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journal homepage: www.JournalofSurgicalResearch.com

Layperson trauma training in low- andmiddle-income countries: a review

Tyler E. Callese,a Christopher T. Richards, MD,b,c,*Pamela Shaw, MSLIS, MS,d Steven J. Schuetz, MD,a Nabil Issa, MD,a

Lorenzo Paladino, MD,e and Mamta Swaroop, MDa

aDivision of Trauma and Critical Care Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern

University, Chicago, IllionisbCenter for Healthcare Studies, Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern

University, Chicago, IllinoiscDepartment of Emergency Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IllinoisdGalter Health Sciences Library, Feinberg School of Medicine, Northwestern University, Chicago, IllinoiseDepartment of EmergencyMedicine, StateUniversity ofNewYorkDownstate School ofMedicine,NewYork,NewYork

a r t i c l e i n f o

Article history:

Received 5 December 2013

Received in revised form

8 March 2014

Accepted 12 March 2014

Available online xxx

Keywords:

Education

Trauma

First-responder

International

Resource-poor

LMIC

Trauma system development

Layperson

Systematic review

Global surgery

* Corresponding author. Department of EmNorthwestern University, Chicago, IL 60611.

E-mail address: c-richards@northwestern0022-4804/$ e see front matter ª 2014 Elsevhttp://dx.doi.org/10.1016/j.jss.2014.03.029

a b s t r a c t

Background: Prehospital trauma systems are rudimentary in many low- and middle-income

countries (LMICs) and require laypersons to stabilize and transport injured patients. TheWorld

Health Organization recommends educating layperson first responders as an essential step in

the development of Emergency Medical Services systems in LMICs. This systematic review ex-

amines trauma educational initiatives for layperson first responders in resource-poor settings.

Materials and methods: Layperson first-responder training and education program publica-

tions were identified using PubMed MEDLINE and Scopus databases. Articles addressing

physicians, professional Emergency Medical Services training, or epidemiologic

descriptions were excluded. Publications were assessed by independent reviewers, and

those included underwent thematic analysis.

Results: Thirteen publications met inclusion criteria. Four themes emerged regarding the

development of layperson first-responder training programs: (1) An initial needs assess-

ment of a region’s existing trauma system of care and laypersons’ baseline emergency care

knowledge focuses subsequent educational interventions; (2) effective programs adapt to

and leverage existing resources; (3) training methods should anticipate participants with

low levels of education and literacy; and (4) postimplementation evaluation allows for

curriculum improvement. Technology, such as online and remote learning platforms, can

be used to operationalize each theme.

Conclusions: Successful training programs for layperson first responders in LMICs identify

and maximize existing resources are adaptable to learners with little formal education and

are responsive to postimplementation evaluation. Educational platforms that leverage

technology to deliver content may facilitate first-responder trauma education in under-

resourced areas. Themes identified can inform the development of trauma systems of care

to decrease mortality and physiological severity scores in trauma patients in LMICs.

ª 2014 Elsevier Inc. All rights reserved.

ergency Medicine and Center for Healthcare Studies, Feinberg School of Medicine,Tel.: þ1 (312) 503 5500; fax: (312) 503 - 2755..edu (C.T. Richards).ier Inc. All rights reserved.

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e72

1. Introduction manuscripts were reviewed for inclusion. Disagreements

An estimated 90% of all trauma-related deaths occur in low-

and middle-income countries (LMICs) [1]. Implementation of

first-responder training programs decreases mortality and

physiological severity scores in LMICs [2]. However, systems of

prehospital care are rudimentary in many LMICs, leaving the

initial stabilization and transportation of the injured to the

untrained layperson [3].

The World Health Organization recommends the devel-

opment of layperson first-responder programs as an essential

step in establishing prehospital systems of care [4]. However,

synthesis of existing trauma educational programs and

formal recommendations directing the development of such

programs for first responders is lacking.

This systematic literature review examines existing

educational initiatives for layperson first responders in LMICs

to inform the design of prehospital trauma care systems in

resource-poor settings.

2. Methods

2.1. Search strategy

The patient population, intervention, comparison, and out-

comes format was used to develop inclusion and exclusion

criteria. Specifically, patients included students of first-

responder courses in resource-poor LMICs. Interventions

included layperson first-responder training programs. Com-

paratorswere informalandunstructured laypersonapproaches

to the care of traumatized patients in LMIC settings. The

outcome assessed was the successful implementation of first-

responder trauma courses for laypersons in LMIC.

PubMed MEDLINE and Scopus databases were queried to

identify relevant peer-reviewed research describing or evalu-

ating the training of layperson responders from 1965 to

November 2013. Search terms were “trauma” and “first

response or first responder or first responders” and “emer-

gency” and “education or training.” To maximize sensitivity

for LMIC training programs, the geographic and economic

characteristics of the study setting were not initially restricted

to LMICs. Studies conducted in non-LMIC settings and non-

English articles were excluded after title and abstract review.

Only English language articles were included for analysis.

Searches returned only two non-English articles. In addition,

bibliographies of reviewed publications were crosschecked for

additional relevant studies.

2.2. Eligibility criteria

Publications that described the current state, evaluation, or

the development of layperson first-responder trauma training

programs were included for review. One independent

reviewer assessed titles and abstracts, and two independent

reviewers assessed full texts in a hierarchal manner. Articles

that met search criteria were obtained, and the full

among reviewers were resolved through consensus.

Exclusion criteria were applied in abstract and full manu-

script review. Publication types labeled as “comments” or

“letters” were excluded to focus on formal evaluations of

existing programs. Studies reporting the epidemiology of

trauma victims in LMICs without mention of training pro-

grams were excluded. Studies describing interventions in

high-income countries were excluded. Manuscripts address-

ing the psychological status of first-responder personnel were

excluded. Studies of populations with a very specific skill set,

such as physician first responders, were excluded. Articles

describing first-responder training limited to only military

personnel were excluded. Articles related to first-responder

training that gave no details of the training methods or

details of the structure of the education program were also

excluded.

2.3. Thematic analysis

A qualitative thematic analysis with a five-stage iterative

process was used to analyze each eligible manuscript: (1)

development of coding schedule, (2) coding of data, (3)

description of main categories, (4) linking of categories to

themes, and (5) development of explanations for relations

among themes. Initial codeswere created inductively from the

manuscripts. One author developed the coding schedule, and

two independent reviewers applied thematic categories to

each eligible manuscript in an iterative manner. Disagree-

ments were resolved by consensus. Major themes were iden-

tified from the categorized manuscripts. Data were managed

using Microsoft Excel (Microsoft Corporation, Seattle, WA).

3. Results and discussion

3.1. Included manuscripts

Searches returned 61 results in MEDLINE and 37 results in

Scopus, with an 82% overlap of results. The total number of

unique results across both databases before exclusion criteria

were applied was 68. Thirteen articles fulfilled the inclusion

criteria (Figure). Six articles described layperson first-

responder training programs in LMICs, providing a compre-

hensive overview of curriculum development, training

protocols, or results of pre- and post-training assessments

(Table 1). Six articles followed up these same previously

implemented programs, assessing curriculum design and

training efficacy. One study described the use of technology to

leverage educational initiatives in rural regions of LMIC

(Table 2). The six programs identified were in six countries

throughout the Middle East, Asia, and Africa.

3.2. Training programs

Six layperson first-responder training programs were identi-

fied in this review. The program implemented in Ghana pro-

vided first-responder training to commercial drivers,

Figure e Flow chart of the selection process for studies included in the systematic review.

j o u rn a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e7 3

including truck, taxi, and bus operators [5]. The curriculum

was developed from Where there is No Doctor [6] and Basic First

Aid [7]. The 6-h course, which consisted of didactic and prac-

tical sections, was specifically oriented toward the education

level of Ghanaian drivers and was completed by 335 taxi

drivers [5].

Layperson first-responder training in Cambodia and

Northern Iraq used a novel “Village University” concept [8].

Mine-infested communities in Cambodia and Northern Iraq

were selected because of the high rates of death and injury

from land mines. The “Village University” concept involved

extensive training of a small number of local health care

providers, who in turn, trained and developed their own net-

works of lay first responders in their respective regions [8]. A

total of 2800 laypersons received first-responder training that

consisted of a 2-d basic first aid course followed by a 1-d

practical [8].

Table 1 e Primary training programs.

Study authors Program summary

Mock et al. [5] Commercial driver trauma education program

Husum et al. [8] “Village University” training program

Nafissi et al. [14] Augment existing treatment chains through tra

Karmacharya et al. [9] Leveraging technology to increase accessibility

training programs

Jayaraman et al. [10] Layperson trauma education program

Sun et al. [11] EFAR

EFAR ¼ Emergency First Aid Responder.

Themes: 1. initial needs assessment; 2. curriculum development; 3. adap

A program in rural Iran focused on augmenting existing

trauma care by providing first-responder training to layper-

sons [9]. Two training courses were developed for laypersons

based on prior experience and level of education. A total of

4649 layperson first responders were trained in this system [9].

The program in Nepal leveraged technology to facilitate

layperson training programs [9]. A free online platform con-

sisting of a didactic portion and a net-based multiple-choice

examination was developed. After successfully demon-

strating proficiency, the trainee would qualify for further

training in regional centers [9].

In Kampala, Uganda, a layperson trauma education pro-

gram was implemented that focused on training emergency

personnel, commercial drivers, and community leaders [10].

The 1-d course consisted of didactic and practical portions

that used pictographic materials and required minimal liter-

acy skills [10].

Setting Themes

Ghana 1,2, 3, 4

Cambodia and Northern Iraq 1, 2, 4

uma training programs Iran 1, 2, 4

of layperson trauma Nepal 1, 3, 4

Uganda 1, 2, 3, 4

South Africa 1, 4

ting curriculum for low education levels; and 4. program evaluation.

Table 2 e Assessments and expansion of primary training programs.

Study authors Program summary Setting Themes

Tiska et al. [17] Assessment of commercial driver trauma education program.

Commercial driver prehospital training is effective at improving the

quality of prehospital trauma care. Universal precautions and airway

protection were identified as areas of emphasis for future training.

Ghana 2, 3, 4

Geduld et al. [12] Expansion of commercial driver program to Madagascar. Twenty-six taxi

Drivers received training in a 1-d workshop.

Ghana 1, 2, 3

Husum et al. [18] Assessment of “village university” program and its effects on

prehospital car.

Cambodia and Northern Iraq 4

Murad et al. [19] Assessment of “village university” in Iraq. Mortality rate was lower for

patients initially managed by first responders.

Cambodia and Northern Iraq 4

Jayaraman et al. [20] Assessment layperson training program. Trainees demonstrate high

level of knowledge retention and confidently use their skills. Program

can be cost-effectively scaled up.

Uganda 4

Saghafinia et al. [16] Assessment of layperson training program. Prehospital training of 4834

first responders decreased PSS scores and land mine mortality.

Iran 2 4

Sun et al. [13] Assessment of a community-based emergency first aid responder

program.

South Africa 1, 2, 4

Themes: 1. initial needs assessment; 2. curriculum development; 3. adapting curriculum for low education levels; and 4. program evaluation.

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e74

The Emergency First Aid Responder (EFAR) systems were

implemented in Cape Town, South Africa [11]. The EFAR sys-

tem provided first-responder training to augment existing

prehospital emergency services through a 1-d course. Trained

first responders were organized into a community network

that works closely with existing Emergency Medical Services

(EMS) providers. EFAR systems are low costs and can easily

adapt to the needs of the target region [11].

3.3. Theme development

Qualitative thematic analysis of included manuscripts

revealed four themes central to layperson first-responder

trauma education initiatives in LMICs.

3.3.1. Needs assessment of existing infrastructure andlayperson trainingThe first theme identified emphasizes that an initial needs

assessment of a region’s existing EMS and trauma systems of

care be performed to focus the planned educational initiative.

Needs assessments were described for all six programs

analyzed. An effective needs assessment should determine

the burden of injury, current prehospital capabilities, and

baseline first aid knowledge of the target trainee population.

Elements of needs assessments included:

� Involvement of key stakeholders. An initial step in the execu-

tion of an effective needs assessment is the identification

and involvement of relevant key stakeholders. A key

stakeholder is defined as a person or entity whose involve-

ment would increase the effectiveness of training initiatives

through facilitating the development of the program,

appropriating the funds, or aiding in curriculum design

[3,12]. These can include leaders from all facets of the target

area and may include police and fire departments, local

government, national government, taxi operators, com-

mercial truck drivers, and physicians and nurses who care

for injured patients. The most effective training initiatives

are those with highly involved local stakeholders and those

where the local stakeholders identify first-responder edu-

cation as a priority [10e12].

Although local leaders play a critical role in facilitating

community involvement and buy-in, the perspective of the

lay public is important to consider in curriculum develop-

ment. In one report, community members identified

increased training of emergency personnel and layperson

training, when asked what should be done to improve the

health of their community [13]. A survey of community

members provides valuable insights into the target commu-

nity, although surveys can be limited by sampling bias [13].

� Burden of injury and EMS capabilities. Long transport times are

common in the care of injured patients in LMICs. Injured

patients in rural regions of LMICs often receive care from

village-based health care providers who commonly do not

have formal training in first aid [14]. In most LMICs, injured

patients are transported to the district hospital by private

vehicles, commercial trucks, taxis, public transportation,

and even on the backs of animals and not in ambulances by

EMS professionals [8e10,12]. Dangerous or impassable roads

make patient transportation even more difficult with one of

the most significant effects being increased travel time [9].

In remote areas, transport times can be as long as 8 h [8],

clearly outside of the “Golden Hour of Trauma” [15].

An important motive for the implementation of layperson

first-responder education initiatives derives from local injury

epidemiology. Road traffic accidents (RTAs) are the primary

cause of injury in LMICs. RTAs cause injuries that can be

effectively treated through the early application of first aid [3].

RTAs are particularly prevalent in LMICs [1]. Land mines

commonly injure children and farmers with 40% mortality in

Northern Iraq, Cambodia, and regions of Iran near the Iraqi

border [14,16]. As with injuries sustained during RTAs, land

mineerelated mortality can be decreased with the early

j o u rn a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e7 5

administration of first aid [14,16]. In regions with undeveloped

prehospital systems, the burden of first aid care falls on lay-

persons, making this population a key focus of first-responder

training initiatives.

� Baseline first aid knowledge. Determining trainees’ baseline

understanding of first aid principles and prior experience

using first aid skills guides curriculum development. Two

studies conducted background interviews of target

populations using convenience sampling and cross-

sectional surveys [5,10]. Both studies gathered trainee

demographics, prior first aid training of trainees, prior

experience providing first aid and transporting patients,

types of emergencies commonly encountered, frequency

and modes of intervention, and trainees’ current access to

first aid supplies. In a survey of commercial drivers in

Ghana, 87% reported having some level of involvement with

injured persons over the year previous to survey adminis-

tration, including the provision of first aid and/or trans-

portation of injured patients [5]. Follow-up interviews of the

target trainee population described the frequency of

trainee-initiated first aid provided to injured persons [5].

3.3.2. Curriculum development builds on existinginfrastructureThe second theme characteristic of layperson first-responder

trauma education programs was the development of training

curricula that acknowledge existing local infrastructure,

available resources, and needs. Curriculum development

should be a collaborative effort involving local stakeholders

and health care providers familiar with the unique challenges

in delivering care in the target region [5,10e12,17]. Key

stakeholders can identify particular first aid skills or mecha-

nisms of injury that can be included in the curriculum. For

example, in one report, birth asphyxia accounted for 25% of

neonatal deaths in Madagascar. At the request of the leaders

of the target population in Madagascar, aspects of maternal

care and delivery were included in their first-responder

training curriculum [12]. In another intervention, key stake-

holders in an area of South Africa identified interpersonal

violence as a common mechanism of injury, and a violent

injury workshop was included in the curriculum [11]. Early

course materials were derived from commonly-used publi-

cations Where There is No Doctor [6] and Basic First Aid [7]. New

manuals were published after initial attempts to implement

training programs were made and these were used as guides

for future programs [12,16]. Common elements of curriculum

development included:

� Program structure. The six training programs identified

included a combination of didactic lectures and hands-on

skills workshops and lasted 1 or 2 d [5,8e12]. Hands-on

learning was emphasized over didactic lectures, and real-

life case studies were used to frame case discussions. One

program used the train-the-trainer model, where a small

number of village health care providers received basic life

support, advanced life support, and advanced trauma life

support training and in turn, established and trained a

network of layperson first responders [8,18]. Course lengths

ranged from 6 h to 2 d, with most programs lasting 1 d

[5,8,10,12e14]. Program costs of $3 per student [5] and $27

per student [10] were reported for two of the programs; the

latter program included the cost of providing a first aid kit to

trainees. Minimizing program costs are essential to promote

sustainable initiatives [8,18].

� Program curricula. The six first-responder training programs

identified had very similar curricula. Subject matter was

oriented toward practical real-world scenarios and empha-

sized hands-on training, which is an effective means to

promote knowledge retention in layperson trainee pop-

ulations [8]. Basic first aid principles included in the training

programs were:

1. External hemorrhage control. External hemorrhage

control was identified as a life threat that laypersons

could treat after minimal training as a way to signifi-

cantly impact long-term mortality from injury.

Training included direct manual pressure, elevation of

bleeding extremity, application of pressure dressings,

and the use of universal precautions [5,8,10,12e14].

2. Airway management. The recovery position described

the most effective method of maintaining a patent

airway in unconscious patients by a layperson in the

absence of equipment [5,10,11]. Techniques such as

the chin life and jaw thrust were thought to be

impractical for long patient transport times and were

only included in one of the training programs [14].

3. Splinting. Techniques for immobilizing injured

extremities without formal equipment were taught in

four programs [5,10,12,13].

4. Spinal precautions. Principles of spinal immobilization

and patient conveyance while maintaining spinal

precautions were included in five programs. However,

advanced techniques involving the use of backboards

and cervical collars were generally thought to be

impractical for the layperson first responder

[5,10,12,17,19].

5. RTA scene management and basic patient triage.

Methods of categorizing injured patients based on an

initial survey and management of RTA scenes were

included in all programs [5,8,10,12e14]. Secondary

accidents are common during RTAs in LMICs because

of poor traffic management [5]. Training included

traffic direction and the basics of incident command.

6. Patient extrication. Layperson first responders

commonly cause secondary injuries to RTA victims

during extrication. Methods of extricating RTA victims

using locally available resources, such as car jacks and

pry bars, were taught [5,10,11].

Implementation of other curriculum elements is less

uniform among programs. First aid kits were included in only

two training programs because of resource limitations

[8,10,18,20]. However, postimplementation follow-up in-

terviews indicated the utility of including first aid kits was

primarily the impact on the use of body substance isolation

and universal precautions [5]. Cardiopulmonary resuscita-

tion (CPR) training was included in the trauma curriculum of

only one program, and active rewarming was taught by only

one program [14].

j o u r n a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e76

3.3.3. Training populations with little formal educationLow levels of literacy and health knowledge of laypersons

present significant challenges in developing trauma-training

programs for the layperson in LMICs [5]. The six training

programs included in this review addressed this challenge in a

similar manner. Local physicians and health care providers

taught courses in laypersons’ native language to reduce lan-

guage barriers and to build rapport with the trainee popula-

tion [5,8,10,12e14]. One initiative developed the following two

parallel first-responder programs: one for uneducated lay-

persons in which trainees learned basic first aid skills and a

second program directed toward trainees with formal educa-

tion, such as high schools students, that added advanced

training in CPR and hemorrhage control [14]. Teaching

methods that made no assumptions of literacy used didactic

lectures using visual diagrams primarily [5,8,10e12,17],

hands-onworkshops [8,11,12,17], and videos [5,10e12,17]. One

program specifically minimized didactic training to 1 h and

primarily used pictographic materials [10].

3.3.4. Program evaluationPostimplementation assessment of the training program is

critical to identify the effectiveness of the training initiative.

Several methods of program evaluation were reported.

The two most common methods were posttraining fund

of knowledge assessments and follow-up interviews

[5,10,13,17,20]. Posttraining assessments should test the same

knowledge as the postcourse knowledge assessment to allow

for comparison of results. Assessments were administered

immediately after completion of the program, and then after 6

mo, 1 y, and 2 y [10,11]. Follow-up interviews are also

commonly used to evaluate training programs and may pro-

vide a more accurate evaluation of the program because one-

on-one interviews circumvent literacy barriers encountered

when administering written assessments [5,10,13,17,20].

Similar to knowledge assessments, follow-up interviews are

usually administered immediately after training and then at

periodic time intervals.

Knowledge retention was high in the six programs

included in this study, suggesting effective curriculum design.

Follow-up interviews identified areas for curriculum

improvement. The most commonly used skills were external

hemorrhage control, splinting of fracture, and RTA scene

management [5,20]. Weaknesses in the use of universal pre-

cautions and overreliance on mouth-to-mouth CPR were

identified [5,20]. Trainees reported high utilization of first aid

kits in the programs that provided kits to participants [17,20].

Program monitoring of health outcomes of people in the

target geographic region is another key component of pro-

gram evaluation. Hospital diagnosis, treatment, and outcome

data were collected and analyzed for trauma patients identi-

fied by first responders or hospital records in two studies

[8,14]. Primary endpoints measured were physiological

severity score (PSS) and mortality. PSS is a simplified version

of the Revised Trauma Score developed for use in LMICs.

Layperson first-responder training programs have been

shown to decrease PSS [8,14,18] and mortality from traumatic

injuries [8,14,18,19]. Postimplementation analysis of unex-

pected deaths revealed that patients in circulatory shock with

an estimated probability of survival >50% who died from

exsanguinating torso injuries on the operating table were

hypothermic due to lack of prehospital hypothermia preven-

tion measures [18].

Surveys, interviews, and postintervention knowledge as-

sessments have several limitations. Self-reported outcomes

collected from follow-up interviews may overreport skill and

equipment use [5,10,13]. Selection bias may affect the general

applicability of training to a larger population because it is

possible that only the most motivated and interested in-

dividuals successfully complete the training programs [5,10].

The presence of unreported prehospital fatalities may affect

primary endpoints because mortality rates will not be accu-

rately captured [8,10,14,18,19]. The limitation to use PSS as a

primary endpoint involve questions related to interrater reli-

ability of the PSS and accuracy of the PSS, as PSS can vary

depending on the patient’s demographics and mechanism of

injury [10,14,18,19].

3.4. Leveraging technology for educational initiatives

Layperson first-responder training programs reduce mortality

from traumatic injuries [5]. Scaling of educational initiatives

in LMICs is difficult because of poor infrastructure and

geographic isolation of rural villages where training can be

most effective [9]. One method of disseminating training

materials and increasing basic first aid knowledge among

laypersons is by leveraging technology. TheNepal Community

Emergency Preparedness Group recognized the need for

layperson basic first aid training and created a website, which

hosts all training materials, enhances program visibility, and

facilitates communication and networking [9]. After a student

passes an online multiple choice examination, the student

proceeds to enroll in hands-on training at a local health care

delivery center. Although <1% of the population in Nepal has

Internet access, many health care centers provide Internet

access points for the online examination and learning mate-

rials [9]. Leveraging technology can be an effective and effi-

cient method of scaling educational initiatives in LMICs.

4. Limitations

This study is a systematic review of published peer-reviewed

articles describing implementation of programs for layperson

educational programs. This search did not extend to include

programs not described in the peer-reviewed literature, such

as governmental and nongovernmental programs. This may

have limited the breadth of the programs included in this

review.

5. Conclusions

First aid administered at the scene of injury by trained first

responders reduces trauma mortality and training programs

for laypersons improves first-responder capabilities in the

absence of formal prehospital trauma systems of care

[5,8,21,22]. Successful training programs involve key stake-

holders, identify and maximize local resources, adapt to

regional education levels, and respond to postimplementation

j o u rn a l o f s u r g i c a l r e s e a r c h x x x ( 2 0 1 4 ) 1e7 7

evaluations [5,8e11,14]. Educational platforms that leverage

technology to deliver content may facilitate implementation

of first-responder training initiatives in underresourced areas.

Acknowledgment

Authors’ contributions: T.E.C., C.T.R., S.J.S, N.I., and M.S.

conceived and designed the study. P.S. performed initial data

collection. T.E.C., C.T.R., and M.S. analyzed the data. T.E.C.

drafted the manuscript. All authors contributed substantially

to its revision.

CTR is supported by an Agency for Healthcare Research

and Quality T32 training grant.

Disclosure

The authors reported no proprietary or commercial interest in

any product mentioned or concept discussed in this article.

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