July–September 2017

Outcomes of a Military Regional Multispecialty Synchronous Telehealth Platform 

and the Importance of the Dedicated Patient Presenter 1

COL Kirk H. Waibel; Stephanie J. Garner, RN; Brandon Carter, RN; Irfan Bojicic, RN; Robin Smith, RN

A Retrospective Analysis: Do Bacterial Culture and Sensitivity Data Support Empiric Use of

Piperacillin-Tazobactam and Antipseudomonal Fluoroquinolones in Hospitalized Patients? 9

CPT Pulkit Saxena; CPT Ryan V. Burkhart; MAJ Craig R. Ainsworth

Low Prevalence of Carbapenem-Resistant Enterobacteriaceae Among Wounded Military Personnel ..12

Katrin Mende, PhD; Miriam L. Beckius, MPH; Wendy C. Zera; Fatma Onmus-Leone, MS; et al

Effects of Mandatory Screening Labs in Directing the Disposition of the Apparently Healthy 

Psychiatric Patient in the Emergency Department . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18

MAJ Karyn E. Kagel; CPT Meghan Smith; CPT Ilya V. Latyshenko; et al

Resilience-Enhancing Relationships: What We Can Learn From Those With a

History of Adverse Childhood Experiences 25

COL Derrick Arincorayan; Larry Applewhite, PhD; MAJ Matthew Garrido; et al

A Randomized Comparison Between Neurostimulation and Ultrasound-Guided

Lateral Femoral Cutaneous Nerve Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .33

Gaurav Gupta, MD, FRCPC; Mohan Radhakrishna, MC, FRCPC; Isacc Tamblyn, PhD; et al

Occlusion Training: Pilot Study for Postoperative Lower Extremity Rehabilitation

Following Primary Total Knee Arthroplasty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39

Capt Christopher L. Gaunder, USAF, MC; CPT Michael P. Hawkinson; et al

Martial Arts-Based High Intensity Interval Training as a Component of Warfighter

Rehabilitation and Tactical Athlete Fitness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .44

Capt Gavin L. Mills, USAF, MC; COL Anthony E Johnson

Martial Arts-Based High Intensity Interval Training in the Rehabilitation of Combat Amputees . . . . . . .53

Capt Gavin L. Mills, USAF, MC; CPT David J. Tennent; LTC Joseph F. Aldrete; COL Anthony E. Johnson

Characteristics of US Combat Veterans (2001-2011) Who Remain on Active Duty

After Upper Extremity Amputations 57

Sara H. Kift, DScOT; Capt Taylor J. Bates, USAF, MC; CPT Nathan A. Franklin; COL Anthony E. Johnson

Temporospatial Angiogenesis-Associated Gene Expression Profiles in Ischemic Rat Skin Flaps . . . . . . 62

LTC Thomas M. Johnson; LCDR Esra Toussaint-Barrett, USPHS; LTC Jose M. Pizarro

Resistance to Abrasion of Extrinsic Porcelain Esthetic Characterization Techniques 71

LTC Woo J. Chi; William Browning, DDS; Stephen Looney, PhD; et al

Effect of Smokeless Tobacco on Surface Roughness of Dental Restorations 80

MAJ Shani O. Thompson; Gerald D. Griffin, PhD; Nicole Meyer; LTC Manuel Pelaez

Placement and Replacement Rates of Amalgam and Composite Restorations

on Posterior Teeth in a Military Population 88

MAJ Benjamin D. Owen; COL Peter H. Guevara; COL William Greenwood

Improved Coding Accuracy in an Academic Practice 95

LTC Dana Nguyen; MAJ Heather O’Mara; CPT Roberty Powell

Winging of the Scapula Diagnosed as Parsonage-Turner Syndrome: A Case Report 99

CPT Christine Carroll; Bill Bass MD

JOURNAL

THE UNITED STATES ARMY

MEDICAL DEPARTMENT
JOURNAL

A Professional Publication

of the AMEDD Community THE UNITED STATES ARMY

MEDICAL DEPARTMENT

Online issues of the AMEDD Journal are available at http://www.cs.amedd.army.mil/amedd_journal.aspx

July–September 2017 US Army Medical Department Center & School PB 8-17-7/8/9

The Army Medical Department Journal [ISSN 1524-0436] is published quarterly 

for The Surgeon General by the AMEDD Journal Office, USAMEDDC&S, AHS CDD

3630 Stanley RD STE B0204, JBSA Fort Sam Houston, TX 78234-6100.

Articles published in The Army Medical Department Journal are listed and 

indexed in MEDLINE, the National Library of Medicine’s premier bibliographic 

database of life sciences and biomedical information. As such, the Journal’s 

articles are readily accessible to researchers and scholars throughout the 

global scientific and academic communities.

CORRESPONDENCE: Manuscripts, photographs, official unit requests to 

receive copies, and unit address changes or deletions should be sent via 

email to usarmy.jbsa.medcom-ameddcs.list.amedd-journal@mail.mil, or by 

regular mail to the above address. Telephone: (210) 221-6301, DSN 471-6301

DISCLAIMER: The AMEDD Journal presents clinical and nonclinical 

professional information to expand knowledge of domestic & international 

military medical issues and technological advances; promote collaborative 

partnerships among Services, components, Corps, and specialties; convey 

clinical and health service support information; and provide a peer-reviewed, 

high quality, print medium to encourage dialogue concerning healthcare 

initiatives.

Appearance or use of a commercial product name in an article published 

in the AMEDD Journal does not imply endorsement by the US Government.

Views expressed are those of the author(s) and do not necessarily reflect 

official policies or positions of the Department of the Army, Department of 

the Navy, Department of the Air Force, Department of Defense, nor any other 

agency of the US Government. The content does not change or supersede 

information in other US Army Publications. The AMEDD Journal reserves the 

right to edit all material submitted for publication (see inside back cover).

CONTENT: Content of this publication is not copyright protected. Reprinted 

ma-terial must contain acknowledgement to the original author(s) and the 

AMEDD Journal.

OFFICIAL DISTRIBUTION: This publication is targeted to US Army Medical 

Department units and organizations, other US military medical organizations, 

and members of the worldwide professional medical community.

By Order of the Secretary of the Army:

Official:

GERALD B. O’KEEFE

Administrative Assistant to the 

Secretary of the Army

Mark A. Milley

General, United States Army

Chief of Staff

DISTRIBUTION: Special 1719803

LTG Nadja Y. West

The Surgeon General

Commander, US Army Medical Command

MG Brian C. Lein

Commander

US Army Medical Department Center and School

US Army Health Readiness Center of Excellence
July – September 2017 1

Telehealth development and implementation within the 

military has continued to grow at a rapid pace. As part of 

the Army Campaign 2020, the US Army Medical Command (MEDCOM) has committed significant resources 

with the initiation of the Telehealth Service Line (THSL) 

in 2010 to develop and implement enterprise-level telehealth strategies.1

 While the majority of telehealth encounters in the military have either been specific for 

behavioral health or via an asynchronous or “store-andforward” modality, telehealth can also encompass multispecialty synchronous or real-time patient interaction, 

remote patient monitoring, and mobile health.2

 For 2014-

2016, the MEDCOM THSL directed efforts to expand 

a comprehensive patient-centered experience using a 

multispecialty synchronous platform; however, multiple 

barriers and challenges exist between regional medical 

centers and remote clinics where specialists and patients 

are located. One major challenge is creating a sustainable workflow process connecting both administrative 

and healthcare personnel at the originating site where 

the patient and presenter are located with the distant site 

where the specialist is located.3

 Unfortunately, there are 

no current dedicated telehealth positions on the US Army’s organizational Table of Distribution and Allowances with the exception of the THSL headquarters located 

under the MEDCOM G-3/5/7 Patient Care Integration. 

Thus, regional health commands and local Army health 

clinics (AHCs) are left to determine how they can support telehealth. Many articles have discussed the roles 

and responsibilities of the telehealth presenter but we 

are unaware of specific reports describing differences 

in presenter capabilities and its effect on telehealth.4-11

Herein, we report the results of a multispecialty synchronous telehealth program after developing 3 different categories of patient presenters. We also discuss specific aspects and lessons learned with dedicated patient 

presenters and their effect on regional telehealth efforts 

and workflow processes.

Outcomes of a Military Regional

 Multispecialty Synchronous Telehealth

 Platform and the Importance of the

 Dedicated Patient Presenter

COL Kirk H. Waibel, MC, USA Irfan Bojicic, RN

Stephanie J. Garner, RN Robin Smith, RN

Brandon Carter, RN

Abstract

Implementing a successful multispecialty synchronous telehealth program requires identifying and overcoming 

numerous barriers. One key aspect of synchronous telehealth involves the telehealth presenter; however, the impact that a dedicated patient presenter has supporting routine multispecialty synchronous telehealth is unknown.

Methods: We conducted a retrospective review of telehealth encounters conducted from a single regional medi- cal center over a two-year period to 12 outlying health clinics which provided one of 3 levels of patient presenter 

support: category 1 locations had a dedicated telehealth registered nurse, category 2 locations had a nondedi- cated registered nurse or licensed vocational nurse, and category 3 locations were supported by an Army medic 

(military occupational specialty 68W).

Results: A total of 4,032 telehealth encounters occurred from January 2014 to December 2015 involving 26 

distinct specialties located within a single regional medical center and 12 outlying health clinics which supported 60,232 beneficiaries. The 3 category 1 locations (3/12, 25%) supported the most telehealth encounters 

per month compared to either category 2 or category 3 locations (P<.0001). Category 1 and category 2 locations 

averaged a 239% and 122% year-to-year growth, respectively. Category 3 locations averaged a year-to-year 

decline of 11.7%.

Comment: This is the first study of which we are aware that has compared different patient presenter levels 

and evaluated its effect on telehealth activity. Regional medical centers initiating a multispecialty synchronous 

telehealth program should strongly consider hiring, educating, and placing dedicated presenters at patient originating sites.
2 http://www.cs.amedd.army.mil/amedd_journal.aspx

Methods

The primary objective of this retrospective review was to assess the number of 

clinical encounters per month in individual AHCs comparing 3 telehealth 

presenter categories. Secondary objectives assessed year-to-year telehealth 

activity and telehealth activity in locations prior to and after implementation 

of dedicated telehealth presenters. From 

January 2014 to December 2015, 98% 

(4,032/4,112) of synchronous telehealth 

encounters in Regional Health Command Europe (RHC-E) were conducted 

by healthcare providers located at the 

Landstuhl Regional Medical Center (K. 

H. W., unpublished data). Landstuhl 

Regional Medical Center (LRMC) is 

the regional strategic specialty medical platform supporting approximately 

60,000 beneficiaries who are enrolled 

in 12 distant AHCs located in Germany, 

Italy, and Belgium (Figure 1). Prior to 

2015, telehealth efforts in RHC-E were 

focused on behavioral health and surgical subspecialties. However, in part 

due to the reluctance of “frontline staff” 

to support telehealth as a routine component of patient care, the European 

Advancement for Regional Telehealth 

project was launched in late 2014, hiring 3 specifically trained telehealth presenters who supported a comprehensive medical, surgical, and behavioral 

health telemedicine platform.3

One clear barrier at the initiation of regional telehealth 

efforts in 2013 centered on consistent patient presentation. Staffing the AHC primary care mission left few additional resources to support regional telehealth efforts, 

despite regional policies directing immediate priority to 

these efforts. Simply put, initial resistance to various pilot projects mirrored known telehealth barriers.3

 Secondary to these initial difficulties and lack of robust uptake, 

a GS-0610-10 position description was developed for a 

Registered Nurse (Clinical) Telehealth Nurse Care Coordinator (TNCC). Further, 3 categories for a telehealth patient presenter were established to model potential assets 

within the AHC: category 1 represented the dedicated 

registered nurse hired specifically to support a multispecialty telehealth platform within the AHC (ie, dedicated 

telehealth presenter); category 2 was a registered nurse or 

licensed vocational nurse (LVN) located within the clinic but telehealth was not their full time duty; category 3 

was a military occupational specialty (MOS) 68W medic 

(Table 1). All clinics received an initial site visit, specific 

education, and competency assessment regarding the 

telehealth processes for each patient encounter. Hired in 

late 2014, Category 1 TNCCs spent an initial week with 

the regional telehealth team, individually met with each 

specialty service, developed service-specific standard 

operating procedures (SOPs) and presentations skills, 

engaged in weekly one-hour telehealth huddles with the 

regional telehealth nurse manager, and returned every 6 

months for refresher training and new service development. Category 2 and 3 locations were assisted with telephonic, video teleconference, and in-person site visits 

as requested.

All telehealth visits regardless of location required written patient or parental consent. Synchronous telehealth 

visits conducted between patients and providers were 

performed on a secure, Health Insurance Portability and 

Accountability Act (HIPAA)-compliant video link. Each 

OUTCOMES OF A MILITARY REGIONAL MULTISPECIALTY SYNCHRONOUS TELEHEALTH PLATFORM

AND THE IMPORTANCE OF THE DEDICATED PATIENT PRESENTER

Italy

Germany

Belgium



Army health clinic with

dedicated health presenter

Landstuhl Regional 

Medical Center

Army health clinic

Figure 1. Locations of Army Regional Health Command–Europe Army health clinics.
July – September 2017 3

THE ARMY MEDICAL DEPARTMENT JOURNAL

AHC supporting telehealth had one 

standardized Polycom HDX 9000 

Practitioner Cart (Polycom, Inc, San 

Jose, CA) which included an AMD2500 General Exam Camera, AMD 

Fiberoptic Otoscope, and AMD Telephonic Stethoscope (AMD Global 

Telemedicine, Chelmsford, MA). All 

presenters, regardless of category, 

were trained on the use of all devices. 

Providers used a desktop computer 

installed with Polycom RealPresence software and camera (Polycom, 

Inc, San Jose, CA). Per current telehealth guidance, all 

clinic encounters at the patient site are coded as a 99499 

visit with an originating site fee: HCPCS (Healthcare 

Common Procedure Coding System) Q3014.

Briefly, patients arriving at their AHC for a telehealth 

visit follow standard clinic operating procedures (ie, 

checked-in, 2-patient identifier verification, placed in 

a HIPAA compliant exam room, vital signs obtained, 

medications reconciled, and consented for telehealth). 

At the allotted appointment time, both the originating 

site where the patient is located and the distant site (ie, 

LRMC specialist) dial-in to a video conference bridge. 

At that time, good audio and video is established, a 

unique access code is provided by the bridge technician 

to both parties, and the bridge technician signs out which 

“locks” the virtual exam room. Two-patient identifier, a 

2016 Ambulatory Care National Patient Safety Goal, is 

established by the specialist and the appointment begins. 

Content such as educational slides for specific diagnoses can be virtually shared or emailed to the patient and 

presenter, respectively. At the request of the specialist, 

the presenter can perform a physical exam using a highdefinition camera and peripheral medical devices to perform any aspect of the ear, eye, nose, throat, heart, lung, 

and skin exam. Category 1 dedicated telehealth presenters also have additional training for specialty-specific 

aspects of the history and physical exam (Table 2).

Study approval was obtained from the LRMC Human 

Research Protection Program. Descriptive 

statistics were used for demographic and 

AHC details. One-way ANOVA was used to 

assess differences for intra- and inter-TNCC 

category encounters. Population-corrected 

telehealth activity between locations was 

calculated using the 2-tailed Mann-Whitney 

U test. An α of less than 0.05 was considered 

statistically significant.

Results

From January 2014 and December 2015, 

4,032 synchronous telehealth encounters occurred among 26 distinct specialties located 

within a single regional medical center and 

12 outlying health clinics. Beneficiary population varied at each AHC with a median 

(range) of 4,184 (411-10,214) with a total beneficiary population of 60,232 (Table 1). The 

median (range) distance from outlying AHCs 

to LRMC was 366 (40-940) kilometers.

Regarding the 12 AHCs: from January to 

October 2014 (10 months) which was prior to 

hiring 3 category 1 dedicated patient presenters, 42% (5/12) were category 3 sites while 

Table 1. Telehealth presenter categories and Army health clinic (AHC) location.

TNCC category

(Nov 2014-Dec 2015) 1 2 3

Skill level Dedicated

presenter (TNCC)

AHC nurse, LVN, 

or 68W medic

68W medic only

AHC location Stuttgart (PCH)

Vilseck (VSK)

Wiesbaden (WBD)

Grafenwoehr (GFW)

Katterbach (KTB)

Shape (SHP)

Vicenza (VCZ)

Baumholder (BHR)

Brussels (BSL)

Hoenfels (HHF)

Illesheim (ILS)

Livorno (LVO)

Median population

(range) 

8,236

(6,968-10,214)

6,157

(3,487-8,548)

1,884

(411-4,141)

Total population 25,418 24,349 10,465

TNCC indicates Telehealth Nurse Care Coordinator; LVN, licensed vocational nurse.

Table 2. Specialty-specific concepts used by category 1 TNCCs.

Specialty Unique capabilities

Allergy/Immunology

Asthma control test; Allergen immunotherapy and 

omalizumab consent forms; spirometry,* peak flow 

measurement

Anesthesia/Preoperative 12-lead ECG, telestethoscope, Mallampati score

Cardiology 12-lead ECG, Holter event monitor*

Dermatology Vibrent Teledermatology

Ear, Nose, and Throat Fiberoptic laryngoscopy, whisper test, Weber and 

Rinne test

General surgery Postoperative wound assessment, suture removal, 

dressing changes, wound VAC changes

Neurosurgery Socrates, complete neurological exam, follow up xray

Occupational therapy Goniometry, dynamometer

Orthopedics Specialized shoulder exam (eg, Neers, O’Briens, 

Hawkins test), specialized knee exam, suture and 

splint removal, CAM boot, goniometry, follow up 

x-rays

Pediatric development Head circumference

Plastic surgery Body measurements for elective surgery

Podiatry Suture/splint removal, CAM boot, goniometry for 

ankle range of motion

Pulmonary Spirometry* and peak flow measurement

Sleep medicine Epworth sleepiness scale, Friedman score, Mallampati score, neck circumference

Urology Postoperative examination, Bladder ultrasound

*Depending on facility capabilities.

TNCC indicates Telehealth Nurse Care Coordinator; CAM, controlled ankle motion.
4 http://www.cs.amedd.army.mil/amedd_journal.aspx

58% (7/12) were category 2 sites. From November 2014 

through December 2015, the 5 category 3 sites remained 

category 3 while 43% (3/7) of category 2 sites were converted to category 1 sites with the hiring and placement 

of 3 dedicated telehealth registered nurses (Figure 2).

The 3 category 1 telehealth nurses worked in their respective clinics for the first 10 months of 2014 prior to 

being hired in a dedicated nurse presenter position, but 

were not engaged with patient presentation prior to being hired. Monthly telehealth encounters for November 

2014 to December 2015 compared to the first 10 months 

of 2014 significantly increased in 75% (8/12) of clinics, 

was not significant in 25% (3/12) of clinics, and had significant decline in one clinic (Figure 2).

The 3 category 1 locations (3/12, 25%) performed the 

most telehealth encounters per month compared to either 

category 2 or category 3 locations (P<.0001) (Figure 3). 

There was no significant difference between the 3 category 1 locations in 2015 (P=.08) which observed an average 

year-to-year growth of 239.3%. Significant differences 

were observed within the 4 category 2 and 5 category 3 

locations, respectively (P <.05), but category 2 locations 

supported significantly greater telehealth appointments 

compared to category 3 locations (P<.0001) with an average year-to-year growth of 122%. Category 3 locations 

had significant interclinic telehealth differences (P<.05) 

but experienced a year-to-year decline of 11.7% (Figure 

3). Category 1 sites’ activity as a percentage of all sites 

increased from an initial 34.9% to 75.7% from November 2014 to December 2015 (Figure 4).

Controlling for population size, 2 category 1 locations 

were not significantly different (P=.82). One category 1 

site was not significantly different from one category 2 

AHC (P=.45) and one category 3 AHC (P=.16). The percentage of the population utilizing telehealth per month 

did not exceed 1% with the exception of 2 category 1 sites 

(Vilseck and Wiesbaden) (Figure 5). For 2015, the mean 

(SD) percentage of the beneficiary population seen via 

telehealth at category 1, 2, and 3 sites were 7.04 (4.65) 

%, 3.0 (1.43) %, and 1.9 (1.22) %, respectively (P<.05). 

When comparing one AHC to another AHC there 

were a number of locations that were statistically 

distinct from one another (Table 3).

Estimated travel distance, travel expenses, and days 

missed if each patient visit was based on a single individual travelling to LRMC for their visit from November 

OUTCOMES OF A MILITARY REGIONAL MULTISPECIALTY SYNCHRONOUS TELEHEALTH PLATFORM

AND THE IMPORTANCE OF THE DEDICATED PATIENT PRESENTER

Figure 2. Comparison of mean telehealth encounters per month at Army health clinics prior to and after hiring 3 Category 1

telehealth nurses.

Notes:  indicates P<.05;  indicates P<.0001; NS indicates not significant.

Army health clinic locations and associated identifiers are listed in Table 1.

Army Health Clinic Location (see Notes below)

Category of Telehealth Nurse

Care Coordinator Service

Category 1

Category 2

Category 3

40

10

0

50

20

60

30

BHR WBD BSL SHP LVO VCZ GFW HHF ILS KTB VSK PCH

 NS NS NS













 

Mean Encounters per Month 
July – September 2017 5

THE ARMY MEDICAL DEPARTMENT JOURNAL

2014 through December 2015 equaled 1.65 million kilometers driven, $1.13 million in travel expenses, and 

4,365 work days missed (Table 4).

Comment

Telehealth can encompass a number of modalities, but 

multispecialty synchronous or real-time telehealth currently provides the best patient satisfaction.12 Further, 

synchronous telehealth fosters the patient-physician relationship through direct communication.13 To be successful, sustainable, and robust, synchronous telehealth 

encounters require the provider, patient, and patient 

presenter. Previous studies have demonstrated how the 

patient presenter can streamline patient presentations 

for specialists, but we are unaware of any studies which 

have compared different levels of patient presenters.14,15

One of the main obstacles for telehealth is achieving 

the acceptance of patient originating sites.3

 It is clear 

that close working relationships between the medical 

neighborhood containing specialists and the primary 

care home is paramount. Herein, we observed that as 

the “dedication” and presenter category increased, so 

did the number of telehealth visits even when controlling for population size. Dedicated telehealth presenters 

functioned as local and, in many instances, subregional 

telehealth champions providing feedback to local providers in morning huddles, interacting weekly with the 

regional telehealth office, and refining workflow processes and examination skills with specialists (Table 2).

The decision to hire a dedicated telehealth presenter is 

often the subject of concern with questions about return 

of investment (ROI). These are appropriate questions, 

but travel expenses, school days missed, work days, decreased deferral to the network, and increased medical 

and surgical recapture should be included in ROI assessments, as well as work relative value units generated.

As a retrospective review, we acknowledge that there are 

a number of limitations of this study. First, perhaps the 

same outcomes could be obtained with a dedicated LVN 

or dedicated MOS 68W medic instead of the registered 

nurses who were hired. The purpose of the registered 

nurse was to allow significant expansion of the clinical 

exam under the training and guidance of the specialist. In fact, as part of the biannual training, category 1 

nurses gained specialty-specific skills which would not 

be permitted with a lower skill level. Further, a registered nurse can conduct and document in the electronic 

health record any aspect of the physical exam required 

by the specialist.

Figure 3. Mean and interquartile plot of monthly mean telehealth encounters within Army health clinics.

Note: Army health clinic locations and associated identifiers are listed in Table 1.

Army Health Clinic Location (see Note below)

WBD VSK PCH SHP VCZ GFW KTB BHR BSL LVO HHF ILS

40

90

10

0

50

20

70

60

30

80

P<.0001

P<.05

P<.05

Not Significant

P<.0001

P<.0001

Mean Encounters per Month 
6 http://www.cs.amedd.army.mil/amedd_journal.aspx

OUTCOMES OF A MILITARY REGIONAL MULTISPECIALTY SYNCHRONOUS TELEHEALTH PLATFORM

AND THE IMPORTANCE OF THE DEDICATED PATIENT PRESENTER

50

0

300

250

200

150

100

Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec

2014 2015

Category of Telehealth Nurse

Care Coordinator Service

Category 1

Category 2

Category 3

Mean Encounters per Month 

Figure 4. Number of telehealth encounters supported by month based on telehealth nurse category.

Figure 5. Percentage of population using telehealth monthly.

Note: Army health clinic locations and associated identifiers are listed in Table 1. Percentage of Population

Army Health Clinic Location (see note below)

WBD VSK PCH SHP VCZ GFW KTB BHR BSL LVO HHF ILS

0.6

1.2

0.2

0

0.4

0.8

1.0
July – September 2017 7

THE ARMY MEDICAL DEPARTMENT JOURNAL

Second, the 3 AHCs with a category 1 registered nurse were 

the initial starting locations for 

each specialty, thereby increasing at least initial monthly activity. While overall telehealth activity increased in 5 category 2 and 

3 locations, there were 2 locations 

which, when corrected for population size, were not statistically 

significant from one category 1 

site: Shape and Brussels AHCs 

(Table 3). The Shape clinic specifically prioritized telehealth by 

identifying and placing a nurse in 

mid-2015 to be dedicated to the 

telehealth mission. Brussels AHC 

was the second smallest clinic site, resulting in a much 

smaller denominator which could significantly skew 

population-based percentage calculations as noted by its 

wider variation of monthly encounters (Figure 5).

Three category 1 presenters (authors I. B., R. S., and B. 

C.) were queried regarding their observations within 

their respective AHCs. One of the most important aspects is to ensure that there is an alternate presenter who, 

in case of personal illness or other reasons, is 

able to present patients. Regarding patients 

who are typically in a remote or small military installation, the opportunity to travel to 

the regional medical center located within a 

larger urban shopping location is a frequently 

identified factor. Some patients also have expressed the desire to visit the specialist in a 

typical “brick and mortar” location which is 

often the local host nation provider close to 

where the patient lives. Additional ancillary 

services such as pulmonary function testing, 

Wood’s lamp, ultrasound, and computed tomography may not be available in some AHCs, 

resulting in the requirement for some patients 

to visit the host nation university hospital or 

LRMC. In a recent publication, it was noted 

that none of the outlying AHCs in RHC-E had 

the capability to perform pulmonary function 

testing, a basic component of asthma management.16 Finally, there is no direct financial 

cost incurred by the Soldier’s unit or AHC for 

the patient to see a host nation provider, as the 

costs are covered by TRICARE. Thus, an unexpected cost of increased telehealth activity 

is an increased likelihood of a recommendation that the patient travel to LRMC, thereby 

directly affecting the unit’s budget. However, 

one published study from an LRMC specialty observed 

that telehealth resulted in less than one-quarter of new 

and follow up visits requiring an in-person visit, thereby 

saving costs and improving individual readiness.16 On 

the other hand, difficulties with obtaining timely and 

translated medical records coupled with minimal time 

lost from work when using synchronous telehealth in an 

individual’s local AHC is clearly nested in the Chief of 

the Army’s priority of readiness.17

Table 4. Estimates of per month travel-related distances and per diem costs 

associated with documented encounter data.

Category AHC

Locationa No. of Encounters Estimated Travel Costs

Before

TNCCb

After

TNCCc

Kilometers

Traveled

(roundtrip)

Missed

Work 

Days 

Per Diem

Costs 

(USD)

1

WBD 3.1 46.6 9,981.6 46.6 3,443.6

VSK 17.4 50.1 37,753.9 100.1 25,542.9

PCH 14.6 37.9 15,702.4 37.9 9,210.2

Category 1 totals 35.1 134.6 63,437.9 184.6 38,196.7

2

SHP 7.7 14.5 10,875.0 29.0 9,551.9

VCZ 6.4 14.1 22,514.3 42.2 18,292.9

GFW 3.1 9.2 7,279.3 18.4 4,814.9

KTB 4.6 10.4 5,613.6 20.7 4,008.1

Category 2 totals 21.8 48.2 46,282.2 110.3 36,667.8

3

BHR 3.3 1.3 102.9 0.6 35.5

BSL 0.7 2.5 1,750.0 5.0 1,603.8

LVO 1.8 1.1 2,250.0 5.4 1,847.7

HHF 2.3 3.1 2,309.7 3.1 1,564.7

ILS 2.7 2.8 1,526.6 2.8 1,083.8

Category 3 totals 10.8 10.8 7,939.2 16.9 6,135.5

Categories 1, 2, 3

totals

67.7 193.6 117,659.3 311.8 81,000.0

Estimated cost totals, Nov 2014-Dec 2015 1,647,230.2 4,365.2 1,134,000.0

AHC indicates Army health clinic; TNCC indicates telehealth nurse care coordinator.

Notes:

a. Army health clinic locations and associated identifiers are listed in Table 1.

b. Per month for the first 10 months of 2014.

c. Per month for 14 months, (November 2014 through December 2015).

Table 3. Population-corrected comparison between telehealth sites and monthly telehealth encounters (January-December 2015). Note: Army health clinic locations and 

associated identifiers are listed in Table 1.

VSK PCH SHP VCZ GFW KTB BHR BSL LVO HHF ILS

WSD 0.82          

VSK          

PCH 0.45     0.16   

SHP     0.051   

VCZ 0.06   0.24 0.17  0.37

GFW    0.09 0.89 0.37

KTB  0.75 0.89  

BHR    0.93

BSL 0.27  

LVO  0.10

HHF 0.67

 indicates P<.05;  indicates P<.01;  indicates P<.001
8 http://www.cs.amedd.army.mil/amedd_journal.aspx

Telehealth remains a top MEDCOM policy and has the 

ability to leverage technology to provide services and 

access to specialists that otherwise are limited or require extensive travel to reach. However, telehealth faces numerous obstacles and challenges, both from providers and staff at both originating and distant sites. We 

observed the direct impact of the dedicated patient presenter who, over 14 months, was the key to solving many 

challenges within the AHC, the regional telehealth office, and communication between patients and specialty 

providers. The telehealth presenter should be considered 

a vital member of the synchronous telehealth encounter, 

and we recommend that other regional medical centers 

developing multispecialty synchronous telehealth platforms ensure appropriate identification and hiring of 

dedicated patient presenters.

References

1. US Army Medical Department. Army Telehealth 

[internet]. Available at: http://armymedicine.mil/

Pages/Virtualhealth.aspx. Accessed May 22, 2016.

2. Center for Connected Health Policy. State Telehealth Laws and Medicaid Program Policies., 

March 2016. Available at: http://www.cchpca.

org/sites/default/files/resources/50%20State%20

FINAL%20April%202016.pdf. Accessed May 18, 

2016.

3. Taylor J, Coates E, Brewster L, Mountain G, Wessels B, Hawley MS. Examining the use of telehealth 

in community nursing: identifying the factors affecting frontline staff acceptance and telehealth 

adoption. J Adv Nurs. 2015;71(2):326-337.

4. Hjelm NM. Benefits and drawbacks of telemedicine. J Telemed Telecare. 2005;11:60-70.

5. Nicolini D. Stretching out and expanding work 

practices in time and space: the case of telemedicine. Hum Relat. 2007;60(6):889-920.

6. Sullivan DH. Technological advances in nursing 

care delivery. Nurs Clin North Am. 2015;50:663-677.

7. Yesenofski L, Kromer S, Hitchings K. Nurses leading the transformation of patient care through telehealth. J Nurs Adm. 2015;45:650-656.

8. Taylor J, Coates L. Caring from a distance: the role 

of telehealth. Nurs Times. 2015;111:18-20.

9. Shore JH, Mishkind MC, Bernard J, et al. A lexicon 

of assessment and outcome measures for telemental health. Telemed J E Health. 2014;20:282-292.

10. Edirippulige S. Readiness of nurses for practicing telehealth. Stud Health Technol Inform. 

2010;161:49-56.

11. Trossman S. Back to the future? Telehealth services, 

tele-nursing are on the rise. Am Nurse. 2014;46;1-6.

12. Weinstock MA, Nguyen FQ, Risica PM. Patient 

and referring provider satisfaction with teledermatology. J Am Acad Dermatol. 2002;47:68-72.

13. Haney T, Kott K, Fowler C. Telehealth etiquette 

in home healthcare: the key to a successful visit. 

Home Healthc Now. 2015;33(5):254-259.

14. Bergman DA, Sharek PJ, Ekegren K, Thyne S, 

Mayer M, Saunders M. The use of telemedicine 

access to schools to facilitate expert assessment 

of children with asthma. Int J Telemed Appl. 2008. 

doi: 10.1155/2008/159276 159276.

15. Brown W, Odenthal D. The uses of telemedicine 

to improve asthma control. J Allergy Clin Immunol 

Pract. 2015;3(2):300-301.

16. Waibel KH. Synchronous telehealth for outpatient 

allergy consultations: a 2-year regional experience. 

Ann Allergy Asthma Immunol. 2016;116:571-575.

17. Milley MA. 39th Chief of Staff of the Army 

Initial Message to the Army [internet]. Available at https://www.army.mil/e2/rv5_down

loads/leaders/csa/Initial_Message_39th_CSA.pdf. 

Accessed June 4, 2016.

Authors

COL Waibel is Staff Allergist, Division of Medicine, 

LRMC, Landstuhl, Germany. He is also Medical Director and Consultant, RHC-E Telehealth, and Allergy/Immunology Consultant to the Office of the Surgeon General of the Army.

Ms Garner is the Regional Telehealth Nurse Director, Landstuhl Regional Medical Center, Landstuhl, 

Germany.

Mr Carter is the Category 1 Telehealth Nurse Care Coordinator and Patient Presenter at the Patch Barracks 

Clinic, Stuttgart, Germany.

Mr Bojicic is the Category 1 Telehealth Nurse Care Coordinator and Patient Presenter at the Wiesbaden Army 

Health Clinic, Wiesbaden, Germany.

Ms Smith is the Category 1 Telehealth Nurse Care Coordinator and Patient Presenter at the Rose Barracks Clinic, 

Vilseck, Germany.

OUTCOMES OF A MILITARY REGIONAL MULTISPECIALTY SYNCHRONOUS TELEHEALTH PLATFORM

AND THE IMPORTANCE OF THE DEDICATED PATIENT PRESENTER
July – September 2017 9

The mortality benefit of early recognition of infection 

with empiric initiation of antibiotics is well documented.1

Pseudomonas aeruginosa has been a particularly problematic bacterial infection whose antibiotic resistance is 

increasing at an alarming rate.2

 Inappropriate empiric 

antibiotic coverage of Pseudomonal blood stream infections has shown mortality rates as high as 43.4%.3

 This 

high mortality rate, in addition to prior studies showing 

an increased mortality rate with empiric monotherapy,4 -6

has led to empiric combination antimicrobial coverage 

becoming the clinical standard for suspected infection 

with gram-negative bacteria. “Double coverage” for 

Pseudomonas infection usually includes the addition of 

an antipseudomonal fluoroquinolone or aminoglycoside 

to an antipseudomonal beta-lactam.

At our institution as well as other military and civilian 

medical centers, it is common to use the antipseudomonal beta lactam piperacillin-tazobactam in combination with a fluoroquinolone for empiric gram-negative 

coverage. Fluoroquinolones are commonly selected for 

double coverage due to the ease of dosing, decreased 

monitoring, and decreased toxicity (compared to aminoglycoside agents). Our institution provides an annual 

cumulative antimicrobial susceptibility report to estimate percentages of resistance of a particular organism 

to an antibiotic. Based on the William Beaumont Army 

Medical Center (WBAMC) 2015 antimicrobial susceptibility report,* 88% of Pseudomonas isolates were 

susceptible to piperacillin-tazobactam, 77% of isolates 

were susceptible to levofloxacin, and 79% of isolates 

were susceptible to ciprofloxacin. In order for our current strategy of double coverage to be effective, (ideally) the 12% of Pseudomonas isolates not susceptible 

to piperacillin-tazobactam would be susceptible to levofloxacin or ciprofloxacin.

We conducted a 6-month retrospective record review to 

determine whether there is bacterial culture data to support our initial empiric gram-negative double coverage 

with extended antipseudomonal beta-lactam (piperacillin-tazobactam) and fluoroquinolones (ciprofloxacin and 

levofloxacin) in our military hospital patient population.

Based on our institution’s antiobiogram, a previous 

study showing no benefit in Pseudomonas coverage 

with use of an antipseudomonal fluoroquinolone and antipseudomonal beta-lactam,7

 along with our knowledge 

of mechanisms of resistance, led us to hypothesize that 

providing “double coverage” for empiric Pseudomonas

coverage with floroquinolones in addition to piperacillin-tazobactam would provide no additional coverage.

Methods

We examined 6-months of culture and sensitivities data 

of Pseudomonas bacteria from urine, blood, sputum, 

wound, joint, or body fluid in our hospitalized patient 

population.

Exclusion criteria for our study were cultures from patients under the age of 18; concomitant gram-positive 

organisms; and gram-negative organisms other than 

Pseudomonas, Proteus, Klebsiella, and E coli. Isolates 

from same anatomical site or person were included as 

separate data points, only if these isolates are phenotypically different.

The terms “susceptible” and “resistant” are determined 

by standard Clinical and Laboratory Standards Institute (http://clsi.org/) guidelines, and criteria used by the 

WBAMC lab. Culture and sensitivities are reported as 

A Retrospective Analysis: Do Bacterial

 Culture and Sensitivity Data Support

 Empiric Use of Piperacillin-Tazobactam

 and Antipseudomonal Fluoroquinolones

 in Hospitalized Patients?

CPT Pulkit Saxena, MC, USA

CPT Ryan V. Burkhart, MC, USA

MAJ Craig R. Ainsworth, MC, USA

*WBAMC Cumulative Antimicrobial Susceptibility Report: 

1Jan2015-31Dec2015. Internal medical facility document not

readily accesible by the general public.
10 http://www.cs.amedd.army.mil/amedd_journal.aspx

“susceptible,” “intermediate,” or “resistant.” Susceptible 

is defined as having been found as susceptible based on 

reported culture data. Given that intermediate sensitivities indicate the level of antibiotic needed to achieve 

the maximum inhibitory concentration approaches or 

exceeds the level of antibiotic that can ordinarily be 

achieved,8

 “resistant” included sensitivities reported as 

intermediate or resistant.

Over a 6-month period, 64 Pseudomonas isolates that 

were sensitive or resistant to levofloxacin, ciprofloxacin, and piperacillin-tazobactam were identified. The 

cultures that were identified as resistant to Piperacillintazobactam were then further evaluated for susceptibility to levofloxacin or ciprofloxacin.

Results

A total of 64 isolates of Pseudomonas were identified 

during a 6-month period. Of these, 32 were from urine, 

11 from sputum, 12 from wound cultures, 3 from blood, 

and 6 from body fluid cultures. Of the cultures, 57 isolates were of Pseudomonas auerginosa and 7 isolates of 

Pseudomonas putida.

Of the 64 isolates of Pseudomonas identified, 90.6% 

(58/64) of isolates were susceptible to piperacillintazobactam, 66.1% (42/64) to levofloxacin, and 67.2% 

(47/64) susceptible to ciprofloxacin. The results are 

graphically represented in the Figure. Four of the isolates were multidrug resistant organisms resistant to all 

fluoroquinolones and beta-lactams. Of the 6 isolates resistant to piperacillin-tazobactam, none of those isolates 

were susceptible to fluoroquinolones.

Comment

Our initial hypothesis questioning the efficacy of empiric 

double coverage of suspected 

pseudomonal infections was 

confirmed by our 6-month retrospective review. None of the 

64 isolates cultured were resistant to piperacillin-tazobactam 

but sensitive to fluoroquinolones. This suggests there is no 

additional coverage or benefit 

conferred with empiric Pseudomonas double coverage 

with an antipseudomonal beta-lactam and an antipseudomonal fluoroquinolone in our hospital population. 

Fluoroquinolone use has associated with adverse effects 

including QT prolongation, photoxicity, tendon rupture, gastrointestinal discomfort, headache, confusion, 

and delirium.9

 These side effects, coupled with the fact 

that no antibacterial coverage improvement is achieved, 

would indicate that double coverage for suspected Pseudomonal infection within our hospital patient population 

would produce more harm than benefit.

The resistance of Pseudomonas isolates to fluoroquinolones when concomitantly resistant to piperacillintazobactam is unsurprising when examining the mechanism by which resistance of the bacteria is developed. 

Fluoroquinolone resistance occurs with mutations to the 

AmpR gene that negatively regulate the Mex-EF-OprN 

efflux which can pump out fluoroquinolones, or changes 

in the quinolone target of type II topoisomerase or type 

IV topoisomerase. Beta-lactam resistance is also mediated in part by the AmpR gene by positively regulating 

AmpC production of beta-lactamase. AmpR is a major 

part of Pseudomonas genome, and is one of the few 

genes that may confer resistance to multiple antibiotic 

classes, including beta-lactams and fluoroquinolones.10

Although this study meets the 30-isolate standard set by 

the Clinical and Laboratory Standards Institute M39-A2 

recommendations for cumulative antiobiogram preparation,11 the study could be improved by an increased sample size, either through duration of retrospective review 

or enrollment of a larger population pool from which to 

extract Pseudomonas isolates. Also, future studies may 

seek to identify which antibiotics can confer the greatest additional antibacterial coverage in the setting of resistance to antibiotics used for empiric therapy, thereby 

creating a double coverage regimen that would provide 

benefit to the patient.

This study brings to the forefront inappropriate antibiotic 

use for a common hospital 

infection. Previously an afterthought, this empiric double coverage can lead to the 

emergence of new multidrug 

resistant antibiotics,12 as well as 

exposing a patient to a medication with significant side effects with no concurrent medical advantage in therapy. Based 

on our institution’s culture 

data, we advocate that each 

institution reevaluate the empiric double coverage of 

gram-negative bacteria with the addition of an antipseudomonal fluoroquinolone or amino-glycoside to an 

antipseudomonal beta-lactam based on their specific 

patient subset.

DO BACTERIAL CULTURE AND SENSITIVITY DATA SUPPORT EMPIRIC USE OF PIPERACILLIN-TAZOBACTAM 

AND ANTIPSEUDOMONAL FLUOROQUINOLONES IN HOSPITALIZED PATIENTS?

2 http://www.cs.amedd.army.mil/amedd_journal.aspx

3VXVFHSWLEOH ́3LQWHUPHGLDWH ́RU3UHVLVWDQW ́6XVFHSWLEOH

LVGH¿QHGDVKDYLQJEHHQIRXQGDVVXVFHSWLEOHEDVHGRQ

UHSRUWHGFXOWXUHGDWD*LYHQWKDWLQWHUPHGLDWHVHQVLWLYLWLHV LQGLFDWH WKH OHYHO RI DQWLELRWLF QHHGHG WR DFKLHYH

WKH PD[LPXP LQKLELWRU\ FRQFHQWUDWLRQ DSSURDFKHV RU

H[FHHGV WKH OHYHO RI DQWLELRWLF WKDW FDQ RUGLQDULO\ EH

DFKLHYHG

3UHVLVWDQW ́LQFOXGHGVHQVLWLYLWLHVUHSRUWHGDV

LQWHUPHGLDWHRUUHVLVWDQW

2YHU D PRQWK SHULRG PseudomonasLVRODWHVWKDW

ZHUH VHQVLWLYH RU UHVLVWDQW WR OHYRÀR[DFLQ FLSURÀR[DFLQ DQG SLSHUDFLOOLQWD]REDFWDP ZHUH LGHQWL¿HG 7KH

FXOWXUHVWKDWZHUHLGHQWL¿HGDVUHVLVWDQWWR3LSHUDFLOOLQ

WD]REDFWDPZHUHWKHQIXUWKHUHYDOXDWHGIRUVXVFHSWLELOLW\WROHYRÀR[DFLQRUFLSURÀR[DFLQ

RESULTS

$WRWDO RI LVRODWHV RIPseudomonas ZHUHLGHQWL¿HG

GXULQJDPRQWKSHULRG2IWKHVHZHUHIURPXULQH

IURPVSXWXPIURPZRXQGFXOWXUHVIURPEORRG

DQGIURPERG\ÀXLGFXOWXUHV2IWKHFXOWXUHVLVRODWHVZHUHRIPseudomonas auerginosaDQGLVRODWHVRI

Pseudomonas putida

2I WKH  LVRODWHV RI Pseudomonas LGHQWL¿HG 

 RI LVRODWHV ZHUH VXVFHSWLEOH WR SLSHUDFLOOLQ

WD]REDFWDP   WR OHYRÀR[DFLQ DQG 

 VXVFHSWLEOH WR FLSURÀR[DFLQ 7KH UHVXOWV DUH

JUDSKLFDOO\ UHSUHVHQWHG LQ WKH )LJXUH )RXU RI WKH LVRODWHVZHUHPXOWLGUXJUHVLVWDQWRUJDQLVPVUHVLVWDQWWRDOO

ÀXRURTXLQRORQHVDQGEHWDODFWDPV2IWKHLVRODWHVUHVLVWDQWWRSLSHUDFLOOLQWD]REDFWDPQRQHRIWKRVHLVRODWHV

ZHUHVXVFHSWLEOHWRÀXRURTXLQRORQHV

COMMENT

2XU LQLWLDO K\SRWKHVLV TXHVWLRQLQJ WKH HI¿FDF\ RI HPSLULF

GRXEOH FRYHUDJH RI VXVSHFWHG

SVHXGRPRQDO LQIHFWLRQV ZDV

FRQ¿UPHG E\ RXU PRQWK UHWURVSHFWLYH UHYLHZ 1RQH RIWKH

 LVRODWHV FXOWXUHG ZHUH UHVLVWDQW WR SLSHUDFLOOLQWD]REDFWDP

EXW VHQVLWLYH WR ÀXRURTXLQRORQHV7KLVVXJJHVWVWKHUHLVQR

DGGLWLRQDO FRYHUDJH RU EHQH¿W

FRQIHUUHG ZLWK HPSLULF Pseudomonas GRXEOH FRYHUDJH ZLWK DQ DQWLSVHXGRPRQDO

EHWDODFWDPDQGDQDQWLSVHXGRPRQDOÀXRURTXLQRORQHLQ

RXU KRVSLWDO SRSXODWLRQ)OXRURTXLQRORQH XVH KDVDVVRFLDWHGZLWK DGYHUVH HIIHFWVLQFOXGLQJ47 SURORQJDWLRQ

SKRWR[LFLW\WHQGRQUXSWXUHJDVWURLQWHVWLQDOGLVFRPIRUW

KHDGDFKHFRQIXVLRQDQGGHOLULXP

7KHVHVLGHHIIHFWV

FRXSOHGZLWKWKHIDFWWKDWQRDQWLEDFWHULDOFRYHUDJHLPSURYHPHQWLVDFKLHYHGZRXOGLQGLFDWHWKDWGRXEOHFRYHUDJH IRU VXVSHFWHGPseudomonalLQIHFWLRQZLWKLQ RXU

KRVSLWDO SDWLHQW SRSXODWLRQ ZRXOG SURGXFH PRUH KDUP

WKDQEHQH¿W

7KH UHVLVWDQFH RI Pseudomonas LVRODWHV WR ÀXRURTXLQRORQHV ZKHQ FRQFRPLWDQWO\ UHVLVWDQW WR SLSHUDFLOOLQ

WD]REDFWDPLVXQVXUSULVLQJZKHQH[DPLQLQJWKHPHFKDQLVP E\ZKLFK UHVLVWDQFH RIWKH EDFWHULDLV GHYHORSHG

)OXRURTXLQRORQHUHVLVWDQFHRFFXUVZLWKPXWDWLRQVWRWKH

$PS5JHQHWKDWQHJDWLYHO\UHJXODWHWKH0H[()2SU1

HIÀX[ZKLFKFDQSXPSRXWÀXRURTXLQRORQHVRUFKDQJHV

LQWKHTXLQRORQHWDUJHWRIW\SH,,WRSRLVRPHUDVHRUW\SH

,9WRSRLVRPHUDVH%HWDODFWDP UHVLVWDQFHLVDOVRPHGLDWHGLQSDUWE\WKH$PS5JHQHE\SRVLWLYHO\UHJXODWLQJ

$PS&SURGXFWLRQRIEHWDODFWDPDVH$PS5LVDPDMRU

SDUW RI Pseudomonas JHQRPH DQG LV RQH RI WKH IHZ

JHQHVWKDWPD\FRQIHU UHVLVWDQFHWRPXOWLSOHDQWLELRWLF

FODVVHVLQFOXGLQJEHWDODFWDPVDQGÀXRURTXLQRORQHV

$OWKRXJKWKLVVWXG\PHHWVWKHLVRODWHVWDQGDUGVHWE\

WKH&OLQLFDODQG/DERUDWRU\6WDQGDUGV,QVWLWXWH0$

UHFRPPHQGDWLRQVIRUFXPXODWLYHDQWLRELRJUDPSUHSDUDWLRQ11WKHVWXG\FRXOGEHLPSURYHGE\DQLQFUHDVHGVDPSOHVL]HHLWKHUWKURXJKGXUDWLRQRIUHWURVSHFWLYHUHYLHZ

RUHQUROOPHQWRIDODUJHUSRSXODWLRQSRROIURPZKLFKWR

H[WUDFWPseudomonasLVRODWHV$OVRIXWXUHVWXGLHVPD\

VHHNWRLGHQWLI\ZKLFKDQWLELRWLFVFDQFRQIHUWKHJUHDWHVWDGGLWLRQDODQWLEDFWHULDOFRYHUDJHLQWKHVHWWLQJRIUHVLVWDQFHWRDQWLELRWLFVXVHGIRUHPSLULFWKHUDS\WKHUHE\

FUHDWLQJDGRXEOHFRYHUDJHUHJLPHQWKDWZRXOGSURYLGH

EHQH¿WWRWKHSDWLHQW

7KLVVWXG\EULQJVWRWKHIRUHIURQW

LQDSSURSULDWH DQWLELRWLF XVH IRU

D FRPPRQ KRVSLWDO LQIHFWLRQ

3UHYLRXVO\DQDIWHUWKRXJKWWKLV

HPSLULF GRXEOH FRYHUDJH FDQ

OHDG WR WKH HPHUJHQFH RI QHZ

PXOWLGUXJUHVLVWDQWDQWLELRWLFV12

DVZHOODVH[SRVLQJDSDWLHQWWRD

PHGLFDWLRQZLWKVLJQL¿FDQWVLGH

HIIHFWVZLWKQRFRQFXUUHQWPHGLFDODGYDQWDJHLQWKHUDS\%DVHG

RQRXULQVWLWXWLRQ¶VFXOWXUHGDWD

ZHDGYRFDWHWKDWHDFKLQVWLWXWLRQUHHYDOXDWHWKHHPSLULF

GRXEOHFRYHUDJHRIJUDPQHJDWLYHEDFWHULDZLWKWKHDGGLWLRQRIDQDQWLSVHXGRPRQDOÀXRURTXLQRORQHRUDPLQRJO\FRVLGHWRDQDQWLSVHXGRPRQDOEHWDODFWDPEDVHGRQ

WKHLUVSHFL¿FSDWLHQWVXEVHW

DO BACTERIAL CULTURE AND SENSITIVITY DATA SUPPORT EMPIRIC USE OF PIPERACILLIN-TAZOBACTAM 

AND ANTIPSEUDOMONAL FLUOROQUINOLONES IN HOSPITALIZED PATIENTS?

Pseudomonas sensitivity.

Note: Cipro is ciproÁo[acin =osyn is pipercilin

ta]obactam /evaTuin is levoÁo[acin.

% Sensitive

Cipro =osyn /evaTuin

67.2% 66.1%

90.6%

20

0

40

60

80

100
July – September 2017 11

THE ARMY MEDICAL DEPARTMENT JOURNAL

References

1. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines 

for management of severe sepsis and septic shock: 

2012. Crit Care Med. 2013;41(2):580-637.

2. Zilberberg MD, Shorr AF. Prevalence of multidrugresistant Pseudomonas aeruginosa and carbapenem-resistant Enterobacteriaceae among specimens 

from hospitalized patients with pneumonia and 

bloodstream infections in the United States from 

2000 to 2009. J Hosp Med 2013;8(10):559-563.

3. Kang C, Kim S, Park W, et al. Pseudomonas aeruginosa bacteremia: risk factors for mortality and 

influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Clin Infect Dis 

2003;37:745-751.

4. Garnacho-Montero J, Ortiz-Leyba C, Herrera-Melero I, et al. Mortality and morbidity attributable to inadequate empirical antimicrobial therapy in patients admitted to the ICU with sepsis: 

a matched cohort study. J Antimicrob Chemother 

2008;61(2):436-441.

5. Kumar A, Ellis P, Arabi Y, et al. Initiation of inappropriate antimicrobial therapy results in a fivefold 

reduction of survival in human septic shock. Chest 

2009;136(5):1237-1248.

6. Lueangarun S, Leelarasamee A. Impact of inappropriate empiric antimicrobial therapy on mortality 

of septic patients with bacteremia: a retrospective 

study. Interdiscip Perspect Infect Dis. 2012:756205. 

Available at: http://www.ncbi.nlm.nih.gov/pmc/ar 

ticles/PMC3419419/. Accessed September 15, 2016.

7. Mizuta M, Linkin DR, Nachamkin I, et al. Identification of optimal combinations for empirical dual antimicrobial therapy of Pseudomonas 

ae-ruginosa infection: potential role of a combination antibiogram. Infect Control Hosp Epidemiol 

2006;27:413-415.

8. Jorgensen JH, Ferraro MJ. Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clin Infect Dis 

2009;49(11):1749-1755. Available at: http://cid.ox 

fordjournals.org/content/49/11/1749. Accessed September 15, 2016.

9. Lipsky BA, Baker CA. Fluoroquinolone toxicity 

profiles: a review focusing on newer agents. Clin 

Infect Dis 1999;28(2):352-364. Available at: http:// 

cid.oxfordjournals.org/content/28/2/352. Accessed 

September 15, 2016.

10. Balasubramanian D, Schneper L, Merighi M, 

et al. 2012. The Regulatory Repertoire of Pseudomonas aeruginosa AmpC Beta-Lactamase Regulator AmpR Includes Virulence Genes. PLoS One 

7(3):e34067. Available at: http://journals.plos.org/ 

plosone/article?id=10.1371/journal.pone.0034067. 

Accessed September 15, 2016.

11. Clinical and Laboratory Standards Institute (CLSI). 

M39-A2: Analysis and Presentation of Cumulative Antimicrobial Susceptibility Test Data. 2nd ed. 

Wayne, PA: CLSI; 2006.

12. Hildreth CJ, Burke AE, Glass RM. Inappropriate Use of Antibiotics. JAMA. 2009;302(7):816. 

Available at: http://jama.jamanetwork.com/article. 

aspx?articleid=184426. Accessed September 15, 

2016.

Authors

CPT Saxena is an Internal Medicine Resident PostGraduate Year 3 at William Beaumont Army Medical 

Center, El Paso, Texas.

CPT Burkhart is a First Year Cardiology Fellow at the 

San Antonio Military Medical Center, San Antonio, 

Texas.

MAJ Ainsworth is the Medical Director, Burn Intensive Care Unit, US Army Institute of Surgical Research, 

Joint Base San Antonio-Fort Sam Houston, Texas.
12 http://www.cs.amedd.army.mil/amedd_journal.aspx

Colonization and infection with multidrug-resistant 

organisms, including extended spectrum β-lactamase 

(ESBL)-producing Enterobacteriaceae, are a global 

health problem and frequently complicate the care of 

wounded military personnel.1-6 Examination of surveillance cultures collected from wounded military personnel on admission to Landstuhl Regional Medical Center (LRMC) in Germany and military hospitals in the 

United States recovered 2,065 colonizing isolates. The 

predominant organisms were Escherichia coli and Klebsiella pneumoniae (50% and 9%, respectively), of which 

37% and 22% were ESBL-producers.7

Recently, the emergence of carbapenem-resistant Enterobacteriaceae (CRE) has become an additional threat 

associated with difficult-to-treat infections, high mortality rates, and potential for wide transmission.8-17 In 

an analysis of healthcare-associated infections in the 

United States, 2%, 2%, and 8% of E coli, Enterobacter spp, and K pneumoniae associated with surgical site 

infections were resistant to carbapenems, respectively.8

The rising prevalence of CREs has further complicated 

patient care in the military health system. Surveillance 

of Department of Defense (DoD)-managed medical facilities within the United States and overseas reported 

a mean annual CRE incident rate of 0.49 per 100,000 

patient-years. It was noted that the proportion of CRE 

increased from 0.033% in 2005 to 0.052% in 2012, with 

a steady rise in the proportion of carbapenem-resistant 

Klebsiella spp between 2005 and 2010.9

 Furthermore, 

approximately 1% of E coli and 8% of K pneumoniae 

isolates recovered from US military personnel and Afghan nationals treated at a deployed US military hospital in Afghanistan were carbapenem-resistant.18

As more combat casualties are surviving grievous injuries, the rate of trauma-related infections has increased.19

With complicated, polymicrobial wounds, the prevalence 

of multidrug-resistant organisms provides a challenge to 

clinicians treating wounded warriors. As carbapenems 

Low Prevalence of Carbapenem-Resistant

 Enterobacteriaceae Among Wounded

 Military Personnel

Katrin Mende, PhD Fatma Onmus-Leone, MS

Miriam L. Beckius, MPH COL Clinton K. Murray, MC, USA

Wendy C. Zera, BS David R. Tribble, MD, DrPH

Abstract

Multidrug-resistant organisms (MDROs) are a global health problem that affect both civilian and military populations. Among wounded warriors, MDROs further complicate the care of trauma-related infections, resulting 

in extended duration of hospitalization, as well as increased morbidity and mortality. During the wars in Iraq 

and Afghanistan, extended spectrum β-lactamase-producing Enterobacteriaceae were frequently isolated from 

wounded warriors. The potential emergence of difficult-to-treat carbapenem-resistant Enterobacteriaceae represented a serious challenge for clinicians. We examined carbapenem-resistant Enterobacteriaceae prevalence 

among wounded military personnel over a 6-year period (2009-2015). Among 4090 Enterobacteriaceae isolates 

collected, 16 (0.4%) were carbapenem-resistant, of which the majority was Enterobacter aerogenes (44%) 

followed by Klebsiella pneumoniae (37%), and Escherichia coli (19%). Five isolates (31%) collected from 2 

patients were carbapenemase-producers with one associated with an infection. All 5 carbapenemase-producing 

isolates were resistant to all tested carbapenems and each carried one carbapenemase gene (4 with blaKPC-3 

and 1 with blaNDM-1). Overall, although a large number of Enterobacteriaceae isolates were collected, only a 

small proportion was carbapenem-resistant and data indicate a lack of a cluster. Due to these limited numbers, 

it is difficult to make any conclusions regarding the association between carbapenem resistance, antibiotic exposure, and clinical outcomes.

Disclaimer: The views expressed are those of the authors and do not necessarily reflect the official views of the Uniformed Services 

University of the Health Sciences, Henry M. Jackson Foundation for the Advancement of Military Medicine, the National Institutes of 

Health or the Department of Health and Human Services, Walter Reed Army Institute of Research, Brooke Army Medical Center, the 

US Army Medical Department, the US Army Office of the Surgeon General, the Department of Defense or the Departments of the Army, 

Navy or Air Force. Mention of trade names, commercial products, or organization does not imply endorsement by the US Government.
July – September 2017 13

are often used to treat gram-negative infections resistant 

to broad-spectrum antibiotics, the emergence of CREs 

is a cause for concern. As a result, we determined the 

prevalence of CREs among wounded military personnel 

and evaluated carbapenem resistance mechanisms.

Methods

As part of the US DoD-Department of Veterans Affairs, 

Trauma Infectious Disease 

Outcomes Study (TIDOS),19

isolates were collected from 

military personnel injured during deployment and medically 

evacuated to LRMC before being transferred to a participating 

military hospital in the United 

States (the Walter Reed National Military Medical Center* or 

San Antonio Military Medical 

Center†). All collected isolates 

were stored in a microbiological repository. Our analysis was 

restricted to Enterobacteriaceae 

isolates collected between June 

1, 2009, and April 31, 2015. Isolates were classified as infecting 

if they were recovered from infection work-ups. Surveillance 

specimens were obtained from 

groin/axilla swabs performed 

within 2 days of hospital admission either at LRMC or the participating military hospitals in the United States. Multidrug resistance was defined as resistance to at least 3 of 

4 antibiotic classes, ESBL production, or carbapenemase 

production.20 For the purpose of our study, carbapenem 

resistance was defined as resistance to all carbapenems 

tested (ie, meropenem, imipenem, doripenem, and ertapenem). Information related to infections, treatment, 

and outcomes was retrieved from the TIDOS infectious 

disease module,19 which supplements the Department of 

Defense Trauma Registry.21

Isolate identities and antimicrobial susceptibilities were 

determined utilizing the BD Phoenix automated microbiology system and NMIC/ID-304 panels (BD Biosciences, Sparks, MD). As the BD Phoenix system does not 

report susceptibility results for certain bacteria/antibiotic combinations, E-test was also performed for all carbapenems.22 Pulsed-field gel electrophoresis (PFGE) was 

conducted for genotyping in accordance with standard 

practices. Three multiplex PCRs for the detection of carbapenemase genes were performed using previously described primers (Table 1).23 The PCRs were carried out 

with the following conditions: 

5 minutes at 94oC, 30 cycles of 

30 seconds at 94oC, 40 seconds 

at 56oC, and 50 seconds at 72oC, 

followed by 5 minutes at 72oC.

The Neo-Rapid CARB Kit 

(Rosco Diagnostica, Taastrup, 

Denmark) was used to identify carbapenemase-producing 

isolates, which were sent to 

the Multidrug-Resistant Organism Repository and Surveillance Network (MRSN) 

for whole genome sequencing 

using the Illumina MiSeq platform. Paired-end sequencing of 

short (550 bp) and mate-paired 

sequencing of long (2-10 kilobase [kb]) genomic fragments 

was performed to obtain finished bacterial genomes. The 

genes encoding carbapenem 

resistance were identified along 

with other antibiotic resistance 

genes by BLASTN analysis 

using comprehensive web-based microbial annotation 

resources and pipelines developed internally by MRSN.

Results

A total of 4090 Enterobacteriaceae isolates were collected from June 2009 through April 2015 (Table 2). Examination of antimicrobial susceptibility determined that 

1391 isolates (34%) were multidrug-resistant and 1302 

(32%) were classified as infecting. E coli was the most 

common (51%), followed by K pneumoniae (13%) and 

Enterobacter cloacae (12%).

A total of 141 isolates (3.4% of 4090) were resistant to 

at least one carabapenem; however, only 16 isolates 

(0.4% of 4090) were resistant to all tested carbapenems 

(100% resistant to doripenem, ertapenem, imipenem, 

and meropenem) with 50% associated with infections 

(Table 2). Enterobacter aerogenes (44%) was predominant, followed by K pneumoniae (37%) and E coli (19%). 

All carbapenem-resistant isolates were ESBL-producers. 

Twelve isolates (75%) were susceptible to amikacin, 9 

THE ARMY MEDICAL DEPARTMENT JOURNAL

*Prior to their consolidation to become the Walter Reed National 

Medical Center in September 2011, both the Walter Reed Army 

Medical Center and the National Naval Medical Center received 

patients from LRMC.

†The Brooke Army Medical Center became part of the newly established San Antonio Military Medical Center in September 

2011.

Table 1. PCR Oligonucleotide Primers for the Amplification of Carbapenemase Genes.

Gene Primer Sequence (5’-3’)

Product 

Size

(base pair)

blaIMP F: GGAATAGAGTGGCTTAAYTCTC

R: GGTTTAAYAAAACAACCACC 232

blaSPM F: AAAATCTGGGTACGCAAACG 

R: ACATTATCCGCTGGAACAGG 271

blaAIM F: CTGAAGGTGTACGGAAACAC

R: GTTCGGCCACCTCGAATTG 322

blaVIM F: GATGGTGTTTGGTCGCATA

R: CGAATGCGCAGCACCAG 390

blaOXA F: GCGTGGTTAAGGATGAACAC

R: CATCAAGTTCAACCCAACCG 438

blaGIM F: TCGACACACCTTGGTCTGAA

R: AACTTCCAACTTTGCCATGC 477

blaBIC F: TATGCAGCTCCTTTAAGGGC

R: TCATTGGCGGTGCCGTACAC 537

blaSIM F: TACAAGGGATTCGGCATCG

R: TAATGGCCTGTTCCCATGTG 570

blaNDM F: GGTTTGGCGATCTGGTTTTC

R: CGGAATGGCTCATCACGATC 621

blaDIM F: GCTTGTCTTCGCTTGCTAACG

R: CGTTCGGCTGGATTGATTTG 699

blaKPC F: CGTCTAGTTCTGCTGTCTTG

R: CTTGTCATCCTTGTTAGGCG 798
14 http://www.cs.amedd.army.mil/amedd_journal.aspx

(56%) to gentamicin, 5 (31%) to nitrofurantoin, 4 (25%) to tetracycline, and 1 

(6%) to tobramycin. All E aerogenes isolates were also susceptible to levofloxacin. The 16 isolates were recovered from 

7 deployed military personnel, of which 

6 were wounded in Afghanistan and one 

was injured in Naples, Italy. Except for 

one isolate obtained from LRMC, the 

carbapenem-resistant isolates were collected from surveillance swabs or clinical cultures obtained at military hospitals in the United States (94%). The proportion of the 16 isolates varied annually, 

with 3 (19%) collected in 2009 (June-December), 4 (25%) in 2010, none in 2011, 5 

(31%) in 2012, 3 (19%) in 2013, and one 

(6%) in 2014.

Examination of PFGE results showed 

that all patients carried different strains 

of the Enterobacteriaceae organisms, indicating a lack of a cluster. Furthermore, 

no patients carried two or more different strains within the same genus. When 

serial isolates collected from patients 

were assessed, there were no genotypic 

changes.

Five K pneumoniae isolates were carbapenemase-producers, of which 4 were 

from surveillance cultures (3 from groin and one rectum) and one was associated with a pneumonia (collected from bronchoalveolar lavage). In addition, 4 were 

serial isolates from one patient collected at 2 separate 

facilities, including the infecting isolate recovered at 

Walter Reed National Military Medical Center 3 days 

after the patient’s first positive groin culture at LRMC. 

One patient sustained a gunshot wound in the Afghanistan combat theater and the other was injured in a fall 

while stationed in Naples, Italy. The 5 carbapenemaseproducing K pneumoniae isolates were sent to MRSN 

for further testing and carbapenemase genes were identified. The PCR results found that one isolate carried the 

blaNDM gene, while the remaining 4 isolates from a 

single patient carried a blaKPC gene.

Whole genome sequencing of the 5 carbapenemase-producing K pneumoniae isolates revealed that the 4 serial 

isolates (from the same patient) were genetically identical and represented a single clone (collected in 2012). 

Specifically, the 4 isolates belonged to MLST ST-258 

and carried the carbapenemase gene blaKPC-3 on an 

approximately 78 kb plasmid that shared more than 98% 

homology to the previously described plasmid pKpQILLS6.24 The single isolate from another patient belonged 

to MLST ST-11 (collected in 2014) and carried the carbapenemase gene blaNDM-1 on an approximately 73.5 

kb plasmid that shared more than 95% homology to 

plasmid pS-300cz (Genbank Accession # KJ958927).

Two surveillance isolates amongst the serial carbapenemase-producing K pneumoniae isolates from one patient 

were collected prior to treatment with meropenem, suggesting that the strain already carried the resistance gene 

and that meropenem exposure did not induce carbapenem 

resistance. For this patient, a carbapenem-susceptible K 

pneumoniae, Staphylococcus aureus, and Acinetobacter 

baumannii-calcoaceticus complex isolates were associated with the same pneumonia along with the carbapenemase-producing K pneumoniae. Treating this patient 

with ampicillin-sulbactam, meropenem, and vancomycin cleared the infection during inpatient hospitalization.

Comment

Carbapenem-resistant Enterobacteriaceae are becoming 

more widespread in healthcare facilities in the United 

Table 2. Most Common Enterobacteriaceae Collected from Wounded Military 

Personnel (2009-2014) with a Focus on Carbapenem Resistance.

Organismsa Surveillance (%) Infecting (%) Total (%)

Escherichia coli 1608 (57.7) 495 (38.0) 2103 (51.4)

Resistant to ≥1 carbapenem 12 (0.7) 9 (1.8) 21 (1.0)

Carbapenem-resistant E coli b 0 3 (0.6) 3 (0.1)

Klebsiella pneumoniae 391 (14.0) 150 (11.5) 541 (13.2)

Resistant to ≥1 carbapenem 15 (3.8) 7 (4.7) 22 (4.1)

Carbapenem-resistant 

K pneumoniae b

5 (1.3) 1 (0.7) 6 (1.1)

Enterobacter cloacae 227 (8.1) 284 (21.8) 511 (12.5)

Resistant to ≥1 carbapenem 6 (2.6) 6 (2.1) 12 (2.3)

Carbapenem-resistant E cloacae b 0 0 0

Enterobacter aerogenes 232 (8.3) 125 (9.6) 357 (8.7)

Resistant to ≥1 carbapenem 17 (7.3) 20 (16.0) 37 (10.4)

Carbapenem-resistant

E aerogenes b

3 (1.3) 4 (3.2) 7 (2.0)

Serratia marcescens 76 (2.7) 120 (9.2) 196 (4.8)

Resistant to ≥1 carbapenem 3 (3.9) 14 (11.7) 17 (8.7)

Carbapenem-resistant

S marcescens b

0 0 0

Total Enterobacteriaceaec 2788 1302 4090

Total Enterobacteriaceae resistant

to ≥1 carbapenem

70 (2.5) 71 (5.5) 141 (3.4)

Total Carbapenem-Resistant 

Enterobacteriaceae b

8 (0.3) 8 (0.6) 16 (0.4)

Notes:

a. The percentage of carbapenem-resistant isolates for each organism is calculated using 

the totals for that specific organism.

b. Carbapenem-resistant Enterobacteriaceae are defined as being resistant to all tested 

carbapenems (ie, meropenem, imipenem, doripenem, and ertapenem).

c. Only the top 5 organisms are presented so the total for the overall Enterobacteriaceae 

is greater than the sum of the columns.

LOW PREVALENCE OF CARBAPENEM-RESISTANT ENTEROBACTERIACEAE

AMONG WOUNDED MILITARY PERSONNEL
July – September 2017 15

THE ARMY MEDICAL DEPARTMENT JOURNAL

States and have been associated with high rates of mortality.8-11,25,26 While the rate of carbapenem resistance is 

still low, the rising prevalence is concerning. As a result, 

we examined isolates for carbapenem resistance collected from military personnel wounded during deployment in support of operations in Iraq and Afghanistan. 

Although a large number of Enterobacteriaceae isolates 

were collected from combat casualties over a study period of approximately 6 years, only 16 (0.4%) were carbapenem-resistant. The distribution of isolates across 

the study years and molecular typing findings indicate a 

lack of a carbapenem-resistant Enterobacteriaceae cluster with this wounded military population.

Prior to 2000, recovery of CREs was rare in the United 

States; however, within the past decade, an increase in 

the incidence of CREs has been observed. Specifically, 

according to the National Healthcare Safety Network, 

the proportion of CREs in US acute care hospitals rose 

from 1.2% in 2001 to 4.2% in 2011 with Klebsiella spp 

having the highest increases (1.6% to 10.4%, respectively).25 Localized hospital outbreaks have also been 

reported in multiple states, including New York, Colorado, Illinois, and West Virginia.26-31 It is notable that 

our analysis reports a lower proportion of CREs (0.4%) 

in combat casualties compared to findings from civilian 

US hospitals, and may be the result of environmental 

factors or the approach to infection control.

Nonetheless, the proportion of CREs in our analysis is 

higher than previous surveillance reports from DoDmanaged medical facilities (overall proportion of 0.055% 

over a period of 2005 to 2012). With regards to specific 

organisms, the proportion of carbapenem-resistant E coli, 

K pneumoniae, and Enterobacter spp (E aerogenes and E 

cloacae) in our study (0.14%, 1.11%, and 0.81%, respectively) is also higher compared to the prior surveillance 

reports (0.041%, 0.116%, and 0.163%, respectively).9

Following recognition of increased carbapenem resistance due to widespread transmission of the blaNDM-1 

gene, a military health system surveillance program 

was implemented in 2010, resulting in the screening 

by MRSN of all carbapenem-resistant isolates for the 

gene. Approximately 13 hospitals, including 5 in combat 

zones, submitted isolates for screening. In 2011, the first 

reported identification of the blaNDM-1 gene was identified in Providencia stuartii isolates recovered from an 

Afghan national burn patient treated at a US/coalition 

combat support hospital in Bagram, Afghanistan.32,33 A 

low number of carbapenem-resistant K pneumoniae isolates (4.2%) have also been collected from hospitals in 

Iraq; however, none were found to carry the blaNDM-1 

or blaKPC-3 genes.34

Five (0.1% of all Enterobacteriaceae isolates; 32% of 

CRE isolates) carbapenemase-producing K pneumoniae

isolates were identified in our study. The 5 carbapenemase-producing isolates were recovered from 2 patients 

and one isolate was associated with an infection (ie, 

pneumonia). All 5 isolates were resistant to all tested 

carbapenems and each isolate carried one carbapenemase gene, indicating that carbapenem resistance was 

due to the presence of the resistance genes. Specifically, 

4 isolates carried blaKPC-3 while blaNDM-1 was only 

identified with one isolate. The patient with the isolates 

carrying blaKPC-3 sustained injuries in Naples, Italy, and was treated initially at a Naples hospital. As a 

carbapenem-resistant ST258 K pneumoniae strain carrying blaKPC-3 has been previously reported in Italy,24

there is the potential that the carbapenemase-producing 

K pneumoniae isolates were acquired through hospital 

transmission by the injured service member. To the best 

of our knowledge, this is the first report of K pneumoniae isolates carrying blaNDM-1 recovered from military 

personnel wounded in Afghanistan.

Due to the low numbers of CREs in our study, it is difficult to analyze the association between carbapenem 

resistance, antibiotic exposure, and clinical outcomes. 

It is also difficult to draw any conclusions regarding 

transmission patterns of CREs in this patient population. Nevertheless, as CREs are becoming widespread 

in both civilian and military health systems, surveillance should continue.

Acknowledgments

We are indebted to the Infectious Disease Clinical Research Program Trauma Infectious Disease Outcomes 

Study team of clinical coordinators, microbiology technicians, data managers, clinical site managers, and administrative support personnel for their tireless hours to 

ensure the success of this project.

Support for this work (IDCRP-024) was provided by the 

Infectious Disease Clinical Research Program, a DoD 

program executed through the Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics. This project has been 

funded by the Global Emerging Infections Surveillance 

and Response System, a Division of the Armed Forces 

Health Surveillance Center and the National Institute of 

Allergy and Infectious Diseases, National Institutes of 

Health, under Inter-Agency Agreement Y1-AI-5072, and 

the Department of the Navy under the Wounded, Ill, and 

Injured Program.

The sponsor of this study had no role in the study design, data analysis and/or interpretation, or writing the 

manuscript. The corresponding author had full access to 

the data and had final responsibility for the decision to 

submit for publication.
16 http://www.cs.amedd.army.mil/amedd_journal.aspx

References

1. Hospenthal DR, Crouch HK, English JF, et al. Multidrug-resistant bacterial colonization of combatinjured personnel at admission to medical centers 

after evacuation from Afghanistan and Iraq. J 

Trauma. 2011;71(suppl 1):S52-S57.

2. Mende K, Beckius ML, Zera WC, et al. Phenotypic 

and genotypic changes over time and across facilities of serial colonizing and infecting Escherichia 

coli isolates recovered from injured service members. J Clin Microbiol. 2014;52:3869-3877.

3. Murray CK, Roop SA, Hospenthal DR, Dooley 

DP, Wenner K, Hammock J, Taufen N, Gourdine 

E. Bacteriology of war wounds at the time of injury. 

Mil Med. 2006;171:826-829.

4. Hospenthal DR, Crouch HK, English JF, et al. 

Response to infection control challenges in the 

deployed setting: Operations Iraqi and Enduring 

Freedom. J Trauma. 2010;69(suppl 1):S94-S101.

5. Keen EF III, Murray CK, Robinson BJ, Hospenthal DR, Co EM, Aldous WK. Changes in the incidences of multidrug-resistant and extensively 

drug-resistant organisms isolated in a military 

medical center. Infect Control Hosp Epidemiol. 

2010;31:728-732.

6. Scott P, Deye G, Srinivasan A, et al. An outbreak 

of multidrug-resistant Acinetobacter baumanniicalcoaceticus complex infection in the US military 

health care system associated with military operations in Iraq. Clin Infect Dis. 2007;44:1577-1584.

7. Weintrob AC, Murray CK, Lloyd BA, et al. Active 

surveillance for asymptomatic colonization with 

multidrug-resistant gram negative bacilli among 

injured service members - a three year evaluation. 

MSMR. 2013;20:17-22.

8. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcareassociated infections: summary of data reported to 

the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. 

Infect Control Hosp Epidemiol. 2013;34:1-14.

9. Lesho EP, Clifford RJ, Chukwuma U, et al. Carbapenem-resistant Enterobacteriaceae and the correlation between carbapenem and fluoroquinolone 

usage and resistance in the US military health system. Diagn Microbiol Infect Dis. 2015;81:119-125.

10. Falagas ME, Lourida P, Poulikakos P, Rafailidis PI, 

Tansarli GS. Antibiotic treatment of infections due 

to carbapenem-resistant Enterobacteriaceae: systematic evaluation of the available evidence. Antimicrob Agents Chemother. 2014;58:654-663.

11. Falagas ME, Tansarli GS, Karageorgopoulos DE, 

Vardakas KZ. Deaths attributable to carbapenemresistant Enterobacteriaceae infections. Emerg Infect Dis. 2014;20:1170-1175.

12. Doi Y, Paterson DL. Carbapenemase-producing 

Enterobacteriaceae. Semin Respir Crit Care Med. 

2015;36:74-84.

13. Lazarovitch T, Amity K, Coyle JR, et al. The complex epidemiology of carbapenem-resistant Enterobacter infections: a multicenter descriptive analysis. 

Infect Control Hosp Epidemiol. 2015;36:1283-1291.

14. Kim SR, Rim CB, Kim Y, et al. Four cases of carbapenem-resistant Enterobacteriaceae infection 

from January to March in 2014. Korean J Fam Med. 

2015;36:191-194.

15. Guh AY, Bulens SN, Mu Y, et al. Epidemiology of carbapenem-resistant Enterobacteriaceae in 7 US communities, 2012-2013. JAMA. 

2015;314:1479-1487.

16. Mayer CL, Haley VB, Giardina R, Hazamy PA, 

Tsivitis M, Knab R, Lutterloh E. Lessons learned 

from initial reporting of carbapenem-resistant Enterobacteriaceae in New York State hospitals, 2013-

2014. Am J Infect Control. 2016;44:131-133.

17. Deutsch RF, Ross JW, Nailor MD. Carbapenem-resistant Enterobacteriaceae: a case series 

of infections at Hartford Hospital. Conn Med. 

2015;79:269-275.

18. Sutter DE, Bradshaw LU, Simkins LH, et al. High 

incidence of multidrug-resistant gram-negative 

bacteria recovered from Afghan patients at a deployed US military hospital. Infect Control Hosp 

Epidemiol. 2011;32:854-860.

19. Tribble DR, Conger NG, Fraser S, et al. Infection-associated clinical outcomes in hospitalized medical 

evacuees after traumatic injury: trauma infectious 

disease outcome study. J Trauma. 2011;71:S33-S42.

20. Centers for Disease Control and Prevention. The 

National Healthcare Safety Network (NHSN) 

Manual. Patient safety component. Protocol multidrug-resistant organism and Clostridium difficile 

infection (MDRO/CDI) module. 2016. Available 

at: https://www.cdc.gov/nhsn/pdfs/pscmanual/pcsmanual_current.pdf.

21. Eastridge BJ, Jenkins D, Flaherty S, Schiller H, 

Holcomb JB. Trauma system development in a theater of war: experiences from Operation Iraqi Freedom and Operation Enduring Freedom. J Trauma. 

2006;61:1366-1372.

22. Clinical and Laboratory Standards Institute. Analysis and Presentation of Cumulative Antimicrobial 

Susceptibility Test Data; Approved Guideline – 

Third Edition. 2009. CLSI document M39-A3. 

Wayne, PA. Available at: http://clsi.org/. 

23. Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase 

genes. Diagn Microbiol Infect Dis. 2011;70:119-123.

LOW PREVALENCE OF CARBAPENEM-RESISTANT ENTEROBACTERIACEAE

AMONG WOUNDED MILITARY PERSONNEL
July – September 2017 17

THE ARMY MEDICAL DEPARTMENT JOURNAL

24. Villa L, Capone A, Fortini D, et al. Reversion to 

susceptibility of a carbapenem-resistant clinical 

isolate of Klebsiella pneumoniae producing KPC-3. 

J Antimicrob Chemother. 2013;68:2482-2486.

25. Centers for Disease Control and Prevention. Vital 

signs: carbapenem-resistant Enterobacteriaceae. 

MMWR Morb Mortal Wkly Rep. 2013;62(9):165-170.

26. Gupta N, Limbago BM, Patel JB, Kallen AJ. Carbapenem-resistant Enterobacteriaceae epidemiology and prevention. Clin Infect Dis. 2011;53:60-67.

27. Frias M, Tsai V, Moulton-Meissner H, Avillan J, 

Hunter J, Arwady MA, Epstein L. Notes from the 

field: New Delhi metallo-β-lactamase-producing 

Escherichia coli associated with endoscopic retrograde cholangiopancreatography-Illinois, 2013. 

MMWR Morb Mortal Wkly Rep. 2014;62:1051.

28. Gaviria D, Greenfield V, Bixler D, et al. Carbapenem-resistant Klebsiella pneumoniae associated 

with a long-term--care facilitiy---West Virginia, 2009--2011. MMWR Morb Mortal Wkly Rep. 

2011;60:1418-1420.

29. Pisney L, Barron M, Jackson S, et al. Notes from 

the field: Hospital outbreak of carbapenem-resistant Klebsiella pneumoniae producing New Delhi 

metallo-beta-lactamase-Denver, Colorado, 2012. 

MMWR Morb Mortal Wkly Rep. 2013;62:108.

30. Epstein L, Hunter JC, Arwady MA, et al. New Delhi metallo-beta-lactamase-producing carbapenemresistant Escherichia coli associated with exposre 

to duodenoscopes. JAMA. 2014;312:1447-1455.

31. Bratu S, Landman D, Haag R, Recco R, Eramo A, 

Alam M, Quale J Rapid spread of carbapenem-resistant Klebsiella pneumoniae in New York City: A 

new threat to our antibiotic armamentarium. Arch 

Intern Med. 2005;165:1430-1435.

32. Storey SA, McGann PT, Lesho EP, Waterman PE. 

Notes from the field: detection of blaNDM-1 carbapenem resistance in a clinical isolate of Providencia stuartii in a US/coalition medical facility

---Afghanistan, 2011. MMWR Morb Mortal Wkly 

Rep. 2011;60(22):756.

33. McGann P, Hang J, Clifford RJ, et al. Complete 

sequence of a novel 178-kilobase plasmid carrying 

blaNDM-1 in a Providencia stuartii strain isolated in Afghanistan. Antimicrob Agents Chemother. 

2012;56:1673-1679.

34. Al Sehlawi ZS, Almohana AM, AlThabab AA. Occurrence and detection of carbapenemase-producing Klebsiella pneumoniae clinical isolates in Najaf 

hospitals. Al-Kufa J Biol 2013;5:e321.

Authors

This report was prepared by the listed authors on behalf of 

the Infectious Disease Clinical Research Program Trauma 

Infectious Disease Outcomes Study Group:

Dr Mende is the Director of the Molecular Biology 

Laboratory for the Infectious Disease Clinical Research 

Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health 

Sciences (Bethesda, Maryland), at the San Antonio 

Military Medical Center, Joint Base San Antonio-Fort 

Sam Houston, Texas. Dr Mende is also employed by the 

Henry M. Jackson Foundation for the Advancement of 

Military Medicine, Inc, Bethesda, Maryland.

Ms Beckius is with the Molecular Biology Laboratory at 

the San Antonio Military Medical Center, Joint Base San 

Antonio-Fort Sam Houston, Texas.

Ms Zera is with Molecular Biology Laboratory for the Infectious Disease Clinical Research Program, Department 

of Preventive Medicine and Biostatistics, Uniformed 

Services University of the Health Sciences (Bethesda, 

Maryland), at the San Antonio Military Medical Center, 

Joint Base San Antonio-Fort Sam Houston, Texas. Ms 

Zera is also employed by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, 

Bethesda, Maryland.

Ms Onmus-Leone is a research microbiologist at the 

Multidrug-resistant Organism Repository and Surveillance Network, Walter Reed Army Institute of Research, 

Silver Spring, Maryland.

COL Murray is Deputy Chief of the US Army Medical 

Corps and Medical Corps Specific Branch Proponent 

Officer, Army Medical Department and School, Health 

Readiness Center of Excellence, Joint Base San AntonioFort Sam Houston, Texas.

Dr Tribble is a Professor in the Department of Preventive Medicine and Biostatistics, Uniformed Services 

University of the Health Sciences, and the Science Director of the Infectious Disease Clinical Research Program, 

Uniformed Services University of the Health Sciences, 

Bethesda, Maryland.
18 http://www.cs.amedd.army.mil/amedd_journal.aspx

Psychiatric complaints are the fastest growing condition 

evaluated in emergency departments (ED) in the United 

States, increasing by 15% in the last decade.1

 In 2012, 

the Carl R. Darnall Army Medical Center Emergency 

Department (Fort Hood, Texas) saw 3,686 patients with 

a mental health concern as a chief complaint, making 

up 4.8% of the emergency department patients seen that 

year.

When the American military entered combat operations 

in Afghanistan and Iraq over 14 years ago, military 

medical departments and the American government 

were woefully unprepared to handle the psychological 

strains that would be placed on some 2.2 million troops 

(and their families) who were deployed over the years. A 

2008 report by the RAND Corporation estimated that 

more than 26% of troops have returned from these combat operations with mental health issues.2

 Along with 

the active duty service member, family members are 

seeking care for their own mental health issues in record 

numbers. In a 2002 study, Calhoun et al 3

 determined 

that partners of Veterans diagnosed with posttraumatic 

Effects of Mandatory Screening Labs

 in Directing the Disposition of the

 Apparently Healthy Psychiatric Patient

 in the Emergency Department

MAJ Karyn E. Kagel, SP, USA

CPT Meghan Smith, MC, USA

CPT Ilya V. Latyshenko, MC, USA

MAJ Christopher Mitchell, MC, USA

LTC Andrew Kagel, MC, USA

Abstract

Objective: To determine whether mandatory psychiatric admission laboratory tests yield results that change the 

disposition of a patient with primary psychiatric complaint from admission to a psychiatric service to admission to a medical service.

Methods: This was a single center retrospective cohort chart review study approved by the facility Institutional 

Review Board in which we used a records database maintained by the emergency department’s social workers 

to access the records of every patient that presented to our emergency department with a psychiatric chief complaint between the dates of December 1, 2011, and December 1, 2013. We focused on those that were admitted 

to either a psychiatric service or a medical service after a thorough evaluation by the department of social work 

and an emergency provider.

We applied our inclusion and exclusion criteria and reviewed the results of the mandatory psychiatric laboratory tests (complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, acetaminophen, 

aspirin, blood alcohol level, urinalysis, urine pregnancy test, urine drug screen) required for admission. Our 

independent variables were the compulsory psychiatric admission laboratory tests and our dependent variable 

was the admission to a medical service.

Results: Of 5,606 laboratory tests that were ordered and produced results for the 682 patients enrolled in our 

study, 51 results were considered clinically significant abnormal results, or results requiring treatment prior to 

psychiatric service admission, by the 2 reviewing emergency physicians. Only one of 682 psychiatric patients 

received a final disposition to a medical service based upon abnormal laboratory studies. That patient presented 

without any medical complaints but a chief complaint of “suicidal ideation,” and was found to have diabetic 

ketoacidosis. Based on our data, the probability that an abnormal laboratory test will result in a change in disposition is 1/682=0.1% (95% CI: 0.0% to 0.9%).

Conclusion: Patients presenting to the emergency department with a psychiatric chief complaint and no physical complaints, abnormal vital signs, or abnormal physical exam findings have less than 1% probability that an 

abnormal laboratory study will change their disposition from a psychiatric admission to a medical admission.
July – September 2017 19

THE ARMY MEDICAL DEPARTMENT JOURNAL

stress disorder (PTSD) experience more caregiver burden and have poorer psychological adjustment than partners of Veterans without PTSD. According to the Veteran’s Administration, partners of Veterans with PTSD 

reported lower levels of happiness and less satisfaction 

in their lives with about half reporting having felt “on 

the verge of a nervous breakdown.” 4

 The psychological 

stress and ongoing struggle for adequate treatment for 

these service members and their families have led to a 

strain on the mental health care system at many of our 

military bases. Several recently published reports attest 

that service members interested in accessing mental 

health care often face long wait lists.5

 Although these 

wait times can vary considerably from one behavioral 

health clinic to another; the Department of Defense 

Mental Health Task Force noted that delays of 30 days 

for an initial mental health appointment are not uncommon. This gap in care leads many service members and 

their families to seek help for their mental health concerns at local EDs.

For adult psychiatric cases that present to the ED and are 

otherwise medically stable, mandatory screening labs 

add unnecessary costs, use limited resources, and extend emergency department stays without changing the 

final disposition of the patient. The screening labs that 

are required for psychiatric admission are often based 

on expert opinion and medical screening performed by 

psychiatrists, who are not trained to evaluate emergency 

patients for medical conditions, rather than emergency 

providers.6

 In a retrospective study of 212 patients, Korn 

et al 7

 concluded that patients with a psychiatric chief 

complaint and normal physical exam findings may be 

safely referred to psychiatric services without the use of 

ancillary testing in the ED. In a similar study, Amin and 

Wang found that patients presenting to the ED with psychiatric chief complaints and benign histories and physical exams have a low likelihood of clinically significant 

laboratory findings.1

We conducted this study to determine if mandatory 

psychiatric admission laboratory tests yield results that 

change the disposition of a psychiatric patient from admission to a psychiatric service to admission to a medical service if that patient has presented with no medical complaints and no abnormal physical exam findings 

following examination by a trained emergency provider. 

We believe that if these mandatory laboratory results 

do not change the patient’s admitting service, the use 

of laboratory testing for psychiatric patients should 

be performed only at the discretion of the evaluating 

emergency medicine provider, thus increasing patient 

throughput in the department, reducing risks to patients 

and staff, and decreasing costs in the healthcare system.

Methods

Study Design

We conducted a single center retrospective cohort chart 

review study.

Setting

This study was conducted at a Level III trauma center 

supporting more than 42,000 military personnel and 

more than 145,000 family members, retirees, and civilian 

emergencies. In 2012, the ED evaluated 77,403 patients, 

with 3,686 (4.8%) of those patients being psychiatric patients. The department has a full time staff of 8 licensed 

social workers that evaluate all psychiatric complaints 

and assist the emergency clinicians with the assessment 

and placement of these patients. The medical center has 

a 15-bed inpatient psychiatric ward and a 5 bed ICU, as 

well as the ability to admit psychiatric patients to 3 offsite inpatient psychiatric treatment facilities.

Selection of Participants

We conducted this study using a database maintained 

by the medical center Department of Social Work of all 

emergent psychiatric patient evaluations and their dispositions. The database records a patient’s name, age, military unit, chief complaint, and disposition. Using SPSS 

software (IBM Inc, Armonk, NY) and the general rule 

for multivariate analysis, we powered our study for 30 

subjects enrolled per independent variable. With 9 independent variables, we determined that we would have to 

enroll at least 270 patients to adequately power our study. 

We performed a post hoc analysis to ensure adequate 

power. We trained an emergency medicine second-year 

resident to apply our specific inclusion and exclusion 

criteria to all patients in the database. In addition to her 

training, our research resident was blinded to our hypothesis and was not involved in the development of our 

study to avoid data collection bias. We instructed her to 

pull paper medical records if electronic medical records 

were not complete and informed her that we would perform quality checks on her data collection and recording. 

She spent 3 months enrolling study participants that met 

criteria. She began by narrowing our search to all patients aged 18-65 years who presented with a psychiatric 

chief complaint at the ED and were admitted to a psychiatric or medical service from the ED during the period 

December 1, 2011 through December 1, 2013. From this 

patient group, she reviewed each medical chart for any 

physical complaints, vital sign abnormalities, or abnormal history and physical exam findings recorded by the 

nurse or emergency department provider. Patients who 

were not strictly psychiatric patients were eliminated. 

After eliminating all patients with concurrent medical 

complaints or physical exam or vital sign abnormalities, 682 patients remained enrolled in the study. After 
20 http://www.cs.amedd.army.mil/amedd_journal.aspx

data was collected, the primary investigator randomly 

reviewed 3 patient charts from each month to ensure 

our data collector had enrolled appropriate patients and 

collected accurate data.

Outcome Measures

Our primary outcome measure was the percentage 

of dispositions that changed from psychiatric admission to medical admission as a result of clinically 

significant laboratory abnormalities in the mandatory screening laboratory tests. To determine the 

percentage, we divided the total number of patients 

who underwent each mandatory laboratory test by 

the total number of patients whose disposition was 

changed to a medical admission based on an abnormality in each laboratory test. We also tabulated the 

total number of clinically significant laboratory abnormalities, defined as laboratory results that would 

require treatment per our hospital protocols, prior 

to disposition, but did not change the disposition of 

the patient. Our hypothesis was that the mandatory 

psychiatric admission laboratory tests do not yield results that change the disposition of a psychiatric patient 

from admission to a psychiatric service to admission to 

a medical service.

Method of Measurement and Data Collection

After finding the 682 patients that met our inclusion and 

exclusion criteria, the data research resident removed 

personal identifications from the data and recorded the 

laboratory results for each patient into an Excel spreadsheet. Normal laboratory results were recorded as “normal,” and abnormal laboratory results were recorded as 

the actual laboratory value. If the research resident encountered missing electronic medical records, the paper 

hardcopy was pulled for review. Using this method, we 

had no incomplete charts or missing data points. The 

results of the mandatory psychiatric screening laboratory tests for the 682 study participants (complete blood 

count (CBC), comprehensive metabolic 

panel (CMP), thyroid stimulating hormone 

(TSH), acetaminophen (APAP), aspirin 

(ASA), blood alcohol level (BAL), urinalysis (UA), urine pregnancy test (UHCG), 

urine drug screen (UDS)) were reviewed 

separately by 2 independent board certified emergency physicians for abnormalities that were clinically significant enough 

to require treatment in the department according to the hospital psychiatric admission protocols. The reviewing physicians 

were blinded to any change in disposition 

that resulted from the laboratory tests and were not involved in the development or execution of this study in 

any way. This study was conducted under a protocol reviewed and approved by the Institutional Review Board 

and in accordance with the approved protocol.

RESULTS

Six hundred eighty-two subjects met our criteria and 

were enrolled in the study. All of the patients presented 

with a chief psychiatric complaint (ie, “life stress,” suicidal ideation, homicidal ideation, depression, anxiety), 

denied concurrent physical ailments, and had normal vital signs and nursing and provider assessments. Descriptive statistics of the subjects are presented in Figures 1 

and 2.

Of 5,606 laboratory tests ordered and results received 

for these patients (682 UA, CMP, BAL, TSH, ASA, 

CBC, UDS, APAP, and 150 UHCG), as shown in Table 

1, there were 59 that were considered clinically significant abnormal results by our 2 reviewing emergency 

physicians. These were laboratory values that, according to our hospital psychiatric admission criteria, would 

require treatment prior to psychiatric admission.

Thirty patients had abnormal UAs and were 

started on treatment for asymptomatic urinary tract infections prior to admission to 

psychiatry. Five patients had hypokalemia 

on their CMP and were treated with K-Dur 

and admitted to psychiatry. The other 2 abnormal CMPs showed elevated creatine for 

which the patients received IV fluids and 

the repeat laboratory values returned to 

normal prior to psychiatric admission. The 

7 patients with elevated BAL had repeat 

laboratory tests drawn until levels were 

under 100, meeting admission standards to psychiatry. 

Thyroxine free (free T4) levels were obtained on the 3 

Figure 1. Number of subjects by age group.

18-25 26-33 34-41 42-49 50-57 58-65

Age Group (years)

Number of Subjects

0

150

100

50

250

200

350

300

400

9 6

34

87

204

350

22%

78%

Figure 2. Percentages of 

subjects by gender.

Male Female

EFFECTS OF MANDATORY SCREENING LABS IN DIRECTING THE DISPOSITION OF THE

APPARENTLY HEALTHY PSYCHIATRIC PATIENT IN THE EMERGENCY DEPARTMENT
July – September 2017 21

THE ARMY MEDICAL DEPARTMENT JOURNAL

patients with abnormal TSH and results were normal, 

eliminating concern for acute thyroid abnormalities. 

These patients were cleared for psychiatric admission with recommendations for repeat laboratory work 

upon discharge. Finally, the patient with elevated ASA 

had serial ASA levels drawn in the emergency department to confirm a downward trend prior to psychiatric 

admission.

Of 682 psychiatric patients, only one received a final 

disposition to a medical service based upon abnormal 

laboratory studies, a probability of 1/682=0.1% (95% 

CI: 0.0% to 0.9%). That patient was a 43-year-old male 

who presented without any medical complaints but a 

chief complaint of “suicidal ideation.” This patient had 

an abnormal CMP (elevated glucose) and UA (glucose 

and ketones present) and was found, through his laboratory work, to have diabetic ketoacidosis (DKA). Upon 

diagnosis, he received IV fluids 

and insulin in the emergency department and was transferred to 

the intensive care unit. The probability that an abnormal laboratory test will result in a change in 

patient disposition is 1/682=0.1% 

(95% CI: 0.0% to 0.9%).

Using Fisher’s Exact Test, we 

found that there was a statistically 

significant difference in the change in 

patient disposition between an abnormal 

and normal CMP (P=.013) and an abnormal and normal UA (P=.047).

Because many of our laboratory tests had 

no abnormal results (CBC, UDS, APAP, 

UHCG), we decided to investigate if the 

probability of an abnormal finding was 

truly “zero” and, if not, what the estimated 

probability is for an abnormal result in one 

of those laboratory tests in the future. Using the Modified Wald Equation and the 

rule of three, among the tests for which 

there were no abnormal results, the estimated probability of an abnormal laboratory finding in the future was 0.4% to 0.7% 

for the CBC, UDS, and APAP, and 2.0% to 

3.1% (high limit of the 95% CI) for UHCG. 

This means that even though our data had 

some laboratory tests with no abnormal results, there is still a small probability that 

there will be abnormal results in future patients. The analysis results are presented in 

Table 2.

There were also laboratory tests for which there were 

abnormal results but no change in disposition (ASA, 

BAL, and TSH), and we estimated the probability of future abnormal results in those laboratory tests as well. 

Using the same Modified Wald Equation, we estimate 

the probability of a future abnormal result in the laboratory tests that already had abnormal results was up to 

1.8% (high limit of the 95% CI), presented in Table 3. 

This means that there is continued probability of these 

laboratory tests resulting abnormally, but this does not 

change the probability that these abnormal results will 

alter disposition in the future.

Comment

Due in part to the demand placed on emergency departments and the prevailing evidence that mandatory psychiatric laboratory tests do not alter a patient’s disposition, 

Table 1. Clinically significant abnormal laboratory tests and results that

changed disposition.

Laboratory Test

UA CMP BAL TSH ASA CBC UDS APAP UHCG

Number of laboratory 

tests ordered

682 682 682 682 682 682 682 682 150

Number of normal

laboratory tests

651 674 675 680 681 682 682 682 150

Number of clinically 

significant abnormal

laboratory tests

31 8 7 2 1 0 0 0 0

Number of dispositions changed due to

laboratory results

1 1 0 0 0 0 0 0 0

UA indicates urinalysis; CMP, complete metabolic panel; BAL, blood alcohol level; TSH, thyroid

stimulating hormone; ASA, aspirin; CBC, complete blood count; UDS, urine drug screen; APAP, 

acetaminophen; UHCG, urinary human chorionic gonadotropin.

Table 2. Estimated probability of a future significant abnormality in laboratory tests 

with no abnormal results.

N Abnormality Normal Probability of an

Abnormality Occurring

in the Future

95% CI Rule 

of

Three

CBC 682 0 682 0.0% 0.4% (-0.1% to 0.7%) 0.4%

APAP 682 0 682 0.0% 0.4% (-0.1% to 0.7%) 0.4%

UDS 682 0 682 0.0% 0.4% (-0.1% to 0.7%) 0.4%

UHCG 150 0 150 1.3% 1.8% (-0.5% to 3.1%) 2.0%

CBC indicates complete blood count; UDS, urine drug screen; APAP, acetaminophen; UHCG, urinary 

human chorionic gonadotropin.

Table 3. Estimated probability of a future significant abnormality in laboratory 

tests with abnormal results.

N Abnormality Normal Probability of an

Abnormality Occurring

in the Future

95% CI

BAL 682 7 675 1.0% (Modified Wald) 0.8% (0.3% to 1.8%)

TSH 682 2 680 0.3% (Modified Wald) 0.6% (0.0% to 1.2%)

ASA 682 1 681 0.1% (Modified Wald) 0.5% (-0.1% to 0.9%)

BAL indicates blood alcohol level; TSH, thyroid stimulating hormone; ASA, aspirin.
22 http://www.cs.amedd.army.mil/amedd_journal.aspx

the American College of Emergency Physicians (ACEP) 

created a clinical policy in 2005 that provided a Level B 

and two Level C recommendations (recommendations 

for patient management that may identify a particular 

strategy that reflect moderate clinical certainty) against 

the routine testing of clinically stable adults that present 

to the emergency department with psychiatric symptoms.8

 Despite these recommendations and the results 

from prior studies, clinical practice has not changed in 

most emergency departments which is, in part, due to 

poor communication between the emergency medicine 

providers and the accepting psychiatrists.

Our results validate the findings from prior studies, such 

as Korn et al,7

 Parmar et al,6 and Amin and Wang,1 in 

the military population. Our study demonstrates that 

these mandatory screening laboratory tests change the 

disposition in psychiatric patients with no physical complaint or abnormal physical exam findings less than 1% 

of the time (high end of 95% CI). With only one exception, none of the performed tests altered a patient’s 

disposition. Our study confirms that extensive screening laboratory tests for medically stable psychiatric patients are very unlikely to change the patient’s disposition. Medicine accepts a reasonable miss-rate order to 

avoid over-testing and unnecessary treatments. Many 

decision-making rules, such as pulmonary embolism 

rule-out criteria, accept the risk of missing a positive at 

anything below 2%. We believe that our results, which 

show a less than 1% probability in a change of disposition, demonstrate that forgoing mandatory screening 

laboratory tests in these stable psychiatric patients is allowing an acceptable level of risk. This risk is further 

mitigated due to these patients being admitted to a hospital psychiatric ward where they will continue to be 

monitored and can be transferred or reevaluated quickly 

if their presentation changes.

In analyzing the individual laboratory tests for clinically 

significant abnormal results, we found many laboratory 

results are often returned as “normal.” However, we 

know that “zero abnormal results” does not mean “zero 

risk,” so we determined the future probability of an abnormal result in those laboratory tests with no abnormal 

results (CBC, APAP, UDS, UHCG) in our study and 

found that, with the exception of the UHCG, there was 

less than a 1% estimated probability. This is a miss rate 

of an abnormal finding that we in the medical field can 

be comfortable with. This means that we can, essentially, stop ordering these tests in stable psychiatric patients 

with a less than 1% chance of missing a clinically significant abnormal result in the future. In the laboratory 

studies with abnormal results that did not alter a patient 

disposition (BAL, TSH, ASA), there is a less than 2% 

estimated probability of a future abnormal result. This 

is a miss rate that we can also be comfortable with, as 

none of these abnormalities ultimately change the patient disposition. This study suggests that these 6 laboratory tests can be safely eliminated from our battery of 

mandatory tests, as none of them altered the patient disposition and there is less than 2% estimated risk for any 

clinically significant abnormal results in future testing. 

The urine pregnancy test was only ordered on female 

patients and a positive result did not alter the disposition 

at our hospital as all inpatient psychiatric facilities are 

capable of treating pregnant patients. This laboratory 

result may direct a treatment plan for the psychiatrist 

but does not alter the disposition of our medically stable 

psychiatric patient. We suggest that the UHCG can be 

ordered by the psychiatrist once the patient is admitted 

rather than in the emergency department where it does 

not alter the patient course.

Again, focusing on the utility of individual laboratory 

tests, the only ones with abnormalities that required a 

change in disposition were the CMP and the UA. Both 

of these laboratory tests were positive for elevated glucose, and the results initiated the workup for DKA in the 

only patient with a disposition change. The reviewing 

physicians believe the CMP results were cause enough 

to alter the disposition, but the UA results did not, on 

their own, result in the disposition change. This patient 

was a new-onset diabetic with no previous workup or 

diagnosis of diabetes and he denied any physical symptoms throughout his ED course, even after he was told of 

his diagnosis and began emergency treatment. These 2 

laboratory results were significant and initiated a formal 

DKA workup due to the hyperglycemia found in each. 

These laboratory tests may be considered redundant or 

may be replaced by the finger-stick glucose test, which 

is much less expensive and faster to rule out DKA in 

the stable psychiatric patient. The non–life-threatening 

diagnoses found by these 2 laboratory tests were mild 

hypokalemia and asymptomatic urinary tract infections 

that required treatment prior to psychiatric admission, 

but add to our concerns for overtreatment of laboratory 

results in asymptomatic patients. From our results, we 

believe that the CMP and UA can be replaced by the 

finger-stick glucose testing to screen for hyperglycemia. With the elimination of these 2 laboratory tests, the 

probability of a disposition change will remain less than 

1% and risk continues to be mitigated as these patients 

are all admitted to the hospital and monitored for symptom changes.

Our results, which would suggest that we only need a 

finger-stick glucose test to ensure no disposition change 

in stable psychiatric patients, differ from those of 

EFFECTS OF MANDATORY SCREENING LABS IN DIRECTING THE DISPOSITION OF THE

APPARENTLY HEALTHY PSYCHIATRIC PATIENT IN THE EMERGENCY DEPARTMENT
July – September 2017 23

THE ARMY MEDICAL DEPARTMENT JOURNAL

Parmar et al 6 in which the laboratory results caught an 

acetaminophen overdose in a medically cleared patient. 

As a result, they recommended keeping the APAP level 

as a screen for suicidal patients.

With these results, a dialogue should begin within the 

hospital system, between the emergency and psychiatric departments, in the hopes of eliminating completely 

or reducing the number of mandatory tests required for 

a psychiatric admission. Because there is no standardized medical clearance for a psychiatric patient, it is 

important that each hospital system review the efficacy 

of the system they have in place. This study shows that 

extensive mandatory screening laboratory tests do not 

change the disposition of psychiatric patients presenting without medical complaint to a military hospital. In 

an era of fiscal limitations within the military and an 

emphasis on decreasing emergency department wait 

times, the departments of emergency medicine and psychiatry could use this study results, in conjunction with 

the 2005 guideline from ACEP and the results of prior 

studies on the matter, to streamline the process of psychiatric admissions within the military and reduce the 

medical screening laboratory tests required for medical 

clearance.

We hypothesized that a thorough history and physical 

exam would be sufficient to find an abnormality in a 

psychiatric patient without any medical complaints 

and that mandatory laboratory tests would not change 

the disposition. Our results show that, with one exception, history and physical exam alone can appropriately 

provide the disposition of medically stable psychiatric 

patients. Emergency providers and psychiatrists should 

work together to create appropriate testing strategies 

and admission criteria for psychiatric patients.

Limitations

Our study site had characteristics distinctive to the military in that our study population was a mean age of 28 

years and over 75% male. The population consisted of a 

relatively healthy active duty population and their family members. Our study site was also unique in that it 

had multiple inpatient psychiatric facilities that were 

able to readily accept our patients, including the inpatient psychiatric ward of the study hospital. This made 

admitting a psychiatric patient relatively less difficult. 

This population and psychiatric disposition resources 

may not reflect all other institutions and may be skewed 

to the military hospitals across the country, however 

the ability for an emergency provider to appropriately 

evaluate psychiatric patients for an underlying medical condition should be universal to emergency departments. We believe that our observations, with regard to 

mandatory testing of psychiatric patients with no physical complaint or abnormal physical exam finding, are 

applicable to multiple emergency department settings.

We performed a retrospective cohort chart review study 

in which we used a second year emergency department 

resident to review all of the patient charts and record 

data over the course of 3 months. We believe that by 

having a single data collector performing this task over 

a short period of time, we decreased the possibility of 

multiple interpretations of the data collection process 

and data recording. Our data collector was blinded to 

our hypothesis to decrease data collection bias. She was 

also informed that we would perform random inspections of her data to ensure accuracy.9

 We pulled paper 

records of all charts that were not complete in the electronic medical records to ensure complete data collection. We also reviewed records that spanned a 2-year 

time period, attempting to get a better long-term picture 

and increase our data points.

Because this was a retrospective review and we only 

had written documentation of the patient encounter, we 

had to trust that documentation as fact. In reviewing 

provider and nursing notes, occasional documentation 

errors were found with regards to normal vital signs and 

laboratory findings. Abnormal laboratory results were 

recorded as normal and abnormal vital signs were recorded as normal. This brings to light the limitations 

of a retrospective study and, while our data collector 

did her best to fully evaluate patient documentation, 

we must acknowledge that due to human error, not all 

documentation made in patient charts may be accurate. 

We could see when abnormal results were recorded as 

normal but we could not see if abnormal physical exam 

findings were recorded as normal; this is always a possibility and a risk when trusting retrospective charts.

Finally, in reviewing retrospective data, we could not 

see the order in which the patient evaluation process occurred. In our department, these mandatory laboratory 

tests may be ordered in triage, prior to an emergency 

provider’s evaluation, or by the provider after the bedside evaluation. If these laboratory tests are ordered in 

triage and results obtained prior to the physical evaluation, those results may guide some providers to a more 

focused and detailed history and physical examination 

with the possibility of discovering abnormalities, thereby excluding that patient from our study. Ideally, to truly 

test the emergency provider’s ability to find a medical 

abnormality in a stable psychiatric patient, the patient 

would be evaluated without the provider’s knowledge of 

the laboratory results so as not to guide the history and 

exam.
24 http://www.cs.amedd.army.mil/amedd_journal.aspx

A prospective validation study, ideally with a more varied patient population, is recommended to more broadly 

apply our findings to other practice centers. A large prospective multicenter study at military hospitals is needed to derive and validate a clinical decision-making rule 

that can be used across the Department of Defense and 

in similar populations for screening of psychiatric patients with no physical complaint.

CONCLUSION

Of 682 patients evaluated with a psychiatric chief complaint and no medical complaint of abnormal physical 

exam findings, one patient disposition was changed 

from psychiatric admission to medical admission based 

on laboratory results alone. Our study validates the findings of previous studies and indicates that these mandatory screening laboratory tests rarely alter a patient’s 

disposition after evaluation by an emergency trained 

provider. By eliminating these laboratory tests we accept a less than 1% miss rate. We believe this is further 

mitigated due to these patients all being admitted to the 

hospital.

References

1. Amin M, Wang J. Routine laboratory testing to 

evaluate for medical illness in psychiatric patients 

in the emergency department is largely unrevealing. West J Emerg Med. 2009;10(2):97-100.

2. Tanielian TL, Jaycox LH, eds. Invisible wounds of 

war: Psychological and Cognitive Injuries, Their 

Consequences, and Services to Assist Recovery. 

Santa Monica, CA: Rand Corporation; 2008.

3. Calhoun PS, Beckham JC, Bosworth HB. Caregiver burden and psychological distress in partners of 

veterans with chronic posttraumatic stress disorder. 

J Trauma Stress. 2002;15(3):205-212.

4. Kulka RA, Schlenger WE, Fairbank JA, et al. 

Trauma and the Vietnam War Generation: Report 

of Findings from the National Vietnam Veterans 

Readjustment Study. New York: Brunner/Mazel 

Inc; 1990.

5. Johnson SJ, Sherman MD, Hoffman JS, et al. The 

Psychological Needs of U.S. Military Service Members and Their Families: A Preliminary Report. 

Washington, DC: American Psychological Association Presidential Task Force on Military Deployment Services for Youth, Families, and Service 

Members; 2007.

6. Parmar P, Goolsby C, Udompanyanan K, et al. Value of mandatory screening studies in emergency 

department patients cleared for psychiatric admission. West J Emerg Med. 2012;13(5):388-393.

7. Korn CS, Currier GW, Henderson SO. “Medical 

clearance” of psychiatric patients without medical 

complaints in the emergency department. J Emerg 

Med. 2000;18:173-176.

8. Lukens TW, Wolf SJ, Edlow JA, et al. Clinical 

Policy: Critical Issues in the Diagnosis and 

Management of the Adult Psychiatric Patient in 

the Emergency Department. Ann Emerg Med. 

2006;47(1):79-84.

9. Worster A, Haines T. Advanced statistics: understanding medical record review (MRR) studies. 

Acad Emerg Med. 2004;11(2):187-192.

Authors

MAJ Kagel, LTC Kagel, and CPT Smith are with the Department of Emergency Medicine, Carl R. Darnall Army 

Medical Center, Fort Hood, Texas.

CPT Latyshenko is with the Department of Emergency 

Medicine, Womack Army Medical Center, Fort Bragg, 

North Carolina.

MAJ Mitchell is Regimental Surgeon, 3rd Cavalry Regiment, Fort Hood, Texas.

EFFECTS OF MANDATORY SCREENING LABS IN DIRECTING THE DISPOSITION OF THE

APPARENTLY HEALTHY PSYCHIATRIC PATIENT IN THE EMERGENCY DEPARTMENT
July – September 2017 25

Adverse childhood experiences (ACE) have long been 

recognized as antecedents to negative physical and mental health outcomes. Felitti and his colleagues, in their 

landmark ACE study,1

 discovered child maltreatment 

and household dysfunction to be associated with many 

of the leading causes of death in adults. Further reports 

from the ACE study linked childhood adversity to psychosocial problems that included suicide attempts,2

alcohol abuse,3

 intimate partner violence,4 depressive 

disorders,5

 hallucinations,6 and generally poorer mental 

health functioning.7

 Since the initial work of Felitti et 

al, others have contributed to the growing understanding of the long-term consequences of childhood trauma. 

A study of young adults from economically disadvantaged, urban communities revealed that those with a 

high rate of ACEs were more likely to experience depressive symptoms, use drugs and engage in antisocial 

behavior.8

 Since the advent of the all-volunteer service, 

increased percentages of service members, particularly 

males, have described personal ACEs.9

 This is reflected 

in the high prevalence of ACEs seen in Soldiers who 

sought treatment for a wide array of behavioral health 

disorders while deployed to a combat zone, with many 

reporting having experienced 3 or more types of adversity.10 Similarly, active duty Marines who reported 

a history of ACEs appeared to be at an increased risk 

for developing posttraumatic stress disorder after returning from a combat deployment.11 Additional studies have correlated childhood adversity with a lifetime 

onset of posttraumatic stress disorder, conduct disorder, 

substance use disorders, suicidal ideation, and anxiety.12-14 Furthermore, ACEs are believed to exacerbate 

the physical and psychological symptoms experienced 

by those with severe mental health disorders.15,16 Much 

of the research on ACEs has shown that the more adversity a child experiences, the more likely they will 

develop physical or psychosocial problems as an adult. 

Nevertheless, embedded in these findings is the revelation that not everyone who endures hardships early in 

life is destined to become psychosocially dysfunctional. 

This evidence suggests that some people become resilient in the face of adversity and emerge from childhood 

trauma to lead psychologically healthy and highly successful professional lives. Thus resilience, characterized 

by achieving positive outcomes despite severe threats to 

growth or adaptation,17 may mitigate the risk of developing the psychological distress and maladaptive behavior 

associated with ACEs. In fact, psychological resilience 

has been shown to protect against the risk of suicide related to childhood trauma and lessens the association 

between being emotionally neglected as a child and 

developing psychiatric symptoms as a young adult.18,19

Furthermore, homeless adolescents with a history of 

ACEs who perceived themselves as resilient were found 

less likely to engage in risky behavior, were less lonely 

and more hopeful.20 Becoming resilient can be achieved 

through various pathways.21 While innate factors and 

environmental influences undoubtedly contribute to resilience, the Kauai longitudinal study on the resilience 

and recovery of at-risk children discovered that relationships with supportive adults mitigate the vulnerabilities 

of adversity and facilitate positive outcomes as adults.22

Resilience and Relationships

The power of human connections to shape individual 

growth and development has been espoused by many 

theoretical perspectives, but none more so than attachment theory. According to John Bowlby, “Attachment 

behavior is any form of behavior that results in a person 

attaining or maintaining proximity to some other clearly 

identified individual who is conceived as better able to 

cope with the world.”23 Accordingly, becoming securely attached has been shown to be positively associated 

with resilience.24 Further support for the influence human relationships can exert in promoting, and in some 

cases restoring, healthy development can be found in the 

literature on resiliency in vulnerable populations. Research has established that older children who live under chronically adverse conditions tend to do better or 

recover more effectively when they have a relationship 

Resilience-Enhancing Relationships:

 What We Can Learn From Those With a

 History of Adverse Childhood Experiences

COL Derrick Arincorayan, MS, USA

Larry Applewhite, PhD

MAJ Matthew Garrido, MS, USA

CPT Victoria Cashio, MS, USA

CPT Meghan Bryant, MS, USA
26 http://www.cs.amedd.army.mil/amedd_journal.aspx

with a competent adult.25 Relatedly, Brooks proposed 

that developing caring relationships in schools, based 

on respect, encouragement, and attentiveness, may help 

young students elude the negative outcomes related to 

environmental threats.26 This idea is congruent with 

the finding that at-risk adolescents desire supportive 

relationships with adults that foster the formation of a 

self-identity grounded in resilience and competence.27

Furthermore, developing a sense of competence, a contributor to resilience, requires caring, competent adults 

to be actively involved in a child’s life.28 Importantly, 

resilience-enhancing relationships are not limited to primary caregivers. Extra-familial adults, such as teachers, 

coaches, clergy and mental health workers, have proven 

to be effective mentors that can serve as a protective 

factor for vulnerable children.29 This may partially explain how mothers who were abused as children were 

able to break the cycle of abuse after receiving emotional support from foster parents and others when they 

were younger.30 Although much resilience research focuses on children, a meta-analysis of the effectiveness of 

resilience-building programs conducted in occupational 

settings found many of the protective factors pertinent 

to children may also apply to adults and that direct resilience training is most beneficial,31 suggesting that 

relating to the “coach” or trainer can enrich the learning process. Additionally, caring relationships in the 

workplace boost resilience and can be transformative 

during times of organizational change.32 Interestingly, 

Laursen and Birmingham, in an ethnographic study of 

adolescents,33 identified the foundational attributes of a 

caring relationship to include trust, attention, empathy, 

availability, affirmation, respect, and virtue. Sebastian 

Junger, one of the directors behind the acclaimed film 

Restrepo (http://restrepothemovie.com/), has written 

about the role social bonds play in helping to sustain 

Soldiers through the stress of a combat deployment and, 

conversely, how the absence of postdeployment social 

support elevates the risk of developing posttraumatic 

stress disorder.34 One of the principal objectives of this 

study is to identify the characteristics of past and present supportive relationships that have helped individuals 

overcome adversity and contributed to them becoming 

resilient Soldiers.

Methods

The study protocol was approved by the Institutional 

Review Board at Tripler Army Medical Center. Investigators adhered to the policies for protection of human subjects as prescribed in 45 CFR §46 and entailed 

a 2-part protocol. First, we used a correlational design 

to explore the relationship between adverse childhood 

experiences and resilience in adulthood followed by 

semistructured interviews to identify characteristics of 

supportive relationships that contributed to individuals 

becoming resilient adults in spite of childhood adversity. A convenience sample of 250 active duty service 

members, recruited at the Soldier Readiness Processing 

Center at Schofield Barracks in Hawaii, completed a 

3-part survey that included basic demographic information, the ACE questionnaire, and the Connor-Davidson 

Resilience Scale (CD-RISC). The ACE questionnaire 

used in this study is an adaptation of the survey used 

in the seminal ACE Study.1

 It contains 10 questions 

written to elicit dichotomous yes/no responses to capture the respondent’s exposure, prior to age 18, to child 

maltreatment, domestic violence, parental separation/

divorce, having a member of the household who was 

mentally ill, abused substances, or was incarcerated. In 

addition to identifying specific types of adverse childhood experiences, each affirmative response is tallied 

to determine a total ACE score. Although the ACE data 

are collected retrospectively, answers to the ACE questions have demonstrated good test-retest reliability indicating that responses tend to be generally stable.35 The 

CD-RISC is a valid and reliable self-reported measure 

of resilience consisting of 25 items rated on a 5-point 

scale (0-4) with higher scores indicative of greater resilience.36 In our current study, we achieved a Cronbach 

α coefficient of 0.93. Except for those individuals who 

further volunteered to be interviewed, participant responses contained no personally identifiable information. Confidentiality was strictly guarded for those who 

voluntarily provided their name and a point-of-contact.

Inclusion criteria for the qualitative portion of the study 

consisted of reporting at least 3 adverse childhood experiences, demonstrating high resilience as evidenced 

by scoring 80 or higher on the CD-RISC and, based on 

their response to question two of the CD-RISC, having a close and secure relationship they could turn to 

in times of stress. From the 36 volunteers who met our 

criteria, we selected a purposive sample of 25 that reflected a representive mix of demographic characteristics. The semistructured interviews consisted of a series 

of open-ended questions with probing follow-up queries 

designed to capture descriptions of the personal characteristics and behavior exhibited by individuals with 

whom participants had a current or past supportive relationship. Interviews were recorded in process and specific descriptors using verbatim participant quotes documented. To control for interviewer bias, another member 

of the research team listened to the recorded interview 

and transcribed key descriptive quotes as well. Finally, 

a third researcher reviewed the 2 independent interview 

summaries for inter-rater reliability, only material documented on both summaries was considered reliable and 

included in the final analysis. The data were organized 

RESILIENCE-ENHANCING RELATIONSHIPS: WHAT WE CAN LEARN

FROM THOSE WITH A HISTORY OF ADVERSE CHILDHOOD EXPERIENCES
July – September 2017 27

THE ARMY MEDICAL DEPARTMENT JOURNAL

into descriptive themes, defined as characteristics or actions, and frequencies tabulated. The 

statistical application SPSS v.22 (IBM Corporation, Armonk, New York) was used to calculate 

the frequency distributions of demographic characteristics, the prevalence of each adverse childhood event, and correlations between ACEs and 

resilience. Significance was set at .05. The Tripler 

Army Medical Center Institutional Review Board 

granted approval to conduct this study.

Results

Demographics

As described in Table 1, the 250 participants were 

predominantly male with a moderate number of 

women. They were relatively young with an average age of 27 years. The sample was rather diverse 

with many self-identifying as Caucasian, followed 

by Hispanic, African American, Asian, Pacific Islander and Native American. Most were married 

while a significant number reported being single. 

Only a few were divorced. They were fairly welleducated as a majority were high school graduates 

or had completed some college courses and a significant number had earned at least a 2-year college 

degree. Some had completed postgraduate education or earned technical degrees or certifications. 

The overwhelming majority were enlisted service 

members with almost half serving in the junior 

grades of E1-E4. A substantial number were junior 

noncommissioned officers (NCO) (E5-E6) with a 

few senior NCOs (E7-E9) represented. Commissioned and warrant officers comprised a modest 

percentage of the sample. Half worked in support 

positions or in the medical field, while many of 

the others served in the combat arms specialties. 

On average, they had almost 6 years of time-inservice with a wide range of 3 months to 28 years 

of military experience. Interestingly, most had not 

deployed to a combat zone. The subset of 25 that 

participated in interviews was similar across most 

demographic variables but were more likely to be 

married, more junior in rank, and less likely to 

have deployed to a combat zone.

Adverse Childhood Experiences

In total, ACE scores ranged from 0 to 10 with a mean of 

2.9 (SD=2.6). As detailed in Table 2, the vast majority 

of Soldiers reported experiencing at least one form of 

childhood adversity with half enduring 3 or more. Of 

the 7 individuals who reported 9 or more types of adverse experiences, only one met the inclusion threshold 

for resiliency but that individual did not volunteer to be 

interviewed. Having parents that divorced or separated 

was the most commonly reported disruption to one’s 

childhood. Experiencing child maltreatment, in its various forms, was reported by a significant number but with 

a relatively small percentage reporting being sexually 

abused. Many indicated growing-up in a household with 

someone who abused alcohol or other substances. A little over a quarter lived with a mentally ill family member. A considerable number had a member of the household incarcerated and one-fifth witnessed the trauma of 

Table 1. Demographic Characteristics of Study Population.

Demographic Variables Survey Only

(n=225)

Interviewees

(n=25)

Total

(n=250)

Mean Age (years) 27.12 27.52 27.16

Mean Time-In-Service (years) 5.7 5.5 5.7

Gender

Female 33(14.7%) 6(24%) 39(15.6%)

Male 192(85.3%) 19(76%) 211(84.4%)

Race

African-American 43(19.1%) 3(12.0%) 46(18.4%)

Asian 17(7.6%) 3(12.0%) 20 (8.0%)

Caucasian 99(44.0%) 13(52%) 112(44.8%)

Hispanic 46(20.4%) 4 (16.0%) 50 (20.0%)

Native American 3(1.3%) 1(4%) 4 (1.6%)

Pacific Islander 14 (6.2%) 1(4%) 15(6%)

Other 3(1.3%) 0 (0%) 3(1.2%)

Marital Status

Single 83(36.9%) 6(24.0%) 89(35.6%)

Married 132(58.7%) 19(76%) 151(60.4%)

Divorced 9(4%) 0 (0%) 9(3.6%)

Unknown 1(0.4%) 0 (0%) 1(0.4%)

Education

High School 68(30.2%) 7(28.0%) 75(30.0%)

Some College 72(32.4%) 10 (40.0%) 83(33.2%)

Tech Certification 8(3.6%) 0 (0%) 8(3.2%)

Associates Degree 31(13.8%) 5(20.0%) 36(14.4%)

Bachelor’s Degree 33(14.7%) 2(8.0%) 35(14.0%)

Master’s Degree 7(3.1%) 1(4.0%) 8(3.2%)

Doctorate 2(0.9%) 0 (0%) 2(0.8%)

Unknown 3(1.3%) 0 (0%) 3(1.2%)

Rank

E1–E4 106(47.1%) 15(60.0%) 121(48.4%)

E5–E6 79(35.1%) 5(20.0%) 84 (33.6%)

E7–E9 8(3.6%) 3(12.0%) 11(4.4%)

Officer 32(14.2%) 2(8.0%) 34 (13.6%)

MOS

Combat Arms 97(43.1%) 12(48.0%) 109(43.6%)

Combat Support 34 (15.1%) 2(8.0%) 36(14.4%)

Combat Service Support 63(28.0%) 3(12.0%) 66(26.4%)

Medical 18(8.0%) 5(20.0%) 23(9.2%)

Unknown 13(5.8%) 3(12.0%) 16(6.4%)

Combat Deployment

No 127(56.4%) 17(68%) 144 (57.6%)

Yes 98(43.6%) 8(32%) 106(42.4%)
28 http://www.cs.amedd.army.mil/amedd_journal.aspx

domestic violence. Predictably, given our criteria 

to be included in the study’s qualitative phase, the 

25 individuals who were interviewed reported experiencing childhood trauma in greater percentages across all measures. We found no statistically 

significant relationships between ACEs and any 

demographic variable.

Resilience

Scores on the CD-RISC ranged from 34 to 100 

with a mean of 78.28 (SD=13.74) and a median 

of 79. A weak but statistically significant negative 

relationship was found between total number of 

ACEs and current resilience as measured by the 

CD-RISC (r=-.138, P=.029). Further analysis using the χ2 test for independence with Yates Continuity Correction was conducted to examine the 

relationship between a high number of ACEs (3 or 

more) and high resilience scores (80 or higher on 

the CD-RISC) and also found a statistically significant, weak, negative correlation (χ2=10.9, P=.001, 

φ=-.217). When high CD-RISC scores (80 or 

higher) were analyzed in relation to each ACE, 

statistically significant negative correlations were 

established with psychological abuse (χ2=11.8, 

P=.001, φ=-.225), physical abuse (χ2=6.3, P=.01, 

φ=-.167), domestic violence (χ2=6.0, P=.015, 

φ=-.164) and household member mental illness 

(χ2=5.5, P=.019, φ=-.157). Therefore, individuals who were physically or psychologically abused, 

who witnessed their maternal figure being abused, 

or grew-up with a mentally ill family member 

tended to be less resilient as measured by the CDRISC. All other adverse childhood experiences 

were not significantly associated, at least statistically, with current resilience.

Relationship Characteristics

All 25 interviewees described having current and 

past supportive relationships that helped them become resilient. An individual’s spouse (44%) or 

mother (24%) were the most frequently identified 

current sources of support followed by extra-familial relationships with peers or supervisors such 

as their platoon sergeant (20%). Some (12%) reported 

gaining strength from their relationship with a spiritual 

or religious entity. Similarly, family members, mostly 

the mother but also fathers, grandparents, siblings and 

an uncle, were described as prominent adult relationships during childhood or adolescence by 68%. People 

outside of the family, such as a foster parent, teacher, 

neighbor and friends, were, and in some instances remain, influential in the lives of almost a third (32%) 

of the sample. As seen in the Figure, 9 characteristics 

reliably emerged from the descriptions of those who 

were identified as supportive and having contributed to 

the development of resilience. The characteristics with 

representative descriptions are:

Available

Always there Would be there 

Just being there Was always there for me 

Always going to be there 

(and in several instances) No matter what

RESILIENCE-ENHANCING RELATIONSHIPS: WHAT WE CAN LEARN

FROM THOSE WITH A HISTORY OF ADVERSE CHILDHOOD EXPERIENCES

Table 2. Prevalence of Adverse Childhood Experiences.

Adverse Childhood

Experience Items

Survey Only

(n=225)

Interviewees

(n=25)

Total

(n=250)

Psychological abuse: insulted, 

humiliated, demeaned, 

sworn at, feared physical 

abuse.

92(40.9%) 20 (80.0%) 112(44.8%)

Physical abuse: pushed, 

grabbed, slapped, targeted 

with thrown objects, struck 

leaving marks or resulting 

in injury.

77(34.2%) 18(72.0%) 95(38.0%)

Sexual abuse: touched, 

fondled, and/or forced to 

touch others in a sexual 

way; oral, anal, or vaginal 

intercourse.

25(11.1%) 9(36.0%) 34 (13.6%)

Emotional neglect: not loved, 

made to feel unimportant, 

not looked after, did not 

feel close or supported.

46(20.4%) 11(44.0%) 57(22.8%)

Physical neglect: not enough 

to eat, wore dirty clothes, 

not protected, parents too 

high or drunk to provide 

care or seek medical care 

for you if needed.

28(12.4%) 7(28.0%) 35(14.0%)

Parental divorce/separation: 

parents ever separated or 

divorced.

118(52.4%) 17(68.0%) 135(54.0%)

Domestic violence:

directed towards mother or 

stepmother.

43(19.1%) 7(28.0%) 50 (20.0%)

Substance abuse: lived with 

a problem drinker, alcoholic, 

or drug abuser.

75(33.3%) 20 (80.0%) 95(38.0%)

Mental illness: household 

member was depressed, 

had a mental illness, or 

attempted suicide.

55(24.4%) 11(44.0%) 66(26.4%)

Incarceration: household 

member went to prison.

45(20.0%) 11(44.0%) 56(22.4%)

Number of ACEs Reported

per Individual

0 56(24.9%) 0 (0%) 56(22.4%)

1-2 70 (31.1%) 0 (0%) 70 (28.0%)

3-4 44 (19.5%) 9(36.0%) 53(21.2%)

5-6 36(16.0%) 9(36.0%) 45(18.0%)

7-8 12(5.3%) 7(28.0%) 19(7.6%)

9-10 7(3.1%) 0 (0%) 7(2.8%)
July – September 2017 29

THE ARMY MEDICAL DEPARTMENT JOURNAL

Communicator

Listens Good listener 

Willing to listen Listened to me 

Would listen before giving advice 

Talked to me like an adult 

Just talking things out Could sit down and talk 

Talks to me No yelling

Caring

Showed me she cares Cares about me 

Would go out of his way to show he cared 

Very nurturing and loving 

Constantly checking up on me 

Willing to help

Role Model

A role model to me Led by example 

Inspiring Respected

Looked up to Always positive

Displayed courage and confidence

Trustworthy

Trusted Can confide in him

Can tell her anything Earned my trust 

Honest 100% faithful

Coach

Taught me a lot Pushed me to be greater 

Encouraged me Pushed me to not give up

Gave me tips on how to do things, 

Showed me the Army thinking process 

Taught me to be more responsible

Guardian

Provided security Tried to protect me 

Made sure I had a place to stay 

Would stand up for us 

Always had my back Always put us first

My mental shield

Nonjudgmental

Didn’t judge me at first sight

Tried to understand Never judged me 

Put herself in my shoes Unbiased

He understands what I’ve been through 

Accepted me

Firm

Direct and stern Tough love 

Very forceful Kicks me in the ass 

Tells me when I’m being a baby, to man up

Comment

Our findings show that a substantial number of Soldiers may come from challenging backgrounds as this 

active duty sample reported experiencing childhood 

adversity at a rate comparable to that reported by a clinical sample of deployed Soldiers10 and exceeding that 

found in the general population.37 Moreover, anyone 

could possibly have a history of ACEs as no specific demographic group was found to be more likely to have 

grown-up in adverse conditions. The large percentage 

of Soldiers that acknowledged having ACEs underscores the Kauai study’s finding that joining the military 

is seen as an opportunity to escape family adversity.21

Therefore, the military may disproportionately attract 

recruits with a difficult upbringing, resulting in a significant number of military personnel at-risk for the psychosocial problems associated with adverse childhood 

experiences. Consequently, it is in the best interests of 

the military services to understand the needs of these 

potentially vulnerable service members and to provide 

leadership and support services to help them achieve 

success in their pursuit of a better life.

Although the strength of the relationship is admittedly 

weak, our findings suggest that enduring maltreatment 

or household dysfunction as a child can have a deleterious effect on how resilient one becomes as an adult. 

This may be particularly true for those individuals who 

were physically or psychologically abused, witnessed 

domestic violence, or lived with a mentally ill family 

member. That said, our findings also indicate that the 

damage ACEs can inflict may be mitigated by a relationship with a supportive adult.

Being considered supportive by others can be accomplished by manifesting certain personal qualities. First, 

and apparently foremost, is being available. Knowing 

that someone who is viewed as “better able to cope 

with the world” will be there when needed establishes 

Characteristics of people as described during participant interviews who were identified as supportive and having contributed to 

the participant’s resilience.

Percentage of Participants Describing Characteristic

Nonjudgmental

Available

Communicator

Caring

Role Model

Trustworthy

Coach

Guardian

Firm

0 20 40 60 80 100

24%

36%

32%

44%

60%

64%

80%

72%

84%
30 http://www.cs.amedd.army.mil/amedd_journal.aspx

a secure base from which to engage the external world 

without fear of being abandoned. In addition, maximizing the benefits of “being there” depends, in part, on 

exercising good communication skills that begin with 

a willingness to listen. A great deal of support appears 

to derive from being allowed to express oneself before 

receiving unsolicited advice or, in a more negative vein, 

disapproval from others. Listening, however, is contingent upon others being willing to open-up. While the experience of being “cared for” is subjective, demonstrating that one cares and can be trusted and nonjudgmental 

fosters a sense of safety that encourages a person to talk 

who may otherwise be reluctant to reveal their innermost thoughts due to their family history. Further, a relationship built on trust provides an opportunity to impart 

wisdom, teach life skills, and promote self-efficacy that 

cultivate a sense of competency leading to enhanced resilience. There are, nonetheless, times when firmly, and 

judiciously, enforcing socially acceptable conduct is necessary to keep someone who may be at-risk for maladaptive behavior on the right track. Being a respected role 

model who conveys humility, confidence, and positivity 

and leads by example appears to facilitate the process.

Our results, however, should be considered within the 

context of limitations inherent in our approach. Using a 

correlational design does not allow us to conclude that 

growing-up with ACEs causes one to be less resilient 

as an adult, only that the two situations are associated 

with one another. Also, relying on a convenience sample 

of volunteers creates the risk of a selection bias that reduces our confidence in generalizing our findings beyond the sample. Furthermore, we only achieved face 

validity in defining the characteristics of a supportive 

relationship. Additional specificity is required to reach 

more precise operational definitions.

Implications

Our findings support the conclusions made by others that 

supportive relationships do make a positive difference in 

the lives of those who experienced childhood adversity 

by contributing to resilience in adulthood. Further, being experienced as supportive entails several prominent 

characteristics that include availability, communication 

that emphasizes listening, caring, trustworthiness, and 

being a respected role model who is willing to coach 

and, as necessary, provide firm guidance on behaving 

in socially acceptable ways without being judgmental. 

While these qualities seem fundamentally applicable to 

all human interactions, they may be most meaningful 

in our family relationships. A supportive family member, either a spouse, mother, or other relative, was most 

frequently identified as being instrumental in helping 

to overcome adversity and contributing to resilience. 

Therefore, incorporating these evidence-based characteristics into family advocacy prevention classes may 

be useful in strengthening marriages as well as provide 

a simple model for healthy parent/child relationships. 

Moreover, since a wide-array of extra-familial relationships were also deemed supportive, these attributes can 

be developed into a skill set for military leaders to apply in mentoring vulnerable Soldiers and used to inform 

the training of junior leaders during their initial leadership schools. Providing supportive leadership based on 

the characteristics found in this current research could 

augment the Army’s efforts to enhance psychological 

resilience through the Comprehensive Soldier and Family Fitness Program.38 Future research should continue 

to focus on those who developed grit despite childhood 

adversity to further refine the attributes of a supportive 

relationship and to determine if there is a critical developmental point in which the benefits of a supportive 

relationship can be optimized.

Conclusions

Much research has clearly established that adverse childhood experiences can lead to an adulthood plagued by 

multiple physical and psychosocial maladies. Nevertheless, there is mounting evidence to show that supportive 

relationships can mitigate the negative effect of childhood trauma by helping to build resilience. More specifically, relationships based on a constellation of seemingly simple actions and basic human qualities contribute 

to the development of the resiliency necessary to overcome current and future adversity. Given the number of 

Soldiers who may have experienced childhood adversity, 

military leaders, in addition to being technically and 

tactically proficient, may become more effective mentors by integrating these qualities into their leadership 

style. Perhaps we should consider applying these supportive attributes in all the relationships in which we 

hope to make a meaningful difference.

References

1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction 

to many of the leading causes of death in adults: the 

adverse childhood experiences (ACE) study. Am J

Prev Med. 1998;14(4):245-258.

2. Dube SR, Anda RF, Felitti VJ, Chapman DP, 

Williamson DF, Giles WH. Childhood abuse, 

household dysfunction and the risk of attempted suicide throughout the life span. JAMA. 

2001;286(24):3089-3096.

3. Dube SR, Anda RF, Felitti VJ, Edwards VJ, Croft 

JB. Adverse childhood experiences and personal alcohol abuse as an adult. Addict Behav. 

2002;27:713-725.

RESILIENCE-ENHANCING RELATIONSHIPS: WHAT WE CAN LEARN

FROM THOSE WITH A HISTORY OF ADVERSE CHILDHOOD EXPERIENCES
July – September 2017 31

THE ARMY MEDICAL DEPARTMENT JOURNAL

4. Whitfield CL, Anda RF, Dube SR, Felitti VJ. Violent childhood experiences and the risk of intimate 

partner violence in adults. J Interpers Violence. 

2003;18(2):166-185.

5. Chapman DP, Whitfield CL, Felitti VJ, Dube SR, 

Edwards VJ, Anda RF. Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord. 2004;82:217-225.

6. Whitfield CL, Dube SR, Felitti VJ, Anda RF. Adverse childhood experiences and hallucinations. 

Child Abuse Negl. 2005;29:797-810.

7. Edwards VJ, Holden GW, Felitti VJ, Anda RF. Relationship between multiple forms of childhood 

maltreatment and adult mental health in community respondents: Results from the adverse 

childhood experiences study. Am J Psychiatry. 

2003;160(8):1453-1460.

8. Schilling EA, Aseltine Jr. RH, Gore S. Adverse 

childhood experiences and mental health in young 

adults: A longitudinal survey. BMC Public Health. 

2007;7:Available at: http://www.biomedcentral.

com/1471-2458/7/Accessed October 6, 2016.

9. Blosnich JR, Dichter ME, Cerulli C, Batten 

SV, Bossarte RM. Disparities in adverse childhood experiences among individuals with a 

history of military service. JAMA Psychiatry. 

2014;71(9):1041-1048.

10. Applewhite L, Arincorayan D, Adams B. Exploring 

the prevalence of adverse childhood experiences in 

soldiers seeking behavioral health care during a 

combat deployment. Mil Med. 2016;181:1275-1280.

11. LeardMann CA, Smith B, Ryan MAK. Do adverse childhood experiences increase the risk of 

postdeployment posttraumatic stress disorder in 

US Marines? BMC Public Health. 2010;10:4Available at: http://www.biomedcentral.com/1471-

2458/10/4Accessed September 22,. 2016.

12. Afifi TO, Enns MW, Cox BJ, Asmundson GJG, 

Stein MB, Sareen J. Population attributable fractions of psychiatric disorders and suicide ideation 

and attempts associated with adverse childhood experiences. Am J Public Health. 2008;98(5):946-952.

13. Afifi TO, Boman J, Fleisher W, Sareen J. The relationship between child abuse, parental divorce, and 

lifetime mental disorders and suicidality in a nationally representative adult sample. Child Abuse

Negl. 2009;33:139-147.

14. Grief Green J, McLaughlin KA, Berglund PA, et al. 

Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication 

I. Arch Gen Psychiatry. 2010;67(2):113-123.

15. Rosenberg SD, Lu W, Mueser KT, Jankowski MK, 

Cournos F. Correlates of adverse childhood events 

among adults with schizophrenia spectrum disorders. Psychiatr Serv. 2007;58(2):245-253.

16. Lu W, Mueser KT, Rosenberg SD, Jankowski 

MK. Correlates of adverse childhood experiences 

among adults with severe mood disorders. Psychiatr Serv. 2008;59(9):1018-26.

17. Masten AS. Ordinary magic: resilience processes 

in development. Am Psychol. 2001;56(3):227-238.

18. Roy A, Carli V, Sarchiapone M. Resilience mitigates the suicide risk associated with childhood 

trauma. J Affective Dis. 2011;133:591-594.

19. Campbell-Sills L, Cohan SL, Stein MB. Relationship of resilience to personality, coping, and psychiatric symptoms in young adults. Behav Res Ther. 

2006;44(4):585-599.

20. Rew L, Taylor-Seehafer M, Thomas NY, Yockey 

RD. Correlates of resilience in homeless adolescents. J Nurs Scholarsh. 2001;33(1):33-40.

21. Bonanno GA. Loss, trauma, and human resilience: 

have we underestimated the human capacity to 

thrive after extremely aversive events?. Am Psychol. 2004;59(1):20-28.

22. Werner EE. The children of Kauai: resiliency and 

recovery in adolescence and adulthood. J Adolesc

Health. 1992;13(4):262-268.

23. Bowlby J. A Secure Base: Parent-child Attachment 

and Healthy Human Development. New York, NY: 

Basic Books, Inc; 1988:26-27.

24. Simeon D, Yehuda R, Cunill R, Knutelska M, Putnam FW, Smith LM. Factors associated with resilience in healthy adults. Psychoneuroendocrinology. 

2007;32:1149-1152.

25. Masten AS, Best KM, Garmezy N. Resilience and 

development: Contributions from the study of children who overcome adversity. Dev Psychopathol. 

1990;2:425-444.

26. Brooks JE. Strengthening resilience in children 

and youths: maximizing opportunities through the 

schools. Child Sch. 2006;18(2):69-76.

27. Ungar M. The importance of parents and other 

caregivers to the resilience of high-risk adolescents. 

Fam Process. 2004;43(1):23-41.

28. Masten AS, Coatsworth JD. The development of 

competence in favorable and unfavorable environments: lessons from research on successful children. Am Psychol. 1998;53(2):205-220.

29. Rak CF, Patterson LE. Promoting resilience in atrisk children. J Couns Dev. 1996;7:368-373.

30. Egeland B, Carlson E, Sroufe LA. Resilience as 

process. Dev Psychopathol. 1993;5(4):517-528.

31. Vanhove AJ, Herian MN, Perez ALU, Harms PD, 

Lester PB. Can resilience be developed at work? 

A meta-analytic review of resilience-building programme effectiveness. J Occup Organ Psychol. 

2016;89(2):278-307.
32 http://www.cs.amedd.army.mil/amedd_journal.aspx

32. Wilson SM, Ferch SR. Enhancing resilience in the 

workplace through the practice of caring relationships. Organizational Dev J. 2005;23(4):45-60.

33. Laursen EK, Birmingham SM. Caring relationships as a protective factor for at-risk youth: an 

ethnographic study. Fam Soc. 2003;84(2):240-246.

34. Junger S. Tribe: On Homecoming and Belonging. 

New York, NY; Hachette Book Group: 2016.

35. Dube SR, Williamson DF, Thompson T, Felitti VJ, 

Anda RF. Assessing the reliability of retrospective 

reports of adverse childhood experiences among 

adult HMO members attending a primary care 

clinic. Child Abuse Negl. 2004;28:729-737.

36. Connor KM, Davidson JRT. Development of a new 

resilience scale: the Connor-Davidson Resilience 

Scale (CD-RISC). Depress Anxiety. 2003;18:76-82.

37. Centers for Disease Control and Prevention. About 

behavioral risk factor surveillance system ACE 

data [internet]. 20Available at: https://www.cdc.

gov/violenceprevention/acestudy/ace_brfss.html. 

Accessed January 4,. 2017.

38. Casey GW. Comprehensive soldier fitness: a vision 

for psychological resilience in the US Army. Am 

Psychol. 2011;66(1):1-3.

Authors

COL Arincorayan is Deputy Chief, Department of Behavioral Health, Schofield Barracks, Hawaii.

Dr Applewhite is a Clinical Associate Professor, US 

Army/Fayetteville State University MSW Program, US 

Army Medical Department and School, JBSA Fort Sam 

Houston, Texas.

MAJ Garrido is Director of Training, Social Work Internship Program, Department of Behavioral Health, 

Schofield Barracks, Hawaii.

CPT Cashio is Behavioral Health Officer, 3rd Infantry 

Division Sustainment Brigade, Fort Stewart, Georgia.

CPT Bryant is Behavioral Health Officer, 210 Field Artillery Brigade, Camp Casey, Republic of Korea.

RESILIENCE-ENHANCING RELATIONSHIPS: WHAT WE CAN LEARN

FROM THOSE WITH A HISTORY OF ADVERSE CHILDHOOD EXPERIENCES
July – September 2017 33

Meralgia paresthetica, a painful mononeuropathy of the 

lateral femoral cutaneous nerve (LFCN), can result from 

injury, compression or mechanical irritation of the latter.1

 Lateral femoral cutaneous nerve block plays an instrumental role in the diagnosis and management of meralgia paresthetica.1

 Techniques for LFCN block include 

blind infiltration, neurostimulation (NS), and utrasound 

(US)-guidance.2-4 In a randomized crossover study, blind 

infiltration was compared to NS.2

 The latter resulted in a 

greater success rate (100% vs 40%; P<.001) coupled with 

a shorter onset time (P<.02).2

 Although several recent 

reports3-4 have advocated US for LFCN block, to date, 

no RCT has compared NS- and US-guided techniques.

In this randomized, volunteer study, we set out to compare NS- and US-guided LFCN blocks. We hypothesized 

that US would provide shorter performance and onset 

times. Thus, the primary outcome was the total anesthesia-related time (ie, the sum of performance and onset 

times). We also aimed to describe the triplanar sensory 

distribution of the LFCN after local anesthetic blocks.

Material and Methods

The current trial was registered at Clinicaltrials.gov 

(Identifier: NCT02577510) on October 14, 2015. After 

obtaining ethics committee approval (Defence Research 

and Development Canada Human Research Ethics Committee) and written informed consent, we enrolled 21 

volunteers. Inclusion criteria were age between 18 and 

60 years, American Society of Anesthesiologists (ASA) 

physical status I to II, and body mass index between 

20 kg/m2

 and 40 kg/m2. Exclusion criteria included 

A Randomized Comparison Between

 Neurostimulation and Ultrasound-Guided

 Lateral Femoral Cutaneous Nerve Block

Gaurav Gupta, MD, FRCPC Atikun Thonnagith, MD

Mohan Radhakrishna, MD, FRCPC Maria Francisca Elgueta, MD

Isaac Tamblyn, PhD MCpl Marie Eve Robitaille, AEC

De QH Tran, MD, FRCPC Roderick J Finlayson, MD, FRCPC

LCol Markus Besemann, MD, FRCPC

Abstract

Background: This prospective, randomized trial compared neurostimulation (NS) and ultrasound (US) guided 

lateral femoral cutaneous nerve (LFCN) block. We hypothesized that US would result in a shorter total 

anesthesia-related time (sum of performance and onset times).

Methods: Twenty-one volunteers were enrolled. The right lower limb was randomized to an NS- or US-guided 

LFCN block. The alternate technique was employed for the left lower limb. With NS, paresthesias were sought 

in the lateral thigh at a stimulatory threshold of 0.6 mA (pulse width=0.3 ms; frequency=2 Hz) or lower. With 

US, local anesthetic was deposited under the inguinal ligament, ventral to the iliopsoas muscle. In both groups, 

5 mL of lidocaine 2% were used to anesthetize the nerve. During the procedure of the block, the performance 

time and number of needle passes were recorded. Subsequently, a blinded observer assessed sensory block in 

the lateral thigh every minute until 20 minutes. Success was defined as loss of pinprick sensation at a point 

midway between the anterior superior iliac spine and the lateral knee line. The blinded observer also assessed 

the areas of sensory block in the anterior, medial, lateral, and posterior aspects of the thigh and mapped this 

distribution onto a corresponding grid.

Results: Both modalities provided comparable success rates (76.2%-95.2%), performance times (162.1 to 231.3 

seconds), onset times (300.0 to 307.5 seconds) and total anesthesia related-times (480.1 to 554.0 seconds). However 

US required fewer needle passes (3.2±2.9 vs 9.5±12.2; P=.009). There were no intergroup differences in terms 

of the distribution of the anesthetized cutaneous areas. However considerable variability was encountered between individuals and between the 2 sides of a same subject. The most common areas of sensory loss included 

the central lateral two-eighths anteriorly and the central antero-inferior three-eighths laterally.

Conclusion: Ultrasound guidance and NS provide similar success rates and total anesthesia-related times for 

LFCN block. The territory of the LFCN displays wide inter- and intra-individual variability.
34 http://www.cs.amedd.army.mil/amedd_journal.aspx

A RANDOMIZED COMPARISON BETWEEN NEUROSTIMULATION- AND ULTRASOUND-GUIDED

LATERAL FEMORAL CUTANEOUS NERVE BLOCK

coagulopathy, pregnancy, breast feeding, hepatic or renal failure, allergy to local anesthetic (LA), prior surgery in the inguinal area, and neuropathy impacting 

sensation of the lateral thigh.

All LFCN blocks were performed by 2 operators (authors G. G. and R. J. F.) experienced with the NS and US 

techniques. They were carried out in a medical facility with access to resuscitative equipment and drugs. 

Volunteers were positioned supine. Using a computergenerated sequence of random numbers and a sealed 

envelope technique, the right lower limb was randomized to an NS- or US -guided LFCN block. The alternate 

technique was employed for the left lower limb.

The NS technique was modified from the earlier description of Shannon et al.2

 After disinfection and draping, a 

skin wheal (using 0.5 mL of lidocaine 1%) was raised 

2 cm medial to the anterior superior iliac spine (ASIS) 

and 1 cm caudal to the inguinal ligament (Figure 1). A 

22-gauge block needle (SonoPlex Stimcannula, Pajunk 

Mediztechnologie, Geisingen, Germany) attached to a 

nerve stimulator (MultiStimSwitch, Pajunk Mediztechnologie, Geisingen, Germany) set at a current of 1.5 

mA (pulse width=0.3 ms; frequency=2 Hz) was then 

inserted. Paresthesias were sought along the lateral aspect of the thigh. If sensory stimulation was not found 

with the initial insertion, the needle was advanced superficially in a fan-like pattern towards the ASIS. After 

confirming the presence of paresthesia at a threshold of 

0.6 mA or lower, 5 mL of lidocaine 2% were injected to 

anesthetize the LFCN.

The US technique was performed according to the description of Hara et al.5

 After skin disinfection and 

draping, a 6-13 MHz linear US probe (probe SL3323, 

MyLabTouch, Esoate, Genova, Italy) was applied in a 

sterile fashion medially to the ASIS and caudally to the 

inguinal ligament, in order to obtain a short axis view of 

the iliopsoas muscle. A skin wheal was raised with 0.5 

mL of lidocaine 1%. Using an out-of-plane technique, a 

22-gauge block needle was advanced until its tip was positioned just ventral to the iliopsoas muscle. Five mL of 

lidocaine 2% were deposited in this location (Figure 2).

For the US group, the imaging time was defined as the 

time interval between contact of the US probe with the 

patient and the acquisition of a satisfactory picture. For 

both groups, the performance time was defined as the 

temporal interval between the start of the procedure 

(skin-probe contact for the US group and skin wheal 

for the NS group) and the end of LA injection through 

the block needle. Imaging and performance times were 

Figure 1. Needle in position for a block of the lateral femoral 

cutaneous nerve using the nerve stimulation technique. A line 

has been drawn (B) between the anterior superior iliac spine 

(ASIS) and the pubic tubercle. The skin puncture site is 2 cm 

medial along this line and 1 cm caudal to it.

2 http://www.cs.amedd.army.mil/amedd_journal.aspx

coagulopathy, pregnancy, breast feeding, hepatic or renal failure, allergy to local anesthetic (LA), prior surgery in the inguinal area, and neuropathy impacting 

sensation of the lateral thigh.

$OO/)&1 EORFNVZHUH SHUIRUPHG E\  RSHUDWRUV **

5-)H[SHULHQFHGZLWKWKH16DQG86WHFKQLTXHV7KH\

ZHUHFDUULHGRXWLQDPHGLFDOIDFLOLW\ZLWKDFFHVVWRUHVXVFLWDWLYHHTXLSPHQWDQGGUXJV9ROXQWHHUVZHUHSRVLtioned supine. Using a computer-generated sequence of 

random numbers and a sealed envelope technique, the 

ULJKWORZHUOLPEZDVUDQGRPL]HGWRDQ16RU86JXLGHG/)&1EORFN7KHDOWHUQDWHWHFKQLTXHZDVHPSOR\HG

IRUWKHOHIWORZHUOLPE

7KH16WHFKQLTXHZDVPRGL¿HGIURPWKHHDUOLHUGHVFULSWLRQRI6KDQQRQHWDO2

 After disinfection and draping, a 

VNLQZKHDO XVLQJP/RIOLGRFDLQHZDV UDLVHG

FPPHGLDOWRWKHDQWHULRUVXSHULRULOLDFVSLQH$6,6

and 1 cm caudal to the inguinal ligament (Figure 1). A 

JDXJH EORFN QHHGOH 6RQR3OH[6WLPFDQQXOD3DMXQN

Mediztechnologie, Geisingen, Germany) attached to a 

QHUYH VWLPXODWRU 0XOWL6WLP6ZLWFK 3DMXQN 0HGL]WHFKQRORJLH *HLVLQJHQ *HUPDQ\ VHW DW D FXUUHQW RI 

P$ SXOVHZLGWK PV IUHTXHQF\ +]ZDVWKHQ

LQVHUWHG3DUHVWKHVLDVZHUH VRXJKWDORQJWKHODWHUDODVSHFWRIWKHWKLJK,IVHQVRU\VWLPXODWLRQZDVQRWIRXQG

ZLWKWKHLQLWLDOLQVHUWLRQWKH QHHGOH ZDV DGYDQFHG VXSHU¿FLDOO\LQDIDQOLNHSDWWHUQWRZDUGVWKH$6,6$IWHU

FRQ¿UPLQJWKHSUHVHQFHRISDUHVWKHVLDDWDWKUHVKROGRI

P$RUORZHUP/RIOLGRFDLQHZHUHLQMHFWHGWR

anesthetize the LFCN.

7KH 86 WHFKQLTXH ZDV SHUIRUPHG DFFRUGLQJ WR WKH

description of Hara et al.

 After skin disinfection and 

GUDSLQJ D 0+] OLQHDU 86 SUREH SUREH 6/,

0\/DE7RXFK (VRDWH *HQRYD ,WDO\ ZDV DSSOLHG LQ D

VWHULOHIDVKLRQPHGLDOO\WRWKH$6,6DQGFDXGDOO\WRWKH

LQJXLQDOOLJDPHQWLQRUGHUWRREWDLQDVKRUWD[LVYLHZRI

WKHLOLRSVRDVPXVFOH$VNLQZKHDOZDVUDLVHGZLWK

mL of lidocaine 1%. Using an out-of-plane technique, a 

JDXJHEORFNQHHGOHZDVDGYDQFHGXQWLOLWVWLSZDVSRsitioned just ventral to the iliopsoas muscle. Five mL of 

OLGRFDLQHZHUHGHSRVLWHGLQWKLVORFDWLRQ)LJXUH

)RUWKH86JURXSWKHLPDJLQJWLPHZDVGH¿QHGDVWKH

WLPHLQWHUYDOEHWZHHQFRQWDFWRIWKH86SUREHZLWKWKH

patient and the acquisition of a satisfactory picture. For 

ERWKJURXSVWKHSHUIRUPDQFHWLPHZDVGH¿QHGDVWKH

WHPSRUDO LQWHUYDO EHWZHHQ WKH VWDUW RI WKH SURFHGXUH

VNLQSUREH FRQWDFW IRU WKH 86 JURXS DQG VNLQ ZKHDO

IRUWKH16JURXSDQGWKHHQGRI/$LQMHFWLRQWKURXJK

WKHEORFNQHHGOH,PDJLQJDQGSHUIRUPDQFHWLPHVZHUH

A RANDOMIZED COMPARISON BETWEEN NEUROSTIMULATION- AND ULTRASOUND-GUIDED 

LATERAL FEMORAL CUTANEOUS NERVE BLOCK

Figure 1. Needle in position for a block of the lateral femoral 

cutaneous nerve using the nerve stimulation technique. A line 

has been drawn (B) between the anterior superior iliac spine 

(ASIS) and the pubic tubercle. The skin puncture site is 2 cm 

medial along this line and 1 cm caudal to it.

2A 2B

Figure 2. Ultrasound guided block of the lateral femoral cutaneous nerve.

2A: an out-of-plane needle (N) has been placed through the inguinal ligament (IL), ventral to the iliopsoas muscle (IPM), 

one centimeter medial to the anterior superior iliac spine (ASIS).

2B: 5 mL of local anesthetic (LA) has been injected, spreading under the inguinal ligament (IL) and ventral to the iliopsoas 

muscle (IPM).
July – September 2017 35

THE ARMY MEDICAL DEPARTMENT JOURNAL

recorded by the (nonblinded) investigator assisting the 

primary operator. The number of needle passes was also 

recorded by the nonblinded assistant. The initial needle 

insertion counted as the first pass. Any subsequent needle advancement that was preceded by a retraction of at 

least 10 mm counted as an additional pass.6

After LA injection through the block needle, LFCN 

block was tested over the lateral aspect of the thigh. 

Measurements were carried out every minute until 20 

minutes by a blinded observer. Block success was defined as loss of sensation to pinprick at a point midway 

between the ASIS and the lateral knee line.2

 Onset time 

was defined as the temporal interval required to achieve 

success. Thus total anesthesia-related time equaled the 

sum of performance and onset times.

In addition to recording anthropometric data, the blinded observer also assessed incidental femoral block (knee 

extension) at 20 minutes and procedural pain using a 

October – December 2016 3

THE ARMY MEDICAL DEPARTMENT JOURNAL

recorded by the (nonblinded) investigator assisting the 

SULPDU\RSHUDWRU7KHQXPEHURIQHHGOHSDVVHVZDVDOVR

recorded by the nonblinded assistant. The initial needle 

LQVHUWLRQFRXQWHGDVWKH¿UVWSDVV$Q\VXEVHTXHQWQHHGOHDGYDQFHPHQWWKDWZDVSUHFHGHGE\DUHWUDFWLRQRIDW

least 10 mm counted as an additional pass.6

After LA injection through the block needle, LFCN 

EORFN ZDV WHVWHG RYHU WKH ODWHUDO DVSHFW RI WKH WKLJK

0HDVXUHPHQWVZHUHFDUULHG RXWHYHU\PLQXWH XQWLO 

PLQXWHV E\ D EOLQGHG REVHUYHU%ORFN VXFFHVV ZDV GH-

¿QHGDVORVVRIVHQVDWLRQWRSLQSULFNDWDSRLQWPLGZD\

EHWZHHQWKH$6,6DQGWKHODWHUDONQHHOLQH2

2QVHWWLPH

ZDVGH¿QHGDVWKHWHPSRUDOLQWHUYDOUHTXLUHGWRDFKLHYH

success. Thus total anesthesia-related time equaled the 

sum of performance and onset times.

In addition to recording anthropometric data, the blinded observer also assessed incidental femoral block (knee 

extension) at 20 minutes and procedural pain using a 

Area Percentage of Thigh “Frozen”

Frequency

2

0

4

6

8

10

12

0 20 40 60 80 100

ȝ=21.01%±13.72%

Neurostimulation (NS) Guided

Area Percentage of Thigh “Frozen”

Frequency

2

0

4

6

8

10

12

0 20 40 60 80 100

ȝ=21.24%±13.97%

Ultrasound (US) Guided

Anterior (right leg) Anterior (left leg) Lateral (left leg) Lateral (right leg) Posterior (left leg) Posterior (right leg)

a

b

c

e

d

g

f

0 4 2 68 10 12 14 16 18 20

Successful Treatments

Figure 3A. Sensory area distribution maps observed for successful nerve blocks. Overlapping areas shared between patients are 

denoted by the area color.

Legend: a. Anterior superior Illiac spine d. Patella (lateral view) g. Popliteal crease

b. Patella (anterior view) e. Lateral joint line

c. Greater trochanter f. Gluteal fold

Figure 3B. Histogram of frozen areas (reported as a percentage of patient thigh surface area) experienced by patients for successful NS and US treatments. Average freeze area percentage for each treatment protocol are shown.
36 http://www.cs.amedd.army.mil/amedd_journal.aspx

A RANDOMIZED COMPARISON BETWEEN NEUROSTIMULATION- AND ULTRASOUND-GUIDED

LATERAL FEMORAL CUTANEOUS NERVE BLOCK

visual analog scale (0 cm indicates no pain; 10 cm indicates worst imaginable pain).

For those patients with successful LFCN blocks at 20 

minutes, the blinded assessor proceeded to determine 

the extent of the sensory loss in all directions from the 

reference point. A mark was made where sensation was 

deemed to have normalized, and the distribution was 

transferred to the respective grid (Figure 3). Using washable markers, the grids were premarked into quartiles 

(based on length) in all views, and then further subdivided into eighths. Anteriorly, quartiles were calculated 

by dividing the distance from the ASIS to superior patella into equal fourths, and then further subdivided into 

eighths with a bisecting line drawn superiorly from the 

midpoint of the patella. Laterally, the distance from the 

superior edge of the greater trochanter 

to the lateral joint line of the knee was 

divided into quartiles, and then further 

subdivided into eighths with a bisecting line drawn superiorly from the midpoint of the lateral joint line. Posteriorly, 

the distance between the gluteal and 

popliteal folds was divided into fourths, and then further subdivided into eighths with a bisecting line drawn 

superiorly from the midpoint of the popliteal fossa.

Statistical Analysis

We expected similar success rates for both groups. Our 

research hypothesis was that performance and onset 

times would be different. Therefore, the main outcome 

was the total anesthesia-related time (sum of performance and onset times). According to Shannon et al,2

the total anesthesia-related time with NS is 10.1±4.7 

minutes. Using a paired t test to compare both techniques, a 30% difference in total time represented an 

effect size of 0.74 and required a total of 17 subjects undergoing bilateral blocks in order to achieve a 2-tailed 

α error of 0.05 and a β error of 0.2. Since onset and 

total anesthesia-related times can only be calculated 

for successful blocks, and since we expected an 85% 

success rate with NS, 20 subjects were needed to 

account for block failure. Because 21 volunteers inquired about study participation, we decided to enroll 

all 21 subjects.

Statistical analysis was performed using SPSS Version 21 statistical software (IBM, Armonk, New 

York). For continuous data, normality was first assessed with the Lilliefors test and then analyzed using a paired t test. Data that did not have a normal 

distribution, as well as ordinal data, was analyzed using Wilcoxon’s signed ranks or McNemar’s test. All P 

values presented were 2-sided and values inferior to .05 

were considered significant.

For territorial mapping of the LFCN, initial digitization 

was handled with a digital scanner. We used a combination of guided curve detection (as implemented in 

GraphClick (Arizona-Software.ch, Neuchatel, Switzerland)) and our own implementation of the flood fill algorithm to segment images between FROZEN and UNFROZEN. All images were area-normalized, allowing 

for comparison between subjects of different physical 

sizes. Subsequently, images were aligned within ±one 

degree. Treatment heat-maps (Figure 3) were generated 

using Matplotlib (http://matplotlib.org). Statistics for 

the sensor distribution were computed using the open 

source python module SciPy (http://scipy.org).

Results

All LFCN blocks were performed over a 

period of 2 days (November 7-8, 2015).

Demographic data are presented in 

Table 1. Both techniques provided similar success rates (76.2%-95.2%), performance times 

(162.1-231.3 seconds), onset times (300.0-307.5 seconds), 

total anesthesia related-times (480.1-554.0 seconds) and 

procedural pain scores (4.0-4.6). However US required 

fewer needle passes (3.2±2.9 vs 9.5±12.2; P=.009) (Table 2). At 20 minutes, one volunteer (US group) displayed 

incidental femoral nerve blockade.

No statistical differences were detected when comparing the distribution of sensory loss between US and 

NS-guided LFCN blocks. The overall average surface 

area coverage was similar, with normative distribution 

observed in the available sample size. However considerable variability was encountered between individuals 

Table 1. Volunteer Characteristics

Age (years) 40.3 (10.0)

Sex (male/female) 17/4

Body mass index 26.7 (3.5)

Continuous variables are presented as 

means (SD). Categorical variables are 

presented as count.

Table 2. Block Performance Data.

Ultrasound

(N=21)

Nerve Stimulation

(N=21)

P value

Imaging time 22.5 (19.6) NA NA

Performance time 162.1 (125.8) 231.3 (210.9) .138

Onset time 307.5 (157.8) 300.0 (236.0) .920

Total anesthesia-related

time

480.1 (251.9) 554.0 (366.9) .443

Success rate (%) 20.0 (95.2) 16.0 (76.2) .125

Number of passes 3.2 (2.9) 9.5 (12.2) .009

Block-related pain

(VAS score)

4.6 (2.2) 4.0 (2.2) .139

Incidental femoral block 1.0 (4.8) 0 (0) >.999

All time variables are in seconds.

Continuous variables are presented as means (SD). Categorical variables 

are presented as count (percentage).

NA indicates not applicable; VAS, visual analog scale.
July – September 2017 37

THE ARMY MEDICAL DEPARTMENT JOURNAL

and between the 2 sides of a same subject (Figure 3). 

The most common areas of sensory loss included the 

central lateral two-eighths anteriorly and the central 

antero-inferior three-eighths laterally.

Comment

In this randomized trial, we compared NS- and USguided LFCN blocks. Our results reveal that both modalities result in similar success rates and total anesthesia-related times. We speculate that the lack of intergroup differences stem from the superficial position of 

the LFCN. Although US confers significant advantages 

for brachial plexus, femoral, and sciatic nerve blocks,7-8

its benefits may not extend to smaller neural structures. 

For instance, Tran et al9

 reported comparable success 

rates (80%-85%) and onset times for US and landmarkguided superficial cervical plexus blocks. Similarly, 

Fredrickson et al10 found no differences in success rate 

(80%-89%) for ankle blocks performed with the conventional infiltrative method (using 30 mL of ropivacaine 

0.5%) or US. Furthermore, in 18 volunteers randomized 

to a landmark-based deep peroneal nerve block on one 

side and a US technique on the other, Antonakakis et 

al11 observed similar sensory and motor block between 

20 and 60 minutes.

We attribute our 76.2%-95.2% success rates to anatomical variations of the LFCN. Instead of being a singular 

structure, the latter can divide into multiple branches 

proximal to the inguinal ligament in 28% of cases.12

For these subjects, NS would provide limited success as 

paresthesias may only reflect needle tip proximity with 

an end branch and not the parent trunk. Furthermore 

the LFCN can be found dorsal, ventral, or lateral to the 

ASIS.13-15 In the event that the nerve is ventral to the 

latter, subinguinal LA deposition (with US guidance) 

would result in failure.

The technique employed in our US group requires discussion. In the literature, most descriptions pertaining 

to US guidance have painstakingly identified the LFCN 

prior to targeting it with LA. In contrast, Hara et al 5

 simply used US to inject LA under the inguinal ligament, 

ventral to the iliopsoas muscle. In 2011, these authors 

compared their subinguinal method to a nerve-targeting 

US technique. A significantly higher success rate was 

achieved with the former (95.9% vs 74.5%; P=.0027).5

Thus, in the current trial, we opted for the subinguinal 

technique because it represents the best evidence-based 

option available. Similarly, for the control group, we purposefully selected NS instead of blind LA infiltration.2

The interindividual variability in the sensory distribution of the LFCN has been previously described. Corujo 

et al16 reported that in 40.9% of patients, the LFCN displayed a “typical” territory (lateral thigh without extension past the midline of the anterior thigh). However, in 

45.5% of the subjects, the sensory distribution of the 

LFCN encompassed both lateral and anterior aspects of 

the thigh. Conversely, in 13.6% of the subjects, it was 

confined to a small, circumscribed area on the lateral 

thigh.16 In 16 patients, Hopkins et al17 found that, after 

a successful LFCN block, the area of sensory loss was 

frequently “pear-drop shaped” with its apex lying over 

or distal to the greater trochanter and its body extending distally and anteriorly towards the knee. However, 

there existed no region of the thigh that was consistently 

anesthetized in all 16 subjects.17 In addition to confirming previous reports by Corujo et al16 and Hopkins et al17

pertaining to interindividual variability, our results also 

reveal for the first time that the sensory innervation of 

the LFCN can vary within the same individual between 

right and left lower limbs.

Our protocol contains some limitations. Firstly, our findings are specific to the 5 mL-injectate. We cannot rule 

out potential differences between NS and US with larger 

LA volumes. However larger injectates may increase the 

risk of incidental femoral nerve block, thereby hindering the diagnostic value of LFCN block for meralgia 

paresthetica. Secondly, the 4.8% rate of femoral block 

(US group) suggests that even volumes as small as 5 

mL can result in LA migration from the LFCN to the 

femoral nerve. Thus dose-finding studies are required 

for LFCN block. Thirdly, the benefits derived from the 

US subinguinal technique (decreased needle passes) 

apply solely to LFCN blocks with LA. Neuroablative 

procedures, such as pulsed radiofrequency, would still 

require targeted identification of the LFCN (with NS 

or US). Finally, there exists no standard method to delineate neural sensory distribution. Any mapping technique inherently carries a certain amount of imprecision. 

Nonetheless, future studies could employ 3-dimensional 

scanning technology to determine the sensory topography for various nerves blocks.

In conclusion, US and NS provide similar success rates 

and total anesthesia-related times for LFCN block. The 

territory of the LFCN displays wide inter- and intraindividual variability: the most common distributions 

in the thigh encompass the central lateral two-eighths 

anteriorly and the central antero-inferior three-eighths 

laterally.

Acknowledgements

We thank Sgt Ann Dostie, Captain Alex Duong, and 

Dr Marco Erak for their significant contributions to the 

administration of this study.
38 http://www.cs.amedd.army.mil/amedd_journal.aspx

References

1. Hui GKM, Peng PWH. Meralgia paresthetica. 

What an anesthesiologist should know. Reg Anesth

Pain Med. 2011;36:156-161.

2. Shannon J, Lang SA, Yip RW, Gerard M. Lateral 

femoral cutaneous nerve block revisited. A nerve 

stimulator technique. Reg Anesth. 1995;20:100-104.

3. Ng I, Vaghadia H, Choi PT, Helmy N. Ultrasound 

imaging accurately identifies the lateral femoral 

cutaneous nerve. Anesth Analg. 2008;107:1070-1074.

4. Hurdle MF, Weingarten TN, Crsostomo RA, 

Psimos C, Smith J. Ultrasound-guided blockade 

of the lateral femoral cutaneous nerve: technical 

description and review of 10 cases. Arch Phys Med 

Rehabil. 2007;88:1362-1364.

5. Hara K, Sakura S, Shido A. Ultrasound-guided 

lateral femoral cutaneous nerve block: comparison of two techniques. Anaesth Intensive Care.

2011;39:69-72.

6. Konrad C, Schupfer G, Wietlisbach M, Gerber H. 

Learning manual skills in Anesthesiology: is there 

a recommended number of cases for anesthetic procedures?. Anesth Analg. 1998;86:635-639.

7. Neal JM, Gerancher JC, Hebl JR, Ilfeld BM, et al. 

Upper extremity regional anesthesia: essentials of 

our current understanding, 2008. Reg Anesth Pain

Med. 2009;34:134-170.

8. Tran DQH, Clemente A, Finlayson RJ. A review 

of approaches and techniques for lower extremity 

nerve blocks. Can J Anesth. 2007;54:922-934.

9. Tran DQH, Dugani S, Finlayson RJ. A randomized 

comparison between ultrasound-guided and landmark-based superficial cervical plexus block. Reg 

Anesth Pain Med. 2010;35:539-543.

10. Fredrickson MJ, White R, Danesh-Clough TK. 

Low-volume ultrasound-guided nerve block provides inferior postoperative analgesia compared to 

a higher-volume landmark technique. Reg Anesth

Pain Med. 2011;36:393-398.

11. Antonakakis JG, Scalzo DC, Jorgenson AS, et al. 

Ultrasound does not improve the success rate of a 

deep peroneal nerve block at the ankle. Reg Anesth

Pain Med. 2010;35:217-221.

12. Grothaus MC, Holt M, Mekhail AO, et al. Lateral 

femoral cutaneous nerve: an anatomic study. Clin 

Orthop Relat Res. 2005;437:164-168.

13. Aszmann OC, Dellon ES, Dellon AL. Anatomical 

course of the lateral femoral cutaneous nerve and 

its susceptibility to compression and injury. Plast

Reconstr Surg. 1997;100:600-604.

14. Murata Y, Takahashi Y, Yamagata M, et al. The 

anatomy of the lateral femoral cutaneous nerve, 

with special reference to the harvesting of iliac 

bone graft. J Bone Joint Surg Am. 2000;82:746-747.

15. Kosiyatrakul A, Nuansalee N, Luenam S, Koonchornboon T, Prachaporn S. The anatomic variation of the lateral femoral cutaneous nerve in relation to the anterior superior iliac spine and the iliac 

crest. Musculoskelet Surg. 2010;94:17-20.

16. Corujo A, Franco CD, Williams JM. The sensory territory of the lateral cutaneous nerve of 

the thigh as determined by anatomic dissections 

and ultrasound-guided blocks. Reg Anesth Pain 

Med. 2012;37:561-564.

17. Hopkins PM, Ellis FR, Halsall PJ. Evaluation of local anaesthetic blockade of the lateral femoral cutaneous nerve. Anaesth. 1991;46:95-96.

Authors

Dr Gupta, a physiatrist, works with the Canadian Forces 

Health Services Centre-Ottawa and the Alan Edwards 

Pain Management Unit of the Department of Anesthesia, 

Montreal General Hospital. He is also an Adjunct Professor at McGill University in Montreal, Quebec.

Dr Radhakrishna is with the Division of Physical Medicine and Rehabilitation, Department of Medicine and the 

Alan Edwards Pain Management Unit of the Department 

of Anesthesia, Montreal General Hospital. He is also an 

Associate Professor at McGill University in Montreal, 

Quebec.

Dr Tamblyn is a Research Officer with the National Research Council of Canada. He is also an Assistant Professor of Physics at the University of Ontario Institute of 

Technology, Oshawa, Ontario.

Dr Tran is with the Department of Anesthesia, Montreal 

General Hospital. He is also an Associate Professor at 

McGill University in Montreal, Quebec.

LCol Besemann, a physiatrist, is head of the Canadian 

Forces physical rehabilitation program at the Canadian 

Forces Health Services Group Headquarters in Ottawa. 

He also works at the Canadian Forces Health Services 

Centre and is a lecturer at the University of Ottawa.

Dr Thonnagith is a Fellow in the Department of Anesthesia, Montreal General Hospital, and now staff within the 

Faculty of Medicine, Chulalongkorn University, Thailand.

Dr Elgueta is a Fellow in the Department of Anesthesia, 

Montreal General Hospital, and affiliated with the Pontificia Universidad Catolica de Chile.

MCpl Robitaille is with the Canadian Forces Health Services Centre-Ottawa, Ontario.

Dr Finlayson is an anesthesiologist with the Alan 

Edwards Pain Management Unit of the Department of 

Anesthesia, Montreal General Hospital. He is also a Professor at McGill University in Montreal, Quebec.

A RANDOMIZED COMPARISON BETWEEN NEUROSTIMULATION- AND ULTRASOUND-GUIDED

LATERAL FEMORAL CUTANEOUS NERVE BLOCK
July – September 2017 39

Total knee arthroplasty (TKA) is a commonly performed 

procedure proven to provide functional improvement 

and pain relief for most patients with advanced knee 

arthritis.1

 Although outcomes of total knee replacement 

are typically excellent, up to 20% of patients continue 

to have postoperative pain, functional limitations, and 

low treatment satisfaction.2-4 Postoperative health-related quality of life and patient satisfaction is now a key 

goal of surgery and important measure of operative 

outcomes.5

 Quadriceps activation has been shown to be 

negatively affected following TKA and its function has 

been directly correlated with outcomes.6-8 Postoperative 

rehabilitation protocols focus specifically on improving 

quadriceps strength in order to improve postoperative 

pain and functional outcomes.6

 Blood flow restriction 

(BFR) training is a form of exercise that uses brief periods of partially restricted venous blood flow during low 

load resistance training to improve muscular strength 

and endurance. These loads are typically 20% to 30% 

of a patient’s single repetition maximum.7-8 This technique has been used with promising results in a wide 

spectrum of patients, from high intensity athletes to the 

elderly.8-12 Occlusion training has recently gained increased attention in the rehabilitation community where 

it has produced significant strength gains and in turn 

earlier, faster rehabilitation.9-10 We present 3 cases of active patients with a primary diagnosis of osteoarthritis 

who underwent primary TKA and participated in BFR 

training as part of their postoperative rehabilitation.

Materials and Methods

All patients were identified and cleared by their operating surgeon to participate in BFR training as an adjunct 

to their standard physical therapy. Patients were given 

the opportunity to participate in these therapy adjuncts 

at the suggestion of their operating surgeon following 

postoperative rehabilitation and restoration of adequate 

range of motion as determined by the operating surgeon.

Patients participated in BFR training 3 times a week, 

during which each person was asked to perform leg extension, leg press, and reverse press during each session 

under occlusion conditions. The weight was determined 

based on that individual’s one-repetition maxium (1RM). 

This was calculated by performing a warm-up at 50% of 

the predicted 1RM, followed by an attempt at an 80% 

load. If successful, after a one minute rest, the patient repeated the exercise at the same load for as many repetitions as could safely be performed. If the first repetition 

of 80% was unsuccessful, the weight was decreased, and 

the process repeated. Each exercise was repeated after 

one minute of rest. Tourniquet pressure was set at 80% 

of the limb occlusion pressure. This was determined by 

first inflating the cuff until the pulse in the dorsalis pedis 

was lost using an ultrasound probe. Tourniquet pressure 

averaged between 100 and 150 mmHg for the 3 patients.

Each exercise was performed in 4 sets, with each set 

to failure, and a 30-second rest between sets. When the 

Occlusion Training: Pilot Study for

 Postoperative Lower Extremity

 Rehabilitation Following Primary

 Total Knee Arthroplasty

Capt Christopher L. Gaunder, USAF, MC

CPT Michael P. Hawkinson, MC, USA

CPT David J. Tennent, MC, USA

COL Creighton C. Tubb, MC, USA

Abstract

With continued emphasis on the value of healthcare, factors such as quality of life and patient reported outcomes are critical in evaluating high-demand procedures such as knee replacement surgery. Equally important 

to the surgery itself is maximizing the effectiveness and efficiency of the treatment, both preoperatively and 

postoperatively, which can significantly affect the final outcome. Technical outcomes of total knee replacement 

are generally considered excellent; however, many patients continue to have postoperative pain, functional 

limitations, and low treatment satisfaction. The recovery process can be difficult and is often prolonged in 

older patient populations. Blood flow restriction (BFR) training is a resistance exercise performed with a venous tourniquet that stimulates local changes in muscle at low resistance. Herein we report on 3 patients who 

participated in BFR exercises as an adjunct to their normal physical therapy following total knee arthroplasty.
40 http://www.cs.amedd.army.mil/amedd_journal.aspx

patient was able to perform any one set for more than 

120 seconds before muscle failure, the weight for that 

exercise was increased by 10% to allow for progression. 

At no time did the occlusion training proceed for greater 

than 30 minutes consecutively.

Isokinetic muscle testing was performed at the baseline 

evaluation and at the conclusion of each patient’s physical therapy period using a Biodex System 3 isokinetic 

dynamometer (Biodex Medical Systems, Inc, Shirley, 

NY 11967). For each patient, peak torque was calculated 

as a measure of maximum strength attained throughout 

the range of motion. Total work, a measure of muscular 

endurance, was calculated as the amount of work performed throughout the range of motion. These measurements were taken at 90 degrees/second of both extension and flexion.

Results

Case 1

A 44-year-old male with left knee pain and radiographic 

osteoarthritic changes to his medial and patellofemoral 

compartments with neutral alignment underwent an uncomplicated primary cruciate retaining TKA. Following 

examination and radiographic work-up, he underwent a 

course of nonoperative treatment for his osteoarthritis 

that failed to provide satisfactory long-term relief. As 

such, he was indicated for a left total knee arthroplasty. 

Six weeks following his procedure, his pain was well 

controlled. He had appropriate wound healing and regained his range of motion although he had persistent 

weakness. His personal goals were to fish, spend time 

with his children, and continue to serve in his role as an 

active duty service member in the Army. After participating in 8 weeks of blood flow restriction training, he 

achieved a 359.3% increase in peak torque during extension and 17.8% increase in flexion peak torque at 90 

degrees/second as shown in Figure 1.

Case 2

A 51-year-old male police officer presented with activity-limiting chronic right osteoarthritic knee pain that 

failed nonoperative treatment modalities. Radiographs 

revealed significant medial joint space narrowing and 

degenerative changes of the patellofemoral articulation 

with a 7 degree varus deformity. The patient underwent 

primary cruciate retaining TKA followed by our routine postoperative physical therapy program. However, 

4-months postoperatively he expressed apprehension in 

returning to his job as a patrolman due to his continued 

quadriceps weakness and resultant functional disability. 

He was subsequently enrolled in a BFR training regimen that included leg extensions, leg press, and standing reverse leg press to improve his quadriceps strength 

deficit. After an 8-week BFR program, he demonstrated 

a 57% increase in peak torque in extension and 2.8% in 

flexion at 90 degrees/second as shown in Figure 2 and 

was able to return to his work related activities.

Case 3

A 60-year-old male presented with chronic right knee 

pain that limited his abilities to perform activities of 

daily living. Radiographs demonstrated tricompartmental osteoarthritis, most severe in medial joint space 

OCCLUSION TRAINING: PILOT STUDY FOR POSTOPERATIVE LOWER EXTREMITY REHABILITATION

FOLLOWING PRIMARY TOTAL KNEE ARTHROPLASTY

Figure 1. Case 1 change in peak torque achieved at 90 degrees/second following 8 weeks of blood flow restriction 

training.

Peak Torque in Extension Peak Torque in Flexion

10

20

0

30

40

50

60

80

70

90

Foot-pounds

Uninvolved

Limb

Involved

Limb (initial)

Involved

Limb (final)

Figure 2. Case 2 change in peak torque demonstrated at 90

degrees/second following 8 weeks of blood flow restriction 

training.

20

0

40

60

80

100

140

120

160

Foot-pounds

Peak Torque in Extension Peak Torque in Flexion

Uninvolved

Limb

Involved

Limb (initial)

Involved

Limb (final)
July – September 2017 41

THE ARMY MEDICAL DEPARTMENT JOURNAL

narrowing and a 7 degree varus deformity. He subsequently failed nonoperative treatment and was indicated 

for a primary cruciate retaining TKA. His course was 

complicated by limited range of motion postoperatively. 

He was indicated for manipulation under anesthesia 20 

days after his index procedure. His range of motion was 

2 to 100 degrees of flexion after his manipulation. One 

month after his manipulation, he was referred to physical therapy for BFR due to continued inability to regain 

his quadriceps strength. After participating in 8 weeks 

of BFR training, he experienced an increase in peak 

torque of 84.1% in extension and 126.9% in flexion at 90 

degrees/second as shown in Figure 3.

Comment

In this case series, we report data on 3 patients who underwent total knee arthroplasty and had postoperative 

functional deficits and physical exam findings indicative 

of quadriceps weakness. All 3 patients had persistent 

weakness despite being enrolled in our standard postoperative physical therapy regimen which emphasizes 

range of motion and quadriceps strength. After participation in an 8-week program of BFR training, all 3 had 

objective improvements in their quadriceps strength and 

in all 3 cases exceeded the peak torque measurements of 

their uninvolved limb as measured prior to initiation of 

BFR therapy. To our knowledge, this is the first report of 

the use of BFR therapy following total knee arthroplasty.

As mentioned previously, quadriceps weakness following total knee arthroplasty is well described in the 

literature. Mizner et al13 demonstrated a 62% decrease 

from 10 days preoperative to 27 days postoperatively, 

and other studies have shown decreased strength compared to healthy controls at time points out to 2 years 

postoperatively.14,15 These studies suggest that the weakness is pervasive throughout the full arc of motion of 

the knee and strength oftentimes never fully reassumes 

its preoperative level. To demonstrate the importance 

of this weakness, clinical studies have documented a 

positive correlation between quadriceps strength and 

scoring on multiple validated patient-reported outcome 

measures.15-17 Given this information, there is certainly 

a role for novel rehabilitation tactics that improve our 

ability to rehabilitate postoperative muscle weakness.

Low-load resistance training with blood flow restriction has been shown to elicit substantial increases in 

muscle mass and strength. While the exact mechanism 

of action is not yet fully understood, studies suggest 

that following BFR training there are increased levels 

of anabolic growth hormones and increased activation 

of signaling pathways, such as mTOR, that regulate 

muscle hypertrophy and proliferation of myogenic stem 

cells.7,18-20 Further research is required to determine the 

significance of these factors, though it is clear that BFR 

therapy results in physiologic changes when compared 

to standard resistance training.

While there were no adverse events related to therapy 

in our series, the sample was too small to support any 

significant conclusions. We did not initiate therapy prior 

to 6 weeks postoperatively in any patient as the effect of 

BFR training on wound healing is unknown. The most 

catastrophic adverse events described in the literature 

related to BFR training are deep venous thrombosis 

(DVT), pulmonary embolism, rhabdomyolysis, and exacerbation of ischemic heart disease, all of which occur 

at less than 1% in the literature.21 Another study looking 

specifically at DVTs reported a rate of 0.055% and further demonstrated that there we no increases in hematologic clotting factors after BFR training.22 Furthermore, 

although literature has demonstrated that intraoperative 

occlusive tourniquet use has been associated with decreased quadriceps function postoperatively, the pressures used in BFR training are subocclusive and significantly lower than those used in these studies.23

A major limitation of this series is the lack of patientreported outcomes measurements recorded before and 

after the implementation of blood flow restriction training and lack of a comparison population. Further clinical studies utilizing validated patient-reported questionnaires in addition to functional outcome measures would 

allow for a more accurate comparison assessing both the 

short- and long-term consequences of knee injury and 

osteoarthritis and the potential benefits of blood flow 

restriction training in the postoperative period. Further studies with larger cohorts should be undertaken 

Figure 3. Case 3 change in peak torque demonstrated at 90

degrees/second following 8 weeks of blood flow restriction 

training.

Peak Torque in Extension Peak Torque in Flexion

20

0

40

60

80

100

120

Foot-pounds

Uninvolved

Limb

Involved

Limb (initial)

Involved

Limb (final)
42 http://www.cs.amedd.army.mil/amedd_journal.aspx

to better characterize these risks. Furthermore, as this 

series of patients is small, we are unable to make definitive treatment recommendations. Larger clinical studies 

are required to better elucidate the benefits and risks of 

occlusion training following primary TKA. Possible 

areas for future research would also include the use of 

BFR training preoperatively as preoperative quadriceps 

strength has also been associated with better postoperative outcomes.24 Lastly, as we recognize the potentially 

devastating complications associated with wound healing complications, this intervention should be used with 

caution in the acute postoperative period and only in 

those patients with uncomplicated postoperative courses.

This series represents our early success using BFR training for postoperative TKA patients. While we recognize 

the limitations of this series, we believe that BFR training may provide patients the opportunity to regain their 

strength more quickly and completely, and potentially 

decrease their total duration of physical therapy. Further 

investigation into this therapeutic modality is clearly 

warranted.

References

1. Dahm DL, Banes SA, Harrington JR, Sayeed 

SA, Berry DJ. Patient-reported activity level 

after total knee arthroplasty. J Arthroplasty. 

2008;23(3):401-407.

2. Jain NB, Higgins LD, Ozumba D, et al. Trends 

in epidemiology of knee arthroplasty in the 

United States, 1990-2000. Arthritis Rheum. 

2005;52(12):928-3933.

3. Shan L, Shan B, Suzuki A, Nouh F, Saxena A. Intermediate and long-term quality of life after total 

knee replacement, a systematic review and metaanalysis. J Bone Joint Surg Am. 2015;97(2):156-168.

4. Brander VA, Stulberg SD, Adams AD, Harden RN, 

Bruehl S, Stanos SP, Houle T. Predicting total knee 

replacement pain: a prospective, observational 

study. Clin Orthop Relat Res. 2003;416:27-36.

5. Shi HY, Mau LW, Chang JK, Wang JW, Chiu HC. 

Responsiveness of the Harris Hip Score and the SF36: five years after total hip arthroplasty. Qual Life 

Res. 2009;18(8):1053-1060.

6. Meier W, Mizner RL, Marcus RL, Dibble LE, Peters C, Lastayo PC. Total knee arthroplasty: muscle 

impairments, functional limitations, and recommended rehabilitation approaches. J Orthop Sports 

Phys Ther. 2008;38(5):246-256.

7. Cook SB, Clark, BC, Ploutz-Snyder LL. Effects 

of exercise load and blood-flow restriction on 

skeletal muscle function. Med Sci Sports Exerc. 

2007;39(10):1708-1713.

8. Iida H, Nakajima T, Kurano M, et al. Effects of 

walking with blood flow restriction on limb venous 

compliance in elderly subjects. Clin Physiol Funct 

Imaging. 2011;31(6):472-476.

9. Abe T, Sakamaki M, Fujita S, et al. Effects of lowintensity walk training with restricted leg blood 

flow on muscle strength and aerobic capacity in 

older adults. J Geriatr Phys Ther. 2010;33(1): 34-40.

10. Loenneke JP, Kearney ML, Thrower AD, Collins 

S, Pujol TJ. The acute response of practical occlusion in the knee extensors. J Strength Cond Res. 

2010;24(10):2831-2834.

11. Pope ZK, Willardson JM, Schoenfeld BJ. Exercise 

and blood flow restriction. J Strength Cond Res. 

2013;27(10): 2914-2926.

12. Stevens JE, Mizner RK, Snyder-Mackler L. Quadriceps strength and volitional activation before and 

after total knee arthroplasty for osteoarthritis. J 

Orthop Res. 2003;21:775-779.

13. Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder-Mackler L. Early quadriceps 

strength loss after total knee arthroplasty: the 

contributions of muscle atrophy and failure of voluntary muscle activation. J Bone Joint Surg AM. 

2005;87(5):1047-1053.

14. Mizner RL, Stevens JE, Snyder-Mackler L. Voluntary activation and decreased force production of 

the quadriceps femoris muscle after total knee arthroplasty. Phys Ther. 2003;83(4):359-365.

15. Silva M, Shepherd EF, Jackson WO, Pratt JA, 

McClung CD, Schmalzried TP. Knee strength 

after total knee arthroplasty. J Arthroplasty. 

2003;18(5):605-611.

16. Yoshida Y, Mizner RL, Ramsey DK, SnyderMackler L. Examining outcomes from total knee 

arthroplasty and the relationship between quadriceps strength and knee function over time. Clin 

Biomech. 2008;23(3):320-328.

17. Mizner RL, Petterson SC, Snyder-Mackler L. 

Quadriceps strength and the time course of functional recovery after total knee arthroplasty. J Orthop Sports Phys Ther. 2005;35(7):424-436.

18. Neilsen JL, Aagaard P, Bech RD, et al. Proliferation 

of myogenic stem cells in human skeletal muscle in 

response to low‐load resistance training with blood 

flow restriction. J Physiol. 2012;590(17):4351-4361.

19. Fujita S, Abe T, Drummond MJ, et al. Blood flow 

restriction during low-intensity resistance exercise 

increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol. 2007:103(3):903-910.

20. Fry CS, Glynn EL, Drummond MJ, et al. Blood 

flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men. J 

Appl Physiol. 2010;108(5):1199-1209.

OCCLUSION TRAINING: PILOT STUDY FOR POSTOPERATIVE LOWER EXTREMITY REHABILITATION

FOLLOWING PRIMARY TOTAL KNEE ARTHROPLASTY
July – September 2017 43

THE ARMY MEDICAL DEPARTMENT JOURNAL

21. Nakajima T, Kurano M, Iida H, et al. Use and safety 

of KAATSU Training: results of a national survey. 

Int J Kaatsu Training Res. 2006;2:5-13.

22. Madarame H, Kurano M, Takano H, et al. Effects 

of low intensity resistance exercise with blood 

flow restriction on the coagulation system in 

healthy subjects. Clin Physiol Funct Imaging. 2010; 

30(3):210-213.

23. Saunders KC, Louis DL, Weingarden SI, Waylonis GW. Effect of tourniquet time on postoperative quadriceps function. Clin Orthop Relat Res. 

1979;143:194-199.

24. Mizner RL, Petterson SC, Stevens JE, Axe 

MJ, Snyder-Mackler L. Preoperative quadriceps strength predicts functional ability one year 

after total knee arthroplasty. J Rheumatology. 

2005;32(8):1533-1539.

Authors

Capt Gaunder is an Orthopaedic Surgery Resident at 

the Brooke Army Medical Center, San Antonio Military 

Medical Center, JBSA-Fort Sam Houston, Texas.

CPT Hawkinson is an Orthopaedic Surgery Resident at 

the Brooke Army Medical Center, San Antonio Military 

Medical Center, JBSA-Fort Sam Houston, Texas.

CPT Tennent is an Orthopaedic Surgery Resident at the 

Brooke Army Medical Center, San Antonio Military 

Medical Center, JBSA-Fort Sam Houston, Texas.

COL Tubb is a staff Orthopaedic Adult Reconstruction 

Surgeon at the Brooke Army Medical Center, San Antonio Military Medical Center, JBSA-Fort Sam Houston, 

Texas.
44 http://www.cs.amedd.army.mil/amedd_journal.aspx

The demands on today’s Warfighter have created unique 

challenges to training and equipping Soldiers for military operations. Rarely are large numbers of Soldiers 

and their equipment marched over great distances relying upon the physical endurance of the troops to reach 

strategic objectives. Since the onset of hostilities following the attacks of September 11, 2001, military engagements have involved Soldiers transported to and from 

the area of combat operations by personnel carriers or 

aircraft with their success and survival far more dependent on individual speed, strength, and tactical agility than upon their 2-mile run time. In addition to the 

changing physical demands of modern warfare, increasing fiscal scrutiny while maintaining a brisk operations 

tempo have driven military leadership to question both 

the effectiveness and cost of current physical training 

methods. A number of studies have demonstrated high 

rates of overuse injuries associated with the long-distance marching within our initial entry trainees, further 

adding to the cost of basic training, delaying combat 

readiness, and causing the discharge of a number of 

recruits before they reach their operational unit. International studies have demonstrated that decreased running mileage can have a profound effect on the number 

of overuse injuries while maintaining physical fitness 

among trainees.1

 Given the disproportionately high rate 

of these overuse injuries among female recruits, modification to current training methods is necessary to fully 

accomplish current advances in the integration of women into combat career fields.

Soldiers in today’s military engagements must be 

equipped with speed, strength, and agility, which are 

primarily anaerobic functions. Additionally, Soldiers 

must have middle-distance running and strength endurance—primarily aerobic functions. Thus, a fully 

optimized Soldier must have peak fitness, both anaerobic and aerobic. The reality of the changing physical 

demands placed on Soldiers and the legitimate shortcomings of traditional endurance training suggests 

further advances, applicable for austere environments, 

are needed in the current methods of physical training 

across the military.

Recent data suggests these requirements can be met using martial arts-based high intensity internal training 

(MA-HIIT) by providing optimal aerobic fitness and 

both extremity and core muscle strength with minimal 

resource needs in an environment that fosters esprit-decorps. In addition to a number of health and fitness benefits, HIIT has also been shown to increase aerobic fitness 

without impeding strength gains when combined with 

resistance strength training. Though there are a number 

of recognized safety concerns with martial arts, various safety precautions can be taken to mitigate the risk 

of injury to apply this type of physical training broadly 

across the military. Integrating martial arts into HIIT 

principles could provide a cost-effective and efficient 

way to train both basic trainees and operational military 

units to meet the high demands of present-day military 

operations. This article highlights the known risks and 

benefits associated with a martial arts-based, high intensity interval training program for consideration to be 

incorporated into training, fitness, and rehabilitation of 

Warfighters.

High Intensity Interval Training

High intensity interval training has become a wellknown and well-studied method of improving cardiopulmonary and skeletal muscle function with several 

known metabolic benefits. Enthusiasts use HIIT as a 

form of both individual fitness and competitive athletic 

training, integrating it into a variety of different athletic 

activities. Additional research has broadened the use of 

HIIT by modifying workouts to achieve activity-specific outcomes all along the aerobic-anaerobic spectrum. 

The training consists of “repeated short (less than 45 

seconds) to long (2 to 4 minute) bouts of rather highintensity exercise interspersed with recovery periods.”2

Optimal cardiovascular and peripheral tissue adaptions 

are believed to occur when the athlete is performing at 

or close to their VO2max over long periods of time. This 

can be achieved through a variety of different exercises, 

including short-distance sprints, stationary or road cycling, or martial arts. Documented benefits of HIIT are 

not limited to physiologic and metabolic function, as 

workouts are commonly much shorter in duration than 

Martial Arts-Based High Intensity Interval

 Training as a Component of Warfighter

 Rehabilitation and Tactical Athlete Fitness

Capt Gavin L. Mills, USAF, MC

COL Anthony E. Johnson, MC, USA
July – September 2017 45

traditional lower-intensity, high-volume workouts, saving both time and money for participants.2,3

Mixed Martial Arts

Mixed martial arts (MMA) is a sport derived from a 

mixture of modern and traditional combat sports that 

incorporates punches and kicks from western boxing, 

kick-boxing, and muay thai, stand-up grappling from 

judo, Greco-Roman and freestyle wrestling, and ground 

fighting from jujitsu, judo, and freestyle wrestling. This 

admixture of various combat sport traditions grew in 

popularity under a variety of different names, including 

ultimate fighting, toughman fighting, extreme fighting, 

and mixed martial arts. The physical requirements of 

MMA are characterized by high-intensity and explosive 

movements over short time intervals combined with the 

strength and power of the contenders to deliver high 

velocity blows and control or grapple their opponents 

to achieve dominant positioning and submission holds. 

Mixed martial arts fights usually last 3 to 5 rounds for 5 

minutes each. The winner is decided by knockout, technical knockout, or submission; or the judges decides the 

winner if time runs out.4,5 As the sport has grown in 

popularity, the use of MMA-based workouts has also 

increased. We recommend a regimen of modified MMA 

exercises that excludes floor combat skills and livesparring, integrated with HIIT that we hereafter refer 

to as martial arts-based high intensity interval training 

(MA-HIIT).

Drawbacks to Implementing Martial Arts-Based

High Intensity Interval Training Programs

Implementing an MA-HIIT fitness regimen broadly 

across the military would come with a number of recognized risks, some of which are presented in Table 1. 

Prominent members within the sports medicine community have long voiced concerns over the safety of 

martial arts overall and western boxing in particular.6,12

Some have argued that the sole intent of boxing is to 

inflict physical damage on the opponent and as such 

is “immoral violence.” 12 In truth, there is evidence to 

support the premise that professional boxers do suffer 

from permanent brain damage with up to 87% of boxers 

demonstrating deficits on 2 or more neurophysiological 

tests.8

 With the rise in popularity, and subsequent profitability of mixed martial arts, this opposition has since 

been extended to all forms of “extreme” fighting, with 

calls for reform in the American Medical Association’s 

position on such sports.13

Given the rise in popularity and involvement of a wide 

range of ages, physicians have taken a closer look at the 

risks associated with the sport. Studies of tournamentstyle fighting demonstrates a wide range of injuries. 

Thirty eight percent of taekwondo tournament fighters 

have evidence of head and neck injury, as well as fractures and one reported fatality.14 With the exception of 

cutaneous hematomas and bruising, musculoskeletal injuries are the most common type of injury seen in MMA 

fighters.9

 Given that there is a broad range of martials 

arts forms and styles, each with varying degrees of 

intensity and contact, coupled with the fact that many 

martial artists never compete in tournaments, Zetaruk 

et al 10 compared the injuries in different types of popular martial arts during both periods of normal training 

and tournament competition. Their results demonstrate 

the obvious correlation between the degree of contact 

and injury severity among martial arts. Taekwondo, for 

example, portrayed a 3-fold increase in risk of injury 

than Shotokan karate (a low-impact form of karate) and 

Tai chi, which has no opponent present, confers a very 

minimal risk of injury even though many participants 

are about the age of 65. In the context of normal practice 

and interspersed tournament play, martial artists sustained varying degrees of injury with 59% of students in 

taekwondo sustaining time loss injuries, 51% in aikido, 

38% in kung fu, 30% in Shotokan karate, and only 14% 

of students in tai chi.10 They also found that participants 

who had been practicing for 3 or more years and were 

aged 18 years or older had a higher risk of sustaining 

injury, indicating that more experienced and stronger 

participants were more capable of inflicting injuries on 

opponents. The implementation of a fitness regimen infused with low contact martial arts would require measured risk analysis with reasonable preventive measures 

THE ARMY MEDICAL DEPARTMENT JOURNAL

Table 1. Unfavorable findings and opinions regarding MA-HIIT 

published in the literature.

Reference Summary

Lundberg6 Boxing is dangerous and immoral.

Weisenthal et al7 CrossFit participants showed 20% injury rate, 

most commonly of the shoulder, lower back 

and knee.

Decreased injury rates seen when trainer 

present.

Casson et al8 87% of boxers in study demonstrated signs of 

brain injury on at least 2 different neurophysiological studies.

James9 Besides bruising and cutaneous hematomas, 

muscle and joint injury are the most common 

type of injury in MMA.

Zetaruk et al10 There is a threefold greater risk of injury in taekwondo than in Shotokan karate.

There is a decreased number of injuries in 

MA participants less than 18 years old and 

an increase risk of injury in participants with 

greater than 3 years of experience.

Bergeron et al11 CrossFit may be associated with increased 

risk of rhabdomyolysis, overuse injuries, 

muscle strain, ligamentous injury, and stress 

fractures.
46 http://www.cs.amedd.army.mil/amedd_journal.aspx

to address known injury risks and widespread concerns 

about the implications of martial arts and western boxing.

The health and fitness market has also seen a rise in a 

variety of extreme conditioning programs (ECP) such as 

CrossFit, P90x and Insanity that are similar in intensity 

to MA-HIIT. A number of concerns have been voiced 

regarding such programs due to the relative intensity of 

the workouts. In 2011, the Consortium for Health and 

Military Performance and American College of Sports 

Medicine consensus paper on extreme ECPs among 

military personnel states that ECPs may be associated 

with increased risk of rhabdomyolysis, overuse injuries, 

muscle strain, ligamentous injury, and stress fractures.11

Another survey of CrossFit athletes showed that the 

most common injuries were to the shoulder, low back, 

and knee with an overall injury rate of 20%.15 These 

data give reason to implement preventive measures to 

mitigate the risk of injury possible in MA-HIIT that are 

discussed later in this review.

Martial arts have grown in popularity in the western 

world as a form of physical fitness regimen and as competitive sports with appeal across a broad age-range for 

both sexes. As physicians are charged with oversight 

of our society’s medical wellbeing, there are a number 

of reasons for medical professionals to have measured 

concern with the promotion of combat sports and high 

intensity fitness regimens. Thus, the advantages of this 

type of training as well as an expansive discussion of 

methods to mitigate known risks must also be considered to perform a thorough, evidence-based risk benefit 

analysis of such training.

Benefits of a High Intensity Interval Training

Program

There are several well-studied advantages to both martial arts and HIIT, some of which are presented in Table 

2. We suggest that integrating martial arts-based exercises with HIIT principles would yield additive benefits 

to create an optimized training program for the unique 

demands of military members. Such benefits include 

observed cardiovascular and metabolic improvements, 

injury prevention rates, increased team building within 

participants, and the low relative costs of these regimens.

A number of studies have investigated the functional performance outcomes of HIIT in variety of settings. HIIT 

has been shown to increase VO2max and O2 consumption and improve exercise-induced cardiac output, translating to improved overall exercise performance.16,17,19

Much of the enthusiasm for HIIT in the physical training 

community stems from the possibility to decrease adaptive interference when improvement in both aerobic and 

anaerobic function is desired. Many experts hold that 

muscle hypertrophy, strength, and power from resistance 

training (ie, low-repetition, heavy-weight lifting) are inhibited with high-volume endurance training (ie, longdistance jogging or cycling).18,38 Thus, in the context of 

the Warfighter or “tactical athlete” who must optimize 

both power and endurance, this dynamic would create 

a tradeoff between these 2 metrics of performance. Essentially, the Soldier can either be relatively weak with 

high long-distance endurance or strong with relatively 

low long-distance endurance. A study by Laird et al18 recently challenged this theory. Twenty-eight recreationally active women were enrolled in either a concurrent 

sprint interval and resistance training (CST) group or a 

control group of resistance training (RT) alone. The results demonstrated significant but equal improvements 

in one repetition max back squat, maximal isometric 

force, average peak anaerobic power testing, and zero 

incline treadmill velocity. More importantly, the results 

showed no evidence of interference of strength adaptations in the CST group and simultaneous improvements 

in both anaerobic and aerobic function when HIIT and 

resistance training are used concurrently.18 Smith et al17

further validated the aerobic improvements achieved by 

HIIT in a group of men and women subjects who underwent a 10-week cycle of high intensity power training.

Metabolic improvements in HIIT have been demonstrated in a number of studies investigating cellular adaptations explaining functional gains in both strength and endurance. Burgomaster et al20 observed an increase in the 

maximal activity of citrate synthase leading to increased 

muscle oxidative potential and twice the endurance capacity in cyclers who performed 6 sessions of 15-minute sprint cycling over a 2-week time period. These data 

demonstrate that workouts consisting of intense, short 

duration, sprint-style intervals can significantly improve 

endurance capacity and muscle oxidative potential at or 

above that of long-distance aerobic training regimens 

over similar time periods. Additionally, Ni Cheilleachair 

et al21 observed similar results in a group of competitive 

male rowers finding that HIIT performed twice weekly, 

in addition to baseline aerobic exercise, demonstrates 

improved endurance performance in rowers and is 

more effective than slow-paced, long-distance training 

at improving associated aerobic physiological variables 

including power output and lactate threshold. Investigation by Gibala and McGee22 showed that a short-term 

HIIT program produced marked increases in oxidative 

enzyme expression, oxidative capacity, improved endurance capacity, and changes in carbohydrate metabolism 

that are comparable to traditional endurance training 

with a fraction of the training time. Research has also 

extended beyond exercise science demonstrating even 

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING AS A COMPONENT

OF WARFIGHTER REHABILITATION AND TACTICAL ATHLETE FITNESS
July – September 2017 47

THE ARMY MEDICAL DEPARTMENT JOURNAL

broader effects of HIIT programs. Cho et al23 saw an improvement in whole-body insulin resistance associated 

with obesity in laboratory mice after exposing them to 

HIIT regimens. Richards et al24 saw similar results in a 

test group of healthy adults after 2 weeks of sprint interval training. Drigny et al looked at the effect of HIIT on 

patients with metabolic syndrome. Improvements were 

seen in a number of physiologic metrics associated with 

metabolic syndrome including body mass index (BMI), 

waist circumference and a decrease in echocardiogram 

QT dispersion parameters which has been hypothesized 

to be associated with metabolic syndrome secondary to 

hyper-sympathetic nervous syndrome at baseline.25

Benefits of Martial Arts

The focus on posture, balance and mind-body control 

has demonstrated a variety of both emotional and physical benefits for those who practice martial arts. Byun et 

al26 studied the effects of a regimented treatment program of noncontact taekwondo movements on a group 

of children with postural deficiencies. The children 

showed significant improvement in posture afterwards, 

Table 2. Positive findings and opinions regarding MA-HIIT published in the literature.

Reference Summary

Coswig et al5 MMA sparring matches achieve moderate to high intensity, yet promote only low to moderate muscle damage or 

inflammation based on serum levels of creatinine kindase, IgA, glucose, and cortisol.

Hwang et al16 8-week HIIT program is associated with improvement in cardiac ejection fraction which was positively related to 

exercise-induced improvements in peak 02 consumptions.

Smith et al17 High intensity power training caused increased VO2max and aerobic fitness.

Laird et al18 HIIT does not interfere with strength adaptations while improving aerobic fitness.

Astorino et al19 HIIT regimens increase VO2max which is related to an increase in cardiac output.

Burgomaster et al20 2 weeks of HIIT showed increased citrate synthase maximal activity and doubled endurance capacity during cycling exercise at 80% VO2max.

Ni Cheilleachair et al21 HIIT performed twice weekly in addition to aerobic exercise demonstrates improved endurance performance in 

rowers and is more effective than long, slow-distance training at improving associated aerobic physiological 

variables including power output at lactate threshold.

Gibala and McGee22 Short-term high-intensity interval training shows marked increase in oxidative enzyme expression, improved oxidative capacity, improved endurance capacity and changes in carbohydrate metabolism that are comparable to 

traditional endurance training with a fraction of the training time.

Cho et al23 HIIT regimen in mice alleviates whole body insulin resistance associated with obesity.

Richards et al24 16 minute sessions of very high-intensity, sprint interval exercise training distributed over 2 weeks increased 

insulin sensitivity.

Drigny et al25 HIIT regimens in patients with metabolic syndrome was associated with decreased BMI, reduced waist circumference, and decreased QTd EKG parameters.

Byun et al26 Basic taekwondo movements are associated with statistically significant improvements in children’s posture.

Bu et al27 Tai Chi studies have demonstrated stress reduction, improved agility and balance, posture control, lower extremity strength improvement and decreased musculoskeletal decline seen in aging individuals.

Yan et al28 12-week Tai Chi regimen is associated with clinically significant improvements in pain, stiffness, and physical 

function in patients with knee osteoarthritis.

Yang et al29 Tai Chi shows beneficial effects by improving motor function, balance, and functional mobility in people with Parkinson’s disease compared to other active therapies.

Woodward30 Martial arts are likely associated with decreased number of falls in elderly, improved relaxation, self-esteem, 

mind-body coordination, decreased depression and sleep disruption, increased self-esteem in cancer patients, 

and possibly an adjuvant therapy for symptom control in ADHD patients.

Tong et al31 Core muscle strength improvements are associated with improved endurance running performance.

Jones et al32 Amount of unit training in terms of running distance and amount of weight-bearing physical training was associated with increased risk of over-use injury.

Santtila et al33 HIIT would be an effective method of training recruits because of observed aerobic improvements and low injury 

rates compared to traditional methods.

Hak et al34 Injury rates similar in CrossFit as Olympic weight lifting, power lifting, and gymnastics.

Shoulder and spine injuries are the most common.

No incidences of rhabdomyolysis

Poston et al35 There is no increased risk of rhabdomyolysis in CrossFit/HIFT participants compared to long distance running.

Dibble et al36 HIIT consisting of resistance training produces increased muscle volume, muscle force, and functional status in 

Parkinson’s disease patients when compared to standard exercise programs.

Dibble et al37 High intensity eccentric resistance training improves muscle force, bradykinesia, and quality of life in Parkinson’s 

disease patients to a greater degree than standard exercise programs.
48 http://www.cs.amedd.army.mil/amedd_journal.aspx

demonstrating the effect of martial arts training on core 

muscle strengthening. Tia chi, a no-contact, no-opponent style of martial arts often practiced by a wide range 

of ages including the elderly, has been associated with 

a variety of health benefits including stress reduction, 

improved agility and balance, posture control, and lower 

extremity strength improvement and has been associated with decreased musculoskeletal decline in aging individuals.27 A meta-analysis of the effects of a 12-week 

regimen of tai chi in patients with symptomatic knee 

osteoarthritis showed improvement in pain, stiffness, 

and physical function.28 The effect of tai chi on neurodegenerative processes and balance in the elderly has 

also shown beneficial effects in improving motor function, balance, and overall functional mobility in people 

with Parkinson’s disease when compared to other active 

therapies.29 Woodward et al30 further studied the broad 

effects of martial arts on health status, suggesting that 

martial arts are likely associated with decreased number of falls in the elderly, relaxation, mind-body coordination, decreased depression and sleep disruption, increased self-esteem in cancer patients, and possibly an 

adjuvant therapy for symptom control in patients with 

attention-deficit hyperactivity disorder. Given the wide 

variety of health benefits and symptom improvements 

seen in patients practicing martial arts, especially in tai 

chi studies, further investigation is needed to determine 

the efficacy of this approach as well as to define the specific training regimens needed to achieve such results. 

Even without such available data, the evidence presented by the studies cited above clearly supports the potential of martial arts to cost-effectively produce significant 

health improvements for a variety of patients.

Benefits of a Martial Arts-Based High Intensity

Interval Training Program

The integration of martial arts-based workouts into 

HIIT principles is based on the number of benefits demonstrated in the literature for both martial arts and HIIT. 

Tong et al31 studied the effect of core muscle strengthening in addition to HIIT on endurance running economy, 

showing that the addition of core strengthening exercises, 

such as MA-HIIT, can add to the aerobic improvements 

seen in HIIT. Coswig et al5

 used time-motion responses 

and biological parameters of fatigue and physiological 

stress to characterize the effect of athletes participating 

in sparring matches outside of actual competition fights. 

They found that MMA sparring achieves moderate to 

high intensity yet only low to moderate muscle damage 

and inflammation based on serum levels of creatinine 

kinase, IgA, glucose, and cortisol. These data show 

MMA sparring is an efficient way to simulate the intensity of a live fight with low physiological effect. This 

further supports the hypothesis that martial arts-based 

drills and sparring are a practical method to achieve the 

level of intensity required for HIIT.

When compared to traditional methodology of training military personnel, MA-HIIT provides an effective 

manner by which to prepare Soldiers for the demands 

of modern warfare, decreases overuse injuries, and 

substantially lowers the cost of preliminary military 

training. Several authors have detailed the physical 

challenges faced by today’s Warfighters unique to that 

of past conflicts.39-41 Mala et al39 described the “anaerobic battlefield” in which Soldiers are often engaged in 

high-intensity combat activities such as moving under 

fire, evacuating casualties, and reacting to contact with 

enemy fire, often in close-range urban settings. During 

recent conflicts, such as Operation Iraqi Freedom and 

Operation Enduring Freedom, troops were often transported with personnel carriers or airborne insertion. 

This is in sharp contrast to traditional warfare where infantry Soldiers had to travel on foot over long distances 

while carrying their personal equipment and weapons 

to wage assaults. Once inserted into in an objective, 

Soldiers today perform anaerobic bursts of sprinting, 

climbing, pulling, or crawling while carrying a large 

amount of heavy gear. Turner et al40 suggests that HIIT 

combined with strength and power training and decreasing running volume would deliver the results needed 

to optimize the modern day Warfighter for such tasks. 

This shift in battlefield requirements has yet to be fully 

realized in the way Soldiers are physically trained in 

preparation for deployments. The dynamics of modern 

warfare necessitate a training program that develops anaerobic total body power and explosiveness while maintaining the cardiovascular capacity to support it.38,39

In addition to the evolving demands of modern warfare, 

the recent advances taken to integrate women into combat career fields requires training programs that accommodate the exercise physiology unique to women. Women, on average, have lower body mass, lower bone mass, 

greater body fat, and less lean body mass then men. Due 

to the low levels of circulating testosterone, women 

have less muscle mass and smaller ratio of fast twitch to 

slow twitch fibers. The circulatory and oxygen delivery 

capacity of women is further limited by smaller hearts, 

less circulating intravascular volume, and lower hemoglobin than men.42 Even in the context of such physiologic challenges to optimizing the female tactical athlete, several studies demonstrate that strategic strength 

and conditioning regimens can significantly decrease 

the sex-based differences in physical performance.43-45

Kraemer et al44 demonstrate that periodical resistance 

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING AS A COMPONENT

OF WARFIGHTER REHABILITATION AND TACTICAL ATHLETE FITNESS
July – September 2017 49

THE ARMY MEDICAL DEPARTMENT JOURNAL

training significantly decreases observed strength difference in men and women. Additionally, they demonstrated that increased aerobic fitness resulted in improved functional strength such as repetitive box lifts. 

Through the ability to accomplish both aerobic fitness 

and concurrent resistance training, MA-HIIT would facilitate both muscular hypertrophy and improve functional strength to optimize the capability of women to 

effectively participate in combat career fields.43,44

One of the strongest factors catalyzing change in military training across several nations is the rate of injuries 

seen in traditional training methods consisting of large 

volume endurance exercises (ie, long-distance running 

or marching) and the associated high cost of these injuries.46 In 1993, Jones et al 32 studied the epidemiology 

of military training injuries, finding that 37% of basic 

trainees incurred lower extremity injuries, 28.4% of 

which were overuse injuries (stress fractures, Achilles tendonitis, or patellofemoral syndrome). More importantly, they found that the amount of unit training 

in terms of running distance was positively correlated 

with overuse injury. Later, in 2001, Knapik et al47 expanded on these findings showing that overuse injuries 

accounted for 75% and 78% of male and female injuries 

respectively and that women were twice as likely to sustain training-related injuries as men. It was previously 

thought that encouraging pretraining in recruits would 

reduce the large number of overuse injuries seen in basic 

trainees. Swissa et al48 explored this theory and found 

that no correlation existed between pre-basic training activity and the number of stress fractures reported. This 

further highlights the need for high-quality, evidencebased training programs in the military. Even among 

highly trained Naval Special Warfare Sea, Air, and Land 

(SEAL) operators that routinely engage in high-risk, tactical missions and training, 20% of all their injuries occur during physical conditioning.49 In the face of these 

high injury-rates, HIIT has been recognized as an adequate method to train basic trainees primarily due to the 

decreased rates of injury as well as the positive effect on 

aerobic fitness.33 In summary, the high rates of overuse 

and musculoskeletal injuries in both basic trainees and 

special operations force units would be decreased while 

increasing physical performance by implementing MAHIIT into military physical training programs.

The ability to actually address the well-known causes of 

overuse injuries has proven more difficult than expected, yet there have been several studies demonstrating 

effective techniques to do so if implemented appropriately. Chalupa et al46 found that Soldiers participating 

in the Army physical readiness program (APRP) had 

reduced overuse and musculoskeletal injuries including 

tarsal bone and femoral neck stress fractures. The primary differences in the APRP from traditional training 

is a decreased amount of long-distance endurance running and integration of interval training. Additionally, 

researchers found that the Israeli military was able to 

reduce high rates of stress fractures in Soldiers by decreasing the total distance marched or ran and increasing the number of hours slept per night by trainees.1

Given the clear association between overuse injuries 

in the military and total distances ran by trainees, MAHIIT would provide an effective way to improve aerobic 

fitness while decreasing long-distance training to minimize overuse injuries.

Strategies to Mitigate Potential Risks of MA-HIIT

Given the relative intensity of MA-HIIT and the known 

risks associated with it, there are several measures that 

can be taken to mitigate such risks. We recommend 

against using exercises that incorporate live strikes to 

the head and groin or choke and submission holds which 

would largely decrease the known risks of head and neck 

injury in combat sports.10,50 We also recommend the use 

of protective gear such as gel gloves and proper punching pads or bags.30 Attention should be given to proper 

technique, as there is data to suggest that adherence 

to correct form and prescribed workout regimen with 

the use of a trained instructor or instructor-participant 

decreases injury.9,15,51 Additionally, in agreement with 

several other sources,11,34 we recommend periodization 

with a proper familiarization period, individualizing 

workouts to Soldiers’ abilities, frequent inspection of 

workout equipment and facilities, and monitoring profile rates that suggest evidence of overtraining within 

units. We also recommend the strict adherence to known 

principles of exercise (ie, PROVERBS* and FITT†) to 

encouraged successful, well-balanced and injury-free 

physical training. Though MA-HIIT is likely associated 

with several risks of injury, implementing rather simple 

methods to decrease such risks enables MA-HIIT to be 

both effective and safe for broad use across the military.

Risk/Benefit Analysis

After sufficient review of the available literature pertaining to the use of MA-HIIT, the recognized risks and 

benefits associated with this type of physical training 

program can be compared. The main risks for participants largely consist of musculoskeletal injury given the 

dynamic exercises used. Using appropriate oversight and 

*Progression, Regularity, Overload, Variety, Recovery, Balance, 

Specificity. Source: US Army Fitness Handbook (http://www.

physicallytrained.com/army-fitness-handbook-1-physical-fitnessprinciples/).

†Frequency, Intensity, Time, Type (http://stretchcoach.com/ar

ticles/fitt-principle/).
50 http://www.cs.amedd.army.mil/amedd_journal.aspx

technical instruction with periods of familiarization for 

participants, these risks can be decreased. Though some 

believe there to be a risk of rhabdomyolysis secondary 

to the intensity of the training, several sources point out 

there is little to no evidence to support such claims, suggesting the overall intensity of MA-HIIT confers minimal 

risk on participants.34,35 Many of the injuries associated 

with competitive martial arts are mitigated by not striking opponents and using safety equipment. The numerous studies demonstrating benefits in HIIT, such as improvements in aerobic fitness without impairing strength 

training and lower rates of overuse injury secondary 

to lower mileage make it an optimal model of physical 

training. A decrease in the number of overuse injuries 

alone could potentially save the military millions of dollars annually. Additionally, MA-HIIT betters equips the 

Warfighter for the anaerobic demands of modern warfare 

with the cardiovascular reserve to sustain prolonged engagements. Given the known risks and benefits of MAHIIT, this program would provide substantial improvement to existing training programs and should be used 

to train military personnel. Since 2010, the Center for the 

Intrepid and the Department of Orthopaedic Surgery at 

Brooke Army Medical Center have incorporated a martial arts-based high intensity interval training program 

in the rehabilitation of over 500 wounded warriors with 

extremity war injuries, both amputees and limb-salvage 

patients, with oversight by Orthopaedic Sports Medicine 

specialists trained in martial arts.

Conclusion

Martial arts-based high intensity interval training, overseen by a qualified instructor and following known 

principles of exercise and sports medicine provides an 

optimal training program for today’s Warfighter, as well 

as rehabilitation/reintegration of the wounded warrior. 

Implementation of MA-HIIT across the military has the 

potential to provide a time and cost effective method of 

training that would improve existing levels of physical 

performance and likely decrease overuse injury rates in 

the military. Further well-formulated, prospective studies are necessary to provide more data for the implementation of MA-HIIT programs across both military and 

civilian organizations.

References

1. Finestone A, Milgrom C. How stress fracture incidence was lowered in the Israeli army: a 25-yr 

struggle. Med Sci Sports Exerc. 2008;40(suppl 

11):S623-S629.

2. Buchheit M, Laursen PB. High-intensity interval 

training, solutions to the programming puzzle. Part 

II: anaerobic energy, neuromuscular load and practical applications. Sports Med. 2013;43(10):927-954.

3. Buchheit M, Laursen PB. High-intensity interval 

training, solutions to the programming puzzle. 

Sports Med. 2013;43(5):313-338.

4. Amtmann JA. Self-reported training methods of 

mixed martial artists at a regional reality fighting 

event. J Strength Cond Res. 2004;18(1):194-196.

5. Coswig VS, de Paula Ramos S, Del Vecchio FB. 

Time-motion and biological responses in simulated 

mixed martial arts sparring matches. J Strength 

Cond Res. 2016;30(8):2156-2163.

6. Lundberg GD. Boxing should be banned in civilized countries. JAMA. 1983;249(2):250.

7. Weisenthal BM, Beck CA, Maloney MD, DeHaven KE, Giordano BD. Injury Rate and Patterns 

Among CrossFit Athletes. Orth J Sports Med. 2014, 

2(4):2325967114531177

8. Casson IR, Siegel O, Sham R, Campbell EA, Tarlau M, DiDomenico A. BRain damage in modern 

boxers. JAMA. 1984;251(20):2663-2667.

9. James LP. Injury Prevention Strategies for Mixed 

Martial Arts. Strength Cond J. 2014;36(5):88-95.

10. Zetaruk MN, Violán MA, Zurakowski D, Micheli 

LJ. Injuries in martial arts: a comparison of five 

styles. Br J Sports Med. 2005;39(1):29-33.

11. Bergeron MF, Nindl BC, Deuster PA, et al. Consortium for Health and Military Performance and 

American College of Sports Medicine consensus 

paper on extreme conditioning programs in military personnel. Curr Sports Med Rep. Nov-Dec 

2011;10(6):383-389.

12. Kriegel M. A step back. New York Times. September 16, 2012.

13. Lundberg GD. Blunt force violence in America-

-shades of gray or red. Ultimate/extreme fighting. 

JAMA. 1996;275(21):1684-1685.

14. Oler M, Tomson W, Pepe H, Yoon D, Branoff R, 

Branch J. Morbidity and mortality in the martial 

arts: a warning. J Trauma. 1991;31(2):251-253.

15. Weisenthal BM, Beck CA, Maloney MD, DeHaven KE, Giordano BD. Injury rate and 

patterns among CrossFit athletes. Orthop J 

Sports Med.. 2014;2(4). Available at: https://doi.

org/10.1177/2325967114531177. Accessed May 3, 

2017.

16. Hwang CL, Yoo JK, Kim HK, et al. Effect of 

high-intensity interval training versus moderateintensity continuous training on cardiac function in 

older adults: Paper presented at: 63rd Annual Meeting of the American College of Sports Medicine; 

June 2, 2016; Boston MA. Abstract available at: 

http://www.acsmannualmeeting.org/wp-content/

uploads/2016/05/ACSM16_Abstracts_Session_C_

vFIN_web_gray.pdf. pS265, presentation 1315. Accessed May 4, 2017.

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING AS A COMPONENT

OF WARFIGHTER REHABILITATION AND TACTICAL ATHLETE FITNESS
July – September 2017 51

THE ARMY MEDICAL DEPARTMENT JOURNAL

17. Smith MM, Sommer AJ, Starkoff BE, Devor ST. 

Crossfit-based high-intensity power training improves maximal aerobic fitness and body composition. J Strength Cond Res. 2013;27(11):3159-3172.

18. Laird RH 4th, Elmer DJ, Barberio MD, Salom LP, 

Lee KA, Pascoe DD. Evaluation of performance 

improvements following either resistance training or sprint interval-based concurrent training. J 

Strength Cond Res. 2016;30(11):3057-3065.

19. Astorino TA, Edmunds RM, Clark A, et al. Effect 

of Various regimes of high intensity interval training (HIIT) on changes in maximal oxygen uptake 

and hemodynamic function. Paper presented at: 

63rd Annual Meeting of the American College of 

Sports Medicine; June 2, 2016; Boston MA. Abstract available at: http://www.acsmannualmeeting.org/wp-content/uploads/2016/05/ACSM16_Ab

stracts_Session_D_vFIN_web_gray.pdf, pg S383, 

presentation 1817. Accessed May 4, 2017.

20. Burgomaster KA, Hughes SC, Heigenhauser GJ, 

Bradwell SN, Gibala MJ. Six sessions of sprint interval training increases muscle oxidative potential 

and cycle endurance capacity in humans. J Appl 

Physiol. 2005;98(6):1985-1990.

21. Ni Cheilleachair NJ, Harrison AJ, Warrington GD. 

The effect of HIIT on blood lactate indices and 

performance in well-trained male rowers. Paper 

presentation 1818 at: 63rd Annual Meeting of the 

American College of Sports Medicine; June 2, 2016; 

Boston MA. Abstract available at: http://www.acs

mannualmeeting.org/wp-content/uploads/2016/05/

ACSM16_Abstracts_Session_D_vFIN_web_gray.

pdf, pg S383, presentation 1818. Accessed May 4, 

2017.

22. Gibala MJ, McGee SL. Metabolic adaptations 

to short-term high-intensity interval training: a 

little pain for a lot of gain?. Exerc Sport Sci Rev. 

2008;36(2):58-63.

23. Cho J, Kim D, Lee I, Chang J, Kang H. high-intensity interval training improves whole body insulin resistance via the hepatic AdipoR1 mediatedsignaling pathway. Paper presented at: 63rd Annual Meeting of the American College of Sports 

Medicine; June 2, 2016; Boston MA. Abstract 

available at: http://www.acsmannualmeeting.org/

wp-content/uploads/2016/05/ACSM16_Abstracts_

Session_D_vFIN_web_gray.pdf, pg S405, presentation 1902. Accessed May 4, 2017.

24. Richards JC, Johnson TK, Kuzma JN, et al. Shortterm sprint interval training increases insulin sensitivity in healthy adults but does not affect the 

thermogenic response to beta-adrenergic stimulation. J Physiol. 2010;588(Pt 15):2961-2972.

25. Drigny J, Gremeaux V, Guiraud T, Gayda M, Juneau M, Nigam A. Long-term high-intensity interval training associated with lifestyle modifications improves QT dispersion parameters in metabolic syndrome patients. Ann Phys Rehabil Med. 

2013;56(5):356-370.

26. Byun S, An C, Kim M, Han D. The effects of an 

exercise program consisting of taekwondo basic 

movements on posture correction. J Phys Ther Sci. 

2014;26(10):1585-1588.

27. Bu B, Haijun H, Yong L, Chaohui Z, Xiaoyuan 

Y, Singh MF. Effects of martial arts on health 

status: a systematic review. J Evid Based Med. 

2010;3(4):205-219.

28. Yan JH, Gu WJ, Sun J, Zhang WX, Li BW, Pan 

L. Efficacy of Tai Chi on pain, stiffness and function in patients with osteoarthritis: a meta-analysis. 

PloS One. 2013;8(4):e61672.

29. Yang Y, Li XY, Gong L, Zhu YL, Hao YL. Tai Chi 

for improvement of motor function, balance and 

gait in Parkinson’s disease: a systematic review and 

meta-analysis. PloS One. 2014;9(7):e102942.

30. Woodward TW. A review of the effects of martial 

arts practice on health. WMJ. 2009;108(1):40-43.

31. Tong TK, McConnell AK, Lin H, Nie J, Zhang H, 

Wang J. “Functional” inspiratory and core muscle 

training enhances running performance and economy. J Strength Cond Res. 2016;30(10);2942-2951.

32. Jones BH, Cowan DN, Tomlinson JP, Robinson 

JR, Polly DW, Frykman PN. Epidemiology of injuries associated with physical training among 

young men in the army. Med Sci Sports Exerc. Feb 

1993;25(2):197-203.

33. Santtila M, Pihlainen K, Viskari J, Kyrolainen H. 

Optimal physical training during military basic 

training period. J Strength Cond Res. 2015;29(suppl 11):S154-S157.

34. Hak PT, Hodzovic E, Hickey B. The nature and 

prevalence of injury during CrossFit training. J 

Strength Cond Res. 2013;epub. Available at: http://

insights.ovid.com/crossref?an=00124278-9000

00000-97557. Accessed May 4, 2017.

35. Poston WS, Haddock CK, Heinrich KM, Jahnke 

SA, Jitnarin N, Batchelor DB. Is high-intensity 

functional training (HIFT)/crossfit safe for military 

fitness training?. Mil Med. 2016;181(7):627-637.

36. Dibble LE, Hale TF, Marcus RL, Droge J, Gerber 

JP, LaStayo PC: High-intensity resistance training 

amplifies muscle hypertrophy and functional gains 

in persons with Parkinson’s disease. Mov Disord. 

2006;21(9):1444-1452.
52 http://www.cs.amedd.army.mil/amedd_journal.aspx

37. Dibble LE, Hale TF, Marcus RL, Gerber JP, LaStayo PC: High intensity eccentric resistance training decreases bradykinesia and improves quality 

of life in persons with Parkinson’s disease: a preliminary study. Parkinsonism Relat Disord. 2009, 

15(10):752-757.

38. Friedl KE, Knapik JJ, Häkkinen K, et al. Perspectives on aerobic and strength influences on military 

physical readiness: report of an international military physiology roundtable. J Strength Cond Res. 

2015;29:S10-S23.

39. Mala J, Szivak TK, Kraemer WJ. Improving performance of heavy load carriage during highintensity combat-related tasks. Strength Cond J. 

2015;37(4):43-52.

40. Turner A. Strength and conditioning for British soldiers. Strength Cond J. 2016;38(3):59-68.

41. Szivak TK, Mala J, Kraemer WJ. Physical performance and integration strategies for women in 

combat arms. Strength Cond J. 2015;37(4):20-29.

42. Greeves JP. Physiological implications, performance assessment and risk mitigation strategies of 

women in combat-centric occupations. J Strength 

Cond Res. 2015;29(suppl 11):S94-S100.

43. Nindl BC. Physical training strategies for military 

women’s performance optimization in combatcentric occupations. J Strength Cond Res. Nov 

2015;29(suppl 11):S101-S106.

44. Kraemer WJ, Mazzetti SA, Nindl BC, et al. Effect 

of resistance training on women’s strength/power 

and occupational performances. Med Sci Sports 

Exerc. 2001;33(6):1011-1025.

45. Yanovich R, Evans R, Israeli E, et al. Differences in 

physical fitness of male and female recruits in gender-integrated army basic training. Med Sci Sports 

Exerc. 2008;40(suppl 11):S654-S659.

46. Chalupa RL, Aberle C, Johnson AE. Observed 

rates of lower extremity stress fractures after implementation of the Army physical readiness training program at JBSA Fort Sam Houston. US Army 

Med Dep J. January-March 2016:6-9.

47. Knapik JJ, Sharp MA, Canham-Chervak M, 

Hauret K, Patton JF, Jones BH. Risk factors for 

training-related injuries among men and women 

in basic combat training. Med Sci Sports Exerc. 

2001;33(6):946-954.

48. Swissa A, Milgrom C, Giladi M, et al. The effect of 

pretraining sports activity on the incidence of stress 

fractures among military recruits. A prospective 

study. Clin Orthop Relat Res. 1989(245):256-260.

49. Lovalekar M, Abt JP, Sell TC, Wood DE, Lephart 

SM. Descriptive epidemiology of musculoskeletal 

injuries in Naval special warfare sea, air, and land 

operators. Mil Med. 2016;181(1):64-69.

50. Nishime RS. Martial arts sports medicine: current 

issues and competition event coverage. Curr Sports 

Med Rep. Jun 2007;6(3):162-169.

51. Sell TC, Abt JP, Nagai T, et al. The Eagle Tactical 

Athlete Program reduces musculoskeletal injuries 

in the 101st Airborne Division (Air Assault). Mil 

Med. 2016;181(3):250-257.

Authors

Capt Mills is with the Department of Orthopaedic Surgery, San Antonio Military Medical Center, JBSA-Fort 

Sam Houston, Texas.

COL Johnson is the Chairman, Department of Orthopaedic Surgery, San Antonio Military Medical Center, 

JBSA-Fort Sam Houston, Texas.

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING AS A COMPONENT

OF WARFIGHTER REHABILITATION AND TACTICAL ATHLETE FITNESS

Articles published in the Army Medical Department Journal are indexed in MEDLINE, the National 

Library of Medicine’s bibliographic database of life sciences and biomedical information. Inclusion 

in the MEDLINE database ensures that citations to AMEDD Journal content will be identified to 

researchers during searches for relevant information using any of several bibliographic search tools, 

including the National Library of Medicine’s PubMed service.
July – September 2017 53

The US armed forces are currently engaged in the longest active period of continuous armed conflict in US 

history. The advancements in tactical combat casualty 

care, rapid medical evacuation, and improvements in 

personal body armor and armored vehicles have resulted in unprecedented survival rates. The second-order 

effect of the improved survival of combat injuries is the 

increased clinical burden of extremity injuries, including amputations.1

 These unique features of casualty care 

within Operations Iraqi Freedom (OIF) and Enduring 

Freedom (OEF), coupled with the widespread use of a 

myriad of improvised explosive devices (IEDs)/roadside 

bombs have given rise to the almost 1,700 individuals 

with major limb amputations from 2001 to 2015.2-5

The long-term nature of musculoskeletal combat injuries has a profound effect on service members’ potential 

for continued military service as well as their quality 

of life after separation from service. In a cohort from 

2001-2005, 69% of unfit-for-duty conditions were orthopaedic/musculoskeletal. In the midst of OIF and OEF, 

many advances were made with regards to rehabilitation 

and reintegration of service members with severe extremity injury, regardless of limb-salvage or amputation. 

Unfortunately, the return to duty rate postamputation is 

low, on average 8.8% for lower extremity amputations 

and 8% for upper extremity amputations.6,7 Furthermore, 

regardless of whether the medical disposition of the injured service member is return to duty, continuation on 

active duty in another military occupational specialty, 

or separation from military service, their emotional 

wellness remains significantly degraded. An estimated 

28.7% to 35% of combat amputees have comorbid depressive symptoms.8,9 The toll that a traumatic amputation has on a Soldier’s physical and mental wellbeing 

cannot be overstated. In a study of resource utilization 

in the care of combat injuries, “extremity injuries require the longest average inpatient stay, were responsible for 64% of total inpatient resource utilization and 

ultimately disabled 64% of those injured.”10 It is clear 

that extremity injuries represent the largest clinical 

burden of the current and recent past military conflicts, 

the most severe of which are combat amputations. Military orthopaedic surgeons are now charged with providing the highest level of treatment and rehabilitation for 

posttraumatic combat amputees to ensure they regain 

the highest possible quality of life regardless of the 

overwhelming challenges they face, while also retaining these critical lessons learned for the betterment of 

casualties from future wars.

Treating the combat amputee requires careful consideration of a number of characteristics unique to these 

patients when compared to amputees amongst the general population. Of the amputations performed in the US 

general population, over 80% are due to nontraumatic 

causes, the majority of which being vascular and oncologic disease.11 These patients are typically older, have 

several comorbidities, are less active at baseline, and 

have decreased functional demands when compared to 

posttraumatic amputees, especially those of the military.12 In fact, nearly half of the patients that receive an 

amputation secondary to vascular disease will die within 5 years of the operation.13 Posttraumatic amputees, 

on the other hand, are often younger, in better physical 

and cardiovascular condition at the time of injury, desire 

more active lifestyles, and have a higher survival rate 

following amputation.14 Many combat amputees also 

sustain other injuries associated with their combat trauma. As many as 16% of amputees have lost more than 

one extremity, 39% also have long bone fractures, 45% 

have active infections, and 12% have peripheral nerve 

injuries.15 Additionally, posttraumatic stress disorder is 

commonly associated with patients with orthopaedic 

combat injuries.6

 Taking into consideration the characteristics unique to the posttraumatic combat amputee is 

essential in providing comprehensive rehabilitative care 

with several nuances that differ from standard noncombat amputee care.

Since the onset of the hostilities following the attacks 

of September 11, 2001, several advances related to the 

Martial Arts-Based High Intensity

 Interval Training in the Rehabilitation

 of Combat Amputees

Capt Gavin L. Mills, USAF, MC

CPT David J. Tennent, MC, USA

LTC Joseph F. Aldrete, MC, USA

COL Anthony E. Johnson, MC, USA
54 http://www.cs.amedd.army.mil/amedd_journal.aspx

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING 

IN THE REHABILITATION OF COMBAT AMPUTEES

rehabilitation of the combat amputee have been developed to achieve maximum function in these patients. 

Research shows a number of positive aspects of exercise routines relevant to combat amputees including improved health outcomes of quality of life, functional capacity and mood states, decreased metabolic cost of ambulation, and reduced anxiety.16-18 Previous studies have 

shown that participation in sports can help amputees 

cope with their perceived physical impairments by providing adaptive athletic opportunities that maximize engagement in new activities while minimizing disability.

Additionally, pursuing sports as an amputee allows patients to discover the options available to them regarding different types of activities and prostheses, as well 

as gain the motor control necessary to control the prosthetic limb for athletic participation.12 One study showed 

that rehabilitation programs with the use of the prosthesis to achieve activity correlates with improved overall quality of life and satisfaction with the prosthesis.19

Specifically, measures of quality of life and self-esteem 

are higher in amputees who participate in sports as well 

as “enhanced psychological well-being, self-confidence, 

and coping behavior.”12 Amputee participation in athletics leads to improvements in the cardiopulmonary system, muscle force generation, and lean body mass, as 

well as decreased rehabilitation time.12 Using sports to 

develop a physical fitness regimen for combat amputees 

is a component of the culturally competent care process 

for veterans that is proving to be essential to their overall rehabilitation.12

High intensity interval training (HIIT) has become a 

popular evidence-based approach to developing cardiovascular fitness as well as improving muscular strength. 

The HIIT programs emphasize short, repetitive intervals of less than 4 minutes of explosive exercises, allowing the trainee to exercise at or close to VO2max over a 

significant period of time.20 Several studies demonstrate 

that HIIT can lead to improvements in cardiopulmonary 

fitness, musculoskeletal strength, and several metabolic 

parameters. The training regimens are modifiable to optimize activity-specific improvements at various points 

along the aerobic-anaerobic spectrum. A number of 

different exercises can be used within the HIIT model including sprints, seated rows, cycling, and martial 

arts. Recently, researchers have investigated the utility 

of modifying HIIT principles to maximize the fitness 

requirements of men and women in the armed forces 

into a program called martial arts-based high intensity 

interval training or MA-HIIT.21

Benefits of an integrated MA-HIIT program include 

“observed cardiovascular and metabolic improvements, 

decreased injury rates, increased team building within 

participants, and the low relative costs of these regimens.”21 The numerous studies demonstrating the benefits of HIIT, such as improvements in aerobic fitness 

without impairing strength training and lower rates of 

military training overuse injury secondary to lower 

running mileage make MA-HIIT an optimal model of 

physical training in the military. Additionally, MA-HIIT 

better equips the warfighter for the anaerobic demands 

of the modern battlefield with the cardiovascular reserve 

to sustain prolonged combat engagements.21

Although conceived as a way to optimize fitness and resilience of the fighting force in general, MA-HIIT is also 

being used to optimize the rehabilitation of combat amputees. Since 2010, the Center for the Intrepid and the 

Department of Orthopaedic Surgery at the San Antonio 

Military Medical Center have used a martial arts-based 

high intensity interval training program to rehabilitate 

over 500 combat veterans who sustained severe extremity injuries, both amputees and limb salvage patients, as 

demonstrated in the Figure. Patients receive coaching 

during MA-HIIT sessions by Orthopaedic Sports Medicine specialists trained in martial arts. While several 

combat amputees have thrived in this program and were 

A combat amputee undergoing martial arts-based high intensity interval training at the Center for the Intrepid at San Antonio Military Medical Center.
July – September 2017 55

THE ARMY MEDICAL DEPARTMENT JOURNAL

very positive in their assessments of its results, there 

remains a dearth of scientific evidence-based practices 

from which to derive best practices on the use of MAHIIT for rehabilitating these combat injured patients. 

Though some authors advocate gradual orientation to 

exercise regimens and limiting amputees to moderate or 

low intensity exercises, little empiric evidence exists to 

support these reservations.22 In fact, one study showed 

similar injury rates among amputees and able bodied 

players competing in noncontact football.12 Patients that 

begin a rehabilitation program sooner after their amputation achieve better walking ability postoperatively.23

Though more studies are needed to explore the effectiveness of MA-HIIT on this subset of traumatic amputees, the potential of providing a comprehensive and effective rehabilitation program remains promising given 

the current body of knowledge.

The combat amputee has several barriers to successful 

rehabilitation to premorbid function that are unique to 

young, healthy, and motivated patients who underwent 

extremely traumatic injuries. MA-HIIT programs offer 

an excellent method to achieve and maintain maximal 

cardiovascular fitness and musculoskeletal strength 

while providing the opportunity for patients to become 

more aware and confident of their control of their residual limb and/or prosthesis. Additionally, working 

together with other amputees overcoming similar challenges to their recovery embodies the warrior ethos and 

encourages comradery amongst wounded warriors and 

their care providers. Creating a rehabilitative program 

that adequately addresses the challenges unique to combat amputees while providing the mental and physical training necessary can likely be achieved through 

implementing MA-HIIT. However, more well-designed 

studies are necessary before adequate definitive data 

is available to support creation of a formal, evidencebased program incorporating MA-HIIT into an overall 

rehabilitative treatment regimen for amputees.

References

1. Cross JD, Ficke JR, Hsu JR, Masini BD, Wenke JC. 

Battlefield orthopaedic injuries cause the majority 

of long-term disabilities. J Am Acad Orthop Surg. 

2011;19(suppl 1):S1-S7.

2. Rabago CA, Clouser M, Dearth CL, et al. The Extremity Trauma and Amputation Center of Excellence: Overview of the Research and Surveillance 

Division. Mil Med. 2016;181(S4):3-12.

3. Kelly JF, Ritenour AE, McLaughlin DF, et al. Injury severity and causes of death from Operation 

Iraqi Freedom and Operation Enduring Freedom: 

2003-2004 versus 2006. J Trauma. 2008;64(suppl 

2):S21-S26, discussion S26-S27.

4. Krueger CA, Wenke JC, Ficke JR. Ten years 

at war: comprehensive analysis of amputation 

trends. J Trauma Acute Care Surg. 2012;73(6 suppl 

5):S438-S444.

5. Stansbury LG, Lalliss SJ, Branstetter JG, Bagg 

MR, Holcomb JB. Amputations in U.S. military 

personnel in the current conflicts in Afghanistan 

and Iraq. J Orthop Trauma. 2008;22(1):43-46.

6. Belisle JG, Wenke JC, Krueger CA. Return-to-duty 

rates among US military combat-related amputees 

in the global war on terror: job description matters. 

J Trauma Acute Care Surg. 2013;75(2):279-286.

7. Tennent DJ, Wenke JC, Rivera JC, Krueger CA. 

Characterisation and outcomes of upper extremity 

amputations. Injury. 2014;45(6):965-969.

8. Kashani JH, Frank RG, Kashani SR, Wonderlich 

SA, Reid JC. Depression among amputees. J Clin 

Psychiatry. 1983;44(7):256-258.

9. Darnall BD, Ephraim P, Wegener ST, et al. Depressive symptoms and mental health service 

utilization among persons with limb loss: results 

of a national survey. Arch Phys Med Rehabil. 

2005;86(4):650-658.

10. Masini BD, Waterman SM, Wenke JC, Owens BD, 

Hsu JR, Ficke JR. Resource utilization and disability outcome assessment of combat casualties from 

Operation Iraqi Freedom and Operation Enduring 

Freedom. J Orthop Trauma. 2009;23(4):261-266.

11. Heikkinen M, Saarinen J, Suominen VP, Virkkunen J, Salenius J. Lower limb amputations: differences between the genders and long-term survival. Prosthet Orthot Int. 2007;31(3):277-286.

12. Bragaru M, Dekker R, Geertzen JH, Dijkstra PU. 

Amputees and sports: a systematic review. Sports 

Med. 2011;41(9):721-740.

13. Robbins JM, Strauss G, Aron D, Long J, Kuba J, 

Kaplan Y. Mortality rates and diabetic foot ulcers: 

is it time to communicate mortality risk to patients 

with diabetic foot ulceration?. J Am Podiatr Med 

Assoc. Nov-Dec 2008;98(6):489-493.

14. Lepantalo M, Matzke S. Outcome of unreconstructed chronic critical leg ischaemia. Eur J Vasc 

Endovasc Surg. 1996;11(2):153-157.

15. Potter BK, Scoville CR. Amputation is not isolated: 

an overview of the US Army Amputee Patient Care 

Program and associated amputee injuries. J Am 

Acad Orthop Surg. 2006;14(10 spec no.):S188-S190.

16. Penedo FJ, Dahn JR. Exercise and well-being: a review of mental and physical health benefits associated with physical activity. Curr Opin Psychiatry. 

2005;18(2):189-193.

17. Ward KH, Meyers MC. Exercise performance 

of lower-extremity amputees. Sports Med. 

1995;20(4):207-214.
56 http://www.cs.amedd.army.mil/amedd_journal.aspx

18. Aşçi FH. The effects of physical fitness training 

on trait anxiety and physical self-concept of female university students. Psychol Sport Exerc. 

2003;4(3):255-264.

19. Akarsu S, Tekin L, Safaz I, Goktepe AS, Yazicioglu K. Quality of life and functionality after lower 

limb amputations: comparison between uni- vs. 

bilateral amputee patients. Prosthet Orthot Int. 

2013;37(1):9-13.

20. Buchheit M, Laursen PB. High-intensity interval 

training, solutions to the programming puzzle. Part 

II: anaerobic energy, neuromuscular load and practical applications. Sports Med. 2013;43(10):927-954.

21. Mills G, Johnson A. Martial arts-based high intensity interval training as a component of warfighter 

rehabilitation and tactical athlete fitness. US Army 

Med Dep J. July-September 2017:33-41.

22. Matthews D, Sukeik M, Haddad F. Return to sport 

following amputation. J Sports Med Phys Fitness. 

2014;54(4):481-486.

23. Sansam K, Neumann V, O’Connor R, Bhakta B. 

Predicting walking ability following lower limb 

amputation: a systematic review of the literature. J 

Rehabil Med. 2009;41(8):593-603.

Authors

Capt Mills is with the Department of Orthopaedic Surgery, San Antonio Military Medical Center, JBSA-Fort 

Sam Houston, Texas.

CPT Tennent is with the Department of Orthopaedic 

Surgery, San Antonio Military Medical Center, JBSAFort Sam Houston, Texas.

LTC Aldrete is the Medical Director, Center for the Intrepid, San Antonio Military Medical Center, JBSA-Fort 

Sam Houston, Texas.

COL Johnson is the Chairman, Department of Orthopaedic Surgery, San Antonio Military Medical Center, 

JBSA-Fort Sam Houston, Texas.

MARTIAL ARTS-BASED HIGH INTENSITY INTERVAL TRAINING 

IN THE REHABILITATION OF COMBAT AMPUTEES
July – September 2017 57

Since 2001, overseas contingency operations (OCOs) in 

support of the Global War on Terrorism have led to a 

large population of combat-related amputees.1

 In contrast to America’s previous conflicts, the majority of 

combat-related injuries and combat-related amputations 

in Iraq and Afghanistan have been the result of explosions (78% and 93%, respectively).1-3 Gunshot wounds 

from those combat areas accounted for 18% and 3.7%, respectively, in the same time period.1-3 Nearly 90% of service members wounded in these conflicts survived their 

initial injury as compared to 75% during the Vietnam 

War.4,5 Decreased mortality rates for those wounded on 

the battlefield can be attributed in part to advancements 

in body armor, casualty evacuation, and tactical combat 

casualty care.4-7 Therefore, the percentage of service 

members with multiple limb amputations has increased 

proportionately as greater numbers of service members 

are able to survive these previously life-threatening injuries.8

 Review of the data of the Military Orthopaedic 

Trauma Registry (MOTR) within the Department of Defense Joint Trauma System as of October 1, 2012, found 

that 1,559 patients with major amputations, defined as 

a hand, arm, leg, or foot, had been treated at military 

treatment facilities, including 481 with multiple amputations and 272 with upper extremity amputations.

A larger body of research has been conducted on amputations involving the lower extremity as such amputations 

Characteristics of US Combat Veterans

(2001-2011) Who Remain on Active Duty

 After Upper Extremity Amputations

Sara H. Kift, DScOT

Capt Taylor J. Bates, USAF, MC

CPT Nathan A. Franklin, MC, USA

COL Anthony E. Johnson, MC, USA

Abstract

Objectives: Return to duty following traumatic amputations has been extensively studied in those with lower 

extremity amputation. As upper extremity amputations occur less frequently, the issue of return to duty for 

those with upper extremity amputations has received relatively little research. The purpose of this study was 

to determine the rate at which service members remain on active duty at least one year after having sustained 

traumatic upper extremity amputations during Operation Iraqi Freedom, Operation Enduring Freedom, and 

other overseas contingency operations of the Global War on Terrorism.

Design: Retrospective.

Setting: Military, Academic Level 1 trauma center.

Patients: One hundred eighteen patients who sustained combat-related upper extremity amputations between 

October 2001 and December 2011.

Intervention: Data was obtained from the medical record for these 118 patients.

Main Outcome Measurements: Percentage of service member remaining on active duty one year following an 

upper extremity amputation, and evaluation of demographic and injury related factors associated with retention.

Results: The overall rate for the upper extremity amputees studied at one year from injury who remained on active duty was 47%. Officers were more likely to remain on active duty than their enlisted counterparts (P=.021) 

and patients who sustained burns were also more likely to remain on active duty than patients with similar 

amputation types without concomitant burn injuries (P=.039).

Conclusions: The rate of service members with traumatic upper extremity amputations who were still on active 

duty status 1-year postinjury was 47%. The presence of burns and rank were significant factors when examining retention on active duty. Further study on war casualties who sustain upper-extremity traumatic amputations with and without burns is required to optimize outcomes in this population.
58 http://www.cs.amedd.army.mil/amedd_journal.aspx

CHARACTERISTICS OF US COMBAT VETERANS (2001-2011) WHO REMAIN

ON ACTIVE DUTY AFTER UPPER EXTREMITY AMPUTATIONS

are far more common than those involving the upper extremity (86% compared to 14%).1

 The ability to return 

to duty has been evaluated as an indicator of a service 

member’s functional outcome.6,9-11 This has led to greater amounts of resources devoted to research, prosthetic 

development, and rehabilitation processes that benefit 

lower extremity amputees and increase return to duty 

rates.6,10-12 However, upper extremity amputees have 

higher disability rates compared with lower extremity 

amputees.12 Despite this, relatively little research has 

been focused on upper limb amputations.

The purpose of our study was to determine the return 

to duty rate at one-year postinjury for service members 

who sustained upper extremity amputations and remain 

on active duty, and to determine if there are specific 

characteristics associated with higher retention rates.

Patients and Methods

Following receipt of institutional review board approval, 

we searched the Department of Defense Trauma Registry (DoDTR) and the MOTR using ICD-9 codes to 

identify all US military service members who sustained 

combat-related, upper extremity amputations from October 7, 2001, to December 18, 2011. Upper extremity 

amputations were defined as any limb loss from digital to shoulder disarticulation. All US military service 

members who were treated for combat-related upper extremity amputation at the San Antonio Military Medical Center (SAMMC) were included. All nontraumatic, 

noncombat related amputations that occurred during 

this time period were excluded from the research. NonUS military personnel, including civilian contractors 

and foreign nationals, were also excluded from the study. 

Electronic medical records at SAMMC were then manually searched.

The data extracted from the inpatient and outpatient 

medical records included rank at the time of injury, military occupation specialty (MOS) or area of concentration, age, branch of service, mechanism of injury, injury 

type, Maximum Abbreviated Injury Severity score and 

Injury Severity Score (ISS), hand dominance, ICD-9 

codes, single or multiple amputations, laterality of amputation, definitive level of amputation, prosthetic use, 

type of prosthetic used, and a range of 

comorbidities.

Army Regulation 40-50113 defines the 

Medical Retention Determination Point 

(MRDP) as the point in treatment and 

rehabilitation (not to exceed 1 year from 

date of injury) at which the service member’s progress is stabilized sufficiently 

to determine that he/she is unlikely to carry out the tasks 

required by their military rank and specialty. Therefore, 

for this study we defined “retention” as the absence of 

initiation of a medical evaluation board (MEB) within 

365 days of injury. The Medical Evaluation Board Internal Tracking Tool was queried to determine the date of 

medical board initiation.

IBM SPSS Statistics 20 was used to perform the statistical calculations. The χ2 test was used to determine 

statistical significance for parametric data, and the Fisher exact test was used in instances where the expected 

count was less than 5 to compare categorical data. All 

continuous variables were tested for normality to determine the appropriate test. The variable ISS score was 

normally distributed and used a Student’s t test. All others were calculated using the Mann-Whitney U test. Statistical significance was set at P≤.05.

Results

Of the 118 service members who met the initial inclusion criteria (combat amputation, ICD-9 code, time period) from the DoDTR/MOTR, 83 were included in the 

final statistical analysis. Reasons for exclusion included: 

(1) amputations performed less than one year prior to the 

conclusion of data collection (August 1, 2012), and had 

not yet reached the MRDP, (2) lack of definitive amputation, (3) lack of treatment at SAMMC, and (4) incomplete medical records (Table 1). Of the 83 subjects who 

met final inclusion criteria, 39 remained on active duty 

one year postinjury, and 44 had initiated a MEB. This 

yields an initial retention rate of 47%.

Of the demographic characteristics available for analysis (Table 2), only rank was correlated significantly with 

retention (P=.021). At one year from injury, MEB processions had been initiated for 66% of junior enlisted 

personnel, 45% of senior enlisted personnel, and only 

15% of officers. Of the comorbid conditions identified 

among our patient population (Table 3), there was a 

demonstrated paradoxical relationship with burn injuries. Medical board proceedings were initiated for 8 of 

the 23 service members (35%) who sustained burns as 

well as an amputation, while 36 of 60 patients (60%) 

who sustained an amputation without any burns entered 

the MEB process, nearly twice the rate 

of those who were burned (P=.039). 

Factors which did not demonstrate statistical significance included branch of 

service, MOS (Table 2), injury type, laterality of amputation, amputation level 

(Table 4), hand dominance, or prosthetic 

use (Table 5).

Table 1. Reasons for exclusion of 

candidates from final study population (N=35).

Reason for Exclusion Number

n(%N)

No definitive amputation 19 (54%)

Limited documentation 3 (9%)

Other 13 (37%)
July – September 2017 59

THE ARMY MEDICAL DEPARTMENT JOURNAL

Comment

This study yielded a statistically significant difference 

in whether a subject remained on active duty based on 

rank (P=.021) and on comorbidity of burns (P=.039).

Increased retention rates with increasing rank is consistent with previous studies.6,10,11 One possible explanation 

is that those who have achieved higher ranks in their 

military careers have, on average, invested a significant 

amount of time in the military and may remain dedicated 

Table 2. Demographics of study population (N=83).

Active Duty

n (%N)

MEB

n (%N)

P Value

Average Age (range in years) .053

18-23 12 (14%) 24 (30%)

24-29 12 (14%) 12 (14%)

30+ 15 (18%) 8 (10%)

Gender .95

Male 38 (46%) 44 (53%)

Female 1 (1%) 0 (0%)

Branch of Service .28

Army 33 (40%) 36 (43%)

Marine 4 (5%) 7 (8%)

Air Force 2 (2%) 0 (0%)

Navy 0 (0%) 1 (1%)

Rank .021

Junior Enlisted: E1-E4 13 (16%) 26 (31%)

Senior Enlisted: E5-E9 16 (19%) 13 (16%)

Commisioned Officer: W01-06 6 (7%) 1 (1%)

Rank Unknown 4 (5%) 4 (5%)

MOS .44

11A - Infantry Officer 3 (4%) 0 (0%)

11B - Infantry Enlisted 7 (8%) 13 (16%)

12B - Combat Engineer 0 (0%) 1 (1%)

13B - Field Artillery 1 (1%) 2 (2%)

19K - Armor Crewman 1 (1%) 2 (2%)

21B - Engineer (Combat) 2 (2%) 3 (4%)

31B - Military Police 2 (2%) 1 (1%)

Other 13 (16%) 11 (13%)

Missing 10 (12%) 11 (13%)

Table 3. Comorbidities among study population (N=83).

Active Duty

n (%N)

MEB

n (%N)

P Value

Traumatic Brain Injury 15 (18%) 11 (13%) .18

Spinal Cord Injury 2 (2%) 1 (1%) .9

Burns 15 (18%) 8 (10%) .039

Fractures 31 (37%) 34 (41%) .81

Soft Tissue 37 (45%) 42 (51%) .7

Nerve 6 (7%) 6 (7%) .82

Polytrauma 34 (41%) 42 (51%) .34

Behavioral Health Diagnosis 21 (25%) 27 (33%) .48

Table 4. Injury characteristics of study population (N=83).

Active Duty

n (%N)

MEB

n (%N)

P Value

Mechanism of Injury .52

Explosive Device 36 (43%) 43 (52%)

Gunshot Wound 3 (4%) 1 (1%)

Type of Injury .54

Penetrating 25 (30%) 31 (37%)

Blunt 11 (13%) 12 (14%)

Burn 3 (4%) 1 (1%)

Amputee # 1

Single 24 (29%) 27 (33%)

Multiple 15 (18%) 17 (20%)

Laterality .48

Unilateral Upper 24 (29%) 27 (33%)

1 Upper 2 Lower 8 (10%) 9 (11%)

1 Upper 1 Lower 1 (1%) 4 (5%)

Bilateral Upper 6 (7%) 3 (4%)

Quad 0 (0%) 1 (1%)

Amputation Level .48

Digital 22 (27%) 19 (23%)

Ray Resection 2 (2%) 1 (1%)

Wrist Disarticulation 2 (2%) 2 (2%)

Transradial 5 (6%) 8 (10%)

Elbow Disarticulation 1 (1%) 1 (1%)

Transhumeral 3 (4%) 11 (13%)

Shoulder Disarticulation 1 (1%) 0 (0%)

Digital & Transradial 1 (1%) 1 (1%)

Digital & Elbow 

Disarticulation

0 (0%) 1 (1%)

Digital & Transhumeral 1 (1%) 1 (1%)

Elbow Disarticulation & 

Transhumeral

1 (1%) 0 (0%)

Table 5. Prosthetic type and use among study 

population (N=83).

Active Duty

n (%N)

MEB

n (%N)

P Value

Hand Dominance .46

Right 30 (36%) 32 (39%)

Left 4 (5%) 7 (8%)

Unknown 5 (6%) 5 (6%)

Prosthetic Use .32

Used 17 (20%) 24 (29%)

Not Used 20 (24%) 18 (22%)

Unknown 2 (2%) 2 (2%)

Type of Prosthetic .55

Body Powered 5 (8%) 5 (8%)

Myoelectric 8 (12%) 18 (28%)

Hybrid 2 (3%) 4 (6%)

Other 9 (14%) 14 (22%)
60 http://www.cs.amedd.army.mil/amedd_journal.aspx

CHARACTERISTICS OF US COMBAT VETERANS (2001-2011) WHO REMAIN

ON ACTIVE DUTY AFTER UPPER EXTREMITY AMPUTATIONS

to fulfilling their obligation for various reasons. In addition, those who have achieved a higher rank are less likely to be required to hold positions that require physical 

labor and the fine use of one or both upper extremities.

Amputees who had sustained burns were more likely to 

remain on active duty than those who were not burned 

(65% compared to 40%). One possible explanation is access to early rehabilitation through the integrated rehabilitation program at the US Army Institute for Surgical 

Research Burn Center. All amputees receive out-patient 

rehabilitation at the Center for the Intrepid, an integrated rehabilitation center. However, patients treated in the 

Burn Center began rehabilitation as inpatients. This is 

in contrast to amputees without burns who were treated 

without an integrated rehabilitation program. Therefore, 

the only difference is the time of exposure to integrated 

rehabilitation. The observation that burn victims were 

more likely to remain on active duty requires further 

study.

When analyzing specific types of prosthetics used, it 

was noted that most prosthetic users used more than one 

type of prosthetic. While none of the type of prosthetics (body-powered, myoelectric, hybrid or other) yielded 

statistically significant differences in whether a service 

member remained on active duty, it should be noted 

that the more costly and technologically advanced myoelectric prosthetics did not increase the retention rates 

within our study. Determining the cause for decreased 

retention rates in those using myoelectric prosthetics 

merits further study.

The major limitation of our study is its retrospective 

nature, thus we are able to show associations only. Respective studies are dependent upon the quality of the 

medical documentation reviewed. During the course of 

the research, multiple discrepancies in the medical records examined were noted. To minimize errors, two 

researchers were utilized to provide a second examination of the collected data and ensure congruency with 

the medical records.

A second weakness in this study was the process used to 

determine retention status. The MEB initiation date is 

often accepted in military medicine literature as a preliminary return to duty date, but it can by no means be 

considered a final determination of return to duty. We 

are unable to determine if our subjects initiated MEB 

proceedings after the Medical Retention Decision Point. 

However, given the scope of our review included a 10-

year period, it is consistent that nearly half of upper-extremity amputees are able to perform well enough to be 

retained beyond the MRDP.

Lastly, this study included only US service members 

treated at SAMMC after sustaining combat-related traumatic upper extremity amputations. Adhering to these 

criteria yielded a relatively small sample size of 118 patients. This decreases the external validity of our study.

Some strengths of this study include the length of time 

utilized (10 years), which encompasses a greater portion of current conflict than most previous research in 

this area. As the study was conducted at one of the only 

three military amputee care centers, the small population of this study is reflective of the overall size of the 

population. This study, therefore, may be thought of as 

an initial study examining the characteristics of upper 

extremity amputees who remain on active duty one year 

post injury.

Initially, 47% of veterans of overseas contingency operations in support of the Global War on Terrorism (primarily OIF and OEF) who were treated at San Antonio 

Military Medical Center remained on active duty one 

year after combat-related, traumatic upper extremity 

amputations. The characteristics that correlated significantly with retention included rank and the presence of 

burns. Increased active duty rate among burn victims 

may, in part, be due to earlier exposure to integrated rehabilitation. This potential relationship warrants future 

study. No other statistically significant correlations were 

found.

Other studies on upper extremity amputees have demonstrated long-term return to duty rates as low as 12%.12

Our study provides characteristics of those patients 

who remain on active duty at one year from their injury. The gap between the status of these patients at one 

year and the final return to duty rates provide areas for 

exploration:

 What changes between the medical decision making point and the final disposition?

 When service members leave the rehabilitative environment, are they still able to access appropriate 

resources when they face setbacks?

 Is there a disconnect between the resources available and service members’ understanding of what 

they may access?

 Could additional resources bridge the gap between 

one year retention and full return to duty?

Further research is necessary to define the prosthetic 

needs of amputee service members who wish to remain 

on active duty following an upper extremity amputation. 

Further qualitative research should also be conducted 

with this population to determine other factors that may 
July – September 2017 61

THE ARMY MEDICAL DEPARTMENT JOURNAL

affect a service member’s desire and his/her ability to 

remain on active military service following an upper extremity amputation.

Treatment of combat casualties in a patient-centered, 

integrated performance unit model such as a musculoskeletal specialty home within the Patient Centered 

Medical Neighborhood is supported and warrants further research.

References

1. Krueger CA, Wenke JC, Ficke JR. Ten years at 

war: comprehensive analysis of amputation trends. 

J Trauma Acute Care Surg. 2012;73:S438-S444.

2. Enad JG, Headrick JD. Orthopedic injuries in U.S. 

casualties treated on a hospital ship during Operation Iraqi Freedom. Mil Med. 2008;173:1008-1013.

3. Owens BD, Kragh JF, Jr., Wenke JC, Macaitis J, 

Wade CE, Holcomb JB. Combat wounds in operation Iraqi Freedom and operation Enduring Freedom. J Trauma. 2008;64:295-299.

4. Arredondo J, Foote N, Pruden JD, McFarland 

MJ, McFarland LV. Wounded warriors’ perspectives: helping others to heal. J Rehabil Res Dev. 

2010;47(4):xxi-xxviii.

5. Robbins CB, Vreeman DJ, Sothmann MS, Wilson 

SL, Oldridge NB. A review of the long-term health 

outcomes associated with war-related amputation. 

Mil Med. 2009;174(6):588-592.

6. Stinner DJ, Burns TC, Kirk KL, Ficke JR. Return to duty rate of amputee soldiers in the current conflicts in Afghanistan and Iraq. J Trauma. 

2010;68(6):1476-1479.

7. Potter BK, Scoville CR. Amputation is not isolated: An Overview of the US Army Amputee Patient 

Care Program and Associated Injuries. J Am Acad 

Orthop Surg. 2006;14(spec no 10):S188-S190.

8. Dougherty PJ, McFarland LV, Smith DG, Esquenazi A, Blake DJ, Reiber GE. Multiple traumatic limb loss: a comparison of Vietnam veterans 

to OIF/OEF servicemembers. J Rehabil Res Dev. 

2010;47(4):333-348.

9. Pasquina PF, Tsao JW, Collins DM, et al. Quality 

of medical care provided to service members with 

combat-related limb amputations: report of patient 

satisfaction. J Rehabil Res Dev. 2008;45(7):953-960.

10. Cross JD, Stinner DJ, Burns TC, Wenke JC, Hsu 

JR. Return to duty after type III open tibia fracture. 

J Orthop Trauma. 2012;26(1):43-47.

11. Kishbaugh D, Dillingham TR, Howard RS, Sinnott 

MW, Belandres PV. Amputee soldiers and their return to active duty. Mil Med. 1995;160(2):82-84.

12. Tennent DJ, Wenke JC, Rivera JC, Krueger CA. 

Characterisation and outcomes of upper extremity 

amputations. Injury. 2014;45(6):965-969.

13. Army Regulation 40-501: Standards of Medical 

Fitness. Washington, DC: US Department of the 

Army; December 22, 2016:76.

Authors

Dr Kift received her DScOT from Baylor University. She 

currently resides in Augusta, Georgia.

Capt Bates is a PGY-1, Department of Orthopaedic Surgery, San Antonio Military Medical Center, JBSA-Fort 

Sam Houston, Texas.

CPT Franklin is a Research Fellow, US Army Institute of 

Surgical Research (Extremity Trauma and Regnerative 

Medicine Area), JBSA-Fort Sam Houston, Texas.

COL Johnson is the Chairman, Department of Orthopaedic Surgery, San Antonio Military Medical Center, 

JBSA-Fort Sam Houston, Texas.
62 http://www.cs.amedd.army.mil/amedd_journal.aspx

Pedicle soft tissue flaps represent a ubiquitous treatment 

modality in plastic and reconstructive surgery, yet flap 

necrosis remains a major complication. Partial or complete flap necrosis can lead to infection, delayed wound 

healing, dehiscence, fistula formation, wound contracture, and poor cosmesis.1,2 A common model for studying 

necrosis is the rat dorsal ischemic skin flap. The first description of a dorsal pedicle soft tissue flap model in the 

rat was by McFarlane in 1965.3

 Numerous investigators 

have sought to improve the survival of rat ischemic skin 

flaps using a wide range of surgical techniques, topical 

and systemic drugs, and angiogenic factors. It is widely 

recognized that angiogenesis is a key process in wound 

healing. Thus, multiple points along the angiogenesis 

pathway have evoked interest as therapeutic targets.4-7

Although emerging therapies designed to improve the 

survival of ischemic tissue include the use of angiogenic 

factors, endogenous expression patterns for these factors have not been well characterized. Such information 

could influence strategies for therapeutic intervention. 

In this article, lower-case abbreviations refer to genes, 

while gene products are denoted in capital letters.

While growth factors are critically important in angiogenesis, the process involves a functionally diverse set 

of genes. Vascular endothelial growth factor and fibroblast growth factor-2 (FGF2), two growth factors that act 

at multiple points in angiogenesis, are among the most 

studied angiogenic factors.5,7-11 Vascular endothelial 

growth factor (VEGF) participates in the initial steps of 

angiogenesis by inducing nitric oxide synthase activity 

in endothelial cells leading to vasodilatation and by increasing vascular permeability.12 Further in the process 

of angiogenesis, VEGF acts as a specific mitogen for 

endothelial cells, while fibroblast growth factors induce 

proliferation more broadly. Platelet derived growth factor 

(PDGF) is a mitogen for mesenchymal cells in multiple 

phases of wound healing. This growth factor is important for the recruitment of pericytes in the development 

of stable, mature vessels.13 Additionally, PDGF may promote vessel maturation by directly inhibiting endothelial 

cells from entering the cell cycle,14 and it also induces 

VEGF mRNA in fibroblasts.15 Cadherin-5 (CDH5) is an 

endothelial specific adhesion molecule and major component of endothelial adherins junctions.16 The integrity 

Temporospatial Angiogenesis-Associated

 Gene Expression Profiles in Rat Ischemic

 Skin Flaps

LTC Thomas M. Johnson, DC, USA

LCDR Esra Toussaint-Barrett, USPHS

LTC Jose M. Pizarro, MS, USA 

Abstract

Objectives: Emerging therapies designed to improve soft tissue flap survival include the use of angiogenic factors. 

However, endogenous expression patterns for these factors have not been characterized. The purpose of this study 

was to identify spatial and temporal variations in expression patterns of angiogenesis-associated genes in ischemic 

rat skin flaps.

Study Design: This is an observational animal study characterizing spatial and temporal angiogenesis associated 

gene expression patterns in rat ischemic skin flaps.

Methods: Dorsal skin flaps were created on 15 male Sprague-Dawley rats. The flap tissue was harvested and sectioned at 1, 3, or 7 days postsurgery. Total RNA was isolated, amplified, labeled with biotin, and hybridized to microarrays containing probes for 113 angiogenesis-associated genes. Microarray analysis revealed unique spatial and 

temporal patterns with statistically significant gene modulation over the length of the flap (P<.05).

Results: The molecular analysis performed in this study correlates with the hemodynamic profile previously published. Expression patterns associated with blood flow were markedly different from patterns associated with stasis 

and avascularity.

Conclusions: To our knowledge, this study is the first to characterize endogenous spatial and temporal angiogenesisassociated gene expression in rat ischemic skin flaps. Further characterization of expression patterns may allow 

clinicians to differentiate ischemic tissue that may be rescued via pharmacological or surgical intervention from 

tissue destined to succumb. Additionally, comparison of the expression profiles observed in this study with profiles 

generated from pharmacologically treated rats may suggest mechanisms for enhanced healing.
July – September 2017 63

THE ARMY MEDICAL DEPARTMENT JOURNAL

of endothelial adherins junctions mediates endothelial 

motility, vascular morphogenesis, and permeability.16

Adherins junctions may also be important in the integration of mechanical and chemical cellular signals.16

Angiogenesis is also under negative control. For example, leukocyte cell derived chemotaxin 1, also known 

as chondromodulin-I, inhibits angiogenesis in avascular 

tissues such as cartilage and avascular compartments 

in the eye.17,18 A combination of angiogenesis inhibitors 

restricts formation of vessels in the eye despite the presence of potent promoters of angiogenesis such as VEGF 

and FGF2.18 One of the most important endogenous inhibitors of angiogenesis is pigment epithelium derived 

factor, also known as serine peptidase inhibitor, clade F, 

member 1.19 This anti-angiogenic factor is produced by 

multiple cell types, and its inhibitory effect results from 

stimulation of endothelial apoptosis.19 Tissue inhibitors 

of metalloproteinases (TIMPs) inhibit angiogenesis by 

preventing metalloproteinase induced matrix degradation.20 However, TIMPs also exert negative control 

on angiogenesis via other mechanisms. For example, 

TIMP3 interferes with VEGF binding its receptor, preventing its stimulatory effect.20

Materials and Methods

All procedures were reviewed and approved by the 

Dwight David Eisenhower Army Medical Center Animal Care and Use Committee and were performed in a 

facility accredited by the Association for the Assessment 

and Accreditation of Laboratory Animal Care, International. Research was conducted in compliance with the 

Animal Welfare Act (Pub L 89-544, 80 Stat 350 (1966)) 

and other federal statutes and regulations pertaining to 

animals and experiments that involve animals and adhered to principles stated in the Guide for the Care and 

Use of Laboratory Animals (NRC, 1996).

A total of 15 male Sprague-Dawley rats (Harlan Sprague-Dawley) weighing approximately 350 

grams were used for this study. 

The rats were housed in an environmentally controlled room on a 

12-hour light-dark cycle and were 

fed standard rat chow and water 

ad libitum. Animals were housed 

in pairs throughout a one-week 

acclimation period until surgery. 

Following surgery, the animals 

were housed individually to prevent injury to skin flaps from 

cannibalism and normal socialization activities.

Modified McFarlane flaps measuring 3 cm x 10 cm were 

created on the dorsal skin of the rats. The myocutaneous 

flaps were elevated from the underlying fascia then returned to their native positions and secured with staples. 

The rats were divided into 3 groups based on a terminal 

evaluation interval of 1, 3, or 7 days.

RNA Isolation

Following euthanasia, flaps were harvested, photographed, and sectioned transversely into four 3 cm x 2.5 

cm zones and stored at -80°C. The zone closest to the 

flap base was defined as Zone IV; the zone furthest from 

the flap base was defined as Zone I, as shown in the Figure. Total RNA was isolated from the skin flaps, using 

a monophase phenol and guanidine thiocyanate isolation reagent according to the manufacturer’s instructions (TriPure, Boerhringer Mannheim, Indianapolis, 

IN). Briefly, 100 mg of tissue was immersed in 1 mL 

of Tripure, homogenized, and centrifuged at 12,000g 

for 10 minutes at 4°C. Homogenized samples were incubated for 5 minutes at room temperature, followed by 

an addition of 0.2 mL of chloroform. The mixture was 

vigorously shaken and incubated for another 15 minutes. 

Samples were then centrifuged at 12,000g for 15 minutes at 4°C. After centrifugation, the solution contained 

3 phases. The upper aqueous phase contained the RNA, 

while the lower organic phase and cloudy interphase 

contained DNA and proteins. Total RNA was recovered 

from the upper phase by isopropanol precipitation. The 

RNA was resuspended in molecular biology grade water, and the quantity and purity of the isolated RNA was 

analyzed on a Bioanalyzer 2100 (Agilent Technologies, 

Cold Spring, NY). The RNA was then stored at -80°C 

until processed.

RNA Amplification and Labeling

Total RNA (25-100 ng) was reverse transcribed into 

complementary DNA (cDNA) using the target Amp 

Modified McFarlane Skin Flap Design. Flaps wre harvested at the appropriate time points 

and sectioned transversely into 3 cm x 2.5 cm zones; zone I is the furthest from the caudal flap base.

Zone I Zone II Zone III Zone IV

0 5 mm 10 mm

0

3 mm
64 http://www.cs.amedd.army.mil/amedd_journal.aspx

1-Round Biotin-aRNA Amplification Kit 104. The resulting cDNA was then used to generate biotin-U labeled 

aRNA as instructed by the manufacturer (Epicentre, 

Madison, WI). The biotin labeled aRNA was purified 

using Qiagen RNeasy Mini Kit according to the manufacturer’s protocol (Qiagen, Valencia, CA) and 2 μg of 

labeled aRNA was used to hybridize to the Angiogenesis specific arrays. Hybtube format rat angiogenesis arrays (ORN24.2, SuperArray, Frederick, MD) containing 

128 positions and 113 unique angiogenesis-associated 

oligonucleotide probes were processed according to the 

manufacturer’s instructions. The resulting images were 

captured using time-lapse image acquisition at a rate of 

one image per 10 minutes for a total of 40 minutes (Kodak ImageStation 2000MM, Kodak, New Haven, CT).

Web-based software (GEArray Analysis Suite 2.0, SuperArray BioScience Corp, Frederick, MD) was used to 

analyze the signal intensity produced for each gene. To 

account for background differences among microarrays, 

the lowest average density spot on each array was found 

and the average intensity across the spot was used as a 

background correction factor. Interquartile normalization of the signal intensity was used, ranking the absolute intensity of each signal then dividing it by the mean 

intensity of the genes that fell between the 25% and 75% 

quartiles. Each zone-time point group (4 flap zones, 3 

time points) contained 5 microarrays. For each zone, 

differences in the mean normalized signal intensity 

were compared over 2 time intervals: early (from day 

1 to day 3) and late (from day 3 to day 7). A Student’s t

test was performed for each comparison. Differences in 

mean normalized signal intensity were deemed statistically significant for P values less than .05.

Results

In an earlier study,21 researchers in our lab used orthogonal polarization spectral imaging to define and report 

mean areas of flap avascularity, areas of stasis exhibiting vessels without flow, and unaffected areas showing 

vessels with blood flow. At day 1, the mean area of avascularity was completely contained within the distal 2.5 

cm of the flap (Zone I). By day 3, Zone I was completely 

avascular. At days 3 and 7, the transition from avascularity to stasis fell between 2.5 cm and 5 cm from the 

distal flap margin (within Zone II). At all time points, 

the total affected area (the area of the flap exhibiting 

stasis or avascularity) fell within Zone II.

Statistically significant (P<.05) changes in signal intensity were observed within all 4 zones over the early (day 1 

to day 3) and late (day 3 to day 7) time intervals. In Zone 

I, more genes showed large changes in signal intensity 

during the early time interval, while more modest gene 

modulation occurred from day 3 to day 7. In Zone II the 

expression profile over the early time interval showed 

few genes with large magnitude changes in signal intensity, while gene modulation over the late time interval 

was much more robust. Fold-changes in signal intensity 

for the 112 genes are presented in Table 1. Table 2 lists 

mean normalized signal intensity for selected genes.

Comment

Immediately after flap elevation, pedicle skin flaps become dependent upon collateral circulation through vessels contiguous with intact vessels in the flap base.22 A 

minimum blood flow of 0.04 cc per gram of tissue per 

minute is required to maintain viability.23 However, skin 

cells can survive up to 12 hours of complete avascularity at body temperature.22 Necrosis ultimately ensues in 

areas where flow is inadequate and does not improve 

before cells perish.22 In modified McFarlane skin flaps, 

a distal flap segment is destined to become necrotic, and 

a larger proximal segment will have adequate blood 

flow irrespective of experimental conditions. The interposed segment is most interesting, because it can either become necrotic or be rescued, depending on the 

experimental parameters. Distinct areas of modified 

McFarlane flaps have been defined using orthogonal polarization spectral imaging, a noninvasive technique for 

visualizing soft tissue microcirculation without the use 

of dyes.5,21,24,25 Hart et al defined an area of necrosis devoid of blood vessels, an area of stasis exhibiting vessels 

without flow, and an unaffected area showing vessels 

with blood flow.21 The area of stasis, containing vessels 

yet absent of blood flow, represents the area of the flap 

susceptible to pharmacological intervention. Hart et al 

showed that the total affected area remained relatively 

constant over time while the mean area of necrosis increased at the expense of the area of stasis.21 While the 

progression of necrosis in ischemic rat skin flaps has 

been studied, endogenous expression patterns for angiogenesis-associated genes remain uncharacterized.21

Angiogenesis-associated gene expression profiles generated in the present study correlated with the progressive 

proximal extension of the avascular segment noted in 

the previously reported orthogonal polarization spectral 

imaging analysis.21 In the area exhibiting near complete 

avascularity by day 1 (Zone I), robust gene modulation 

occurred during early time interval. Platelet endothelial cell adhesion molecule (PECAM-1) and CDH5 are 

among the genes that showed significant modulation 

(P<.05) in this area. Both of these genes are associated 

with the vasodilatation and endothelial permeability 

seen during the initiation of angiogenesis.

TEMPOROSPATIAL ANGIOGENESIS-ASSOCIATED GENE

EXPRESSION PROFILES IN RAT ISCHEMIC SKIN FLAPS
July – September 2017 65

THE ARMY MEDICAL DEPARTMENT JOURNAL

Table 1 (part 1 of 3). Early and late fold changes in signal intensity by zone.

Genebank ID Gene Name Symbol Fold Change 

Zone 1

Fold Change 

Zone 2

Fold Change 

Zone 3

Fold Change 

Zone 4

Early Late Early Late Early Late Early Late

NM_053546 Angiopoietin 1 Adra2b -2.45 -3.54* -1.46 -2.88* -1.50 -1.70 -1.06 -1.09

NM_138505 Adrenergic receptor, alpha 2b Aggf1 1.39 1.01 2.05 1.36 -1.61 1.21 1.36 2.05

XM_226709 Angiogenic factor with G patch and 

FHA domains 1 Akt1 -1.68 -1.65 1.19 -1.95 -2.33 1.34 1.16 1.48

NM_033230 Thymoma viral proto-oncogene 1 Angpt1 1.70 1.63 1.41 1.03 -2.42 1.89 -1.40 1.36

XM_344544 Angiopoietin 2 Angpt2 2.23 1.11 2.68 2.70 -2.45 1.67 1.44 3.21

NM_199115 Angiopoietin-like 4 Angptl4 1.73 1.61 1.09 3.30 -1.27 1.45 -1.54 -1.21

NM_031012 Alanyl (membrane) aminopeptidase Anpep -2.41 -2.46 -1.70 -1.64 -2.07 1.25 -1.66* 1.44

XM_220907 ADP-ribosylation factor-like 12 Arl12 -1.68 -1.13 -1.35 1.34 1.03 -2.41 2.03 1.14

XM_343260 Brain-specific angiogenesis inhibitor 1 Bai1 1.75 1.59 1.45 3.24 -2.67 -1.70 -1.84 1.37

NM_019205 Chemokine (C-C motif) ligand 11 Ccl11 -2.05* 1.20 -1.21 1.20 1.43 1.46 1.08 -2.86

NM_031530 Chemokine (C-C motif) ligand 2 Ccl2 1.62 1.20 2.09* 2.77 -2.78 -1.55 1.30 2.31

XM_226213 Cadherin 5 Cdh5 -4.52* -7.65* 1.00 -3.21* -1.09 -3.03* 1.66 -2.55

XM_241632 Procollagen, type XVIII, alpha 1 Col18a1 5.36 5.47 2.26 11.45 1.77 -1.21 1.36 -1.80*

XM_343607 Procollagen, type IV, alpha 3 Col4a3 1.35 1.18 1.55 2.44 -1.88 1.64 -1.71 -1.33

NM_017104 Colony stimulating factor 3

(granulocyte) Csf3 -1.20 -1.25 1.00 2.10 -1.18 1.89 1.28 -1.80

NM_022266 Connective tissue growth factor Ctgf 2.22 -2.20 1.11 1.07 -2.29 -1.57 -2.29 1.42

NM_030845 Chemokine (C-X-C motif) ligand 1 Cxcl1 -1.27 1.05 -1.31 1.08 -1.68 -1.04 1.11 1.46

NM_139089 Chemokine (C-X-C motif) ligand 10 Cxcl10 -1.42 -1.81 -1.42 -1.01 -3.13 -1.56 -1.67 1.42

NM_182952 Chemokine (C-X-C motif) ligand 11 Cxcl11 -2.54 -6.70 1.32 -1.38 2.47 1.78 3.48 -2.86

NM_053647 Chemokine (C-X-C motif) ligand 2 Cxcl2 -1.68 -1.66 1.74 1.11 -2.86 -1.22 1.07 1.80

NM_001007729 Chemokine (C-X-C motif) ligand 4 Cxcl4 8.85 7.19 1.34 13.23 -1.47 -1.73 -1.19 1.11

NM_022214 Chemokine (C-X-C motif) ligand 5 Cxcl5 -1.42 1.28 -1.54* -1.16 -1.39 -1.10 2.18 1.10

NM_145672 Chemokine (C-X-C motif) ligand 9 Cxcl9 -6.80* -4.13 -1.29 -2.24 -1.31 -2.55 * 2.37 -1.92

NM_001012122 Endothelial cell growth factor 1

(platelet-derived) Ecgf1 -9.52 -7.19 -2.50* -5.74* -1.38 1.00 -1.59* 1.26

NM_017301 Endothelial differentiation sphingolipid 

GPCR 1 Edg1 1.70* 1.52 1.49 2.38 1.56 1.15 -1.35 1.21

NM_053599 Ephrin A1 Efna1 1.68 -1.19 1.42 1.82 -2.74 -2.64 -1.56 1.39

XM_234903 Ephrin A2 Efna2 2.56* 1.83 1.18 3.91 -3.17 -1.07 -1.84 1.16

XM_574979 Ephrin A3 Efna3 1.56 1.59 1.46 1.37 -2.12 2.10 -1.51 1.75*

NM_012842 Epidermal growth factor Egf -2.00 -1.73 -4.11 -4.76 -1.01 2.10 * -2.06 1.23

NM_001010968 Endoglin Eng -1.59 -1.37 -1.49 -1.76 1.24 -1.05 1.71* 1.05

NM_023090 Endothelial PAS domain protein 1 Epas1 -5.63* -3.00* -5.06* -5.61* -1.38 1.11 -1.85* 1.05

NM_021689 Epiregulin Ereg -3.91* -3.75* -2.43* -3.19* -1.10 1.18 -1.49 -1.87

NM_022924 Coagulation factor II F2 1.82 1.20 -1.73 1.80 -1.32 -1.24 -2.18 1.43

NM_012846 Fibroblast growth factor 1 Fgf1 1.41 1.77 -1.12 1.63 -1.91 -1.60 -1.89 1.16

NM_019305 Fibroblast growth factor 2 Fgf2 1.18 -1.02 1.04 2.28 -1.43 1.05 -1.24 1.42

NM_131908 Fibroblast growth factor 6 Fgf6 2.53* 2.04 1.11 1.63 1.35 1.85 * -1.39 1.14

NM_053429 Fibroblast growth factor receptor 3 Fgfr3 1.30 1.18 1.27 1.41 -2.66* 1.23 -2.32 -1.13

NM_031761 C-fos induced growth factor Figf 1.95 2.93 1.32 1.11 -2.20 1.50 -1.49 1.11

NM_019306 FMS-like tyrosine kinase 1 Flt1 8.41 7.19 1.03 20.09 -1.23 1.40 -1.33 1.06

NM_173838 Frizzled homolog 5 (Drosophila) Fzd5 1.43 1.41 -1.25 -1.31 -1.32 2.43 * -1.53 1.03

NM_001013119 Guanine nucleotide binding protein, 

alpha 13 Gna13 -1.76 -2.19 -1.96 2.00 1.06 -1.29 -1.32 -1.02

NM_022696 Heart and neural crest derivatives 

expressed transcript 2 Hand2 -1.34 1.05 -1.18 1.79 -1.07 -1.06 -1.33 1.20

NM_017017 Hepatocyte growth factor Hgf 1.54 1.21 1.35 2.35 -1.81 -2.46 -1.77 1.69

*Statistically significant (P<.05)
66 http://www.cs.amedd.army.mil/amedd_journal.aspx

Table 1 (continued, part 2 of 3). Early and late fold changes in signal intensity by zone.

Genebank ID Gene Name Symbol

Fold Change 

Zone 1

Fold Change 

Zone 2

Fold Change 

Zone 3

Fold Change 

Zone 4

Early Late Early Late Early Late Early Late

NM_024359 Hypoxia inducible factor 1, alpha 

subunit Hif1a 1.74 1.28 1.06 1.91 1.13 -1.15 1.15 1.37

NM_001014786 Interferon-alpha 1 Ifna1 -2.34 -2.83* -2.18 -1.60 1.09 1.22 -1.67 -1.09

NM_138880 Interferon gamma Ifng 1.50 1.48 1.62 5.12 -1.55 1.16 -1.61 1.03

NM_178866 Insulin-like growth factor 1 Igf1 1.98 2.18 -1.46 2.59 1.14 1.77 -1.20 -1.08

NM_012854 Interleukin 10 Il10 20.62 15.31 1.03 33.20 -2.01 1.13 1.08 1.07

NM_053390 Interleukin 12a Il12a -3.08* -2.35* -1.38 -2.87* 1.01 -1.26 -1.33 -1.10

NM_019165 Interleukin 18 Il18 1.43 -1.37 -1.95 -1.53 1.30 1.29 -1.40 1.22

NM_031512 Interleukin 1 beta Il1b 10.84 5.74 1.41 17.16 -1.74 -1.42 -1.30 1.80

NM_012589 Interleukin 6 Il6 1.06 -1.11 1.02 1.58 -1.02 -1.05 -1.36 1.33

XM_230950 Integrin alpha V Itgav -10.16* -12.68* -3.59 -16.39* -1.83 -2.07 1.10 -1.37

NM_153720 Integrin beta 3 Itgb3 -1.71 -3.73* -1.06 -1.24 2.68* 1.21 2.26 -1.79

NM_019147 Jagged 1 Jag1 -1.68 -1.41 -1.36 -1.74 2.46* 1.80 1.23 -1.16

NM_013062 Kinase insert domain protein receptor Kdr -1.55 1.43 1.72 1.65 1.68 1.52* 1.15 -1.24

XM_215963 Laminin, alpha 5 Lama5 1.27 -1.12 1.05 1.39 2.05* 1.06 1.33 1.01

NM_030854 Leukocyte cell derived chemotaxin 1 Lect1 15.72 13.15* 2.74 42.73 -2.41 -2.25 -1.16 -1.50*

NM_013076 Leptin Lep 5.51 4.80 1.13 11.05 -1.00 1.08 -1.12 1.22

NM_031020 Mitogen activated protein kinase 14 Mapk14 -1.35 -1.06 1.47 1.05 1.88* 1.26 1.36 1.24

NM_030859 Midkine Mdk 2.66 2.38 1.41 5.29 -1.53 1.08 -1.24 -1.05

XM_222317 Matrix metalloproteinase 19 Mmp19 1.20 1.69* 1.36 1.23 1.11 1.82* -1.06 -1.12

NM_031054 Matrix metallopeptidase 2 Mmp2 1.93 2.43* 2.22* 2.56* 1.15 2.08* 1.02 -1.19

NM_031055 Matrix metallopeptidase 9 Mmp9 1.16 1.29 -1.41 -1.39 -1.81* 1.73* -1.46 1.43

NM_001002827 Notch homolog 4 Notch4 2.10 3.62* 1.97* 3.11* 1.18 1.46* -1.22 1.12

NM_031545 Natriuretic peptide precursor type B Nppb 1.65 1.24 1.96* 1.70* -1.71 -1.31 -1.62 1.39

NM_012613 Natriuretic peptide receptor 1 Npr1 -1.02 2.14 1.25 1.00 -1.47 1.30 -1.73 -1.08

NM_145098 Neuropilin 1 Nrp1 -2.51 1.10 1.07 -2.07 -1.09 -1.03 -1.50 -1.57

NM_030869 Neuropilin 2 Nrp2 7.95 4.05 2.10* 9.90 -1.16 -1.50 1.12 -1.27

NM_181363 Nudix (nucleoside diphosphate linked 

moiety X)-type motif 6 Nudt6 -3.20* -2.40* -1.49* -2.96* -1.13 1.25 -1.59* -1.69*

NM_012801 Platelet derived growth factor, alpha Pdgfa 1.27 1.52 1.46 2.06 1.85 1.06 2.09* -1.56

XM_343293 Platelet derived growth factor, B 

polypeptide Pdgfb 2.04 -1.47 1.30 1.41 -1.98 -1.58 -1.87 1.64*

NM_031591 Platelet/endothelial cell adhesion 

molecule Pecam 3.06* 1.74 1.87* 2.88* -1.96 -1.59 -1.82 1.36

NM_053595 Placental growth factor Pgf -1.22 -1.28 -1.34 -1.03 1.01 -1.42 1.22 1.02

NM_013085 Plasminogen activator, urokinase Plau 1.23 -1.14 1.18 1.08 -1.44* -1.40* -1.16 1.07

XM_574314 Plasminogen Plg -3.15* -3.12* 1.90* -1.68 2.73* -1.53 2.29 -2.17

NM_001002278 Protein O-fucosyltransferase 1 Pofut1 1.13 -1.00 1.19 -2.00* -1.36 1.36 -1.14 -1.06

NM_138852 Prokineticin 2 Prok2 2.65 1.63 1.06 1.07 -1.19 1.69* -1.12 -1.09

NM_031606 Phosphatase and tensin homolog Pten 2.74 1.34 1.39 1.54 -2.26 -1.98 -2.10 -1.78

NM_017043 Prostaglandin-endoperoxide synthase 

1 Ptgs1 2.77* 2.94* 1.59 3.82 -1.20 -1.71 -1.03 1.19

NM_017232 Prostaglandin-endoperoxide synthase 

2 Ptgs2 -2.05 -1.58 -1.30 -2.08 1.61 1.15 1.17 1.25

NM_017066 Pleiotrophin Ptn 1.15 2.41 1.36 1.20 1.13 1.13 -1.18 -1.05

XM_341781 SAPS domain family, member 1 Saps1 -1.58 -1.75* -1.20 -2.64* 1.31 1.13 1.03 -1.03

NM_177927 Serine (or cysteine) peptidase inhibitor, 

clade F, member 1 Serpinf1 -3.82* -7.67* -3.51* -5.27* 1.83* -1.36 2.80 -1.94

NM_207605 SH2 domain protein 2A Sh2d2a -2.21 -1.88* -1.13 -2.88 1.06 -1.37 1.62* -1.23

*Statistically significant (P<.05)

TEMPOROSPATIAL ANGIOGENESIS-ASSOCIATED GENE

EXPRESSION PROFILES IN RAT ISCHEMIC SKIN FLAPS
July – September 2017 67

THE ARMY MEDICAL DEPARTMENT JOURNAL

During the late time interval, changes in signal intensity in Zone I were much less pronounced, presumably 

because few cells in the distal zone retained normal cellular function. However, complete absence of RNA was 

neither expected nor observed. Even when the dermal 

flap surface appears black, viable cells may exist across 

the thickness of the flap. Zone II, which did not exhibit 

avascularity during the early time interval, showed a relatively modest pattern of gene modulation from day 1 to 

day 3. Once the avascular segment extended into Zone 

II (in the late time interval), this area exhibited a more 

robust expression pattern, analogous to early observations in Zone I. Furthermore, some of the same genes 

modulated early in Zone I were modulated later in Zone 

II. For example, the following genes exhibited statistically significant (P<.05) modulation early in Zone I and 

late in Zone II: CDH5, PECAM-1, SERPINF1, TGFBR1, 

Endothelial cell growth factor-1 (Ecgf1), Endothelial 

PAS domain protein-1 (Epas1), Epiregulin (Ereg), Interleukin 12a (Il12a), Integrin αV (Itgav), Nudix-type 

motif 6n (Nudt6), and Tumor necrosis factor ligand superfamily member-12 (Tnfsf12). As shown in Table 1, 

other genes followed this trend: Il1b, Lect1, Procollagen 

type XVIII α1 (Col18a1), Chemokine (C-X-C motif) ligand-4 (Cxcl4), FMS-like tyrosine kinase-1 (Flt1), Interleukin-10 (Il10).

Overall, the expression patterns observed, in the context 

of the previously reported proximal progression of avascularity, suggest that necrosis may trigger modulation 

of numerous genes in adjacent tissue during the normal 

healing of pedicle soft tissue wounds. This speculation 

Table 1 (continued, part 3 of 3). Early and late fold changes in signal intensity by zone.

Genebank ID Gene Name Symbol

Fold Change 

Zone I

Fold Change 

Zone II

Fold Change 

Zone III

Fold Change 

Zone IV

Early Late Early Late Early Late Early Late

NM_021692 MAD homolog 5 (Drosophila) Smad5 -1.82 -1.78 -1.67 -3.15* 1.19 1.44 -1.09 -1.07

NM_133386 Sphingosine kinase 1 Sphk1 2.04 1.36 1.21 1.45 -1.97 -1.18 -1.91* 1.19

XM_214279 Stabilin 1 Stab1 1.96* 1.08 -1.29 1.33 1.35 -1.52* -1.02 -1.12

XM_238531 Stabilin 2 Stab2 -1.15 -1.73* -1.05 -1.67* -1.09 1.10 1.22 1.19

XM_341009 T-box 1 Tbx1 1.24 -1.03 1.37 1.46 -1.61* -1.50 -1.05 1.16

XM_220811 T-box 4 Tbx4 1.69 1.42 1.22 -2.79* -1.92* -1.28 -1.16 1.14

XM_342863 Endothelial-specific receptor tyrosine 

kinase Tek 1.36 1.29 -1.12 -1.62 -1.19 1.25 -1.10 -1.14

NM_012671 Transforming growth factor alpha Tgfa 1.20 1.34 1.42 1.40 1.07 1.35 1.18 -1.20

NM_021578 Transforming growth factor, beta 1 Tgfb1 1.24 1.48 -1.47 -1.91* -1.42 1.18 -1.20 -1.22

NM_031131 Transforming growth factor, beta 2 Tgfb2 1.49 -1.20 1.10 1.18 -1.37 -1.38 -1.68 1.52

NM_013174 Transforming growth factor, beta 3 Tgfb3 1.34 -1.19 1.06 1.69 -1.40 -1.61 -1.27 1.35

NM_012775 Transforming growth factor, beta 

receptor 1 Tgfbr1 -3.99* -6.20* -1.74 -5.92* -1.82 -1.86 -1.04 -1.12

XM_214778 Thrombospondin 2 Thbs2 -2.11 -2.30* -1.04 -1.62 1.69 -1.04 1.58 -1.01

XM_233462 Tyrosine kinase with Ig-like and EGFlike domains 1 Tie1 1.15 1.57 -1.06 -1.06 1.36 1.20 1.11 1.01

NM_053819 Tissue inhibitor of metallopeptidase 1 Timp1 1.73* 1.02 1.30 -1.67 -1.83* -1.01 -1.01 1.07

NM_021989 Tissue inhibitor of metalloproteinase 2 Timp2 -1.29 2.34 -1.16 1.13 1.54 2.08* -1.24 1.43

NM_012886 Tissue inhibitor of metalloproteinase 3 Timp3 -1.24 -1.44 -1.08 -1.60 1.87 4.44 -1.27 1.88

XM_235768 Transmembrane serine protease 6 Tmprss6 1.57 1.74* 1.13 1.46 -1.10 1.00 -1.43 1.37

NM_012675 Tumor necrosis factor (TNF 

superfamily, member 2) Tnf -1.04 1.56 -1.11 -1.22 -1.61* -1.63 -1.30 1.63

NM_181086 Tumor necrosis factor receptor 

superfamily, member 12a Tnfrsf12a -1.36 -1.12 -2.49* -2.42* -2.70 2.46 -1.92 2.24

NM_001001513 Tumor necrosis factor ligand 

superfamily member 12 Tnfsf12 -3.75* -3.57* -2.60 -5.13* -2.19* 1.00 -1.39 1.41

NM_145765 Tumor necrosis factor (ligand) 

superfamily, member 15 Tnfsf15 1.11 1.10 1.10 -1.88* 1.14 1.17 -1.18 -1.07

NM_134388 Troponin T1, skeletal, slow Tnnt1 -2.14 -1.6 -1.93 -2.27* -1.52 1.00 1.09 1.24

NM_031836 Vascular endothelial growth factor A Vegfa 1.62 1.33 1.41 1.18 -1.74 1.14 -1.02 1.14

NM_053549 Vascular endothelial growth factor B Vegfb 1.75* 1.15 1.17 1.16 -1.03 1.78 -1.02 1.08

NM_053653 Vascular endothelial growth factor C Vegfc 1.39 1.43 1.23 3.76* -2.02 -1.12 -1.57 2.38

NM_001013167 WAS protein family, member 2 Wasf2 2.02 1.63 1.28 2.40 -2.05 -1.36 -2.03 1.84

 *Statistically significant (P<.05)
68 http://www.cs.amedd.army.mil/amedd_journal.aspx

is supported by the observed modulation of cytokines 

as viable tissue succumbed to necrosis in the stasis zone. 

Modulation of immunoregulatory molecules may be 

expected adjacent to necrotic tissue since necrosis is 

known to elicit an intense immune response.27 In the 

present study, Il10 and Il1β exhibited some of the largest magnitude changes in expression. Large magnitude 

modulation of these 2 genes occurred in Zones I and II 

at time points when avascularity was present and relatively minor in the area of blood flow (Zones III and IV). 

IL-1β, a signature proinflammatory cytokine of macrophages, has been shown to be essential for angiogenesis 

in multiple settings including rheumatoid arthritis, endometriosis, myocardial infarction, and wound healing.28-31 However, IL-1β influences on angiogenesis may 

be complex, since it has also been shown to inhibit one 

of the most potent angiogenic factors, VEGF-D.32 IL-10 

is an anti-inflammatory cytokine that functions primarily to limit inflammation but also promotes growth and 

maturation of multiple cell types including vascular endothelial cells.33

In addition to immunoregulatory molecules, adhesion 

molecules also showed large magnitude modulation in 

this study. Integrin αvβ3 is an adhesion receptor expressed in wound granulation tissue but not in normal 

skin.34 Antagonists of Integrin αvβ3 block angiogenesis 

induced by FGF-2 or tumor necrosis factor-α (TNF-α) 

and promote tumor regression by inducing apoptosis of 

endothelial cells in angiogenic vessels.34,35 Both Integrin 

αv (Itgav) and Integrin β3 (Itgb3) subunits exhibited statistically significant modulation in this study, with the 

αv subunit showing more than 10-fold reduction in signal intensity over the early time interval in the necrotic 

zone.

Few transcription factors that initiate programs of angiogenesis-associated gene expression showed statistically 

Tgfbr1

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 98.5±38.5 24.7±24.3 15.9±11.7

Zone II 81.0±36.3 46.6±33.3 13.7±16.3

Zone III 27.3±15.5 15.0±2.5 14.7±10.3

Zone IV 15.4±3.5 14.8±5.4 13.7±6.8

Epas

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 6.79±3.17 1.21±0.99 2.26±1.85

Zone II 10.4±7.2 2.06±0.94 1.86±1.75

Zone III 9.37±4.12 6.80±1.31 10.4±3.57

Zone IV 11.1±4.52 6.00±1.84 11.6±5.92

Nrp2

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 0.69±0.19 5.53±4.71 2.81±2.58

Zone II 0.65±0.13 1.37±0.37 6.45±7.19

Zone III 1.44±0.54 1.24±0.67 0.96±0.19

Zone IV 1.07±0.29 1.20±0.55 0.85±0.14

Serpinf1

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 25.5±5.38 6.66±11.69 3.32±3.97

Zone II 15.6±8.58 4.43±2.75 2.95±3.69

Zone III 2.00±0.88 3.66±1.23 1.47±1.14

Zone IV 1.83±1.66 5.14±3.89 0.95±0.17

Vegfa

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 0.46±0.19 0.78±0.37 0.64±0.31

Zone II 0.57±0.11 0.81±0.43 0.67±0.36

Zone III 0.52±0.33 0.30±0.13 0.59±0.18

Zone IV 0.53±0.15 0.52±0.57 0.60±0.31

Vegfc

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 0.71±0.14 0.99±0.85 1.02±0.88

Zone II 0.75±0.30 0.92±0.40 2.82±1.87

Zone III 0.51±0.50 0.25±0.16 0.46±0.26

Zone IV 0.47±0.19 0.30±0.28 1.11±0.90

Fgf2

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 0.67±0.07 0.79±0.34 0.65±0.59

Zone II 0.43±0.21 0.44±0.19 0.97±0.67

Zone III 0.37±0.15 0.25±0.06 0.38±0.06

Zone IV 0.38±0.26 0.30±0.15 0.53±0.24

Pdgfa

mean normalized signal intensity±sd

Day 1 Day 3 Day 7

Zone I 2.66±0.65 3.37±5.31 4.03±4.16

Zone II 1.80±1.65 2.63±1.65 3.71±4.54

Zone III 2.37±2.17 4.38±1.22 2.50±2.19

Zone IV 2.25±0.99 4.71±2.12 1.45±1.32

Table 2. Mean Normalized Signal Intensity for Selected Genes.

TEMPOROSPATIAL ANGIOGENESIS-ASSOCIATED GENE

EXPRESSION PROFILES IN RAT ISCHEMIC SKIN FLAPS
July – September 2017 69

THE ARMY MEDICAL DEPARTMENT JOURNAL

significant modulation in this study, and none showed 

large magnitude changes. A well-known stimulus for 

gene expression is hypoxia. Although oxygen tension 

was not measured in this study, an oxygen gradient 

was expected to exist along the length of the flap. The 

most distal aspect of the flap most likely had the lowest 

partial pressure of oxygen, owing to early loss of blood 

flow. In a hypoxic state, the hypoxia inducible factor-1α 

(HIF-1α) protein exhibits a diminished degradation rate, 

permitting association with HIF-1β.36 This functional 

transcription factor complex initiates a program of hypoxia-inducible gene expression.36 In the present study, 

expression levels of HIF-1α were low across the length 

of the flap at all time points, and there were no statistically significant changes in HIF-1α signal intensity. It 

is possible that the time-points that we examined were 

too late to detect changes in signal intensity in the range 

exhibited by this transcription factor.

Results from this study will provide a basis for comparison for ongoing research involving ischemic skin 

flap healing in diabetic rats and ischemic rat skin flaps 

treated with pharmacological agents. Identification of 

the molecular basis for derangement or pharmacological 

enhancement of angiogenesis may be possible. Future 

studies should also aim at identifying the cell types expressing important angiogenic factors using techniques 

such as laser capture microdissection. Further characterization of the complex sequence of events that occurs 

during the skin flap healing process may provide new 

directions for adjunctive therapies.

Conclusion

In a previous study,21 researchers in our lab defined distinct zones in ischemic rat skin flaps using orthogonal 

polarization spectral imaging. We now correlate these 

zones with spatial and temporal variations in angiogenesis associated gene expression. Future experiments 

will focus on differences in expression profiles between 

treatment and nontreatment groups in diabetic and nondiabetic rats.

Acknowledgements

We thank Dr Jill Lewis, College of Dental Medicine 

and Graduate College of Biomedical Sciences, Western 

University of the Health Sciences, Pomona, California; 

Dr Ulf ME Wikesjö, Department of Periodontics, Oral 

Biology Laboratory for Applied Periodontal & Craniofacial Regeneration, Augusta University, The Dental College of Georgia, Augusta, Georgia; and Dr Carol Lapp, 

Department of Oral Biology, Medical College of Georgia 

(now Augusta University), Augusta, Georgia, for their 

technical advice, input to the conduct of this study, and 

editing of this manuscript. We also thank the Southern 

Academy of Periodontology for support of this project 

through the Billy M. Pennel Research Competition.

References

1. Tuz M, Eroglu E, Dogru H, Delibas N, Tunc B, 

Uygur K. The effect of replacement fluids and normovolaemic haemodilution on the survival of dorsal skin flaps in rats. Clin Otolaryngol Allied Sci. 

2004;29:80-83.

2. Slate RK, Ryan M, Bongard FS. Dependence 

of tissue oxygen on oxygen delivery. J Surg Res. 

1996;61:201-205.

3. McFarlane RM, Deyoung G, Henry RA. The design 

of a pedicle flap in the rat to study necrosis and its 

prevention. Plast Reconstr Surg. 1965;35:177-182.

4. Hsu OK, Gabr E, Steward E, et al. Pharmacologic 

enhancement of rat skin flap survival with topical 

oleic acid. Plast Reconstr Surg. 2004;113:2048-

2054; discussion 2055-2046.

5. Tsai JW, Ayubi FS, Hart KL, et al. Evaluation 

of the effect of sildenafil and vascular endothelium growth factor combination treatment on 

skin flap survival in rats. Aesthetic Plast Surg. 

2008;32:624-631.

6. Zamierowski DS. Pharmacologic enhancement 

of rat skin flap survival. Plast Reconstr Surg. 

2005;115:2145; author reply 2145-2146.

7. Zheng Y, Yi C, Xia W, et al. Mesenchymal stem 

cells transduced by vascular endothelial growth 

factor gene for ischemic random skin flaps. Plast 

Reconstr Surg. 2008;121:59-69.

8. Xiong B, Yi CX, Chen HD, et al. Vascular endothelial growth factor gene transfection and survival of 

the random skin flap in rats [in Chinese]. Di Yi Jun 

Yi Da Xue Xue Bao. 2004;24(7):794-797.

9. Presta M, Dell’Era P, Mitola S, Moroni E, Ronca 

R, Rusnati M. Fibroblast growth factor/fibroblast 

growth factor receptor system in angiogenesis. Cytokine Growth Factor Rev. 2005;16:159-178.

10. Nogami M, Hoshi T, Kinoshita M, Arai T, Takama 

M, Takahashi I. Vascular endothelial growth factor expression in rat skin incision wound. Med Mol 

Morphol. 2007;40:82-87.

11. Bauer SM, Bauer RJ, Liu ZJ, Chen H, Goldstein L, 

Velazquez OC. Vascular endothelial growth factorC promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen 

gels. J Vasc Surg. 2005;41:699-707.
70 http://www.cs.amedd.army.mil/amedd_journal.aspx

12. Distler JH, Hirth A, Kurowska-Stolarska M, Gay 

RE, Gay S, Distler O. Angiogenic and angiostatic 

factors in the molecular control of angiogenesis. Q 

J Nucl Med. 2003;47:149-161.

13. Benjamin LE, Hemo I, Keshet E. A plasticity window for blood vessel remodelling is defined by 

pericyte coverage of the preformed endothelial 

network and is regulated by PDGF-B and VEGF. 

Development. 1998;125(9):1591-1598.

14. Kimura I, Honda R, Okai H, Okabe M. Vascular 

endothelial growth factor promotes cell-cycle transition from G0 to G1 phase in subcultured endothelial cells of diabetic rat thoracic aorta. Jpn J Pharmacol. 2000;83:47-55.

15. Hoeben A, Landuyt B, Highley MS, Wildiers H, 

Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol 

Rev. 2004;56:549-580.

16. Wallez Y, Cand F, Cruzalegui F, et al. Src kinase 

phosphorylates vascular endothelial-cadherin in 

response to vascular endothelial growth factor: 

identification of tyrosine 685 as the unique target 

site. Oncogene. 2007;26:1067-1077.

17. Suzuki F. Cartilage-derived growth factor and antitumor factor: past, present, and future studies. Biochem Biophys Res Commun. 1999;259:1-7.

18. Shukunami C, Oshima Y, Hiraki Y. Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis inhibitors found in hypovascular 

connective tissues. Biochem Biophys Res Commun. 

2005;333:299-307.

19. Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C. Angiogenic and antiangiogenic factors in 

proliferative diabetic retinopathy. Curr Diabetes 

Rev. 2006;2:71-98.

20. van Hinsbergh VW, Engelse MA, Quax PH. Pericellular proteases in angiogenesis and vasculogenesis. 

Arterioscler Thromb Vasc Biol. 2006;26:716-728.

21. Hart K, Baur D, Hodam J, et al. Short- and longterm effects of sildenafil on skin flap survival in 

rats. Laryngoscope. 2006;116:522-528.

22. Myers B. Understanding flap necrosis. Plast Reconstr Surg. 1986;78:813-814.

23. Risau W. Mechanisms of angiogenesis. Nature. 

1997;386:671-674.

24. Olivier WA, Hazen A, Levine JP, Soltanian H, 

Chung S, Gurtner GC. Reliable assessment of skin 

flap viability using orthogonal polarization imaging. Plast Reconstr Surg. 2003;112:547-555.

25. Groner W, Winkelman JW, Harris AG, et al. Orthogonal polarization spectral imaging: a new 

method for study of the microcirculation. Nat Med. 

1999;5:1209-1212.

26. Carmeliet P, Collen D. Molecular basis of angiogenesis. Role of VEGF and VE-cadherin. Ann N 

Y Acad Sci. 2000;902:249-262; discussion 262-264.

27. Frangogiannis NG. Chemokines in ischemia and 

reperfusion. Thromb Haemost. 2007;97:738-747.

28. Geiger T, Towbin H, Cosenti-Vargas A, et al. Neutralization of interleukin-1 beta activity in vivo 

with a monoclonal antibody alleviates collageninduced arthritis in DBA/1 mice and prevents the 

associated acute-phase response. Clin Exp Rheumatol. 1993;11:515-522.

29. Voronov E, Shouval DS, Krelin Y, et al. IL-1 is 

required for tumor invasiveness and angiogenesis. 

Proc Natl Acad Sci U S A. 2003;100(5):2645-2650.

30. Lebovic DI, Bentzien F, Chao VA, Garrett EN, 

Meng YG, Taylor RN. Induction of an angiogenic phenotype in endometriotic stromal cell 

cultures by interleukin-1beta. Mol Hum Reprod. 

2000;6:269-275.

31. Arend WP, Dayer JM. Inhibition of the production 

and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis. Arthritis Rheum. 

1995;38:151-160.

32. Mountain DJ, Singh M, Singh K. Downregulation 

of VEGF-D expression by interleukin-1beta in cardiac microvascular endothelial cells is mediated 

by MAPKs and PKCalpha/beta1. J Cell Physiol. 

2008;215:337-343.

33. Moore KW, de Waal Malefyt R, Coffman RL, 

O’Garra A. Interleukin-10 and the interleukin-10 

receptor. Annu Rev Immunol. 2001;19:683-765.

34. Brooks PC, Clark RA, Cheresh DA. Requirement 

of vascular integrin alpha v beta 3 for angiogenesis. 

Science. 1994;264:569-571.

35. Brooks PC, Montgomery AM, Rosenfeld M, et al. 

Integrin alpha v beta 3 antagonists promote tumor 

regression by inducing apoptosis of angiogenic 

blood vessels. Cell. 1994;79:1157-1164.

36. Chi JT, Wang Z, Nuyten DS, et al. Gene expression 

programs in response to hypoxia: cell type specificity and prognostic significance in human cancers. 

PLoS Med. 2006;3:e47.

Authors

LTC Johnson is the Assistant Director, US Army Advanced Education Program in Periodontics, Fort Gordon, 

Georgia.

LCDR Toussaint-Barrett is with the Office of Public 

Health Preparedness and Response, Centers for Disease 

Control and Prevention, Atlanta, Georgia.

LTC Pizarro is Deputy Project Manager, Neurotrama 

and Psychological Health PMO, US Army Medical Materiel Development Activity, Fort Detrick, Maryland.

TEMPOROSPATIAL ANGIOGENESIS-ASSOCIATED GENE

EXPRESSION PROFILES IN RAT ISCHEMIC SKIN FLAPS
July – September 2017 71

Resistance to Abrasion of Extrinsic Porcelain

 Esthetic Characterization Techniques

LTC Woo J. Chi, DC, USA J. Rodway Mackert, DMD

William Browning, DDS Richard J. Windhorn, DMD

Stephen Looney, PhD Frederick Rueggeberg, DDS, MS

January – March 2017 1

Although ceramic restorations are considered to be 

color-stable, a gradual change in shade may be noticed 

starting a few years after placement.1

 While there could 

be any number of reasons for this change, removal of a 

thin layer of colorants by toothbrush abrasion may be a 

contributing factor. According to Aker et al, toothbrush 

abrasion was found to gradually remove the colorant 

layer applied to the surface of metal ceramic crowns.2

The colorant layer was completely removed after 10 to 

12 years of simulated toothbrushing, while colorants 

having a glaze overcoat were removed after 30 years of 

simulated toothbrushing because the layer of clear glaze 

had to be worn away before the colorant layer could be 

affected.2,3 In another study, most of the colorant layer 

was removed after 11 years of simulated brushing resulting in a signi cantly rough surface and shade mismatch.4

A novel dental ceramic characterization technique was 

introduced by a master dental laboratory technician during hands-on training at the US Army Prosthodontic Residency Program to fabricate longer lasting esthetic dental 

restorations with improved wear resistance properties 

Resistance to Abrasion of Extrinsic Porcelain

 Esthetic Characterization Techniques

MAJ Woo J. Chi, DC, USA J. Rodway Mackert, DMD

William Browning, DDS COL Richard Windhorn, DC, USA

Stephen Looney, PhD Frederick Rueggeberg, DDS, MS

ABSTRACT

Statement of Problem: A novel esthetic porcelain characterization technique involves mixing an appropriate amount of 

ceramic colorants with clear, low-fusing porcelain (LFP), applying the mixture on the external surfaces, and  ring the 

combined components onto the surface of restorations in a porcelain oven. This method may provide better esthetic qualities and toothbrush abrasion resistance compared to the conventional techniques of applying color-corrective porcelain 

colorants alone, or applying a clear glaze layer over the colorants. However, there is no scienti c literature to support this 

claim.

Purpose: This research evaluated toothbrush abrasion resistance of a novel porcelain esthetic characterization technique 

by subjecting specimens to various durations of simulated toothbrush abrasion. The results were compared to those obtained using the conventional characterization techniques of colorant application only or colorant followed by placement 

of a clear over-glaze.

Method and Materials: Four experimental groups, all of which were a leucite reinforced ceramic of E TC1 (Vita A1) 

shade, were prepared and  red in a porcelain oven according to the manufacturer’s instructions. Group S (stain only) 

was characterized by application of surface colorants to provide a de nitive shade of Vita A3.5. Group GS (glaze over 

stain) was characterized by application of a layer of glaze over the existing colorant layer as used for Group S. Group SL 

(stain+LFP) was characterized by application of a mixture of colorants and clear low-fusing add-on porcelain to provide 

a de nitive shade of Vita A3.5. Group C (Control) was used as a control without any surface characterization. The 4 

groups were subjected to mechanical toothbrushing using a 1:1 water-to-toothpaste solution for a simulated duration of 

32 years of clinical use. The amount of wear was measured at time intervals simulating every 4 years of toothbrushing. 

These parameters were evaluated longitudinally for all groups as well as compared at similar time points among groups.

Results: In this study, the novel external characterization technique (stain+LFP: Group SL) did not signi cantly enhance 

the wear resistance against toothbrush abrasion. Instead, the average wear of the applied extrinsic porcelain was 2 to 3 

times more than Group S (stain only) and Group GS (glaze over stain). Application of a glaze layer over the colorants 

(Group GS) showed a signi cant improvement on wear resistance. Despite its superior physical properties, the leucite 

reinforced ceramic core (Group C) showed 2 to 4 times more wear when compared with other test groups.

Conclusion: A conventional external esthetic characterization technique of applying a glaze layer over the colorants 

(Group GS) signi cantly enhanced the surface wear resistance to toothbrush abrasion when compared with other techniques involving application of colorants only (Group S) or mixture of colorant and LFP (Group SL). The underlying core 

ceramic had signi cantly less wear resistance compared with all externally characterized specimens. The novel esthetic 

characterization technique showed more wear and less color stability, and is thus not advocated as the “best” method for 

surface characterization.

Clinical Implications: Application of a glaze layer provides a more wear resistant surface from toothbrush abrasion when 

adjusting or extrinsically characterizing leucite reinforced ceramic restorations. Without the glaze layer, the restoration is 

subjected to a 2 to 4 times faster rate and amount of wear leading to possible shade mismatch.
72 http://www.cs.amedd.army.mil/amedd_journal.aspx

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

2 http://www.cs.amedd.army.mil/amedd_journal.aspx

and color stability. The method involves mixing an appropriate amount of ceramic colorants with incisal, or 

clear, low-fusing porcelain (LFP). The mixture is then 

applied to the external ceramic surfaces and  red. Dental 

laboratory technicians can characterize dental restorations faster since this technique requires only one  ring 

cycle, whereas conventional characterization technique 

involves 2 separate cycles of  ring colorants and glaze 

layer. The master technician also claims that suspending 

colorants throughout the matrix of clear porcelain creates more esthetic and natural looking restorations by 

increasing the depth of perception. The wear resistant 

property and color stability using this novel technique 

have not been published in the dental literature, but may 

surpass those of placing and  ring a separate colorant 

layer, then covering it with a low fusing glaze (Figure 1).

The effects of toothbrush abrasion on dental restorations 

are studied in vitro using a reciprocating, mechanical 

device to hold toothbrushes against the restoration 

surface in a slurry mixture of water and dentifrice 

to simulate the in vivo state. This condition simulates a three body wear system that involves frictional contact among toothbrush bristles, dentifrice 

slurry, and the restorative material.5

 Furthermore, 

there are additional factors that are related to toothbrush and dentifrice abrasion. The combination of 

the effects of dentifrice, toothbrush, brushing force, 

brushing habits, and pH of the slurry solution contribute to abrasion of tooth and restoration surfaces.4,6 The effect of brushing force on wear of dental 

ceramics has been studied using an in vitro 3-body wear 

test.7

 Studies have shown a direct relationship between 

brushing force and the amount of wear.7

 In addition, De 

Boer et al showed that abrasion is linearly correlated to 

the number of strokes.6

Aker et al reported that 1 hour of brushing or 16,000 

brush strokes in the toothbrushing machine was projected to be equal to brushing each tooth 22 strokes twice 

a day, 365 days a year.2

 In addition, Bergvall et al estimated 14,000 strokes per year whereas Heath and Wilson estimated 20 000 strokes per year.8,9 Another study 

reported that, on average, one surface of a tooth receives 

19 strokes each time of brushing resulting in approximately 14,000 strokes per year.10 More strokes were used 

to brush the mandibular than the maxillary teeth, more 

for the labial and buccal than for occlusal and lingual 

surfaces.10,11 These studies imply that the labial surface 

of anterior teeth or restorations will receive more brush 

strokes compared to other tooth surfaces in the mouth, 

hence enhancing the adverse effects of toothbrush abrasion in the esthetic zone.

MATERIALS AND METHODS

Ceramic Specimen Preparation

One master specimen (14.5 mm by 11.5 mm by 3.0 mm) 

was cut from a 3 mm thick clear plastic vacuum matrix material (Biostar, Great Lakes Orthodontics). Four 

dimples, approximately 50 μm deep, were carved on the 

corners of the master specimen. An impression of the 

master specimen was made in a disposable plastic box 

(Plastic Boxes Clear/Blue 1”, #1011740LL, Zahn Dental) 

using polyvinyl siloxane impression material (Extrude, 

Light Body, #29177, Kerr Dental). Melted dental dipping 

wax (Bellewax, Kerr Dental) was  owed into the impression and allowed to cool to room temperature and 

harden. A total of 16 wax-patterns of the master specimen were generated in this manner. The wax-patterns 

were sprued and invested in a phosphate-bonded investment (Microstar Dental, LLC) for 15 minutes, allowed 

to harden, and then transferred into a burn-out oven 

(In nity L30, Jelrus) preheated to 1600°F. After 60 minutes in the oven, 2 ceramic ingots with Vita A1 shade 

(IPS Empress, E TC1 Esthetic Ingot, Ivoclar Vivadent) 

were pressed into the investment in a porcelain oven 

(EP 500; Ivoclar Vivadent) according to manufacturer’s 

instructions. Thus, a total of 16 leucite-reinforced ceramic blocks were fabricated from the wax-patterns. 

The shade of each processed specimen was measured 

with a calibrated intraoral dental spectrophotometer 

(VITA Easyshade, Vident). The spectrophotometer was 

secured on a stand with clamps and the specimens were 

raised on a  at platform perpendicular to the probe. The 

initial surface characteristics as well as the thickness 

of the materials above the plane connecting 3 of the 4 

dimple bottoms of each specimen were obtained by using a scanning pro lometer (Taylor Hobson Pneumo, 

Taylor Hobson Precision) before the application of the 

surface colorants. The dimple bottoms were not covered 

with surface colorants because they served as reference 

points for comparing within each specimen throughout 

clinically simulated toothbrushing (CST) (Figure 2).

Surface colorants (IPS Empress Universal stain A2/A3/

A3.5, Ivoclar Vivadent) were applied to the specimens in 

Group S and Group SL to achieve the de nitive shade 

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

Figure 1. Different techniques of ceramic esthetic characterization by 

application of components to surface of existing ceramic restoration.

Mixture of Colorant

and LFP Application

Colorant Application

Glaze Application Colorant Application

Veneering Porcelain

Esthetic

Characterization
July – September 2017 73

THE ARMY MEDICAL DEPARTMENT JOURNAL

January – March 2017 3

THE ARMY MEDICAL DEPARTMENT JOURNAL

of Vita A3.5. These specimens were 

then  red in a porcelain oven at the 

manufacturer recommended temperature. A clear glaze layer (IPS 

Empress Universal Glaze, Ivoclar 

Vivadent) was applied only to the 

4 specimens in Group GS and then 

 red in the same porcelain oven. A 

mixture of clear, add-on low-fusing 

porcelain (IPS Empress Add-On, 

Ivoclar Vivadent) and color corrective porcelain colorants was made 

and applied to the 4 specimens in 

Group SL. The specimens were  red 

in the same porcelain oven. The 

specimens in Group C were used as 

a control without any external esthetic characterization.

The prepared specimens were 

scanned again using the surface 

pro lometer. The scanned, 3-dimensional images of each specimen were 

compared with the correlated images scanned before the characterization (Figure 3).

Toothbrush Abrasion of the Ceramic Groups

Specimen holders for the toothbrushing machine were 

made by placing 2 specimens on a 2 mm-thick clear 

plastic block and pressing down a heated 0.6 mm-thick 

vacuum matrix material (Biostar, Great Lakes Orthodontics) on the top of the specimens.

The middle portion of the vacuum matrix material was 

cut out while protecting the dimples (Figure 4). A toothbrushing machine (V-8 Cross Brushing Apparatus, Sabri Enterprises) that holds up to 8 manual toothbrushes 

(47 Tufts Medium Toothbrush, Ranir Co.) simulated 

toothbrush abrasion on the groups 

under a slurry solution composed 

of 37.5 g of neutral toothpaste (Sparkling White Cinnamon Mint Toothpaste, Colgate Oral Pharmaceuticals) 

and 37.5 ml of distilled water. The 

force applied on each brush was adjusted to 200 gf (1.96 N). The toothbrushing machine was adjusted to 

provide 19,000 reciprocal strokes 

(de ned as 1 cycle of downward and 

upward motion) to the specimens 

to simulate one year of clinical use. 

The number of reciprocal strokes 

and force applied was determined 

based on 8 published abrasion studies (Table 1).

Initial measurements of the surface 

pro le were recorded before subjecting the specimens to simulated toothbrush abrasion. The specimens were 

then placed in the toothbrushing machine and the abrasion process was 

started. After each 76,000 strokes, the specimens were 

removed and tested and rotated 180°. In addition, the 

slurry solution and toothbrushes were replaced every 

76,000 reciprocal strokes.

Surface Profilimetry

Three dimensional images of the scanned specimens 

were produced using pro lometer software (Talymap 

Software, Taylor Hobson Precision). The 3-dimensional 

images were properly oriented and leveled using a reference plane formed by connecting the bottom of 3 specific dimples. Then, a surface pro le of the leveled images, 

diagonally connecting 2 speci c dimples, was produced 

for every 4 years of simulated toothbrushing up to 32 

years of CST (Figure 5).

The surface pro les were exported to Microsoft Excel (2003) and a superimposed image was produced 

for each group (Figure 6).

The average height loss over time and percentage 

loss of colorant layer in each group over time were 

calculated using the digitized areas under these 

curves. First, unnecessary areas under the incline of 

the dimples as well as the shoulder areas between the 

top of the dimples to the beginning of the colorant 

layer were removed (Figures 7 and 8). In order to calculate the average height of colorant layer above the 

ceramic core, the average height of the core above 

the bottom of the dimples was subtracted from the 

Figure 2. Schematic diagram portraying 

each specimen group with composition in 

cross section.

Group SL

Colorant+LFP (A3.5)

IPS Empress (A1)

Group GS

Clear Glaze

Colorant (A3.5)

IPS Empress (A1)

Group S

Colorant (A3.5)

IPS Empress (A1)

Group C

Thickness of material above

plane of dimple boƩ om

IPS Empress (A1)

Dimples

Figure 3. Group GS: glaze layer over colorant layer.

Distance Across Specimen (mm)

Height (mm)

0 468 2 10 12 14

0.00

0.02

0.04

0.06

0.08

0.10

0.12

Prestain Poststain

Colorant &

Glaze Layers

Ceramic Core
74 http://www.cs.amedd.army.mil/amedd_journal.aspx

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

4 http://www.cs.amedd.army.mil/amedd_journal.aspx

average height of the colorant layer from the bottom 

of the dimples (Figure 8). This method was applied to 

calculate initial thickness of characterization layers in 

Groups S, GS, and SL. The average initial thickness 

of colorants in Group S was 16 μm. The average initial thickness of colorants and glaze layer in Group GS 

was 34 μm. The initial thickness of glaze layer above 

colorants was 18 μm. The average initial thickness of 

mixture of colorants and LFP was 40 μm.

The average height of colorant layer was calculated every 4 years until 32 years of CST. The average height 

loss as well as percentage loss was calculated every 4 

years of CST. The average height loss and percentage 

loss over time was plotted.

Statistical Analysis

For each data, repeated measures analysis of variance 

(ANOVA) were used to test the null hypothesis that there 

was no interaction between groups (stain only, Group S; 

glaze over stain, Group GS; stain+LFP, Group SL; Control, Group C) and time (0, 4, 8, 12, 16, 20, 24, 28, 32 

years). If no signi cant interaction was found, pro les 

for each group were assumed to be parallel. In this case, 

the next step was to (1) test the main effect for “group”, 

which was the null hypothesis that the group pro les 

were coincident, and (2) test the main effect for “time”, 

which was the null hypothesis that the group pro les 

were level. Failure to reject the null hypothesis in (1) 

would have shown that there was no difference among 

groups, regardless of time. Failure to reject the null hypothesis in (2) would have shown that there was no difference with regard to time, regardless of group. All 3 of 

these tests were performed at the 0.05 signi cance level.

In this study, the group-by-time interaction was statistically signi cant. Therefore, the 4 groups were compared 

separately at each of the time points, and the time points 

were compared separately within each of the 4 groups. 

Each of the tests of the group effect and each of the tests 

of the time effect were performed at a Bonferroni-adjusted signi cance level of 0.05/(number of tests performed), 

so that the family-wise error rate for the tests of the 2 factors (group and time) could be controlled at the 0.05 level.

Regardless of whether there was signi cant interaction 

or not, the Tukey-Kramer method of multiple comparisons for repeated measures designs was used to perform 

all possible pair-wise comparisons among groups and 

among time points, using the same signi cance level as 

the test of the corresponding main effect.

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

Figure 4. Design of specimen holder.

Protective

plastic lip

Area subjected to

toothbrush abrasion

Create areas not subjected 

to wear to preserve the 

reference dimples from 

toothbrush abrasion.

Create dimples so that 

specimens can be 

oriented for volumetric 

wear measurements.

Create area to accomodate 

width of toothbrushing 

machine test brush setup.

Figure 5. Cross-sectional image generated every 4 years of clinical simulation of toothbrushing for each specimen.

0 468 2

2

0

4

6

8

9

7

3

5

1

10

11

12

(mm)

(mm) (μm)

20

0

40

60

80

200

240

180

140

160

120

100

220

260

Distance Across Specimen (mm)

Height (mm)

0 468 2 10 12 14

0.00

0.02

0.04

0.06

0.08

0.10

0.12

Prestain Poststain

Ceramic Core

Addition of

Colorants Cross Section
July – September 2017 75

THE ARMY MEDICAL DEPARTMENT JOURNAL

January – March 2017 5

THE ARMY MEDICAL DEPARTMENT JOURNAL

RESULTS

Average Height Loss (μm)

The novel external characterization technique (stain+LFP, Group SL) did not significantly enhance the wear resistance against 

toothbrush abrasion when compared with 

conventional techniques. Instead, the average height loss of the applied extrinsic porcelain was 2 to 3 times more than Group 

S (stain only) and Group GS (glaze over 

stain) after 32 years of CST.

Application of a glaze layer over the colorants (Group GS) showed a signi cant improvement on wear resistance, starting as 

early as the 12-year mark, when compared 

with Group SL (stain+LFP) and Group S 

(stain only). After 32 years of CST, only 9 μm (average height loss), or 27% (average percentage loss), of the 

initial applied glaze layer (Group GS) had been abraded 

away, whereas 15 μm (81%) loss was observed in the 

colorant layer (Group S) and 24 μm (52%) loss was observed when the colorants were mixed with LFP (Group 

SL). This result was consistent with the protective effect 

of a glaze layer against toothbrush abrasion.4

Merely applying and  ring colorants (Group S) showed 

a signi cant improvement in wear resistance as early as 12 years of CST when compared with the novel 

Table 1. Summary of previously published studies on toothbrush abrasion.

Study Number of 

Reciprocal 

Strokes/Year

Weight (g) 

Applied

Dentifrice 

Water 

Ratio

Slurry

Replacement

Cycle

Substrate

Aker 2 7,920 450 1:1 None Porcelain

Bativala 4 14,118 250 1:1 None Porcelain

Bergwall 8 7,000 450 1:1 None Acrylic Resin

Cannon12 N/A 250 1:1 None Porcelain

Goldstein13 10,000 283 1:1 None Composite

Heath 9 10,000 N/A N/A N/A N/A

Kanter 14 4,320 N/A N/A N/A Composite

Tanoue15 10,000 350 1:1 20,000 strokes Composite

Wictorin16 7,380 450 1:1 None Acrylic Resin

Wang 17 23,809 200 N/A N/A Composite

Average 10,505 335 1:1 N/A N/A

Figure 6. Superimposed cross-sectional views over time.

Distance Across Specimen (mm)

0 2 468 10 12 14

Height of Specimen (mm)

0.00

0.02

0.04

0.06

0.08

0.10

0.12

28 Years Wear

32 Years Wear

Prestain

Stained

4 Years Wear

8 Years Wear

12 Years Wear

16 Years Wear

20 Years Wear

24 Years Wear

Ceramic Core

Colorant & FLP

Distance of the Colorant Layer
76 http://www.cs.amedd.army.mil/amedd_journal.aspx

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

6

technique (Group SL). Despite its superior 

physical properties, the leucite reinforced ceramic core (Group C) showed 2 to 4 times 

more wear over 32 years of CST when compared with other test groups. Statistically signi cant height loss of the ceramic core was 

observed, starting as early as the 8-year mark, 

when compared with other test groups.

Although average height loss among the characterized specimens showed a positive relationship with increased duration of simulated 

toothbrushing, each group demonstrated different rates of wear. For example, the least 

average height loss (9±1.74 μm) among the 

characterized specimens was observed in Group GS 

(glaze over stain) after 32 years of CST. The largest average height loss (35±2.74 μm) was observed in Group 

C (Control). Group S (stain only) had a lower average 

height loss (13±2.47 μm) when compared with Group 

SL (stain+LFP) (21±2.28 μm) (Figure 9, Table 2).

Average Percentage Stain Loss

Average percentage loss among the characterized specimens also showed a positive relationship with increased 

duration of simulated toothbrushing. Each group demonstrated a different rate of percentage loss. For example, Group S (stain only) showed 80%±12% of the 

original external colorants gradually removed after 32 

years of CST. Group SL (stain+LFP) showed 52%±7% 

of the external colorant layer gradually abraded away. 

Group GS (glaze over stain) showed only 27%±6% of 

the external glaze and colorant layer abraded away over 

32 years of CST (Figure 10, 

Table 3).

Group GS (glaze over stain) 

demonstrated a signi -

cantly reduced percentage 

loss, starting as early as the 

12-year point, when compared with other test groups. 

Overall, this group showed 

the least amount of percentage loss of the characterized 

surface over 32 years of CST 

(Figure 10).

Group SL (stain+LFP) 

showed a signi cantly smaller percentage loss starting at 

the 16-year mark when compared with Group S (stain 

only). This  nding was due 

to increased initial thickness of the characterization layer in Group SL that was 2 times thicker than the colorant 

layer in Group S. The average thickness of the colorants 

in Group S (stain only) was 16 μm compared with that 

of 40 μm in Group SL (stain+LFP).

COMMENT

In this study, using the novel external characteristic 

technique of mixing LFP with colorants (Group SL) 

did not enhance the wear resistance against simulated 

toothbrush abrasion. Instead, the average height and 

percentage loss were 2 to 3 times greater when compared to Group S (stain only) and Group GS (glaze over 

stain). This substantial wear of the LFP and colorant 

mixture may have resulted from its less dense and more 

porous surface characteristics compared with a stained 

and glazed surface. Therefore, the novel esthetic characterization technique may lead to more adverse effects 

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

Figure 7. Area of interest de ned.

Distance Across Specimen (mm)

Height (mm)

0 468 2 10 12 14

0.00

0.02

0.04

0.06

0.08

0.10

0.12

Area of Interest

Shoulder

Top of

Dimple

Bottom of 

Dimple

Prestain Poststain

Figure 8. Area of interest after removal of unnecessary areas.

Distance Across Specimen (mm)

0 2 468 10 12 14

Height (mm)

0.00

0.02

0.04

0.06

0.08

0.10

0.12

Prestain Poststain

Average height of ceramic ingot

from bottom of dimples=40 μm

Average height of colorants from 

bottom of dimples=75 μm

Average height of colorants

35 μm (75 μm - 40 μm)
July – September 2017 77

THE ARMY MEDICAL DEPARTMENT JOURNAL

January – March 2017 7

THE ARMY MEDICAL DEPARTMENT JOURNAL

rather than improving the 

physical and esthetic qualities of a restoration.

Application of a glaze layer 

over the colorants (Group 

GS) improved the wear 

resistance compared with 

other characterization techniques. After 32 years of 

CST, only 9 μm (average 

height loss), or 27% (average percentage loss), of the 

initial applied glaze layer 

(Group GS) was abraded 

away, whereas 15 μm (81%) 

loss was observed in the 

colorant layer (Group S) 

and 24 μm (52%) loss was 

observed when the colorants were mixed with LFP 

(Group SL). These results 

were consistent with the 

protective effect of a glaze 

layer against toothbrush abrasion.2,4 Therefore, application of a clear glaze layer over 

the colorants is recommended to enhance the 

wear resistance against toothbrush abrasion.

Despite its superior physical properties, the 

leucite-reinforced core ceramic (Group C) 

showed 2 to 4 times more wear over 32 years 

of CST compared with the extrinsic colorants and glaze. Lower wear resistance of 

the ceramic core may be due to higher crack 

growth pattern of the leucite-reinforced ceramics in an aqueous slurry solution with 

neutral pH when they are subjected to mechanical toothbrushing. The increase in solubility of leucite crystals may be another explanation of this undesired property of the ceramic core. 

Further research should be conducted to investigate the 

correlation between the solubility of leucite-reinforced 

ceramics and the potential of a higher wear rate compared with dental ceramics without leucite crystals.

A pilot study was conducted for up to 32 years of CST 

using 2 specimens in each group in order to determine the number of specimens needed in each group 

for this experiment. Eight specimens per group were 

determined to be necessary based on the results from 

the pilot study. Although only 4 specimens per group 

were used in this experiment due to limited time and 

resources, statistically signi cant differences among 

groups were found. Experimental modi cations, such as 

rotating the specimens 180° every 4 years of CST, using 

 at toothbrush bristles, and using more abrasive toothpastes, were made from the pilot study to facilitate even 

patterns of wear. A larger sample might have provided 

additional precision to detect differences among groups 

with shorter periods of follow-up corresponding to those 

that are more commonly found in clinical studies.

Parameters including the force applied to the specimens, 

number of reciprocal strokes in 1 year of CST, and the 

area of the toothbrush bristles had be considered. In 

an attempt to correlate these factors, Equation 1 was 

formulated:

Figure 9. Average accumulated height loss (μm) of external porcelain characterization layer over 

32 years of clinically simulated toothbrushing.

Note: n=4 specimens per group. SD values not included to enhance clarity (refer to Table 2).

Accumulated Simulated Years of Toothbrushing

Average Height Loss (μm)

25

0

10

15

5

20

30

40

35

0-4 0-8 0-12 0-16 0-20 0-24 0-28 0-32

Statistically not significant Statistically significant

Glaze over Stain (Group GS)

Stain Only (Group S)

Stain plus LFP (Group SL)

Control (Group C)

Table 2. Average accumulated height loss over accumulated years of clinically simulated toothbrushing (CST).

Accumulated

Years of CST

Accumulated Height loss (μm)

Group Sa Group GSb Group SLc Group Cd

Avg SD CV Avg SD CV Avg SD CV Avg SD CV

0-4 0.8 0.5 57 1.1 0.3 27 1.2 0.3 24 2.1 0.5 23

0-8 1.9 0.5 25 2.3 0.6 28 3.8 0.7 18 5.3 0.2 5

0-12 4.1 0.5 12 2.9 0.4 16 7.2 1.1 15 10.3 1.2 11

0-16 5.7 0.5 10 3.4 0.2 5 9.4 1.1 11 14.3 0.3 2

0-20 7.7 0.4 5 4.3 0.4 9 12.3 1.5 12 19.2 1.2 6

0-24 9.3 0.8 8 5.6 0.5 10 15.0 1.5 10 24.2 1.4 6

0-28 10.7 1.4 13 7.2 1.5 21 17.9 1.7 10 29.2 2.2 8

0-32 12.9 2.5 19 9.0 1.7 19 20.7 2.3 11 34.7 2.7 8

a: stain only c: stain+LFP Note: CV indicates Coef cient of variation b: glaze over stain d: Control
78 http://www.cs.amedd.army.mil/amedd_journal.aspx

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

8 http://www.cs.amedd.army.mil/amedd_journal.aspx

where:

PD = pressure applied times distance traveled (work)

F= weight applied to the toothbrush (N)

Lb=length of bristles (mm)

Wb= width of bristles (mm)

S= number of reciprocal strokes for 1 year of CST

This equation shows that the weight (grams-force) applied on the toothbrush and the total distance the toothbrush bristles traveled on a specimen in 1 year of CST 

has an inverse relationship with the area of the bristles 

that are in contact with the specimen. For example, the 

average parameters of 8 different abrasion studies from 

Table 1 are shown below:

Average weight applied to toothbrush=335 gf

(3.29 N)

Average number of reciprocal strokes for 1 year of 

CST=10,505 strokes

Length of bristles=25 mm

Width of bristles=8 mm

PD =(335 g×10,505 reciprocal strokes×25 mm)/

(8 mm×25 mm)=

(87,979,375 gf reciprocal strokes mm)/(200 mm2)=

439,897 gf strokes/mm

A researcher can calculate the appropriate number 

of reciprocal strokes in 1 year of CST with different 

parameters using 439,897 

gf strokes/mm as a constant value. In this study, 

the number of reciprocal 

strokes was calculated to 

be 19,000 per year since the 

maximum amount of force 

the toothbrushing machine 

could generate was 200 gf 

(1.96 N), which was 135 

gf (1.32 N) less than the 

average force applied on 

the toothbrush. Therefore, 

the number of reciprocal 

strokes was increased to 

compensate for the decrease in force applied on 

the toothbrush using Equation 1.

CONCLUSIONS

A conventional external esthetic characterization technique of applying a glaze layer over the colorants (Group 

GS) signi cantly enhanced the surface wear resistance 

to toothbrush abrasion, and improved the surface color 

stability when compared with other techniques involving application of colorants only (Group S) or mixture 

of colorant and LFP (Group SL). The underlying core 

ceramic had signi cantly less wear resistance properties 

compared with all externally characterized specimens. 

The novel esthetic characterization technique showed 

more wear and is thus not advocated as the “best” method for surface characterization.

REFERENCES

1. Anil N, Bolay S. Effect of toothbrushing on the 

material loss, roughness, and color of intrinsically 

and extrinsically stained porcelain used in metalceramic restorations: an in vitro study. Int J Prosthodont. 2002;15:483-487.

2. Aker DA, Aker JR, Sorensen SE. Toothbrush abrasion of color-corrective porcelain stains applied to 

porcelain-fused-to-metal restorations. J Prosthet 

Dent. 1980;44:161-163.

3. Yilmaz C, Korkmaz T, Demirkoprulu H, Ergun 

G, Ozkan Y. Color stability of glazed and polished 

dental porcelains. J Prosthodont. 2008;17:20-24.

4. Bativala F, Weiner S, Berendsen P, Vincent GR, 

Ianzano J, Harris WT Jr. The microscopic appearance and effect of toothbrushing on extrinsically stained metal-ceramic restorations. J Prosthet 

Dent. 1987;57:47-52.

RESISTANCE TO ABRASION OF EXTRINSIC PORCELAIN ESTHETIC CHARACTERIZATION TECHNIQUES

Figure 10. Average accumulated percentage loss of external porcelain characterization layer over 

32 years of clinically simulated toothbrushing.

Note: n=4 specimens per group. SD values not included to enhance clarity (refer to Table 2). Average Percentage Loss (μm)

Statistically not significant Statistically significant

Accumulated Simulated Years of Toothbrushing

50

0

20

30

10

40

60

80

90

70

0-4 0-8 0-12 0-16 0-20 0-24 0-28 0-32

Stain Only (Group S) Stain plus LFP (Group SL) Glaze over Stain (Group GS)
July – September 2017 79

THE ARMY MEDICAL DEPARTMENT JOURNAL

January – March 2017 9

THE ARMY MEDICAL DEPARTMENT JOURNAL

5. al-Hiyasat AS, Saunders WP, Smith GM. Threebody wear associated with three ceramics and 

enamel. J Prosthet Dent. 1999;82:476-481.

6. De Boer P, Duinkerke AS, Arends J. In uence 

of tooth paste particle size and tooth brush stiffness on dentine abrasion in vitro. Caries Res. 

1985;19:232-239.

7. Kon M, Kakuta K, Ogura H. Effects of occlusal 

and brushing forces on wear of composite resins. 

Dent Mater J. 2006;25:183-194.

8. Bergwall O, Brannstrom M, Wictorin L. The effect of tooth brushing and removal of excess  lling 

on the surface of composite restorative resins. Sven 

Tandlak Tidskr. 1971;64:347-356.

9. Heath JR, Wilson HJ. The effect of water on the 

abrasion of restorative materials. J Oral Rehabil. 

1977;4:165-168.

10. Macgregor ID, Rugg-Gunn AJ. Toothbrushing duration in 60 uninstructed young adults. Community 

Dent Oral Epidemiol. 1985;13:121-122.

11. Macgregor ID, Rugg-Gunn AJ. Survey of toothbrushing duration in 85 uninstructed English 

schoolchildren. Community Dent Oral Epidemiol. 

1979;7:297-298.

12. Cannon ML, Marshall GW Jr, Marshall SJ, Cooley RO. Surface resistance to abrasion of preformed laminate resin veneers. J Prosthet Dent. 

1984;52:323-330.

13. Goldstein GR, Lerner T. The effect of toothbrushing on a hybrid composite resin. J Prosthet Dent. 

1991;66:498-500.

14. Kanter J, Koski RE, Martin D. The relationship of 

weight loss to surface roughness of composite resins from simulated toothbrushing. J Prosthet Dent. 

1982;47:505-513.

15. Tanoue N, Matsumura H, Atsuta M. Wear and surface roughness of current prosthetic composites after toothbrush/dentifrice abrasion. J Prosthet Dent. 

2000;84:93-97.

16. Wictorin L. Effect of toothbrushing on acrylic resin 

veneering material. I. A study of abrasion in vitro. 

Sven Tandlak Tidskr. 1971;64:247-254.

17. Wang L, Garcia FC, Amarante de Araujo P, Franco 

EB, Mondelli RF. Wear resistance of packable resin composites after simulated toothbrushing test. 

J Esthet Restor Dent. 2004;16:303-314; discussion 

14-15.

AUTHORS

MAJ Woo is a former resident, US Army Advanced Education Program in Prosthodontics, Tingay Dental Clinic, 

Fort Gordon, Georgia.

Dr Browning is a Professor and IDA Endowed Chair in 

Restorative Dentistry, School of Dentistry, Indiana University, Indianapolis, Indiana.

Dr Looney is a Professor, Department of Biostatistics, 

Georgia Regents University, Augusta, Georgia.

Dr Mackert is a Professor, Department of Graduate Studies, Oral Rehabilitation and Oral Biology, College of 

Dental Medicine, Georgia Regents University, Augusta, 

Georgia.

COL Windhorn is Commander, US Army Dental Clinic, 

Fort Richardson, Alaska.

Dr Ruggeberg is a Professor, Department of Graduate 

Studies, Oral Rehabilitation and Oral Biology, College of 

Dental Medicine, Georgia Regents University, Augusta, 

Georgia.

Table 3. Statistical analysis of average accumulated height loss between groups 

over time

Height Loss

(n=4 specimens per group)

Time

(years)

IPS Empress

vs

Group GSa

IPS Empress

vs

Group SLb

IPS Empress

vs

Group Sc

Group GSa

vs

Group SLb

Group GSa

vs

Group Sc

Group SLb

vs

Group Sc

4 1.000 1.000 0.989 1.000 1.000 1.000

8 0.003d 0.877 <0.001d 0.890 1.000 0.557

12 <0.001d 0.002d <0.001d <0.001d 0.994 0.002d

16 <0.001d <0.001d <0.001d <0.001d 0.130 <0.001d

20 <0.001d <0.001d <0.001d <0.001d <0.001d <0.001d

24 <0.001d <0.001d <0.001d <0.001d <0.001d <0.001d

28 <0.001d <0.001d <0.001d <0.001d <0.001d <0.001d

32 <0.001d <0.001d <0.001d <0.001d <0.001d <0.001d

a: glaze over stain c: stain only

b: stain+LFP d: indicates statistical signi cance with P<.05

Authors

LTC Woo is a Prosthodontist with the 65th Medical Brigade, US Army Garrison Yongsan, Seoul, Republic of 

Korea.

Dr Browning is a Professor and IDA Endowed Chair in 

Restorative Dentistry, School of Dentistry, Indiana University, Indianapolis, Indiana.

Dr Looney is a Professor, Department of Oral Health and 

Diagnostic Sciences, The Dental College of Georgia at 

Augusta University, Augusta, Georgia.

Dr Mackert is a Professor, Department of Restorative 

Sciences, Restorative Services, The Dental College of 

Georgia at Augusta University, Augusta, Georgia.

Dr Windhorn is Assistant Dean for Digital Dentistry, 

University of Kentucky College of Dentistry, Lexington, 

Kentucky.

Dr Ruggeberg is a Professor, Department of Restorative 

Sciences, Restorative Services, Oral Biology, The Dental College of Georgia at Augusta University, Augusta, 

Georgia.
80 http://www.cs.amedd.army.mil/amedd_journal.aspx

Despite notable progress in reducing the prevalence of 

cigarette smoking in the military, smokeless tobacco use 

continues to increase.1

 Based on data from the Millennium Cohort Study, deployment and combat exposure in 

the US military are associated with an increased level of 

smokeless tobacco use and smoking.2

 According to the 

Murtha Cancer Center, Department of Defense Cancer 

Center of Excellence, the prevalence of smokeless tobacco use in the military is almost 4 times greater compared 

to use in the US civilian population.3

 Symptoms of posttraumatic stress disorder also increase the odds for use.2

Dental caries is one of the most prevalent diseases causing the demineralization of tooth structure. Streptococcus species are the predominant oral bacterial acids 

produced.4

 Defective restorations lead to additional loss 

of tooth structure due to restoration and caries removal. Factors contributing to restoration defects include: 

marginal leakage, polymerization shrinkage, or plaque 

build-up due to high surface roughness.

Three restorative materials presently used for class 

V lesions include amalgam, resin composite, and 

resin-modified glass ionomer (RMGI). Amalgam continues to serve as an excellent and versatile material in 

dentistry for more than 150 years, with an estimated 

100 million Americans having amalgam restorations.5

Amalgam is the material of choice for larger carious 

lesions in posterior teeth due to its strength, durability, 

ease of use, and low cost.6

 Amalgams were commonly 

placed in class V preparations due to their hydrophilic 

quality, decreasing the need for moisture control. Amalgam limitations include poor esthetics and increased 

tooth structure removal for mechanical retention.

Composite restorations increased in popularity as a result of their tooth-like appearance and ability to conserve 

tooth structure, and now represent the preferred restoration among patients in the United States. Improvements 

such as refinement of filler materials with wear properties comparable to human enamel have made resin materials more predictably reliable in clinical use.7

 Composite resins are more technique sensitive, require bonding 

agents to maintain retention, and typically fail sooner 

than amalgams.

Effect of Smokeless Tobacco on Surface

 Roughness of Dental Restorations

MAJ Shani O. Thompson, DC, USA

Gerald D. Griffin, PhD

Nicole Meyer

LTC Manuel Pelaez, DC, USA

Abstract

Clinical Relevance: Surface alterations of dental restorations can result in increased plaque biofilm. This leads to 

increased risk of premature restoration failure. Smokeless tobacco, in common use by some US military personnel, 

represents a potential source for surface alteration. If smokeless tobacco causes an untoward effect, selection of a 

more resistant restorative material could increase restoration longevity, thus minimizing lost work time and costs associated with replacement of failed restorations.

Purpose: Comparatively assess the effect of smokeless tobacco/salivary substitute mixture on altering surface roughness 

of amalgam, composite resin, and resin modified glass ionomer (RMGI) restorations.

Materials and Methods: Sixty cubic restorations (3 groups of 20) were fabricated using a 4 mm by 3 mm Teflon mold. 

One examiner assessed the restorations at time points representing zero days, one day, one week, 2 weeks, one month, 

and 3 months. The data obtained were collected using a surface profilometer, measured in micrometers. Data were statistically analyzed using 2-way analysis of variance (ANOVA) test. A difference was significant if P< .05.

Results: Confidence levels with a 95% overall rating received a clinically acceptable classification. The 2-way ANOVA 

test detected significant differences between baseline, one day, one week, 2 weeks, one month, and 3-month data for surface roughness (P<.05). With respect to time and restoration type, results proved statistically significant with P<.0001. 

All restorations were statistically significant with respect to change in surface roughness with RMGIs showing the greatest surface roughness alteration.

Conclusion: Smokeless tobacco mixed with a salivary substitute altered restoration surface roughness over time. Resinmodified glass isonomer restorations demonstrate the greatest alteration of surface roughness, with amalgam restorations 

showing the least. Amalgam remains the preferential restorative material in patients who use smokeless tobacco.
July – September 2017 81

Resin-modified glass ionomers (RMGIs) have the same 

ion-releasing glass filler particles seen in conventional 

GIs, but smaller. They are synthesized by reacting methacrylate with polyacrylic acid.8

 The setting reaction 

for RMGIs is dual cure and light activated, as well 

as an acid-base reaction after absorption of water. 

They are excellent for class V restorations due to 

their fluoride releasing properties in these nonesthetic 

regions. Their “smart behavior,” which can change 

their behavior in response to various stimuli such 

as stress, heat, moisture, electricity, and pH, helps to 

prevent dimensional changes in moist environments.9

Compared to other restorative materials, one advantage 

of glass isonomers is that they may be placed in cavities without the need for bonding agents.10 Despite these 

positive biocompatible features, their weakness lies in 

the lack of sufficient strength and toughness.8

 To improve some of these weak glass ionomer properties, the 

creation of RMGIs improved fl exural strength through 

the introduction of hydrophilic monomers and polymers 

like hydroxylethyl methacrylate.11

Resin composites and RMGIs are the most common 

types of adhesive materials used to restore cervical lesions.12 Ideal esthetic properties of composite resins and 

the fluoride releasing properties of RMGIs make these 2 

restorations a good fi t. The more comparable modulus of 

elasticity of both restorations compared to enamel also 

allows for ideal abfractive properties. Amalgams have 

a solid record of longevity far outlasting those of composite resins and RMGIs with less inclination to recurrent decay. Understanding these properties help dentists 

decide which restorative material to use when treating 

deploying Soldiers who use smokeless tobacco.

Smokeless tobacco, which contains high sugar content 

and acidic properties, also contributes to caries onset, 

destruction of enamel and other tooth structures.13 As 

a result, smokeless tobacco use could result in a greater 

number of early failures of restorations, especially class 

V cervical restorations.

Various studies investigated the influence of surface 

structure and composition of dental restorative materials on bacterial adhesion.14 The overall conclusion from 

these studies is that surface roughness is positively correlated with plaque accumulation.15 Findings also demonstrate that increased surface roughness would prompt 

nonuniform stress distribution, mainly due to the shape 

differences in the surface layer.16 Ultimately, this leads 

to craze lines, cracks, or even fractures in the restoration causing inflammation of the dental pulp if not properly treated. Mecholsky et al 17 developed the theory that 

initiation of cracks starts at stress concentration points 

caused by surface roughness.

Given the relatively high rate of smokeless tobacco use 

in the armed forces, it is critical to understand how different dental materials respond to smokeless tobacco 

THE ARMY MEDICAL DEPARTMENT JOURNAL

Materials to test the effect of smokeless tobacco exposure on surface roughness.

Material Type Contents Manufacturer

Amalgam Valiant PhD (regular set) 59% Ag, 13% Cu, 43% Hg, 28% Sn Kerr

Charlotte, NC

Composite resin Filtek Supreme Ultra

Universal

Bis-GMA, UDMA, TEGDMA, Bis-EMA (6) resins,

silica filler, zirconia filler

3M ESPE

St. Paul, MN

Resin modified

glass ionomer

Fuji II LC Silicate glass powder, polyalkenoic acid, HEMA, UDMA GC America

Alsip, IL

Copenhagen

Tobacco

long cut, straight Water, tobacco, sodium chloride binders, natural and

artificial flavors, ammonium chloride, ethyl alcohol,

ammonium sodium carbonate preservatives (10 mg)

US Smokeless Tobacco Company

Nashville, TN

Surface

profilometer

Surface Roughness

Tester, Surftest SJ-210

2.4 in color graphic LCD, calculation results assessed

profiles, load and amplitude curves

Mitutoyo Corporation

Japan

Dykstra EMS

Embedding Mold

Stepped Microtome

Catalog # 70907

Teflon Electron Microscopy Sciences

Hatfield, PA

Curing Light Mini LED #303677-019 Power module, handpiece, eyeshield Acteon North America

Mount Laurel, NJ

Simulated salivary 

extract

Hanks Balanced

Salt Solution, 1X

10 mL Corning Cellgro

Manassas, VA

Matrix Strips DuPont Mylar

10 cm by 0.95 cm

MFG#20 95-8205

Plastic strips measure 4 in by 3/8 in by 0.002 in Patterson Dental Supply

Montreal, Quebec

Laboratory 

incubator

Heratherm Oven

Model # 3700-87

97.2°F temperature Thermo Scientific

Anaheim, CA

Reclosable

container & lid

0.55 liter clear plastic None Solo Cup Operating Corporation

Highland Park, IL
82 http://www.cs.amedd.army.mil/amedd_journal.aspx

exposure. To answer this question, the present study 

evaluated the effect of smokeless tobacco/salivary extract on 3 commonly used dental materials with differing surface roughness (Ra, μm).

Materials and Methods

Sixty restorations, divided into equal groups of twenty 

(20 amalgam, 20 RMGI, and 20 composite resin), were 

used to evaluate effects of smokeless tobacco and salivary extract solution combined liquid extract (Copenhagen long cut straight and Hanks Balanced Salt Solution) 

on the surface roughness of different restorations. Materials used, compositions, and product manufacturers 

used are listed in the Table.

Specimen Preparation

The restorative materials called for the preparation of 20 

cubic specimens each, using a 4 mm x 3 mm Heliotest 

Teflon mold (Electron Microscopy Science, Hat field, 

PA) (Figure 1). The prepared materials slightly overfilled the molds. Careful preparation of the composite 

resin and RMGI occurred with proper isolation and light 

cure with the use of a Mylar strip (DuPont Mylar, Montreal, Quebec) to help remove voids and excess material. 

A LED light cure unit (Mini LED, Acteon North America, Mount Laurel, NJ) with a light intensity of 665 mW/ 

cm cured and polymerized the composite and RMGI according to the manufacturers’ instructions. Amalgams 

fully set over the 24-hour setting period. Figure 2 shows 

restoration placement in the embedding molds.

Following specimen preparation, all restorations were 

polished, then soaked in normal saline at 37°C for 24 

hours. Preparations were blotted dry and initial measurements taken with a surface profilometer (Mitutoyo 

Surftest SJ-210) to determine baseline surface roughness. Baseline measurements represent control values.

The examiner stored specimens in a 97.2°F Heratherm 

laboratory incubator (Thermo Scientific, Anaheim, CA) 

during the duration of the experiment to represent the 

average temperature of the human mouth. Ten mg of 

the Copenhagen smokeless tobacco (Figure 3) and 10 

ml of the salivary substitute liquid mix fully covered 

each type of restorative material for 24 hours a day (Figure 4). The examiner measured the surface roughness 

after 6 hours (representing one day), 2 days (representing one week), 3.5 days (representing 2 weeks), 6 days 

(representing one month), and 15 days (representing 2 

months). The need to evaluate the surface degradation at 

shorter time intervals occurred due to the limited time 

constraints. The surface profilometer (Figure 5), an 

instrument which measures a surface’s profile in order 

to quantify its roughness, helped evaluate and quantify 

the surface roughness of the restorations. The average 

surface roughness (Ra) is the average value of the height 

of the surface profile above and below the centerline 

throughout the determined sampling length.18

In total, 60 prepared specimens divided into 3 groups 

were evaluated: Group 1, Valiant PhD (n=20); Group 

2, Filtek Supreme Ultra Universal (n=20); and Group 3, 

Fuji II LC (n=20).

Evaluation and Data Collection

One independent examiner placed and evaluated all restorations and collected data. The examiner accurately 

calibrated the Surftest SJ-210 surface profilometer by 

measuring the precision roughness specimen supplied 

with the profilometer set per manufacturer guidelines. 

The examiner also adjusted the gain to ensure the measured value equaled the nominal Ra value of the precision roughness specimen.

Figure 1. Top - restoration materials: (A) RGMI; (B) Composite; 

(C) Amalgam. Bottom - sample embedding mold.

EFFECT OF SMOKELESS TOBACCO ON SURFACE ROUGHNESS OF DENTAL RESTORATIONS
July – September 2017 83

THE ARMY MEDICAL DEPARTMENT JOURNAL

A calibrated surface profilometer found the average 

surface roughness (Ra, in micrometers) of the specimen. An initial roughness measurement represented the 

roughness value, unless the profilometer could not read 

an initial roughness value. If this occurred, the examiner moved the profilometer to an area where the device 

could obtain a reading. If the surface was too rough to 

gain a second reading, a null value was annotated.

Statistical Methods

A 2-way ANOVA test, using the same materials, analyzed intragroup comparisons between baseline and 

varying timelines. Evaluating row and column factors 

tested statistical significance of results with respect to 

time, restoration, and the interaction between the 2 factors. The alpha value was set at 0.05. Data are represented as means (±SEM) and experimental manipulations were performed in a parallel manner. Dunnett’s 

multiple comparisons test indicated the data collected 

were dis-tributed normally and are statistically significant. Graph Pad Prism statistical software was used for 

all statistical analyses.

Results

No restorations were lost due to misplacement or extreme chemical wear. Fifty-two readings were discarded 

because the profilometer could not read the roughness 

measurement range for specific time points. Initial illegible readings presented at hour 222 of data collection. 

Despite illegible readings at a specific time point, restorations presented a legible reading on the next available 

measurement period.

Time

When evaluating the change percentage of surface 

roughness over time, all restorations showed a steady 

to large change in roughness. Amalgams showed an 

overall 20% increase during the modeled 2-month 

testing period. Figure 6 portrays a small increase in 

surface roughness from baseline to completion of the 

data collection. There was a steady movement with a 

slight change over time. The highest surface roughness 

recording appeared at the simulated one month and one 

day mark (186 hours) and the lowest surface roughness 

recording appeared at baseline.

The RMGI showed the greatest overall percentage 

change with a 237% increase over the represented 

2-month period. Figure 6 shows a large increase over 

time from baseline to completion. The highest surface 

roughness recording appeared at the modeled 2-month 

period (360 hours) and the lowest recording appeared at 

baseline. Composites showed the most fluctuation with 

an overall 31% decrease over the represented simulated 

2-month period as shown in Figure 6. The highest surface roughness recording emerged at the one-week mark 

(45 hours) and the lowest 

recording emerged just 

short of one month.

All of the results followed 

suit with the hypothesis 

showing statistical significance for an increase in 

surface roughness overall. The total percentage 

Figure 2. Amalgam (left), composite resin (center), and glass ionomer (right) restoration materials in embedding molds.

Figure 3. Copenhagen Long Cut Straight smokeless tobacco.
84 http://www.cs.amedd.army.mil/amedd_journal.aspx

of variation for all restorations combined showed a 

row factor of 0.7672, yielding P<.0001 suggesting the 

results are statistically significant and stay within the 

confidence interval.

Restorations

Examination of the restorations from a clinical standpoint revealed a significant change in color and clinical roughness existed for all restorations. The RMGIs 

showed a distinct staining and change in surface texture 

(Figure 7). The percentage of total variation for the column factor was 67.73, yielding P<.0001, satisfying the 

confidence interval.

Interaction of Time with Respect to Restoration

Data shows that the amalgam restoration did not change 

surface roughness much over time, compared to the 

gradual, then rapid rise in surface roughness detected 

in the glass ionomer material. With regard to the effect 

of time with respect to the restoration, data shows statistical significance with a total percentage of variation 

of 4.2%. Surface roughness measurements of different 

restoration types yielded statistically significant variances among them after smokeless tobacco exposure 

(F(60, 3425) =1.607; P<.005). There was a significant 

interaction between time and restoration type (F(2, 

3425) = 4255; P<.0001).

The P value (P<.0001) satisfied the confidence interval of greater than 95%. The 2-way ANOVA evaluated 

comparisons of specimen mean scores. The ANOVA 

revealed statistically significant variances for all restoration types with respect to time (F(120, 3425)=4.398; 

P<.0001). 

Comment

Studies have shown an increased use of smokeless tobacco, especially among deployed military personnel.2

Reasons for smokeless tobacco use include helping to 

stimulate moisture in the mouth, addiction to nicotine, 

and peer pressure. Ingredients found in smokeless tobacco include: polonium 210, N-nitrosamines, formaldehyde, nicotine, cadmium, cyanide, arsenic, benzene, 

and lead, to name a few. Natural and artificial flavors, 

preservatives, and sugars are also added. Polynuclear 

aromatic hydrocarbons, polonium 210, and N-nitrosamines represent the chemical carcinogens.19 Another 

study shows 70% of tobacco-specific N-nitrosamines 

becomes extracted from one dip of snuff when kept in 

the mouth for 30 minutes.20

The pH of smokeless tobacco ranges from 5.84 to 8.1 

with a nicotinic content ranging from 0.42% to 2.73%.21

Although the average pH is more neutral to basic, the 

large amount of sugar, preservatives, and chemical carcinogens of smokeless tobacco have an association with 

gingival recession, tooth wear, and dental caries in users.22 Long-term clinical success of dental restorations 

depends on various factors, including the physical properties of the material, clinical proficiency of the treating 

dentist, and proper maintenance and patient care. Understanding whether there is a change in surface roughness 

is important because, according to Yalcin and Gurgan, 

“irregularities in surface texture enhance bacterial adhesion, and roughened materials may suffer from increased 

staining.”23 Increased bacterial adhesion increases the 

incidence of recurrent decay and defective restorations.

The 3 restorative materials used in this study showed 

varying results most likely due to the differences in 

their material structure. Due to their organic matrix, 

resin materials are more prone to chemical alteration 

compared to metal or ceramic restorations.14 This could 

explain why the amalgam group showed the smallest 

change in surface roughness compared to the composite 

resin and RMGI groups.

Studies comparing amalgam and resin-based composites as restorative materials suggest amalgam has greater 

Figure 4. The embedding mold filled with RMGI restoration 

material covered with the smokeless tobacco/salivary substitute mix. The other 2 embedding molds were covered in a 

similar manner.

Figure 5. Surface roughness tester (Surftest SJ-210 profilometer.

EFFECT OF SMOKELESS TOBACCO ON SURFACE ROUGHNESS OF DENTAL RESTORATIONS
July – September 2017 85

THE ARMY MEDICAL DEPARTMENT JOURNAL

longevity than resin-based composites. One randomized 

clinical trial24 revealed the risk of experiencing secondary caries as 3.5 times greater with composites. Amalgam outperformed resin- based–composites, showing a 

94.4% amalgam survival rate at 7 years compared with 

85.8% for resin-based composites at 7 years. Improved 

survival rates of amalgams may be attributed to the less 

technique sensitive nature of placing them, expansion 

of amalgam upon setting which decreases onset of marginal leakage, and a greater ability to withstand occlusal 

forces.

The RMGI showed the greatest change in surface roughness with a statistically significant steady and gradual 

increase noted throughout the entire 360 hours of testing. This increase also showed clinical evidence with 

visible roughness and staining. The large sensitivity 

of RMGI to smokeless tobacco may be attributed to a 

weak organic matrix. While RMGIs perform well with retention and postsensitivity, it is not reliable in terms of marginal 

characteristics, surface properties, and 

color stability.25 For this reason, RMGI 

may not be the restoration of choice for a 

patient using smokeless tobacco.

Smokeless tobacco also had a significant effect on the surface roughness of composite 

resin. The results for this material fluctuated differently from the amalgam and RMGI. 

Values for the surface roughness remained 

steady for the first half of the experiment 

until a sharp drop in roughness was 

measured around the halfway point. From 

that point on, the roughness continued to 

gradually increase. This is the only restoration which reacted contrary to initial 

clinical expectations clinically. Despite the 

clinical variability, statistics showed a significant overall increase in roughness.

Composite resins may have reacted with such clinical 

variability due to human error. Future studies may benefit from an extended time period of testing, which may 

help show a larger data set of the clinical exposure of 

the restoration composition change. In a previous study 

observing the effect of in-office bleaching agents carbamide peroxide and hydrogen peroxide,14 results showed 

a slight increase in the surface roughness of the composite resin tested, but the increase in this experiment did 

not show statistical significance.

Filtek Supreme Ultra Universal, the nanofil resin used 

in this study, has a well-rounded appeal because of its 

equal mix of esthetics and strength. Its translucency is 

also appealing. Composite resins, in this experiment, 

did not show the high resistance to smokeless tobacco 

of amalgam, but it also did not show the large change 

Figure 6. Change in surface roughness over time for each tested material.

Time (hours)

Surface Roughness (μm)

0.5

0

1

1.5

4

3.5

3

2.5

2

0 6 48 84 144 360

Composite Ionomer Amalgam

Figure 7. Amalgam (left), composite resin (center), and glass ionomer (right) restoration materials after 360 hours of testing.
86 http://www.cs.amedd.army.mil/amedd_journal.aspx

in roughness in comparison to RMGIs. Additional testing focusing on the relationship smokeless tobacco has 

on the composite resin may be helpful in gaining more 

understanding.

When reviewing and evaluating overall experiment results, it is important to remember that this study only 

takes into account the effect a smokeless tobacco mix 

has on the surface roughness of dental restorations solely from a chemical perspective. Objectively, smokeless 

tobacco use has more than just a chemical effect. The 

largest effect is abrasive in nature. The natural state 

of the tobacco is a graininess, which contributes the 

abrasive effects. Additional studies accounting for both 

chemical and abrasive effects of smokeless tobacco will 

provide an even greater understanding of this topic. In 

retrospect, the gold standard for truly measuring the 

surface roughness of a specimen would be use of a scanning electron microscope (SEM).

Nonetheless, the results of this study demonstrate distinct, measurable differences among common dental 

restoration materials when exposed to smokeless tobacco. These findings provide a framework for future studies such as SEM experiments. Additionally, the results 

presented here add to the literature to better inform dental clinicians, particularly those treating military personnel, when selecting restoration materials.

Conclusion

Both quantitative and clinical observations show the 

distinct effect that smokeless tobacco/salivary substitute mix has on surface roughness of common dental 

restorations. Amalgam (Valiant PhD), which represents 

the oldest and strongest restoration, showed the smallest change over time. The RMGI (Fuji II) showed the 

greatest percentage of surface roughness change with 

a distinct clinical staining over a period equivalent to 2 

months.

Acknowledgments

Sincerest thanks to COL (Ret) Linda L. Smith, a Comprehensive Dentist, and former Commander, US Army 

Dental Activity, US Military Academy, West Point, NY, 

as well as Assistant Director, Advanced Education in 

General Dentistry-1 Year Training Program, US Army 

Dental Activity, Baumholder, Germany. Thank you for 

your organizational guidance and editorial review of this 

manuscript.

References

1. Bondurant S, Wedge R, eds. Combating Tobacco 

Use in Military and Veteran Populations. Washington, DC: National Academies Press; 2009.

2. Hermes ED, Wells TS, Smith B, et al. Smokeless 

tobacco use related to military deployment, cigarettes and mental health symptoms in a large, prospective cohort study among US service members. 

Addiction. 2012;107(5):983-994.

3. Kangmin Z, Lee S. Smokeless tobacco use in the 

US military: accelerating progress against cancer 

through collaboration. Presentation at Walter Reed 

National Military Medical Center/John P. Murtha 

Cancer Center, Bethesda, MD; June 23, 2014. 

Available at: http://www.wrnmmc.capmed.mil/

CancerCenter/Shared%20Documents/16-Lee%20

-%20MCCCancer.pdf. Accessed September 9, 2016.

4. Gomez J. Detection and diagnosis of the early caries lesion. BMC Oral Health. 2015;15(suppl 1):S3.

5. Ritter AV. Talking with patients: dental amalgam. J 

Esthet Restor Dent. 2003;15(5):319.

6. Bharti R, Wadhwani KK, Tikku AP, Chandra A. 

Dental amalgam: an update. J Conserv Dent.

2010;13(4):204-208.

7. Christensen GJ. Should resin-based composite 

dominate restorative dentistry today?. J Am Dent 

Assoc. 2010:141:1490-1493.

8. Keshanif, Khoroushi M. A review of glassionomer: From conventional glass-ionomer to 

bioactive glass-ionomer. Dent Res J (Isfahan).

2013;10(4):411-420.

9. McCabe JF, Yan Z, Al Naimi OT, Mahmoud G, 

Rolland SL. Smart materials in dentistry--future 

prospects. Dent Mater J. 2009 Jan; 28(1):37-43.

10. Choi JY, Kim HW, Lee HH. Bioactive sol-gel 

glass added ionomer cement for the regeneration of tooth structure. J Mater Sci Mater Med.

2008;19(10):3287-3294.

11. Lassila LV, Närhi T, Vallittu PK, Yli-Urpo H. 

Compressive strength and surface characterization 

of glass ionomer cements modified by particles of 

bioactive glass. Dent Mater J. 2005;21(3):201-209.

12. Heintze SD, Roulet JF. Glass ionomer derivates 

have better retention rates in cervical restorations 

compared to self-etching adhesive systems. J Evid 

Based Dent Pract. 2010;10(1):18-20.

13. Tomar SL, Winn DM. Chewing tobacco use and 

dental caries among US men. J Am Dent Assoc.

1999;130(12):1700.

14. Mourouzis P, Koulaouzidou E, Helvatjoglu-Antoniades M. Effect of in-office bleaching agents 

on physical properties of dental composite resins. 

Quintessence Int. 2013;44(4):295-302.

15. Rashid H. The effect of surface roughness on ceramics used in dentistry: a review of literature. Eur 

J Dent. 2014;8(4):571-579.

EFFECT OF SMOKELESS TOBACCO ON SURFACE ROUGHNESS OF DENTAL RESTORATIONS
July – September 2017 87

THE ARMY MEDICAL DEPARTMENT JOURNAL

16. Davidson CL, de Jager N, Feilzer AJ. The influence 

of surface roughness on porcelain strength. Dent 

Mater J. 2000;16(6):381-388.

17. Mecholsky J, Freiman S, Rice R. Effect of grinding on flaw geometry and fracture of glass. J Am 

Ceram Soc. 1977;60:114-117.

18. Filho H, Azevedo M, Nagem H, Marsola F. Surface 

roughness of composite resins after finishing and 

polishing. Braz Dent J. 2003;14(1):37-41.

19. Main JH, Lecavalier DR. Smokeless tobacco and 

oral disease. J Can Dent Assoc. 1988;54:586-91.

20. Prokopczyk B, Wu M, Cox JE, Amin S, Desai D, 

Idris AM, Hoffmann D. Improved methodology 

for the quantitative assessment of tobacco-specific 

N-nitrosamines in tobacco by super critical fluid 

extraction. J Agric Food Chem. 1995;43:916-922.

21. Brunnemann KD, Hoffmann D, Qi J. Chemical 

profile of two types of oral snuff tobacco. Food 

Chem Toxicol. 2002;40:1699-1703.

22. Walsh P, Epstein J. The oral effects of smokeless 

tobacco. J Can Dent Assoc. 2000;66:22-25.

23. Yalcin F, Gurgan S. Effect of two different bleaching regimens on the gloss of tooth colored restorative materials. Dent Mater J. 2005;21:464-468.

24. Bernardo M, Luis H, Martin MD, et al. Survival 

and reasons for failure of amalgam versus composite posterior restorations placed in a randomized 

clinical trial. J Am Dent Assoc. 2007;138(6):775-783.

25. Sidhu SK. Clinical evaluations of resin-modified glass-ionomer restorations. Dent Mater J.

2010;26(1):7-12.

Authors

MAJ Thompson is Commander, Fort Leavenworth Dental Clinic, Fort Leavenworth, Kansas. When this study 

was conducted, she was a 2nd Year Resident, Advanced 

Education in General Dentistry, US Army Dental Activity, Fort Bragg, North Carolina.

Dr Griffin is a Neuroscientist, Virologist, and Assistant 

Professor of Psychology and Biology at Hope College, 

Holland, Michigan.

Ms Meyer, a clinical research assistant, is a junior at 

Hope College, Holland, Michigan.

LTC Pelaez is a Periodontal Mentor, Advanced Education in General Dentistry-2 Year Training Program, US 

Army Dental Activity, Fort Bragg, North Carolina.
88 http://www.cs.amedd.army.mil/amedd_journal.aspx

In the past several decades, major changes have occurred in both dental treatment philosophies (surgical 

vs medical model)1

 and direct dental restorative materials (amalgam and composite)2

 which have the potential 

to change the longevity of directly placed dental restorations. The most frequently cited reason for replacing direct dental restorations is secondary caries.3-11 Therefore, 

it stands to reason that if one lowers the caries risk of the 

patient by using Anderson’s medical model1

 or Featherstone’s CAMBRA approach (caries management by risk 

assessment),12,13 the placed dental restoration will fare 

better and last longer.

Similarly, using the dental restorative materials with 

the greatest longevity potential and caries resistant 

properties would be beneficial. The 2 most commonly 

placed direct dental restorations are resin composite 

and amalgam. Reasons for choosing either amalgam 

or composite for direct dental restorations may include 

cost, esthetics, ease of use, caries risk of the patient, and 

the material of preference (either for the patient or doctor).14,15 There is an ongoing debate in the literature over 

which restorative dental material has better longevity in 

the oral cavity.2,4,8,11,14,16 It should be noted that, regardless of the current debate, amalgam has a longer history 

of success, but the longevity of properly placed resin 

composite, is greatly improving.

The US Department of Health and Human Services 

estimates that “60 to 70 percent of restorative work is 

Placement and Replacement Rates of

 Amalgam and Composite Restorations

 on Posterior Teeth in a Military Population

MAJ Benjamin D. Owen, DC, USA

COL Peter H. Guevara, DC, USA

COL William Greenwood, DC, USA

Abstract

Objective: Replacement rates of direct dental restorations have been reported to be 37% to 70%, occupying a 

large proportion of a general dentist’s time. Variations in the rate of initial placement and replacement of direct 

den-tal restorations may be associated with material placed (amalgam or composite), age, caries risk of the 

patient, and other factors. The purpose of this research was to clarify where the majority of patient care time is 

spent as a restorative Army dentist regarding either the initial placement or replacement of failed restorations; 

and how the location, caries risk, and material used (amalgam or composite) affects replacement rates.

Methods: This retrospective cross-sectional study gathered data from 600 randomly selected military patient 

dental records. All paper records were reviewed and cross checked with the digital record and digital x-raydatabases. Record review was limited to all direct dental restorations placed in the posterior dentition within 

the past 2 years (March 2011 to March 2013). Statistical analysis was accomplished using chi-square tests and 

logistic regression analyses.

Results: Of the 600 charts reviewed, 525 were male, 75 were female, with an average age of 26 years (SD=6), 

ranging from 17 to 54 years. A third of the patients were classified as high, moderate, and low caries risk, respectively. The total number of posterior direct dental restorations placed was 2,117. Initial restorations totaled 

1,429 (67.5%), and replacement restorations placed totaled 688 (32.5%). Four hundred forty-one of the 688 

direct dental restorations replaced were amalgam (64%), the 247 remaining direct restorations replaced were 

composite (36%). Mandibular first molar dental restorations were replaced the most often (23.1%) while mandibular first premolar restorations were replaced the least often (0.9%). Older patients were more likely to have 

replacement of an existing restoration.

Conclusions: Military dentists spend about one-third (32.5%) of their time replacing existing direct dental restorations. The majority of direct dental restorations placed and replaced were amalgam. No significant difference was found between composite and amalgam restorations. Location was shown to be significant with first 

molars and second molar restorations failing with the highest frequency. There was no significant difference 

found between male and female patients. As patient’s age increased, the number of replacement restorations 

also increased.
July – September 2017 89

replacement of existing restorations.”17 Composite restorations have become the material of choice, being 

placed as direct restorations more frequently by practitioners than at any time in the past.18 Are we compromising longevity and retention for esthetics? Or, have materials and methods changed so much that composites can 

now be used interchangeably with amalgam in most if 

not all clinical situations?2

In a military population the idea of placing a functional, lasting, and retentive dental restoration is critical.19 

Today’s Soldiers experience a myriad of environments 

and their access to care is a constantly changing variable. 

Oral health is directly reflected in wellness and military 

readiness. This research seeks to improve upon existing 

treatment philosophies and aid in improving Soldier care.

The purpose of this research is to show where the majority of patient care time is spent by a restorative Army 

dentist on either the initial placement or replacement 

of failed restorations, and how the size, location, caries 

risk, and material used (amalgam or composite) affects 

replacement rates. The following scientific hypothesis 

will be tested: more than 50% of restorative work done 

by military dentists is replacing existing restorations; 

composite restorations fail more frequently; and permanent mandibular first molars require the replacement of 

existing restorations the most often.

Methods

For this research project, 600 dental records were selected (using an online random number generator) from 

the over 12,000 active dental records maintained at the 

Schofield Barracks Dental Clinic. To ensure records 

were randomly chosen and that no record was looked 

at twice, 60 records at a time were selected from each 

of the 10 color jackets used to sort records in the clinic. Once those 60 records were reviewed from each of 

the 10 sections a total of 600 patient charts had been 

reviewed.

The paper records were assessed concurrently with our digital record (CDA) 

and digital x-rays (DEVAA) databases 

for information confirming the types 

of dental restorations and restoration 

replacement rates. Record review was 

limited to all direct dental restorations 

placed in the posterior dentition within 

the previous 2 years (March 2011-March 

2013). This data mining included looking at restorative materials (amalgam 

vs composite) being placed, replaced, and treatment 

planned within the past 2 years; the age, gender, and 

caries risk of the patient; restoration location; and the 

size (number of surfaces) of the restorations.

Exclusion criteria included any patient record that did 

not have direct dental restorations in the posterior of the 

mouth placed, replaced, or treatment planned in the past 

2 years, and patients who did not have an annual exam 

with recent caries risk annotated in the past 2 years.

Statistical Analysis

Chi-square tests and logistic regression analyses were 

used to assess whether replacements are associated with 

factors such as age, risk of caries (high, moderate, or 

low), and material used (amalgam vs composite). Analyses were also done to evaluate whether type of restoration differs by location of tooth (eg, upper vs lower, or 

molar vs premolar).

Results

A total of 600 charts were reviewed; 525 of male patients, 

75 female patients, with an average age of 26 years (SD= 

6), ranging from 17 to 54 years. Patients were evenly 

divided among high, moderate, and low caries risk. As 

shown in Figure 1, there was no significant difference 

associated with gender and caries risk.

The total number of direct dental restorations (composite and amalgam) placed 

in the posterior dentition from the 600 

reviewed patient charts was 2,117. Initial restorations totaled 1,429 (68%), and 

replacement restorations placed totaled 

688 (32%) (Figure 2).

As shown in Figure 3, of the 1,429 initial 

direct restorations initially placed, 1,026 

were amalgam (71.8%) and 403 were 

composite (28.2%). A total of 441 of the 

688 direct dental restorations replaced 

were amalgam (64%). The 247 remaining direct restorations replaced were composite (36%).

THE ARMY MEDICAL DEPARTMENT JOURNAL

Figure 1. Caries risk by gender.

36 37

32 31 32 32

20

30

0

40

50

10

Female Male

Low Moderate High

Percentage of Patients

Caries Risk

68%

32%

Figure 2. Posterior direct dental 

restorations.

Replacement

Initial

Placement
90 http://www.cs.amedd.army.mil/amedd_journal.aspx

Younger patients were more likely than 

older patients to have an initial restoration placed. As patients increased 

in age, there was markedly less initial 

placement of restorations and more 

replacement of restorations. As shown 

in Figure 4, this transition typically 

occurred among patients aged 30-40 

years.

As shown in Figure 5, restorations located on first and second molars were 

replaced the most often. Mandibular first molars were 

replaced most frequently, accounting for 23.1% (159 restorations) of all restorations replaced. Maxillary first molars were a close second, with a replacement rate of 22% 

(152 restorations). In order, from most often replaced to 

least often, the remaining locations were mandibular 

second molars, maxillary second molars, maxillary second premolars, maxillary first premolars, mandibular 

second premolars, and mandibular first premolars.

Five hundred twenty-five of the 600 randomly chosen 

charts were male patients (88%) and 75 were female patients (13%). This aligns well with the overall distribution of gender in the Army. In 2013, Defense Manpower 

Research showed enlisted strength to be 86.8% male and 

13.2% female, while officers were 84.5% male and 15.5% 

female.20 Therefore, the random sample used for this research closely reflects an average sampling of the Army. 

Female patients were noted to be about 2 years older on 

average than male patients, 27.5 vs 25.6 years. As mentioned earlier, a comparison of the distribution of caries 

risk by gender reveals no significant differences (Figure 

1). However, the data showed that men were more likely 

than women to have an initial restoration placed, and that amalgam was 

more likely to be used for replacement 

restorations for males than for females 

(83% vs 71%, P=.007). Figure 6 presents those distributions.

The age range of our random patient 

sample of 600 was 17-54 years of age. 

There is a close to significant difference by age (P=.055), which is partly 

because younger patients are more 

likely to be classified as high caries risk than older patients (eg, 37% of patients aged 17-25 years are high risk 

vs 26% of patients aged 26-54 years) (Figure 7).

Another significant difference is that younger patients 

were more likely than older patients to have amalgam for 

initial restorations (79% of patients aged 17-21 years vs 

49% of patients aged 36-55 years) (Figure 8).

Comment

Previous research has demonstrated that practicing general dentists spend a majority of their time replacing 

restorations, with a replacement rate between 37% and 

70%.2-10 However, the results from this research show 

that the majority of the military dentist’s time (over twothirds) is spent placing initial restorations. The hypothesis that more than 50% of an Army dentist’s time is 

spent replacing restorations was shown not to be true. 

The authors believe that this is directly related to the 

unique subpopulation being treated by the Army dentist. 

Factors leading to this result could include the age of the 

patients (average age of 26 years), prevalent high caries 

risk of patients (almost one-third of all patients seen), 

poor oral hygiene of patients (often associated with stress), and the high intake 

of fermentable carbohydrates (snacks, 

sodas, energy drinks; all common for 

Soldiers to consume). The average civilian practice sees patients that are, on 

average, older, lower caries risk, and often represent a highly motivated patient 

group with excellent oral hygiene.

This research indicated that in the Army, 

the majority of direct dental restorations 

being replaced are amalgams (64%). It 

should be noted that the vast majority of 

restorations being initially placed in the 

Army are also amalgams. In fact, within 

the confines of this research, of the 1,429 

initial direct restorations placed and reviewed, 1,026 were amalgams (71.8%) 

Figure 3. Distribution of restorative 

materials used in initial and replacement restorations.

Initial Replacement

Placement

403 441

247

1,026

Amalgam Composite

PLACEMENT AND REPLACEMENT RATES OF AMALGAM AND COMPOSITE RESTORATIONS

ON POSTERIOR TEETH IN A MILITARY POPULATION
July – September 2017 91

THE ARMY MEDICAL DEPARTMENT JOURNAL

and 403 were composites (28.2%). Therefore, the minority of restorations placed in the Army are composites 

(28.2%), and a slightly larger minority of restorations 

replaced (36%) are composites. Considering this, it is 

apparent that a larger percentage of composites are being replaced in comparison to composites that are being 

initially placed within the Army’s large group practice. 

This may represent a higher failure rate of composite 

restorations, even though fewer overall are being placed 

and replaced than amalgam restorations.

Older research shows that amalgam restorations routinely last longer than composite, exhibiting better wear, 

durability, and longevity.2,15,16 However, newer research 

concludes that there is now 

no evident difference between amalgam and composite in longevity/failure 

rates.21 It is interesting to 

note that higher failure 

rates were associated with 

both older patients and an 

increase in the number of 

surfaces being restored.21

This newer research, 

which shows that amalgam 

and composite are becoming more equivalent, more 

accurately reflects the 

newer materials and methods being used by today’s 

dentists.

A relational trend is present in the analysis of patient age and replacement rates of dental restoration. As 

patients age, there is a shift from initial placement 

of restorations to replacement of restorations. In the 

military, the vast majority of the population seeking 

dental treatment is young, which is part of the reason 

why more initial restorations are being placed. The average civilian dentist will be placing many more replacement restorations across an older (on average) 

patient base. Therefore, the implication is that civilian 

dentists with older patient bases will spend more time 

replacing restorations.

The data did confirm the hypothesis that location of 

the restoration affected the replacement rate. Restorations placed the on the permanent mandibular first molars were replaced the most often, at 159 restorations or 

23.1%. The maxillary first molars were replaced at almost the exact same rate at 22% (152 restorations). The 

mandibular and maxillary second molars had very similar replacement rates to each other (16.7% and 16.4%) 

and came in at the 3rd and 4th most replaced locations, 

respectively. The posterior tooth that had replacement 

restorations completed the least often was the mandibular first premolar which had only 6 restorations (0.9%) 

replaced.

High caries risk patients should be treated medically 

because surgical replacement of missing tooth structure 

is insufficient treatment on its own. The disease process (caries) should be addressed. If the treating dentist 

“drills and fills” without regard for treating the active infectious disease, then those restorations will likely fail 

and require replacement in the future. Anderson et al1 

Percentage of Teeth 40

50

0

30

60

20

80

90

10

70

74

65

72 69

83

61

71

58

Initial

Restoration

Initial

Restoration,

Amalgam

Replaced

Amalgam

Replaced

with

Amalgam

Figure 6. Distribution by gender of initial restorations and use 

of amalgam in restorations.

Female Male

Number of Replacement Restorations

Mandibular 1st Molar

Mandibular 2nd Molar

Maxillary 2nd Premolar

Maxillary 1st Premolar

Maxillary 1st Molar

Maxillary 2nd Molar

Mandibular 1st Premolar

Mandibular 2nd Premolar

6

42

41

115

60

113

152

159

Figure 5. Distribution of replacement restorations by location.

0 20 40 60 80 100 120 140 160 180
92 http://www.cs.amedd.army.mil/amedd_journal.aspx

addressed this concern in 1993 when they suggested 

dentists follow 7 steps for high caries patients:

1. Caries control and diet analysis

2. Use of sealants

3. Use of chlorhexidine and fluoride varnish

4. Use of xylitol gum

5. Use of fluoride rinse

6. Recall after the end of treatment, and bacteriologic testing

7. Definitive restorations of temporaries

The above protocol described by Anderson’s medical 

model is still applicable today. Featherstone et al12,13 described a newer technique for high caries management 

in 2003: caries management by risk assessment (CAMBRA). According to this model, dental caries progression or reversal depends upon the balance between demineralization and remineralization of tooth structure.

The “caries balance” is determined by the relative weight 

of the sums of pathological factors and protective factors. If a patient is well advised of this and decreases the 

unfavorable factors (frequency and amount of fermentable carbohydrates, bacterial load, and poor saliva quality) while increasing the protective/favorable factors (saliva, sealants, antibacterials, fluoride, and an effective 

diet), the balance will shift towards remineralization of 

tooth structure and overall caries risk will decrease. If 

the techniques mentioned here are employed correctly 

by dentists and patients, replacement rates of dental restorations would go down as caries is consistently found 

to be the primary reason for replacing restorations.

This research revealed that military dentists place and 

replace direct dental restorations with amalgam more 

frequently than with composite. Why is amalgam the 

material of choice in the Army? Amalgam costs less, is 

more forgiving when placing in difficult environments, 

is less technique sensitive, has an excellent record, and 

is proven to be durable. Composite, 

having improved greatly in the areas 

of durability, fracture resistance, and 

longevity, is still very technique sensitive. In addition, compared to amalgam, composite requires up to 2.5×

more time to properly place a composite restoration.14 A poorly placed, 

incompletely cured composite will not 

last as long as, or function as well as, 

an amalgam restoration. The belief 

held by many dentists that high risk 

caries patients should not receive composite restorations is another reason 

that amalgam restorations are favored 

Figure 8. Distribution by age group of initial restorations and use of amalgam in restorations. Percentage of Teeth

60 60

68

80

44

49

68

85

68

76

62

77 79

60

85

79

20

10

40

30

60

80

90

50

70

0

Age Range (years): 17-25 22-25 26-35 36-54

Initial Restoration Initial Restoration, Amalgam Replaced Amalgam Replaced with Amalgam

10

0

50

40

30

20

Figure 7. Caries risk by age group.

43

32

26

37 39

25

30

33

37

26

37 37

Low Moderate High

Percentage of Patients

Age Range (years): 17-25 22-25 26-35 36-54

Caries Risk

PLACEMENT AND REPLACEMENT RATES OF AMALGAM AND COMPOSITE RESTORATIONS

ON POSTERIOR TEETH IN A MILITARY POPULATION
July – September 2017 93

THE ARMY MEDICAL DEPARTMENT JOURNAL

by Army dentists. In the less than ideal environments in 

which the military often finds itself, amalgam continues 

to have an advantage over composite. In summary, some 

advantages of amalgam:

• cost,

• time,

• ease of placement,

• BHA free,

• forgiving nature of the material,

• longevity;

while some advantages of composite include:

• esthetics,

• mercury free,

• improving durability, and

• longevity.

Conclusion

As materials and methods for use of composite resin as 

a dental restorative material continue to improve, clinical performance will continue to improve as well. The 

choice of restorative material may be considered less 

consequential in the future, and dental professionals 

will need to focus more on preventive treatment, such 

as CAMBRA, to decrease caries risk, decrease replacement rates, and increase restoration longevity.

Military dentists spend 32.5% of their time replacing 

existing direct dental restorations, and the majority of 

the direct dental restorations placed and replaced are 

amalgam. No significant difference was found between 

composite and amalgam restorations. Location was 

shown to be significant with first molars and second molar restorations failing with the highest frequency. There 

was no significant difference found between male and 

female patients. As patients’ ages increased, the number 

of replacement restorations also increased.

References

1. Anderson MH, Bales DJ, Omnell KA. Modern 

management of dental caries: the cutting edge is not 

the dental bur. J Am Dent Assoc. 1993;124:36-44.

2. Christensen GJ. Restoration longevity versus esthetics, a dilemma for dentists and patients. J Am 

Dent Assoc. 2011;142(10): 1194-1196.

3. Chrysanthakopoulos NA. Reasons for placement and replacement of composite dental restorations in an adult population in Greece. J Dent Res 

Dent Clin Dent Prospect. 2011;5(3):87-93. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/ 

PMC3442453/. Accessed September 6, 2016.

4. Mjör IA. Amalgam and composite resin restorations: longevity and reasons for replacement. Paper 

presented at: International Symposium on Criteria 

for Placement and Replacement of Dental Restorations; October 19-21, 1989, Lake Buena Vista, FL.

5. Burke FJ, Cheung SW, Mjör IA, WilsonNH. Reasons for the placement and replacement of restorations in vocational training practices. Prim Dent 

Care. 1999;6(1):17-20.

6. Deligeorgi V, Wilson NH, Fouzas D, Koulaki E, 

BurkeFJ, Mjör IA. Reasons for placement and 

replacement of restorations in student clinics 

in Manchester and Athens. Eur J Dent Educ. 

2000;4(4):153-159.

7. Mjör IA, Moorhead JE, Dahl JE. Reasons for replacement of restorations in permanent teeth in general dental practice. Int Dent J. 2000;50(6):361-366.

8. Hickel R, Manhart J. Longevity of restorations in 

posterior teeth and reasons for failure. J Adhes 

Dent. 2001;3(1):45-64.

9. Al Negrish AR. Reasons for placement and replacement of amalgam restorations in Jordan. Int Dent J. 

2001;51(2):109-115.

10. Frost PM. An audit on the placement and replacement of restorations in a general dental practice. 

Prim Dent Care. 2002;9(1):31-36.

11. Palotie U, Vehkalahti M. Reasons for replacement and the age of failed restorations in posterior 

teeth of young Finnish adults. Acta Odontol Scand. 

2002;60:325-329.

12. Featherstone JD, Adair SM, Anderson MH, et al. 

Caries management by risk assessment: consensus 

statement. J Calif Dent Assoc. 2003;31(3):257-269.

13. Young DA, Featherstone JD, Roth JR. Curing 

the silent epidemic: caries management in the 

21st century and beyond. J Calif Dent Assoc. 

2007;25(10):681-685.

14. Roulet JF. Benefits and disadvantages of 

toothcoloured alternatives to amalgam. J Dent. 

1997;25(6):459-473.

15. Correa MB, Peres MA, Peres KG, Horta BL, Barros AD, Demarco FF. Amalgam or composite 

resin? Factors influencing the choice of restorative 

material. J Dent. 2012;40(9):703-710.

16. Leinfelder KF. Do restorations made of amalgam 

outlast those made of resin-based composite?. J Am 

Dent Assoc. 2000;131(8):1186-1187.

17. Health.gov. IV Dental Amalgam Benefits Analysis 

[internet]. Office of Disease Prevention and Health 

Promotion. Available at: https://web.health.gov/ 

environment/amalgam1/appendixI-sectionIV.

htm. Accessed September 6, 2016.
94 http://www.cs.amedd.army.mil/amedd_journal.aspx

18. Ottenga ME, Mjör IA. Amalgam and composite 

posterior restorations: curriculum versus practice 

in operative dentistry at a US dental school. Oper 

Dent. 2007;32(5):524-528.

19. MacInnis WA, Ismail A, Brogan H. Placement and 

replacement of restorations in a military population. J Can Dent Assoc. 1991;57(3):227-231.

20. Statistic Brain. Demographics of Active Duty U.S. 

Military [internet]. August 12, 2016. Available at: 

http://www.statisticbrain.com/demographics-of-active-duty-u-s-military/. Accessed September 6, 2016.

21. McCracken MS, Gordan VV, Litaker MS, et al. A 

24-month evaluation of amalgam and resin-based 

composite restorations: findings from the National 

Dental Practice-Based Research Network. J Am 

Dent Assoc. 2013;144(6):583-593.

Authors

MAJ Owen is the Officer-in-Charge, Vilseck Dental, 

Clinic, US Army Dental Activity Bavaria, Germany.

COL Guevara is Program Director, Advanced Education 

in General Dentistry-2, Schofield Barracks, Hawaii. He 

is also the General Dentistry Consultant to The Army 

Surgeon General and a Professor at the Uniformed Services University of the Health Sciences.

COL Greenwood is Commander, Fort Benning Dental 

Activity, Fort Benning, Georgia.

PLACEMENT AND REPLACEMENT RATES OF AMALGAM AND COMPOSITE RESTORATIONS

ON POSTERIOR TEETH IN A MILITARY POPULATION
July – September 2017 95

Practice management has become an increasingly important component of graduate medical education. Lessons learned in training will carry forward to every 

practice environment; private, academic, and military. 

One of the most critical aspects of practice management 

is documentation and coding for physician services, as 

they directly affect the financial success of any practice. 

This importance is also emphasized by the Accreditation Council for Graduate Medical Education mandate 

for training in coding and billing. Current (2015) program requirements for training in family medicine necessitate 100 hours (or one month) of health system management instruction, including current billing practices 

and determining value in the marketplace.1

The need for improved training in coding is recognized by residents and faculty alike. A survey of 600 

residents at the University of Louisville demonstrated 

that residents identified deficits in their coding and billing knowledge. Further, knowledge deficits on healthcare care costs did not improve with subsequent years 

of training.2 A survey of 60 surgical residents and 46 

attending physicians from 5 training programs revealed 

that 82% of residents and 89% of attending physicians 

felt they had not been adequately trained in documenting 

and coding for physician services. Ninety-two percent 

of residents in this survey thought expertise in documentation and coding would improve their practice, and 

85% thought it an important part of residency training.3

Coding accuracy has a significant effect on the financial 

success of academic medical centers, where initial coding is performed by resident physicians. Under-coding 

errors can lead to decreased financial recoupment for a 

Improving Coding Accuracy

 in an Academic Practice

LTC Dana Nguyen, MC, USA

MAJ Heather O’Mara, MC, USA

CPT Robert Powell, MC, USA

Abstract

Practice management has become an increasingly important component of graduate medical education. This applies to every practice environment; private, academic, and military. One of the most critical aspects of practice 

management is documentation and coding for physician services, as they directly affect the financial success of 

any practice. Our quality improvement project aimed to implement a new and innovative method for teaching billing and coding in a longitudinal fashion in a family medicine residency. We hypothesized that implementation of 

a new teaching strategy would increase coding accuracy rates among residents and faculty.

Methods

Design: single group, pretest-posttest.

Setting: military family medicine residency clinic.

Study populations: 7 faculty physicians and 18 resident physicians participated as learners in the project.

Educational intervention: monthly structured coding learning sessions in the academic curriculum that involved 

learner-presented cases, small group case review, and large group discussion.

Main outcome measures: overall coding accuracy (compliance) percentage and coding accuracy per year group 

for the subjects that were able to participate longitudinally.

Statistical tests used: average coding accuracy for population; paired t test to assess improvement between 2 intervention periods, both aggregate and by year group.

Results

Overall coding accuracy rates remained stable over the course of time regardless of the modality of the educational intervention. A paired t test was conducted to compare coding accuracy rates at baseline (mean (M)=26.4%, 

SD=10%) to accuracy rates after all educational interventions were complete (M=26.8%, SD=12%); t24=-0.127, 

P=.90.

Conclusions

Didactic teaching and small group discussion sessions did not improve overall coding accuracy in a residency 

practice. Future interventions could focus on educating providers at the individual level.
96 http://www.cs.amedd.army.mil/amedd_journal.aspx

practice. An internal medicine residency program affiliated with the Mayo Clinic conducted a study to develop 

an instrument for billing in resident clinics, compare billing practices among residents of different training levels, 

and estimate financial losses from inaccurate resident 

billing. The authors found higher rates of coding errors 

among junior residents compared to senior residents. 

The rates of under billing was 74.2% for PGY-1, 48.8% 

for PGY-2, and 42.9% for PGY-3 residents, respectively 

(P<.01). Further, there was significantly less overbilling among PGY-1 residents compared with PGY-2 and 

PGY-3 residents (9.7% versus 24.4% and 17.9%, respectively (P<.05). Based on the 100 chart sample, the authors estimated that in a residency class of 48 residents, 

approximately $450,368.64 annually was lost to inaccurate coding, 50% of which was attributable to the PGY1 level.4

 In an effort to improve resident knowledge on 

incentive-based reimbursement, Carter et al designed an 

educational intervention with emergency medicine residents. Residents attended a one-hour lecture, were given a pocket card on documentation, received biweekly 

newsletters, and received weekly case-specific feedback 

from their billing department. These interventions resulted in an increase in total relative value units (RVUs) 

per hour, from 3.17 to 3.71 (P=.0001). With an average 

of 70,000 patient encounters per year, the authors estimated a projected billing increase of $1.5 million from 

this educational intervention.5

Several educational experiences have been successfully 

directed toward residents at improving coding accuracy. 

Benke et al evaluated the effect of a single 90-minute 

training session covering basic coding procedures and 

common errors at an ENT program with 14 practitioners with varying coding experience. Those inexperienced with coding (10 providers) showed an improved 

error rate of 8%, however, this error rate was significantly lower than that of more experienced coding practitioners.6

 In an effort to improve generalized practice management knowledge, a surgery program implemented a 

multifaceted approach. Surgery and medicine residents 

attended a series of 10 monthly lectures covering various aspects of practice management. In addition, surgical residents met monthly for didactic sessions with the 

business office to discuss billing and coding. Finally, the 

coding team and program director provided real time 

outpatient visit coding feedback. Surgical coding compliance among residents increased from 33% to 88% 

over a 12-month period.7

Objective

Our quality improvement project aimed to implement a 

new and innovative method for teaching billing and coding in longitudinal fashion in a family medicine residency.

Methods

Design, Setting, Study Population

This study received institutional approval as a quality 

improvement project. It was conducted as a local quality improvement initiative within a family medicine 

residency clinic. Ten faculty physicians and 24 resident 

physicians participated in monthly educational sessions 

about coding rules and regulations for outpatient encounters. Seven faculty and 18 residents were present 

over both academic years spanned by this project.

Intervention

We implemented 2 different educational interventions 

over a 12-month period. Initially, the educational sessions were learner-presented cases followed by large 

group discussion. Every 4 weeks, 3 residents and one 

faculty member were identified by the authors as having 

a chart coding “error.” The deficient encounters were selected from a series of charts identified by the clinic coders as common errors by the resident and faculty providers in the clinic. The selected residents and faculty were 

placed in coding “time out” and were instructed to sit 

with the coders to review their errors. The coders then 

provided one-on-one instruction regarding the appropriate way to code the encounter. During morning report 

once monthly, the selected providers then summarized 

the encounter, how the encounter was initially coded, 

and instructed the group on the appropriate coding or 

how improve documentation to justify their coding. The 

coders were present during this session to answer any 

questions generated by the large group discussion. The 

providers were subsequently released from “time out” 

and a new group of residents and faculty were chosen 

for the following cycle.

Over the second 6-month period, we changed the format 

of the educational sessions. In lieu of learner-presented 

cases, we facilitated small group case reviews followed 

by large group discussion. Each month, the authors identified common coding errors in the practice as reviewed 

with the clinic coding staff. Three outpatient encounters 

were selected and distributed to 3 small groups during 

the monthly educational sessions. Each small group received a different encounter with both patient and provider identifying information removed. Residents and 

faculty worked together in teams to discuss the appropriate diagnosis, current procedural terminology (CPT) 

code, and evaluation and management (E/M) code to 

assign to the encounter. Small groups then presented to 

the large group, while the authors facilitated discussion, 

highlighted teaching points, and emphasized proper 

coding practice. Again, coding staff attended to answer 

any questions or provide clarifying points from the large 

IMPROVING CODING ACCURACY IN AN ACADEMIC PRACTICE
July – September 2017 97

THE ARMY MEDICAL DEPARTMENT JOURNAL

group discussion. Of note, on arrival at the residency 

program, providers are given a coding “cheat sheet” for 

coding requirements for common family medicine encounters and procedures.

Outcomes

Coding accuracy rates were assessed monthly for individual providers. Prior to, and for the duration of this 

project, coders were collocated in the clinic. As standard 

practice, the coders reviewed 50% to 60% of total outpatient clinical encounters for all providers and were readily available for any questions. A monthly provider/coder 

comparison chart was already generated at the hospital 

level with provider diagnosis, CPT, and E/M codes followed by the correction after coder review. This report 

was obtained and reviewed every month by the authors. 

Encounters were considered “accurate” or “compliant” 

if the provider assigned E/M code matched the correct 

coder assigned E/M code. SPSS Statistics (IBM Corp, 

Armonk, NY) was used to conduct paired t test to assess 

for overall coding accuracy for the large group. Paired t

test and ANOVA was used to assess subgroups as organized into faculty and residency class year.

Results

As this study crossed 2 academic years, only 

those who were present for the entire intervention period were included in the data 

analysis, shown in Table 1. All listed participants were present during both the preintervention and postintervention time periods.

To ensure a large enough sample, a 3-month period, 

starting the month prior to the first educational intervention, was used as the baseline. Table 2 shows the results of the total group coding accuracy rates before and 

after the educational intervention period. The average 

coding accuracy for the learners in this study for this 

baseline period was 26.44% (mean (M)=26.44, 

SD=10.25) for 1,420 encounters. A 2-month 

period at the completion of the 2 interventions 

was evaluated for our comparison data. Average 

coding accuracy for the 899 encounters during 

this period was 26.79% (M=26.79, SD =11.38), 

t24=-0.127, P=.90. This suggests no significant 

coding accuracy differences after the first intervention.

The average change in coding accuracy between educational intervention by year group was also assessed; first 

year residents who progressed to second year residents 

(R1/2), second year residents who progressed to third 

year residents, and faculty. The data is shown in Table 3.

A one-way between subjects ANOVA was conducted 

to compare the effects of the educational interventions 

within and between each of these subgroups. There 

were no significant differences between the groups 

(F2,22=1.50, P=.25). Among all levels of learners, no 

group showed significant benefit from the training. Also, 

none of the groups had benefits in coding accuracy rates 

compared to each other.

Comment

There was no improvement in coding accuracy (as reflected in correct E/M) after the 2 intervention periods. There was no statistically significant difference 

when the data was aggregated and when individual year 

groups were assessed. Ideally, we would be able to assess long-term individual performance data in an educational practice. However, academic environment restrictions prevented this assessment at the individual level. 

Interns work in clinic on average once weekly, with increasing weekly clinics per year group. Thus the number 

of encounters, particularly from the interns, during the 

assessment period was small.

Although the upper level residents and faculty generated more clinical encounters, many 

individuals in these subgroups were not present in the residency program during the preintervention and postintervention period. As 

a consequence, only 8 upper level residents 

and 7 faculty formed the additional subgroups. Thus, participation in the educational interventions is a potential confounder. The educational sessions 

occurred during morning report, which is mandatory but 

may not be attended based on current rotation, vacation, 

etc. Attendance at each session was not recorded to subsequently note any potential trends in coding accuracy 

(ie, correlation between number of sessions attended and 

change in accuracy at an individual level).

Table 1. Provider Role.

Provider Number of

Participants

Intern/R2 8

R2/R3 10

Faculty 7

Table 2. Coding Accuracy Rates Before and After Educational Intervention.

Before

Intervention

After

Intervention

95% CI

for Mean

Difference

Outcome

M SD M SD n t df

26.44% 10.25 26.79% 11.38 25 -6.11 to 5.40 -0.127

(P=.90)

24

Table 3. Change by Year Group in Coding Accuracy After Educational Interventions.

Learner N Mean Coding

Accuracy Change

After Educational

Interventions

SD SE 95% CI for Mean

Lower 

Bound

Upper 

Bound

R1/R2 8 -3.86 13.61 4.81 -15.24 7.51

R2/R3 10 6.13 15.02 4.75 -4.61 16.88

Faculty 7 -3.08 11.44 4.32 -13.65 7.50
98 http://www.cs.amedd.army.mil/amedd_journal.aspx

Prior studies demonstrated improvement after focused 

individual educational sessions and large group training.4-7 It is unclear why these same methods were not 

effective in this project. In addition to the limitations 

listed above, it may be due to the fact that this is a military environment. Anecdotally, military providers have 

less incentive for “accurate” coding as they do not receive direct compensation for physician services. We 

hypothesize that due to the absence of financial incentive, providers have less motivation to learn and practice 

coding and billing skills.

There was also some resistance during this project based 

on perceptions of the role of the physician and frustration 

with the electronic medical record. During this quality 

improvement process the authors learned of implementation by the local coders of the Army Leveling Tool, 

resulting in down-coding of several conditions based 

on disease complexity, despite documentation provided. 

Although the coding staff understood and implemented 

the tool, experienced faculty providers had never been 

educated into its purpose or use. Therefore, it was conceptually more difficult to understand and teach residents ways to improve documentation and coding skills 

in the absence of experience or “corporate knowledge.”

Over the last decade, the AMEDD has brought more 

emphasis to quality of care and population health measures, as compared to the previously emphasized RVU/

FTE metric. However, decisions regarding staffing/personnel, space allocation, and density of clinic schedules 

are still largely based on a productivity metric. However, 

military facilities largely provide inadequate coding 

and billing education support to primary care providers. 

Low coding accuracy rates likely reflect poor knowledge or competency levels at the individual provider 

level. Leaders should consider that these low accuracy 

rates likely lead to inaccurate data management and assessment at the upper echelons, and may increase the 

work-load burden on front-line providers.

We were not able to define and measure a successful intervention to improve individual provider coding knowledge and competency. We recommend that other academic and clinical programs within the AMEDD experiment with other teaching and learning modalities. We 

suspect that more personal and individual educational interventions would be more beneficial. This would require 

increased administrative support resources and time, but 

could provide specific and timely feedback on errors.

Future interventions could also include a more detailed 

analysis of coding error to determine the types of coding errors on which to focus training.

Conclusion

Practice management, specifically documentation and 

coding for physician services, is an important facet of 

resident education. While this study did not demonstrate an improvement in coding accuracy using individual and small group sessions and subsequently small 

group sessions with facilitated large group discussion, a 

combination of educational strategies is likely beneficial. 

Programs should tailor their approach based on practice 

structure and learning needs.

References

1. Accreditation Council for Graduate Medical Education. Program Requirements for Graduate Medical Education in Family Medicine. September 29, 

2013; revised June 14, 2015; effective July 1, 2015. 

Available at: http://www.acgme.org.

2. Roberts JL, Ostapchuk M, Hughes Miller K, 

Ziegler CH. What residents know about health care 

reform and what we should teach them. J Grad 

Med Educ. 2011;3(2):155-161.

3. Fakhry SM, Robinson L, Hendershot K, Reines 

HD. Surgical residents’ knowledge of documentation and coding for professional services: an opportunity for a focused educational offering. Am J 

Surg. 2007;194(2):263-267.

4. Kapa S, Beckman TJ, CHA SS. A reliable billing 

method for internal medicine resident clinics. J 

Grad Med Educ. 2010;2(2):181-187.

5. Carter KA, Dawson BC, Brewer K, Lawson L. 

RVU ready? Preparing emergency medicine resident physicians in documentation for an incentive-based work environment. Acad Emerg Med. 

2009;16(5):423-428.

6. Benke JR, Lin SY, Ishman SL. Directed educational training improves coding and billing skills 

for residents. Int J Pediatr Otorhinolaryngology. 

2013;77(3):399-401.

7. Jones K, Lebron RA, Mangram A, Dunn E. Practice management education during surgical residency. Am J Surg. 2008;196(6):878-881.

Authors

LTC Nguyen is an Associate Professor and Clerkship Director, Department of Family Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD.

MAJ O’Mara is with the Department of Family Medicine, Madigan Army Medical Center, Tacoma, WA.

CPT Powell is with the Department of Family Medicine, 

General Leonard Wood Army Community Hospital, Fort 

Leonard Wood, MO.

IMPROVING CODING ACCURACY IN AN ACADEMIC PRACTICE
July – September 2017 99

Parsonage-Turner syndrome is a rare syndrome of unknown etiology affecting the brachial plexus. It is considered a rare disorder with an incidence of 2 per 100,000. 

Patients affected range from 3 months to 75 years of age 

with highest incidence between 30-70 years old.1,2

It is also known as brachial plexus neuritis, neuralgic 

amyotrophy, brachial plexitis, brachial plexus neuropathy, or shoulder girdle syndrome or neuritis.1,3 Parsonage-Turner syndrome (PTS) is characterized by the inflammation of nerves that innervate the muscles of the 

chest, shoulders and arms. Viral illness or autoimmune 

responses have been considered the most common risk 

factors for PTS, although it can also be idiopathic and 

hereditary.1,3,4

It is a peripheral nervous system disorder that presents 

with acute upper extremity pain and multifocal paresis, 

and it may have a complicated recovery course in many 

of those affected.2,3 The syndrome may be associated 

with scapular winging. The variable location and the severity of symptoms depend on which parts of the plexus 

are affected. The long thoracic, suprascapular, and the 

axillary nerves are most affected. Even if it mostly affects the upper trunk, the lower trunk can be affected 

as well.3

 Muscles most commonly affected include the 

deltoid, supraspinatus, infraspinatus, serratus anterior, 

biceps, and triceps.5

Parsonage-Turner syndrome varies in presentation and 

nerve involvement. It is usually characterized by the 

sudden onset of severe shoulder and upper arm pain followed by motor involvement several days later. The pain 

may extend to the trapezius, upper arm, forearm and 

hand.1,2 If paralysis is present, it may persist for months 

but recovery is usually complete.1

Case Report

A 24-year-old female Soldier presented to the emergency department (ED) as a return visit for right shoulder 

pain. The first visit was 4 weeks prior after slipping and 

trying to catch herself with her right arm. She was seen 

in same ED 2 weeks after the injury and diagnosed with 

rotator cuff dysfunction after negative shoulder x-rays. 

On this subsequent return visit, she was complaining of 

worsening right shoulder pain with burning, stinging, 

and electrical shock-like pain with radiation from the 

posterior/lateral shoulder to the upper right back. She 

also complained of numbness over the deltoid and dorsal 

fingers, cold like sensation, swelling and weakness of 

the right arm, but denied any neck pain or trauma.

Neurological exam showed 4/5 strength in deltoid, biceps, and supraspinatus. Tendon reflexes were equal 

bilaterally. She had decreased sensation over the dorsal 

right hand with lack of discrimination sharp/dull. The 

hand was also cooler to touch and had mild swelling.

Clinical examination of the right shoulder revealed a 

normal but painful passive range of motion. Active mobilization of the right shoulder showed scapular winging. 

Rotator cuff muscle weakness was absent, other than the 

one noted with supraspinatus. Middle deltoid atrophy 

was noted. Vascular examination was normal.

Previous ED chart and follow up orthopedics and physical therapy visits were reviewed. Patient had a right 

shoulder arthrogram that was read as negative. She was 

Winging of the Scapula Diagnosed as

 Parsonage-Turner Syndrome: A Case Report

CPT Christine Carroll, MC, USA

Bill Bass, MD

Abstract

A 24-year-old active duty female Soldier complained of right shoulder burning, stinging, electrical shock-like 

pain with radiation to the right hand after completing a ruck march. She also complained of swelling and feelings of her cold right hand. Examination showed a deficit in the deltoid, upper trapezius, supraspinatus, and also 

right winging of the scapula. She also exhibited weakness to right arm, weak right hand grip, and decreased 

sensation over the dorsal right hand. The right hand was also noticed to be colder to touch than the left one. She 

had tenderness to palpation over right paracervical muscles from C3 to C7. A previous magnetic resonance 

arthrogram of the right shoulder revealed no findings. The cervical magnetic resonance imagery showed mild 

disc protrusion at C5-C6 without spinal cord impingement. Based on the history and the physical findings, the 

patient was diagnosed with Parsonage-Turner syndrome.
100 http://www.cs.amedd.army.mil/amedd_journal.aspx

WINGING OF THE SCAPULA DIAGNOSED AS PARSONAGE-TURNER SYNDROME: A CASE REPORT

referred to physical therapy and during treatment she 

noticed worsening pain and weakness. Concerned for 

spinal cord impingement, patient was sent to ED for 

further evaluation.

The magnetic resonance imagery (MRI) of the cervical 

spine obtained on the repeat ED visit showed mild disc 

protrusion at C5-C6 without spinal cord impingement.

Findings were discussed with the neurologist on call. 

Parsonage-Turner syndrome was suspected. Patient 

was released home with opioids and short term steroid 

course. Upon further review during subsequent visits, 

patient was referred to an out of network neurologist and 

her case was lost to follow up.

Comment

Parsonage-Turner syndrome may involve several nerve 

trunks and vary in presentation, thus being often misdiagnosed as cervical disc disease or rotator cuff dysfunction/tear.4

 Diagnosis is based on the history and physical 

findings.1,4 The characteristic presentation is an acute, 

severe neurogenic pain in the shoulder or arm lasting 

for several days or weeks, followed by muscle weakness, atrophy, and sensory loss as the pain diminishes.4,5

Pain is the most common presenting symptom in almost 

95% of patients, mostly aggravated by movement of the 

shoulder, but not by neck movements.5

The symptoms do not always correlate with a single 

nerve root distribution and are often described as patchy, 

with involvement of multiple muscles and dermatomal 

regions that do not coincide with a single or specific 

neurologic source.4

In addition to motor nerve symptoms, sensory nerve involvement occurs in up to 78% of cases with patchy paresthesia and hypoesthesia.4,5 Most frequently, the sensory loss is incomplete and occurs over the lateral shoulder 

and upper arm or the radial surface of the forearm.5

Autonomic dysfunction in the form of trophic skin and 

nail changes, edema, temperature dysregulation, and increased sweating is less frequently seen.4,5

Electrodiagnostic studies and neuroimaging have high 

sensitivity for detecting which nerve trunks are involved 

and the degree of muscle denervation. However, they 

lack specificity, they cannot display the anatomic detail 

needed for precise localization and treatment planning, 

and they are usually performed more than 3 weeks from 

clinical onset.1

The duration of pain lasts for 1 to 2 weeks or longer. 

Once initial pain subsides, weakness and muscle atrophy may develop.2,5

Testing passive shoulder range of motion may be difficult in patients with PTS secondary to guarding. To 

make an accurate diagnosis, it is critical to complete a 

thorough neurologic and musculoskeletal examination 

of both the symptomatic and the asymptomatic extremities, including testing manual muscle strength, range of 

motion, sensation, and reflexes as well as evaluating the 

shoulder for signs of impingement, adhesive capsulitis, 

rotator cuff injury, and scapular dyskinesis.5

Magnetic resonance imagery remains the test of choice 

for diagnosis. Cervical MRI may reveal cervical disc 

disease or nerve root compression. Shoulder MRI may 

identify other causes of shoulder pain, including rotator cuff tears, labral tears, shoulder impingement, nerve 

entrapment, or mass lesions. Abnormalities signifying 

denervation may be detected on MRI in cases of early 

PTS, such as diffuse high signal intensity, or atrophy 

and fatty infiltration in later stages of PTS.

Magnetic resonance imaging may not be sensitive 

enough to detect early (within the first 2 to 3 weeks) 

changes in PTS. However, magnetic resonance neurography may show not only early hyperintense thickening 

of the involved areas of the brachial plexus,5

 but also 

nerve inflammation and muscle denervation in addition 

to assessing response to therapy.1

The best treatment for PTS remains unknown. There is 

some evidence stating that early use of oral corticosteroids shortens the time of intense pain and hastens motor nerve recovery. In addition, pain may be treated with 

a combination of nonsteroidal anti-inflammatory drugs 

and opioids.4

 Laboratory studies are of no benefit and do 

not help with diagnosis determination.5

The prognosis of PTS for the majority of patients is good, 

with an estimated three quarters of all patients making 

a complete recovery within 2 years.2

 However, some of 

the patients may still experience pain, and may develop 

adhesive capsulitis and shoulder subluxation years after 

the diagnosis was made.5

Conclusion

Parsonage-Turner syndrome is an under-recognized 

condition. It should be considered as a diagnosis in 

the setting of an abrupt onset of upper extremity pain 

followed by progressive neurologic deficits including 
July – September 2017 101

THE ARMY MEDICAL DEPARTMENT JOURNAL

weakness, atrophy and occasional sensory abnormalities. Treatment with a multidisciplinary approach that 

includes both physical therapy and multiple medications 

is acceptable with a goal of maintaining range of motion and preventing loss of function. In addition, other 

therapies such as nerve stimulators and acupuncture 

should be considered, based on the patient’s response.5

If conservative treatment fails, early (within 6 months) 

surgical treatment such as neurolysis, nerve grafts, and 

nerve transfers may be considered.5

References

1. Zara G, Gasparotti R, Manara R. MR imaging of peripheral nervous system involvement: 

Parsonage-Turner syndrome. J Neurol Sci. 

2012;315(1-2):170-171.

2. Sinanovic O, Zukic E, Jusufovic M, Muminovic 

Umihanic M, Barucija M, Muftic M. Recurrent 

form of Parsonage-Turner syndrome: case report. 

J Neurol Sci. 2015;357(suppl 1):e345. doi:10.1016/j.

jns.2015.08.1225

3. Stutz C. Neuralgic amyotrophy: Parson- age-Turner syndrome. J Hand Surg Am. 2010;35(12):2104-2106.

4. Smith, CC, Bevelaqua, AC. Challenging pain 

syndromes. Phys Med Rehabil Clin N Am. 

2014;25(2):265-277.

5. Van Tongel A. Schreurs M, Bruyninckx F, 

Debeer P. Bilateral Parsonage-Turner syndrome with unilateral brachialis muscle wasting: a case report. J Shoulder Elbow Surg. 

2010;19(8):e14-e16.

Authors

CPT Carroll is an Emergency Medicine Resident at the 

Darnall Army Medical Center, Fort Hood, Texas.

Dr Bass is an Attending Physician, Emergency Medicine 

Residency Program, Darnall Army Medical Center, Fort 

Hood, Texas.
102 http://www.cs.amedd.army.mil/amedd_journal.aspx

The US Army Health Readiness Center of Excellence

The Army Medical Department Center and School

Envision, Design, Train, Educate, Inspire

Joint Base San Antonio-Fort Sam Houston, Texas
July – September 2017 103

THE ARMY MEDICAL DEPARTMENT JOURNAL
104 http://www.cs.amedd.army.mil/amedd_journal.aspx

This page intentionally left blank.
Submission of Manuscripts to the Army Medical Department Journal

The United States Army Medical Department Journal is published quarterly to expand knowledge of domestic and international 

military medical issues and technological advances; promote collaborative partnerships among the Services, components, Corps, 

and specialties; convey clinical and health service support information; and provide a professional, high quality, peer reviewed print 

medium to encourage dialogue concerning health care issues and initiatives.

Review Policy

All manuscripts will be reviewed by the AMEDD Journal’s Editorial Review Board and, if required, forwarded to the appropriate 

subject matter expert for further review and assessment.

Identification of Potential Conflicts of Interest

1. Related to individual authors’ commitments: Each author is responsible for the full disclosure of all financial and personal relationships that might bias the work or information presented in the manuscript. To prevent ambiguity, authors must state explicitly 

whether potential conflicts do or do not exist. Authors should do so in the manuscript on a conflict-of-interest notification section 

on the title page, providing additional detail, if necessary, in a cover letter that accompanies the manuscript.

2. Assistance: Authors should identify Individuals who provide writing or other assistance and disclose the funding source for this 

assistance, if any.

3. Investigators: Potential conflicts must be disclosed to study participants. Authors must clearly state whether they have done so 

in the manuscript.

4. Related to project support: Authors should describe the role of the study sponsor, if any, in study design; collection, analysis, 

and interpretation of data; writing the report; and the decision to submit the report for publication. If the supporting source had 

no such involvement, the authors should so state.

Protection of Human Subjects and Animals in Research

When reporting experiments on human subjects, authors must indicate whether the procedures followed were in accordance with 

the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki 

Declaration of 1975, as revised in 2000. If doubt exists whether the research was conducted in accordance with the Helsinki Declaration, 

the authors must explain the rationale for their approach and demonstrate that the institutional review body explicitly approved the 

doubtful aspects of the study. When reporting experiments on animals, authors should indicate whether the institutional and national 

guide for the care and use of laboratory animals was followed.

Informed Consent

Identifying information, including names, initials, or hospital numbers, should not be published in written descriptions, photographs, 

or pedigrees unless the information is essential for scientific purposes and the patient (or parent or guardian) gives written informed 

consent for publication. Informed consent for this purpose requires that an identifiable patient be shown the manuscript to be 

published. Authors should disclose to these patients whether any potential identifiable material might be available via the Internet 

as well as in print after publication. Patient consent should be written and archived, either with the Journal, the authors, or both, 

as dictated by local regulations or laws.

Guidelines for Manuscript Submissions

1. Manuscripts may be submitted either via email (preferred) or by regular mail. Mail submissions should be in digital format (preferably an MS Word document on CD/DVD) with one printed copy of the manuscript. Ideally, a manuscript should be no longer than 

24 double-spaced pages. However, exceptions will always be considered on a case-by-case basis.

2. The American Medical Association Manual of Style governs formatting in the preparation of text and references. All articles 

should conform to those guidelines as closely as possible. Abbreviations/acronyms should be limited as much as possible. Inclusion of a list of article acronyms and abbreviations can be very helpful in the review process and is strongly encouraged.

3. A complete list of references cited in the article must be provided with the manuscript, with the following required data:

• Reference citations of published articles must include the authors’ surnames and initials, article title, publication title, 

year of publication, volume, and page numbers.

• Reference citations of books must include the authors’ surnames and initials, book title, volume and/or edition if appropriate, 

place of publication, publisher, year of copyright, and specific page numbers if cited.

• Reference citations for presentations, unpublished papers, conferences, symposia, etc, must include as much identifying 

information as possible (location, dates, presenters, sponsors, titles).

4. Either color or black and white imagery may be submitted with the manuscript. Color produces the best print reproduction 

quality, but please avoid excessive use of multiple colors and shading. Digital graphic formats (JPG, TIFF, GIF) are preferred. 

Editable versions with data sets of any Excel charts and graphs must be included. Charts/graphs embedded in MS Word cannot 

be used. Prints of photographs are acceptable. If at all possible, please do not send photos embedded in PowerPoint or MS Word. 

Images submitted on slides, negatives, or copies of X-ray film will not be published. For clarity, please mark the top of each 

photographic print on the back. Tape captions to the back of photos or submit them on a separate sheet. Ensure captions and 

photos are indexed to each other. Clearly indicate the desired position of each photo within the manuscript.

5. The authors’ names, ranks or academic/certification credentials, titles or positions, current unit of assignment, and contact 

information must be included on the title page of the manuscript. Submit manuscripts to:

DSN 471-6301

Comm 210-221-6301

Email: usarmy.jbsa.medcom-ameddcs.list.amedd-journal@mail.mil

Editor, AMEDD Journal

DOTAA Borden Institute

3630 Stanley RD STE B0204 

JBSA Fort Sam Houston, TX 78234-7697
PIN: 202119-000