. The
total number of registrants for each series was 30
(90 for all 3 series). Fifty-five registrants, including
non-family caregivers (85%) and family caregivers
who decided not to participate in the study (15%)
as well as 7 people who missed the post-tests, were
excluded from the analysis. Finally, the sample of
the study consisted of 28 family caregivers who
attended all 6 classes and completed the pre- and
post-tests. This study was approved by the GHS
Institutional Review Board before the start date of
the first series in January 2015.
Measurement
Self-efficacy was measured using 10 items from
the self-reported self-efficacy survey for dementia
caregivers.8 Each item had 10 response categories
scoring from 1 (Not at all) to 10 (Very certain).
The first 5 items measured caregivers’ self-efficacy
in managing dementia symptoms; the remaining
5 items measured use of social support services
(Table 2, right). Validity (internal consistency)
and reliability of the measurement were high with
Cronbach’s alpha = .77 and .78, respectively.8
Characteristics of participants, including chronological age, gender, race, education, marital status,
relationship to care recipients, and living arrangeGHS Proc. November 2016; 1 (2): 121-125
DEMENTIA EDUCATION, SELF-EFFICACY, FAMILY CAREGIVERS
ment with care recipients, were collected. Education was defined as the highest level of degree
that the family caregiver had received. Living
arrangements were defined as whether the family
caregiver was living with the care recipient by the
time of study. In addition, self-rated health was a
confounder and measured by a global question
on caregivers’ general health status with 5-Likert
scale response categories from “Poor” to “Excellent.”
Analysis
Descriptive statistics (eg, mean ± standard
deviation and percentage) were used to examine
characteristics of participants. Cohen’s d analysis
was used to estimate effect size. Repeated-measure of linear regression (ANOVA) with a Greenhouse-Geisser correction was used to examine
the changes in the mean of self-efficacy before and
after the program. Post hoc tests using the Bonferroni correction was used to decide how much the
mean of self-efficacy changed before and after the
training. All analyses were conducted using IBM
SPSS Statistics 23.0.
ing with the care recipients (50.0%) by the time of
study. All participants in our study scored their
self-rated health as Good/Very good (78.6%) or
Excellent (21.4%) (Table 1).
Figure 1
Difference in caregiver self-efficacy scores pre-training and posttraining.
Mean Total Scores of Self-Efficacy
P < .001
®
®
Results
Participant characteristics are described in Table
1 (left). Most of the 28 caregivers were Caucasian
(96.4%) women (75.0%) with a mean age of 62 ± 6
years. Most were married (82.1%) and had earned
college degrees (57.1%). Most of the caregiver participants were adult children (67.9%) and were liv-
50
45
40
40.29
35
37.07
30
25
26.68
24.61
20
15
10
5
0
Managing Dementia
Symptoms
Pre-training Score
Finding Social
Support
Post-training Score
Table 2
Effect of dementia education on caregiver self-efficacy (pre-post) ANOVA test.
Self-Efficacy Items
Dementia symptom management (overall)
Pre-training Score Post-training Score
(mean ± SD)
(mean ± SD)
P Value
26.7 ± 10.8
40.3 ± 5.8
<.001
1
Handle any problems like memory loss
5.5 ± 2.9
7.9 ± 1.4
<.001
2
Deal with frustration of caring
4.4 ± 2.7
8.0 ± 1.1
<.001
3
Handle problems that come up in future
5.2 ± 2.4
7.5 ± 1.6
<.001
4
Do something to keep relative independent
5.7 ± 2.8
8.2 ± 1.7
<.001
5
Care for relative without help from organizations or agencies
5.9 ± 2.0
8.7 ± 1.2
<.001
24.6 ± 9.5
37.1 ± 7.2
<.001
Find ways to pay for services
4.1 ± 2.7
5.6 ± 2.8
<.01
Finding social support (overall)
6
7
Get answers to all questions about services
5.5 ± 2.5
8.5 ± 1.6
<.001
8
Find organizations or agencies that provide services
5.5 ± 2.3
8.5 ± 1.4
<.001
9
Arrange for services yourself
4.7 ± 2.4
7.7 ± 1.9
<.001
10
Get answers to all your questions about your relative’s care
4.8 ± 2.9
6.9 ± 2.2
<.001
Note: Each item had 10 response categories scoring from 1 (Not at all) to 10 (Very certain). The first 5 items measured caregivers’ selfefficacy in managing dementia symptoms, and the remaining 5 items measured the use of social support services (max overall score = 50).
GHS Proc. November 2016; 1 (2): 121-125
123
Abbreviations and
Acronyms
ADRD = Alzheimer’s
disease and related
dementia; US =
United States; GHS =
Greenville Health
System; SC = South
Carolina
Correspondence
Address to:
Xi Pan, PhD, Greenville
Health System, Center
for Success in Aging,
255 Enterprise Blvd,
Suite 101, Greenville, SC
29615 (tidypan2009@
gmail.com)
The mean scores of self-efficacy before and after
the training were significantly different based on
the ANOVA test (Fig. 1 and Table 2). As shown
in Table 2, the mean post-training score of self-efficacy in managing dementia symptoms was significantly higher than that of pre-training (40.3
vs. 26.7; P < .001). An increase was also seen with
regard to self-efficacy in finding social support
services among caregivers who participated in the
program (24.6 vs. 37.1; P < .001).
Discussion
Findings of this study suggest that this comprehensive, multisession, professionally guided, and
in-person program was beneficial in providing
significant knowledge, skills, and confidence
to family caregivers. Caregivers also learned
to address disease-related safety issues such as
driving, cooking, and other activities that may
require supervision. Therefore, the effectiveness
of training of such brevity suggests that this intervention should be developed into a protocol and
implemented as a part of routine clinical care in
Upstate SC.
This study also supports the family-centered program of dementia care. Caregiving has a strong
impact on family relationships and might determine the level of conflict within the family.12 The
class of “Communication, Caring, and Coping”
helps primary caregivers clarify expectations
of caregiving among family members, identify
potential sources of support, and address conflict resolutions. Positive and supportive family
relationships have been found to be significantly
associated with less strain and burden among
caregivers, compared to caregivers with poor
family functioning.12 The Caregiver ABCs program achieved the goal of increasing caregiver
confidence in multifaceted dementia care, which
helps health providers develop family-centered
comprehensive dementia care for caregivers in
other similar community settings.
Study limitations include small sample size, lack
of control group, and inability to collect information on the severity of dementia among care
recipients. Our sample also lacks diversity since
the participants were mainly Caucasian married
women with higher education. However, exist-
124
ing literature has suggested that caregivers who
participate in psychoeducation tend to be female
Caucasians with higher education.13
To have a greater population health impact and
to reach a greater percentage of the 45 million
Americans and families affected by dementia and
related diseases, expanding our study to include
a more diverse cohort of participants at multiple
sites is our future direction. As telehealth strategies are becoming increasingly popular, an online
or computer-based psychoeducation model will
be a promising supplement to our existing in-person sessions.
A big strength of internet-based psychoeducation is the removal of some barriers, such as the
inability to leave the care recipient to attend a
program.14 Existing evidence has shown that
computer-based psychoeducation can improve
caregiving confidence or mastery (ie, self-efficacy)
among dementia caregivers.14,15 It is possible that
an online program might accomplish similar outcomes among dementia caregivers in Upstate SC.
Such a program can be provided to caregivers who
have difficulty leaving the care recipient to attend
in-person sessions. Thus, the combination of both
programs may increase the recruitment, enhance
participant diversity, and improve the interactivity between instructors and participants.
In addition, we plan to expand the follow-up
investigation with longer intervals and to include
a comparison group. It is unclear if this intervention would have been as effective in those with
lower education or those less likely to take advantage of this type of program.
A comparison group with people who have lower
education will be included in future studies. It is
important to examine the influence of educational
level on the relationship between self-efficacy and
the intervention. Furthermore, qualitative studies such as interview or focus group are needed
to understand why participants drop out from
the program or decline to participate. Increased
marketing and cultural sensitivity are also areas
that we plan to expand. Last, correlating the stage
of dementia with the pre- and post-training sessions will provide even more strength to our novel
intervention.
GHS Proc. November 2016; 1 (2): 121-125
DEMENTIA EDUCATION, SELF-EFFICACY, FAMILY CAREGIVERS
References
1. Weuve J, Hebert LE, Scherr PA, Evans DA. Prevalence of Alzheimer disease in US states. Epidemiology.
2015;26:e4-6.
2. Alzheimer’s Association. 2015 Alzheimer’s disease facts
and figures. Alzheimers Dementia. 2015;11:332-84.
3. Au A, Lai MK, Lau KM, Pan PC, Lam L, Thompson L,
Gallagher-Thompson D. Social support and well-being
in dementia family caregivers: the mediating role of
self-efficacy. Aging Ment Health. 2009;13:761-8.
4. Nicolaou P, Egan S, Gasson N, Kane R. Identifying
needs, burden, and distress of careers of people with
Frontotemporal dementia compared to Alzheimer’s
disease. Dementia. 2010;9:215-35.
5. Lilly MB, Robinson CA, Holtzman S, Bottorff JL. Can
we move beyond burden and burnout to support the
health and wellness of family caregivers to persons
with dementia? Evidence from British Columbia, Canada. Health Soc Care Community. 2012;20:103-12.
6. Gilliam CM, Steffen AM. The relationship between
caregiving self-efficacy and depressive symptoms
in dementia family caregivers. Aging Ment Health.
2006;10:79-86.
7. Zeiss AM, Gallagher-Thompson D, Lovett S, Rose J,
McKibbin C. Self-efficacy as a mediator of caregiver
coping: development and testing of an assessment
model. J Clinic Geropsychol. 1999;5:221-30.
8. Fortinsky RH, Kercher K, Burant CJ. Measurement and
correlations of family caregiver self-efficacy for managing dementia. Aging Ment Health. 2002;6:153-60.
GHS Proc. November 2016; 1 (2): 121-125
9. Romero-Moreno R, Losada A, Mausbach BT, MárquezGonzález M, Patterson TL, López J. Analysis of the
moderating effect of self-efficacy domains in different
points of the dementia caregiving process. Aging Ment
Health. 2011;15:221-31.
10.Semiatin AM, O’Connor MK. The relationship
between self-efficacy and positive aspects of caregiving
in Alzheimer’s disease caregivers. Aging Ment Health.
2012;16:683-8.
11. Gallagher D, Mhaolain AN, Crosby L, et al. Self-efficacy for managing dementia may protect against burden and depression in Alzheimer’s caregivers. Aging
Ment Health. 2011;15:663-70.
12.Etters L, Goodall D, Harrison BE. Caregiver burden
among dementia patient caregivers: a review of the literature. J Am Acad Nurse Pract. 2008;20:423-8.
13. Pinquart M, Sörensen S. Helping caregivers of persons
with dementia: which interventions work and how
large are their effects? Int Psychogeriatr. 2006;18:57795.
14. Lewis ML, Hobday JV, Hepburn KW. Internet-based
program for dementia caregivers. Am J Alzheimers Dis
Other Demen. 2010;25:674-9.
15. Hayden LJ, Glynn SM, Hahn TJ, Randall F, Randolph
E. The use of Internet technology for psychoeducational and support with dementia caregivers. Psychol
Serv. 2012;9:215-8.
125
Original Research
Insurance Status of Deceased Organ Donors
John D. Cull, MD; Tara L. Spivey, MD; Samuel Kingsley, MD; David A. Ansell, MD, MPH; Kimberly
Joseph; and Edie Y. Chan, MD
From the Department of Surgery, Greenville Health System, Greenville, SC (J.D.C.); Department of
General Surgery, Rush Medical College, Chicago, Ill (T.L.S., E.Y.C.); Department of Trauma, John H.
Stroger Hospital of Cook County, Chicago, Ill (S.K., K.J.); and Department of Medicine, Rush Medical
College, Chicago, Ill (D.A.A.)
Abstract
Background: Some critics believe that a disparity in insurance status exists between organ donors
and organ recipients. Few studies, however, have examined this criticism. The aim of this study was
to examine the insurance status of deceased organ transplant donors in one Donor Service Area to
determine whether a disparity in insurance status exists between organ donors and organ recipients.
Methods: We performed a retrospective chart review from a prospective database on all patients
who had organs procured from one organ procurement organization between January 2010 and
December 2012. Data collection included donor age, sex, race, citizenship, and insurance status.
Results: During the study period, 816 deceased organ transplant donors were identified. The majority of patients were men (59%) and either Caucasian (59%) or African American (27%). Median
donor age was 45 years (range, 1 month−85 years). Donor insurance status was unattainable in 128
patients. From the remaining 688 patients, 485 (70%) were insured and 203 (30%) had no insurance. African American (P = .017) and Latino (P < .0001) donors were less likely to have insurance
compared to Caucasians. Approximately 3.5% (n = 24) of donors were not United States citizens.
Conclusions: Our findings showed that a significant number (~30%) of organ donors do not have
health insurance. As previous reports reflect a very low rate of uninsured organ recipients (<1%),
our data suggest that although many organs are procured from the uninsured, very few uninsured
patients are likely to receive an organ.
T
here is a large and increasing demand for
organ transplantation. In the United States
(US), approximately 9000 people donate
organs each year, but more than 120 000 people are in need of a lifesaving organ transplant.1
According to the United Network for Organ
Sharing (UNOS), organs are matched with
transplant candidates using medical and logistical factors alone, with social characteristics,
including insurance coverage, playing no role
in transplant priority.2 However, to be matched,
the patient must first be added to the national
waiting list, an action determined by a hospital’s
transplant team.
Organs are a scarce resource, and the longterm viability of transplanted organs is a major
concern for transplant centers, as failure can
126
negatively impact their program’s percentile of
successful transplants. Transplantation is also
expensive, ranging from about $334 000 for a kidney to over $1.2 million for a heart transplant.3
Moreover, these initial costs do not include the
necessary antirejection drugs past 180 days, the
cost of which can exceed $2500 per month.3 As
a result, patients are unlikely to be placed on
the transplant waiting list if they are uninsured,
underinsured, and/or lack sufficient financial
resources for the transplant surgery and the subsequent follow-up and antirejection medication
required posttransplant.4
In contrast, financial and insurance status are not
considered necessary for organ donation. Due to
this discrepancy, some critics believe the organ
allocation system to be unequitable.5 Few studies,
GHS Proc. November 2016; 1 (2): 126-129
INSURANCE STATUS OF DECEASED ORGAN DONORS
however, have examined this criticism. The aim
of this study was to evaluate the insurance status of deceased organ transplant donors within
a single Donor Service Area (DSA) to determine
whether a disparity in insurance status exists
between organ donors and organ recipients.
Methods
Rush University Medical Center’s Institutional
Review Board approved this study. We performed
a retrospective chart review from a prospective
database on all patients whose organs were procured in Northern Illinois and Northwestern
Indiana between January 2010 and December
2012 from the organ procurement organization
(OPO), Gift of Hope. Data collection included
donor age, sex, race, citizenship, and insurance
status. Data were evaluated using student’s t-test
and Fisher’s exact test. Statistical significance was
assessed using alpha = .05. All data analysis was
generated using SAS software, Version 9.1.3 (Statistical Analysis System, Cary, NC).
ance status was available (n = 688), 70.5% (485)
were insured and 29.5% (203) had no insurance
(Table 2). African American (P = .017) and Latino
(P < .0001) organ donors were less likely to have
insurance when compared to their Caucasian
counterparts. Approximately 3.5% (n = 24) of
donors were non-US citizens, all of whom were
uninsured.
Discussion
In 2008, Herring et al reported a story of a young,
previously healthy, uninsured day laborer who
presented to an emergency department in need
of a heart transplant.6 The patient was ultimately
deemed unsuitable, as he did not have the ability to pay for the long-term immunosuppressive
therapy required for successful recovery; the
patient died 2 weeks later. This experience acted
as an impetus for the Herring et al study, which
Table 2
Results
Transplant donor ethnicity and insurance status.
During the study time frame, 816 organ transplant donors were identified and evaluated for
transplant purposes. Donor characteristics are
described in Table 1. The majority of patients
were men (59%) and either Caucasian (59%) or
African American (27%). The median donor age
was 45 years, with a range of 1 month to 85 years.
Patients, N
816
Caucasian, no.
481
Donor insurance status was not attainable in
128 patients (16%). From donors in whom insur-
Table 1
Transplant donor characteristics.
Patients, N
816
Age, median
45
Gender, no. (%)
Male
482 (59.1)
Female
334 (40.9)
Race, no. (%)
Yes, no. (%)
315 (65.5)
No
98 (20.4)
Unknown
68 (14.1)
African American, no.
218
Yes, no. (%)
119 (54.6)
No
58 (26.6)
Unknown
41 (18.8)
Latino, no.
94
Yes, no. (%)
46 (48.9)
No
40 (42.6)
Unknown
Asian, no.
8 (8.5)
14
Yes, no. (%)
6 (42.9)
Caucasian
481 (58.9)
No
5 (35.7)
African American
218 (26.7)
Unknown
3 (21.4)
Latino
94 (11.5)
Asian
14 (1.8)
Other
9 (1.1)
Non-US citizens, no. (%)
24 (3.5)
GHS Proc. November 2016; 1 (2): 126-129
Other, no.
9
Yes, no. (%)
3 (33.3)
No
5 (55.6)
Unknown
1 (11.1)
127
Acknowledgments
This work was
supported in part by
Health Resources
and Services
Administration
contract 234-2005370011C. The content
is the responsibility of
the authors alone and
does not necessarily
reflect the view
or policies of the
Department of Health
and Human Services,
nor does mention
of trade names,
commercial products,
or organizations imply
endorsement by the
US government.
This work was
supported through
grant funding by Gift
of Hope. The content
is the responsibility of
the authors alone and
does not necessarily
reflect the view or
policies of Gift of
Hope.
analyzed the insurance status of US organ donors
by using the 2003 National Inpatient Sample
(NIS). Their study included 1447 organ donors
and 4962 transplant recipients, from which 16.9%
of organ donors were uninsured, compared to
0.8% of transplant recipients. Similar to our
study, most organ donors in the NIS database
were Caucasian (69.4%) and in their early 40s
(mean age, 40.4 years). Their study, however, had
slightly more female donors (56.1%), while ours
reported more men (59.1%).
Our findings showed that 30% of deceased organ
transplant donors were uninsured. There were,
however, 128 donors with an unknown insurance
status. If all of these 128 donors happened to be
insured, the rate of uninsured donors at this single OPO would still be 25%. In 2005, King and
colleagues queried the Siminoff’s National Study
of Family Consent Donation database and found
that approximately 23% of all organ donors are
uninsured.7
Approximately 4% of patients in our study were
non-US citizens. Between 1988 and 2007, 0.63%
of organ transplants were received by patients of
unknown citizenship; this same population, however, accounted for 2.5% of all organs donated.8
Another barrier to receiving an organ transplant
is underinsurance. In 2012, more than 31 million
Americans were defined as underinsured—an
insured person who spends a high share of their
income on medical care.9 Moreover, a report
from the Department of Labor shows that only
45% of private industry health plans cover organ
and tissue transplantation.10
The Patient Protection and Affordable Care Act
(ACA) seeks to increase the number of insured
patients in the US. However, it is unclear whether
all insurance types provided under the ACA
will cover transplantation. The ACA mandates
coverage for basic primary care needs, but coverage for transplant care is not well understood.
The ACA also explicitly prohibits undocumented
immigrants in the US (12.5 million people) from
participating on the healthcare exchanges or in
Medicaid expansion.11 Future research is needed
to determine the impact of the ACA on donor
recipient rates.
The authors concede that the insurance status of
transplant donors and transplant recipients is not
entirely comparable. Transplant recipients often
have chronic diseases that mandate expensive
health care. These patients also typically have
time to obtain insurance through government
128
programs such as Medicare or Medicaid. In contrast, patients who are transplant donors often
die suddenly and may not have chronic diseases
that mandate expensive health care and need for
insurance.
Proponents of the current organ allocation system
may argue that many of these uninsured donors
would be insurable if they themselves needed a
transplant, and that the observed disparity in
insurance status between donors and recipients is
exaggerated. The distinction between “insurable
uninsured” and “uninsurable uninsured,” however, is a theoretical argument with limited practical application. First, it is not possible to differentiate between these two groups at the time of
organ donation. Furthermore, insurance status of
the organ donor (living or deceased) is not taken
into consideration when soliciting organs while it
is almost universally mandated for organ recipients. Last, yes, an uninsured patient in need of a
transplant may acquire federal insurance (Medicare or Medicaid) over time and then get placed
on the waitlist; however, as illustrated by Herring et al, it is not uncommon for transplantable
patients to die prior to receiving the insurance
needed to be added to the waiting list.6
The authors also concede that long-term viability of transplanted organs is a major concern
for transplant surgeons and transplant centers.
The field of transplant surgery arguably has the
highest level of regulation, making good outcomes almost mandatory. Transplant centers are
reviewed by the Centers for Medicare & Medicaid
Services (CMS) on the basis of their 1-year patient
and organ survival rates. Ramifications for a low
survival rate can include lengthy and expensive
corrective processes, as well as the possibility of
having to terminate the program.
Moreover, transplant surgeons often feel pressured to get the most good out of a very scarce
resource. Transplant centers may argue that,
because of the CMS and the pressure to deliver
a very high success rate, their hands are tied and
that patients with insurance are a safer and more
strategic long-term choice. Some people in the
transplant community do admit that disparities exist; however, it should be noted that many
from the transplant community have also fought
against certain utilitarian proposals—those proposing that organ priority be given to those most
likely to live the longest instead of those next in
line—in an effort to prevent further disparities.
Despite the intent of UNOS and the Organ
Procurement and Transplantation Network to
GHS Proc. November 2016; 1 (2): 126-129
INSURANCE STATUS OF DECEASED ORGAN DONORS
promote equity in transplantation access, our
findings show that a disparity in insurance status does exist between organ donors and organ
recipients. Transplantation is profitable to pharmaceutical companies, organ procurement organizations, and hospitals. This profit is contingent
upon organ donation from both insured and
uninsured patients. This fact makes the equity
concerns about access to transplantation for the
uninsured even more acute.
This study has all of the inherent limitations of
a retrospective study from a prospective database. This study was also limited in size and
scope, as we only reviewed the insurance status of
deceased organ donors from a single DSA and did
not review the insurance status of living organ
donors or donor recipients.
Conclusion
Society solicits organ donations from all of its
members; however, there is a disparity between
eligibility for organ donation versus eligibility
for organ transplantation. Although insurance
is mandatory to receive an organ transplant, this
study demonstrates that many organ donors do
not have health insurance.
References
7. King LP, Siminoff LA, Meyer DM, Yancy CW, Ring
WS, Mayo TW, Drazner MH. Health insurance and
cardiac transplantation: a call for reform. J Am Coll
Cardiol. 2005;45:1388-91.
2. United Network for Organ Sharing (UNOS). How
organs are matched. https://www.unos.org/transplantation/matching-organs/. Accessed August 29,
2016.
8. Artiga S, Damico A, Young K, Cornachione E, Garfield R. Health coverage and care for immigrants.
Executive summary. http://kff.org/disparities-policy/issue-brief/health-coverage-and-care-for-immigrants/. Published January 20, 2016.
4. Organ procurement and transplantation network—
HRSA. Final rule with comment period. Fed Regist.
1998:16296-338.
5. Simmerling M. Beyond scarcity: poverty as a contraindication for organ transplantation. Am Med Assoc J
Ethics. 2007;9:441-5.
6. Herring AA, Woolhandler S, Himmelstein DU.
Insurance status of U.S. organ donors and transplant
recipients: the uninsured give, but rarely receive. Int J
Health Serv. 2008;38:641-52.
GHS Proc. November 2016; 1 (2): 126-129
US = United States;
UNOS = United
Network for Organ
Sharing; DSA = Donor
Service Area; OPO =
organ procurement
organization; NIS =
National Inpatient
Sample; ACA =
Affordable Care Act;
CMS = Centers for
Medicare & Medicaid
Services
Correspondence
1. U.S. Department of Health & Human Services.
Organ procurement and transplantation network.
https://optn.transplant.hrsa.gov/. Accessed June 21,
2016.
3. Hanson S, Bentley TS. Milliman Research Report.
2014 U.S. organ and tissue transplant cost estimates
and discussion. www.milliman.com/uploadedFiles/
insight/Research/health-rr/1938HDP_20141230.pdf.
Accessed June 14, 2016.
Abbreviations and
Acronyms
Address to:
John D. Cull, MD,
Greenville Health
System, Department
of Surgery, 890 W
Faris Rd, Suite 310,
Greenville, SC 29605
([email protected])
9. Schoen C, Hayes SL, Collins SR, Lippa JA, and Radley
DC. America’s underinsured: a state-by-state look at
health insurance affordability prior to the new coverage expansions. The Commonwealth Fund. http://
commonwealthfund.org/publications/fund-reports/2014/mar/americas-underinsured. Published
March 25, 2014. Accessed July 22, 2016.
10. Gupta C. Immigrants and organ sharing: a one-way
street. Virtual Mentor. 2008;10:229-34.
11.Labor Department. Selected Medical Benefits:
A report from the Department of Labor and the
Department of Health and Human Services. www.
bls.gov/ncs/ebs/sp/selmedbensreport.pdf. Published
April 15, 2011. Accessed July 22, 2016.
129
Case Studies
Catastrophic Upper Gastrointestinal Bleed in Roux-en-Y
Gastric Bypass Patients From Ulcer Erosion Into the Splenic
Artery: Details of Rapid Surgical Management
Andrew J. Jones, BS, BA; Nathaniel Walsh, MD; Aaron Bolduc, MD; Sean Lee, MD; and Brian Lane, MD
From the Department of Surgery, Augusta University Health, Augusta, Ga (A.J.J., N.W., A.B., S.L.,
B.L.); Medical College of Georgia at Augusta University, Augusta, Ga (A.J.J., N.W., A.B., S.L., B.L.);
and Department of Minimally Invasive and Digestive Diseases Surgery, Augusta University Health,
Augusta, Ga (S.L., B.L.)
Abstract
Postoperative ulcer disease continues to be a long-term concern in patients who undergo Roux-en-Y
gastric bypass (RYGB). This case series details the hospital courses and surgical interventions for
2 patients who survived catastrophic bleeding events from marginal ulcer and gastric pouch ulcer
erosion into the proximal splenic artery. In both cases, endoscopic therapy failed and urgent surgical
intervention was necessary due to patient instability. The Veith maneuver was employed in Patient
A for supraceliac aortic control, and Patient B underwent a series of operations to repair the erosion
and gastric pouch. The surgical approaches for management and a discussion of RYGB complications are included.
P
ostoperative ulcer disease continues to be a
long-term concern in patients who undergo
Roux-en-Y gastric bypass (RYGB). The true
incidence of this complication is difficult to determine and varies depending on follow-up. Literature has described incidence ranging between
0.6% to 25%.1 Though the causes of marginal
ulcers in these patients is often multifactorial, the
most consistent risk factors appear to be recurrent use of nonsteroidal anti-inflammatory drugs,
tobacco abuse, and Heliobacter pylori infection.2
Diabetes mellitus has also been described as a
risk factor because of microangiopathic disease
that predisposes the patient to ischemia and ulcer
formation.2
Patients often present with nonspecific symptoms
such as epigastric pain, dysphagia, nausea, and
vomiting.3 The majority of marginal ulcer disease
cases are treated medically with proton pump
inhibitors, sucralfate, and patient counseling.4
Medical management is successful in approximately 68% of patients.3
In cases involving significant gastric pouch or
marginal ulcer bleeding, standard endoscopic
130
hemostatic techniques are the first line of therapy.4 Angiographic hemostasis techniques have
also been utilized.5 We report 2 cases of RYGB
patients who had catastrophic bleeding events
from marginal ulcer and gastric pouch ulcer
erosion into the proximal splenic artery where
endoscopic therapy failed and urgent surgery was
necessary due to patient instability.
Case Descriptions
Patient A
Patient A is a 52-year-old woman with metastatic
cholangioadenocarcinoma on palliative chemotherapy who presented to our emergency department (ED) with sharp epigastric pain and bright
red hematemesis for several hours. She had a past
surgical history of RYGB. The malignancy was
discovered incidentally following the RYGB 1 year
before her presentation to our facility. She had
developed chronic anemia, attributed to malignancy and/or chemotherapy, which was being
treated with serial transfusions. The patient stated
that she had chronic nausea since the discovery of
her malignancy but very little vomiting prior to
that day.
GHS Proc. November 2016; 1 (2): 130-132
ROUX-EN-Y ULCER EROSION INTO SPLENIC ARTERY
In the ED, she was tachycardic and mildly hypotensive. Her hemoglobin was 6.7 grams per deciliter, which was below her baseline of 8.0 grams per
deciliter measured 3 days prior. She received 2 units
of packed red blood cells (pRBC) and was admitted to the intensive care unit (ICU). Gastroenterology performed an esophagogastroduodenoscopy
(EGD) that revealed bleeding from a marginal
ulcer at the gastrojejunal anastomosis.
Twenty-four hours later, the patient collapsed following an episode of frank hematemesis in the
restroom. A code blue was called and the patient
was resuscitated with endotracheal intubation,
fluid boluses, pRBC transfusion, and pressor support. The patient’s instability required emergent
transfer to the operating room (OR).
The first operation was an exploratory laparotomy
that revealed perforation of the gastric pouch adjacent to the left lobe of the liver with a dark blood
clot. The clot was gently removed, and active arterial bleeding was noted from the splenic artery.
Direct pressure failed to provide adequate control
of bleeding, and the Veith maneuver was employed.
The Veith maneuver is a technique for obtaining
supraceliac aortic control. The lesser omentum
is divided, and the stomach and distal esophagus
are retracted to the left. Blunt, manual dissection
around the gastroesophageal junction allowed it
to be encircled with a Penrose drain and retracted
laterally, which exposes the supraceliac aorta just
below the diaphragmatic hiatus and allows for control with a clamp or direct pressure.
Arterial bleeding was then controlled; oversewing
of the splenic artery followed. This operation was
followed by delayed reconstruction with gastric
pouch resection and esophagojejunostomy. Distal
enteral feeding access and delayed abdominal wall
closure were performed as well. Following closure,
the patient developed a perihepatic abscess, which
was managed uneventfully with placement of a
drain by interventional radiology (IR). Patient A
was discharged to a rehabilitation facility after a
1-month stay in our hospital.
Patient B
Patient B is a 53-year-old woman who presented
as a referral from Gastroenterology for recurrent
epigastric pain, refractory gastroesophageal reflux
disease, dysphagia, and surgical history of RYGB
22 years prior to presentation. She stated that she
previously used cocaine and smoked cigarettes,
but did not currently use any drugs or tobacco
products. The patient had maintained a 100-pound
weight loss for nearly 20 years before developing an
GHS Proc. November 2016; 1 (2): 130-132
increase in hunger with mild dysphagia to solids.
EGD revealed marginal ulcers, which were treated
with proton pump inhibitors and sucralfate. The
patient returned to prebypass weight within 2 years.
She was taken to the OR for laparoscopic excision
of 2 large gastro-gastric fistulas, lysis of adhesions,
and gastrostomy tube placement. She developed
fever and tachycardia postoperatively, and upper
gastrointestinal series confirmed a lateral gastric pouch leak. She was taken to the OR a second
time for EGD and esophageal stent placement. The
patient was discharged from the hospital after a
39-day stay complicated by recurrent fever, vomiting, and abdominal pain with multiple endoscopies
for repositioning of the stent.
She returned to the hospital multiple times over the
next 6 months for fever, vomiting, and abdominal
pain—all managed nonoperatively. Eventually, the
esophageal stent was removed endoscopically due
to intractable abdominal pain and vomiting. Laparoscopic cholecystectomy was also performed
after HIDA (hepatobiliary) scan revealed chronic
cholecystitis. The patient was discharged but presented to the ED 3 weeks later with epigastric pain
radiating to the back, lightheadedness, diarrhea,
and 6 episodes of hematemesis in 24 hours. The
patient was admitted to the surgery inpatient service, but she soon began vomiting bright red blood
and was transferred to the surgical ICU. The patient
received 1 unit of pRBC after becoming tachycardic
and hypotensive. IR was contacted for management
of the upper gastrointestinal bleed, but patient load
precluded transfer to the IR suite.
The patient was then taken to the OR for exploratory laparotomy where dense subhepatic adhesions to the gastric pouch were noted. Due to concern for marginal ulcer erosion into the proximal
splenic artery, pressure was applied to the celiac
trunk. Arterial pulsations were noted at the posterior aspect of the gastric pouch, but visualization of
the bleeding site was difficult due to the liver adhesions. A partial left hepatectomy was performed
and a gastroscope was employed for better visualization of the bleeding vessel. This vessel, which
was identified as the splenic artery, was oversewn
for control of the hemorrhage.
The patient underwent a total of 5 operative procedures as she required additional second-look
operations for a bile leak that healed conservatively. A partial colectomy was required followed
by reconstruction with gastric pouch resection and
esophagojejunostomy. A leak at the esophagojejunostomy was successfully treated with a fully covered self-expanding metal stent. Patient B was dis131
Correspondence
Address to:
Andrew J. Jones, BS,
BA, Department of
Surgery, Augusta
University Health,
1120 15th St, BI-4070,
Augusta, Ga 30912
([email protected])
charged to a rehabilitation facility after a 1-month
stay in our hospital.
Both patients survived despite massive transfusion requirements and prolonged hospitalization. Additionally, they both retained their
spleens though Patient B suffered multiple splenic
infarcts and was consequently immunized.
Discussion
As illustrated in the above cases, splenic artery
erosion from marginal ulcers can precipitate
severe gastrointestinal bleeding and lead to
instability and life-threatening shock. Bariatric complications increase with patient age and
time elapsed since the initial operation.6 Patients
with complications often present acutely and are
therefore treated by nonbariatric surgeons.6
Commonly reported diagnoses include anastomotic leak, pulmonary embolism, internal hernia,
small bowel obstruction, gastric band slippage
or restriction, biliary disease, perforated ulcer
with or without vessel erosion, and gastric outlet
obstruction.5-7 Late complications include pouch
enlargement, band erosion, gastric remnant syndrome, anastomotic stenosis, dumping syndrome,
gastroesophageal reflux, and vitamin deficiencies.8,9 The majority of these complications do not
progress to critical levels, and minimally invasive
techniques are appropriate in most cases.6
Despite multiple reports of gastric ulcer perforation following RYGB, there are few case reports
detailing arterial erosion.10 Sidani et al describe
a case in which the patient developed gross
hematemesis following RYGB.5 During exploratory laparotomy, the spleen appeared dusky and
was excised allowing for angiographic embolization of the splenic artery. The authors proposed
consideration of preoperative embolization to
allow a safer surgical repair of the RYGB.5
Bleeding marginal ulcers can be treated surgically
with either open or laparoscopic procedures with
identification and ligation of bleeding vessels.
Sasse et al recount 7 individual case presentations
of perforated marginal ulcer.10 Six required open
or laparoscopic exploration with oversewing and
omental patch. The seventh patient expired intraoperatively from multiple organ failure.10 Patients
presenting without severe bleeding who maintain
hemodynamic stability can be treated endoscopically while those presenting en extremis will typically require surgical intervention.5,10
Conclusion
Although rare, massive upper gastrointestinal
bleeding from ulcer erosion into the proximal
splenic artery may require urgent and specific
surgical therapy. Strong consideration should be
given to interventional radiographic angiography
for recurrent or initial severe upper gastrointestinal bleeds in RYGB patients. Our institution
has established this protocol in light of the cases
described above. Operative intervention, including the Veith maneuver for supraceliac aortic
control, may be necessary if angiography fails or
is not readily available.4 The bariatric and acute
care surgeon should have a working knowledge
of approaches to this particular life-threatening
scenario.
References
1. Carr WRJ, Mahawar KK, Balupuri S, Small PK. An
evidence-based algorithm for the management of
marginal ulcers following Roux-en-Y gastric bypass.
Obes Surg. 2014;24:1520-7.
2. El-Hayek K, Timratana P, Shimizu H, Chand B. Marginal ulcer after Roux-en-Y gastric bypass: what have
we really learned? Surg Endosc. 2012;26:2789-96.
3. Sola R, Avery MJ, Fischer PE, Christmas AB, Green
JM, Heniford BT, et al. Bariatric complications for the
acute care surgeon: perforated marginal ulcer after a
Roux-en-Y gastric bypass. Am Surg. 2015;81:E269-70.
4. Azagury DE, Abu Dayyeh BK, Greenwalt IT, Thompson CC. Marginal ulceration after Roux-en-Y gastric
bypass surgery: characteristics, risk factors, treatment, and outcomes. Endoscopy. 2011;43:950-4.
5. Sidani S, Akkary E, Bell R. Catastrophic bleeding
from a marginal ulcer after gastric bypass. JSLS.
2013;17:148-51.
6. Bradley JF 3rd, Ross SW, Christmas AB, Fischer PE,
132
Sachdev G, Heniford BT, et al. Complications of bariatric surgery: the acute care surgeon’s experience.
Am J Surg. 2015;210:456-61.
7. Montravers P, Augustin P, Zappella N, Dufour G,
Arapis K, Chosidow D, et al. Diagnosis and management of the postoperative surgical and medical complications of bariatric surgery. Anaesth Crit Care Pain
Med. 2015;34:45-52.
8. Healy P, Clarke C, Reynolds I, Arumugasamy M,
McNamara D. Complications of bariatric surgery—
what the general surgeon needs to know. Surgeon.
2016;14:91-8.
9. Tack J, Deloose E. Complications of bariatric surgery:
dumping syndrome, reflux and vitamin deficiencies.
Best Pract Res Clin Gastroenterol. 2014;28:741-9.
10. Sasse KC, Ganser J, Kozar M, Watson RW, McGinley
L, Lim D, et al. Seven cases of gastric perforation in
Roux-en-Y gastric bypass patients: what lessons can
we learn? Obes Surg. 2008;18:530-4.
GHS Proc. November 2016; 1 (2): 130-132
Case Studies
Dexmedetomidine-Induced Adrenal Crisis in an Infant
Jeremy M. Loberger, MD; Robert S. Seigler, MD; and Michael G. Avant, MD
From the Internal Medicine and Pediatrics Residency Program, Greenville Health System, Greenville,
SC (J.M.L.), and Department of Pediatrics, Division of Pediatric Critical Care, Greenville Health System, Greenville, SC (R.S.S., M.G.A.)
Abstract
Dexmedetomidine is a selective alpha-2 adrenergic agonist with sedative, analgesic, and anxiolytic
effects. It has a similar structure to another sedative, etomidate, which is known to cause adrenal
suppression. Therefore, there has been theoretical concern that dexmedetomidine may have the
same effect. In this case report, we present a young infant who developed adrenal crisis shortly after
receiving a high-dose dexmedetomidine infusion. To our knowledge, this incident is only the second
case report documenting this potential side effect in the pediatric population and the first of such
severity. The use of dexmedetomidine is increasing in pediatric patients. Therefore, it is important to
publish this case to increase awareness of this potential side effect.
D
®
exmedetomidine (Precedex , Hospira) is a
selective alpha-2 adrenergic agonist. It was
initially approved by the Food and Drug
Administration in 1999 for sedation in mechanically ventilated adult patients, for periods less than
24 hours. In addition to its sedative effects, it also
possesses mild analgesic and anxiolytic properties
coupled with minimal respiratory depression.1
Use in pediatrics is currently off label, consistent with the use of many other sedatives in
this patient population. Nonetheless, it has seen
increasing usage in the past few years, primarily
in procedural sedation. It is also used for sedation
in mechanical ventilation and clinical situations
requiring longer term sedation. Adult studies
have also demonstrated utility as a narcotic sparing agent in postsurgical patients.2
Dosing regimens for dexmedetomidine are not
well defined in pediatric patients. Limited data
suggest that a suitable range is 0.1–2.0 mcg/kg/
hr.3 Other publications have documented doses
as high as 2.7 mcg/kg/hr.4,5
Adrenal crisis is a syndrome that occurs either
with acute onset adrenal insufficiency or in a
patient with chronic adrenal insufficiency who
experiences significant physiologic stress. The
syndrome is usually associated with deficiencies
in both mineralocorticoids (eg, aldosterone) and
GHS Proc. November 2016; 1 (2): 133-135
glucocorticoids (eg, cortisol), but can also be
partial. The most dangerous issues are caused by
mineralocorticoid
deficiency—hyponatremia,
hyperkalemia, metabolic acidosis, and hypotension. Acute drops in serum sodium can result in
seizures, and acute rises in potassium can result
in cardiac dysrhythmias. Glucocorticoid deficiency causes hypoglycemia, fatigue, nausea, and
muscle weakness. Significant hypoglycemia can
also result in seizures. In severe cases, the patient
may develop shock and cardiovascular collapse.6
In this case report, we present an infant who developed adrenal crisis following the use of high-dose
dexmedetomidine over 11 hours for sedation in
our Pediatric Intensive Care Unit (PICU). To our
knowledge, this instance is the first reported case
of adrenal crisis and only the second case documenting clinically significant adrenal side effects
associated with this medication.
Case Description
A 49-day-old, ex-term male infant presented to
our PICU with respiratory syncytial virus-induced bronchiolitis. The patient had no significant past medical history at the time of admission. After failing heated high-flow nasal cannula
and CPAP (continuous positive airway pressure),
he was intubated for persistent, severe respiratory
distress and hypoxia.
133
Initially, continuous midazolam and fentanyl
were used for sedation and analgesia. He required
paralysis with continuous vecuronium shortly
after intubation and intermittently as his course
progressed.
On the day following intubation, two 2.5 mg (0.4
mg/kg/dose) doses of methylprednisolone were
administered due to concern for a reactive airway component. No other steroids were used as
his course progressed. He continued to require
frequent rescue doses of midazolam and fentanyl
for sedation. Adequate sedation was challenging, and he was trialed on continuous propofol,
scheduled lorazepam, and scheduled methadone.
On hospital day 11 (mechanical ventilation day
9), he was transitioned to dexmedetomidine in
hopes of decreasing narcotic and benzodiazepine
cumulative dosing. An initial loading bolus of 3
mcg (0.5 mcg/kg) was administered followed by
a continuous maintenance infusion at a rate of 3
mcg/kg/hr. The maintenance infusion rate was
decreased to 2 mcg/kg/hr 6 hours later due to
hypotension.
Approximately 11 hours after the infusion
started, the patient had onset of generalized
seizure activity. An electrocardiogram demonstrated right bundle branch block and junctional
escape. Serum chemistry at that time showed
sodium of 121 mMol/L, potassium of 9.8 mMol/L
(nonhemolyzed), bicarbonate of 18 mMol/L, and
glucose of 91 mg/dL. Random, nonstimulated
serum cortisol at that time was 10 mcg/dL.
Electroencephalogram confirmed generalized
seizure activity. Dexmedetomidine was discontinued, and stress dose intravenous hydrocortisone was started in addition to antiepileptics and
3% saline. A lumbar puncture was performed,
and studies were not indicative of meningitis.
By that afternoon, the patient’s serum sodium
had normalized and seizure activity had terminated. Hydrocortisone was slowly tapered and
ultimately discontinued over the next 4 days.
The patient had a complete recovery and was discharged home on hospital day 29 without any steroids or antiepileptics.
Discussion
Etomidate is a sedative medication that is well
known to cause adrenal suppression. The mechanism is direct inhibition of the 11β-hydroxylase enzyme in the adrenal cortex. Etomidate’s
imidazole ring structure is responsible for this
inhibition.7 The structure of dexmedetomidine is
134
similar to etomidate in that both have an imidazole ring.
As a result, there has been concern that dexmedetomidine could have similar effects on adrenal
function. One animal study showed decreased
serum cortisol and decreased cortisol response
to adrenocorticotropic hormone stimulation following exposure to dexmedetomidine.8 However,
studies in humans have largely shown no clinically significant impact on adrenocortical function,5,8,9 likely because dexmedetomidine causes
adrenal suppression at concentrations above 10-6
M while the therapeutic concentration in humans
is 10-9 M.5
There is at least 1 case report of transient adrenal suppression occurring with clinical use in a
pediatric patient.4 In that report, dexmedetomidine was administered to a 10 kg pediatric burn
patient for 6.5 days with a maximum dose of 2.7
mcg/kg/hr. The patient developed transient adrenal suppression 4 days after the infusion was discontinued. His presenting symptoms were lethargy and hypotension. This use is similar to our
maximum dose, but a much longer duration than
in our case.
Our patient had a more rapid onset of symptoms
with significant electrolyte abnormalities and seizures after a shorter duration of treatment. This
timeline correlated directly with the addition
of dexmedetomidine only 11 hours earlier and
corrected rather rapidly after it was discontinued and hydrocortisone was started. A random
cortisol was low, but not as significantly as one
would expect given the severity of the electrolyte
disturbances.
It is important to note that the serum cortisol
would be expected to be much higher in the setting of this patient’s critical illness. Furthermore,
the serum glucose was normal. This finding
argues for partial adrenal insufficiency primarily
impacting mineralocorticoid production rather
than complete insufficiency with concomitant
glucocorticoid deficiency. It is possible that continuation of the infusion may have ultimately
resulted in complete adrenal insufficiency.
The infusion rate administered to our patient was
higher than what is commonly reported in the
literature. The initial higher dose of 3 mcg/kg/hr
was chosen given the patient’s increased threshold for sedation noted with previous medications.
After decreasing to 2 mcg/kg/hr, the dosing was
within commonly accepted dosing ranges. The
high dose coupled with his critical illness may
GHS Proc. November 2016; 1 (2): 133-135
DEXMEDETOMIDINE-INDUCED ADRENAL CRISIS
explain the profound impact on adrenocortical
function. In follow-up, our patient has not experienced recurrence of his adrenal insufficiency that
would suggest an underlying adrenal pathology.
It is plausible that his serum drug concentrations rose above the 10-6 M level known to result
in adrenal suppression. There was no suggestion
of hepatic or renal impairment that could have
blunted metabolism or clearance of the drug
resulting in higher serum concentrations. Our
patient had not been treated with high-dose or
prolonged courses of steroids and was not receiv-
ing any other medications known to cause adrenal suppression. Thus, the most likely etiology for
his adrenal crisis is dexmedetomidine.
Conclusion
This case report suggests that, contrary to what
is reported in the current literature, the potential exists for considerable adrenocortical impact
from high-dose dexmedetomidine. As a result,
caution should be exercised when this medication
is used at high doses or in patients with possible
underlying adrenal pathology.
Correspondence
Address to:
Jeremy Loberger, MD,
Greenville Health
System, Internal
Medicine/Pediatrics,
701 Grove Rd,
Greenville, SC 29605
([email protected])
References
1. Phan H, Nahata M. Clinical uses of dexmedetomidine
in pediatric patients. Pediatr Drugs. 2008;10:49-69.
2. Bhana NL, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000;59:269-70.
3. Hayden JC, Breatnach C, Doherty DR, et al. Efficacy
of alpha-2-agonists for sedation in pediatric critical
care: a systematic review. Pediatr Crit Care Med.
2016;17:e66-75.
4. Tucker EW, Cooke DW, Kudchadkar SR, Klaus SA.
Dexmedetomdine infusion associated with transient
adrenal insufficiency in a pediatric patient: a case
report. Case Rep Pediatr. 2013;2013:207907.
5. Venn RM, Bryant, A, Hall GM, Grounds RM. Effects
of dexmedetomidine on adrenocortical function,
and the cardiovascular, endocrine and inflammatory
response in post-operative patients needing sedation
in the intensive care unit. Br J Anaesth. 2001;86:650-6.
6. Donohoue PA. Causes and clinical manifestations of primary adrenal insufficiency in children.
GHS Proc. November 2016; 1 (2): 133-135
UpToDate.
http://www.uptodate.com/contents/
causes-and-clinical-manifestations-of-primary-adrenal-insufficiency-in-children?source=search_
result&search=Causes+and+clinical+manifestations+of+primary+adrenaa+insufficiency+in+children&selectedTitle=1%7E76. Updated March 8, 2016.
Accessed June 28, 2016.
7. Albert SG, Ariyan S, Rather A. The effect of etomidate on adrenal function in critical illness: a systematic review. Intensive Care Med. 2011;37:901-10.
8. Maze M, Virtanen R, Daunt D, Banks SJ, Stover EP,
Feldman D. Effects of dexmedetomidine, a novel
imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies. Anesth
Analg. 1991;73:204-8.
9. Kallio A, Scheinin M, Koulu M, Ponkilainen R,
Ruskoaho H, Viinamäki O, Scheinin H. Effects of
dexmedetomidine, a selective alpha 2-adrenoceptor
agonist, on hemodynamic control mechanisms. Clin
Pharmacol Ther. 1989;46:33-42.
135
Case Studies
Radiographic Evidence of Diffuse Large B-cell Lymphoma
Presenting as Carpal Tunnel Syndrome
Anthony J. Horton, BS, and Jeffrey R. Wienke, MD
From the University of South Carolina School of Medicine Greenville, Greenville, SC (A.J.H., J.R.W.),
and Department of Radiology, Greenville Health System, Greenville, SC (J.R.W.)
Abstract
Any space-occupying lesion in the carpal tunnel can present with median nerve compression and
the symptomatology of carpal tunnel syndrome (CTS). Typically, history and physical examination
reveal sufficient findings to warrant further investigation with electrophysiologic testing; imaging
studies, however, are not routinely considered. Here, we present a case of CTS resulting from carpal tunnel infiltration by a soft-tissue, non-Hodgkin lymphoma as evidenced by non-contrast MRI
(magnetic resonance imaging).
Compression of the median nerve at the wrist,
or carpal tunnel syndrome (CTS), is the most
common disorder affecting the median nerve.
The etiology is multifactorial, with structural and
genetic factors playing a much more significant
role than the classic teaching of occupational
factors such as repetitive hand use and microtrauma.1 However, infiltration of the transverse
carpal ligament (as in amyloidosis or multiple
myeloma) or thickening of the connective tissue
(as occurs in rheumatoid arthritis, acromegaly,
mucopolysaccharidosis, and hypothyroidism)
can create median nerve impingement as well.
This compression produces a syndrome of sensory loss and paresthesia affecting the palmar
aspect of the thumb, index, and middle fingers,
in addition to the radial half of the ring finger.
Weakness and atrophy of intrinsic muscles of the
hand innervated by the median nerve, such as
the abductor pollicis brevis, typically occurs in
advanced or prolonged cases of compression.
Diagnosis relies on clinical history, physical examination maneuvers such as the Phalen’s maneuver,
and the presence of Tinel’s sign, though the diagnosis is typically confirmed via nerve conduction
studies demonstrating a delayed impulse.2 Complex clinical presentations or cases that are refractory to standard treatment may warrant additional
diagnostics and management as discussed in this
case report of an atypical etiology for CTS.
136
Case Description
M.R. is a 78-year-old Caucasian man with a past
medical history of hypertension, hyperlipidemia,
hemochromatosis, and left testicular lymphoma
with disease-free status following orchiectomy,
chemotherapy, and radiation therapy that began
3 years prior to presentation. Initially, M.R. presented to his primary care provider with right
hand weakness, tingling, and occasional numbness. Physical examination was notable for reproducibility of paresthesias with wrist flexion,
subtle thenar atrophy, and mild anterior wrist
swelling without erythema.
Diagnostic work-up, including nerve conduction
studies, revealed delayed nerve conduction of
the median nerve across the carpal tunnel along
with mild reduction in conduction velocity along
the ulnar nerve at the cubital tunnel. The patient
subsequently underwent elective right carpal and
cubital tunnel release, during which the median
nerve was found to be intact with nonspecific
hyperemic changes beneath the transverse carpal
ligament. Postoperative care was notable for acute,
same-day right hand pain that was subsequently
treated with pregabalin on an outpatient basis.
In the ensuing weeks after carpal and cubital tunnel release, the patient experienced moderate resolution of weakness and paresthesias of his right
hand; however, on postoperative week 6, M.R. preGHS Proc. November 2016; 1 (2): 136-139
DLBCL PRESENTING AS CARPAL TUNNEL SYNDROME
sented to his primary care physician with recurrent edema, new erythema, and significant pain
in his right wrist with radiation into the hand in
a median nerve distribution. Physical examination
revealed a well-healed surgical scar with no signs of
infection or dehiscence, but sensory loss along the
distribution of the distal median nerve was noted.
Subsequent non-contrast MRI (magnetic resonance imaging) of the right upper extremity
revealed mild median nerve thickening with
extensive, lobulated soft-tissue abnormalities
throughout the hand, particularly at the distal
ulnar margin of the thenar eminence surrounding
the flexor tendons. Insinuating extensions projected between the second, third, and fourth metacarpals. Lobulated soft-tissue abnormalities were
further noted in the dorsum of the first web space
and surrounding the hypothenar musculature.
Discussion
Lymphomas are an assorted group of malignancies classically arising from lymph nodes or
lymphatic tissues such as the spleen, Waldeyer’s
ring, and the thymus. However, extranodal presentations of non-Hodgkin lymphomas occur at
reported incidence rates of 25%–40%. When they
occur, extranodal lesions are more common in
Figure 1
Coronal T1 MRI of the right hand reveals lobulated soft-tissue
abnormality with signal intensity slightly higher than surrounding
musculature.
Compared to surrounding musculature, this
abnormal tissue presented with moderately
increased signal intensity on T1 and T2 images
(Figs. 1–2). Additionally, proton density fat saturation images of the lobulated masses revealed
mildly increased signal compared to surrounding
soft tissue (Fig. 3). No bony destruction or erosive changes were identified. Ultimately, the differential diagnosis based on the imaging studies
included a recurrence of soft-tissue lymphoma,
fibromatosis, or postoperative infection contributing to tenosynovitis.
Given the patient’s history of testicular lymphoma, new imaging findings, acute initial onset
of symptoms, and recurrence of painful swelling
at the right wrist following carpal and cubital tunnel release, an excisional biopsy of the mass was
performed. Biopsy samples identified a diffuse
large B-cell lymphoma, which likely represented a
recurrence of his prior testicular lymphoma.
Whole-body nuclear medicine positron emission topography (PET) with overlying computed
tomography (CT) images were obtained for staging purposes. Multifocal hypermetabolic activity
was noted throughout the right upper extremity,
including the right wrist and numerous lymph
nodes tracking to the right axilla. Further hypermetabolic activity was noted in a right adrenal
mass, proximal right tibial shaft, distal left thigh
in the anteromedial subcutaneous tissue, and the
left orbit (Fig. 4). With this advanced stage and
tumor burden, chemotherapy with rituximab,
etoposide, steroid (methylprednisolone), Ara-C
(cytarabine), and platinum (cisplatin) (R-ESHAP
therapy) and palliative upper extremity radiation
therapy were initiated.
GHS Proc. November 2016; 1 (2): 136-139
Figure 2
Axial T2 MRI of the right hand shows soft-tissue abnormality with
very mildly increased signal that is isointense to adjacent muscle and
fat tissue.
137
Figure 3
Axial proton density fat saturation MRI demonstrates extensive, lobulated
soft-tissue abnormality throughout the right hand, particularly at the distal
margin of the thenar eminence surrounding the flexor tendons insinuating
between the second to fourth metacarpals. The lesion is isointense to
surrounding soft-tissue structures.
Figure 4
Whole-body Nuclear Medicine Positron Emission Topography with
overlying Computed Tomography (NM PET/CT) demonstrates multifocal
hypermetabolic activity in the right hand, right upper-extremity lymph
nodes, right adrenal gland, and subcutaneous proximal right thigh among
other scattered foci.
men and have been documented in almost every
organ system.3
Most commonly, extranodal presentations of
non-Hodgkin lymphoma occur with simultaneous involvement of lymphatic structures, and an
extranodal site is only considered to be the primary lesion if no additional evidence of neoplasia
is discovered during staging.4 Even so, the presence of a tumor or mass outside of lymph node
tissue is often not considered a lymphoma until
after tissue biopsy and histopathology establish
the diagnosis, with the most common histological subtypes being follicular and diffuse large
B-cell lymphomas. Specific to this case, only 0.2%
of extranodal non-Hodgkin lymphomas present
with hand involvement.5
Imaging characteristics of lymphoma vary
depending on location and specific subtype of
disease. Computed tomography is the mainstay
of imaging, specifically for its role in tumor staging. However, MRI has particular utility in central nervous system lymphomas, and ultrasound
(US) techniques can be used to access disease
with lymph node involvement.6
For the patient presenting with median nerve
compression, imaging studies are neither explicitly necessary nor routinely ordered. Still, imaging may be useful when there is a suspicion for
local structural disease such as bony deformity,
primary bone or joint disease, or tumor. Wrist
films and CT are only indicated to evaluate carpal tunnel stenosis or bone tumors, with MRI or
high-frequency US being more useful for direct
visualization of the median nerve and other soft
tissues.
Use of MRI or US is appropriate to identify a
space-occupying lesion in the soft tissue such
as a tumor, ganglion cyst, lipoma, or muscle
fiber hypertrophy, with MRI in particular having a 96% sensitivity and 33%−38% specificity
for this purpose.7 More recently, several studies
have demonstrated the utility of ultrasonography to detect CTS due to the apparent increase
in cross-sectional area of the median nerve in the
diseased state, though a defined cut-off for diagnosis has not been adequately determined.8
For this case of rapid recurrence of CTS following surgical correction, detailed imaging of the
affected hand, including MRI of the wrist or US
of the carpal tunnel, was warranted to evaluate
for atypical etiologies of median nerve compression, especially given the patient’s history of lymphoma and lack of structural abnormalities on
138
GHS Proc. November 2016; 1 (2): 136-139
DLBCL PRESENTING AS CARPAL TUNNEL SYNDROME
physical exam. Review of the literature reveals
that this instance is not an isolated presentation
of disease, as there have been case reports of other
neoplastic processes, including T-cell lymphoma
and primary non-Hodgkin lymphoma, infiltrating the distal median nerve and leading to CTS.9,10
ents with isointense to intermediate hyperintensity on both T1 and T2 images when compared
to surrounding muscle and fat tissue, while tenosynovitis may present with intermediate signal
debris in the tendon sheath itself plus high intensity on T2 weighted images.6
Consistent with the images in this case, nonosseous musculoskeletal lymphomas present with
isointense or intermediate hyperintensity on T1
and T2 images when compared to surrounding muscle and fat. This finding is reiterated on
proton density fat saturation MR images, where
soft-tissue lymphoma may be isointense to surrounding soft tissues as in this case.
Conclusion
Fibromatosis and tenosynovitis were considered
in the differential of this patient’s imaging findings. However, fibromatosis more classically pres-
Neoplastic processes, including primary and
metastatic non-Hodgkin lymphomas, can infiltrate the wrist, compress the median nerve, and
present as CTS; thus, neoplastic disease should
remain in the differential diagnosis for all
patients, particularly when disease is unilateral.
When an infiltrative process is suspected, MRI is
the imaging modality of choice, though high-frequency US of the median nerve traversing the
carpal tunnel is another viable option.
Correspondence
Address to:
Jeffrey R. Wienke,
MD, Greenville Health
System, Greenville
Radiology, 1210 W
Faris Rd, Greenville,
SC 29605
([email protected])
References
1. Calderon S, Anthony S, Ring D. The quality and
strength of evidence for etiology: example of carpal
tunnel syndrome. J Hand Surg Am. 2008;33:525-38.
Press OW, Burns LJ, Caligiuri M. eds. Williams
Hematology. 9th ed. New York, NY: McGraw-Hill;
2015:1569-86.
2. Ropper AH, Samuels MA, Klein JP. Chapter 46. Diseases of the peripheral nerves. In: Ropper AH, Samuels MA, Klein JP, eds. Adams & Victor’s Principles
of Neurology. 10th ed. New York, NY: McGraw-Hill;
2014:1251-1325.
6. Frampas E. Lymphomas: Basic points that radiologists should know. Diagn Interv Imaging.
2013;94:131-44.
3. Newton R, Ferlay J, Beral V, Devesa SS. The epidemiology of non-Hodgkin’s lymphoma: comparison of nodal and extra-nodal sites. Int J Cancer.
1997;72:923-30.
8. Cartwright MS, Hobson-Webb LD, Boon AJ, et al.
Evidence-based guideline: neuromuscular ultrasound for the diagnosis of carpal tunnel syndrome.
Muscle Nerve. 2012;46:287.
4. Scutellari PN, Orzincolo C, Franceschini F. The
hand in hematologic disease. Minerva Medica.
1993:84:511-21.
9. Chevalier X, Hermine O, Authier FJ, Gaulard P,
Gherardi RK. Carpal tunnel syndrome due to T cell
lymphoma. Arthritis Rheum. 1995;38:1707-9.
5. Press OW, Lichtman MA. Chapter 95. General considerations for lymphomas: epidemiology, etiology,
heterogeneity, and primary extranodal disease. In:
Kaushansky K, Lichtman MA, Prchal JT, Levi MM,
10. Evans GR, King JC, McGinnis MR, Wilgis EF. Primary non-Hodgkin’s lymphoma presenting in the
upper extremity: a case report. J Hand Surg Am.
1993;18:612-4.
GHS Proc. November 2016; 1 (2): 136-139
7. Kleopa KA. Carpal tunnel syndrome. Ann Intern
Med. 2015;163:ITC1.
139
Case Studies
Management of Brujeria, a Culture-Bound Syndrome
Joseph T. Mingoia, MD, and Taral R. Sharma, MD, MBA
From the Department of Psychiatry, Carilion Clinic, Roanoke, Va (J.T.M.), and University of South
Carolina School of Medicine Greenville, Greenville, SC (T.R.S.)
Abstract
In medicine, a culture-bound syndrome is an array of aberrant behavior phenomena often recognized as illness by most participants of a particular culture. Although considered uncommon in the
United States (US), various culture-bound syndromes have been reported in Hispanic populations.
The population of Hispanic immigrants in the US is on the rise, and the presence of such syndromes
should not be overlooked. Presently, published literature describing culture-bound syndromes, specifically Brujeria—Spanish for witchcraft—is very limited. The aim of this report is to provide a detailed description of a patient with Brujeria, including presentation and subsequent psychiatric and
medical management.
A
culture-bound syndrome is an array of
aberrant behavior phenomena often recognized as illness by most participants
of a particular culture.1 Although uncommon
in the United States (US), various culture-bound
syndromes have been reported in Hispanic populations.2 According to the US Census Bureau,
Hispanics constitute the nation’s largest ethnic
minority (55 million/17%).3 As such, the presence of such syndromes should not be surprising or overlooked. Presently, published literature
describing culture-bound syndromes, specifically Brujeria—the Spanish word for witchcraft
—is very limited.4 This case report describes the
presentation and management of a 27-year-old
Honduran woman with Brujeria.
Case Description
A 27-year-old Honduran woman with a medical
history significant for chronic migraines presented to our Emergency Department (ED) with
an intractable headache. The patient immigrated
to the US 6 years prior and spoke little English.
Through a Spanish-speaking, hospital-based interpreter, the patient reported severe (10, on a pain
scale of 10), intermittent headaches, usually located
in her bitemporal regions, that progressively worsened 4 days prior to ED presentation.
The headaches were uncontrolled by over-thecounter naproxen and caused photophobia,
140
blurry vision, and pain around her right eye. The
patient also complained of bilateral leg weakness
with sharp, stabbing, and squeezing pain in both
legs. She was admitted to the medical service and
underwent a head CT (computed tomography),
lumbar puncture with cerebrospinal fluid exam,
syphilis screen, thyroid panel, comprehensive
metabolic profile, complete blood count, urinalysis, urine drug screen, and urine pregnancy
test—all of which were inconclusive of any acute
medical problems.
Within a short time (1–2 days), the patient started
displaying symptoms of depression and Psychiatry was consulted. The patient reported anhedonia, poor concentration, guilt, and low energy,
which she attributed to financial constraints and
unemployment. She also reported paranoia that
her neighbors and friends from Honduras were
talking about her. She denied any manic symptoms, any history of suicidal or homicidal ideations, and any alcohol or illicit substance abuse.
The patient’s boyfriend said that during her episodes at home she would hold onto the walls to
walk, did not appear to know where she was, and
would often talk to people who were not present
and motion as if speaking to someone on the telephone. The patient acknowledged having visual
hallucinations, specifically of a young child with
a pale face lying next to her in bed.
GHS Proc. November 2016; 1 (2): 140-142
MANAGEMENT OF BRUJERIA, A CULTURE-BOUND SYNDROME
At this point, one of the hospital interpreters
disclosed an earlier event when the patient was
visited by her spiritual advisor. According to the
interpreter, shortly after the spiritual advisor’s
visit, the patient began writhing and twisting
as if being attacked or stabbed. The interpreter
went on to explain how this reaction was consistent with Brujeria from their home culture. The
patient admitted to feeling possessed during her
advisor’s visit and later disclosed that her aunt
practiced witchcraft and had persecuted others in
a similar fashion.
Mental status examination revealed the patient
to be in mild distress, but cooperative, alert, and
oriented to person, place, and time. There were
no fluctuations in consciousness, and no deficits were noted following the mini-mental state
examination. Differential diagnosis included
Brujeria, somatoform disorder, conversion disorder, major depression disorder, generalized anxiety disorder, and panic disorder.
Both patient and boyfriend believed in Brujeria
as a culture-bound syndrome and associated
her current symptoms with this syndrome. The
patient elected prayer (led by the Psychiatric consult team) and spiritual healing over medication
management; no psychotropic medications were
administered. Following the prayer, the patient’s
headache and leg weakness improved significantly. The patient was discharged on hospital
day 4 and encouraged to pray with her boyfriend,
seek the help of their spiritual advisor, and follow-up with her primary care physician.
Discussion
Each human society has its own distinct body
of beliefs. Brujeria is a specific type of witchcraft
associated with Afro-Latin religious systems that
frequently entails invocation of various spells and
deities for either good or evil.5 It is believed that
life problems and/or psychosomatic complaints
may result from Brujeria. The practice of Brujeria (eg, rituals, spellwork, healing, etc.) is diverse
and dependent on location and dominant religion. Published literature on the treatment of
culture-bound syndromes is sparse, especially in
the US. Reported treatments, however, include
psychoanalysis, cognitive behavioral therapy, and
incorporation of culture-specific treatments from
values prevalent in the population (eg, shaman,
priest, curandero, spiritual leader, family, etc.).6
In this case report, the value of the interpreter
should not be underestimated. If available, hospital-based and/or professional interpreters
GHS Proc. November 2016; 1 (2): 140-142
should be utilized, as one of our interpreters
provided valuable information regarding the
symptoms that became manifest in the presence
of the patient’s spiritual advisor, ultimately leading to the identification of the cultural association. Knowledge of the social context is central
to diagnosing the syndrome. Without understanding contextual association, many similar
presentations could go unrecognized. If a symptom cluster does not represent a normal response
and testing is inconclusive, we recommend that
clinicians consider asking patients if they have a
preconceived notion of a cultural cause for their
condition. The clinician should also assess if there
are any language barriers in eliciting symptoms
or understanding the patient’s expressions. If so,
once again, we recommend use of an interpreter.
Correspondence
Address to:
Taral Sharma, MD,
Patrick B. Harris
Psychiatric Hospital,
130 Highway 252,
Anderson, SC 29621
([email protected])
We do, however, recognize that our case was
unique, as most professional interpreters do not
have the training or expertise to conduct an
assessment of complex psychological issues, nor
should they be expected to assess the patient’s
religious behavior. Most hospitals have the ability to consult staff chaplains; this group my prove
helpful to the clinician and patient, as they typically have expertise and experience in working
with diverse religious populations and persons
presenting with various spiritual values and
beliefs.
Another important aspect exposed in this case
report was the need for open communication
between the clinicians (psychiatry and medicine)
and the patient. Once our patient believed Brujeria to be the cause of her illness and symptoms,
specific conversations regarding her expectations
and preferences for medications or therapy followed, ultimately ending in no medications being
administered. Some patients may believe the psychological disorder to be somatically based and
should be treated with medication, while others
may view medication as too simplistic and prefer psychotherapy. The earlier the clinician can
involve the patient in a treatment/management
conversation so as to establish realistic expectations for rate of recovery, the better.
Conclusion
In conclusion, we present a case of patient suffering from Brujeria, a culture-bound syndrome
considered uncommon in the US and rarely
described in the literature. As the US immigrant
population continues to grow, so does the need
for clinicians to increase their cultural awareness
of possible culture-bound syndromes.
141
References
1. American Psychiatric Association. Outline for cultural formulation and glossary of culture-bound
syndromes. In: Diagnostic and Statistical Manual of
Mental Disorders. 4th ed. Washington, DC; American Psychiatric Association; 2000:843-850.
2. Sadock BJ, Sadock VA, Ruiz P. Culture-bound syndromes. In: Sadock BJ, Sadock VA, Ruiz P, eds.
Kaplan and Sadock’s Comprehensive Textbook of
Psychiatry. 9th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009:2519-2538.
3. United States Census Bureau. FFF: Hispanic Heritage Month 2015. http://www.census.gov/newsroom/
142
facts-for-features/2015/cb15-ff18.html. Updated September 14, 2015. Accessed July 12, 2016.
4. Wetli CV, Martinez R. Brujeria: manifestations of
Palo Mayombe in South Florida. J Fla Med Assoc.
1983;70:629-34.
5. Sandoval MC. Santeria as a mental health care system:
an historical overview. Soc Sci Med. 1979;138:137-51.
6. Sandoval M. Santeria: Afro-Cuban concepts of
disease and its treatment in Miami. J Oper Psych.
1977;8:52-63.
GHS Proc. November 2016; 1 (2): 140-142
Case Studies
Levamisole-Induced Necrosis Syndrome Associated With
Cocaine Use
Richard O’Neal, MD, and Sheena Henry, MD
From the Department of Medicine, Greenville Health System, Greenville, SC (R.O., S.H.)
Abstract
With the increasing prevalence of levamisole contamination of cocaine, there has been a concurrent rise in patients presenting with a vasculitis-like syndrome characterized by purpura, hemorrhagic bullae, and skin necrosis. The following case describes a 43-year-old woman who presented
with rapidly worsening painful purpura on her extremities and nose, leukopenia, and perinuclear
anti-neutrophil cytoplasmic antibodies (p-ANCA) following cocaine use. She developed extensive
necrosis necessitating multiple wound debridements but eventually recovered with supportive care
and cessation of cocaine.
W
ith the continued demand for cocaine,
and an estimated 1.5 million active
users in the United States (US), various adulterants are added during its production and distribution. In 2003, levamisole was
first detected in cocaine, and by 2014, the US
Drug Enforcement Administration reported up
to 78% of cocaine in the US now tested positive
for levamisole.1,2 As an additive, levamisole is
thought to potentiate the stimulatory effect of
cocaine by blocking the reuptake of dopamine in
presynaptic neurons.3
Historically, levamisole was authorized for use
as a chemotherapy drug, as well as a treatment of
rheumatoid arthritis and pediatric nephrotic syndrome.2,4-6 Feared complications from levamisole
use were first documented in 1978 and included
agranulocytosis, arthritis, skin ulcers, and cutaneous vascultitis.2,6,7 Due to increasing concerns
over side effects, the Food and Drug Administration removed the drug from the market in
2000.2,6 Although levamisole is still available as
a veterinary antihelminthic, it has been adopted
by the drug trade as a cutting agent.1,3,4,8 Whereas
levamisole-induced necrosis had previously been
an iatrogenic side effect, by 2009 this complication was experiencing a resurgence due to its correlation with cocaine use.2
GHS Proc. November 2016; 1 (2): 143-146
Case Description
A 43-year-old African American woman with a
history of sarcoidosis and chronic anemia presented with a 4-day history of painful areas of
deep violet discoloration that had been expanding bilaterally along the lower extremities. Examination revealed broad, circumferential areas of
intensely warm and painful purpura (Fig. 1). In
addition, cutaneous necrosis was noted at the tip
of the nose (Fig. 2) and helix of the ears.
Figure 1
Purpura fulminans with hemorrhagic bullae associated with
levamisole-contaminated cocaine.
143
On admission, the patient was anemic and leukopenic (Table 1). Review of records revealed the
patient had a history of intermittent leukopenia, a work-up for which had been negative just
5 months before her current presentation. On
admission, intravenous methylprednisolone was
administered to treat a possible leukocytoclastic
vasculitis.
dorsal portions of the lower extremities. On day
2 of hospitalization, a venous duplex was negative for the presence of deep vein thromboses. A
subsequent vasculitis work-up (Table 2) revealed
elevated perinuclear anti-neutrophil cytoplasmic
antibodies (p-ANCA); however, a skin biopsy
revealed only necrosis without evidence of vasculitis.
During the first 24 hours of admission, the purpuric lesions worsened, with the patient developing large bilateral hemorrhagic bullae along the
Upon further investigation, the patient reported
that 3 days prior to admission she had begun using
crack cocaine again. Review of the literature at
that time revealed similarities to Levamisole-Induced Necrosis Syndrome (LINES), given the positive p-ANCA markers, recent cocaine use, and
cutaneous symptoms. The patient was provided
supportive care with hydration, wound care, and a
long steroid taper. After 9 days of hospitalization,
the patient was discharged home with physical
therapy. At time of discharge, the purpura had
improved, but the large bullae persisted.
Figure 2
Necrosis of the nose associated with levamisole-contaminated cocaine.
Sixteen days after discharge, the patient was readmitted to the hospital after rupture of the large
bullae with complaints of purulent drainage.
X-rays of the lower extremities revealed diffuse
soft-tissue swelling bilaterally with evidence of
gas within the soft tissue. A new area of purpura,
now also with concern for infection, was even
present on the right upper extremity. Surgery was
consulted, and the patient was started on vancomycin, meropenem, and metronidazole. Tissue cultures taken from her wounds ultimately
revealed Escherichia coli. A muscle biopsy on
day 4 of hospitalization revealed necrotic skeletal
muscle with patchy acute inflammation, necessitating extensive debridement by vascular surgery
twice during her hospital stay (days 4 and 19)
and skin grafting. Below-knee amputation was
considered due to the extent of necrosis, but was
able to be avoided. After 44 days of hospitalization, the patient was discharged with close primary care provider and wound care follow-up.
Eleven months posthospitalization, the patient
reported continued abstinence from cocaine
without recurrence of purpura or necrosis; her leg
wounds resolved, but there was autoamputation
of the tip of her nose.
Discussion
LINES, also known as levamisole-induced pseudovasculitis, is an entity that has only been characterized within the last decade.2 LINES has a
gender partiality for females (3:1), with a mean
age of onset of 44 years.2 Although definitive
diagnostic criteria have not yet been established,
cases of LINES share certain clinical features.2,9,10
144
GHS Proc. November 2016; 1 (2): 143-146
LEVAMISOLE-INDUCED NECROSIS SYNDROME AND COCAINE USE
As described in this case, affected patients often
have a tender rash of purpuric lesions on the
extremities, nasal tip, ears, as well as on the
trunk of the body and the digits of the hands and
feet.2,9,10 The most severe cases present with the
tender retiform coalescing purpura, hemorrhagic
bullae, and skin necrosis as seen in this patient.4
In some instances, the degree of necrosis may
necessitate amputation.4
Laboratory analysis often reveals elevated
inflammatory markers, agranulocytosis, antineutrophil cytoplasmic antibodies, antiphospholipid antibodies, and antihuman elastase antibodies.2,3,6,7,9 Given the chronicity of cocaine use
in this patient, there may have been an element
of levamisole that was causing her chronic leukopenia, which had yielded a negative work-up
in the months prior to this hospitalization. Also,
the patient later revealed that she had small purpuric lesions in the past that were less severe and
had resolved without intervention. The patient’s
positive p-ANCA and antimyeloperoxidase antibodies, although not specific to LINES (Table 3),
are often presenting factors of this syndrome as
well. 2,3,6,7,9 Though not available at all institutions,
urine or blood gas chromatography and mass
spectrometry within 48 hours can often detect
levamisole, but is not required for diagnosis.3,6
Pathologic findings may vary from leukocytoclastic vasculitis of the small vessels to thrombotic microangiopathy.2,9 However, biopsies often
reveal only gross tissue necrosis, leading some to
classify this disease as a pseudovasculitis.2
The vast majority of illicit drug users exposed
to levamisole do not develop clinical symptoms;
however, those who do may require hospitalization and supportive care to minimize the morbidity associated with tissue necrosis and agranulocytosis. The mainstay of treatment is cocaine
cessation.1,3,4,8,11
Conclusion
With the increasing prevalence of levamisole-contaminated cocaine and the number of
illicit drug users potentially exposed, it is crucial
that healthcare providers be aware of this condition. Though some laboratory tests are of value
(p-ANCA, antihuman elastase antibodies, antiphospholipid antibodies), the most important
aspect of diagnosis is recognition of clinical exam
findings in the presence of cocaine exposure.
Through early recognition and diagnosis, healthcare providers can not only initiate appropriate
supportive care early, but also educate patients on
the importance of cocaine cessation.
GHS Proc. November 2016; 1 (2): 143-146
Table 1
Admission laboratory values.
Hematology
Result
Reference Interval
2.7
4.5–11.0
Neutrophils
65%
50%–70%
Bands
14%
0%–5%
Lymphocytes
15%
20%–40%
Monocytes
4%
0%–10%
Basophils
2%
0%–0.2%
7.7
12–16
Hematocrit (%)
22.9
36–48
Platelet (10*3/uL)
432
140–440
Mean corpuscular volume (fL)
63.5
80–100
Reticulocyte (%)
3.8
0.5-1.5
Result
Reference Interval
62
<20
1:80
<1:40
>1:640
<1:20
Myeloperoxidase antibody
1.8
<1.0
Angiotensin 1-converting enzyme
81
9–67
Phosphatidylserine antibodies (IgM)
89
<25
White blood cell count (10*3/uL)
Hemoglobin (g/dL)
Table 2
Vasculitis-specific laboratory values.
Immunology
Erythrocyte sedimentation rate
Serum antinuclear antibodies
p-ANCA
Table 3
Differential diagnoses.
Positive p-ANCA
Positive Anti-myeloperoxidase
Antibodies
Ulcerative colitis, Crohn’s disease
Microscopic polyangiitis
Autoimmune chronic active
hepatitis
Polyarteritis nodosa
Primary biliary cirrhosis
Eosinophilic granulomatosis with
polyangiitis
Primary sclerosing cholangitis
Granulomatosis with polyangiitis
Rheumatoid arthritis
Idiopathic crescentic
glomerulonephritis
Eosinophilic granulomatosis with
polyangiitis
Focal necrotizing and crescentic
glomerulonephritis
Anti-glomerular basement
antibody disease
Warfarin-induced skin necrosis
Heparin-induced
thrombocytopenia
145
Correspondence
Address to:
Richard O’Neal, MD,
Greenville Health
System, Department
of Medicine, 5th Floor
Support Tower, 701
Grove Rd, Greenville,
SC 29605 (roneal@
ghs.org)
References
1. Gross RL, Brucker J, Bahce-Altuntas A, et al. A
novel cutaneous vasculitis syndrome induced by
levamisole-contaminated cocaine. Clin Rheumatol.
2011;30:1385-92.
2. Roberts JA, Chevez-Barrios P. Levamisole-induced
vasculitis: a characteristic cutaneous vasculitis associated with levamisole-adulterated cocaine. Arch Pathol
Lab Med. 2015;139:1058-61.
3. Souied O, Baydoun H, Ghandour Z, Mobarakai N.
Levamisole-contaminated cocaine: an emergent
cause of vasculitis and skin necrosis. Case Rep Med.
2014;434717.
4. Arora NP, Jain T, Bhanot R, Natesan Sk. Levamisole-induced leukocytoclastic vasculitis and neutropenia in a patient with cocaine use: An extensive case
with necrosis of skin, soft tissue, and cartilage. Addict
Sci Clin Pract. 2012;7:19.
5. Amery WK, Bruynseels JP. Levamisole, the story and
the lessons. Int J Immunopharmacol. 1992;14:481-6.
6. Lee KC, Ladizinski B, Federman DG. Complications
associated with use of levamisole-contaminated
cocaine: an emerging public health challenge. Mayo
Clin Proc. 2012;87:581-6.
146
7. Macfarlane DG, Bacon PA. Levamisole-induced vasculitis due to circulating immune complexes. Br Med
J. 1978;1:407-8.
8. Mouzakis J, Somboonwit C, Lakshmi S, Rumbak
M, Sinnott J, Cherpelis B, Keshishian J. Levamisole
induced necrosis of the skin and neutropenia following intranasal cocaine use: a newly recognized syndrome. J Drugs Dermatol. 2011;10:1204-7.
9. Bose N, Calabrese LH. Recognizing rheumatologic
aspects of cocaine abuse. Psychiatric Times. http://
w w w.psychiatrictimes.com/ar ticles/recognizing-rheumatologic-aspects-cocaine-abuse. Published
March 2, 2012. Accessed December 1, 2015.
10. Graf J, Lynch K, Yeh CL, et al. Purpura, cutaneous
necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine.
Arthritis Rheum. 2011;63:3998-4001.
11. Metwally O, Hamidi M, Townsend L, Abualula H,
Zaitoun A, Lall T. The cocaine trail: levamisole-induced leukocytoclastic vasculitis in a cocaine user.
Subst Abus. 2013;34:75-7.
GHS Proc. November 2016; 1 (2): 143-146
Cancer Institute: Making Lives Longer
On the national stage, GHS’ Cancer Institute is making breakthroughs in cancer research and treatment—and making
innovative, comprehensive care available close to home for upstate patients:
• In 2014, 34 programs were lauded by the National Cancer Institute as a leader in community-site care delivery and
research: GHS’ Cancer Institute is the only community-based program originating in SC to attain this distinction
• GHS’ Institute for Translational Oncology Research includes a Phase I clinical research unit, a biorepository services
platform, and proteomics and genomics capabilities: Thus far, it has enrolled in excess of 1100 patients in 150
studies, including 17 first-in-human trials, with 12+ drugs moving to FDA approval and 40+ articles published
• GHS’ Blood and Marrow Transplant Program, the first in SC to receive accreditation for autologous transplantation,
provides both autologous and allogeneic transplants from matched related, unrelated and haplotype donor sources
• GHS’ Center for Integrative Oncology and Survivorship, one of the first programs of its kind in the nation, offers
evidence-based complementary therapies in addition to conventional cancer treatment and research studies
For more information, please call (864) 455-7070.
ghs.org/cancer
16-0316
November 2016 | Volume 1 | Issue 2
Viewpoint
89 OPINION Monoclonal Antibodies, Blood-Brain
Barrier and Disability in Multiple Sclerosis:
Time for Combination Therapies by J Avasarala
92 TEACHABLE MOMENT Do I Really Need to
Stop Taking Estrogen? by CW Fox et al
94 VALUE VIGNETTE Choosing High-Value
Care in Suspected Lower Extremity Deep Vein
Thrombosis by M Won and S Connelly
Special Article
97 Perceptions of and Preferences for a Mobile
Health Clinic for Underserved Populations
by M Gillispie et al
Original Research
105 The Gynecology and Obstetrics Fundamentals
of Residency Internship Training (GO FOR IT)
Trial by FS Nuthalapaty et al
113 Blood Loss and Transfusions After Pericardial
Closure Using a Porcine-Derived Extracellular
Matrix by TG Johnson et al
121 Does Comprehensive Dementia Education
Impact Self-Efficacy Among Family Caregivers
in the Community? by X Pan et al
126 Insurance Status of Deceased Organ Donors
by JD Cull et al
Case Studies
130 Catastrophic Upper Gastrointestinal Bleed in
Roux-en-Y Gastric Bypass Patients From Ulcer
Erosion Into the Splenic Artery: Details of
Rapid Surgical Management by AJ Jones et al
133 Dexmedetomidine-Induced Adrenal Crisis in
an Infant by JM Loberger et al
136 Radiographic Evidence of Diffuse Large B-cell
Lymphoma Presenting as Carpal Tunnel
Syndrome by AJ Horton and JR Wienke
140 Management of Brujeria, a Culture-Bound
Syndrome by JT Mingoia and TR Sharma
143 Levamisole-Induced Necrosis Syndrome
Associated With Cocaine Use
by R O’Neal and S Henry
117 Impact of Methicillin-Resistant Staphylococcus
aureus (MRSA) Decolonization Protocol on
Colonization and Infection Rates in a Level III
Neonatal Intensive Care Unit by M Griffin et al
16-0467
11/16