Greenville Health System Proceedings vol 2 issue 1 by Prisma Health

June 2017 | Volume 2 | Issue 1

ISSN 2475-837X (print)

ISSN 2475-8434 (online)

Greenville Memorial Hospital, Greenville, SC (part of Greenville Health System)

Clinical and Translational Research Graduate Certificate hsc.ghs.org/clinical-translational-research-certificate/ Clemson University’s Department of Public Health Sciences and Greenville Health System (GHS) have partnered in offering a graduate-level certificate program in Clinical and Translational Research. The goal of this program is to enhance the research capabilities of GHS physicians, nurses, research support staff, and allied health professionals to conduct a continuum of clinical and translational research in chronic disease, value-based care, medical and nursing education, health disparities, cancer, and other focus areas. Students in the program will experience first-hand the integral role multidisciplinary team science plays in contemporary research. Graduates of the program are expected to help lead research in their respective clinics or nursing units. Graduates will have acquired the skills to author research funding proposals, research protocols, to conduct

the research, analyze the results, and summarize findings.

Curriculum

This program has been carefully designed to meet the needs of GHS employees. Courses are offered once a week on weekday evenings at the University Center of Greenville (UCG). Most students take only one course a semester while completing the certificate. Upon completion, students may elect to apply the credits toward Clemson’s new MS in Applied Health Research & Evaluation degree also offered at UCG.

The Graduate Certificate in Clinical and Translational Science curriculum requires 12 credits which include a 8-credit core of required 800-level HLTH courses and 4 elective credits at the 800-level. Courses must be selected from the curriculum below.

We are now recruiting the third cohort of students who will start the program in midAugust. To learn more about the program, GHS tuition assistance policy and how to apply please visit the website: http://hsc.ghs.org/clinicaltranslational-research-certificate/.

REQUIRED COURSES • HLTH 8120 - Clinical & Translational Science (2) • HLTH 8210 - Health Research I: Design & Measurement (3) • HLTH 8090 - Epidemiological Research (3)

ELECTIVE COURSES • HLTH 8140 - Health System Quality Improvement (2) • HLTH 8130 - Population Health & Research (2) • *MTHSC 8050 - Data Analysis (3)

Benefits of Completing this Certificate Program The benefits of earning this graduate certificate in clinical and translational research include: • Improve readiness to launch clinical and translational research studies • Improve grantsmanship necessary to attract research funding • Improve ability to analyze research data • Improve formal presentation and publication success rate • Improve patient care and health outcomes For More Information

•

David Cull, MD

Physician Champion DCULL@ghs.org (864) 455-6363

•

• *MTHSC 8070 - Applied Multivariate

Analysis (3) *MTHSC courses are offered on Clemson’s main campus.

Completion of this certificate is excellent preparation for continuing in the Master of Science in Applied Health Research and Evaluation (MS) degree at Clemson University.

Joy Green-Hadden, DNP Nursing Champion JGreenHadden@ghs.org (864) 455-7376

•

Ron Gimbel, Ph.D.

Clemson University RGIMBEL@clemson.edu (864) 656-1969

June 2017 Volume 2 | Issue 1

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, wbolton@ghs.org Managing Editor: Ally Hale, BA, ahale@ghs.org 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, MPH, PhD; 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; J. Terrill Huggins, MD; 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; Bryan S. Moon, 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, MPH; 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; David J. Walsh, MD; Thomas L. Wheeler, MD; Michael W. Wiederman, PhD; Christopher C. Wright, MD; Steven L. Young, 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 quality publications on healthcare innovation and delivery (university.GHS.org/Proceedings). All statements and opinions expressed in GHS Proceedings are those of the authors and not necessarily those of Greenville Health System, its board of trustees, or any of its affiliates. To receive upcoming issues by email, contact Ally Hale at AHale@ghs.org. Copyright © 2017 Greenville Health System. All rights reserved.

GHS Proc. June 2017; 2 (1)

Table of Contents Viewpoint

Review Article

QUESTION & ANSWER Radiology Imaging by Jeffrey W. Hanna

TEACHABLE MOMENT Clostridium difficile Testing: A Hard Look at Loose Stools by Sarah J. Tennant and Carmen M. Faulkner-Fennell

43 Irritable Bowel Syndrome and Endometriosis: Twins in Disguise by Meredith Aragon and Bruce A. Lessey

Special Article 11

Neonatal Abstinence Syndrome: An Epidemic by Kara Barlow, Alexis Cannon, Kindal Dankovich, Alysa James, Madison Merritt, and Jennifer A. Hudson

Meaningful Analysis of Small Data Sets: A Clinician’s Guide by Justin Collins, Jordan Brown, Christine Schammel, Kevin Hutson, and W. Jeffery Edenfield

Original Research 20 Orthostatic Intolerance and Other Autonomic Symptoms in Adolescents With Headaches by Augusto Morales, Andreea I. Stoichita, and Jessica D. Wharton 26 Impact of an Antimicrobial StewardshipDriven Initiative to Assess Appropriateness of Asymptomatic Bacteriuria or Funguria Treatment by Pooja J. Shah, Carmen M. Faulkner-Fennell, Jessica M. Odom, John H. Schrank Jr, Jennifer R. Meredith, and Jun Wu 32 Body of Knowledge: Using Prosections to Teach Pelvic Anatomy in OB/GYN Residency—A Randomized Study by Andrew S. Lane, Shanna E. Williams, Sharon D. Keiser, and Jeffrey W. Elder

Barriers and Beliefs Contributing to Excessive Gestational Weight Gain in LowIncome Women by Brittany E. Brodsky and John V. Logomarsino

Case Studies 56 Robotic Transabdominal Preperitoneal Repair of Bilateral Arcuate Line Hernias by Sam Weimer, Daniela Cocco, and Conrad Ballecer 59 Severe Pulmonary Hypertension in an 87-Year-Old Woman With Scimitar Syndrome by Tamara van de Star, Maximilien Rappaport, Manisha S. Patel, and Armin Meyer 62 Adamantinoma of the Forearm: A Chronologic Presentation of a SlowGrowing Malignancy by Richard W. Gurich Jr, Luminita Rezeanu, and Scott E. Porter 67 Spontaneous Iliac Vein Rupture by Nathaniel J. Walsh, Ashley Schlafstein, Caleb J. Mentzer, and Steven B. Holsten Jr

Miscellany 70 2017 Graduates of Greenville Health System and University of South Carolina School of Medicine Greenville 71

2016 Publications of Greenville Health System’s Medical and Scientific Staff

38 The Relationship Between Third-Year Clerkship Allocation Method and Specialty Choice by Francis S. Nuthalapaty, Tameika T. F. Lewis, Anne Zinski, and James R. Jackson

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, Attn: Ally Hale, Greenville Health System, 701 Grove Rd, 3rd Flr Support Tower, Greenville, SC 29605).

GHS Proc. June 2017; 2 (1)

Question & Answer

Radiology Imaging Jeffrey W. Hanna, MD From the Department of Radiology, Greenville Health System, Greenville, SC (J.W.H.)

Patient Description

65-year-old woman presents with 12 months of low back pain radiating into the left leg. Previous history of surgeries includes breast reduction, abdominoplasty, right

hip replacement, and jaw surgery. MRI of the left hip/pelvis and lumbar spine were performed to further evaluate for structural causes of her pain (Fig 1.). Based on the below images, what is this patientâ&#x20AC;&#x2122;s diagnosis? Answer on following page.

Imaging Figure 1 MRI of patientâ&#x20AC;&#x2122;s left hip/pelvis and lumbar spine. Figure Legend: A) Coronal T1 image of upper pelvis; B) Coronal T1 image of the lumbar vertebra; C) Axial T2 image at level of L4/5 disc; D) Sagittal T2 of lateral lower lumbar spine.

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Answer Figure 2 Retro-psoas right common iliac artery. Figure Legend: A) Coronal T1 image demonstrates abnormal origin of right common iliac artery (arrows) with nearly 70Â° angle from aorta. B) Coronal T1 image further posteriorly shows right common iliac artery (arrow) posterior to the psoas muscle along the posterior third of the 4th and 5th lumbar vertebra contiguous with the lumbosacral plexus.

C) Axial T2 image at level of L4/5 disc shows common iliac artery (CI) at lateral margin of the right intervertebral foramen abutting the right L4 nerve root (arrow). D) Sagittal T2 shows CI coursing caudally along the lateral margins of the L4/5 and L5/S1 right intervertebral foramina with the right L5 nerve root (arrow) seen just caudal to the artery.

Retro-Psoas Right Common Iliac Artery

these include singular reported cases by Vohra in 1991,1 Sonneveld in 1998, 2 Jain in 2008, 3 Delasotta in 2012,4 and Yang in 2015.5 Overall, it appears the anomaly was incidental to the patientâ&#x20AC;&#x2122;s presenting symptoms and/or pathology in all reported cases.

This anomaly of the iliofemoral arterial system is rare. Just a few cases have been published describing this anomaly over the last 25 years;

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QUESTION & ANSWER: RADIOLOGY IMAGING The patient reported by Vohra had iliac artery stenosis, but no causation was suggested.1 Sonneveld discovered the anomaly as an incidental finding with unrelated but clinically significant abdominal aortic aneurysm.2 Jain encountered this anomaly in the setting of iliac fossa renal transplantation,3 and Delasotta was evaluating a patient for possible spinal fusion through a far lateral approach.4 Finally, Yang et al discovered their case in the evaluation of a patient requiring pelvic surgery for urothelial malignancy.5 Unlike the more common iliofemoral anomaly of a persistent sciatic artery, which is predisposed to aneurysm formation, the few reported cases of retro-psoas iliac artery were found incidentally.

Embryology The lower limb vasculature arises as a continuation of the internal iliac artery but largely degenerates. The external iliac artery becomes its primary supply, which arises from the fifth lumbar intersegmental artery.6 Sonneveld proposed that “the common iliac and external iliac arteries are derived from the umbilical arteries at the end of the fourth week of gestation. The umbilical arteries develop a secondary connection to the fifth lumbar intersegmental branches of the aorta; these new trunks form the common iliac arteries from which the external iliac arteries subsequently arise. It may be possible that the retro-psoas iliac artery in our case embryologically was derived from an abnormal secondary connection between the umbilical artery and the fourth, instead of the fifth, lumbar intersegmental artery.”2

Significance Delasotta initially raised the concern that the position of the retro-psoas iliac artery could pose an unexpected hemorrhagic problem in managing patients with lumbar disc disease.4 Whether being managed by discectomy or transforaminal steroid injection, the juxtaposition of this vessel may cause difficulty.

Correspondence Address to: Jeffrey W. Hanna, MD, Greenville Health System, Department of Radiology, 1210 W Faris Rd, Greenville, SC 29605 (jhanna@ghs.org)

While vascular complications from these procedures are uncommon, life-threatening hemorrhage from vascular injury in far lateral disc surgery7 and caudal spine cord infarction in foraminal steroid injections have been reported.8 Furthermore, the incidence of far lateral disc protrusions attributed as the source of radicular symptoms has increased, incidence of far lateral disc herniation ranging between 0.7%–1.7% of all disc herniations, with the increased use of MRI for diagnosis.9 Certainly, the limited surgical exposure and close approximation of the retro-psoas iliac artery to the far lateral disc protrusion will make knowledge of this anomaly before the surgical approach helpful. Similarly, the typical posterolateral approach to transforaminal epidural steroid injection results in high likelihood of arterial puncture. Overall, while the retro-psoas iliac artery is not associated with an apparent inherent increase in pathology, the few reported cases have illustrated how knowledge of this anomaly may reduce the likelihood of difficulty when involved with pelvic or lumbar surgical procedures.

References 1. Vohra R, Leiberman DP. An anomalous right iliac artery presenting as iliac stenosis. Eur J Vasc Surg. 1991;5:209. 2. Sonneveld DJ, van Dop, HR, van der Tol A. Anomalous retro-psoas iliac artery in a patient with an abdominal aortic aneurysm. Eur J Vasc Endovasc Surg. 1998;16:85-6. 3. Jain A, Patil VP, Horton P, et al. Common iliac artery lying posterior to psoas major identified during kidney transplantation. Transplantation. 2008;86:623-4. 4. Delasotta LA, Radcliff K, Sonagli MA, Miller L. Aberrant iliac artery: far lateral lumbosacral surgical anatomy. Orthopedics. 2012;35:e294-7. 5. Yang CJ, Tzeng WS, Shu G, Cheng HM. Anomalous

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retro-psoas iliac artery: a case report. J Radiol Sci. 2015;40:13-6. 6. Schoenwolf GC, Bleyl SB, Brauer PR, Francis-West PH. Larsen’s Human Embryology. (5th edition) Elsevier, Churchill Livingstone, Philadelphia (2015). 7. Harrington JF Jr. Far lateral disc excision at L5–S1 complicated by iliolumbar artery incursion: case report. Neurosurgery. 2001;48:1377-9. 8. Murthy NS, Maus TP, Behrns CL. Intraforaminal location of the great anterior radiculomedullary artery (artery of Adamkiewicz): a retrospective review. Pain Med. 2010;11:1756-64. 9. Al-Khawaja DO, Mahasneh T, Li JC. Surgical treatment of far lateral lumbar disc herniation: a safe and simple approach. J Spine Surg. 2016;2:21-4.

Teachable Moment

Clostridium difficile Testing: A Hard Look at Loose Stools Sarah J. Tennant, PharmD, MS, BCPS, and Carmen M. Faulkner-Fennell, PharmD, BCPS From the Department of Pharmacy, Greenville Health System, Greenville, SC (S.J.T., C.M.F.-F.)

Story From the Front Line

is a 75-year-old woman with multiple medical problems, including chronic constipation. Her outpatient daily bowel regimen included senna-docusate, bisacodyl suppositories, and polycarbophil. She presented to Greenville Memorial Hospital secondary to mental status changes and increased abdominal girth. Her caregiver stated that the patient had not had a bowel movement in several days. CB was admitted to the intensive care unit for septic shock secondary to a urinary tract infection (UTI) and evidence of a right lower lobe pneumonia based on chest X-ray. Allergies to penicillins and cephalosporins were documented in the electronic medical record, so broad-spectrum antibiotics of aztreonam, vancomycin, and ciprofloxacin were initiated on hospital day 2 because of illness severity. Ciprofloxacin and vancomycin were discontinued on hospital days 3 and 4, respectively, and aztreonam was continued until day 7 to treat an Escherichia coli UTI. Tube feedings were started on hospital day 1 and continued until day 10 when the tube was displaced and not replaced. Proton-pump inhibitor therapy was started on hospital day 1 and continued until discharge. CB was not taking acid-suppressive medications before hospital admission. On hospital day 2, an abdominal and pelvis CT scan showed gaseous distention of the transverse colon with formed stool throughout the left colon. The rectum and sigmoid colon were distended with formed stool suggesting constipation. There was no evidence of small bowel obstruction. A bowel regimen consisting of daily polyethylene glycol (17 g packets), bisacodyl suppositories (10 mg), and senna tablets (8.6 mg) was started in addition to a 1-time dose of lactulose solution (40 g) and of sodium polystyrene suspension (30 g).

The patient had 6 documented loose bowel movements on hospital day 2. CB continued to have 0â&#x20AC;&#x201C;2 soft or loose stools documented per day until hospital day 11 when 3 watery stools were charted. A Clostridium difficile (C difficile) polymerase chain reaction (PCR) test was ordered. Daily bisacodyl and polyethylene glycol doses were discontinued after administration on hospital day 11. After discontinuation, the documented bowel movements were again 0â&#x20AC;&#x201C;2 soft or loose stools per day for the remaining hospital stay. Senna was administered until hospital day 14. On hospital day 12, the C difficile PCR test resulted positive, and the patient was started on metronidazole by mouth (500 mg every 8 hours).

Teachable Moment Clostridium difficile is the most common pathogen implicated in hospital-acquired infections. National surveillance data estimates C difficile was responsible for 500 000 infections and 29 000 deaths in 2011. The 30-day crude case fatality rate for C difficile infections is 9.3%.1 The cost of C difficile infection (CDI) is high, with data from 2008 estimating up to $4.8 billion in excess cost for acute care facilities.2 Antibiotic exposure remains the most important risk factor for CDI. Combination antibiotic use and prolonged antibiotic therapy increase the risk of CDI; however, perioperative antibiotic exposure also introduces risk for infection.3 One study demonstrated the rate of CDI in patients who received only perioperative antibacterial prophylaxis to be 7.3 per 1000 surgical procedures.4 Antibiotic agent selection may also be a contributing risk factor, as clindamycin, fluoroquinolones, cephalosporins, and aminopenicillins have been shown to be associated with CDI.5,6 Use of proton pump inhibitors has been shown in some

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CLOSTRIDIUM DIFFICILE TESTING AND LOOSE STOOL studies to increase the risk for CDI because of modification of normal stomach acidity and gastrointestinal microbiota.6,7 Advanced age is another risk factor, with patients over 65 years having an 8-fold increased risk of CDI when compared to younger patients.1 While C difficile is most commonly associated with the healthcare setting, community-associated infection is also on the rise with 159 700 community-associated cases reported in 2011.1 C difficile in the community setting, however, tends to affect younger patients and risk factors remain unclear.8 The endotoxins released by the bacteria, and the resultant inflammatory changes in the colonic epithelium, cause colitis and diarrhea in susceptible patients with clinical CDI.9 A significant number of people are asymptomatic carriers of C difficile but do not develop overt clinical signs of infection. Therefore, detection of C difficile from stool is just one way to diagnose CDI. A variety of testing methods are available, but diagnostic tests capable of detecting toxins are the most clinically useful. Currently, toxigenic culture and cell cytotoxicity assay are considered the gold standard testing methods. These tests are time-intensive and are mainly used for epidemiologic purposes. Enzyme immunoassay-based tests offer a shorter turnaround time, but at the expense of sensitive results. Nucleic acid amplification testing methods, such as PCR, are more sensitive and specific, but can identify C difficile toxin in the stool of asymptomatic patients. Some clinical microbiology laboratories utilize a 2-step testing method to increase sensitivity, combining a test for detection of organism that, if positive, reflexes to a test for presence of toxin.10 Greenville Health System utilizes a PCR test for C difficile that detects the genes that regulate production of toxin A and toxin B and the presence of genes for the B1/NAP1/027 hypervirulent strain. Because PCR can detect the toxin genes in stool of asymptomatic patients, adequate patient selection and sample collection are paramount to accurate diagnosis of C difficile infection. The Infectious Diseases Society of America recommends that C difficile testing only be performed on diarrheal stools.11 Diarrhea is defined as the acute onset of 3 or more loose stools in

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a 24-hour period. Diarrheal stools are watery, loose, or unformed; one rule of thumb is that the stool specimen should take the shape of the sample container.10 C difficile testing on formed stools decreases the specificity of diagnosis. Asking patients questions that characterize their acute diarrhea can be an important part of subjective assessment. It is important to understand the factors that can confound assessment of a patient with acute diarrhea; these include medications, diet, and disease. A scheduled bowel regimen that includes laxatives and stool softeners can cause loose stools. If clinical suspicion exists that a patient has acute diarrhea, it would be prudent to discontinue the bowel regimen and observe the patient for another 24–48 hours. Diarrhea is a chief complaint of patients on enteral tube feeds because of the absence of fiber and starches. Use of enteral tube feeds may promote a colonic environment susceptible to CDI resulting from increased small bowel colonization by colonic flora and decreased motility.12 Oncology patients are also at risk of developing acute diarrhea, as this condition can be an adverse effect of their chemotherapy regimen or a complication of their malignancy. The importance of assessing other causes of diarrhea is important from a regulatory, public reporting, and financial standpoint. At the Centers for Disease Control and Prevention (CDC), C difficile case definition is based only on laboratory identification (LabID) of a positive C difficile result.13 Therefore, a patient with clinical CDI and a patient colonized with C difficile would both count as CDC LabID event. C difficile cases are further classified as either community onset—identification occurs on or before hospital day 3—or facility-associated— if identification occurs on or after hospital day 4.14 Facility-associated C difficile rates are now reportable to the public. Greenville Memorial Hospital was included on a 2016 Consumer Reports list of hospitals in the United States that received the lowest or second-lowest rating in preventing facility-associated C difficile.15 The Centers for Medicare & Medicaid Services no longer reimburses hospital systems for facility-associated C difficile cases.13 In summary, C difficile infection is a clinical syndrome. As such, laboratory testing should be

Correspondence Address to: Sarah J. Tennant, PharmD, Greenville Health System, Department of Pharmacy, 701 Grove Rd, Greenville, SC 29605 (stennant@ghs.org)

coupled with patient assessment. Inappropriate laboratory testing can be minimized by taking an accurate patient history and minimizing factors that exacerbate acute diarrhea. CB had a history of chronic constipation with inpatient and outpatient use of aggressive laxative therapy. The number of stools per day decreased with the discontinuation of part of her bowel regimen; however, because the C difficile PCR test

was positive, she was labeled as a facility-associated C difficile case. Incidence of CDI is on the rise; therefore, prevention is paramount. C difficile is the focus of antimicrobial stewardship programs across the country as judicious use of antimicrobials can minimize the risk of infection. Using antibiotics only when necessary and for the shortest effective duration are principles that can help curb incidence of CDI.

References 1. Lessa FC, Mu Y, Bamberg WM, et al. Burden of Clostridium difficile infection in the United States. N Eng J Med. 2015;372:825-34.

9. Bagdasarian N, Rao K, Malani PN. Diagnosis and treatment of Clostridium difficile in adults: a systematic review. JAMA. 2015;313:398-408.

2. Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55:S88-92.

10. Brecher SM, Novak-Weekley SM, Nagy E. Laboratory diagnosis of Clostridium difficile infections: there is light at the end of the colon. Clin Infect Dis. 2013;57:1175-80.

3. Owens RC, Donskey CJ, Gaynes RP, Loo VG, Muta CA. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect Dis. 2008;46:S19-31. 4. Carignan A, Allard C, Pepin J, Cossette B, Nault V, Valiguette L. Risk of Clostridium difficile infection after perioperative antibacterial prophylaxis before and during an outbreak of infection due to a hypervirulent strain. Clin Infect Dis. 2008;46:1838-43. 5. Gerding DN. Clindamycin, cephalosporins, fluoroquinolones, and Clostridium difficileâ&#x20AC;&#x201C;associated diarrhea: this is an antimicrobial resistance problem. Clin Infect Dis. 2004;38:646-8. 6. Leffler DA, Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015;372:1539-48. 7. Dial S, Delaney JAC, Barkun AN, Suissa S. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989-95. 8. Chitnis AS, Holzbauer SM, Belflower RM, et al. Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med. 2013;173:1359-67.

11. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America. Infect Control Hosp Epidemiol. 2010;31:431-55. 12. Oâ&#x20AC;&#x2122;Keefe SJD. Tube feeding, the microbiota, and Clostridium difficile infection. World J Gastroenterol. 2010;16:139-42. 13. Centers for Disease Control and Prevention. CMS Requirements 2014. https://www.cdc.gov/nhsn/cms/ index.html. Accessed January 2017. 14. Dubberke ER, Carling P, Carrico R, et al. Strategies to prevent Clostridium difficile infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol. 2014;35:628-45. 15. Interlandi J. Consumer reports names hospitals with high C. diff infection rates. 2016. http://www. consumerreports.org/doctors-hospitals/consumerreports-names-hospitals-with-high-c-diff-infectionrates. Updated September 27, 2016. Accessed December 1, 2016.

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Special Article

Neonatal Abstinence Syndrome: An Epidemic Kara Barlow, MD; Alexis Cannon, MD; Kindal Dankovich, MD; Alysa James, MD; Madison Merritt, MD; and Jennifer A. Hudson, MD From the University of South Carolina School of Medicine Greenville, Greenville, SC (K.B., A.C., K.D., A.J., M.M., J.A.H.), and Children’s Hospital of Greenville Health System, Greenville, SC (J.A.H.)

ales of opioid pain medications in the United States (US) have increased nearly fivefold since 2000.1,2 Pregnant women as a distinct population have also experienced a threefold to fourfold increase in prescription opioid use.3 These data are concerning because chronic opioid use is associated with significant adverse effects, including cardiac complications, depression, and drug dependence.4,5 For pregnant women, however, concerns are not limited to the mother, since numerous studies have shown opioid use to adversely impact fetal development6-9 and can often result in neonatal abstinence syndrome (NAS).4,10 The National Library of Medicine defines NAS as “problems that occur in a newborn who was exposed to addictive opiate drugs while in the mother’s womb.”11 Manifestations of this group of “problems” vary, as do the severity and duration of symptoms that infants with NAS experience post-birth. Between 2000–2012, national rates of NAS increased 383% from 1.2 per 1000 births to 5.8 per 1000 births.2,12 Hospital costs associated with the diagnosis and treatment of NAS have also increased, with infants with NAS averaging a longer hospital stay of 12.4 days when compared to infants without NAS (Table 1).12 Currently, no national standard of care for managing NAS exists, and there is no consistency in laws or regulations on reporting substance misuse in pregnancy or NAS cases. Several individual states, however, have implemented measures to address and treat their rising NAS rates. This report aims to increase awareness surrounding the rise in opioid use in pregnant women and the subsequent danger of NAS and to provide several prevention strategies to reverse this growing epidemic.

$1.5 billion in national healthcare expenditures.12 The rate of NAS in South Carolina (SC) has also increased significantly—from 0.9 per 1000 births in 2000 to 3.9 per 1000 births in 2013.13,14 These data are troubling for several reasons: they represent the unnecessary suffering many infants are experiencing post-birth, the increasing number of pregnant women (and Americans in general) potentially experiencing complications of chronic opioid use/misuse, and the significant financial burden this epidemic is placing on payers, hospitals, and the US. In 2000, the mean total charges generated for hospitalization of a newborn with NAS was $39 400. By 2012, that total had increased to $68 700 for infants with NAS and $93 400 for pharmacologically treated NAS infants, compared to $3500 for uncomplicated infant births (Table 1).12 Although median hospital length of stay for an infant with NAS has not changed significantly over time, it does remain more than 5 times longer than nonNAS infants (17 days vs. 3 days). Also of note, approximately 81% of all NAS-related hospital charges are billed to Medicaid.12 Neonatal abstinence syndrome primarily results from chronic late-gestation exposure to opioids.

Table 1 Trend in NAS diagnosis and associated hospital costs between years 2000–2012.

Rate of NAS per 1000 hospital births

Neonatal Abstinence Syndrome

NAS newborn hospitalization costs

As of 2012, an infant with NAS was born every 25 minutes in the US, accounting for more than

Patrick et al12

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2000

2009

2012

1.2

3.39

5.8

$39 400

$53 400

$68 700

Withdrawal symptoms can begin as early as birth but may not peak in severity until day 3 or 4 of life.15 Neurologically, infants with NAS may exhibit tremors, hypertonia, hyperreflexia, irritability, sleep disturbance, a high-pitched cry, and/ or seizures. They may also experience autonomic dysfunction, manifesting as sweating, fever, nasal congestion, sneezing, or skin mottling. Gastrointestinal manifestations include poor feeding, vomiting, diarrhea, and failure to thrive. Tachypnea, apnea, and skin excoriations can also be present. Symptoms have been found to persist for as long as 4–6 months, with neurologic irritability occasionally extending into the seventh or eighth month of life.15 Clinical presentation of NAS differs from infant to infant in manifestation, severity, and duration, and is often based on the type and amount of opioid exposure, gestational age, maternal nicotine use, and other maternal medications.4 Unfortunately, no clear correlation between the prenatal dose or duration of exposure and the severity of symptoms has been established, which makes it difficult to predict how an infant with NAS will appear in the first few days of life. Also, manifestations of NAS involving autonomic dysfunction, such as tachypnea and fever, are characteristic of many newborn illnesses and can make it challenging to distinguish the presence of withdrawal if the prenatal history of substance use/misuse is not known. Previous studies have shown infants with NAS to have a significantly higher rate of post-birth complications compared to non-NAS infants.12 Additional conditions associated with NAS include preterm delivery, low birth weight, and a prolonged hospital stay.4,12,16 Few studies have examined the long-term impact on developmental outcomes, but further research is warranted.

Prescription Opioid Use The majority of women will experience some pain during pregnancy. The most common complaints are back pain, abdominal pain, headaches, and/ or joint pain.17 As a result, it is not surprising that pain relievers are desired. Prescription opioid use during pregnancy, however, can be strongly associated with neonatal complications, especially in the presence of additional risk factors, such as alcohol, smoking, antidepressant use, or other drug misuse.18 Despite the known risks associated with opioid use during pregnancy, the rates of opioid prescriptions being dispensed are increasing. National studies show between 14%–22% of all women will fill a prescription for an opioid med12

ication during pregnancy,17,18 with the most common being hydrocodone, followed by codeine, oxycodone, and propoxyphene.17 Challenges abound in reducing opioid use in pregnant women. First, many women may be unaware that they are pregnant; approximately 50% of US pregnancies are unplanned. Moreover, 86% of pregnancies in women who misuse opioids are unintended.19,20 Opioid use during pregnancy, however, is not limited to lack of awareness. In 2015, Palmsten et al found that 82% of pregnant women enrolled in Medicaid were dispensed at least 1 opioid prescription.16 Study results showed that the proportion of prescriptions dispensed increased from 52% before pregnancy to 57% through the third trimester, with 2 out of 5 pregnancies including at least 1 prescription for a Pregnancy Category D or X drug.16 In 2013, approximately 52% of women of reproductive age (ages 15–44) in SC filled an opioid prescription. The 5 most common prescriptions included fentanyl transdermal, morphine, hydrocodone-acetaminophen, oxycodone-acetaminophen, and buprenorphine sublingual. Most of these drugs were prescribed for 6 months continuously, with 67% of hydrocodone-acetaminophen users being prescribed for the entire year. 21

Preventing NAS Primary Prevention At the practitioner level, office strategies can be implemented to improve education surrounding factors that increase the risk of an infant experiencing NAS. Primary prevention in the “preconception” phase should minimize prescription opioid use before pregnancy. Open dialogue and promotion of family planning, including effective contraception pre-pregnancy and post-delivery, are important; so is education surrounding the potential impact short- and long-term opioid use may have on future pregnancy, health, and wellness. Other strategies also include offering brochures in waiting rooms and restrooms that describe risks of opioid use, as well as utilizing social media and public education campaigns to raise awareness. Secondary Prevention Prescription Drug Monitoring Program A Prescription Drug Monitoring Program (PDMP) is a state-level database that monitors controlled prescription drugs dispensed by pharmacies. Currently, 49 states have a PDMP, including SC. Data for specific patients are available to practitioners with access, and the PDMP is a helpful resource GHS Proc. June 2017; 2 (1): 11-15

NEONATAL ABSTINENCE SYNDROME: AN EPIDEMIC for reporting other medications the patient has recently been prescribed, and by whom. The PDMP in SC is known as the South Carolina Reporting and Identification Prescription Tracking System (SCRIPTS). SCRIPTS requires all dispensing practitioners and pharmacists to collect and report distribution of all class II–IV controlled substances.22 According to SC’s Department of Health and Environmental Control, only 28% of physicians in SC are currently using this valuable tool. Obtaining SCRIPTS access requires the practitioner and/or pharmacist to complete an online-training module, complete a notarized database access request form, sign a privacy statement, and submit a copy of his or her driver’s license. The process is free and takes approximately 15 minutes to complete. Access is typically granted by email in 3–5 business days.22 Although there are limitations to the database, 72% of SC prescribers may be missing opportunities to detect and prevent prescription misuse.

Screening Tools Substance use disorders affect all genders, races, ages, and socioeconomic groups. As such, screening should not be limited to supposed “high risk” patients. The Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based screening tool that can be used in the office setting to detect and treat patients struggling with substance misuse.23 Originally, SBIRT was used as a screen for alcohol and tobacco misuse, but the current version also screens for family violence, prescription, and illicit substance use problems. Few studies have examined the effectiveness of SBIRT on lowering substance misuse. However, a large federally funded study by Madras et al saw significant improvements in illicit substance use (68% lower) and heavy alcohol use (39% lower) following implementation of SBIRT.24 The American Medical Association (AMA) has approved billing codes that will allow hospital systems to be reimbursed by third-party payers for implementing SBIRT. South Carolina’s Department of Health and Human Services (DHHS) has been reimbursing obstetric providers since 2012 for SBIRT screening of pregnant women funded by Medicaid. Reimbursement ranges from $26.78 (SBI Code 99408, 15–30 minutes) to $52.29 (SBI Code 99409, >30 minutes).25 Taking the time to screen all pregnant women and provide brief intervention or referrals to those patients in need can potentially decrease substance misuse during pregnancy and ultimately lead to fewer cases of NAS and fewer maternal health complications. GHS Proc. June 2017; 2 (1): 11-15

Urine drug testing during pregnancy may also provide benefit within prevention models. The American Congress of Obstetricians and Gynecologists (ACOG) currently states that maternal urine drug testing is indicated in the setting of late or no prenatal care in the hospital setting and with diagnosis of stillbirth or placental abruption. Positive history, physical exam findings, and concerning behaviors may also prompt providers to order a urine drug test. Detection of substance use can help direct appropriate care for both infants and mothers. However, maternal testing should be done only with her knowledge and consent, including an understanding of the consequences of a positive test, which can vary from state to state.26 Several states require physicians to report suspected substance misuse during pregnancy. The results of these reports and prenatal drug tests can then be used in criminal proceedings.27 Currently, 18 states consider substance misuse during pregnancy to be child abuse.26 The SC Supreme Court considers a viable fetus to be a “person”; maternal acts that endanger the life, comfort, or health of that “person” are considered criminal child abuse.26 Criminal prosecution of substance misuse during pregnancy has historically led pregnant women to avoid prenatal care, leading the AMA to reject the idea of criminalizing pregnant women using drugs.27 ACOG experts have also stated that such legal actions “have proved to be ineffective in reducing the incidence of alcohol or drug abuse.”28 Colorado has implemented a bill—HB12-1100— that prohibits information gained from drug screening or testing to be used in criminal proceedings.27 This bill may serve as a model for other states, as women with substance use disorders may be more willing to disclose issues without fear of criminalization, allowing for physicians to provide treatment options sooner and optimize clinical outcomes for the mother and the fetus and/or infant.

Managing NAS Currently, no nationwide standard of care exists for managing NAS. Reporting of NAS, as well as medical treatment for NAS, varies by state and often by medical provider. Tennessee was among the first to begin to address the NAS epidemic, targeting multiple levels of prevention, data collection, and treatment. One of Tennessee’s initial interventions included collaboration with other states to petition the US Food and Drug Administration for a black box warning on certain opioids related to their use during pregnancy.27 The state 13

Abbreviations and Acronyms US = United States; NAS = neonatal abstinence syndrome; SC = South Carolina; PDMP = prescription drug monitoring program; SCRIPTS = South Carolina Reporting and Identification Prescription Tracking System; SBIRT = Screening, Brief Intervention, and Referral to Treatment; AMA = American Medical Association; DHHS = Department of Health and Human Services; ACOG = American Congress of Obstetricians and Gynecologists; BOI = Birth Outcomes Initiative; MAiN = Managing Abstinence in Newborns

Correspondence Address to: Jennifer Hudson, MD, Greenville Health System, Department of Pediatrics, 701 Grove Rd, Greenville, SC 29605 (jhudson@ghs.org)

also made NAS a reportable condition and established a web-based reporting system, requiring physicians to report an NAS case within 30 days of diagnosis. As opposed to the initial surveillance through Medicaid and hospital discharge data, the web-based reporting portal system now allows Tennessee to gather data in real time, which provides greater insight into the source of NAS and geographic hotspots. Additional intervention strategies in the state allow infants diagnosed with NAS to qualify for several assistance programs including Tennessee Early Intervention Services, Help Us Grow Successfully, and Children’s Special Services.27 In 2013, Maine established the Centers for Disease Control and Prevention Snuggle ME Guidelines, which addressed screening for substance use during pregnancy, and provided information related to intrapartum, postpartum, and newborn management; educational resources for families; and additional resources for medical providers. Through a unified approach, these guidelines were distributed to all birthing hospitals in the state.29 Other states and organizations have implemented quality improvement projects for NAS to help improve standards of care. In Ohio, the Nationwide Children’s Hospital (NCH) sought to enhance managing NAS by establishing a pharmacologic protocol for initiating and weaning morphine and appropriate use of adjunctive therapy. NCH implemented training for nurses to accurately use abstinence scoring and initiated monthly interdisciplinary meetings to evaluate needs for staff education. Following protocol implementation, NCH experienced a reduction in length of stay for infants with NAS (31 days to 24 days), improved reliability of abstinence scores, and added educational resources for patients and

staff.27 The Vermont Oxford Network, an alliance of neonatal intensive care units around the world, has also created an internet-based quality improvement project focused on standardizing prevention and management strategies.27

NAS Care in SC In 2011, the SC DHHS established the SC Birth Outcomes Initiative (BOI)—a statewide collaboration of stakeholders aiming to improve health outcomes for newborns. Core objectives of the BOI include reducing preterm births and neonatal intensive care days and increasing SBIRT use by obstetric providers during prenatal care. Developing a management model for NAS care in low-acuity nurseries has also been an area of focus since the initiative’s inception. One management model called MAiN (Managing Abstinence in Newborns) was developed and studied at Greenville Health System in Greenville, SC. MAiN involves a multidisciplinary and coordinated approach that targets collaboration among clinicians caring for opioid-dependent mothers and their newborns. More specifically, MAiN combines standardized early treatment, inpatient stabilization (while rooming-in with mother), and outpatient weaning in a medical home. The MAiN model has been shown to be safe, effective, and cost-efficient, generating less than $11 000 in hospital charges per case.30

Conclusion Substance use disorders are treatable conditions, similar to other chronic diseases encountered in pregnancy. With heightened practitioner awareness, effective prevention and screening strategies, and operational treatment and support systems, the NAS epidemic can be addressed in SC and nationwide.

References 1. Centers for Disease Control and Prevention. Vital Signs: Overdoses of prescription opioid pain relievers—United States, 1999–2008. MMWR. 2011;60;1487-92. 2. Patrick SW, Schumacher RE, Benneyworth BD, Krans EE, McAllister JM, Davis MM. Neonatal abstinence syndrome and associated health care expenditures: United States, 2000-2009. JAMA. 2012;307:1934-40. 3. Whiteman VE, Salemi JL, Mogos MF, et al. Maternal opioid drug use during pregnancy and its impact on perinatal morbidity, mortality, and the costs of medical care in the United States. J Pregnancy. 2014;2014:906723.

4. Yazdy MM, Desai RJ, Brogly SB. Prescription opioids in pregnancy and birth outcomes: a review of the literature. J Pediatr Genet. 2015;4:56-70. 5. Warner EA. Opioids for the treatment of chronic noncancer pain. Am J Med. 2012;125:1155-61. 6. Broussard CS, Rasmussen SA, Reefhuis J, Friedman JM, Jann MW, Riehle-Colarusso T, Honein MA. Maternal treatment with opioid analgesics and risk for birth defects. Am J Obstet Gynecol. 2011;204:314 (e1-11). 7. Shaw GM, Malcoe LH, Swan SH, Cummins SK, Schulman J. Congenital cardiac anomalies relative to selected maternal exposures and conditions during early pregnancy. Eur J Epidemiol. 1992;8:757-60.

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NEONATAL ABSTINENCE SYNDROME: AN EPIDEMIC 8. Nezvalova-Henriksen K, Spigset O, Nordeng H. Effects of codeine on pregnancy outcome: results from a large population-based cohort study. Eur J Clin Pharmacol. 2011;67:1253-61. 9. Yazdy MM, Mitchell AA, Tinker SC, Parker SE, Werler MM. Periconceptional use of opioids and the risk of neural tube defects. Obstet Gynecol. 2013;122:838-44. 10. Osborn DA, Jeffery HE, Cole MJ. Opiate treatment for opiate withdrawal in newborn infants. Cochrane Database Syst Rev. 2010:CD002059. 11. Lee KG. Neonatal abstinence syndrome. MedlinePlus. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/007313.htm. Updated April 19, 2016. Accessed March 1, 2017. 12. Patrick SW, Davis MM, Lehman CU, Cooper WO. Increasing incidence and geographic distribution of neonatal abstinence syndrome: United States 20092012. J Perinatology. 2015;35:650-5. 13. Gareau S, Lòpez-DeFede A, Finney C (2015). South Carolina newborn illicit substance use and Neonatal Abstinence Syndrome. A report created by the SC Birth Outcomes Initiative Data Committee for the SC Birth Outcomes Initiative Behavioral Health Committee. 14. Ko JY, Patrick SW, Tong VT, Patel R, Lind JN, Barfield WD. Incidence of neonatal abstinence syndrome—28 states, 1999–2013. MMWR Morb Mortal Wkly Rep. 2016;65:799-802. 15. Burgos AE, Burke BL. Neonatal abstinence syndrome. NeoReviews. 2009;10: e222-9. 16. Palmsten K, Hernandez-Diaz S, Chambers CD, Mogun H, Lai S, Gilmer TP, Huybrechts KF. The most commonly dispensed prescription medications among pregnant women enrolled in the US Medicaid program. Obstet Gynecol. 2015;126:465-73. 17. Bateman BT, Hernandez-Diaz S, Rathmell JP, et al. Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology. 2014;120:1216-24. 18. Desai RJ, Huybrechts KF, Hernandez-Diaz S, et al. Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ. 2015;14:h2102.

21. Gareau S, Cummings T, Lòpez-De Fede A. Opioid use among female Medicaid recipients of reproductive age. A report developed by the USC Institute for Families in Society, Division of Medicaid Policy Research for SC HealthViz. 2014. http://www. schealthviz.sc.edu/Data/Sites/1/media/scmedicaid_ opioidusestudy2014.pdf. Published August 2014. Accessed March 2, 2017. 22. South Carolina Department of Health and Environmental Control; Prescription Monitoring. Columbia, SC, 2014. Available at https://www.scdhec.gov/ Health/FHPF/DrugControlRegisterVerify/PrescriptionMonitoring. Accessed March 2, 2017. 23. Agerwalal SM, McCance-Katz EF. Integrating Screening, Brief Intervention, and Referral to Treatment (SBIRT) into clinical practice settings: a brief review. J Psychoactive Drugs. 2012;44:307-17. 24. Madras BK, Compton WM, Avula D, Stegbauer T, Stein JB, Clark HW. Screening, brief interventions, referral to treatment for illicit drug and alcohol use at multiple healthcare sites: comparison at intake and 6 months. Drug Alcohol Depend. 2009;99:280-95. 25. SBIRT Reimbursement. Institute for Research, Education and Training in Addictions (IRETA). Pittsburg, PA, 2015. Available at http://my.ireta.org/ sbirt-reimbursement-map. Accessed March 2, 2017. 26. Guttmacher Institute. State policies in brief: Substance abuse during pregnancy. Available at http://w w w.guttmacher.org/statecenter/spibs/ spib_SADP.pdf. Published March 1, 2015. Accessed March 4, 2017. 27. Association of State and Territorial Health Officials (astho™). Neonatal abstinence syndrome: how states can help advance the knowledge base for primary prevention and best practices of care. 2014. http:// w w w.astho.org/prevention/nas-neonatal-abstinence-report/. Accessed March 4, 2017. 28. American College of Obstetricians and Gynecologists. Substance abuse reporting and pregnancy: the role of the obstetrician-gynecologist. Committee Opinion No. 473. Obstet Gynecol. 2011;117:200-1.

19. Finer LB, Zolna MR. Declines in unintended pregnancy in the United States, 2008-2011. N Engl J Med. 2016;374:843-52.

29. Association of State and Territorial Health Officials 2013. Maine CDC Snuggle ME guidelines developed to standardize care for drug-affected babies. http:// www.astho.org/Maine-CDC-Snuggle-ME-Guidelines/. Accessed March 1, 2017.

20. Heii SH, Jones HE, Arria A, et al. Unintended pregnancy in opioid-abusing women. J Subst Abuse Treat. 2011;40:199-202.

30. Hudson J, Mayo R, Dickes L, et al. Early treatment for neonatal abstinence syndrome: a palliative approach. Amer J Perinatol. 2017;34:576-84.

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Special Article

Meaningful Analysis of Small Data Sets: A Clinician’s Guide Justin Collins, BS; Jordan Brown, BS; Christine Schammel, PhD; Kevin Hutson, PhD; and W. Jeffery Edenfield, MD From the Institute for Translational Oncology Research, Greenville Health System, Greenville, SC (J.C., W.J.E.); Department of Mathematics, Furman University, Greenville, SC (J.B., K.H.); and Pathology Consultants, Greenville, SC (C.S.)

Abstract A well-known problem in clinical research is the size of accessible data sets. When analyzing any data set the goal is always to find the actual correlations, quantify these correlations, and assess the likelihood the correlations are not random. Large data will allow for detection of smaller magnitude significant differences between groups, though this statistical significance does not immediately imply clinical relevance. Large research institutions have the resources to curate large databases; however, their patient cohorts differ from patient populations of smaller regional/local medical institutions. Often, smaller hospitals lack the patient volume and resources to maintain large databases. Additionally, access to dedicated medical statisticians may be limited at these places. Thus, these institutions face unique difficulties in statistical analysis. Smaller data sets are not unusable; they merely require a slightly different approach. As smaller institutions outnumber large institutions and provide healthcare locally, the majority of patients will be seen at these places. Properly defining techniques to extract meaningful information from small data sets would allow these hospitals to leverage their patient cohorts, which more closely resemble a random representative sample of the average patient nationally. To date, the methodology of data analysis on small medical data sets has not been expounded on. This paper targets clinicians doing their own statistical analysis and explains the basics of hypothesis testing. Additionally, it sheds light on common problems found in analyzing small medical data sets, provides methods to combat them, and explains why small cohort analysis does not preclude generalizability.

well-known problem in clinical research is the size of accessible data sets. When analyzing any data set, a differentiation between the signal—the actual pattern that comes from a difference between groups or some explainable connection between variables—and the noise—the random variation in a variable— must be elucidated.1 This differentiation requires hypothesis testing in which the null hypothesis is often defined as the assumption that the variables have no relationship to each other. Specifically, under the null hypothesis, 2 patient cohorts should look and test as if they come from a single patient population rather than 2 disparate groups. Statistical tests are used to determine the probability that the null hypothesis is true, evaluating the likelihood that 2 (or more) groups in the cohort are from the same sample.

Large data sets allow for more precise attenuation of the signal and, thus, have lower perceived noise, thus allowing a smaller magnitude of difference between groups to be considered statistically significant, and the null hypothesis is more likely to be rejected. Because the power and efficacy of statistical analyses most often used rely on the size of the patient population and data set, conclusions from these large institutions often result in novel medical treatments and add to the generalizable knowledge of the field. The assumption of these data is that larger samples represent a random sampling of the demographic; however, while large research institutions have the resources to compile and analyze large data sets, large centers operate primarily on referrals and may decline patients based on fiduGHS Proc. June 2017; 2 (1): 16-19

FINDING MEANING IN SMALL DATA SETS ciary eligibility. Additionally, treatments at a distance from patient homes are often cost prohibitive. As such, these large cohorts may not be truly representative random samples of the population as a whole and the conclusions found may not translate practically into practice at smaller institutions. These smaller institutions, which greatly outnumber large institutions, provide care for the majority of the population. However, smaller centers have neither the patient volume nor the resources to maintain large databases. As such, an intentional and practical approach to analysis is required to derive meaning from smaller cohorts. Properly using statistical techniques to extract information from small data sets would allow for data more representative of the average cohort to be included in the literature. In addition, many clinicians have insufficient training regarding statistics to critically analyze statistical analysis in published articles and, as a result, hold the misconception that their own research, made up of small cohorts, has nothing to contribute to the literature as a whole. This fact perpetuates the void in the literature from regional medical institutions. Lacking access to large data sets or statisticians willing to work with small data sets further exacerbates this problem. Elucidating the specifics of statistical hypothesis tests commonly used in medical literature, explaining the considerations of small data sets, and clarifying the generalizations that can or cannot be made from the statistical information will empower clinicians at small regional medical centers to collect, analyze and publish their research, thus filling the previously created void in the body of medical literature.

Background Overgeneralized statements are one of the biggest obstacles in analyzing and evaluating the results of small data sets. As such, it is imperative to evaluate the statistical tests most commonly used in medical research and understand the effect of small data sets on the results of these tests, the assumptions built into each of the tests, and the actual mathematical question each test is designed to answer. While published methods address the caveats and statistical validity of smaller data sets,2-5 effective use of these methods is scarce, necessitating a better understanding for the purpose of empowering smaller institutions.

Student’s T-test The student’s t-test6 , the most frequently used test in medical statistical analysis, attempts to determine if the difference between the means of 2 GHS Proc. June 2017; 2 (1): 16-19

data sets arises from random variation. Often, the threshold for statistical significance is arbitrarily defined as P ≤ .05. For example, in medical research, t-tests are usually used to compare 2 different treatment groups based on continuous outcome variables such as BMI. Each of the 2 groups will be treated by some changing parameter (drug type, surgery type, etc.), and the outcomes will be compared. The value returned from the t-test is compared to the z-distribution and yields a probability score defining the likelihood that the difference in means is the result of sampling error. This probability can be given from a 1- or 2-tailed version of the test. If the directionality of the relationship of the variables is known, a 1-tailed t-test is appropriate; however, because effects of individual variables on specific outcomes are typically ambiguous, a 2-tailed t-test is appropriate if the relationship between variables is unknown or under investigation. In general, very specific information about variable relationships must exist for a 1-tailed t-test to be appropriate. Assumptions for performing these tests are as follows: samples in each group are independent, the 2 populations being compared are normally distributed, and the 2 samples should have equal variance. If these conditions are not met, or good reason exists to doubt whether they are fulfilled, a non-parametric test would be more appropriate. For example, survival in days is almost never normally distributed. Additionally, the variance in each sample compared to the other can be unequal. In this case, the student’s t-tests would be appropriately replaced by a Welch’s t-test.

Chi-square Test The Chi-square test allows for hypothesis testing for categorical variables and categorical outcomes. In medical research, rare frequencies of certain outcomes can make tests challenging to use routinely; however, when data can be classified into a contingency table, a Chi-square test is an appropriate statistical option. For Chi-square analysis, events must be mutually exclusive and have a total probability of one. Contraindications for Chi-square analysis include events with a very low probability or low frequency; for these scenarios, a Fisher’s exact test (if the data are in a 2x2 contingency table), binomial test, or a g-test would be more accurate.7 When the test statistic is computed and then transformed into a probability score, the P value returned gives the likelihood the groups are from the same distribution, meaning the probability that the test groups’ difference is the result of random sampling error. 17

For example, Chi-square tests are used when you have 2 or more groups based on treatment with a categorical outcome such as mortality.

ANOVA An analysis of variance (ANOVA) is optimally used when data will have more than 2 groups and consist of continuous outcomes. Like the t-test, ANOVA attempts to determine if the difference between the means of multiple data sets (3 or more groups) arises from random variation. While technically this difference could be determined by running pairs of t-tests with all possible groups, the likelihood of incurring type-I errors is high, causing the null hypothesis to be rejected and a statistically significant false positive to be found.8 Type-I errors, also known as false positives, are when the null hypothesis is mistakenly rejected. Type-II errors, on the other hand, are also called false negatives. These occur when the null hypothesis is mistakenly accepted. In ANOVA, observations among groups must be independent, the groups must each have a normal distribution, and variances among groups must be equal to evaluate the null hypothesis. In medicine, this situation requires control over the 3 or more groups for all possible variables when investigating whether a single factor affects the means of the groups. The probability, calculated from the F-statistic, gives the likelihood that the difference in the groupsâ&#x20AC;&#x2122; means is the result of random sampling error. While this test is widely used in medicine, sometimes there are not large samples for each of the different groups. This scenario will cause ANOVA to produce type-II errors, meaning the null hypothesis will fail to be rejected even when it should be rejected, producing a false negative. In analysis of medical data, ANOVA analysis is used just like a t-test but for more than 2 treatment groups.

Tests That Are Not Parametric Measures exist to determine if data meet the appropriate assumptions for analysis using parametric tests like t-tests, Chi-square tests, and ANOVA. For example, the Shapiro-Wilk test, a test for normality, can determine if the samples from a population have a normal distribution, thus indicating the ability to use a t-test/ANOVA. If the Shapiro-Wilk test returns a P value below the specified alpha level (usually P < .05), the null hypothesis that the data come from a normal distribution would be rejected; analysis must commence using non-parametric tests.9 Non-parametric equivalents of almost all parametric statistical tests exist. In each case, they 18

make far fewer assumptions but sacrifice sensitivity. As an example, some non-parametric tests transform the data into rank order, allowing for comparison of the medians instead of the means. This method eliminates the need for data to be normally distributed and also lowers the variability, thus eliminating the effect of outliers. The drawback of non-parametric tests is a reduction of power when compared to its parametric counterpart, which then requires larger cohorts to show a significant difference of equal magnitude. While too many non-parametric analogs of parametric tests exist to list here, some examples include the Kruskal-Wallis (One-way ANOVA), Mann-Whitney U-test (t-test), and the Wilcoxon signed-rank test (paired t-test). In medicine, age is often compared between groups; however, because age is related to many disease processes and outcomes, it is rarely normally distributed and, thus, is often analyzed with non-parametric tests.

Potential Problems Too Few Patients, Too Many Groups In medical research at smaller institutions with a limited sample size, groups may exist that contain only a few patients. In these cases, many hypothesis tests are unlikely to reveal any significant group differences, necessitating another analytic approach.Â Oftentimes, patients can be clinically reclassified to reduce the degrees of freedom, yielding more patients per group and, thus, a more balanced analysis. This situation requires a biological understanding of the underlying question asked of the data. For example, a data set of patients that received various chemotherapy regimens for multiple myeloma containing 77 patients across 14 different groups could be analyzed via ANOVA. However, to strengthen the power of the analysis, an evaluation of the mechanism of action of the drugs in each regimen was completed to reduce the number of treatment regimens in this cohort. Patients were then reclassified by combined mechanism of action of the drugs in each respective regimen. This reclassification yielded only 5 biologically and clinically different groups instead of the previous 14, allowing for a more sensitive analysis. The importance of understanding the medicine and biology behind the data cannot be overstated. Many times, when working with small medical data sets, a familiarity with the underlying science is necessary to solve problems that are not immediately straightforward. This scenario is what makes working with small medical data sets simultaneously difficult and rewarding. GHS Proc. June 2017; 2 (1): 16-19

FINDING MEANING IN SMALL DATA SETS Categorical Data With No Expected Values Binary categorical outcome variables can be recoded as 0 and 1, respectively, and then analyzed via t-test. This method would be applicable when the assumptions for a Chi-square or Fisher’s exact test cannot be met; however, while the data will likely follow a binary distribution, it may approximate a normal distribution. When using this method, if the output variable is non-binary, a more sophisticated layering of binary variables is required (see effects coding or contrast coding for more information).

Small Data Sets Are Generalizable The most pronounced problem in analyzing small data sets is the perceived deficiency in the generalizable nature of the conclusions. Typically, hypothesis tests consider the sample size being analyzed such that a statistically significant difference in a small cohort is just as valid as those found in larger cohorts. The difference between small and large data sets lies in the magnitude of difference needed to reject the null hypothesis with an alpha level of .05. For example, if an actual difference of 25% between groups could be detected by a certain size data set, a larger cohort of patients would be required to detect a 10% difference. Thus, smaller data sets avoid false positives by requiring a larger difference between cohorts. This means that statistically significant findings from a small data set with a particular alpha level (compared to the same finding in a larger data set at the same alpha level) are likely of equal or greater magnitude than that of the larger data set without a loss of confidence. Thus, statistical significance in small data sets occurs much less frequently and only when the difference between the groups is large; however, there is difficulty in contributing to the

generalizable knowledge when the null hypothesis must be rejected to achieve a “statistically significant difference” between groups.

Conclusion In exploring some of the possible problems and solutions in analyzing small data sets, the goal is to demonstrate the logic and intentionality required to find meaning in this information. While research at smaller centers is currently under-represented in medical literature, this review illustrates some common problems and the solutions to facilitate the inclusion of the data generated at these centers into the body of generalizable medical knowledge. Additionally, it can serve as a call-to-arms of sorts for small medical institutions to begin meaningful research while simultaneously giving them the tools necessary to analyze their data. Specifically, this work can help clinicians who want, or need, to analyze their own data know where to start. The key is to understand the statistical tests, what they mean, how data must be appropriately coded, meaning of the output produced by a particular analysis, and power/ limitations in applicability. The most important rule in these analyses is to assure all transformations of the data do not affect the information stored therein. This fact requires knowledge of the underlying science and how the statistical test used deals with the data on a computational level.

Correspondence Address to: W. Jeffery Edenfield, MD, Greenville Health System, Institute for Translational Oncology Research, 900 W Faris Rd, Greenville SC 29605 (jedenfield@ghs.org)

As medicine moves toward evidence-based practice, the findings generated by these tools at smaller institutions will serve the patient population well, allowing clinicians to modify practice that more accurately reflect their demographic. Additionally, the generalizability of statistically significant hypothesis testing from small cohorts should not be dismissed outright but, rather, critically evaluated for what the statistical testing actually shows.

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2. Bacchetti P, Wolf LE, Segal MR, McCulloch CE. Ethics and sample size. Am J Epidemiol. 2005;161:105-10.

6. Du Prel J, Röhrig B, Hommel G, Blettner M. Choosing statistical tests: part 12 of a series on evaluation of scientific publications. Dtsch Arztebl Int. 2010;107:343-8.

3. Biau DJ, Kerneis S, Porcher R. Statistics in brief: the importance of sample size in the planning and interpretation of medical research. Clin Orthop Relat Res. 2008;466:2282-8. 4. van de Schoot R, Broere JJ, Perryck KH, Zondervan-Zwijnenburg M, van Loey NE. Analyzing small data sets using Bayesian estimation: the case of posttraumatic stress symptoms following mechanical ventilation in burn survivors. Eur J Psychotraumatology. 2015;6:25216.

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7. Ludbrook J, Dudley H. Issues in biomedical statistics: analyzing 2 x 2 tables of frequencies. Aust N Z J Surg. 1994;64:780-7. 8. Laerd statistics. One-way ANOVA in SPSS statistics. https://statistics.laerd.com/spss-tutorials/one-way-anova-using-spss-statistics.php. Accessed June 18, 2016. 9. Whitley E, Ball J. Statistics review 6: nonparametric methods. Crit. Care. 2002; 6:509-13.

Original Research

Orthostatic Intolerance and Other Autonomic Symptoms in Adolescents With Headaches Augusto Morales, MD; Andreea I. Stoichita, MD; and Jessica D. Wharton, MD From the Department of Pediatrics, Division of Pediatric Neurology, Greenville Health System, Greenville, SC (A.M.); Department of Pediatrics, Greenville Health System, Greenville, SC (A.I.S.); and Department of Pediatrics at Vanderbilt University School of Medicine, Nashville, Tenn (J.D.W.)

Abstract Background: The identification of autonomic comorbidity in adolescents with headaches could provide additional treatment strategies. The objective of this study was to identify and quantify autonomic symptoms in adolescents with headaches during a clinic visit using the COMPASS 31 questionnaire. Methods: The Institutional Review Board at Greenville Health System approved chart review of 92 adolescents seen in a pediatric neurology clinic with headache or syncope. All had active orthostatic testing and completed the COMPASS 31 and SCARED questionnaires. A 40 BPM (beats per minute) heart rate increase indicated postural orthostatic tachycardia. A score of >50% was considered high for the COMPASS 31 domains. A SCARED score >24 indicated anxiety. The relationship between high scores in COMPASS 31 domains and overall headache was studied by bivariate analysis and Fisher’s exact test; headache type by odds ratio; and headache frequency, anxiety, syncope, and orthostatic tachycardia by Chi-square analysis. Results: Eighty subjects had headaches, from which 65 were girls. Twelve subjects had syncope only, and 19 had both headache and syncope. Thirteen had orthostatic tachycardia; 43 had anxiety. Fifty-four subjects with headaches had high scores in the orthostatic intolerance (OI) domain, 37 in the pupillomotor domain, 17 in the vasomotor domain, and 8 in the gastrointestinal domain. OI was the only statistically significant domain when comparing subjects with and without headaches. Female sex, migraines, frequent headaches, and worsening headaches were statistically associated with OI domain high scores. Conclusions: The COMPASS 31 can be used in a busy clinic to identify and quantify OI in adolescents with headaches. Girls with migraine headaches, high headache frequency, and worsening headaches were more likely to have OI.

eadache is one of the most common health problems in adolescents. They can result in significant disability, poor quality of life, and school absenteeism.1 Adolescents with headaches are frequently refractory to pharmacologic interventions2 and can have significant comorbidity.3 They account for a significant number of referrals to the neurology clinic. Associations between headaches and the autonomic nervous system are well recognized. Many symptoms of migraine headaches are the result

of autonomic dysfunction. Dizziness and photophobia are prominent migraine symptoms.4 Migraineurs have a high prevalence of orthostatic intolerance (OI) and syncope.5 Teenagers with Persistent Orthostatic Tachycardia Syndrome (POTS), a disorder of the autonomic nervous system with chronic OI, report headaches very frequently. These patients may have “orthostatic headaches” in which standing up or lightheadedness may trigger or worsen headaches. Impaired cerebrovascular regulation may explain orthostatic headaches.6 GHS Proc. June 2017; 2 (1): 20-25

ORTHOSTATIC INTOLERANCE AND HEADACHES The mechanisms of headaches in adolescents are not well understood. Studies regarding the autonomic function in children and adolescents with headaches are limited and controversial. A sympathetic dysfunction, cranial parasympathetic dysfunction, or both has been postulated to explain migraine headaches.7 The identification of different types of autonomic symptoms in adolescents with headaches may be helpful to better diagnose a certain type of headache syndrome. It may also identify comorbid states that may provide additional treatment strategies to the physician treating adolescents with headaches. A comprehensive assessment of autonomic symptoms and functions is usually achieved using established questionnaires. Typically, these questionnaires are extensive and require computer analysis for score generation. They are used in autonomic disorder centers and are not easily completed on a single visit to a busy pediatric neurology/headache clinic. At the Mayo Clinic, a refined and abbreviated composite autonomic symptom score (COMPASS), based on the well-established 169 questions of the Autonomic Symptom Profile, 8 has been developed and consists of only 31 questions that address 6 autonomic domains. These include OI, as well as vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor dysfunction. This new questionnaire is user friendly, broadly applicable, and easy to administer in a short time without the need for computer analysis. Known as the COMPASS 31, it provides a global autonomic severity score, and specific domain scores that are clinically and scientifically meaningful. Higher scores indicate a larger number of symptoms, increased severity of symptoms, or symptom progression in each domain.9 The objective of this study was to identify and quantify autonomic symptoms in adolescents with headaches during a routine visit to the pediatric neurology clinic.

Methods Following Institutional Review Board approval, chart review of 92 consecutive adolescent patients seen in the pediatric neurology clinic with complaints of headache or syncope was conducted. The patients were seen between January 1, 2013– April 24, 2015. Patients were referred to the clinic because of the severity of their headaches and failure to respond to standard treatment by their primary care pediatrician. Subjects were evaluated with a clinical history, physical exam, and neurologic exam. In addition, during a single

GHS Proc. June 2017; 2 (1): 20-25

visit, these subjects had an autonomic/psychogenic evaluation that included active orthostatic testing at the bedside, completion of the COMPASS 31 self-assessment autonomic symptom questionnaire, and completion of the Screen for Child Anxiety Related Emotional Disorders (SCARED) questionnaire.10 During the chart review, the presence or absence of headache, syncope, and OI symptoms was noted. Headaches were first classified according to the International Classification of Headache Disorders 3 (ICHD3). They were grouped into 1 of 3 headache groups, which included tension-type headache, migraine headache, and daily persistent headache. Subjects with syncope and no headaches were used as a control group of patients with autonomic dysfunction but no headaches. Headache symptom duration was classified as recent (<3 months), subacute (3–6 months) and chronic (>6 months). Headaches were also classified as frequent (>7 headaches in a 15-day period), worsening (increase frequency over the last 3 months), improving (decreased frequency over the last 3 months), and transforming (changing headache type). The COMPASS 31 and the SCARED questionnaires were completed consecutively by the patient in the examining room. A score of >50% on each domain of the COMPASS 31 was considered a high score indicative of significant autonomic symptoms in each domain. A total score of 25 or more in the SCARED questionnaire was considered positive and indicative of anxiety. Active bedside orthostatic testing was performed by a nurse in the examining room after a rest period of 20 minutes in which the patient was lying supine. Blood pressure and heart rate were noted while supine, then immediately after standing, and again at 5 and 10 minutes. Presence or absence of orthostatic symptoms was noted. An increase in heart rate of 40 BPM (beats per minute), systolic hypotension of 20 mmHg, or diastolic hypotension of 10 mmHg were considered significant during active bedside orthostatic testing. The relationship between high scores in COMPASS 31 domains and overall headache was studied by bivariate analysis and Fisher’s exact test; headache type by odds ratio; and headache frequency, anxiety, syncope, and orthostatic tachycardia by Chi-square analysis.

Results Demographics and Chart Review Ninety-two consecutive subjects were studied. There were 65 females and 27 males ages 12â&#x20AC;&#x201C;18 years (mean age of 15 years). Eighty subjects (88%) had recurrent headaches, 66 (83%) had chronic headaches, and 50 (63%) had a high headache frequency. Nineteen (23%) had headache and syncope, while 14 subjects (18%) had headaches only with no syncope or symptoms of OI. Fifty subjects (63%) had migraine headaches; 14 subjects (18%) had tension-type headaches. Thir-

Figure 1 Patient characteristics: headache type.

Number of patients 60 50 40 30 20 10 0

Migraine

Tension type

Daily persistent

Mixed

Figure 2 Patient characteristics: anxiety, total score, and anxiety subsets according to SCARED questionnaire.

Number of patients 50 45 40 35 30 25 20 15 10 5 0

Total score

Panic/somatic Generalized symptoms anxiety

Separation anxiety

Social anxiety

School avoidance

teen (16%) had daily persistent headaches, and 3 subjects (4%) had headaches with mixed features. The control group consisted of 12 subjects (13%) with syncope and no headaches (Fig. 1).

SCARED Questionnaire Forty-three subjects (52%) with headaches had a high total score of 25 or more, indicative of anxiety. Thirty-one subjects (39%) had scores that may indicate panic disorder or significant somatic symptoms. Twenty-nine (35%) had scores that may indicate general anxiety disorder. Twenty-six (33%) had scores that may indicate separation anxiety. Thirty (38%) had scores that may indicate social anxiety. Forty subjects (50%) had scores that may indicate significant school avoidance (Fig. 2) Active Bedside Orthostatic Intolerance Testing Thirty subjects (38%) with headaches had 1 or more symptoms during testing. Twenty-four reported dizziness or lightheadedness. Six had a headache, 3 of whom reported an orthostatic headache. Two subjects had nausea, while 2 others had numbness. One subject had tinnitus, and 1 felt hot. There were no cases of syncope. Two had systolic hypotension and extreme dizziness. In these 2 patients, testing was discontinued after determination of hypotension. Thirteen subjects (16%) had an increase in heart rate of more than 40 BPM, indicative of orthostatic tachycardia. Five of these subjects had symptoms. Fifteen subjects had symptoms and no abnormalities noted in blood pressure or pulse during testing. COMPASS 31 Data Of the 80 patients with headaches, 54 subjects (68%) had a high score for the OI domain. Only 5 subjects (6%) did not report OI symptoms. Twenty-seven subjects (34%) had a high score for the pupillomotor domain, while only 10 subjects (13%) had no symptoms in this domain. Seventeen subjects (21%) had a high score for vasomotor domain; 54 (68%) had no symptoms in this domain. Eight subjects (10%) had a high score for gastrointestinal domain, and 8 (10%) had no symptoms in this domain. Two subjects (3%) had high scores in the secretomotor domain, while 54 (68%) had no symptoms in this domain. No subjects had high scores for bladder domain; 63 (79%) had no symptoms at all in this domain. From the 12 subjects in the control group, 2 subjects had a high score in the OI domain, and 2 subjects had no symptoms in this domain. When subjects with headache were compared to the GHS Proc. June 2017; 2 (1): 20-25

ORTHOSTATIC INTOLERANCE control group, OI was the only COMPASS 31 domain that was significant (P = .001) (Table 1).

High Score on the Orthostatic Intolerance Domain of COMPASS 31 Of the 54 subjects with headaches and high scores on the OI domain, 46 (82%) were girls. Thirty-five subjects (62.5%) had migraine headaches, 36 (64.3%) had frequent headaches, and 20 (37.7%) had worsening headaches. When compared with subjects with headaches and low OI scores, the following categories were significant: female sex (P = .002), migraine headaches (P = .005), high headache frequency (P = .017), and worsening headaches (P = .019). A history of syncope, high anxiety scores on the SCARED questionnaire, or OI in heart rate during active bedside orthostatic testing was not found to be significant between these 2 groups (Table 2).

Table 1 COMPASS 31 domain high scores in subjects with headaches and controls. High Score (>50%) in COMPASS 31 Domain

No.

Headache N = 80

Control N = 12

P value

Orthostatic intolerance

.001

Vasomotor

.44

Secretomotor

.99

Gastrointestinal

.99

Bladder

Pupillomotor

.09

Table 2 Subjects with high score on OI domain versus low scores and other subject characteristics.

Discussion We studied adolescents referred to a subspecialty clinic with a longstanding history of frequent headaches with comorbidities of syncope and anxiety. The female sex preponderance noted in our study is not unusual in adolescents with headaches.11 We used the COMPASS 31 questionnaire to identify and quantify autonomic dysfunction. All subjects had standard active orthostatic testing at the bedside to document OI features and also completed the SCARED questionnaire to study the possible effects of anxiety on the results. Most subjects had autonomic symptomatology noted on the different domains of COMPASS 31. Significantly high scores indicative of high symptom frequency, symptom severity, and symptom progression were noted only in the OI domain. Many subjects had high scores in the pupillomotor and vasomotor domains, but these did not achieve statistical significance. Less-than-expected scores in the pupillomotor domain may result from a dilution effect of the number of patients who had non-migraine headaches. Very few subjects had high scores in the gastrointestinal and secretomotor domain, and none in the bladder domain. Lack of bladder symptoms is likely because this autonomic domain is mainly controlled by the caudal parasympathetic system. The absence of high scores in other autonomic domains suggests that headaches in adolescents may not be associated with a widespread dysautonomia. OI can be defined by the inability to tolerate the upright posture because of signs and symptoms that are relieved by lying down. OI is manifested by lightheadedness, blurred vision, decreased GHS Proc. June 2017; 2 (1): 20-25

No. Total, N

OI High Score N = 56

OI Low Score N = 36

Gender, no. (%) Girls

.002 65

46 (82.1)

19 (52.8)

Type of headache, no. (%)

.005

No headache

2 (3.6)

10 (27.8)

Migraine

35 (62.5)

15 (41.7)

Tension headache

7 (12.5)

7 (19.4)

Daily persistent

9 (16.1)

4 (11.1)

Headache frequency (within 15 day period), no. (%) ≥7 days

. 017 50

36 (64.3)

14 (38.8)

Tachycardia >40 BPM, no. (%) Yes

.95 13

8 (14.3)

5 (13.8)

Syncope, no. (%) Present

.92 19

13 (23.2)

6 (16.7)

Total anxiety score, no. (%) High score

P value

.10 43

30 (53.6)

13 (36.1)

Change in headache symptoms, no. (%)

.019

Transformation

30 (56.6)

30 (83.3)

Worsening

20 (37.7)

5 (13.9)

Improvement

1 (1.9)

1 (2.8)

BPM, beats per minute

Acknowledgment The authors acknowledge the valuable assistance of Nirav T. Patil, MBBS, MPH, who provided consultation and performed the statistical analyses. We are also grateful for the additional services provided by our clinic nurses.

Abbreviations and Acronyms OI = orthostatic intolerance; POTS = Postural Orthostatic Tachycardia Syndrome; COMPASS = Composite Autonomic Symptom Scale; ASP = Autonomic Symptom Profile; SCARED = Screen for Children Anxiety Related Emotional Disorders; ICHD3 = International Classification of Headache Disorders 3; BPM = beats per minute

Correspondence Address to: Augusto Morales MD, Greenville Health System, Department of Pediatrics, Division of Pediatric Neurology, 200 Patewood Dr, Suite A350, Greenville, SC 29615 (amorales@ghs.org)

hearing, vertigo, and altered cognition. Some patients experience sudden syncope shortly after standing up or after prolonged standing.12 OI may be the manifestation of multiple underlying mechanisms. OI is noted in subjects with migraine, dysautonomia,13 peripheral neuropathy,14 POTS,15 chronic fatigue syndrome,16 and genetic conditions.17 OI can also occur after excessive recumbence, deconditioning, and hypovolemia.18 OI symptoms are also noted in psychogenic dizziness.19 The evaluation of patients with OI requires a methodical search for the mechanism involved as treatment will greatly depend on the etiology.20 Bedside active orthostatic testing and Head-Up Tilt testing are frequently used to demonstrate orthostatic hypotension or orthostatic tachycardia. A tachycardia of more than 40 BPM is necessary for a diagnosis of POTS in adolescents.

frequency—do not address whether OI symptoms are related to headaches. The subjects with significant OI in our study had headaches of high frequency or worsening frequency, and the majority had migraine headaches. High headache/migraine frequency may cause excessive recumbence, deconditioning, and frequent vomiting that may lead to hypovolemia causing OI by these indirect mechanisms.

The scope of our study did not address all possible causes for OI. Orthostatic hypotension and postural orthostatic tachycardia were studied with active bedside orthostatic testing. Sixteen percent of our patients had orthostatic tachycardia, while 3% had orthostatic hypotension. Therefore, a small number of our subjects could be characterized as having POTS and having orthostatic hypotension. The rest of the subjects, despite having similar clinical profiles of subjects with POTS, could not be diagnosed with this condition. It is possible that they may have a milder, early, or similar form of this common autonomic condition. OI could also be the result of additional stress to the regulatory capabilities of the circulatory system imposed by frequent headaches. The questions of the COMPASS 31— focused on daily life OI symptom severity and

In this study, OI was frequently noted in adolescents with headaches. The COMPASS 31 is an instrument that can be easily used in a busy clinic to identify and quantify OI. Girl patients with migraine headaches, high headache frequency, and worsening headaches were more likely to have OI.

Conclusion

Early diagnosis of OI using minimally invasive procedures available in an outpatient clinic can provide the physician a better understanding of the usually complex problems that adolescents with headaches experience. Once OI has been identified, a careful evaluation may identify the mechanisms of OI in each patient, providing an additional treatment approach that is likely to improve the quality of life for the adolescent with headaches.

References 1. Krogh AB, Larsson B, Linde M. Prevalence and disability of headache among Norwegian adolescents: a cross-sectional school-based study. Cephalalgia. 2015;35:1181-91. 2. Powers SW, Coffey CS, Chamberlin LA, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376:115-23. 3. Blaauw BA, Dyb G, Hagen K, et al. The relationship of anxiety, depression, and behavioral problems with recurrent headache in late adolescence—a YoungHunt follow-up study. J Headache Pain. 2015;16:10. 4. Drummond PD. Relationships among migrainous, vascular, and orthostatic symptoms. Cephalalgia. 1982; 2:157-61. 5. Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG. Syncope in migraine: the

Psychogenic issues are always a concern when dealing with patients with OI symptoms and refractory headaches. In our study, there were a large number of subjects with anxiety and panic/ somatic symptom disorders. Anxiety was present in patients with high OI scores and in patients with low OI scores and did not have a significant statistical effect.

population-based 2006;66:1034-7.

CAMERA

study.

Neurology.

6. Khurana R, Eisenberg L. Orthostatic and non-orthostatic headache in postural tachycardia syndrome. Cephalalgia. 2010;31:409-15. 7. Yakinci C, Mungen B, Er H, Durmaz Y, Karabiber H. Autonomic nervous system function in childhood migraine. Pediatrics International. 1999;41:529-533. 8. Suarez GA, Opfer-Gehrking TL, Offord KP, Atkinson EJ, O’Brien PC, Low PA. The autonomic symptom profile: a new instrument to assess autonomic symptoms. Neurology. 1999;52:523-8. 9. Sletten DM, Suarez GA, Low PA, Mandrekar J, Singer W. COMPASS 31: a refined and abbreviated composite autonomic symptom score. Mayo Clin Proc. 2012;87:1196-201.

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ORTHOSTATIC INTOLERANCE AND HEADACHES 10. Muris P, Merckelbach H, van Brakel A, Mayer B, van Dongen L. The screen for child anxiety related emotional disorders (SCARED): relationship with anxiety and depression in normal children. Personality and Individual Differences. 1998;24:451-6. 11. Huguet A, Tougas ME, Hayden J, et al. Systematic review of childhood and adolescent risk and prognostic factors for recurrent headaches. J Pain. 2016;17:855-73. 12. Stewart JM. Common syndromes of orthostatic intolerance. Pediatrics. 2013;131:968-80. 13. Grubb BP, Kosinski. Syncope resulting from autonomic insufficiency syndromes associated with orthostatic intolerance. Med Clin North Am. 2001;85:457-72. 14. Novak V, Freimer ML, Kissel JT, et al. Autonomic impairment in painful neuropathy. Neurology 2001;56:861-8. 15. Freeman R, Wieling W, Axelrod FB, et al. Consensus

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statement on the definition of orthostatic hypotension, neutrally mediated syncope and the postural tachycardia syndrome. Clin Auton Res.2011;21:69-72. 16. Stewart JM, Gewitz MH, Weldon A, Arlievsky N, Li K, Munoz J. Orthostatic intolerance in adolescent chronic fatigue syndrome. Pediatrics. 1999;103:116-21. 17. De Wandele I, Rombaut L, De Backer T, et al. Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos syndrome. Rheumatology. 2016;55:1412-20. 18. Stewart JM Chronic orthostatic intolerance and the postural tachycardia syndrome (POTS). J Pediatrics. 2004;145:725-30. 19. Blad H, Lamberts RJ, van Dijk JG, Thijs RD. Tilt-induced vasovagal syncope and psychogenic pseudosyncope. Neurology. 2015;85:2006-10. 20. Qubty W, Kedia S. Dizziness and orthostatic intolerance in pediatric headache patients. Semin Pediatr Neurol. 2016;23:71-8.

Original Article

Impact of an Antimicrobial Stewardship-Driven Initiative to Assess Appropriateness of Asymptomatic Bacteriuria or Funguria Treatment Pooja J. Shah, PharmD; Carmen M. Faulkner-Fennell, PharmD, BCPS; Jessica M. Odom, PharmD, BCPS, BC-ADM; John H. Schrank Jr, MD; Jennifer R. Meredith, PhD, HCLD; and Jun Wu, PhD From the Department of Pharmacy, Greenville Health System, Greenville, SC (P.J.S., C.M.F.-F.); Department of Internal Medicine, Greenville Health System, Greenville, SC (J.M.O.); Department of Infectious Disease, Greenville Health System, Greenville, SC (J.H.S.); Department of Laboratory Services, Greenville Health System, Greenville, SC (J.R.M.); and Presbyterian College School of Pharmacy, Clinton, SC (J.W.)

Abstract Background: Urinary tract infections are misdiagnosed in 40% of patients. Inappropriate use of antimicrobials leads to increased resistance, expense, and adverse drug reactions. Despite guideline recommendations, studies report that 45%–65% of patients receive inappropriate treatment. A stewardship initiative could prevent further antimicrobial resistance, improve patient safety, and reduce expenses. Methods: This research was a single center, retrospective and concurrent, cohort study. The primary outcome was to determine the difference in the days of antimicrobial therapy between retrospective and concurrent groups. Secondary outcomes included baseline asymptomatic bacteriuria or funguria rate, baseline rate of asymptomatic bacteriuria or funguria treated inappropriately with antimicrobials, and stewardship recommendation acceptance rate during the concurrent period. Results: Sixty-nine patients were included: 46 in the retrospective cohort and 23 in the concurrent cohort. The mean ± standard deviation in the days of antimicrobial therapy was 8.26 ± 10.9 in the retrospective group compared to 4.70 ± 2.9 in the concurrent group (P = .0426). Baseline rate of asymptomatic bacteriuria or funguria was 39.1% in the retrospective group and 17.4% in the concurrent group (P = .1002); the baseline rate of asymptomatic bacteriuria or funguria inappropriately treated with antimicrobials was 77.8% in the retrospective group and 50% in the concurrent group (P = .2920). Stewardship recommendations were made and accepted in 60.9% of patients in the concurrent group. Conclusions: Active pharmacist-led stewardship in patients with positive urine cultures led to a significant reduction in antimicrobial days of therapy, as well as optimization of antimicrobial therapy.

pproximately 40% of urinary tract infections (UTIs) are inappropriately diagnosed, which leads to increased and unwarranted antimicrobial use.1 Inappropriate antimicrobial treatment of asymptomatic bacteriuria or funguria results in increased antimicrobial resistance, expense, and adverse drug reactions such as Clostridium difficile infections (CDI).2

The Infectious Diseases Society of America (IDSA) published guidelines in 2005 for the diagnosis and treatment of asymptomatic bacteriuria, which are undergoing updates to be released in spring 2017. Based on current guidelines, patients with positive urine cultures without symptoms should not receive antimicrobial therapy unless pregnant, undergoing urologic procedures with

GHS Proc. June 2017; 2 (1): 26-31

ASYMPTOMATIC BACTERIURIA AND STEWARDSHIP anticipated mucosal bleeding, undergoing transurethral resection of prostate (TURP), or if bacteriuria persists for greater than 48 hours postcatheter removal.2 These recommendations are based on several published trials that evaluated the effects of prescribing antimicrobial treatment for asymptomatic bacteriuria or funguria in elderly institutionalized patients, ambulatory elderly residents, non-pregnant premenopausal females, patients with diabetes, and those who are catheterized. While the trials demonstrated no difference in mortality in the treatment compared to the nontreatment groups, there was an increase in re-infection rates and adverse drug reactions.3-8 Despite evidence-based IDSA guideline recommendations, studies report approximately 45%–65% of patients receive inappropriate antimicrobial treatment for UTIs.9,10 A few studies have demonstrated that education regarding inappropriate use of antimicrobial therapy in patients with asymptomatic bacteriuria and electronic alerts to prescribers to discontinue use of inappropriate antimicrobials can have a positive impact on reduction of antimicrobial days. Those effects, however, were not sustained without active antimicrobial stewardship.10,11 Based on available data, a pharmacist-driven antimicrobial stewardship initiative to reduce antimicrobial use for asymptomatic bacteriuria or funguria could reduce the number of antimicrobial days of therapy, prevent further antimicrobial resistance, improve patient safety, and reduce expenses.1,5 The objective of this study was to assess the impact of an antimicrobial stewardship-driven initiative to determine appropriateness of asymptomatic bacteriuria or funguria treatment in hospitalized adult patients with a positive urine culture.

Methods Study Design This retrospective and concurrent cohort study was conducted at a single-center, acute care hospital. The retrospective cohort included adult patients with at least 1 positive urine culture between January 2015–March 2015. The concurrent cohort included adult patients with at least 1 positive urine culture between January 2016– March 2016. Patients in the concurrent cohort were assessed for appropriateness of antimicrobial therapy and were contacted by telephone or in person to provide stewardship recommendations as needed. The study was granted approval by Greenville Health System’s Institutional Review Board with waiver of consent before study initiation. GHS Proc. June 2017; 2 (1): 26-31

Inclusion and Exclusion Criteria As demonstrated in Table 1, patients in the retrospective cohort and the concurrent cohort were included if they were 18 years of age or older with at least 1 positive urine culture and admitted as an inpatient to Greenville Health System’s Greenville Memorial Hospital or its Roger C Peace Rehabilitation Hospital. Patients were excluded if they met 1 or more of the following criteria: pregnancy, undergoing TURP procedure, undergoing a urologic procedure with anticipated mucosal bleeding, bacteriuria persisted for greater than 48 hours postcatheter removal, neutropenic (absolute neutrophil count <1000), history of renal transplant, history of ureteral stents, or no urinalysis documented for the admission period. Data Collection Patients in the retrospective cohort were identified via a report of positive urine cultures from the Table 1 Baseline characteristics.

Characteristic N

Retrospective Cohort

Concurrent Cohort

Gender, no. (%)

.38

Male

14 (30.4)

4 (17.4)

Female

32 (69.6)

19 (82.6)

Age, mean years

P Value

Race, no. (%)

--.61

Caucasian

35 (76.1)

20 (87.0)

African American

8 (17.4)

3 (13.0)

Other

3 (6.5)

0 (0)

Antimicrobial allergies, no. (%)

<.0001

Beta-lactams

9 (19.6)

0 (0.0)

Sulfa

2 (4.4)

3 (13.0)

Tetracyclines

0 (0.0)

Other/Multiple allergies

19 (41.3)

1 (4.4)

No known drug allergies

16 (34.8)

19 (82.6)

History of UTIs, no. (%)

<.0001

Yes

3 (6.5)

13 (56.5)

43 (93.5)

10 (43.5)

UTI, urinary tract infection

microbiology lab. Patients in the concurrent cohort were identified daily by a pharmacist via Sentri7 , a clinical surveillance software program, which identified patients with a positive urine culture in real-time. Appropriateness of current therapy and recommendations were provided with guidance from the antimicrobial stewardship team.

Data points collected included baseline characteristics (eg, gender, allergies), urinalysis results (eg, squamous epithelial cell count), lab values (eg, serum creatinine), sites and results of all cultures, UTI-related symptoms (eg, flank pain), type of UTI, antimicrobials used, and days of antimicrobial therapy. Antimicrobial stewardship intervention type and acceptance of intervention within a 48-hour period were collected in the concurrent cohort only.

Outcomes The primary outcome was the number of antimicrobial days of therapy (DOT). Antimicrobial DOT was defined as the administration of a single agent on a given day regardless of the number of doses administered or dosage strength; in essence, 1 DOT was the administration of at least 1 dose of a single agent on a given day. Secondary outcomes included baseline rate of asymptomatic bacteriuria or funguria, baseline rate of asymptomatic bacteriuria or funguria inappropriately treated with antimicrobials, average cost of antimicrobial therapy, squamous epithelial cell count in urinalysis results, and rate of stew-

Table 2 Urine culture microorganisms. Retrospective Cohort no. (%)

Concurrent Cohort no. (%)

Escherichia coli

11 (23.9)

10 (43.5)

Enterococcous species

11 (23.9)

5 (21.7)

Pseudomonas aeruginosa

2 (4.4)

1 (4.4)

Klebsiella species

7 (15.2)

3 (13)

Candida species

5 (10.9)

1 (4.4)

Coagulase-negative staphylococcus

0 (0.0)

1 (4.4)

Citrobacter species

1 (2.2)

0 (0.0)

Proteus mirabilis

5 (10.9)

1 (4.4)

Enterobacter species

1 (2.2)

0 (0.0)

Characteristic N

ardship recommendation acceptance during study concurrent period. Stewardship recommendations included de-escalation, discontinuation, length of therapy, dose and/or interval adjustments, and intravenous-to-oral (IV-to-PO) transitions.

Statistical Analysis Student’s t-tests for continuous variables and Chisquare tests for categorical variables were used to compare baseline patient characteristics between retrospective and concurrent cohorts. T-tests or Wilcoxon rank-sum tests were used to assess the effect of intervention on the primary outcome (days of antimicrobial therapy) and secondary outcomes (treatment cost). Chi-square tests were used to examine the associations between the intervention and other secondary outcomes (baseline asymptomatic bacteria or funguria, CDI, and acceptance of stewardship recommendation). Statistical significance was defined as P < .05. All analyses were performed by SAS 9.4 software.

Results Patients In the retrospective period, 50 patients were assessed. Four patients were excluded because of no documented urinalysis; thus, 46 patients were included. In the concurrent period, 27 patients were assessed. Four patients were excluded because of a history of ureteral stents and renal transplants; thus, 23 patients were included. Characteristics of included patients are shown in Table 1. The majority in both cohorts were older Caucasian women. A significantly lower number of patients with a history of UTIs occurred in the retrospective cohort compared to the concurrent cohort, which may be attributed to clearer past medical histories provided in a new electronic health record (EHR) system. Also, approximately 50% of patients had urine cultures positive for Escherichia coli and Enterococci in the retrospective period compared 65% of patients in the concurrent period (Table 2).

Primary Outcome The mean ± standard deviation (SD) number of days of antimicrobial therapy was 8.26 ± 10.9 in the retrospective period compared to 4.70 ± 2.9 in the concurrent period (P = .0426). Overall, there was approximately a 3.5-day reduction with active stewardship intervention. Secondary Outcomes As referenced in Table 3, the baseline rate of asymptomatic bacteriuria or funguria was 39.1% in the retrospective cohort and 17.4% in the conGHS Proc. June 2017; 2 (1): 26-31

ASYMPTOMATIC BACTERIURIA AND STEWARDSHIP current cohort (P = .1002). The baseline rate of asymptomatic bacteriuria or funguria inappropriately treated with antimicrobials was 77.8% in the retrospective cohort and 50.0% in the concurrent cohort (P = .2920). The mean ± SD cost of antimicrobial therapy in the retrospective cohort was $45.5 ± $139.5 compared to the concurrent cohort, which was $11.4 ± $10.5 (P = .2479). No patients in the retrospective group with reported urinalysis results had squamous epithelial cell counts greater than 20, while 2 patients in the concurrent group had counts greater than 20. Approximately 70% of patients in both groups had squamous epithelial cell counts less than 10, indicating low levels of urinalysis contamination. Of note, almost 25% of patients in both groups had no squamous epithelial cell counts reported (Table 4). In the concurrent cohort, 60.9% of patients had stewardship recommendations that were completely or partially accepted, while 30.4% of patients had no recommendations thanks to appropriate therapy. Only 9% of patients had recommendations to discontinue antimicrobial treatment for asymptomatic bacteriuria or funguria. However, a majority of patients were recommended to continue therapy with adjustments after confirmation of UTI-related symptoms (Table 5). The most common adjustments were stop dates and de-escalations (Table 6).

Discussion Treatment of asymptomatic bacteriuria is a major source of unnecessary antimicrobial use among hospitalized patients and is, therefore, a target for antimicrobial stewardship programs. Our study demonstrated that a pharmacist-led stewardship initiative can lead to a significant reduction in antimicrobial DOT. Although the baseline rate of asymptomatic bacteriuria or funguria and the baseline rate of asymptomatic bacteriuria or funguria cases inappropriately treated with antimicrobials were not statistically different, a distinct numerical difference exists between the groups. Interestingly, urinalysis contamination was not found to be a reason for overuse of antimicrobials, as no patients in the retrospective group and 2 patients in the concurrent group had over 20 squamous epithelial cells. Notably, approximately 25% of patients from both groups had no reported squamous epithelial cell counts, which is generally helpful in guiding clinicians as to whether urinalysis results are interpretable. Also, no statistically significant reduction in expenses took place. However, other stewGHS Proc. June 2017; 2 (1): 26-31

Table 3 Baseline rate of asymptomatic bacteriuria or funguria.

Characteristic

Retrospective Cohort

Concurrent Cohort

18 (39.1)

4 (17.4)

.1002

14 (77.8)

2 (50.0)

.2920

N Asymptomatic bacteriuria or funguria, no. (%) Asymptomatic bacteriuria or funguria inappropriately treated with antimicrobials, no. (%)

P Value

Table 4 Squamous epithelial cell count from urinalysis.

Squamous cells/hpf N

Retrospective Cohort Concurrent Cohort no. (%) no. (%) 46

32 (69.6)

15 (65.2)

11–20

2 (4.3)

1 (4.3)

>20*

0 (0.0)

2 (8.7)

Not reported

12 (26.1)

5 (21.7)

<10

hpf, high-power field/*Contaminated urinalysis

Table 5 Rate of stewardship acceptance within 48 hours of recommendation. Stewardship acceptance Yes, no. (%)

Concurrent Cohort (N = 23) 12 (52.2)

Partial, no. (%)

2 (8.7)

No, no. (%)

2 (8.7)

No recommendation, no. (%)

7 (30.4)

Table 6 Stewardship recommendation for adjustment(s) to therapy.

Adjustments

Concurrent Cohort (N = 23)

Stop date, no. (%)

10 (66.7)

De-escalation, no. (%)

7 (46.7)

Bug-drug mismatch, no. (%)

2 (13.3)

Repeat urinalysis, no. (%)

1 (6.7)

IV to PO conversion, no. (%)

1 (6.7)

Dose and/or interval adjustment, no. (%)

1 (6.7)

Abbreviations and Acronyms UTI = urinary tract infection; CDI = Clostridium difficile infections; IDSA = Infectious Diseases Society of America; TURP = transurethral resection of prostate; DOT = days of therapy; IV = intravenous; PO = oral; EHR = electronic health record; SD = standard deviation

Correspondence Address to: Carmen FaulknerFennell, PharmD, BCPS, Greenville Health System, Department of Pharmacy, 701 Grove Rd, Greenville, SC 29607 (cfaulkner@ ghs.org)

ardship-related published studies with larger sample sizes have shown meaningful expense reductions.12-15 Of note, the most common microorganisms identified in urine cultures during both periods were Escherichia coli and Enterococci. Specifically, no patients included in the study had urine cultures with extended-spectrum beta-lactamase microorganisms. Overall, the high recommendation acceptance rate in our study reinforced the strong value of pharmacist-led stewardship initiatives as supported by other published studies.15,16 Laible and colleagues implemented a pharmacist-led antimicrobial stewardship service on 1 medical/surgical ward at a 545-bed community teaching hospital.16 Over a 2-year period, approximately 70% of recommendations were accepted using primarily a prospective audit and feedback approach. This pharmacist-led antimicrobial stewardship program successfully optimized and de-escalated antimicrobial treatment as well as prevented significant adverse drug events such as CDIs. This study has several limitations. The institution transitioned to a different EHR during the concurrent period, which affected documentation practices. Before the EHR transition, the medical record was a hybrid of paper and electronic documentation, which led to difficulties assessing if patients truly had symptoms of a UTI or asymptomatic bacteriuria or funguria in the retrospective group. Therefore, if no symptoms were documented, it was assumed the patient had asymptomatic bacteriuria or funguria. Despite the transition to the EHR during the concurrent period, there was still a notable absence of UTI symptoms documented in the medical record. This limitation was overcome because

strong pharmacist and prescriber professional relationships allowed for the ability to clarify the presence and type of UTI symptoms and to discuss the appropriateness of antimicrobial treatment. Another limitation was use of antimicrobials for other indications, which at times was a confounding factor to being able to solely focus on appropriate therapy for a positive urine culture. Our study identified and included adult patients with positive urine cultures. In the concurrent cohort, only 9% of antimicrobial stewardship recommendations were to discontinue antimicrobial therapy. The percentage of recommendations to discontinue therapy was low and could represent the need to identify asymptomatic bacteriuria patients through additional routes, including urine specimen ordered and collected, urinalysis, UTI indication selection on a specific antimicrobial, or documentation in the medical chart. The identification of patients by positive urine culture only could also have contributed to the fact there were just 2 patients identified in the concurrent cohort with squamous cell counts greater than 20, representing contamination. At the time of this study, the EHR was in transition and the positive urine culture list was the only available method of identification.

Conclusion This study illustrates that pharmacist-led active stewardship focusing on patients with positive urine cultures can lead to significant improvements in patient care, such as optimized antimicrobial therapy and a reduction in antimicrobial DOT. The study also provided pivotal opportunities to increase awareness on the importance of documenting UTI symptoms to aid in determining whether antimicrobial therapy is warranted, and to re-educate healthcare professionals about IDSA asymptomatic bacteriuria guidelines.

References 1. Dull R, Friedman S, Risoldi Z, Rice E, Starlin R, Destache C. Antimicrobial treatment of asymptomatic bacteriuria in noncatheterized adults: a systematic review. Pharmacotherapy. 2014.34:941-60. 2. Nicolle L, Bradley S, Colgan R, Rice J, Schaeffer A, Hooton T. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643-54. 3. Abrutyn E, Mossey J, Berlin J, et al. Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med. 1994;120:827-33.

4. Asscher A, Sussman M, Waters W, et al. The clinical significance of asymptomatic bacteriuria in the nonpregnant woman. J Infect Dis. 1969;120:17-26. 5. Gross PA, Patel B. Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria. Clin Infect Dis. 2007;5:42-5. 6. Harding G, Zhanel G, Nicolle L, Cheang M. Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med. 2002; 347:1576-83. 7. Hooton T, Bradley S, Cardenas D, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 international clin-

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ASYMPTOMATIC BACTERIURIA AND STEWARDSHIP ical practice guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010;50:625-63. 8. Kauffman C, Vazquez J, Sobel J, et al. Prospective multicenter surveillance study of funguria in hospitalized patients. The National Institute for Allergy and Infectious Diseases (NIAID) Mycoses Study Group. Clin Infect Dis. 2000;30:14-8. 9. Chowdhury F, Sarkar K, Branche A, et al. Preventing the inappropriate treatment of asymptomatic bacteriuria at a community teaching hospital. J Community Hosp Intern Med Perspect. 2012;2(2). 10. Pavese P, Saurel N, LabarĂ¨re J, et al. Does an educational session with an infectious diseases physician reduce the use of inappropriate antibiotic therapy for inpatients with positive urine culture? A controlled before and after study. Infect Control Hosp Epidemiol. 2009;30:596-9. 11. Linares L, Thornton D, Strymish J, Baker E, Gupta K. Electronic memorandum decreases unnecessary antimicrobial use for asymptomatic bacteriuria and culture-negative pyuria. Infect Control Hosp Epidemiol. 2011;32:644-8.

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12. Martin C, Ofotokun I, Rapp R, et al. Results of an antimicrobial control program at a university hospital. Am J Health-Sys Pharm. 2005;62:732-8. 13. Gross R, Morgan A, Kinky D, Weiner M, Gibson G, Fishman N. Impact of a hospital-based antimicrobial management program on clinical and economic outcomes. Clin Infect Dis. 2001;33:289-95. 14. Nowak M, Nelson R, Breidenbach J, Thompson P, Carson, P. Clinical and economic outcomes of a prospective antimicrobial stewardship program. Am J Health Syst Pharm. 2012;17:1500-8. 15. Newland J, Stach L, De Lurgio S, et al. Impact of a prospective-audit-with-feedback antimicrobial stewardship program at a childrenâ&#x20AC;&#x2122;s hospital. J Pediatric Infect Dis Soc. 2012;3:179-86. 16. Laible B, Nazir J, Assimacopoulos A, Schut J. Implementation of a pharmacist-led antimicrobial management team in a community teaching hospital: use of pharmacy residents and pharmacy students in a prospective audit and feedback approach. J Pharm Pract. 2010;23:531-5.

Original Research

Body of Knowledge: Using Prosections to Teach Pelvic Anatomy in OB/GYN Residency—A Randomized Study Andrew S. Lane, MD; Shanna E. Williams, PhD; Sharon D. Keiser, MD; and Jeffrey W. Elder, MD From the Department of OB/GYN, Greenville Health System, Greenville, SC (A.S.L.); University of South Carolina School of Medicine Greenville, Greenville, SC (S.E.W., S.D.K., J.W.E.); Department of OB/GYN, Division of Maternal-Fetal Medicine, Greenville Health System, Greenville, SC (S.D.K.); and Department of OB/GYN, Division of Gynecologic Oncology, Cancer Institute of Greenville Health System, Greenville, SC (J.W.E.)

Abstract Background: As medical schools continue to revamp educational curricula, lab-based anatomic education is often eliminated because of high costs and time constraints. The result is a new generation of residents with a knowledge deficit in pelvic anatomy. The purpose of this study was to determine the effect of a 1-hour structured review of pelvic anatomy using cadaveric prosections on written and practical examinations of pelvic anatomy. Methods: All OB/GYN (obstetrics and gynecology) resident physicians at Greenville Health System took baseline written and practical examinations and were then randomized into 2 groups within postgraduate year (PGY) levels. Both groups completed a self-directed reading assignment. The intervention group received an additional 1-hour structured review of pelvic anatomy using prosections prepared from the same cadavers used by our medical students. Both groups then completed follow-up examinations. Results: Fifteen of 23 residents completed the study. The intervention group showed a significant improvement over the control group in practical exam scores (P = .01), but not on written (P = .77) or combined scores (P = .09). Within groups, the intervention group showed significant improvement in its combined (P < .01) and practical scores (P < .01) compared to that group’s baseline exam. The control group showed significant improvement in its combined (P < .01), written (P = .04), and practical (P = <.01) scores compared to that group’s baseline exam. Conclusions: We demonstrated the ability of a straightforward educational intervention that affects anatomic practical exam performance. We also showed that all residents benefited from an anatomy review. This study is important in its comparison of 2 modalities of resident anatomic education. Use of 1 guided prosection session provided a measurable benefit. Additionally, a simple reading assignment on pelvic anatomy was beneficial and should not be overlooked in our resource-intensive age.

he study of human anatomy has been a cornerstone of medical education from the inception of formal medical education. Since Leonardo da Vinci’s first accurate depiction of a fetus in the womb, our understanding of female anatomy has grown exponentially.1,2 While the Uniform Anatomical Gift Act of 1968 effectively put an end to unscrupulous practices,

such as grave robbing, to satisfy the demands of medical schools, the current state of anatomic education in medical curricula is as controversial as ever.3 As medical schools continue to reexamine and update curricula to include new areas of interest such as ethics and problem-based learning, anat-

GHS Proc. June 2017; 2 (1): 32-37

BODY OF KNOWLEDGE omy—with its time-consuming dissections and relatively high cost—receives reduced emphasis. Newer surgical approaches such as laparoscopy, endoscopy, and robotic surgery offer different views of the same anatomy than the “open” approach of traditional dissection. Some institutions have gone so far as to deem cadaveric dissections obsolete, and have replaced traditional dissection with other methods such as prosections, plastic models, body painting, virtual simulation procedures, radiology, mixed multimedia packages, and synthetic cadavers.4,5 Less time in the anatomy lab, however, can be detrimental, even though other methods of education are available. Medical students prefer dissection to any other method for learning anatomy and believe their training is compromised when time in the anatomy lab is reduced.6 Despite this fact, most of the anatomy learned in medical school is forgotten by the start of residency.7 When surveyed, 24% of surgery residency directors believed that anatomic knowledge of new residents was seriously lacking, and 52% believed that current trainees had less anatomic knowledge than 10 years before.8 Previous studies have attempted to address these deficiencies with various interventions in resident education. Studies show that sculpting clay models, laparoscopic dissection, and traditional dissection significantly increase the knowledge of pelvic anatomy in OB/GYN (obstetrics and gynecology) residents.9-12 Authors of these studies have concluded that a more time-conservative method with similar effects would be beneficial to resident education. We sought to address this problem by using cadaveric prosections prepared by our medical school’s anatomy department. Our objective was to determine the effect of a 1-hour structured review of pelvic anatomy using cadaveric prosections on resident performance on written and practical examinations of pelvic anatomy.

Methods We piloted a randomized, controlled trial from March 2015–May 2015 at the University of South Carolina School of Medicine Greenville in Greenville, SC. Participants were recruited from the OB/GYN residency program. Inclusion criteria were current resident in good standing and ability to take part in all sessions. Exclusion criteria were inability to take part in all sessions and resident physicians who were also study investigators. Written consent was obtained from all

GHS Proc. June 2017; 2 (1): 32-37

participants. Greenville Health System’s Institutional Review Board approved this study. All participants took baseline practical and written examinations on female pelvic anatomy. The practical examination consisted of identifying 20 tagged structures on cadaveric prosections, with 1 minute allowed for each written response (Table 1). The written examination consisted of 20 multiple-choice questions with 20 minutes to complete the examination. Participants were not given feedback on their performance. Five prosections were used. The cadavers used to make the prosections were the same ones used by our medical students in the gross anatomy course. All prosections were prepared by one of the investigators (S.E.W.), a trained anatomist. Tagged structures on the practical exam were determined based on quality of the specimen and relevance to pelvic surgery (Table 1). All cadavers were obtained from the Willed Body Program. Written examinations were developed with the use of anatomy guidelines from the Council on Resident Education in Obstetrics and Gynecology’s Educational Objectives to assess knowledge of clinical correlations to pelvic anatomy.13 All examinations were scored by one of the study investigators (S.E.W.) who was “blinded” to the identities of the subjects. Individual results were not shared with subjects. Randomization was then performed by placing index cards with a study ID into 1 of 4 opaque envelopes by one of the study investigators (J.W.E.). Each envelope corresponded to year of residency training and contained 6 cards. The study ID consisted of a 2-digit number. The first digit corresponded to year in training; the second corresponded to intervention or control groups. Each resident blindly drew a card from the envelope, which was overseen by a research nurse. Two weeks later, the intervention group was given a 1-hour interactive review of pelvic anatomy by one of the investigators (J.W.E.) using the prosections. During the review, residents were asked to demonstrate anatomic relationships and to describe clinical correlations assessed in the baseline exams. The investigator reviewed all clearly defined pelvic anatomy on each prosection, but did not review only the features that would be emphasized on the follow-up exam as that was prepared by another investigator (S.E.W.). Control group members were allowed to spend this time at their own discretion.

All participants returned for a follow-up examination 3 weeks after the randomization. Before the follow-up exam, both groups were instructed to read the anatomy chapter in Williams Gynecology.14 The practical examination was similar to the baseline exam, involving identification of 20

Table 1 Anatomic structures tested on practical examinations. General Category

Anatomic Structures

Pelvic organs

Ovary Fimbriae

Muscles of the abdomen and pelvis Coccygeus m. Rectus abdominis m. Bulbospongiosus m. Levator ani m. Psoas major m. Iliacus m. Perineal body m. Superficial transverse perineal m. Vascular structures

External iliac a. Inferior mesenteric a. Inferior epigastric a. Ovarian v. Common iliac a. Internal iliac a. Superior vesical a. External iliac v. Inferior vena cava Posterior division of the internal iliac a.

Nerves

Femoral n. Genitofemoral n. Obturator n. Iliohypogastric n.

Urinary tract

Ureter Bladder/trigone

Gastrointestinal tract

Rectum

Landmarks

Arcuate line

m., muscle; a., artery; v., vein; n., nerve

structures. The written test consisted of the same 20 multiple-choice questions used in the baseline exam, but arranged in a different sequence. Once follow-up testing was complete, residents randomized to the control group were given the option to attend a 1-hour anatomy review session, identical to the session previously attended by the intervention group. The primary outcomes were the differences in practical, written, and combined scores between each cohort after the intervention. Secondary outcomes were the differences in scores after the intervention within each cohort and between combined cohorts. The Mann-Whitney U test was used to analyze scores between and within cohorts. Statistical analysis was performed with SPSS version 16.0 (IBM, New York, New York). The study followed CONSORT (consolidated standards of reporting trials) reporting guidelines.

Results Our OB/GYN residency consists of 6 residents per postgrad year with a complement of 23 total residents at the time of the study (Table 2). Fifteen of 23 residents (65%) completed the study. Participants included PGY1 (n = 3), PGY2 (n = 4), PGY3 (n = 4), and PGY4 (n = 4) residents. Exclusions included no preintervention exam (n = 4), no postintervention exam (n = 3), and 1 study investigator (A.S.L.). The control group contained 8 subjects (PGY1, n = 1; PGY2, n = 2; PGY3, n = 2; PGY4, n = 2); the intervention group contained 7 subjects (PGY1, n = 1; PGY2, n = 2; PGY3, n = 2; PGY4, n = 2). Mean scores and standard error of the mean on the baseline examinations for the intervention group were 57.1 ± 6.7 (combined), 70 ± 2.9 (written), and 44.3 ± 5.8 (practical). Mean scores on the baseline examinations for the control group were 53.4 ± 7 (combined), 68.1 ± 4.2, and 38.8 ± 5.2. No significant differences existed between the groups in combined (P = .62), written (P  = 1), or practical (P = 1) baseline exam scores (Table 3). Mean scores and standard errors of the mean on the follow-up examinations for the intervention group were 80.2 ± 3.7 (combined), 76.4 ± 3.6 (written), and 83.9 ± 3.5 (practical). Mean scores on the follow-up examinations for the control group were 72 ± 4.2 (combined), 78.1 ± 2.7 (written), and 65.9 ± 4.5 (practical). Postintervention, there was a statistically significant improvement in practical exam scores of the intervention group over the control group (P = .01). No significant GHS Proc. June 2017; 2 (1): 32-37

BODY OF KNOWLEDGE differences were found between the groups in combined (P = .09) or written (P = .77) follow-up exam scores (Table 3). Within groups, the intervention group showed significant improvement in its combined (P < .01) and practical (P < .01), but not written (P = .25), follow-up exam scores. The control group showed significant improvement in its combined (P < .01), written (P = .04), and practical (P < .01) follow-up exam scores. Combining both cohorts showed that, overall, significant improvements were made in combined (P < .01), written (P = .03), and practical (P < .01) follow-up exam scores. Of note, the practical exam scores of all participants in both groups improved on the follow-up exam, while 9 of 15 residents did as well or better on the written exam (Table 4). Post-hoc power analysis showed 88.4% power to detect a statistically significant difference between the cohorts’ scores on practical examinations.

dissections, and prosection review.12 The authors concluded that further studies, which randomize residents to intervention and control groups, would allow for a better comparison. We sought to answer this challenge by assessing whether we could obtain similar results using the more cost-effective and time-efficient prosection. Our study showed that a 1-hour guided review of pelvic anatomy using cadaveric prosections had significant improvements in practical examina-

Table 2 Demographics of the OB/GYN residency 2015 academic year. Demographics N

Age, mean ± SD Gender, no. (%)

Discussion

Male

Even though OB/GYN residents are now starting residency with less traditional anatomic study than in the past, they are still expected to master pelvic surgery in 4 years. Also, there are concerns that the 2011 Accreditation Council for Graduate Medical Education work-hour restrictions have led to decreased resident case volumes and less hands-on time learning anatomy. However, there have been mixed reviews on the effects of this restriction in general surgery residencies; and the effects on obstetrical residents are unknown.15,16 In reality, most anatomic training in residency comes from self-study and on-the-job training in the operating room (OR) with senior residents and attending surgeons.

Female

Several previous studies have assessed interventions to improve anatomic knowledge among OB/ GYN residents. A 4-hour anatomy course, consisting of laparoscopic dissection of fresh-tissue cadavers, has been shown to increase resident satisfaction in pelvic anatomy education.9 A 2-hour session of sculpting clay models of pelvic anatomy was shown to improve scores and retention over lecture alone.10 Additionally, a guided, traditional dissection course on pelvic anatomy has been shown to lead to significant increases in examination scores compared to protected study time.11 A study by Corton and colleagues demonstrated that a comprehensive 3-week pelvic dissection course significantly improved OB/GYN resident proficiency in surgical anatomy. The course consisted of lectures, videos, reading assignments, GHS Proc. June 2017; 2 (1): 32-37

29.3 ± 2.6

5 (21.7) 18 (78.3)

Ethnicity, no. (%) Caucasian

20 (87.0)

African American

2 (8.7)

Hispanic

1 (4.3)

Relationship status, no. (%) Married

14 (61.0)

Single

9 (40.0)

SD, standard deviation

Table 3 Baseline and follow-up examination scores between groups. Intervention Group

Control Group

57.1 ± 6.7

53.4 ± 7.0

.62

Written

70.0 ± 2.9

68.1 ± 4.2

Practical

44.3 ± 5.8

38.8 ± 5.2

80.2 ± 3.7

72.0 ± 4.2

.09

Written

76.4 ± 3.6

78.1 ± 2.7

.77

Practical

83.9 ± 3.5

65.9 ± 4.5

.01

N Baseline examination scores, mean ± SEM

Follow-up examination scores, mean ± SEM

P Value

SEM, standard error mean

tion scores over self-directed study alone. However, this intervention did not lead to significant improvements in written or combined written and practical scores. The intervention group showed significant improvement in combined and written scores over its baseline, while the control group showed significant improvements in combined, written, and practical examinations over its baseline. Combining both cohorts showed that, overall, everyone benefited from this anatomy review with significantly improved scores on all examinations compared to baseline. Additionally, subjective feedback, or this additional time in the anatomy laboratory, was encouraging as residents felt more comfortable with pelvic anatomy and were more interested in taking time to point out anatomic features during subsequent OR cases. Our study had several strengths. Unlike previous studies, we randomized the participants. We used pre- and postintervention assessments similar to Corton’s to allow for better comparisons. A trained anatomist prepared all prosections. Our

Table 4 Baseline and follow-up examination scores within groups. Intervention Group Baseline Exam

Intervention Group Follow-up Exam

57.1 ± 6.7

80.2 ± 3.7

<.01

Written

70.0 ± 2.9

76.4 ± 3.6

.25

Practical

44.3 ± 5.8

83.9 ± 3.5

<.01

Control Group Baseline Exam

Control Group Follow-up Exam

P Value

53.4 ± 7.0

72 ± 4.2

<.01

Written

68.1 ± 4.2

78.1 ± 2.7

.04

Practical

38.8 ± 5.2

65.9 ± 4.5

<.01

N Combined, mean ± SEM

P Value

Combined Groups Combined Groups Baseline Exam Follow-up Exam P Value N

55.2 ± 3.5

75.8 ± 2.1

<.01

Written

69.0 ± 2.6

77.3 ± 2.2

.03

Practical

41.3 ± 3.9

74.3 ± 3.8

<.01

Combined, mean ± SEM

SEM, standard error mean

approach is significantly less time-consuming than previous approaches that require multiple hours to several weeks. This intervention is also more cost-effective than obtaining additional cadavers for traditional dissection or other supplies as we were able to use the same cadavers as our first-year medical students. Our study also had several limitations. Our sample size was limited by the use of a single residency program and logistic considerations of having all residents outside of the hospital at a given time. The small sample size and large standard deviations could have limited our statistical analysis; any perceived statistical differences may have been the result of the small sample size rather than an actual difference. Although different structures were tagged on the baseline and follow-up examination, we did use the same cadavers for both exams. Results may have been different with a new set of cadavers, though doing so would add cost. We also used the same multiple-choice questions in different order as in previous studies. Improvements may have been that students were better prepared to take this exam and not an exam on pelvic anatomy specifically. While the control group was encouraged to spend the hour of time the other residents were in the 1-hour prosection session reviewing the anatomy chapter, it is unknown what the participants did during that period. It may be that this study emphasizes the importance of protected education time. We realize that this study benefited from an on-campus medical school with an anatomy department supportive of our study. However, all programs might not have these resources, possibly limiting external validity. Improvements in scores could have been related to self-directed study with the required reading alone or baseline differences in resident knowledge. A structured 1-hour review of pelvic anatomy using cadaveric prosections significantly improves performance on practical examinations of pelvic anatomy compared to self-study alone. Self-study alone, with and without this prosection review, also significantly improves performance on both written and practical examinations of pelvic anatomy. Usage of cadaveric prosections may be an alternative to time-consuming dissection courses to teach pelvic anatomy to residents and an excellent adjunct to self-directed study. Additionally, using cadavers as a subject of study may lead to a more useful understanding of pelvic anatomy. We found this approach to be effective and well-liked approach at our institution. GHS Proc. June 2017; 2 (1): 32-37

BODY OF KNOWLEDGE

Conclusion The most important intervention a program can make to ensure high-quality knowledge of pelvic anatomy among residents is to set aside time for anatomy in its formal education. Programs should use the resources available to them, be they prosections, traditional dissections, animal

labs, plastic models, or just protected study time for self-directed review. Ensuring the strength of anatomic education in our residencies will assure that the next generation of pelvic surgeons is ready to face the challenges of modern medicine as we continue to revamp anatomic education in medical training.

2. Perloff JK. Human dissection and the science and art of Leonardo da Vinci. Am J Cardiol. 2013;111:775-7. 3. Garment A, Lederer S, Rogers N, Boult L. Let the dead teach the living: the rise of body bequeathal in 20th-century America. Acad Med. 2007;82:1000-5. 4. Sugand K, Abrahams P, Khurana A. The anatomy of anatomy: a review for its modernization. Anat Sci Educ. 2010;3:83-93. 5. SynDaver Surgical Model. SynDaver™Labs. http:// syndaver.com/shop/syndaver/syndaver-synthetic-human-copy. Accessed May 17, 2016. 6. Azer SA, Eizenberg N. Do we need dissection in an integrated problem-based learning medical course? Perceptions of first- and second-year students. Surg Radiol Anat. 2007;29:173-80. 7. Hamilton GC, Nagy F. A course in anatomy for emergency medicine residents. J Emerg Med. 1985;3:71-4. 8. Cottam WW. Adequacy of medical school gross anatomy education as perceived by certain postgraduate residency programs and anatomy course directors. Clin Anat. 1999;12:55-65. 9. Cundiff GW, Weidner AC, Visco AG. Effectiveness of laparoscopic cadaveric dissection in enhancing resident comprehension of pelvic anatomy. J Am Coll Surg. 2001;192:492-7.

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OB/GYN = obstetrics and gynecology; PGY = postgraduate year; OR = operating room

Correspondence

References 1. Mavrodi A, Paraskevas G, Kitsoulis P. The history and the art of anatomy: a source of inspiration even nowadays. Ital J Anat Embryol. 2013;118:267-76.

Abbreviations and Acronyms

10. Myers DL, Arya LA, Verma A, Polseno DL, Buchanan EM. Pelvic anatomy for obstetrics and gynecology residents: an experimental study using clay models. Obstet Gynecol. 2001;97:321-4. 11. Gordinier ME, Granai CO, Jackson ND, Metheny WP. The effects of a course in cadaver dissection on resident knowledge of pelvic anatomy: an experimental study. Obstet Gynecol. 1995;86:137-9.

Address to: Andrew Lane, MD, EVMS MaternalFetal Medicine, 825 Farifax Ave, Suite 310, Norfolk, VA 23507 (laneas@evms.edu)

12. Corton MM, Wai CY, Vakili B, Boreham MK, Schaffer JI, Coleman RL. A comprehensive pelvic dissection course improves obstetrics and gynecology resident proficiency in surgical anatomy. Am J Obstet Gynecol. 2003;189:647-51. 13. CREOG Education Committee. Educational Objectives: Core Curriculum in Obstetrics and Gynecology. 10th ed. http://med.unr.edu/Documents/unsom/ obgyn/CREOGEducationalObjectives10thEdition. pdf. Published in 2013. Accessed April 4, 2015. 14. Hoffman BL SJ, Schaffer JI, Halvorson LM, Bradshaw KB, Cunningham G, Calver LE. Williams Gynecology. 2nd ed. New York, NY: McGraw-Hill Education; 2012. 15. Kamine TH, Gondek S, Kent TS. Decrease in junior resident case volume after 2011 ACGME work hours. J Surg Educ. 2014;71:e59-63. 16. Antiel RM, Reed DA, Van Arendonk KJ, et al. Effects of duty hour restrictions on core competencies, education, quality of life, and burnout among general surgery interns. JAMA Surg. 2013;148:448-55.

Original Research

The Relationship Between Third-Year Clerkship Allocation Method and Specialty Choice Francis S. Nuthalapaty, MD; Tameika T.F. Lewis, MD; Anne Zinski, PhD; and James R. Jackson, PhD From Greenville Health System/University of South Carolina School of Medicine Greenville, Greenville, SC (F.S.N., T.T.F.L.), and Department of Medical Education, University of Alabama School of Medicine, Birmingham, Ala (A.Z., J.R.J.)

Abstract Background: A lack of research surrounds the impact of third-year clinical clerkship scheduling tactics on timing of specialty choice. The objective of this study was to compare the timing of clerkship experience and eventual specialty choice between 2 medical schools that use random and non-random third-year clerkship allocation methodologies. Methods: We conducted a retrospective cohort study using data for the graduating classes of 2003– 2006 at the University of Alabama School of Medicine (UASOM) and the Medical University of South Carolina (MUSC). The third year was divided into 6 sequential clerkship blocks at both institutions. At UASOM, clerkship allocation was non-random, with students making 3 “wishes” in which they specified the clerkship, the block, and an alternate. At MUSC, clerkship positions were allocated randomly. Clerkship block order was determined for all graduates who matched into 1 of 4 specialties (Internal Medicine, Pediatrics, Obstetrics and Gynecology, and General Surgery). For each specialty at each institution, clerkship block order was compared to a uniform distribution using a Chi-square goodness of fit test. Results: When the clerkship allocation method was non-random, the distribution of specialty choice across blocks differed significantly (P < .05) from a uniform distribution for each specialty, with the largest percentage matching in the fourth block for each specialty. When clerkships were assigned randomly, the distribution of specialty choice across blocks did not differ significantly from a uniform distribution for each specialty. Conclusions: Random allocation of clerkship order was associated with an even distribution of specialty interest throughout all clerkship blocks. Allowing students a choice in clerkship scheduling resulted in clustering of specialty interest into the middle 2 clerkship blocks, with the largest percentages matching in the fourth block.

he process by which medical students make a specialty choice is complex and multifactorial. This decision is influenced by both intrinsic (eg, socioeconomic background, age, motivation, personality) and extrinsic (eg, educational debt, length of residency, medical faculty, expected income, lifestyle) factors.1,2 Chief among the factors is students’ clerkship experiences during the third year of medical school.3 More than half of students change their specialty choice from the time they complete their preclinical coursework in the first 2 years to the time of

graduation.4 This fact suggests a range of both commitment and exploration to a preferred specialty before beginning clerkship rotations. Faculty and administrators who inform policies regarding the scheduling of the third-year clerkships must consider an array of program and student-level factors to maximize outcomes. For instance, students with a firm specialty choice may prefer to time their specialty clerkship experience in a way that will maximize potential for residency match. Recent investigations have posited GHS Proc. June 2017; 2 (1): 38-42

CLERKSHIP ALLOCATION METHOD AND SPECIALTY CHOICE that the sequence of specific clerkships are associated with exam scores in that discipline.5,6 It is also established that third-year medical students’ scores on the National Board of Medical Examiners subject examinations tend to increase as they progress through the third-year curriculum.7 Medical schools must also consider faculty grading tendencies and associated outcomes to neutralize potential effects of clerkship block order,7 as students may strategically delay clerkships in their preferred specialty.3 In addition, as the letter of recommendation is cited as a factor in granting residency interviews by 86% of Residency Program Directors,8 students who seek to garner a favorable recommendation letter through their clerkship performance may choose to schedule the associated clerkship in the second half of the year or when they are likely to be at their peak clinical performance.7 However, for the balance of students who have yet to solidify their specialty choice by the beginning of the third year, the priority may be to provide adequate opportunities for breadth and quantity of clerkship experiences to encourage exploration of all career options and maximize performance, regardless of timing. For example, Campos-Outlat et al demonstrated that the implementation of a required third-year family practice clerkship in any sequence led to an immediate, significant increase in the proportion of students choosing family practice.9 Additionally, Paiva et al showed that, for previously undecided students, clerkships taken early in the clinical experience sequence were associated with eventual specialty choice, and students who had identified other specialties as a potential career path were likely to switch to psychiatry following clerkship exposure.3 Further, other investigations showed no association with clerkship timing, performance, and ultimate specialty choice, indicating that random clerkship sequencing may be equally appropriate.10-12 In the United States, 2 primary approaches to clerkship scheduling are commonly employed.13 The first allows students an opportunity to give input to their clerkship block schedule to determine their clerkship timing. The second approach eliminates student choice and assigns clerkship sequence randomly. Some educators advocate for the former system as it may allow students the opportunity to maximize their clerkship grade and opportunities to obtain letters of recommendation.14 Although both approaches are common, very little research has compared clerkship scheduling tactics with regard to eventual specialty choice. Therefore, the objective of this study was to compare the distribution of specialty selecGHS Proc. June 2017; 2 (1): 38-42

tion within clerkship blocks between 2 medical schools that used random and non-random thirdyear clinical clerkship allocation methods.

Methods We designed a retrospective cohort study that used data gathered from the Medical University of South Carolina (MUSC) and the University of Alabama School of Medicine (UASOM), both of which offer Liaison Committee for Medical Education-accredited 4-year medical degree programs. This investigation was reviewed and granted exempt status by Greenville Health System’s Institutional Review Board and the University of Alabama at Birmingham Institutional Review Board. The study sample included all students graduating with an MD degree from the 2 institutions in 2003–2006, and who matched into 1 of the 4 primary specialties required in the third-year curriculum (Internal Medicine, Pediatrics, Obstetrics and Gynecology, and General Surgery). Students who had a prolonged or interrupted third or fourth year or who lacked a complete set of data (eg, transfer students and dual-degree students) were not included. Both institutions scheduled third-year clerkship rotations in 6 blocks through the academic year. At UASOM, clerkship allocation was facilitated by the use of a locally developed computerized scoring algorithm. Students were allowed to make 3 “wishes” in which they specified the clerkship, the block, and an alternate block for each of their 3 wishes. In addition, students were permitted to indicate which clerkship they did not want during block 1. The scoring algorithm then tried to meet as many of a student’s wishes as possible, starting with the top-ranked wish. It was common practice for some medical student advisors at UASOM to recommend that students who had identified their desired specialty pursue a clerkship in that specialty in the middle of the academic year. Conversely, at MUSC, students were not allowed to select the order of their clerkship sequence; rather, the rotations were randomly assigned using a locally developed computerized algorithm. Students were, however, able to switch rotations among one another to a very limited extent for special circumstances. The third-year clerkship schedules for all eligible MUSC and UASOM graduates from 2003–2006, along with their specialty matches, were obtained from institutional records. 39

The percentage of students matching into the 4 specialties was determined at each institution, and the association between institution and specialty was examined with a Chi-square test of independence. Clerkship block order was determined for all graduates who matched into 1 of 4 specialties. For each specialty at each institution, clerkship block order was compared to a uniform distribution using a Chi-square goodness of fit test. IBM SPSS Statistics (version 22.0, (IBM, Armonk, NY) was used for all analyses, and an alpha level of .05 was used as the criterion for statistical significance.

significant, indicating that the percentages of students matching into the 4 specialties at each institution were similar (Table 1). Internal Medicine was the most common specialty choice, accounting for at least one third of the 4 specialties in each institutional cohort. Pediatrics accounted for more than one quarter of all included graduates. The pattern of distribution of graduates across the 6 rotation blocks for each specialty was similar within each institutional cohort. At UASOM, where a non-random clerkship allocation method was used, the distribution of specialty choice across blocks differed significantly (P < .05) from a uniform distribution for each specialty (Table 2 and Fig. 1). A consistent clustering in the 2 middle blocks, with the highest percentages in block 4 (30.2%–41.9%) occurred and the second-highest percentages in block 3 (20.0%–29.7%).

Results During the study period, 277 students at UASOM and 224 students at MUSC met the eligibility criteria for inclusion. The association between institution and specialty choice was not statistically

By comparison, at MUSC, where a random clerkship allocation method was used, the distribution of specialty choice across blocks did not differ significantly (P > .05) from a uniform distribution for each specialty (Table 2 and Fig. 2).

Table 1 Specialty match distribution for graduates of the University of Alabama School of Medicine (UASOM) and the Medical University of South Carolina (MUSC), 2003–2006. UASOM (N = 277)

MUSC (N = 224)

Discussion

P Value

Specialty Match Distribution, no. (%)

.220

Internal Medicine

106 (38.2)

74 (33.0)

Pediatrics

74 (26.7)

65 (29.0)

General Surgery

50 (18.1)

33 (14.7)

Obstetrics & Gynecology

47 (17.0)

52 (23.3)

These findings demonstrate that contrasting approaches to clerkship allocation are associated with patterns of specialty interest within clerkship blocks. In the non-random allocation system, higher percentages of students participated in clerkships in their eventual specialty match during the middle 2 blocks of the academic year,

Table 2 Number and percent of students who matched in a specialty by clerkship block for specialty and institution. Clerkship Block for Specialty 1

Total

P Value

Internal Medicine

3 (2.8)

14 (13.2)

24 (22.6)

32 (30.2)

19 (17.9)

Pediatrics

6 (8.1)

5 (6.8)

22 (29.7)

31 (41.9)

8 (10.8)

Obstetrics & Gynecology

1 (2.1)

3 (6.4)

10 (21.3)

16 (34.0)

7 (14.9)

General Surgery

4 (8.0)

10 (20.0)

20 (40.0)

9 (18.0)

Internal Medicine

9 (12.2)

10 (13.5)

14 (18.9)

17 (23.0)

9 (12.2)

15 (20.3) 74 (100.0)

.747

Pediatrics

8 (12.3)

10 (15.4)

15 (23.1)

7 (10.8)

10 (15.4) 65 (100.0)

.366

Obstetrics & Gynecology

8 (15.4)

11 (21.2)

8 (15.4)

10 (19.2)

5 (9.6)

52 (100.0)

.439

2 (6.1)

5 (15.2)

6 (18.2)

3 (9.1)

10 (30.3)

7 (21.2)

33 (100.0)

.183

Institution UASOM, no. (%) 14 (13.2) 106 (100.0) 2 (2.7)

<.001

74 (100.0)

<.001

10 (21.3) 47 (100.0)

.002

3 (6.0)

50 (100.0)

<.001

MUSC, no. (%)

General Surgery

GHS Proc. June 2017; 2 (1): 38-42

CLERKSHIP ALLOCATION METHOD AND SPECIALTY CHOICE Figure 1 Percent of students who matched in a specialty by clerkship block for specialty at UASOM.

Percent of Students Who Matched in a Specialty

45%

Figure Legend: The

distribution of specialty matches across 6 sequential clerkship blocks, among 277 student graduates of the UASOM Birmingham Campus, from 2003â&#x20AC;&#x201C;2006. This institution used a nonrandom clerkship allocation method. A clustering appears in the middle rotation blocks, regardless of specialty, with 60% of graduates completing their clerkship in their eventual chosen specialty during rotation blocks 3 and 4, as compared to 14% in rotation blocks 1 and 2, and 26% in rotation blocks 5 and 6.

Internal Medicine (n=106; p<.001*)

40%

Pediatrics (n=74; p<.001*) Obstetrics & Gynecology (n=47; p<.002*)

35%

General Surgery (n=50; p<.001*)

30% 25% 20% 15% 10% 5% 0%

Clerkship Block for Specialty

Figure 2 Percent of students who matched in a specialty by clerkship block for specialty at MUSC. Percent of Students Who Matched in a Specialty

45%

Figure Legend: The

distribution of specialty matches across 6 sequential clerkship blocks, among 224 student graduates of the MUSC, from 2003â&#x20AC;&#x201C;2006. This institution used a random clerkship allocation method. A uniform distribution appears across the year, with 28% of students completing their clerkship in their chosen specialty during rotation blocks 1 and 2, compared with 39% in rotation blocks 3 and 4, and 33% in rotation blocks 5 and 6.

Internal Medicine (n=74; p=.439)

40%

Pediatrics (n=65; p=.366) Obstetrics & Gynecology (n=52; p=.747)

35%

General Surgery (n=33; p=.183)

30% 25% 20% 15% 10% 5% 0%

Clerkship Block for Specialty

whereas the cohort with random allocation displayed evenly distributed specialty interest across the academic year. While evidence suggests that non-random clerkship order may benefit students who have a clear specialty choice, it may also lead to practical challenges. First, a concentrated group of students may select their desired clerkship specialty in the middle of the academic year, building increased GHS Proc. June 2017; 2 (1): 38-42

competition for patient care and procedural experiences. Second, a lack of student enrollment in specific clerkships early or later in the academic year could negatively impact faculty and resident motivations, as well as yield very large or small cohorts for which to provide clerkship oversight and feedback. Importantly, although the non-random allocation method appears to show lower percentages of spe41

Abbreviations and Acronyms UASOM = University of Alabama School of Medicine; MUSC = Medical University of South Carolina

Correspondence Address to: Francis S. Nuthalapaty, MD, Greenville Health System, Department of OB/GYN, 890 W Faris Rd, Suite 470, Greenville, SC 29605 (fnuthalapaty@ghs.org)

cialty match interest among students in early and late blocks, these students constitute a notable portion of graduates. This finding seems to support the notion that the clerkship experience remains an important determinant of specialty choice. Therefore, it would be beneficial for faculty and residents to remain motivated in their teaching throughout the academic year, not only to enhance learning, but also to stimulate student interest in their specialty. The primary limitation of this study is in the potential generalizability of the findings to diverse curricular environments. This study is representative of 2 accredited medical programs in the southern United States with random and non-random clerkship scheduling during the third year. These do not speak to the variety of current approaches to third-year clinical curricula, including longitudinal clerkships, community-based preceptor clerkships, and subspecialty electives, which may impact student specialty interest. Faculty who design policies regarding the scheduling of third-year clerkships may want to give consideration to allocation method. The benefits of even distribution of student specialty interest across the academic year seem to be in the best interest of both students and faculty. This

approach has the potential to negate faculty bias toward students, based on the timing of their clerkships, and could presumably increase the quality of interactions, and hence, the education of students overall. This approach might also eliminate the competitive pressure created when too many students in a clerkship block share the same specialty aspirations. Finally, for those students who have yet to make a career choice, the random allocation methods may decrease stress and anxiety regarding clerkship selection in their second year, before they have had a chance to perform any rotations at all. Further investigation of these potential benefits is recommended.

Conclusion This investigation showed that the patterns of specialty choice across clerkship blocks varied between institutions with random and non-random scheduling allocation. This finding is important in a little-studied area, as the association of clerkship timing and preference with eventual specialty match has not been explored extensively, but may affect grading, faculty burden and motivation, and availability of patient cases in each clerkship. As clerkship timing has been associated with test achievement, specialty choice, and clinical performance, this investigation posits that clerkship allocation model must also be explored.

References 1. Kiker BF, Zeh M. Relative income expectations, expected malpractice premium costs, and other determinants of physician specialty choice. J Health Soc Behav. 1998;39:152-67. 2. Maiorova T, Stevens F, Scherpbier A, van der Zee J. The impact of clerkships on students’ specialty preferences: what do undergraduates learn for their profession? Med Educ. 2008;42:554-62.

9. Campos-Outlat D, Senf J. A longitudinal, national study of the effect of implementing a required thirdyear family practice clerkship or a department of family medicine on the selection of family medicine by medical students. Acad Med. 1999;74:1016-20.

3. Paiva RE, Vu NV, Verhulst SJ. The effect of clinical experiences in medical school on specialty choice decisions. J Med Educ. 1982;57:666-74.

10. Potts MJ, Brazeau NK. The effect of first clinical clerkship on medical students’ specialty choices. Med Educ. 1989;23:413-5.

4. McLaughlin MA, Daugherty SR, Rose WH, Goodman LJ. Specialty choice during the clinical years: a prospective study. Acad Med. 1993;68:10.

11. Allen SS, Sherman MB, Bland CJ, Fiola JA. Effect of early exposure to family medicine on students’ attitudes toward the specialty. J Med Educ. 1987;62:911-7.

5. Kies SM, Roth V, Rowland M. Association of thirdyear medical students’ first clerkship with overall clerkship performance and examination scores. JAMA. 2010;304:1220-6.

12. Park RS, Chibnall JT, Morrow A. Relationship of rotation timing to pattern of clerkship performance in psychiatry. Acad Psychiatry. 2005;29:267-73.

6. Ouyang W, Cuddy MM, Swanson DB. US medical student performance on the NBME subject examination in Internal Medicine: do clerkship sequence and clerkship length matter? J Gen Intern Med. 2015;30:1307-12. 7. Cho JE, Belmont JM, Cho CT. Correcting the bias of clerkship timing on academic performance. Arch Pediatr Adolesc Med. 1998;152:1015-8. 8. Results of the 2014 NRMP Program Director Survey. National Resident Matching Program, Wash-

ington, DC. http://www.nrmp.org/wp-content/ uploads/2014/09/PD-Survey-Report-2014.pdf. Published June 2014. Accessed March 15, 2017.

13. Clerkship Selection. Organization of Student Representatives (OSR) Listserv Questionnaire Results. Association of American Medical Colleges, Washington, DC. https://www.aamc.org/download/268830/ data/clerkship_selection.pdf. Published December 2011. Accessed March 15, 2017. 14. Baciewicz FA Jr, Arent L, Weaver M, Yeastings R, Thomford NR. Influence of clerkship structure and timing on individual student performance. Am J Surg. 1990;159:265-8.

GHS Proc. June 2017; 2 (1): 38-42

Review

Irritable Bowel Syndrome and Endometriosis: Twins in Disguise Meredith Aragon, MD, MPH, and Bruce A. Lessey, MD, PhD From the Department of OB/GYN, Greenville Health System, Greenville, SC (M.A., B.A.L.)

hronic pelvic pain (CPP) is a debilitating, lifelong struggle for some individuals. The diagnosis and treatment of CPP also contribute to significant annual healthcare costs in the United States (US).1 The most common diagnoses associated with CPP include endometriosis, interstitial cystitis, irritable bowel syndrome (IBS), myofascial pain, pelvic floor hypertonia, and dysmenorrhea.2,3 In reality, CPP in women often represents undiagnosed endometriosis that may contribute to these other associated pain syndromes. Since a diagnosis of endometriosis requires surgery, there is a delay in the diagnosis of endometriosis of greater than 11 years in the US.4,5 For some practitioners, symptoms including bowel, bladder, and pelvic complaints are recognized manifestations of endometriosis. For other healthcare providers, the diagnosis of endometriosis is rarely considered. A lack of appreciation for the morbidity associated with endometriosis may be the primary reason for our failure to diagnose the majority of patients who present with CPP.6 Irritable bowel syndrome is a common functional gastrointestinal disorder associated with diarrhea (IBS-D), constipation (IBS-C), or both (IBS-M). IBS is diagnosed on the basis of a characteristic cluster of symptomsâ&#x20AC;&#x201D;recurring bouts of abdominal discomfort or pain relieved by defecation and associated with a change in the frequency and/or consistency of stoolsâ&#x20AC;&#x201D;in the absence of structural or biochemical abnormalities. Diagnostic criteria are often loosely applied in the clinical setting, and the underlying cause is never defined in many individuals. Diet7 and changes in the bowel microbiome8,9 have been implicated in the etiology of IBS. Bile acid malabsorption has also been documented in up to a third of individuals with IBS-D.10 GHS Proc. June 2017; 2 (1): 43-50

IBS patients incur higher annual healthcare costs compared to those without IBS,11 with spending ranging from $1562 to $7547 per year for the average IBS patient. Annually, IBS is estimated to result in $1.6 billion in direct costs and $19.2 billion in indirect costs in the US alone. It can be argued that IBS is a constellation of symptoms that includes bloating, diarrhea, constipation, and varied other bowel complaints, rather than a defined disease.12,13 In general, gastroenterologists (GIs) and others specializing in gastroenterology complaints are largely unaware of the strong links between IBS and endometriosis; therefore, it is rarely included in the differential diagnosis for bowel complaints. This fact may contribute to the poor satisfaction of patients with current IBS treatments. In a recent survey, IBS caused daily symptoms in 43% of patients; under 20% were satisfied with treatments they had received.14 A better understanding of the pathophysiology of this disorder would likely lead to more effective treatments and earlier resolution of symptoms. The pathophysiology of IBS includes immune activation, increased gut permeability, and visceral hypersensitivity.12 Endometriosis is also a highly inflammatory and immune-regulated disorder,15 raising the possibility that IBS could well be a response to local or systemic inflammatory changes associated with this disease.16,17 C-reactive protein (CRP) has been used to differentiate IBS from irritable bowel disease (IBD).18 CRP has also been shown to be systemically elevated in women with endometriosis.19 Autoimmune dysfunction is common in endometriosis, 20-22 but autoimmunity has been reported in patients with IBS as well.23 In population studies, the majority of patients with IBS are women.24,25 Female sex is the single 43

greatest risk factor for development of IBS.12 Over 50% of women report cycle-dependent worsening of IBS during menses. All of these associations suggest that endometriosis may be a major contributor to IBS in women. In this review, we will address these questions and provide a case series in support of this hypothesis.

Dysmenorrhea results in large part to prostaglandin release,45 and women with IBS are more likely to experience dysmenorrhea than women without IBS.46 In women with IBS, estrogen and progesterone may have an impact on visceral pain thresholds, and prostaglandins released during menstruation might influence those thresholds.

Effect of Female Sex and Hormones on IBS

The menstrual cycle has been shown to have an impact on bowel function in other ways. Gastroenterology transit time is prolonged in the luteal phase of the menstrual cycle47 and reduced when estrogen and progesterone levels fall right before menses. Stools tend to become loose during menses in women with IBS,28,31 suggesting faster gastrointestinal transit may be related to this symptom.

Menstrual Cycles and IBS IBS has been noted to be highly related to female sex and to age, but not to race.26 There is a 2:1 ratio of women to men with IBS,27 and symptoms of IBS are frequently related to the menstrual cycle.28 Women with IBS report significantly more abdominal pain, bloating, intestinal gas, constipation, and diarrhea at the time of menses compared to controls.29-31 Whitehead and colleagues found that 50% of female IBS patients compared to 34% of non-IBS patients reported worsening bowel symptoms during menses.31 Heitkemper and colleagues reported prospective data confirming that IBS patients report worse stomach pain, nausea, and diarrhea during menses compared to healthy controls.32 The worsening of IBS symptoms with menses is analogous to symptoms reported by women with endometriosis, who report increasing dysmenorrhea at the time of menses.33-35 The link between endometriosis and IBS is strengthened further by the observation that dysmenorrhea itself is associated with IBS.36,37 Treatment with GnRH agonist therapy to suppress endometriosis and cause cessation of menses improves symptoms in both IBS38 and endometriosis sufferers.39,40 Symptoms of IBS are improved after menopause,27 similar to what is reported for endometriosis.

Menstrual Cycle Effects on Pain The menstrual cycle affects pain sensitivity, with distinct differences in somatic compared to visceral pain. In the rat model, which has a 4-day estrus cycle, heightened somatic sensitivity to skin stimulation occurs during proestrus and estrus phases (high estrogen), while visceral pain sensitivity was higher during metestrus and diestrus phases,41 comparable to perimenstrual or menstrual phase in women. The relationship between pain sensitivity and phase of the menstrual cycle, while variable in women, follows a similar pattern with somatic pain sensitivity greatest in mid-cycle42 and visceral pain sensitivity greatest at menses, at least in IBS patients.43,44 44

Bharadwaj and colleagues suggested that prostaglandins, which are higher during menses, primarily contribute to IBS symptoms including abdominal pain, bloating, and diarrhea.47 Crowell and colleagues reported that women with dysmenorrhea had greater menstrual-related variation in pain sensitivity. The higher levels of prostaglandins in menstrual fluid is associated with a greater risk of having endometriosis.37 The inflammation associated with endometriosis promotes cyclooxygenase-2 expression and prostaglandin production.48,49 IBS symptoms at menses may, therefore, be exaggerated specifically in the setting of endometriosis, raising the question of whether IBS is merely gastrointestinal reaction to having endometriosis. This association also raises the question of whether endometriotic implants on or near the bowel is required for the symptoms of menstrual-related IBS.

Menopause The influence of sex hormones on IBS is supported by data from women in menopause. Prevalence of IBS in women decreases markedly after menopause.26 In a survey of 5430 households in the US, frequency of IBS decreased after age 45 in women while remaining unchanged in men.50 Similar trends have been reported in the United Kingdom (UK)51 and Germany52 that document an age-related decrease in IBS in women after age 50â&#x20AC;&#x201C;65, although symptoms may worsen in the perimenopause before improving later after menopause.53 Mathias and colleagues have demonstrated that artificial menopause induced with GnRH agonist leuprolide decreased IBS symptoms.54-57 Conversely, a cohort study in the UK reported an increase in IBS symptoms in hormone replacement therapy (HRT) users compared to non-users.58 Fillingim and Edwards showed a decrease GHS Proc. June 2017; 2 (1): 43-50

IBS AND ENDOMETRIOSIS in somatic pain thresholds (increased pain sensitivity) in postmenopausal women receiving hormone therapy.59

Pregnancy Sex hormone levels are high during late pregnancy. Early survey data from the University of North Carolina found that a majority of women with IBS reported a reduction in symptoms during pregnancy,60 which may reflect lack of hormone fluctuations and absence of menses during the 9 months of pregnancy. Pregnant women have a higher likelihood of being constipated, perhaps because of the smooth muscle relaxation effect of progesterone or the compression of the bowel by the growing fetus.

Endometriosis Endometriosis is an estrogen-dependent, inflammatory condition affecting women from menarche to menopause.33 It is present in 5%â&#x20AC;&#x201C;10% of the general population but in up to 70% of women with pelvic pain. Endometriosis is characterized by a constellation of symptoms including painful periods (dysmenorrhea), painful intercourse (dyspareunia), and painful bowel movements (dyschezia). In addition, subtle signs of endometriosis have been recognized, and are related to a hormonal disturbance known as progesterone resistance, leading to infertility, spotting before menses, and luteal phase defect. Systemic manifestations of the inflammatory milieu associated with endometriosis are also thought to contribute to more global symptoms including malaise, chronic fatigue, and IBS.22 Endometriosis is defined as the presence of ectopic endometrium, composed of glandular and/ or stromal elements outside of the uterine cavity. This material gets deposited inside the pelvis at the time of menstruation, likely from retrograde menstruation.61 Genetic predisposition plays a dominant role in its pathogenesis.62,63 We, and others, have documented that the presence of this ectopic tissue in the pelvis and elsewhere can generate a significant systemic inflammatory response.16,64-66 Inflammatory changes have been shown to improve after treatment, but as a relapsing disease, a return of inflammation can occur as menstruation resumes.

Association Between Endometriosis and IBS Bowel and bladder complaints are common in women with endometriosis.67 Up to a third of women with endometriosis report gastrointestiGHS Proc. June 2017; 2 (1): 43-50

nal changes at the time of mensesâ&#x20AC;&#x201D;over 50% of women with IBS note cycle-specific worsening of symptoms.68 Compared to controls, women with endometriosis are 3.5 times more likely to have an IBS diagnosis.69 Implants of endometriosis on the bowel have been reported in 3.8%â&#x20AC;&#x201C;37% of women diagnosed with endometriosis.70 Essentially all studies exploring the association between endometriosis and IBS have focused on women first diagnosed with endometriosis. Wu et al studied 6076 subjects with endometriosis and found that 15% had IBS.71 Hansen compared endometriosis patients to controls and reported that 22% had symptoms of IBS.67 Surprisingly, no studies to date have examined women with IBS and asked how many have endometriosis. While up to a third of endometriosis patients have bowel implants, it remains unknown how many women with IBS have endometriosis and how many of those have lesions on or near the bowel. Most women with IBS are under- or misdiagnosed.72 Nasim et al points out that bowel endometriosis is often not considered or included in the differential diagnosis for acute or chronic abdominal complaints.73 In our practice, we perform laparoscopy routinely for CPP and have examined a subset of women with complaints specific to IBS. This study is the first to examine women with IBS and perform laparoscopy for determination of endometriosis. As shown in Table 1, the finding of endometriosis was uniformly positive in these women. In 12 consecutive laparoscopies in women identified with IBS, 12/12 (100%; 95% CI: 75% to 100%) were found to have endometriosis present. The 95% confidence interval (CI) reflects an important finding, worthy to pursue further investigation. Perhaps more important, the stage of disease was generally minimal or mild disease; in all but 1 case, endometriosis was found on or near the rectum, in the pouch of Douglas (posterior cul-de-sac). Although these data are preliminary, they suggest that endometriosis is a predominant finding in women with menstrual cycle-related IBS and may reflect direct irritation of endometriosis on nearby bowel. As women with IBS have other symptoms of endometriosis (eg, dysmenorrhea), it would be important to better define this population in future studies. This finding of posterior cul-de-sac disease in the majority of IBS patients suggests that local inflammation secondary to the endometriotic implant may directly contribute to symptoms of IBS. Only 45

Table 1 Findings at laparoscopy and at pathology for women with symptoms of IBS. Case # Age Parity

Operative Findings

Pathology

Stage On Bowel?

Endometriosis everywhere but especially on rectum. Implants on anterior and posterior cul-du-sac. Normal uterus and bilateral tubes/ovaries.

Confirmed, endometriosis; proliferative endometrium

yes

Posterior pelvic sidewalls, none in cul-de-sac. There were multiple obvious endometriosis implants along the left pelvic side wall.

Confirmed, endometriosis; secretory phase endometrium

Adjacent to rectum on right. Normal appearing bilateral fallopian tubes with small endometriosis implant on right mesosalpinx.

Confirmed, endometriosis

yes

Endometriosis adjacent to rectum on left. Uterus: enlarged, multinodular. Fibroids: 3.5 cm fundal near left cornual region; 5 cm right anterior subserosal. Left ovary: several surface implants of endometriosis with 8 mm endometrioma.

Confirmed, endometriosis; secretory phase endometrium

yes

G3P3003

Endometriosis on rectum. Absent right tube and ovary. Multiple areas of white stellate scarring consistent with endometriosis on midline posterior cul-de-sac

Confirmed, endometriosis; proliferative phase endometrium

yes

Posterior cul-de-sac and left side wall endometriosis. Abnormal with peritoneal window and thickened peritoneum. Left ovary: abnormal adherent to omentum and bowel on left.

Confirmed, endometriosis; inactive endometrium

yes

G1P1

Endometriosis seen on posterior cul-de-sac on rectum. Normal uterus; surgically absent left tube and ovary.

Confirmed, endometriosis

yes

Posterior cul-de-sac disease. Anterior cul-de-sac: abnormal with endometriosis across the bladder. Midline posterior cul-de-sac: abnormal with endometriosis to the right of the rectum and above, near the termination of the uterosacral ligament. Left pelvic sidewall below the area of the ureter. Left ovary: endometriosis.

Confirmed, endometriosis; benign proliferative phase endometrium

2-3

yes

Endometriosis on rectum, multiple endometriotic implants identified and resected including left and right ovarian lesions, a lesion under the ovary on the left, and implants across the left uterosacral.

Confirmed, endometriosis

yes

Endometriosis on rectum; endometrioma on left ovary, endometriosis throughout left pelvic sidewall, posterior culde-sac, right pelvic sidewall, bilateral uterosacral ligaments, bilateral ovaries, posterior uterine serosa, and small endometriosis implant on anterior cul-de-sac.

Confirmed, endometriosis; early secretory phase endometrium

yes

Endometriosis with large nodule on rectum; left ovary stuck to sidewall. Endometriosis on bladder, left sidewall, cul-desac, right side wall, out of the pelvis on the right abdominal wall, and on the right ovary. Endometriosis on appendix, which was twisted on itself because of endometriosis.

Confirmed, endometriosis; proliferative phase endometrium

yes

G2P2002

Nodules on small intestine and colon. Endometriosis of the right pelvic sidewall, right ovary, left pelvis, anterior abdominal wall left side, 2 areas on the large intestine (sigmoid colon), 1 area on the small intestine at the area of the cecum (terminal ileum).

Confirmed, endometriosis

yes

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IBS AND ENDOMETRIOSIS 1 other study suggests that location of implants might be critical to symptoms of IBS.74 In that study, it was reported that both mild, superficial disease and deep, infiltrating endometriosis (DIE) were associated with IBS symptoms. Women with DIE involving the rectum were more likely to experience cycle-dependent dysmenorrhea, while superficial disease contributed more to painful sex (dyspareunia). Interestingly, women with superficial disease reported cyclic constipation and cyclic dyschezia in 38% and 33% of cases, respectively. Studies in rats suggest a mechanism for the association between endometriosis and bowel dysfunction. Li and colleagues showed in the rat model that endometriosis caused inflammation with an increase in substance P immunoreactivity in dorsal root ganglia neurons innervating both uterus and colon.75 In human endometriosis, Remorgida and colleagues examined the relationship between gastrointestinal complaints and histologic findings in women with endometriosis.76 In this important study, 18% of women with endometriosis had bowel lesions. They found that women experienced bowel complaints only when the subserosal layer of the bowel was interrupted, damaging the interstitial cajal cells. Mast cells have been implicated in IBS.77 Intestinal mast cells are involved in low-grade inflammation of the bowel and are capable of releasing a variety of factors in response to different stimuli.78 Mast cells can be activated by IgE as well as pro-inflammatory cytokines through specific receptors, including TNF-Îą and IL-6, shown to be elevated in rectovaginal endometriotic tissues.79 Mast cells have been shown to be elevated in endometriotic tissues.80 In addition, using nanostring technology for immune transcriptomic profiling, we recently reported that several genes involved in mast cell biology (major basic protein, Fc fragment of IgE high affinity I receptor for alpha peptide, Fc fragment of IgE, high affinity I receptor for gamma polypeptide, and sphinogosine-1phosphate receptor I) were differentially expressed in endometriotic tissues.17 We also recently found that mast cells were associated with stem cell factor, a growth factor critical for mast cell expansion, differentiation, and survival (work in progress). These interactions leading to mast cell expansion at sites of endometriosis may represent new therapeutic targets for treating both endometriosis and IBS.

GHS Proc. June 2017; 2 (1): 43-50

A true association between endometriosis and IBS would be supported by reduced symptoms after treating endometriosis. Both surgical and medical treatments for endometriosis have been described.81 Drossman identified 13 women with IBS who had endometriosis treated surgically by resection.82 They reported that 83% of participants experienced complete relief of symptoms following surgery. Medical therapy has also been reported to improve IBS symptoms. Ferrero treated 6 patients with colorectal endometriosis with 6 months of norethindrone acetate (2.5 mg/d) and the aromatase inhibitor Letrozole (2.5 mg/d) and reported improvement in 67% of subjects (4/6). Neither study included controls, and the number of treated subjects was low. Prospective studies are needed to further study the effect of treating IBS in women with endometriosis.

Summary and Conclusions Recognizing the association between endometriosis and IBS represents a great challenge for clinicians treating women. Endometriosis is rarely included in the differential diagnosis for gastrointestinal complaints, even though evidence now strongly suggests it may be a primary cause of both IBS and a similar syndrome, interstitial cystitis. Most female IBS patients are never diagnosed with endometriosis, even though a causeand-effect relationship exists. Both medical and surgical treatments for endometriosis reduce IBS symptoms, and cessation of menses either medically or after menopause decreases symptoms in both conditions. Mechanisms of IBS may reflect local inflammation caused by endometriosis on or near the bowel in affected individuals. This finding is supported by our case study in which 11 of 12 subjects had posterior, rectal endometriotic implants present. GIs and clinicians treating gastrointestinal complaints should consider endometriosis as a likely diagnosis in reproductive-aged women with IBS, especially when symptoms worsen at menses. Future studies are planned to prospectively and rigorously define IBS and to determine the prevalence of endometriosis in this group of women. Further, it will be important to study whether surgical resection or medical treatment of endometriosis will lessen or eradicate the symptoms of this common condition, given that effective and long-term cures for IBS remain limited.

Abbreviations and Acronyms CPP = chronic pelvic pain; US = United States; IBS = irritable bowel syndrome; IBS-D = irritable bowel syndrome with diarrhea; GIs = gastroenterologists; CRP = C-reactive protein; UK = United Kingdom; HRT = hormone replacement therapy; CI = confidence interval; DIE = deep infiltrating endometriosis

Correspondence Address to: Bruce Lessey, MD, PhD, Greenville Health System, Department of OB/GYN, 890 W Faris Rd, Suite 470, Greenville, SC 29605 (blessey@ghs.org)

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52. Icks A, Haastert B, Enck P, Rathmann W, Giani G. Prevalence of functional bowel disorders and related health care seeking: a population-based study. Z Gastroenterol. 2002;40:177-83. 53. Triadafilopoulos G, Finlayson M, Grellet C. Bowel dysfunction in postmenopausal women. Women Health. 1998;27:55-66. 54. Mathias JR, Clench MH, Abell TL, et al. Effect of leuprolide acetate in treatment of abdominal pain and nausea in premenopausal women with functional bowel disease: a double-blind, placebo-controlled, randomized study. Dig Dis Sci. 1998;43:1347-55. 55. Mathias JR, Clench MH, Reeves-Darby VG, et al. Effect of leuprolide acetate in patients with moderate to severe functional bowel disease. Double-blind, placebo-controlled study. Dig Dis Sci. 1994;39:1155-62. 56. Mathias JR, Clench MH, Roberts PH, Reeves-Darby VG. Effect of leuprolide acetate in patients with functional bowel disease. Long-term follow-up after double-blind, placebo-controlled study. Dig Dis Sci. 1994;39:1163-70. 57. Mathias JR, Ferguson KL, Clench MH. Debilitating “functional” bowel disease controlled by leuprolide acetate, gonadotropin-releasing hormone (GnRH) analog. Dig Dis Sci. 1989;34:761-6.

43. Jackson NA, Houghton LA, Whorwell PJ, Currer B. Does the menstrual cycle affect anorectal physiology? Dig Dis Sci. 1994;39:2607-11.

58. Ruigómez A, García Rodríguez LA, Johansson S, Wallander MA. Is hormone replacement therapy associated with an increased risk of irritable bowel syndrome? Maturitas. 2003;44:133-40.

44. Houghton LA, Lea R, Jackson N, Whorwell PJ. The menstrual cycle affects rectal sensitivity in patients

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pain responses in postmenopausal women. Pain. 2001;92:229-34. 60. Palsson OS, Turner MJ, van Tilburg MA, Kanazawa M, Whitehead WE. Survey of the effects of changes in female sex hormones on irritable bowel symptoms. Gastroenterology. 2003;124:A396-7. 61. Sampson JA. Endometrial carcinoma of the ovary, arising in endometrial tissue in that organ. Arch Surg. 1925;10:1-2.

72. Soumekh A, Nagler J. Gastrointestinal endometriosis causing subacute intestinal obstruction with gradual development of weight loss and misdiagnosed as irritable bowel syndrome. Case Rep Gastroenterol. 2014;8:51-5.

62. Kennedy S. The genetics of endometriosis. J Reprod Med. 1998;43:263-8.

73. Nasim H, Sikafi D, Nasr A. Sigmoid endometriosis and a diagnostic dilemmaâ&#x20AC;&#x201D;A case report and literature review. Int J Surg Case Rep. 2011;2:181-4.

63. Painter JN, Anderson CA, Nyholt DR, et al. Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis. Nat Genet. 2011;43:51-4.

74. Roman H, Ness J, Suciu N, et al. Are digestive symptoms in women presenting with pelvic endometriosis specific to lesion localizations? A preliminary prospective study. Hum Reprod. 2012;27:3440-9.

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65. Yoo JY, Jeong JW, Fazleabas AT, Tayade C, Young SL, Lessey BA. Protein Inhibitor of Activated STAT3 (PIAS3) is down-regulated in eutopic endometrium of women with endometriosis. Biol Reprod. 2016;95:11. 66. Agic A, Xu H, Finas D, Banz C, Diedrich K, Hornung D. Is endometriosis associated with systemic subclinical inflammation? Gynecol Obstet Invest. 2006;62:139-47. 67. Hansen KE, Kesmodel US, Baldursson EB, Kold M, Forman A. Visceral syndrome in endometriosis patients. Eur J Obstet Gynecol Reprod Biol. 2014;179:198-203. 68. Moore J, Barlow D, Jewell D, Kennedy S. Do gastrointestinal symptoms vary with the menstrual cycle? Br J Obstet Gynaecol. 1998;105:1322-5. 69. Seaman HE, Ballard KD, Wright JT, de Vries CS. Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case-control study--part 2. BJOG. 2008;115:1392-6. 70. Tong YL, Chen Y, Zhu SY. Ileocecal endometriosis and a diagnosis dilemma: a case report and literature review. World J Gastroenterol. 2013;19:3707-10. 71. Wu CY, Chang WP, Chang YH, Li CP, Chuang CM. The risk of irritable bowel syndrome in patients with

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Review

Barriers and Beliefs Contributing to Excessive Gestational Weight Gain in Low-Income Women Brittany E. Brodsky, MS, RD, LD, and John V. Logomarsino, PhD, RD, LDN From the Department of Human Environmental Studies, Central Michigan University, Mount Pleasant, Mich (B.E.B., J.V.L.)

ccording to the American Heart Association, 1 in 3 children (31.8%) and nearly 70% of adults in the United States (US) are either obese or overweight.1 Women of childbearing age (20â&#x20AC;&#x201C;39 years old) are included in this obesity epidemic: 35.8% are obese and an additional 24% are overweight.2 These data are significant as pregnant women who are obese are at increased risk for gestational diabetes, hypertension, preeclampsia, postpartum weight retention, and labor and delivery complications.3-6 In addition, neonates born to women who are obese have an increased risk of congenital anomalies and neonatal death7; they also have an increased risk of being overweight or obese during childhood.8 Although a significant number of US women are overweight before gestation, studies have shown that more than 40% of mothers exceed recommended weight gain guidelines during pregnancy from the Institute of Medicine (IOM).9 Rates of obesity in childbearing women also vary by ethnicity and income, with a higher proportion of African American women and low-income women being overweight or obese.10,11 In the US, approximately 50% of infants receive Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) services.12 The majority of these infantsâ&#x20AC;&#x2122; mothers participate in WIC prenatally as well, illustrating the sizable population of low-income mothers in the US. According to the Centers for Disease Control and Prevention, more than 50% of low-income women are overweight or obese before pregnancy, and 48% exceed the weight gain recommended by the IOM.13 Despite knowledge of adverse health outcomes, excessive gestational weight gain (GWG) has been a problem affecting almost 1 out of 2 women for GHS Proc. June 2017; 2 (1): 51-55

the last 10 years.3 Public health programs have made great strides to ensure that low-income women have access to nutritional foods and nutrition education to promote healthy pregnancies. Current data, however, reveal that providing these resources may not be enough to ensure moderate healthy weight gain during pregnancy within the IOM guidelines.14,15 The aim of this qualitative literature review is to identify and describe the most common psychosocial barriers contributing to excessive GWG in low-income women.

Methods Three databases were searched to obtain articles for this review: PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Web of Science. The MeSH (Medical Subject Headings) descriptors used for the initial search included pregnancy, poverty, attitudes, weight gain, obesity, postpartum period, and pregnancy nutrition. All 3 databases were searched using combinations of the keywords and related terms until saturation of the content was achieved. Articles were reviewed and sorted according to MeSH categorization, study methodology (quantitative vs. qualitative study), location (US vs. non-US study), and study population (low-income status vs. other). Selected articles were reviewed further, and common themes contributing to excessive GWG in low-income women were identified. In this review, only qualitative studies were included, as individual behaviors and perceptions can be difficult to quantify. Moreover, only studies performed in the US that involved pregnant or postpartum women of low socioeconomic status were included. Low socioeconomic, or low-income, status was determined according to each articleâ&#x20AC;&#x2122;s study population. The majority of 51

studies defined low-income as participants whose gross income fell below 185% of the US poverty income guidelines and/or those who participated in federally supported health insurance. Excessive GWG was defined according to IOM weight gain recommendations, which is determined by body mass index (BMI) (Table 1).16

Results Eight qualitative articles met the search criteria (Table 2). From these, 5 recurring themes associated with excessive GWG in low-income women were identified: 1) perceptions and beliefs on weight gain; 2) diet and nutrition; 3) physical activity; 4) family, friends, and healthcare professionals; and 5) general health.

Perceptions and/or Beliefs on Weight Gain Multiple studies have found a mother’s perception and/or belief on weight gain during pregnancy Table 1 Gestational weight gain recommendations from the Institute of Medicine.16 Pregnancy Weight Category

Body Mass Index (kg/m2)

Recommended Range of Weight Gain (lbs)

<18.5

28–40

Normal weight

18.5–24.9

25–35

Overweight

25.0–29.9

15–25

≥30.0

11–20

Underweight

Obese

Table 2 Qualitative studies on excessive gestational weight gain in low-income women. Author

Year

Primary Barrier(s) to Healthy GWG

2012

Perceptions and Beliefs

Allison et al10

2012

120

General Health

Herring et al15

2012

Perceptions and Beliefs; Family and Friends

Groth et al17

2013

Physical Activity; Diet and Nutrition

Reyes et al14

2013

Diet and Nutrition; Family and Friends

Paul et al11

2013

Perceptions and Beliefs; Diet and Nutrition; Physical Activity; General Health

Wright et al19

2013

101

Perceptions and Beliefs; General Health

Anderson et al18

2015

Perceptions and Beliefs; Family, Friends, and Healthcare Professionals

Groth et al

GWG, gestational weight gain

to impact her risk of excessive GWG.11,14,15,17,18 In 2012, a focus group study on pregnant, low-income African American women found that participants were not concerned with limiting their weight gain. In fact, most of the women believed significant weight gain to be necessary for a healthy baby. These mothers also believed postpartum weight retention to be normal.16 A second focus group study published in 2012 discovered comparable findings. Study participants—low-income pregnant women—expressed the belief that consumption of more calories was essential to a baby’s health. Moreover, the possibility that poor weight gain could result in poor fetal outcomes was a real concern; this perception and fear proved more prevalent than poor fetal outcomes stemming from excessive weight gain.18 In 2013, Reyes et al interviewed 21 low-income pregnant women with the aim of understanding factors that influenced their diet. Although this study was primarily focused on diet and nutrition, conversations revealed that some women were actually scared that they may starve their babies if they did not consume enough food. As expected, this perception often resulted in persistent snacking, large portions, and overconsumption.14

Diet and Nutrition A balanced diet, paired with consistent physical activity, is considered by many to be the answer to a healthy life. Likewise, Reyes et al found that low-income pregnant women also believe consumption of fruits and vegetables to be good for their baby’s health, as well as their own. However, the mothers readily admitted that they are still more likely to eat foods high in fat and sugar because it is more convenient, costs less, and tastes better.14 Paul et al and Groth et al showed similar results.11,18 Participants in Groth’s study described having good intentions, but then explained that 1) eating out is simply a way of life and that 2) their cravings for dense high-fat and palatable foods were just too strong.18 Unlike the majority of the studies, Paul et al included low-income and high-income focus groups. In Paul et al, all participants, regardless of income, agreed that eating fruits and vegetables would be good for the baby. The low-income women, however, believed that certain fruits and vegetables would cause heartburn, that eating would help them feel better when stressed, that they were eating for 2, that weight did not equal health, and that it was not possible to control their cravings, binges, or weight gain.

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BARRIERS OF EXCESSIVE GWG IN LOW-INCOME WOMEN The low-income participants also reported a preference for fast food and/or foods high in fat.11

feelings included time constraints, other appointment priorities, and a lack of training.19

Physical Activity Comprehension of what constitutes physical activity, as well as the role it can play in an individual’s overall health, is valuable. Several studies, however, suggest that knowledge and education surrounding physical activity in this population may be lacking.11,14,18

General Health In 2013, Wright et al evaluated 101 low-income postpartum women, the majority of whom were African American (66%) or Hispanic (22%).20 More than half (58%) were overweight or obese before gestation, and 49% gained an excessive amount of weight while pregnant. Survey data from this study showed that women with a greater sense of self-efficacy and internal locus of control were associated with less GWG; presence of perinatal depression, however, was associated with excessive GWG.20

In Paul et al, the low-income focus groups described any amount of walking as exercise; they also believed daily living to be a form of physical activity. When it came to performing physical activity during pregnancy, they said they could not exercise when tired, uncomfortable, or busy. In contrast, the high-income group of pregnant women described physical activity as structured and recreational. They also believed that exercise would make them feel better during pregnancy, would help control their weight gain, and that they could modify their physical activity to remain active throughout their pregnancy.11 Groth et al also reported on physical activity, finding that participants reported a decreased level of physical activity since pregnancy. Most participants described feeling fatigued with little desire or motivation to exercise.18

Family, Friends, and Healthcare Professionals External influences, such as parents, friends, spouses, coworkers, and/or children, often play a role in the decisions people make and on the environments in which they live. Multiple studies reported that participants were strongly encouraged, if not pressured, by friends and parents to consume more food while pregnant; the popular expression “you’re eating for 2 now” was common.11,16,19 Paul et al11 and Anderson et al19 found that a notable proportion of study participants live in multigenerational homes, with the mother or mother-in-law being in charge of grocery shopping and meal preparation. This fact resulted in participants being reliant on others and feeling as if they had little to no control over what food was prepared and served. In addition to having multiple focus groups of low-income pregnant women, Anderson et al also had 1 focus group of obstetrics and gynecology (OB/GYN) healthcare providers. These participants reported feeling uncomfortable with counseling patients on GWG. Reasons for these

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Allison et al sought to identify contributors of excessive GWG in low-income, overweight African American pregnant women by evaluating their sleep, mood, and eating patterns over 10 weeks (gestational age: 14–24 weeks).10 Study participants reported an average of 7.1 hours of sleep per night and a mean of 4.3 awakenings per week. Approximately 18% of women reported some level of depression. Of note, women with better sleep were less likely to feel depressed. In terms of disordered eating and eating patterns, 32% of women reported eating one-quarter of their daily caloric intake after dinner. Allison et al reported that 58% of their study population experienced excessive GWG. Although many variables were analyzed, only 1 variable was found to be predictive of excessive GWG in these women—eating due to cravings.10

Discussion One recurring theme throughout the literature is lack of awareness surrounding appropriate GWG. Although disconcerting, these findings are not novel. Stotland et al found that only 1 in 3 women will receive weight gain advice from a prenatal care provider.21 Possible explanations for why women do not receive GWG goals from their OB/ GYN providers include lack of awareness, familiarity, and/or agreement with IOM guidelines.21 As previously described, Anderson et al found that some OB/GYNs felt inadequately trained to counsel patients about GWG.19 They also reported having limited time for appropriate education and needing to prioritize more pressing issues. The focus group of OB/GYNs also expressed the need for improved communication between nutritionists/dietitians and the physician team so that the physician can reinforce the dietitian’s recommendations. Last, some OB/GYNs were

Abbreviations and Acronyms US = United States; IOM = Institute of Medicine; WIC = Special Supplemental Nutrition Program for Women, Infants, and Children; GWG = gestational weight gain; BMI = body mass index

Correspondence Address to: Brittany E. Brodsky, MS, RD, LD, 5910 Olde Atlanta Parkway, Suwanee, GA 30024 (ellis1be@cmich.edu)

hesitant to make recommendations regarding healthy eating and physical activity because they did not know whether their patients could adopt these behaviors.19 Studies have shown counseling and education of GWG guidelines to be associated with improved GWG outcomes.21-24 However, both Reyes et al and Herring et al showed study participants to have some nutrition knowledge, as they knew they should be consuming healthy foods (eg, fruits and vegetables).14,15 This knowledge, however, was not enough to combat unhealthy choices or excessive GWG. In 2013, Mehta-Lee et al reported that pregnant women from urban populations are less likely to engage in lifestyle modifications when they do not understand their appropriate GWG goal and its importance.25 This study suggests that there may be a significant difference between having an awareness that fruit and vegetables are good for you and having a more complete understanding of the risks and benefits associated with healthy, or unhealthy, eating while pregnant. Based on the results from 4 focus groups, Herring et al recommended 3 tips for counseling low-income women during pregnancy: 1) explain additional

caloric requirements needed in each trimester; 2) discuss internal and external hunger cues; and 3) communicate weight goals early in pregnancy to prevent excessive GWG rather than reacting to excessive GWG after it has already occurred.15 In addition, a recent study by Wang et al reported peer-facilitated group classes on exercise, cooking, personal finance, child development, and stress management to be educational and desirable; group classes in which personal stories and guest experts presented were also welcomed.26

Conclusion The current rate of low-income pregnant women in the US who are overweight or obese is alarming. However, the lack of awareness surrounding the numerous associated risk factors, for both mother and child, is even more disconcerting. New educational materials for low-income women of childbearing age are needed. These materials should focus on combatting the specific barriers to healthy weight gain described in this paper (eg, misperceptions, cravings, nutrition, exercise, etc.). Additional conversations between patients and healthcare practitioners are also needed. More specifically, dietitians or physicians should make every effort to explain the reasoning (health risks and benefits) behind their lifestyle recommendations.

References 1. Understanding the American Obesity Epidemic. http:// www.heart.org/HEARTORG/HealthyLiving/WeightManagement/Obesity/Understanding-the-American-Obesity-Epidemic_UCM_461650_Article. jsp#.WPDgc2nyvDA. American Heart Association. Updated March 9, 2016. Accessed April 4, 2017.

8. Norman JE, Reynolds RM, Reynolds R. The consequences of obesity and excess weight gain in pregnancy. Proc Nutr Soc. 2011;70:450-6.

2. Flegal KM, Carroll D, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999–2010. JAMA. 2012;307:491-7.

10. Allison KC, Wrotniak BH, Paré E, Sarwer DB. Psychosocial characteristics and gestational weight change among overweight, African American pregnant women. Obstet Gynecol Int. 2012;2012:878607.

3. Koleilat M, Whaley SE. Trends and predictors of excessive gestational weight gain among Hispanic WIC participants in Southern California. Matern Child Health J. 2013;17:1399-1404. 4. Baeten JM, Bukusi EA, Lambe M. Pregnancy complications and outcomes among overweight and obese nulliparous women. Am J Public Health. 2001;91:436-40. 5. Cedergren MI. Maternal morbid obesity and the risk of adverse pregnancy outcome. Obstet Gynecol. 2004;103:219-24. 6. Phelan S. Pregnancy: a “teachable moment” for weight control and obesity prevention. Am J Obstet Gynecol. 2010;202:135.e131-8. 7. Fitzsimons KJ, Modder J, Greer IA. Obesity in pregnancy: risks and management. Obstet Med. 2009;2:52-62.

9. Viswanathan M, Siega-Riz AM, Moos MK, et al. Outcomes of maternal weight gain. Evid Rep Technol Assess. 2008;168:1-223.

11. Paul KH, Graham ML, Olson CM. The web of risk factors for excessive gestational weight gain in low income women. Matern Child Health J. 2013;17:344-51. 12. Oliveira V, Frazão E. The WIC program: background, trends, and economic issues, 2009 edition. Washington, D.C.: US Dept of Agriculture, Economic Research Service; 2009. 13. Nutrition, Physical Activity and Obesity Data, Trends and Maps. Centers for Disease Control and Prevention. http://nccd.cdc.gov/NPAO_DTM/IndicatorSummary.aspx?category=28&indicator=59. Updated November 2, 2013. Accessed October 19, 2015. 14. Reyes NR, Klotz AA, Herring SJ. A qualitative study of motivators and barriers to healthy eating in pregnancy for low-income, overweight, African-American mothers. J Acad Nutr Diet. 2013;113:1175-81.

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BARRIERS OF EXCESSIVE GWG IN LOW-INCOME WOMEN 15. Herring SJ, Henry TQ, Klotz AA, Foster GD, Whitaker RC. Perceptions of low-income African-American mothers about excessive gestational weight gain. Matern Child Health J. 2012;16:1837-43. 16. Institute of Medicine (US) and National Research Council (US) Committee to Reexamine IOM Pregnancy Weight Guidelines. In: Rasmussen KM, Yaktine AL, eds. Weight Gain During Pregnancy: Reexamining the Guidelines. Washington (DC): National Academies Press (US); 2009. 17. Groth SW, Morrison-Beedy D, Meng Y. How pregnant African American women view pregnancy weight gain. J Obstet Gynecol Neonatal Nurs. 2012;41:798-808. 18. Groth SW, Morrison-Beedy D. Low-income, pregnant, African American women’s views on physical activity and diet. J Midwifery Womens Health. 2013;58:195-202. 19. Anderson CK, Walch TJ, Lindberg SM, Smith AM, Lindheim SR, Whigham LD. Excess gestational weight gain in low-income overweight and obese women: a qualitative study. J Nutr Educ Behav. 2015;47:404-11. 20. Wright C, Bilder D, DeBlasis T, Mogul M, Rubin D, Shea JA. Psychosocial factors associated with gesta-

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tional weight gain in a low-income cohort. J Health Care Poor Underserved. 2013;24:332-43. 21. Stotland NE, Haas JS, Brawarsky P, Jackson RA, Fuentes-Afflick E, Escobar GJ. Body mass index, provider advice, and target gestational weight gain. Obstet Gynecol. 2005;105:633-8. 22. Phelan S. Pregnancy: a “teachable moment” for weight control and obesity prevention. Am J Obstet Gynecol. 2010;202:135.e131-8. 23. Cogswell ME, Serdula MK, Hungerford DW, Yip R. Gestational weight gain among average-weight and overweight women—what is excessive? Am J Obstet Gynecol. 1995;172:705-12. 24. 30. Taffel SM, Keppel KG. Advice about weight gain during pregnancy and actual weight gain. Am J Public Health. 1986;76:1396-9. 25. Mehta-Lee SS, Lischewski Goel JL, Xu L, Brittner MR, Bernstein PS, Bonuck KA. Perception of weight status and its impact on gestational weight gain in an urban population. Matern Child Health J. 2013;17:1931-9. 26. Wang ML, Arroyo J, Druker S, Sankey HZ, Rosal MC. Knowledge, attitudes and provider advice by pre-pregnancy weight status: a qualitative study of pregnant Latinas with excessive gestational weight gain. Women Health. 2015;55:805-28.

Case Report

Robotic Transabdominal Preperitoneal Repair of Bilateral Arcuate Line Hernias Sam Weimer, MD; Daniela Cocco, MD; and Conrad Ballecer, MD, FACS From the Maricopa Integrated Health System, Phoenix, Ariz (S.W., D.C., C.B.); Center for Minimally Invasive and Robotic Surgery, Peoria, Ariz (C.B.); Banner Thunderbird Medical Center, Glendale, Ariz (S.W., D.C., C.B.); and Abrazo Arrowhead Hospital, Abrazo Community Health Network, Glendale, Ariz (S.W., D.C., C.B.)

Abstract Arcuate line hernias (ALH) are uncommon defects with poorly understood etiology and only a few published reports in regard of diagnosis and repair. Prevalence is unknown because it is frequently misdiagnosed, rarely symptomatic, and, therefore, even more rarely surgically intervened. The authors present a case of a 51-year-old woman who presented to the emergency department with chronic diffuse abdominal pain, nausea, and anorexia. CT (computed tomography) scan of the abdomen and pelvis revealed bilateral ALH. The patient underwent a robotic transabdominal preperitoneal (rTAPP) repair. To our knowledge, this report is the first to describe a successful robotic approach for bilateral ALH repair using the TAPP technique.

rcuate line hernias (ALH) are uncommon and poorly understood with only a few published reports documenting diagnosis and subsequent repair. The arcuate line, also known as linea semicircularis of Douglas, is defined as the inferior margin of the posterior rectus sheath, approximately at the level of the anterior superior iliac spine, which splits from the

aponeurosis of the internal oblique to envelop the rectus muscles. ALHs result from disruption of the posterior sheath from the overlying rectus abdominis muscles, allowing for herniation of visceral content, such as small bowel. It is generally categorized as an internal or intraparietal hernia, as there is

Figure 1 Axial and sagittal views of CT scan revealing bilateral arcuate line hernias with incarcerated small bowel. Solid arrow: posterior rectus sheath. Dashed arrow: small bowel.

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ROBOTIC TAPP REPAIR OF ALH no true abdominal wall defect.1 The cause of such disruption is largely unknown, but an association with previous abdominal wall surgery can be identified in several cases.

Figure 2 Intracorporeal view of bilateral arcuate line hernias. Solid arrow: right hernia. Dashed arrow: left hernia.

Actual prevalence of this type of hernia is unknown as it is frequently misdiagnosed, usually as a Spigelian hernia, and rarely symptomatic.2,3 Patients found to have ALHs most commonly complain of abdominal pain that may be diffuse or lateralized, depending on the side the hernia is located on, or they complain of a palpable bulge.1-5 Open and laparoscopic repairs have been described in the literature, where different methods have been used, including intraperitoneal onlay mesh, transabdominal preperitoneal (TAPP), and even primary repairs without mesh.1-3,6 This report describes the first robotic TAPP (rTAPP) repair with mesh.

Case Description

Figure 3 Primary closure of left arcuate line hernia defect.

A 51-year-old woman presented to the emergency department complaining of chronic abdominal pain, nausea, and inability to tolerate oral intake; she had a surgical history of an abdominoplasty in the remote past. Abdominal CT (computed tomography) scan revealed small bowel loops extending in-between the posterior rectus sheath and rectus muscles of the abdominal wall bilaterally (Fig. 1). Final diagnosis was consistent with bilateral ALH. This patient underwent an rTAPP repair requiring 3 ports in the lateral abdomen bilaterally. Bilateral ALHs were easily identifiable upon intraperitoneal access (Fig. 2). A TAPP approach was initiated by incising the peritoneum at the midline with subsequent dissection of the peritoneum off the posterior sheath on the side contralateral to initial port configuration. Reduction of the hernia sac was performed; in addition, a large preperitoneal plane was created to accommodate mesh to adequately overlap the defect in all directions.

Figure 4 Preperitoneal placement of 15 cm x 15 cm flat polypropylene mesh.

The ALH was primarily closed by re-approximation of the posterior sheath to the overlying rectus muscle and anterior sheath with barbed suture (Fig. 3). A 15 cm x 15 cm flat polypropylene mesh was placed and secured in a preperitoneal position with tack fixation (Fig. 4). Mirror image trocars were placed on the contralateral abdomen, the robot was re-docked, and repair of the right ALH was executed in a similar fashion. The mesh was re-peritonealized by re-approximation of the peritoneal flap to the abdominal wall. The postoperative course was uneventful and the patient was discharged home on postoperative GHS Proc. June 2017; 2 (1): 56-58

Correspondence Address to: Conrad Ballecer, MD, Center for Minimally Invasive and Robotic Surgery, 14155 N 83rd Ave, Suite A105, Peoria, AZ 85381 (cballecer1@mac.com)

day 1. Subsequent follow-up visits over 1 year have revealed no further issues or recurrences.

robotic repair of this type of hernia using the rTAPP technique.

Discussion

Use of the robot is becoming increasingly popular in general surgery and is proving to be an accepted tool in the armamentarium of a general surgeon. The authors contend that the potential benefits of mesh placed in a preperitoneal position include decreased fixation requirement that contributes to postoperative pain, decreased costs with use of an uncoated mesh, and mesh protected by autologous tissue from the visceral content.

Few cases of ALHs have been reported in the literature, but bilateral arcuate line hernias are even rarer. In the present case, the previous abdominoplasty is suspected to be the most likely contributing factor to hernia development. Given the paucity of documented cases, there is currently no accepted standard for repair. Both open and laparoscopic techniques have been described previously.1-3,5 Most reports of laparoscopic repair note primary closure of the hernia defect using transfascial sutures or tacks with some repairs describing mesh reinforcement in an intraperitoneal position.1,6 Even fewer reports have mentioned a true laparoscopic TAPP technique with primary closure of the defect to protect intra-abdominal contents from the mesh.2 To our knowledge, this case is the first reported

Conclusion ALHs have been sporadically reported in the literature, with bilateral ALHs representing an even rarer finding. No accepted standard repair exists, with cases of both open and laparoscopic repairs reported in the literature. The current case demonstrates that the robotic approach is a safe alternative for the repair of complex hernias such as bilateral ALHs.

References

1. Cappeliez O, Duez V, Alle JL, Leclercq F. Bilateral arcuate-line hernia. Am J Roentgenol. 2003; 180:864-5.

4. Coulier B. Multidetector computed tomography features of linea arcuata (arcuate line of Douglas) and linea arcuata hernias. Surg Radiol Anat. 2007;29:397-403.

2. Montgomery A, Petersson U, Austrums E. The arcuate line hernia: operative treatment and a review of the literature. Hernia. 2013;17:391-6.

5. Abasbassi M, Hendrickx T, CaluwĂŠ G, Cheyns P. Symptomatic linea arcuata hernia. Hernia. 2011;15:229-31.

3. von Meyenfeldt EM, van Keulen EM, Erenberg JP, Hendriks ER. The linea arcuata hernia: a report of two cases. Hernia. 2010;14:207-9.

6. Messaudi N, Amajoud Z, Mahieu G, Bestman R, Pauli S, van Cleemput M. Laparoscopic arcuate line hernia repair. Surg Laparosc Percutan Tech. 2014;24:110-2.

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Case Report

Severe Pulmonary Hypertension in an 87-Year-Old Woman With Scimitar Syndrome Tamara van de Star, MD; Maximilien Rappaport, DO; Manisha S. Patel, MD; Armin Meyer, MD From the University of South Carolina School of Medicine Greenville, Greenville, SC (T.V.S.), and Department of Medicine, Greenville Health System, Greenville, SC (M.R., M.S.P., A.M.)

Abstract Scimitar syndrome is a rare congenital cardiovascular disorder characterized by terminal insertion of the right pulmonary vein into the inferior vena cava. Right lung hypoplasia, dextraposition of the heart, and anomalous systemic collaterals from the aorta to the right lung are also seen. Patients with scimitar syndrome typically present in infancy with pulmonary hypertension or heart failure, or as asymptomatic adults, in which scimitar is incidentally discovered during imaging studies. In this case, we describe an 87-year-old woman with scimitar syndrome who presented with severe pulmonary hypertension. The patient remained asymptomatic until 2014 when she presented with dyspnea on exertion. An echocardiogram showed a right ventricular systolic pressure (RVSP) of 120 mmHg–125 mmHg. She was started empirically on phosphodiesterase-5 inhibitor with improvement in symptoms and decreased RVSP. The patient, however, deteriorated and died of right heart failure 5 months after initiation of therapy. Few cases of adults with scimitar syndrome and pulmonary hypertension have been reported. This article highlights a rare case of scimitar syndrome in an elderly woman with transient improvement of pulmonary hypertension on empiric phosphodiesterase-5 inhibitors. To our knowledge, this patient represents the oldest case of scimitar with associated pulmonary hypertension.

cimitar syndrome, a variant of partial anomalous pulmonary venous connection, is a rare congenital cardiovascular disorder that occurs in less than 1% of the general population.1 It is characterized by terminal insertion of the right pulmonary vein into the inferior vena cava and is associated with right lung hypoplasia, dextraposition of the heart, and anomalous systemic collaterals from the aorta to the right lung.2,3 On chest X-ray, the anomalous vein appears as a curved shadow that resembles a scimitar—a Turkish sword. Scimitar syndrome typically presents during infancy or in adulthood. Infant presentation is associated with signs of heart failure and pulmonary hypertension, including hemoptysis, tachypnea, and poor growth.4-6 These young patients often require early surgical intervention and have a poor prognosis.4-6 In contrast, adults with scimitar are often diagnosed incidentally during imag-

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ing studies. Adults with unrepaired scimitar can be asymptomatic, but they may also have a history of recurrent pulmonary infections and exertional dyspnea; adult patients rarely require intervention.3-5,7 The infantile and adult forms of scimitar likely represent extremes on a continuum of disease presentation.

Case Description We present a novel case of an 87-year-old woman with unrepaired scimitar syndrome who developed severe pulmonary hypertension late in life. The patient’s medical history is significant for atrial fibrillation, aortic insufficiency, stroke, and hypertension. Computed tomography (CT) of the chest was performed in 2004 because of an abnormal chest radiograph finding. To our knowledge, this was the first imaging study in this patient to detail the partial anomalous pulmonary venous return, congenital hypoplasia of the right lung, large pulmonary arteries, aberrant arterial supply 59

to a portion of the right lower lobe, and dextrocardia consistent with scimitar syndrome (Fig. 1). Mild pulmonary hypertension with a right ventricular systolic pressure (RVSP) of 60 mmHg was first noted during a 2009 echocardiogram performed for a transient ischemic attack. We have no char-

Figure 1 Chest CT (A) and 3D chest CT (B) denoting the scimitar vein (right arrow) originating from upper lobe of the right lung connecting to the inferior vena cava (left arrow). The top arrow indicates the enlarged pulmonary artery.

acterization of the patient’s level of dyspnea or any record that she obtained pulmonary follow-up. In 2011, she had her first complication—pneumonia with an exudative pleural effusion. The pneumonia resolved with antibiotics and the pleural effusion was drained by a thoracentesis. In 2014, the patient presented to her primary care physician with increasing dyspnea upon minimal exertion, cough, fatigue, and changes in her exercise capacity. An echocardiogram demonstrated an RVSP of 120 mmHg–125 mmHg with severe right ventricular enlargement, severe right atrial enlargement, and preserved left ventricular systolic function with moderate aortic stenosis. CT angiogram demonstrated persistent dilation of pulmonary arterial tree with no evidence of pulmonary embolism. Further hemodynamic evaluation, including heart catheterization, was recommended but declined by the patient. She was started on a phosphodiesterase-5 (PDE5) inhibitor, bronchodilators, and nocturnal oxygen. Following 1 month of treatment, the patient’s symptoms improved: Her basic natriuretic peptide (BNP) levels decreased (1762 pg/mL to 618 pg/ mL), and her 6-minute walking distance remained stable (255 m to 243 m). Three months after starting PDE5 inhibitor, the patient experienced worsening dyspnea and lower extremity edema and was started on a loop diuretic. During this time, her BNP levels ranged from 269 pg/mL–778 pg/ mL, and an additional 6-minute walking test showed a sizable decrease in distance (109 m). A repeat echocardiogram, however, demonstrated an improvement in pulmonary hypertension with an RVSP of 65 mmHg–70 mmHg. Unfortunately, the patient deteriorated and died of right heart failure 5 months after initiation of therapy.

Discussion The authors suspect that this woman had a significant left-to-right shunt through the scimitar vein resulting in overcirculation of the pulmonary vasculature and increased pulmonary vascular resistance. This left-to-right shunt is the result of recirculation of oxygenated pulmonary venous blood through the pulmonary vasculature. The fraction of blood being shunted depends on the proportion of anomalous drainage compared with the total pulmonary venous return. This fraction is influenced by the number and size of anomalous pulmonary veins, pulmonary segment from which the scimitar vein originates as a result of differences in distribution of blood flow to each segment, relative resistance of the pulmonary veins, and compliance of the respective receiving chambers.8

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PULMONARY HYPERTENSION IN LATE SCIMITAR SYNDROME The patient’s condition most closely resembles the World Health Organization’s Group 1 classification of pulmonary arterial hypertension (PAH), which is associated with congenital heart disease. This case, however, is unusual in that the initial presentation of PAH was both late and severe. Possible contributing factors to the patient’s pulmonary hypertension include aortic stenosis, aortic insufficiency, paroxysmal atrial fibrillation, and hypertension leading to increased left ventricular end diastolic pressures, diastolic heart failure, and consequent pulmonary hypertension. Because of the absence of invasive hemodynamic testing, the exact cause of her pulmonary hypertension is unknown. Treatment with a PDE5 inhibitor was, therefore, empiric and not without risk. The decision to treat her PAH was undertaken only after extensive discussions with the patient and her family, who desired a minimally invasive and palliative approach. The patient initially improved with treatment, but then succumbed to the natural progression of her advanced pulmonary hypertension. It is unknown whether the PDE5 inhibitor contributed to worsening pulmonary venous congestion secondary to a decrease in pulmonary vascular resistance. Although several cases of scimitar with pulmonary hypertension in adults have been described in the literature, no case has reported the severity of pulmonary hypertension seen in this patient.3,7,9-12

Scimitar syndrome is a rare condition that is generally asymptomatic in adults. However, when adults with scimitar present with PAH, it can result in debilitating symptoms and a poor prognosis, similar to the infantile form of scimitar.7 We propose that identifying causes of pulmonary hypertension in adult scimitar may allow physicians to identify and prevent PAH in adults with asymptomatic scimitar syndrome. Additionally, optimal treatment of this condition is unknown.2 Although PDE5 inhibitors are a standard therapy in managing PAH, their use in relation to infantile scimitar has been published in the literature only once.6,13

Correspondence Address to: Tamara van de Star, MD, University of South Carolina School of Medicine Greenville, 607 Grove Rd, Greenville, SC 29605 (tamaravdstar@ gmail.com)

This case suggests the need to include a cardiologist within the treatment team, the importance of right-heart catheterization to better understand the causes, the need to consider other treatment modalities besides pulmonary vasodilators (such as angiotensin-converting enzyme inhibitors and diuretics), and the need to involve an experienced adult congenital team member in complex multimorbidity cases.7,9

Conclusion In conclusion, we have presented a rare case of scimitar syndrome with severe pulmonary hypertension in an elderly woman with symptomatic and hemodynamic improvement, albeit transient on empiric PDE5 inhibitor. To our knowledge, this patient is the oldest case of scimitar syndrome with associated pulmonary hypertension in the literature.

References 1. Wang CC, Wu ET, Chen SJ, et al. Scimitar syndrome: incidence, treatment and prognosis. Eur J Pediatr. 2008;167:155-60. 2. Grech V, Xuereb R, Xuereb M, Manche A, Schembri K, DeGiovanni JV. Late presentation and successful treatment of classical scimitar syndrome. Images Paediatr Cardiol. 2003;5:49-62. 3. Gupta ML, Bagarhatta R, Sinha J. Scimitar syndrome: a rare disease with unusual presentation. Lung India. 2009;26:26-9. 4. Gao YA, Burrows PE, Benson LN, Rabinovitch M, Freedom RM. Scimitar syndrome in infancy. J Am Coll Cardiol. 1993;22:873-82. 5. Huddleston CB, Exil V, Canter CE, Mendeloff EN. Scimitar syndrome presenting in infancy. Ann Thorac Surg. 1999;67:154-9. 6. Rukban HA, Ghaihab MA, Tamimi O, Al-Saleh S. Clinical spectrum of infantile scimitar syndrome: a tertiary center experience. Ann Pediatr Cardiol. 2014;7:29-33. 7. Yehia BR, Bachmann JM, Traill TA. Scimitar syndrome: a rare cause of dyspnea in adults. South Med J. 2010;103:578-80.

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8. Ward KE, Mullins CE. Anomalous pulmonary venous connections, pulmonary vein stenosis, and atresia of the common pulmonary vein. In: Garson A Jr, Bricker JT, Fisher DJ, Neish SR, eds. The Science and Practice of Pediatric Cardiology. Baltimore: Williams and Wilkins;1998:1431. 9. Zagol B, Book S, Krasuki RA. Late “adult form” scimitar syndrome presenting with “infant form” complications. J Invasive Cardiol. 2006;18:E82-5. 10. Guo SJ, Shen YC, Wen FQ. Scimitar syndrome in an adult with atrial septal defect and severe pulmonary hypertension. Chin Med J. 2013;126:3199. 11. Humphries JA, Sullivan BL, Panse PM, Tajik AJ. A rare congenital finding in an elderly lady—scimitar syndrome with dextrocardia in a 79 year old. Congenit Heart Dis. 2010;5:188-90. 12. Rajaii-Khorasani A, Kahrom M, Mottaghi H, Kahrom H. Scimitar syndrome: report of a case and its surgical management. Ann Saudi Med. 2009;29:50-2. 13. Buckley MS, Staib RL, Wicks LM, Feldman JP. Phospodiesterase-5 inhibitors in management of pulmonary hypertension: safety, tolerability, and efficacy. Drug Healthc Patient Saf. 2010;2:151-61.

Case Report

Adamantinoma of the Forearm: A Chronologic Presentation of a Slow-Growing Malignancy Richard W. Gurich Jr, MD; Luminita Rezeanu, MD; and Scott E. Porter, MD, MBA, FACS From the Department of Orthopaedic Surgery, Greenville Health System, Greenville, SC (R.W.G., S.E.P.), and Department of Pathology, Greenville Health System, Greenville, SC (L.R.)

Abstract The purpose of this report is to present a unique case of an uncommon tumor. Adamantinomas are inherently rare, low-grade malignant primary bone tumors that almost always involve the tibia. Although cases have been reported of these tumors involving the long bones of the upper extremity, we present an instance in which both bones of the forearm were affected with documented radiographic changes over a 7-year span. Surgical management is the mainstay of treatment for these tumors and usually requires limb reconstruction following resection. We also present an interesting reconstruction option for upper extremity limb salvage following surgical resection of these tumors.

damantinomas are slow-growing, lowgrade malignant tumors usually found in the long bones. These tumors were first described in 1900. In 1913, Fischer coined the term “adamantinoma.”1 These tumors are uncommon, representing less than 1% of all malignant bone tumors.2 They are characterized as affecting the tibia in 80%–90% of cases and usually occur in patients in the second and third decades of life.3 Although adamantinomas show a predilection for involvement of the tibia, other skeletal sites have been reported, including the femur, radius, and ulna.4 Because of their malignant characteristics, adamantinomas of the long bones are usually treated with wide resection and reconstruction. Surveillance for distant recurrence when treating these tumors is mandatory as metastases are observed in 10%–30% of cases. Reports of involvement of the radius or ulna are limited to fewer than 10 cases, and we are unaware of any cases with simultaneous involvement of the radius and ulna. We report a unique case of an upper extremity adamantinoma ultimately affecting both the radius and ulna after a long period of preoperative observation. Treatment, therefore, included a wide resection of both the proximal radius and ulna and a subsequent reconstruction of the proximal ulna and ulnohu-

meral joint using an allograft-prosthesis composite. The aspects of this case—including its unique location, histopathology, and reconstruction using a total elbow arthroplasty-allograft composite—are discussed in the following sections.

Case Description A 60-year-old, right-handed woman was referred to our institution for evaluation of a right forearm mass. Her medical history was significant for thyroid cancer in the remote past and a longstanding radiographic diagnosis of fibrous dysplasia of the right ulna. At the time of presentation, her main complaint was an increase in right forearm pain and of swelling and progressive decrease in her functional range of motion. She had received no other treatment beyond X-ray imaging before this presentation, and the progressive nature of the changes prompted referral (Figs. 1 and 2). Physical exam revealed asymmetry of her right proximal forearm as compared to the contralateral side. A palpable mass was observed that appeared to be nonmobile. The flex-extension arc for elbow range of motion was observed to be 25 degrees of extension to 100 degrees in flexion, 0 degrees of pronation, and 20 degrees of supination. Neurovascular examination of the right upper extremity was unremarkable.

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ADAMANTINOMA OF THE FOREARM

Figure 1 Earliest available (7 years before referral) anteroposterior (A) and lateral (B) radiographs of the right forearm showing a lytic lesion of the proximal ulna.

Figure 2

Follow-up radiographs (24 months before referral) are shown in (A) and (B), and X-rays obtained after referral to our institution are shown in (C) and (D); note the increased destruction of the ulna and involvement of the radius.

Earliest available radiographs of the right forearm were from an outside visit 6 years before her presentation (Fig. 1). When compared to current radiographs, the stark changes were consistent with a very narrow differential diagnosis of adamantinoma, osteofibrous dysplasia, metastatic disease from her thyroid cancer history, or other primary malignancy of bone. The severity of these diagnoses prompted magnetic resonance imaging (MRI) of the right forearm, a computer tomography (CT) scan of the thorax, and a whole-body nuclear medicine bone scan under the belief that the findings were suggestive of a malignancy. The CT scan of the thorax and bone scan were negative. The MRI of the right forearm, as seen in Figure 3, showed involvement of the ulna and radius with an extensive soft tissue mass. A CT-guided needle biopsy was then performed, and pathology was consistent with an adamantinoma of the radius and ulna with osteofibrous dysplasia-like areas. GHS Proc. June 2017; 2 (1): 62-66

D C

Figure 3 Axial T1 fat suppressed with contrast (A) and coronal T2 fat suppressed (B)â&#x20AC;Żwith magnetic resonance images from the patientâ&#x20AC;&#x2122;s right forearm. Both radius and ulna are involved, and dimensions of the soft tissue mass are shown.

The patient was offered continued observation vs. limb ablation vs. surgical intervention to include wide resection and reconstruction of the right forearm. The patient elected to pursue limb salvage with wide resection of both the radius and the ulna along with allograft prosthetic reconstruction of the ulnohumeral joint.

Surgical Technique The surgical technique required a posterior incision that coursed from the distal third of the posterior humerus to the distal ulnar border of the forearm. Given the extensive soft tissue mass, a volar forearm incision was also used to access the radius and help provide visualization of the

Figure 4 Immediate postoperative anteroposterior (A) and lateral (B) forearm radiographs showing the total elbow arthroplasty-allograft composite. Sixteenmonth follow-up lateral forearm (C), anteroposterior and oblique (D), and lateral elbow (E) radiographs show stable appearance of the allograft-prosthesis composite and a wellhealed distal allografthost bone junction.

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ADAMANTINOMA OF THE FOREARM involved interosseous membrane and neurovascular structures. The mass was removed en bloc following soft-tissue dissection of it, osteotomies of both ulna and radius, and transection of the triceps insertion on the proximal ulna. Planned reconstruction involved an allograftprosthetic reconstruction. An allograft with dimensions similar to the patientâ&#x20AC;&#x2122;s native bone was obtained from the Musculoskeletal Transplant Foundation. The allograft was an entire ulna with its soft tissue attachments. A total elbow arthroplasty was cemented into the patientâ&#x20AC;&#x2122;s native humerus and the ulna allograft. The triceps mechanism of the elbow was reconstructed by suturing the remaining native triceps to the allograft triceps remnant. The distal tendon of the biceps was sutured into the remaining anterior soft tissues of the ulna allograft. Distally, the ulnar allograft-host bone junction was secured via compression plating with a plate and screw construct (Fig. 4). The wound was irrigated and closed, and the patient was placed in a long arm splint for 2 weeks.

Adamantinomas are slow-growing malignant tumors with metastatic potential. Histologically, these tumors are typically biphasic, consisting of malignant epithelial cells juxtaposed against a spindle cell stroma.5-7 The epithelial component of the tumor will stain positive for keratin. Adamantinomas can be divided into classic and differentiated (osteofibrous dyslasia-like) types. The difference resides in the amount of epithelial/ neoplastic component present, which is abundant in the classic type and very sparse in the differentiated adamantinoma. The epithelial component is further subdivided into basaloid, squamoid,

Figure 5 Representative image from histologic analysis of the patientâ&#x20AC;&#x2122;s right forearm mass biopsy. Note the biphasic histology composed of a fibrous stroma with cords of epithelial cells consistent with adamantinoma.

Postoperative Course Clear surgical margins were obtained. Both gross and histologic examinations were performed by a musculoskeletal pathologist. Histologic section showed large multilobulated nests of adamantinoma composed of cords of epithelial-like cells in a myxoid stroma. In addition, osteofibrous dysplasia-like areas were present. Focal highgrade areas exhibiting more epithelioid features in cellularity were also identified (Fig. 5). Simple areas of fibrous dysplasia were not reported. Postoperatively, the patient had pronation to 90 degrees, supination to neutral, and a 105-degree flexion-extension arc. The patient had allografthost bone junction healing at 10 months. Follow-up at 16 months has shown no evidence of local recurrence or metastasis.

Discussion This report outlines a unique case regarding an adamantinoma of the upper extremity involving both the ulna and radius. Although adamantinomas affecting the radius or ulna have been reported, we are unaware of any with simultaneous involvement of both bones of the forearm after such a long period of observation. Further, the total elbow allograft prosthetic composite secured with compression plating techniques presents an interesting method of reconstruction.

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Correspondence Address to: Scott E. Porter, MD, MBA, FACS, Greenville Health System, 2nd Floor Support Tower, Department of Orthopaedic Surgery, 701 Grove Rd, Greenville, SC 29605 (sporter@ghs.org)

tubular, and spindle variants, according to its histologic appearance. Also, some clinicians have placed osteofibrous dysplasia and adamantinoma on a spectrum of disease, given some similarities in their histological appearance.8 As mentioned above, these tumors are usually found in the anterior cortex of the tibia.2,3 The presentation of these tumors is analogous to the presentation in this patient with pain, swelling, and/or deformity.2 Secondary to the tumor’s inherent malignant characteristics and insensitivity to chemotherapy or radiation,9 treatment entails surgical management. En bloc resection followed by the appropriate reconstruction is the usual pathway for surgical treatment. Studies reporting patient survival are limited to small patient numbers because of the rarity of the tumor. Published mortality rates related to adamantinomas, however, have been reported to range from 13%–18%8; the rate of metastases ranges from 15%–30%.2,10 Additionally, local recurrence of these tumors can occur 5–15 years after diagnoses, mandating that these patients be followed for an indefinite time.11 Adamantinomas isolated to either the radius or ulna have been reported previously in the litera-

ture. Bourne et al reported on an adamantinoma involving the radius treated with en bloc excision and reconstruction using a vascularized fibula graft.12 Keeney et al studied 85 cases of adamantinomas located in various anatomic locations treated at their institution—only 2 involved the ulna and 1 the radius.3 Gianoutsos et al and Sherman et al published reports of adamantinomas of the ulna, while Soucacos reported on a case of an adamantinoma of the olecranon; this latter case was unique for both its location and its subsequent bony metastases.13-15 However, none of the above reports illustrated the chronological progression of disease or the simultaneous involvement of both bone of the forearm that our case presents.

Conclusion Our case report illustrates a unique presentation of an adamantinoma of the upper extremity. This case is not only unique for its areas of involvement, but also its progression before and after referral to our institution. These tumors are traditionally slow-growing; however, our report was able to chronologically follow the progression of this particular patient’s malignancy, ultimately treated with en bloc resection and a unique reconstruction method.

References 1. Rakhn LB. Adamantinoma, osteofibrous dysplasia and differentiated admantinoma. Skeletal Radiol. 2003;32:245-58. 2. Most MJ, Sim FH, Inwards CY. Osteofibrous dysplasia and adamantinoma. J Am Acad Orthop Surg. 2010;18:358-66. 3. Keeney GL, Unni KK, Beabout JW, Pritchard DJ. Admantinoma of long bones: a clinicopathologic study of 85 cases. Cancer. 1989;64:730-7. 4. Papagelopoulous PJ, Mavrogenis AF, Galanis EC, Savvidou OD, Inwards CY, Sim FH. Clinicopatholofical features, diagnosis, and treatment of adamantinoma of the long bones. Orthopedics. 2007;30:211-5. 5. Hauben E, van den Broek LC, Van Marck E, Hogendoorn PC. Adamantinoma-like Ewing’s sarcoma and Ewing’s-like adamantinoma. The t(11;22), t(21,22) status. J Pathol. 2001;195:218-21. 6. Jain D, Jain VK, Vasishta RK, Ranjan P, Kumar Y. Adamantinoma: a clinicopathological review and update. Diagn Path. 2008;3:8.

9. Hazelbag HM, Taminiau AH, Fleuren GJ, Hogendoorn PC. Adamantinonma of the long bones: A clinciopathological study of thirty two patients with emphasis on histological subtype, precursor lesion, and biological behavior. J Bone Joint Surg Am. 1994;76:1482-99. 10. Quereshi AA, Shott S, Mallin BA, Gietlis S. Current trends in the management of adamantinoma of long bones: an international study. J Bone Joint Surg Am. 2000;82:1122-31. 11. Filippou DK, Papadopoulos V, Kiparidou E, Demertzis NT. Adamantinoma of tibia: a case of late recurrence along with lung metastases. J Postgrad Med. 2003;49:75. 12. Bourne MH, Wood MB, Shives TC. Adamantinoma of the radius. A case report. Orthopedics. 1988;11:1565-6. 13. Gianoutsos MP, Marsden FW, McCarthy SW, Lee KK. Ulnar adamantinoma: en bloc excision and fibular osteoseptocutaneous free flap reconstruction. J Hand Surg Am. 1994;19:495-9.

7. Desai SS, Jambhekar N, Agarwal M, Puri A, Merchant N. Adamantinoma of tibia: a study of 12 cases. J Surg Oncol. 2006;93:429-33.

14. Sherman GM, Damron TA, Yang Y. CD99 positive adamantinoma of the ulna with ispilateral discrete osteofibrous dysplasia. Clin Orthop Relat Res. 2003;408:256-61.

8. Gleason BC, Leigl-Atzwanger B, Kozakewich HP, et al: Osteofibrous dysplasia and adamantinoma in children and adolescents: A clinicopathologic reappraisal. Am J Surg Pathol. 2008;32:363-76.

15. Soucacos PN, Hartofilakidis GK, Touliatos AS, Theodorou V. Adamantinoma of the olecranon. A report of a case with serial metastasizing lesions. Clin Orthop Relat Res. 1995;310:194-9.

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Case Report

Spontaneous Iliac Vein Rupture Nathaniel J. Walsh, MD; Ashley Schlafstein, BS; Caleb J. Mentzer, DO; and Steven B. Holsten Jr, MD From the Department of Surgery, Medical College of Georgia–Augusta University, Augusta, Ga (N.J.W., A.S., C.J.M., S.B.H.)

Abstract Although exceedingly rare, spontaneous iliac vein rupture is a known surgical emergency. These injuries are morbid and present a great challenge given the difficulty in making this diagnosis of exclusion. We present an interesting case involving a woman who presented in extremis as a trauma patient following a ground-level fall. She was taken to the operating room emergently because of hemoperitoneum and unstable vital signs. Based on the absence of other traumatic injuries, we believe a spontaneous iliac vein rupture and subsequent hypotension caused the patient’s fall, and not vice versa. This case demonstrates the need for early diagnosis and treatment of spontaneous iliac vein rupture given the life-threatening nature of these injuries.

pontaneous iliac vein rupture is an uncommon diagnosis. While many reported incidents are unrelated to any precipitating pathology, correlations have been reported with deep venous thrombosis (DVT), May-Thurner syndrome (MTS), and connective tissue disorders. Early diagnosis and treatment are paramount, as these patients typically present in extremis, and morbidity and mortality from this injury remain high. While a few cases are reported with non-operative management, the overwhelming majority requires surgical intervention.1 In this report, we will present an interesting case of spontaneous iliac vein rupture, review the literature, and comment on risk factors and outcomes.

Case Description A 45-year-old woman presented to the emergency department (ED) after reportedly sustaining a ground-level fall at home. The patient had been discharged from the hospital earlier that day on Eliquis for a left femoral DVT discovered during her admission. She was started on Eliquis a day before discharge and received 3 doses before leaving the hospital.

Upon arrival to the ED, the patient was alert but complaining of severe abdominal pain. She was hypotensive, tachypneic, and tachycardic. Physical examination revealed a soft, but distended and tender abdomen, and 1+ peripheral pulses

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bilaterally. No signs of external trauma were visible, aside from some minor abrasions on her knees. Her hemoglobin was 6.3 g/dL. Focused Assessment with Sonography for Trauma (FAST) revealed fluid in her left lower quadrant and pelvis. The abdominal plain film was negative; the computed tomography scan from her previous admission (1 day before discharge) showed a 1.2 cm splenic artery aneurysm, but no iliac DVTs. The hospital’s protocol for massive transfusion was initiated; the patient received tranexamic acid, despite the risk for progression of her left femoral DVT. The patient, however, remained hypotensive and was taken to the operating room for an exploratory laparotomy because of suspected hemoperitoneum. On initial exploration, a large zone 3 hematoma extending from the left pelvis to the left upper quadrant was appreciated and had displaced the colon and small bowel to the right. No apparent injury was detected to her abdominal organs and no intraperitoneal bleeding. Furthermore, no internal sign existed of abdominal wall or flank contusion/hematoma. The patient remained hypotensive despite all resuscitative efforts, including intraoperative blood transfusion, and the hematoma was observed to be expanding into zone 2.

To better view the retroperitoneum, a left medial visceral rotation was conducted. Splenectomy was then performed resulting from concern that her splenic artery aneurysm had ruptured. The hematoma, however, continued to expand. The hematoma was opened with a small incision and decompressed following a thorough exploration. The left paracolic gutter, pelvis, and left lower quadrant were packed. The aorta was compressed manually near the celiac artery. The site of active bleeding remained concealed while the patient continued to decompensate, with systolic blood pressures dropping to 30 mmHg–40 mmHg. The patient remained unresponsive to all resuscitative efforts including multiple blood transfusions. Since prolonged exploration failed to elucidate the source of the hemorrhage, the decision was made to perform a left thoracotomy to cross-clamp the aorta. We believed this would also allow for cardiac massage and other more direct cardiopulmonary resuscitative measures, if necessary. Thoracotomy was performed in the standard fashion. The aorta was cross-clamped, which allowed the anesthesia team to continue the resuscitation and preserve blood flow to the heart, lungs, and brain. The cross clamp was intermittently released over the next 30 minutes while exploration continued to minimize the risk of ischemic injuries to distal organs. The patient’s blood pressure improved, and the clamp was removed. Further exploration revealed a venous bleed in the patient’s left lower quadrant and pelvis. Vascular Surgery was consulted because of concern for iliac vessel injury. Ultimately, a spontaneous injury to the left external iliac vein was discovered in an area where no surgical dissection had occurred. The retroperitoneal tissue around the iliac vein injury appeared to have been auto-dissected by the hematoma, suggesting the rupture was spontaneous. The rupture was significant, with bleeding anteriorly and posteriorly; the vein was ligated to control the hemorrhage. The vein appeared to be grossly normal on cursory examination during the emergent exploration. The left lower quadrant, pelvis, and left chest were packed following ligation of the left external iliac vein, as the patient remained hypothermic and coagulopathic. The abdomen was temporarily closed with negative pressure wound therapy, and the thoracotomy was covered with a sterile towel

and ioban for temporary closure. The patient remained intubated and was taken to the surgical intensive care unit for further resuscitation. Her left chest was closed on postoperative day (POD) 2, and her abdomen was closed POD5. The patient had a protracted hospital course but was eventually discharged to a long-term rehabilitation facility in good condition and on oral anticoagulation. She had slight progression of her DVT on repeat ultrasound, but never developed a pulmonary embolism despite her noncompliance with anticoagulation. The patient has since been followed for 12 months. She has reported some mild, persistent left leg swelling but is doing well overall.

Discussion Spontaneous iliac vein rupture is rare, with fewer than 50 cases reported in the literature.2 Typically, injuries to the iliac veins are iatrogenic (ie, surgery, enodovascular procedures, central lines) or related to trauma. Hossne et al reported the first case of spontaneous iliac vein rupture in 1961.3 In 2006, a review of the literature described 33 cases. The majority occurred in older (mean age of 60.6 years) women (85%).4 The majority of patients were also left-sided (94%) and reported clinical or histological evidence of DVT or thrombophlebitis before presentation (79%).4 To our knowledge, 12 additional instances have been reported,1,2,5 including a report of 9 cases (8 involving women) at a single institution.1 The literature over the last 10 years is consistent with the 2006 review, with the majority of cases reporting a history of thrombophlebitis and occurring in women 39–70 years of age. Our case is similar to the literature in that it occurred in a middle-age woman, involved the left iliac vein, and was treated with open surgery. The etiology of spontaneous iliac vein rupture remains unclear. Proposed mechanisms include mechanical (intra-abdominal mass, DVT), inflammatory (thrombophlebitis), and hormonal factors (pregnancy). In patients with MTS, disturbance or stasis of blood flow is one example of a mechanical factor that could cause spontaneous vein rupture.5 MTS involves compression of the left iliac vein against the spine as the vessel courses under the right common iliac artery. Symptoms can range from leg swelling and pain to DVT and vein rupture.

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SPONTANEOUS ILIAC VEIN RUPTURE The majority of reported cases have been managed with open repair.1,4 However, some ruptures were managed nonoperatively, and 3 with endovascular repair (1 being combined open and endovascular).1,4 Surgical management options include ligation of the vein, bypass, or primary suture repair of the injury. Endovascular treatment has not been widely reported and would certainly be a challenge depending on the nature of the vein injury and clinical condition of the patient. One of the major limitations to endovascular treatment appears to be the difficulty of diagnosing the rare injury. Associated morbidity is as high as 50%,1 with a mortality rate up to 27%.4 The most commonly reported long-term sequelae are leg swelling and chronic venous insufficiency.1 These conditions are often seen with iliac vein ligation or with residual iliac vein stenosis or thrombus. Our case of a spontaneous left external iliac vein rupture is unique. Although the patient presented

as a trauma patient following a ground-level fall, her spontaneous iliac vein injury, along with subsequent hemorrhagic shock, most likely caused the fall. She had no signs of external or internal trauma aside from some minor abrasions on her knees. Pelvic X-ray immediately postoperatively was negative for any fractures.

Conclusion As previously reported in the literature, this case illustrates the importance of early diagnosis, prompt initiation of resuscitation in unstable patients, and immediate operative intervention in almost all cases. Furthermore, this diagnosis should be a consideration in patients with unexplained retroperitoneal hematomas, DVT, thrombophlebitis, recent pregnancy, or a combination of the aforementioned diagnoses. While spontaneous iliac vein rupture remains a rare occurrence, physicians—especially trauma and vascular surgeons—need to be aware of the diagnosis to facilitate immediate resuscitation and treatment.

Correspondence Address to: Nathaniel J. Walsh, MD, Medical College of Georgia– Augusta University, Department of Surgery, 1120 15th St, BI 4070, Augusta, GA 30912 (nwalsh@ augusta.edu)

References 1. Jiang, J, Ding X, Zhang G, Su Q, Wang Z, Hu S. Spontaneous retroperitoneal hematoma associated with iliac vein rupture. J Vasc Surg. 2010;52:1278-82. 2. Hosn MA, Katragunta N, Kresowik T, Sharp WJ. May-Thurner syndrome presenting as spontaneous left iliac vein rupture. J Vasc Surg Venous Lymphat Disord. 2016;4:479-81. 3. Hossne WS, Nahas PS, Vasconcelos E. Spontaneous

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rupture of the iliac vein: acute abdomen. Arq Cir Clin Exp. 1961;24:27-30. 4. Tannous H, Nasrallah F, Marjani M. Spontaneous iliac vein rupture: case report and comprehensive review of the literature. Ann Vasc Surg. 2006;20:258-62. 5. Kim DH, Park HS, Lee T. Spontaneous iliac vein rupture. Vasc Specialist Int. 2015;31:62-5.

Graduates of 2017

2017 GHS Residents and Fellows Family Medicine David Diamant, MD Casey Hurst, MD Elizabeth Morris, MD Amanda Palich, MD James Reed, MD Bettina Rodriguez, MD Brian Schutzbach, MD Primary Care Sports Medicine Mallory Shasteen, MD General Surgery James Davis, MD Michael Harling, MD Harold Howe, MD David Jacobs, MD Megan Straughan, MD Colin Webb, MD Minimally Invasive Surgery Lucas Beffa, MD Francisco Couto, MD Vascular Surgery John Dooley, MD

Internal Medicine Faustine Dinh, DO Clay Evans, MD Ryan Fields, DO Jennifer Fletcher, DO Samuel Franklin, MD Gretchen Junko, DO Sean Kitch, MD Richard Oâ&#x20AC;&#x2122;Neal, MD Meenu Varghese, DO Katharine Whitfield, DO Moon Won, DO Arwa Zakaria, DO

Pediatrics Elizabeth Colvin, DO Kym Do, MD Cristina Lopez, MD Adam Reis, MD Shanika Rutledge, MD Brent Speer, MD Kyle Torni, MD Megan Witrick, MD Julie Yeh, MD

Internal Medicine/Pediatrics Nicole Gammon, MD Rebekah Hovland, MD Jeremy Loberger, MD Sarah Wells, MD Bernadette Wood, MD

Orthopaedic Surgery Aaron Creek, MD Richard Gurich, MD Dustin Price, MD Erick Torres, MD

Obstetrics & Gynecology Lee Brodie, MD Chelsea Fox, MD Misty McDowell, MD Megan Nguyen, MD M. Darcy Slizewski, MD John Van Deman, MD

Developmental-Behavioral Pediatrics Charles Hatcher, MD

Orthopaedic Sports Medicine Walter Choate, MD Steven Hendrix, MD Amit Momaya, MD Jason Rogers, MD Psychiatry Louis Viamonte, MD

USC School of Medicine Greenville Class of 2017 Line Abdul Rahman Elizabeth Barton Megan Bradham Caroline Brooks Inga Brown Jose Chaves Laura Cook Benjamin DeMarco Morgan Diven Taylor Elser Michelle Ertel Lily Fatula William Gasque

Geevan George Ryan Gill Tyler Goff Laura Harbin Rachel Heidt Jessica Himmelstein Anthony Horton Quinn Hunt Ahan Hunter Michael James Reema Kashif Thomas Kellam Christopher Lagnese

Eric Lawson Tristan Lawson Lydia Maleknia Cole Matthews Michelle Matthews Rachel Nelson Victoria Newsome Kimberly Overton Payal Patel Anna Quantrille Lindsey-Thomas Rish Zachary Rogers Kristin Rowland

Tariq Salim Ryan Smith Garrett Snipes Caroline Stoddard Cameron Sutton Benjamin Swartz Joshua Tadlock Amy Trammell Tamara van de Star Dana Westerkam Ashley Williams-Hernandez Lindsay Young

GHS Proc. June 2017; 2 (1)

2016 Publications

2016 Publications of Greenville Health System Medical and Scientific Staff Cancer Institute

Hodi FS, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA. Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol. 2016;17:1558-68. Janelsins MC, Peppone LJ, Heckler CE, Kesler SR, Sprod LK, Giguere J, et al. YOCAS© yoga reduces self-reported memory difficulty in cancer survivors in a nationwide randomized clinical trial: investigating relationships between memory and sleep. Integr Cancer Ther. 2016;15:263-71.

Brown C, Ben-Or S, Walker P, Bowling M. The impact of electromagnetic navigational bronchoscopy on a multidisciplinary thoracic oncology program. J Natl Compr Canc Netw. 2016;14:181-4.

Callihan P, Ghazalpour A, Edenfield WJ. A revertant of the pathogenic germline mutation in BRCA1 as a possible cause of breast cancer chemoresistance. GHS Proc. 2015;1:52-4.

Edenfield WJ, Mattar B, Anthony SP, Mutch P, Chanas B, Smith M. Phase 1, open-label, randomized, bioequivalence study of 2 bendamustine hydrochloride formulations; a readyto-dilute low-volume, rapid infusion solution and a lyophilized powder formulation. Blood. 2015;126:4857.

Edenfield J, Schammel C, Collins J, Schammel D, Edenfield WJ. Metaplastic breast cancer: molecular typing and identification of potential targeted therapies at a single institution. Clin Breast Cancer. 2017;17:e1-10.

Gandhi AK, Vincent R, Carpio C, Stoppa AM, Gharibo MM, Damian S, Rasco DW, Ysebaert L, Cordoba R , Santoro A, Edenfield WJ, Pinto A, Lopez-Martin JA, Sancho JM, Panizo C, Wei X, Hagner P, Waldman M, Hege K, Chopra R, Pourdehnad M. CC-122 expands activated and memory CD4 and CD8 T cells in vivo and induces T cell activation ex vivo in subjects with relapsed or refractory diffuse large B cell lymphoma and multiple myeloma. Blood. 2015;126:2704.

10. Kelly KR, Gabrail NY, Edenfield WJ, Lockhart AC, Olszanski AJ, Reddy G. An open-label, phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/ refractory advanced solid tumors or advanced lymphoma/myeloma patients with mild, moderate, and severe renal impairment. Blood. 2015;126:3966.

Garcia-Manero G, Gore SD, Kambhampati S, Scott B, Tefferi A, Cogle CR, Edenfield WJ, Hetzer J, Kumar K, Laille E, Shi T, MacBeth KJ, Skikne B. Efficacy and safety of extended dosing schedules of CC-486 (oral azacitidine) in patients with lower-risk myelodysplastic syndromes. Leukemia. 2016;30:889-96.

Gluck WL. Prolonged survival of a patient with relapsed, metastatic, SPARC-overexpressed lung adenocarcinoma treated with low-dose nab-paclitaxel. Personalized Med Onc. 2016;5:3.

GHS Proc. June 2017; 2 (1): 71-82

11. Kunitake H, Russell MM, Zheng P, Yothers G, Land SR, Petersen L, Fehrenbacher L, Giguere JK, Wickerham DL, Ko CY, Ganz PA. Quality of life and symptoms in long-term survivors of colorectal cancer: results from NSABP protocol LTS-01. J Cancer Surviv. 2017;11:111-8. 12. Ligibel JA, Alfano CM, Hershman D, Ballard RM, Bruinooge SS, Courneya KS, Daniels EC, Demark-Wahnefried W, Frank ES, Goodwin PJ, Irwin ML, Levit LA, McCaskill-Stevens W, Minasian LM, O’Rourke MA, Pierce JP, Stein KD, Thomson CA, Hudis CA. Recommendations for obesity clinical trials in cancer survivors: American Society of Clinical Oncology Statement. J Clin Oncol. 2015;33:3961-7. 13. Malangone S, Campen CJ. Hypercalcemia of malignancy. J Adv Pract Oncol. 2015;6:586-92. 14. Montgomery B, Eisenberger MA, Rettig MB, Chu F, Pili R, Stephenson JJ, Vogelzang NJ, 71

Koltsky AJ, Nordquist LT, Edenfield WJ, Mamlouk K, Ferrante KJ, Taplin ME. Androgen Receptor Modulation Optimized for Response (ARMOR) phase I and II studies: galeterone for the treatment of castration-resistant prostate cancer. Clin Cancer Res. 2016;22:1356-63. 15. Page BR, Shaw EG, Lu L, Bryant D, Grisell D, Lesser GJ, Monitto DC, Naughton MJ, Rapp SR, Savona SR, Shah S, Case D, Chan MD. Phase II double-blind placebo-controlled randomized study of armodafinil for brain radiationinduced fatigue. Neuro Oncol. 2015;17:1393-401. 16. Ramirez KG, Koch MD, Edenfield WJ. Irinotecan-induced dysarthria: A case report and review of the literature. J Oncol Pharm Pract. 2016;23:226-30. 17. Rappaport MJ, Showell DL, Edenfield WJ. Metastatic ghost cell odontogenic carcinoma: description of a case and search for actionable targets. Rare Tumors. 2015;7:5813. 18. Sharman JP, Farber CM, Mahadevan D, Schreeder MT, Brooks HD, Kolibaba KS, Fanning S, Klein L, Greenwald DR, Sportelli P, Miskin HP, Weiss MS, Burke JM. Ublituximab (TG-1101), a novel, glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/ or refractory chronic lymphocytic leukemia: results of a phase 2 trial. Br J Haematol. 2017;176:412-20. 19. Unger JM, Hershman DL, Arnold KB, Loomba R, Chugh R, Hwang JP, O’Rourke MA, Bhadkamkar NA, Wang LX, Siegel AB, Cooley TP, Berenberg JL, Bridges BB, Ramsey SD. Stepwise development of a cancer care delivery research study to evaluate the prevalence of virus infections in cancer patients. Future Oncol. 2016;12:1219-31. 20. Yu H, Batenchuk C, Badzio A, Boyle TA, Czapiewski P, Chan DC, Lu X, Gao D, Ellison K, Kowalewski AA, Rivard CJ, Dziadziuszko R, Zhou C, Hussein M, Richards D, Wilks S, Monte M, Edenfield W, Goldschmidt J, Page R, Ulrich B, Waterhouse D, Close S, Jassem J, Kulig K, Hirsch FR. PD-L1 expression by two complementary diagnostic assays and mRNA in situ hybridization in small cell lung cancer. J Thorac Oncol. 2017;12:110-20.

Care Coordination Institute 21. Egan BM. Treatment resistant hypertension. Ethn Dis. 2015;25:495-8. 22. Egan BM. Treatment resistant hypertension. A pragmatic management approach. Hypertension J. 2015;1:106-10. 72

23. Egan BM, Laken MA, Sutherland SE, Qanungo S, Fleming DO, Cook AG, Hester WH, Jones KW, Jebaily GC, Valainis GT, Way CF, Wright MB, Davis RA. Aldosterone antagonists or renin-guided therapy for treatment-resistant hypertension: a comparative effectiveness pilot study in primary care. Am J Hypertens. 2016;29:976-83. 24. Egan BM, Sutherland SE, Childers WF, Dahlheimer RM, Helmrich GA, Lapeyrolerie DA, Markle N, Murphy DW, Simmons L, Davis RA, Tilkemeier P, Sinopoli A. Comparative impact of implementing the 2013 or 2014 cholesterol guideline on vascular events in a quality improvement network. Ther Adv Cardiovasc Dis. 2016;10:56-66. 25. Egan BM, White K. Weight loss pharmacotherapy: brief summary of the clinical literature and comments on racial differences. Ethn Dis. 2015;25:511-4. 26. Egan BM, Kai B, Wagner CS, Henderson JH, Chandler AH, Sinopoli A. Blood pressure control provides less cardiovascular protection in adults with than without apparent treatment-resistant hypertension. J Clin Hypertens (Greenwich). 2016;18:817-24. 27. Egan BM, Li J, Fleming DO, White K, Connell K, Davis RA, Sinopoli A. Impact of implementing the 2013 ACC/AHA Cholesterol Guidelines on vascular events in a statewide community-based practice registry. J Clin Hypertens (Greenwich). 2016;18:663-71. 28. Egan BM, Li J, Wagner CS. Systolic Blood Pressure Intervention Trial (SPRINT) and target systolic blood pressure in future hypertension guidelines. Hypertension. 2016;68:318-23. 29. Lopes HF, Corrêa-Giannella ML, Consolim-Colombo FM, Egan BM. Visceral adiposity syndrome. Diabetol Metab Syndr. 2016;8:40. 30. Motta JM, Lemos TM, Consolim-Colombo FM, Moyses RM, Gusmão MA, Egan BM, Lopes HF. Abnormalities of anthropometric, hemodynamic, and autonomic variables in offspring of hypertensive parents. J Clin Hypertens (Greenwich). 2016;18:942-8. 31. Poveromo LB, Michalets EL, Sutherland SE. Midodrine for the weaning of vasopressor infusions. J Clin Pharm Ther. 2016;41:260-5. 32. Puckrein GA, Egan BM, Howard G. Social and medical determinants of cardiometabolic health: the big picture. Ethn Dis. 2015;25:521-4. 33. Sutherland S, Egan B, Davis R, Rutledge V, Sinopoli A. Diving into the pool of ACO quality measures: MSSP year 2 performance metrics. Health Affairs. 2015. GHS Proc. June 2017; 2 (1): 71-82

2016 PUBLICATIONS 34. Sutherland SE, Egan BM, Fleming DO, Helmrich GA, Davis RA, Rutledge V, Sinopoli A. Medicare Shared Saving Program second-year results: predictors of success. GHS Proc. 2016;1:22-7.

Emergency Medicine 35. Blackwell TH, Halsey RM, Reinovsky JH. Emergency medical technician training for medical students: a two-year experience. Prehosp Emerg Care. 2016;20:518-23. 36. Clinkscales JD, Fesmire FM, Hennings JR, Severance HW, Seaberg DC, Patil N. The effect of emergency medicine residents on clinical efficiency and staffing requirements. Acad Emerg Med. 2016;23:78-82. 37. Dix A, Lutz M, Heyne C. Utilizing simulation to improve outcomes from out-of-hospital cardiac arrest. MedSim. 2015;4:16-9. 38. Eisentstat M, Fabiano S, Collins B. Case report: not just another kidney stone. Emerg Med. 2015;47:507-9. 39. Faul M, Aikman SN, Sasser SM. Bystander intervention prior to EMS arrival: comparing assistance across types of medical emergencies. Prehosp Emerg Care. 2016 25:1-7. 40. Faul M, Stevens JA, Sasser SM, Alee L, Deokar AJ, Kuhls DA, Burke PA. Older adult falls seen by emergency medical service providers: a prevention opportunity. Am J Prev Med. 2016;50:719-26. 41. Faul M, Zu L, Sasser SM. Hospitalized traumatic brain injured patients: trauma center utilization and high interfacility transfers among older adults. Prehosp Emerg Care. 2016;20:594-600. 42. Gray JD, Wilson CJ. Streptococcus gallolyticus (bovis): a rare presentation of meningitis in the ED. Am J of Emerg Med. 2016;34:677. 43. Haley KB, Lerner EB, Guse CE, Pirrallo RG: The effect of system-wide interventions of the assessment and treatment of pain by emergency medicine services providers. Prehosp Emerg Care. 2016;18:1-7. 44. Kopec K, Yen M, Bitner M, Evans CS, Gerarado C. Marked hypofibrinogenemia and gastrointestinal bleeding after copperhead (agkistrodon contortrix) envenomation. Wilderness Environ Med. 2015;26:488-90. 45. Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; GHS Proc. June 2017; 2 (1): 71-82

Resuscitation Outcomes Consortium Investigators (Pirrallo RG). Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;375:802-3. 46. Leacock R, Sternberg S, Polley K, Frederick J, Rochester A, et al. A teenager with an acute stroke while at school. J Neurol Stroke. 2015;3:00093. 47. Nichol G, Leroux B, Wang H, Callaway CW, Sopko G, Weisfeldt M, Stiell I, Morrison LJ, Aufderheide TP, Cheskes S, Christenson J, Kudenchuk P, Vaillancourt C, Rea TD, Idris AH, Colella R, Isaacs M, Straight R, Stephens S, Richardson J, Condle J, Schmicker RH, Egan D, May S, Ornato JP for the ROC Investigators (Pirrallo RG). Trial of continuous or interrupted chest compressions during CPR. N Engl J Med. 2015;373:2203-14. 48. Pittman MA, Yarris LM, Lall MD, Smith JL, Wills CP, Ufberg JW, Hegarty CB, Love JN. Do emergency medicine residency graduates feel prepared to manage closed fractures after training? Acad Emerg Med. 2017;24:92-7. 49. Sundararaj K1, Pleasant DL, Moschella PC, Panneerselvam K, Balasubramanian S, Kuppuswamy D. mTOR Complexes repress hypertrophic agonist-stimulated expression of connective tissue growth factor in adult cardiac muscle cells. J Cardiovasc Pharmacol. 2016;67:110-20.

Family Medicine 50. Albano AW Jr, Senter C, Adler RH, Herring SA, Asif IM. The legal landscape of concussion: implications for sports medicine providers. Sports Health. 2016;8:465-8. 51. Annett S, Sease F. Posterior Shoulder Pain in a High School Football Lineman: 3436 June 3 4:35 PM-4:55 PM. Med Sci Sports Exerc. 2016;48:970. 52. Asif IM, Drezner JA. Cardiovascular screening in young athletes: evidence for the electrocardiogram. Curr Sports Med Rep. 2016;15:76-80. 53. Asif IM, Price DE, Ewing A, Rao AL, Harmon KG, Drezner JA. The impact of diagnosis: measuring the psychological response to being diagnosed with serious or potentially lethal cardiac disease in young competitive athletes. Br J Sports Med. 2016;50:163-6. 54. Drezner JA, Harmon KG, Asif IM, Marek JC. Why cardiovascular screening in young athletes can save lives: a critical review. Br J Sports Med. 2016;50:1376-8. 55. Drezner JA, Oâ&#x20AC;&#x2122;Connor FG, Harmon KG, Fields KB, Asplund CA, Asif IM, Price DE, Dimeff RJ, 73

Bernhardt DT, Roberts WO. AMSSM position statement on cardiovascular preparticipation screening in athletes: current evidence, knowledge gaps, recommendations, and future directions. Curr Sports Med Rep. 2016;15:359-75. 56. Drezner JA, O’Connor FG, Harmon KG, Fields KB, Asplund CA, Asif IM, Price DE, Dimeff RJ, Bernhardt DT, Roberts WO. AMSSM position statement on cardiovascular preparticipation screening in athletes: current evidence, knowledge gaps, recommendations, and future directions. Clin J Sport Med. 2016;26:347-61. 57. Drezner JA, Owens DS, Prutkin JM, Salerno JC, Harmon KG, Prosise S, Clark A, Asif IM. Electrocardiographic screening in National Collegiate Athletic Association athletes. Am J Cardiol. 2016;118:754-9. 58. Emerson JF, Welch M, Rossman WE, Carek S, Ludden T, Templin M, Moore CG, Tapp H, Dulin M, McWilliams A. A multidisciplinary intervention utilizing virtual communication tools to reduce health disparities: a pilot randomized controlled trial. Int J Environ Res Public Health. 2015;13. 59. Gardner JK, Klipple G, Stewart C, Asif I, Zhang S. Acute effects of lateral shoe wedges on joint biomechanics of patients with medial compartment knee osteoarthritis during stationary cycling. J Biomech. 2016;49:2817-23. 60. Harmon KG, Asif IM, Maleszewski JJ, Owens DS, Prutkin JM, Salerno JC, Zigman ML, Ellenbogen R, Rao A, Ackerman MJ, Drezner JA. Response to letter regarding article, “Incidence, cause, and comparative frequency of sudden cardiac death in National Collegiate Athletic Association athletes: a decade in review.” Circulation. 2016;133:e447. 61. Hull S, Weidner A, Michener JL; ADFM Healthcare Delivery Transformation Committee, Tallia A, Alexander C, Bryan S, Gilchrist V, Giobbie L, Hull S, Jeremiah M, Michener JL, Pallay R, Rabovsky M, Speer L, Tavallali L, Davis A, Weidner A. Partnering for transformation: a menu of many points of entry for your department. Ann Fam Med. 2015;13:593-5.

64. Toresdahl BG, Asif IM. Update on Zika virus: considerations for the traveling athlete. Sports Health. 2016;8:438-43.

Internal Medicine 65. Avasarala J. Letter by Avasarala regarding article, “2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients with Acute Ischemic Stroke Regarding Endovascular Treatment: a Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association.” Stroke. 2015;46:e234. 66. Avasarala J. Diagnosing lymphomatosis cerebri. JAMA Neurol. 2015;72:1536. 67. Avasarala J. Computer-aided therapeutics in treating autoimmune encephalitis. JAMA Neurol. 2016;73:127-8. 68. Avasarala JR. Applying the principles of McDonaldization to medicine. JAMA Neurol. 2016;73:478-9. 69. Avasarala J. The TOUCH program and natalizumab: Fundamental flaw in patient protection. Version 3. F1000Res. 2015;4:1450. 70. Avasarala J. Is a neurologist needed to diagnose acute stroke in the Emergency Department?: too many cooks might spoil the broth. JAMA Neurol. 2016;73:1273-4. 71. Avasarala J, Sotirchos ES, Bhargava P, Calabresi PA. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology. 2016;87:445-6. 72. Avasarala J, Biousse V, Newman NJ. Overdiagnosis of idiopathic intracranial hypertension. Neurology. 2016;86:2216. 73. Beale C, Tilkemeier P. Understanding the past to appropriately guide us in the future. J Nucl Cardiol. 2016;23:693-4. 74. Clayton SB, Patel R, Richter JE. Clinical features, manometry, timed barium esophagram, and treatment outcomes of patients with functional and anatomic esophago-gastric junction outflow obstruction. Clin Gastroenterol Hepatol. 2016;14:907-11.

62. Rao AL, Asif IM, Drezner JA, Toresdahl BG, Harmon KG. Suicide in National Collegiate Athletic Association (NCAA) athletes: a 9-year analysis of the NCAA Resolutions Database. Sports Health. 2015;7:452-7.

75. Dendy JM, Tilkemeier P. Successful innovation: a time for change? J Nucl Cardiol. 2017;24:134-7.

63. Rao AL, Poon S, Drezner JA, Zigman M, Asif IM, Harmon KG. Death by homicide in National Collegiate Athletic Association athletes between 2003 and 2013. Br J Sports Med. 2016;50:172-5.

77. Grim SA, Layden JE, Roth P, Gallitano S, Adams W, Clark NM. Latent tuberculosis in kidney and liver transplant patients: a review of treatment practices and outcomes. Transpl Infect Dis. 2015;17:768-77.

76. Geschwind MD, Paras N. Deutetrabenazine for treatment of chorea in Huntington disease. JAMA. 2016;316:33-5.

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2016 PUBLICATIONS 78. Heldman DA, Pulliam CL, Urrea Mendoza E, Gartner M, Giuffrida JP, Montgomery EB Jr, Espay AJ, Revilla FJ. Computer-guided deep brain stimulation programming for Parkinson’s disease. Neuromodulation. 2016;19:127-32.

85. Roth PJ, Grim SA, Gallitano S, Adams W, Clark NM, Layden JE. Serial testing for latent tuberculosis infection in transplant candidates: a retrospective review. Transpl Infect Dis. 2016;18:14-21.

79. Henry Gomez T, Holkova B, Noreika D, Del Fabbro E. Warfarin improves neuropathy in monoclonal gammopathy of undetermined significance. BMJ Case Rep. 2016;2016.

86. Windle JR, Katz AS, Dow JP Jr, Fry ET, Keller AM, Lamp T, Lippitt A Jr, Paruche MP, Resnic FS, Serwer GA, Slotwiner DJ, Tcheng JE, Tilkemeier PL, Weiner BH, Weintraub WS. 2016 ACC/ASE/ASNC/HRS/SCAI Health Policy Statement on Integrating the Healthcare Enterprise. J Am Coll Cardiol. 2016;68:1348-64.

80. Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D, O’Neill C, Vaughan C, Goldstein J, Herzog M, Snively V, Whaley J, Wong C, Suter G, Jankovic J, Jimenez-Shahed J, Hunter C, Claassen DO, Roman OC, Sung V, Smith J, Janicki S, Clouse R, Saint-Hilaire M, Hohler A, Turpin D, James RC, Rodriguez R, Rizer K, Anderson KE, Heller H, Carlson A, Criswell S, Racette BA, Revilla FJ, Nucifora F Jr, Margolis RL, Ong M, Mendis T, Mendis N, Singer C, Quesada M, Paulsen JS, Brashers-Krug T, Miller A, Kerr J, Dubinsky RM, Gray C, Factor SA, Sperin E, Molho E, Eglow M, Evans S, Kumar R, Reeves C, Samii A, Chouinard S, Beland M, Scott BL, Hickey PT, Esmail S, Fung WL, Gibbons C, Qi L, Colcher A, Hackmyer C, McGarry A, Klos K, Gudesblatt M, Fafard L, Graffitti L, Schneider DP, Dhall R, Wojcieszek JM, LaFaver K, Duker A, Neefus E, Wilson-Perez H, Shprecher D, Wall P, Blindauer KA, Wheeler L, Boyd JT, Houston E, Farbman ES, Agarwal P, Eberly SW, Watts A, Tariot PN, Feigin A, Evans S, Beck C, Orme C, Edicola J, Christopher E. Effect of deutetrabenazine on chorea among patients with Huntington disease: a randomized clinical trial. JAMA. 2016;316:40-50. 81. Jamal H, Abrams G. A corny cause of cerebrospinal fluid ascites: A case report and review of literature. SAGE Open Med Case Rep. 2016;4. 82. Jindal M, Hudson MF, Blackhurst DW, Coltman K, McCoy GD. The impact of electronic cues and provider education on colorectal cancer screening referral and patients’ screening decision stage. J South Car Med Assoc. 2016;112:140-77. 83. Kelly JW, Blackhurst D, McAtee W, Steed C. Electronic hand hygiene monitoring as a tool for reducing health care-associated methicillin-resistant Staphylococcus aureus infection. Am J Infect Control. 2016;44:956-7. 84. Qureshi K, Abrams GA. Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome. Clin Obes. 2016;6:117-23.

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OB/GYN 87. Ahn JI, Yoo JY, Kim TH, Kim YI, Ferguson SD, Fazleabas AT, Young SL, Lessey BA, Ahn JY, Lim JM, Jeong JW. cAMP-Response Element-Binding 3-Like Protein 1(CREB3L1) is required for decidualization and its expression is decreased in women with endometriosis. Curr Mol Med. 2016;16:276-87. 88. Fox C, Eichelberger K. Maternal microbiome and pregnancy outcomes. Fertil Steril. 2015;104:1358-63. 89. Fox C, Morin S, Jeong JW, Scott RT Jr, Lessey BA. Local and systemic factors and implantation: what is the evidence? Fertil Steril. 2016;105:873-4. 90. Gareau S, Lòpez-De Fede A, Loudermilk BL, Cummings TH, Hardin JW, Picklesimer AH, Crouch E, Covington-Kolb S. Group prenatal care results in Medicaid savings with better outcomes: a propensity score analysis of CenteringPregnancy participation in South Carolina. Matern Child Health J. 2016;20:1384-93. 91. Gray SL, Lackey BR, Boone WR. Effects of Panax ginseng, zearalenol, and estradiol on sperm function. J Ginseng Res. 2016;40:251-9. 92. Heberlein EC, Frongillo EA, Picklesimer AH, Covington-Kolb S. Effects of group prenatal care on food insecurity during late pregnancy and early postpartum. Matern Child Health J. 2016;20:1014-24. 93. Hess LM, Huang HQ, Hanlon AL, Robinson WR, Johnson R, Chambers SK, Mannel RS, Puls L, Davidson SA, Method M, Lele S, Havrilesky L, Nelson T, Alberts DS. Cognitive function during and six months following chemotherapy for front-line treatment of ovarian, primary peritoneal or fallopian tube cancer: an NRG oncology/gynecologic oncology group study. Gynecol Oncol. 2015;139:541-5. 94. Illston JD, Garris JB, Richter HE, Wheeler TL 2nd. Pain scores and exposure rates after poly-

propylene mesh for pelvic organ prolapse. South Med J. 2015;108:715-21. 95. Malter HE. Micromanipulation in assisted reproductive technology. Reprod Biomed Online. 2016;32:339-47. 96. Monsanto SP, Edwards AK, Zhou J, Nagarkatti P, Nagarkatti M, Young SL, Lessey BA, Tayade C. Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients. Fertil Steril. 2016;105:968-77. 97. Olivera C, Meriwether K, El-Nashar S, Grimes CL, Chen CC, Orejuela F, Antosh D, Gleason J, Kim-Fine S, Wheeler T, McFadden B, Balk EM, Murphy M. Nonantimuscarinic treatment for overactive bladder: a systematic review. Am J Obstet Gynecol. 2016;215:34-57. 98. Pradhan A, Page-Ramsey S, Buery-Joyner SD, Craig LB, Dalrymple JL, Forstein DA, Graziano S, Hampton BS, Hopkins L, McKenzie M, Wolf A, Abbott JF. Undergraduate obstetrics and gynecology medical education: why are we underrated and underappreciated? Am J Obstet Gynecol. 2016;214:345-7. 99. Rothenberg SE, Keiser S, Ajami NJ, Wong MC, Gesell J, Petrosino JF, Johns A. The role of gut microbiota in fetal methylmercury exposure: insights from a pilot study. Toxicol Lett. 2016;242:60-7. 100. Schellinger MM, Abernathy MP, Amerman B, May C, Foxlow LA, Carter AL, Barbour K, Luebbehusen E, Ayo K, Bastawros D, Rose RS, Haas DM. Improved outcomes for Hispanic women with gestational diabetes using the CenteringPregnancy© group prenatal care model. Matern Child Health J. 2017;21:297-305. 101. Strug MR, Su R, Young JE, Dodds WG, Shavell VI, Díaz-Gimeno P, Ruíz-Alonso M, Simón C, Lessey BA, Leach RE, Fazleabas AT. Intrauterine human chorionic gonadotropin infusion in oocyte donors promotes endometrial synchrony and induction of early decidual markers for stromal survival: a randomized clinical trial. Hum Reprod. 2016;31:1552-61. 102. Tollånes MC, Strandberg-Larsen K, Eichelberger KY, Moster D, Lie RT, Brantsæter AL, Meltzer HM, Stoltenberg C, Wilcox AJ. Intake of caffeinated soft drinks before and during pregnancy, but not total caffeine intake, is associated with increased cerebral palsy risk in the Norwegian mother and child cohort study. J Nutr. 2016;146:1701-6. 103. Yoo JY, Jeong JW, Fazleabas AT, Tayade C, Young SL, Lessey BA. Protein inhibitor of activated STAT3 (PIAS3) is down-regulated in

eutopic endometrium of women with endometriosis. Biol Reprod. 2016;95:11.

Orthopaedics 104. Adams JD Jr, Della Rocca GJ. Management of posterior articular depression in tibial plateau fractures. J Knee Surg. 2016;29:28-33. 105. Bhandari M, Petrisor BA, Jeray KJ. Wound irrigation in initial management of open fractures. N Engl J Med. 2016;374:1789-90. 106. Bottoni CR, Smith EL, Shaha J, Shaha SS, Raybin SG, Tokish JM, Rowles DJ. Autograft versus allograft anterior cruciate ligament reconstruction: a prospective, randomized clinical study with a minimum 10-year follow-up. Am J Sports Med. 2015;43:2501-9. 107. Bray CC, Watson ST. Current review of juvenile osteochondritis dissecans of the knee. Curr Orthop Pract. 2015;26:466-74. 108. Cameron JI, Pulido PA, McCauley JC, Bugbee WD. Osteochondral allograft transplantation of the femoral trochlea. Am J Sports Med. 2016;44:633-8. 109. FLOW Investigators. A trial of wound irrigation in the initial management of open fracture wounds. N Engl J Med. 2015;373:2629-41. 110. Gurich RW Jr, Pappas ND. Lipoma of the tendon sheath in the fourth extensor compartment of the hand. Am J Orthop. 2015;44:561-2. 111. Hawkins RJ. Recommendations for evaluating and selecting appropriately valued outcome measures. Instr Course Lect. 2016;65:587-92. 112. Janssen SJ, Teunis T, Guitton TG, Ring D; Science of Variation Group. Do surgeons treat their patients like they would treat themselves? Clin Orthop Relat Res. 2015;473:3564-72. 113. Jeray KJ, Swiontkowski M. Osteoporosis and fragility fractures: what progress have we made? J Bone Joint Surg Am. 2015;97:1553-4. 114. Jiwanlal A, Jeray KJ. Outcome of posterior tibial plateau fixation. J Knee Surg. 2016;29:34-9. 115. Mellema JJ, Doornberg JN, Molenaars RJ, Ring D, Kloen P; Traumaplatform Study Collaborative & Science of Variation Group (Collaborator: Jeray KJ). Interobserver reliability of the Schatzker and Luo classification systems for tibial plateau fractures. Injury. 2016;47:944-9. 116. Mellema JJ, Doornberg JN, Molenaars RJ, Ring D, Kloen P; Traumaplatform Study Collaborative & Science of Variation Group (Collaborator: Jeray KJ). Tibial plateau fracture characteristics: reliability and diagnostic accuracy. J Orthop Trauma. 2016;30:e144-51. 117. Noonan TJ, Thigpen CA, Bailey LB, Wyland

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2016 PUBLICATIONS DJ, Kissenberth M, Hawkins RJ, Shanley E. Humeral torsion as a risk factor for shoulder and elbow injury in professional baseball pitchers. Am J Sports Med. 201644:2214-9. 118. Ratner D, Millon SJ, Porter SE. Outcomes of treatment with radiation therapy for residual soft tissue sarcoma of the hand following unplanned initial resection. GHS Proc. 2016;1:60-3.

alomedullary fixation. J Bone Joint Surg Am. 2016;98:1097-102. 129. Wyland DJ. Letter to the editor: subchondral calcium phosphate is ineffective for bone marrow edema lesions in adults with advanced osteoarthritis. Clin Orthop Relat Res. 2015;473:3976-7.

119. Shaha JS, El-Othmani MM, Saleh JK, Bozic KJ, Wright J, Tokish JM, Shaha SH, Saleh KJ. The growing gap in electronic medical record satisfaction between clinicians and information technology professionals: issues of most concern and suggested remediations. J Bone Joint Surg Am. 2015;97:1979-84.

Paediatrics

120. Shanley E, Bailey L, Sandago MP, Pinkerton A, Singleton SB, Thigpen CA. The use of a pitch count estimator to calculate exposure in collegiate baseball pitchers. Phys Ther Sport. 2015;16:344-8.

131. Casanova EL, Sharp JL, Chakraborty H, Sumi NS, Casanova MF. Genes with high penetrance for syndromic and non-syndromic autism typically function within the nucleus and regulate gene expression. Mol Autism. 2016;7:18.

121. Thigpen CA, Noonan TJ, Shanley E, Bailey LB, Wyland DJ, Kissenberth M, Hawkins RJ. Humeral retrotorsion in pitchers with GIRD: response. Am J Sports Med. 2015;43:NP19.

132. Greenberg RG, Cochran KM, Smith PB, Edson BS, Schulman J, Lee HC, Govindaswami B, Pantoja A, Hardy D, Curran J, Lin D, Kuo S, Noguchi A, Ittmann P, Duncan S, Gupta M, Picarillo A, Karna P, Cohen M, Giuliano M, Carroll S, Page B, Guzman-Cottrill J, Walker MW, Garland J, Ancona JK, Ellsbury DL, Laughon MM, McCaffrey MJ. Effect of catheter dwell time on risk of central line-associated bloodstream infection in infants. Pediatrics. 2015;136:1080-6.

122. Thigpen CA, Shaffer MA, Gaunt BW, Leggin BG, Williams GR, Wilcox RB 3rd. The American Society of Shoulder and Elbow Therapistsâ&#x20AC;&#x2122; consensus statement on rehabilitation following arthroscopic rotator cuff repair. J Shoulder Elbow Surg. 2016;25:521-35. 123. Tokish JM, Alexander TC Jr. Implementation of a comprehensive orthopaedic registry system. Instr Course Lect. 2016;65:593-9. 124. Tokish JM, Beicker C. Superior capsule reconstruction technique using an acellular dermal allograft. Arthrosc Tech. 2015;4:e833-9. 125. Torres EG, Lindmair-Snell JM, Langan JW, Burnikel BG. Is preoperative nasal povidone-iodine as efficient and cost-effective as standard methicillin-resistant taphylococcus aureus screening protocol in total joint arthroplasty? J Arthroplasty. 2016;31:215-8. 126. Waterman BR, Chandler PJ, Teague E, Provencher MT, Tokish JM, Pallis MP. Shortterm outcomes of glenoid bone block augmentation for complex anterior shoulder instability in a high-risk population. Arthroscopy. 2016;32:1784-90. 127. Waterman BR, Hoffmann JD, Laughlin MD, Burks R, Pallis MP, Tokish JM, Belmont PJ Jr. Success of high tibial osteotomy in the United States military. Orthop J Sports Med. 201512:3. 128. Watson ST, Schaller TM, Tanner SL, Adams JD, Jeray KJ. Outcomes of low-energy basicervical proximal femoral fractures treated with ceph-

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130. Brooks J, Kellett J, Seeanner J, Jenkins C, Buchanan C, Kinsman A, Kelly DP, Pierce S. Training the motor aspects of pre-driving skills of young adults with and without autism spectrum disorder. J Autism Dev Disord. 2016;46:2408-26.

133. Hunnicutt AH, Morales A, Blouin RB, Foster ET, Cass, AL, Patel M. Levetiracetam as initial monotherapy in pediatric epileptic patients. GHS Proc. 2016;1:28-31. 134. Hutsler JJ, Casanova MF. Review: cortical construction in autism spectrum disorder: columns, connectivity and the subplate. Neuropathol Appl Neurobiol. 2016;42:115-34. 135. Kelly D. The challenge of assessing response to psychotropic medication trials in very young children with fragile X syndrome: a cautionary note. J Dev Behav Pediatr. 2016;37:657-8. 136. Lucas J. Sudden cardiac death in school aged athletes. J SC Med Assoc. 2016;112:185-90. 137. Muir AB, Wang ML, Metz D, Falk G, Markowitz J, Spergel JM, Liacouras CA. Proton pump inhibitor-responsive oesophageal eosinophilia: too early to change clinical practice. Gut. 2016;0:1. 138. Muschick KD, LaCroix R, McAdams J. Fingernail carriage of methicillin-resistant staphylococcus aureus and possible correlation with soft tissue infections in children. South Med J. 2016;109:236-9.

139. Oberman LM, Enticott PG, Casanova MF, Rotenberg A, Pascual-Leone A, McCracken JT; TMS in ASD Consensus Group. Transcranial magnetic stimulation in autism spectrum disorder: Challenges, promise, and roadmap for future research. Autism Res. 2016;9:184-203. 140. Onoriobe U, Miloro M, Sukotjo C, Mercuri LG, Lotesto A, Eke R. How many temporomandibular joint total joint alloplastic implants will be placed in the United States in 2030? J Oral Maxillofac Surg. 2016;74:1531-8. 141. Pierce SB, Gulsuner S, Stapleton GA, Walsh T, Lee MK, Mandell JB, Morales A, Klevit RE, King MC, Rogers RC. Infantile onset spinocerebellar ataxia caused by compound heterozygosity for Twinkle mutations and modeling of Twinkle mutations causing recessive disease. Cold Spring Harb Mol Case Stud. 2016;2:a001107. 142. Saul RA, Meredith SH. Beyond the genetic diagnosis: providing parents what they want to know. Pediatr Rev. 2016;37:269-78. 143. Sokhadze EM, Casanova MF, Tasman A, Brockett S. Electrophysiological and behavioral outcomes of Berard auditory integration training (AIT) in children with autism spectrum disorder. Appl Psychophysiol Biofeedback. 2016;41:405-20. 144. Sokhadze EM, Tasman A, Sokhadze GE, El-Baz AS, Casanova MF. Behavioral, cognitive, and motor preparation deficits in a visual cued spatial attention task in autism spectrum disorder. Appl Psychophysiol Biofeedback. 2016;41:81-92. 145. Estate M. Sokhadze, Manuel F. Casanova, Ayman S. El-Baz, Heba Elsayed Farag, Xiaoli Li, Yao Wang. TMS-based neuromodulation of evoked and induced gamma oscillations and event-related potentials in children with autism. Neuroregulation. 2016;3:101-26. 146. Wang Y, Hensley MK, Tasman A, Sears L, Casanova MF, Sokhadze EM. Heart rate variability and skin conductance during repetitive TMS course in children with autism. Appl Psychophysiol Biofeedback. 2016;41:47-60. 147. Wang Y, Sokhadze EM, El-Baz AS, Li X, Sears L, Casanova MF, Tasman A. Relative power of specific EEG bands and their ratios during neurofeedback training in children with autism spectrum disorder. Front Hum Neurosci. 2016;9:723. 148. Wegiel J, Flory M, Schanen NC, Cook EH, Nowicki K, Kuchna I, Imaki H, Ma SY, Wegiel J, London E, Casanova MF, Wisniewski T, Brown WT. Significant neuronal soma volume deficit in the limbic system in subjects with 15q112-q13 duplications. Acta Neuropathol Commun. 2015;3:63. 78

149. Yee ME, Shah A, Anderson AR, Boudreaux J, Bray RA, Gebel HM, Josephson CD. Class I and II HLA antibodies in pediatric patients with thalassemia major. Transfusion. 2016;56:878-84. 150. Zeidán-Chuliá F, de Oliveira BH, Casanova MF, Casanova EL, Noda M, Salmina AB, Verkhratsky A. Up-regulation of oligodendrocyte lineage markers in the cerebellum of autistic patients: evidence from network analysis of gene expression. Mol Neurobiol. 2016;53:4019-25.

Pathology 151. Stowman AM, Hsia LL, Kanner WA, Mahadevan MS, Bullock GC, Patterson JW. Multiple cutaneous lymphoproliferative disorders showing a retained tumor clone by T-cell receptor gene rearrangement analysis: a case series of four patients and review of the literature. Int J Dermatol. 2016;55:e62-71. 152. Stowman AM, Griffin MM, Kanner WA, Tchernev G, Chokoeva AA, Wollina U, Lotti T, Fioranelli M, Roccia MG, Maximov GK, Patterson JW. Coexistent trichilemmoma and trichoblastoma without associated nevus sebaceus. J Biol Regul Homeost Agents. 2016;30:17-20.

Psychiatry 153. Goodbar NH, Foushee JA, Nash K, Connolly LA, Webster LM. Hypothermia associated with thioridazine use in an intellectually disabled patient. J Pharm Pract. 2016;29:250-2. 154. Holder SM, Rogers K, Peterson E, Shoenleben R, Blackhurst D. The impact of mental health services in a pediatric emergency department: the implications of having trained psychiatric professionals. Pediatr Emerg Care. 2016. [Epub ahead of print]. 155. Holder SM, Shoenleben R, Ellison-Daigneault R, Smith L, Jones A, Rogers K. Promoting well-being and resilience in employing a relationship centered approach: a case study of a pre-adolescent boy. Adolescent Psychiatry. 2015;5:31-9. 156. Rogers KM, Peterson E. Juvenile justice in the United States: minority youth. Adolescent Psychiatry. 2015;4:261-9.

Radiology 157. Parti N. Things to consider when looking for your first job: advice from a young radiologist. J Am Coll Radiol. 2015;12:1335-6.

Surgery 158. Almasri J, Alsawas M, Mainou M, Mustafa RA, Wang Z, Woo K, Cull DL, Murad MH. GHS Proc. June 2017; 2 (1): 71-82

2016 PUBLICATIONS Outcomes of vascular access for hemodialysis: a systematic review and meta-analysis. J Vasc Surg. 2016;64:236-43. 159. Blas JV, Carsten CG 3rd, Gray BH. Heparininduced thrombocytopenia associated with a heparin-bonded stent graft. Ann Vasc Surg. 2016;33:227.e1-4. 160. Bour ES. Comment on: Technique or technology? Evaluating leaks after gastric bypass. Surg Obes Relat Dis. 2016 May;12:931-2. 161. Brown C, Ben-Or S, Walker P, Bowling M. The impact of electromagnetic navigational bronchoscopy on a multidisciplinary thoracic oncology program. J Natl Compr Canc Netw. 2016;14:181-4. 162. Brzezienski MA, Jarrell JA 4th. Autologous fat grafting to the breast using REVOLVE system to reduce clinical costs. Ann Plast Surg. 2016;77:286-9. 163. Chawla V, Simionescu A, Langan EM III, LaBerge M. Influence of clinically relevant mechanical forces on vascular smooth muscle cells under chronic high glucose: An in vitro dynamic disease model. Ann Vasc Surg. 2016;34:212-26. 164. Davis LA, Stewart SE, Carsten CG 3rd, Snyder BA, Sutton MA, Lessner SM. Characterization of fracture behavior of human atherosclerotic fibrous caps using a miniature single edge notched tensile test. Acta Biomater. 2016;43:101-11. 165. Davis JR, Villarreal JE, Cobb WS, Carbonell AM, Warren JA. Interparietal hernia complicating retromuscular ventral hernia repair. Am Surg. 2016;82:658-9. 166. English W, Williams B, Scott J, Morton J. Covering bariatric surgery has minimal effect on insurance premium costs within the Affordable Care Act. Surg Obes Relat Dis. 2016;12:1045-50. 167. Erwin PA, Blas JV, Gandhi S, Romero ME, Gray BH. Visceral fibromuscular dysplasia in a patient with chronic abdominal pain. Vasc Med. 2016;21:170-1. 168. Gandhi SS, Blas JV, Lee S, Eidt JF, Carsten CG III. Nonoperative management of grade III blunt thoracic aortic injuries. J Vasc Surg. 2016;64:1580-6. 169. Gray BH, Buchan JA. The treatment of superficial femoral artery in-stent restenosis: the jury is still out. JACC Cardiovasc Interv. 2016;9:1393-6. 170. Green R, Gu X, Kline-Rogers E, Froehlich J, Mace P, Gray B, Katzen B, Olin J, Gornik HL, Cahill AM, Meyers KE. Differences between the pediatric and adult presentation of fibromuscular dysplasia: results from the US RegisGHS Proc. June 2017; 2 (1): 71-82

try. Pediatr Nephrol. 2016;31:641-50. 171. Habenicht KI, Wright CJ, Hunter CT, Adraktas DD, Hathuc VM, Kaiser ML, Hildreth AN, Miller PR. Do radiographic findings of gangrenous cholecystitis in the preoperative setting influence patient outcome? Am Surg. 2016;82:28-30. 172. Hale AL, Twomey K, Ewing JA, Langan EM 3rd, Cull DL, Gray BH. Impact of sarcopenia on long-term mortality following endovascular aneurysm repair. Vasc Med. 2016;21:217-22. 173. Hale AL, Bolton WD. Launching a new kind of medical schoolâ&#x2C6;&#x2019;the University of South Carolina School of Medicine Greenville. GHS Proc. 2016;1:9-12. 174. Hammad TA, Yousefzai R, Venkatachalam S, Lowry A, Gornik HL, Jaber W, Bartholomew JR, Kim SH, Cerqueira M, Gray BH, Blackstone EH, Shishehbor MH. The association between ischemic and jeopardized myocardia and all-cause mortality in patients with peripheral artery disease. Vasc Med. 2016;21:113-9. 175. Hudson MF, McLeod JJ, Dunphy KM, Bristow WM Jr, Genal GS, Jones YR, Johnson BL, Wagner PJ, Cull DL, Taylor SM. Contemporary indications for vascular surgery fail to achieve desired patient-centered outcomes when applied to critical limb ischemia. GHS Proc. 2016;1:13-21. 176. Kadian-Dodov D, Gornik HL, Gu X, Froehlich J, Bacharach JM, Chi YW, Gray BH, Jaff MR, Kim ES, Mace P, Sharma A, Kline-Rogers E, White C, Olin JW. Dissection and aneurysm in patients with fibromuscular dysplasia: findings from the U.S. Registry for FMD. J Am Coll Cardiol. 2016;68:176-85. 177. Koleilat I, Jaeggli M, Ewing JA, Androes M, Simionescu DT, Eidt J. Interobserver variability in physician-modified endograft planning by comparison with a three-dimensional printed aortic model. J Vasc Surg. 2016;64:1789-96. 178. Kwolek CJ, Jaff MR, Leal JI, Hopkins LN, Shah RM, Hanover TM, Macdonald S, Cambria RP. Results of the ROADSTER multicenter trial of transcarotid stenting with dynamic flow reversal. J Vasc Surg. 2015;62:1227-34. 179. Le VH, Brant KN, Blackhurst DW, Schammel CM, Schammel DP, Cornett WR, McKinley BP. The impact of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial: an institutional review. Breast. 2016;29:117-9. 180. Mentzer CJ, Yon JR, King R, Warren JA. Complex perirectal abscess extending to the preperitoneum and space of retzius. GHS Proc. 2016;1:49-51. 79

181. Nosoudi N, Nahar-Gohad P, Sinha A, Chowdhury A, Gerard P, Carsten CG, Gray BH, Vyavahare NR. Prevention of abdominal aortic aneurysm progression by targeted inhibition of matrix metalloproteinase activity with batimastat-loaded nanoparticles. Circ Res. 2015;117:e80-9. 182. O’Connor S, Gornik HL, Froehlich JB, Gu X, Gray BH, Mace PD, Sharma A, Olin JW, Kim ES. Smoking and adverse outcomes in fibromuscular dysplasia: U.S. Registry report. J Am Coll Cardiol. 2016;67:1750-1. 183. Patel PP, Warren JA, Mansour R, Cobb WS 4th, Carbonell AM. A large single-center Experience of open lateral abdominal wall hernia repairs. Am Surg. 2016;82:608-12. 184. Patel PP, Love MW, Ewing JA, Warren JA, Cobb WS, Carbonell AM. Risks of subsequent abdominal operations after laparoscopic ventral hernia repair. Surg Endosc. 2017;31:823-8. 185. Powell BC, Webb CB, Ewing JA, Smith DE. Gluteal fascial advancement for pilonidal cyst disease: a 10-year review. Am Surg. 2016;82:622-5. 186. Raines A, Ward SC, Springhart WP. Diagnostic management of urinary retention: why multiple sclerosis should be included as a differential diagnosis. GHS Proc. 2016;1:64-7. 187. Richey JS, Manning BM, Jones WB. Outcomes of endoscopic stenting for traumatic biliary and pancreatic fistulae. Am Surg. 2016;82:588-93. 188. Rochester SN, Farrar R, Sanders RJ, Straughan MK, Kaiser ML. Fatal clostridium difficile enteritis as a delayed complication of loop ileostomy for fulminant C difficile colitis. GHS Proc. 2016;1:56-9. 189. Rosen MJ, Bauer JJ, Harmaty M, Carbonell AM, Cobb WS, Matthews B, Goldblatt MI, Selzer DJ, Poulose BK, Hansson BM, Rosman C, Chao JJ, Jacobsen GR. Multicenter, prospective, longitudinal study of the recurrence, surgical site infection, and quality of life after contaminated ventral hernia repair using biosynthetic absorbable mesh. Ann Surg. 2017;265:205-11. 190. Scott JD. Comment on: Decreased serum betatrophin levels correlate with improved fasting plasma glucose and insulin secretion capacity after Roux-en-Y gastric bypass in obese Chinese patients with type 2 diabetes: a 1-year follow up. Surg Obes Relat Dis. 2016;12:1349-50. 191. Singapogu R, Jagannathan A, Nagarajan N, Moody C, Zhang G, Cull D. A capacitance-based sensor for hemodialysis cannulation training: a proof-of-concept study. Stud Health Technol Inform. 2016;220:379-82. 192. Taylor SM. Transformation: a new kind of 80

academic health center and the pursuit of high self-mastery. J Am Coll Surg. 2016;222:337-46. 193. Vorst AL, Kaoutzanis C, Carbonell AM, Franz MG. Evolution and advances in laparoscopic ventral and incisional hernia repair. World J Gastrointest Surg. 2015;7:293-305. 194. Warren JA, Cobb WS IV, Carbonell AM. Modern management of abdominal wall hernias. GHS Proc. 2016;1:38-46. 195. Warren JA, Cobb WS, Ewing JA, Carbonell AM. Standard laparoscopic versus robotic retromuscular ventral hernia repair. Surg Endosc. 2017;31:324-32. 196. Wells JT, Lewis CR, Danner OK, Wilson KL, Matthews LR. Klebsiella pneumoniae liver abscess and metastatic endophthalmitis. J Investig Med High Impact Case Rep. 2016;4.

Academy for Leadership & Professional Development 197. Walker EJ, Prince YB, Wingold ME, Gimbel RW. Training tomorrow’s cardiovascular sonographers. J Am Soc Echocardiogr. 2016;29:A24-5.

Institute for Advancement of Health Care 198. Allen RW, Pruitt M, Taaffe KM. Effect of resident involvement on operative time and operating room staffing costs. J Surg Educ. 2016;73:979-85.

Nursing 199. Durham PE, Weissenbach ME, Steed C. Electronic-assisted surveillance following a construction-related event to improve patient safety. Am J Infect Control. 2016;44:S77-8. 200. Hobbs MA, Robinson S, Neyens DM, Steed C. Visitor characteristics and alcohol-based hand sanitizer dispenser locations at the hospital entrance: effect on visitor use rates. Am J Infect Control. 2016;44:258-62. 201. Moureau N, Chopra V. Indications for peripheral, midline and central catheters: summary of the MAGIC recommendations. Br J Nurs. 2016;25:S15-24. 202. Tedder M, Shi L, Si M, Franco R, Chen L. eMindfulness therapy—a study on efficacy of blood pressure and stress control using mindful meditation and eating apps among people with high blood pressure. Medicines. 2015;2: 298-309.

Pharmacy 203. Goodbar NH, Foushee JA, Nash K, Connolly LA, Webster LM. Hypothermia associated with GHS Proc. June 2017; 2 (1): 71-82

2016 PUBLICATIONS thioridazine use in an intellectually disabled patient. J Pharm Pract. 2016;29:250-2. 204. Nash K, Carter KJ. Treatment options for the management of pervasive developmental disorders. Int J Psychiatry Med. 2016;51:201-10. 205. Sawyer RT, Odom JM, Jennings J, Orr J, Cass AL. Discharge mEdication reconciliation by Pharmacists to improve Transitions following Hospitalizations (DEPTH). GHS Proc. 2016;1:32-7. 206. Tennant SJ, Burgess DR, Rybak JM, Martin CA. Utilizing Monte Carlo simulations to optimize institutional empiric antipseudomonal therapy. Antibiotics. 2015;4:643-52. 207. Watts CS, Sciasci JN, Pauley JL, Panetta JC, Pei D, Cheng C, Christensen CM, Mikkelsen TS, Pui CH, Jeha S, Relling MV. Prophylactic trimethoprim-sulfamethoxazole does not affect pharmacokinetics or pharmacodynamics of methotrexate. J Pediatr Hematol Oncol. 2016;38:449-52.

Rehabilitation 208. McConomy S, Brooks J, Venhovens P, Xi Y, Rosopa P, DesJardins J, Kopera K, Lococo K, An improved seating accommodation model for older and younger drivers. SAE Technical Paper. 2016-01-1444. 209. Schaupp G, Seeanner J, Jenkins C, Manganelli J, Hennessy S, Truesdail C, Swift L, Venhovens P, Brooks J. Wheelchair usersâ&#x20AC;&#x2122; ingress/egress strategies while transferring into and out of a vehicle. SAE Technical Paper. 2016-01-1433. 210. Seeanner J, Brooks J, Mossey M, Jenkins C, Venhovens P, Truesdail C. The riding habits and technology use of aging motorcycle riders. SAE Technical Paper. 2016-01-1440.

USC School of Medicine Greenville: Biomedical Sciences Faculty, Staff & Students 211. Binks A. Measuring the breathless brain: is real life too noisy? Eur Respir J. 2015 Dec;46:1554-6. 212. Fazzone B, Morris G, Black L, Williams J, Leacock R, Sternberg S, Blackhurst D, Nelson A, Nathaniel TI. Exclusion and inclusion criteria for thrombolytic therapy in an ischemic stroke population. J Neurol Disord Stroke. 2016;4:1112. 213. Eno V, Mehalingam S, Nathaniel TI. The Patient Protection and Affordable Care Act (ACA) and utilization of preventive health care services. SAGE Open. 2016;6:1-13. 214. Fredwall M, Sternberg S, Blackhurst D, Lee A, Leacock R, Nathaniel TI. Gender differences in exclusion criteria for recombinant tissue-type plasminogen activator. J Stroke Cerebrovasc Dis. 2016;25:2569-74. GHS Proc. June 2017; 2 (1): 71-82

215. Gregg AR, Skotko BG, Benkendorf JL, Monaghan KG, Bajaj K, Best RG, Klugman S, Watson MS. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016;18:1056-65. 216. Hivert MF, Arena R, Forman DE, Kris-Etherton PM, McBride PE, Pate RR, Spring B, Trilk J, Van Horn LV, Kraus WE; American Heart Association Physical Activity Committee of the Council on Lifestyle and Cardiometabolic Health; the Behavior Change Committee, a joint committee of the Council on Lifestyle and Cardiometabolic Health and the Council on Epidemiology and Prevention; the Exercise, Cardiac Rehabilitation, and Secondary Prevention Committee of the Council on Clinical Cardiology; and the Council on Cardiovascular and Stroke Nursing. Medical training to achieve competency in lifestyle counseling: an essential foundation for prevention and treatment of cardiovascular diseases and other chronic medical conditions: a scientific statement from the American Heart Association. Circulation. 2016;134:e308-27. 217. Imeh-Nathaniel A, Adedeji A, Huber R, Nathaniel TI. The rewarding properties of methamphetamine in an invertebrate model of drug addiction. Physiol Behav. 2015;153:40-6. 218. Kennedy AB, Schenkelberg M, Moyer C, Pate R, Saunders RP. Process evaluation of a preschool physical activity intervention using web-based delivery. Eval Program Plann. 2017;60:24-36. 219. Kennedy AB, Cambron J, Sharpe PA, Travillian RS, Saunders RP. Process for massage therapy practice and essential assessment. J Bodyw Mov Ther. 2016;20:484-96. 220. Kennedy AB, Cambron JA, Sharpe PA, Travillian RS, Saunders RP. Clarifying definitions for the massage therapy profession: the results of the best practices symposium. Int J Ther Massage Bodywork. 2016;9:15-26. 221. Khalil MK, Elkhider IA. Applying learning theories and instructional design models for effective instruction. Adv Physiol Educ. 2016;40:147-56. 222. Kim JH, Trilk JL, Smith R, Asif I, Maddux PT, Ko Y, Emery MS. Cardiac structure and function in elite para-cyclists with spinal cord injury. Med Sci Sports Exerc. 2016;48:1431-7. 223. LeClair R, Binks AP. Combining the M1 and M2 classroom: an effective method for vertical and horizontal integration of core competencies. Med Sci Educ. 2016;26:77-83. 224. Nathaniel TI, Cochran T, Chaves J, Fulmer E, Sosa C, Yi S, Fredwall M, Sternberg S, Black81

hurst D, Nelson A, Leacock R. Co-morbid conditions in use of recombinant tissue plasminogen activator (rt-PA) for the treatment of acute ischaemic stroke. Brain Inj. 2016;30:1261-5. 225. Nathaniel TI, Soyinka JO, Adedeji A, ImehNathaniel A. Correction to “Molecular and physiological factors of neuroprotection in hypoxia-tolerant models: pharmacological clues for the treatment of stroke.” J Exp Neurosci. 2015;9:87. 226. Palomaki GE, Ashwood ER, Best RG, Lambert-Messerlian G, Knight GJ. Is maternal plasma DNA testing impacting serum-based screening for aneuploidy in the United States? Genet Med. 2015;17:897-900. 227. Parasaram V, Nosoudi N, LeClair RJ, Binks A, Vyavahare N. Targeted drug delivery to emphysematous lungs: Inhibition of MMPs by doxycycline loaded nanoparticles. Pulm Pharmacol Ther. 2016;39:64-73. 228. Platts-Mills TF, Quigley BR, Duronio JP, Hoover MV, Burgh ET, LaMantia MA, Davis SM, Weaver MA, Zimmerman S. Development and validation of a brief interactive educational

video to improve outpatient treatment of older adults’ acute musculoskeletal pain. J Am Geriatr Soc. 2016;64:880-1. 229. Sansone RA, Bohinc RJ, Wiederman MW. Healthcare adherence among patients who report the self-sabotage of their own medical care. Innov Clin Neurosci. 2015;12:10-2. 230. Sallis RE, Matuszak JM, Baggish AL, Franklin BA, Chodzko-Zajko W, Fletcher BJ, Gregory A, Joy E, Matheson G, McBride P, Puffer JC, Trilk J, Williams J. Call to action on making physical activity assessment and prescription a medical standard of care. Curr Sports Med Rep. 2016;15:207-14. 231. Stoutenberg M, Stasi S, Stamatakis E, Danek D, Dufour T, Trilk JL, Blair SN. Physical activity training in US medical schools: preparing future physicians to engage in primary prevention. Phys Sportsmed. 2015;43:388-94. 232. Xie Y, Jiang H, Zhang Q, Mehrotra S, Abel PW, Toews ML, Wolff DW, Rennard S, Panettieri RA Jr, Casale TB, Tu Y. Upregulation of RGS2: a new mechanism for pirfenidone amelioration of pulmonary fibrosis. Respir Res. 2016;17:103.

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Reach Your Dreams ... With the Support of a Leading Partner in Health. For more than a century, Greenville Health System has served as the Upstateâ&#x20AC;&#x2122;s premier healthcare resource. By leading the way in medical education and clinical research, transforming patient care through integrated programs and interconnected teams, and offering community residents the right care at the right time in the right place, we also help people pursue their dreams. To learn how GHS can partner with you to help you enjoy the best health possible, visit ghs.org.

ghs.org

17-0536

June 2017 | Volume 2 | Issue 1

Viewpoint

Review Article

QUESTION & ANSWER Radiology Imaging by JW Hanna

TEACHABLE MOMENT Clostridium difficile Testing: A Hard Look at Loose Stools by SJ Tennant and CM Faulkner-Fennell

43 Irritable Bowel Syndrome and Endometriosis: Twins in Disguise by M Aragon and BA Lessey 51 Barriers and Beliefs Contributing to Excessive Gestational Weight Gain in Low-Income Women by BE Brodsky and JV Logomarsino

Special Article

Case Studies

56 Robotic Transabdominal Preperitoneal Repair of Bilateral Arcuate Line Hernias by S Weimer et al

Neonatal Abstinence Syndrome: An Epidemic by K Barlow et al

16 Meaningful Analysis of Small Data Sets: A Clinician’s Guide by J Collins et al

Original Research 20 Orthostatic Intolerance and Other Autonomic Symptoms in Adolescents With Headaches by A Morales et al 26 Impact of an Antimicrobial StewardshipDriven Initiative to Assess Appropriateness of Asymptomatic Bacteriuria or Funguria Treatment by PJ Shah et al 32 Body of Knowledge: Using Prosections to Teach Pelvic Anatomy in OB/GYN Residency— A Randomized Study by AS Lane et al 38 The Relationship Between Third-Year Clerkship Allocation Method and Specialty Choice by FS Nuthalapaty et al

59 Severe Pulmonary Hypertension in an 87-YearOld Woman With Scimitar Syndrome by T van de Star et al 62 Adamantinoma of the Forearm: A Chronologic Presentation of a Slow-Growing Malignancy by RW Gurich Jr et al 67 Spontaneous Iliac Vein Rupture by NJ Walsh et al

Miscellany 70 2017 Graduates of Greenville Health System and University of South Carolina School of Medicine Greenville 71 2016 Publications of Greenville Health System’s Medical and Scientific Staff

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