Pediatric Annals

CME Article 

Pediatric Musculoskeletal Examination for Juvenile Arthritis

Renee F. Modica, MD, MSED; Sukesh Sukumaran, MD; Diana Milojevic, MD

Abstract

CME Educational Objectives

1. Recognize the historical features of a patient with inflammatory arthritis.

2. Understand and apply the “pGALS” (pediatric Gait, Arms, Legs, Spine) screening examination approach to the musculoskeletal exam.

3. Develop an appropriate intervention program through the identification of common physical findings from the musculoskeletal examination.

Despite the prevalence of musculoskeletal disorders in the United States, physicians often receive insuffi cient training during medical school on how to examine, diagnose, and manage these conditions. Previous studies have revealed that physicians feel defi cient in their knowledge and skills regarding musculoskeletal diseases.

A 2007 Centers for Disease Control and Prevention study estimates that 1 in 250 US children have been diagnosed with arthritis or another rheumatologic condition. Even with this growing prevalence, musculoskeletal complaints are under-recognized by primary care providers, often leading to delayed diagnosis.

Pediatricians face unique challenges regarding the musculoskeletal exam, ranging from getting a child to cooperate to differentiating swelling from obesity. The patient with juvenile idiopathic arthritis (JIA) may present while his or her arthritis symptoms still are evolving; the practitioner must be able to differentiate arthritic musculoskeletal complaints from nonarthritic ones.

In the absence of diagnostic laboratory test for JIA, a physical exam is essential in differentiating arthralgias from infl ammatory arthritis. The pediatric Gait, Arms, Legs, Spine (pGALS) test may provide a quick, effective, and easy-to-use musculoskeletal screening examination for children with joint complaints. This article provides useful tips and illustrations for the practitioner on how to handle these challenges
and determine the appropriate treatment.


Abstract

CME Educational Objectives

1. Recognize the historical features of a patient with inflammatory arthritis.

2. Understand and apply the “pGALS” (pediatric Gait, Arms, Legs, Spine) screening examination approach to the musculoskeletal exam.

3. Develop an appropriate intervention program through the identification of common physical findings from the musculoskeletal examination.

Despite the prevalence of musculoskeletal disorders in the United States, physicians often receive insuffi cient training during medical school on how to examine, diagnose, and manage these conditions. Previous studies have revealed that physicians feel defi cient in their knowledge and skills regarding musculoskeletal diseases.

A 2007 Centers for Disease Control and Prevention study estimates that 1 in 250 US children have been diagnosed with arthritis or another rheumatologic condition. Even with this growing prevalence, musculoskeletal complaints are under-recognized by primary care providers, often leading to delayed diagnosis.

Pediatricians face unique challenges regarding the musculoskeletal exam, ranging from getting a child to cooperate to differentiating swelling from obesity. The patient with juvenile idiopathic arthritis (JIA) may present while his or her arthritis symptoms still are evolving; the practitioner must be able to differentiate arthritic musculoskeletal complaints from nonarthritic ones.

In the absence of diagnostic laboratory test for JIA, a physical exam is essential in differentiating arthralgias from infl ammatory arthritis. The pediatric Gait, Arms, Legs, Spine (pGALS) test may provide a quick, effective, and easy-to-use musculoskeletal screening examination for children with joint complaints. This article provides useful tips and illustrations for the practitioner on how to handle these challenges
and determine the appropriate treatment.


Despite the prevalence of musculoskeletal disorders in the United States, aspiring physicians often receive insufficient training during medical school on how to examine, diagnose, and manage these conditions.1 Previous studies have revealed that physicians feel deficient in their knowledge and skills regarding musculoskeletal diseases.2

A 2007 Centers for Disease Control and Prevention study estimates that 1 in 250 US children younger than age 18 years have been diagnosed with arthritis or another rheumatologic condition.3,4 Even with this prevalence, musculoskeletal complaints are under-recognized by primary care providers, often leading to delayed diagnosis.5

Pediatricians face unique challenges regarding the musculoskeletal exam, ranging from getting a child to cooperate on the exam to differentiating swelling from obesity. This article describes how to handle these challenges and make these determinations, as well as providing useful tips and illustrations for the practitioner.

Features of Arthritis

Eliciting a history of inflammatory symptoms is essential to differentiate arthritis from arthralgia. When assessing for inflammatory arthritis, there are three key historical features that increase suspicion: persistent and chronic joint pain; morning stiffness; and modification of daily activities.

The typical case of juvenile idiopathic arthritis (JIA) begins insidiously, with the slow development of signs and symptoms over weeks to months. Typically, arthritis pain is neither brief, sharp, intermittent, nor solely related to activities. A verbal child will often describe the nature of arthritic pain as dull and long lasting.

By contrast, pain that awakens a child at nighttime usually is not characteristic of arthritis pain. If this is the case, in a child who is growing well and is not ill appearing, then one should consider hypermobility and growing pains if the symptoms are symmetrical; osteoid osteoma if the symptoms are unilateral.6,7 Alternatively, if the child appears sick, has weight loss, night pain, or fever, one should consider malignancy such as leukemia, neuroblastoma, or bone tumors.8

Morning stiffness that persists for 1 hour or more is usually the first feature of inflammatory arthritis and is especially characteristic of JIA. Similar stiffness can occur after long periods of inactivity such as after napping, a long car ride, or prolonged sitting. The duration of stiffness can be a useful gauge of the inflammatory activity of the disease. In contrast, patients with non-inflammatory causes of joint pain will not complain of stiffness.6

Children with arthritis may not outwardly complain about pain; rather, they compensate for pain by modifying how they accomplish things or avoid the activity altogether. An example of this is an antalgic gait or history of prolonged limping. The parent of a younger or nonverbal child might mistake these changes as behavioral.

A child with arthritis may have difficulty with daily self-care activities. The ability or inability to perform these activities of daily living (ADLs) is a useful measurement of the functional status of a patient in regards to level of disability. Arthritis can affect ADLs by a variable degree and this measurement is also influenced by the severity of arthritis, treatments, and patients’ pain threshold.

Although JIA is an inflammatory disease, only rarely are there signs of systemic inflammation present such as fever and weight loss. If fever is present, systemic JIA (sJIA) must be considered based on the pattern of fever as well as the associated extra-articular features. Weight loss can be seen in sJIA or polyarticular JIA if the joint involvement is extensive and unrecognized for a long period of time. Other conditions associated with these signs of systemic inflammation and joint symptoms include infection, malignancy, inflammatory bowel disease and other systemic rheumatic conditions.9

Physical Examination

Most physicians are familiar with the five classic signs of inflammation: tumor (swelling); rubor (redness); dolor (pain); calor (heat); and functio laesa (loss of function).10 Akin to the Latin counterparts above, there are four key physical features in JIA that increase our index of suspicion for inflammatory arthritis: 1) joint swelling due to either effusion or synovial hypertrophy; 2) warmth to the involved joint; 3) pain at end range of motion (ROM) and on palpation; and 4) limited range of motion. Redness is not a characteristic sign of arthritis in JIA.

Joint Anatomy

Joints may be classified according to the amount of mobility. Fibrous and cartilaginous joints (eg, sacroiliac and symphysis pubis, respectively) have little or no motion. The diarthroid joints (eg, knee) are designed for motion and are further sub-classified according to shape (eg, hinge, ball and socket, etc). These joints are lined with synovium, a vascular tissue with important regulatory functions, which also produces synovial fluid for lubrication and nutrition.

In JIA, the synovium is targeted by the immune system, leading to an increased permeability and an influx of inflammatory cells. Furthermore, since synovium lines tendon sheaths and bursae, these structures may also be a target of inflammation. In the spondyloarthropathies, an additional target of inflammation is the attachment site of tendons, ligaments, fascia and joint capsule to bone known as the enthesis.11

Joint Examination

The joint examination should be approached in a step-wise manner that incorporates inspection, palpation, and range of motion. Because joint pain can be referred, it is important to examine the joints proximal and distal to the symptomatic joint. When patients have unilateral symptomatology, it is helpful to compare the affected side to the unaffected side.12

Inspection and Palpation

A commonly recognized feature of arthritis is joint swelling, often a result of an effusion or synovial hypertrophy that presents with obscuration of the joint’s normal contour and recesses (see Figures 1 and 2). Excessive adipose tissue may be mistaken for joint swelling; however, unlike the fluid “bulge” from the effusion, adipose tissue spares the recess of the joint. For synovial joints, localized swelling near the joints suggests tendonitis or bursitis, whereas generalized swelling of the entire joint suggests arthritis.13

(A) Dorsal wrist swelling noted in this patient that obscures visualization of the radial and ulnar styloids (arrows), and (B) extends along the dorsal wrist surface (arrowhead).All images courtesy of Renee F. Modica, MD, MSED. Reprinted with permission.

Figure 1. (A) Dorsal wrist swelling noted in this patient that obscures visualization of the radial and ulnar styloids (arrows), and (B) extends along the dorsal wrist surface (arrowhead).All images courtesy of Renee F. Modica, MD, MSED. Reprinted with permission.

In this patient with metacarpophalangeal (MCP) arthritis, there is obscuring of the knuckle due to synovial hypertrophy (arrow). The valleys in between the MCP joints feel thickened and are tender to palpation when squeezed together.

Figure 2. In this patient with metacarpophalangeal (MCP) arthritis, there is obscuring of the knuckle due to synovial hypertrophy (arrow). The valleys in between the MCP joints feel thickened and are tender to palpation when squeezed together.

When arthritis is evolving, there may be only a minimal effusion and joint swelling may be subtle. In such cases, “milking down” the fluid may be necessary to evaluate for effusion (see Figure 3). An effusion feels “boggy” on palpation, whereas thickened synovium feels “squishy” like foam (see Figure 4). If a large effusion distends the knee joint, the patella will ballot.13 Redness of the skin overlying the joint is not a feature of chronic arthritis in JIA.

(A) “Milking down fluid” to enhance the visibility of a minor effusion is accomplished by the examiner circumferentially placing a hand on the patient’s mid-thigh and sliding it down the leg just superior to the knee joint. In order to find the “patellar gutter” (the depressed areas lateral and medial to the patella) and observe a bulge of fluid that obscures the joint’s normal contour (arrows). (B) When comparing this same patient’s involved left knee to the uninvolved right knee prior to milking down the fluid, a minor effusion is substantially less noticeable.

Figure 3. (A) “Milking down fluid” to enhance the visibility of a minor effusion is accomplished by the examiner circumferentially placing a hand on the patient’s mid-thigh and sliding it down the leg just superior to the knee joint. In order to find the “patellar gutter” (the depressed areas lateral and medial to the patella) and observe a bulge of fluid that obscures the joint’s normal contour (arrows). (B) When comparing this same patient’s involved left knee to the uninvolved right knee prior to milking down the fluid, a minor effusion is substantially less noticeable.

Notice the effacement of joint recess anterior to the lateral malleolus due to synovial hypertrophy. Note the extra synovial tissue around the examiner’s thumb when palpating in the ankle recess.

Figure 4. Notice the effacement of joint recess anterior to the lateral malleolus due to synovial hypertrophy. Note the extra synovial tissue around the examiner’s thumb when palpating in the ankle recess.

Acutely inflamed joints in JIA may be painful on palpation, especially along the line of the capsular attachment. However, the pain is most frequently elicited only on deeper palpation and not on light touch. Pain to light touch may suggest septic arthritis, cellulitis, or allodynia from a pain syndrome.

When palpating synovial joints for warmth, it is important to note that this is a relative assessment. If you place your hand directly onto the joint, it may not feel warm until you compare it to the surrounding tissue by sliding your hand back and forth. An unaffected joint should feel cooler than the surrounding tissue. In JIA, the affected joint may feel warmer. Symmetrical joints should have similar temperature, but different joints in the body have different temperatures. Ankles are usually warmer than knees. Hence, one should compare the warmth of symmetrical joints in the body. This finding is helpful only if arthritis is not symmetrical. Keep in mind that this finding may not differentiate septic arthritis from JIA.

In order to accommodate the excess intra-articular fluid with arthritis, joints are held in flexion by the patient. If they are unable to fully extend the joint, this may indicate pathology. A younger child may compensate for pain by limiting joint range of motion during activities.14 This limitation, if prolonged, may lead to subtle muscle atrophy (see Figure 5) or flexion contractures (Figures 6 and 7). Inflammation in the joint affects the growth plates of the adjacent bones. Linear growth disturbances due to inflammation of the growth plates can lead to either accelerated growth (eg, leg length discrepancy caused by knee arthritis, see Figure 8) or growth retardation (migrognathia caused by temporo-mandibular joint arthritis, see Figure 9).15

Prolonged limping leads to muscle atrophy. (A) Subtle thigh and (B) calf muscle atrophy are indicated by arrows. Comparing sides for asymmetrical findings is helpful.

Figure 5. Prolonged limping leads to muscle atrophy. (A) Subtle thigh and (B) calf muscle atrophy are indicated by arrows. Comparing sides for asymmetrical findings is helpful.

(A) This patient is bearing weight unequally and keeps right knee flexed while standing, which implies pain or flexion contracture. (B) The flexion contracture is also visible from the lateral view. When full extension is present, the posterior patella should touch the examination table.

Figure 6. (A) This patient is bearing weight unequally and keeps right knee flexed while standing, which implies pain or flexion contracture. (B) The flexion contracture is also visible from the lateral view. When full extension is present, the posterior patella should touch the examination table.

Hip flexion contracture while standing noted in this patient. In order to maintain upright posture, the patient compensates by increasing lumbar lordosis.

Figure 7. Hip flexion contracture while standing noted in this patient. In order to maintain upright posture, the patient compensates by increasing lumbar lordosis.

Joint inflammation affects the growth plates leading to longitudinal growth disturbances of the adjacent bones. This patient has a leg length discrepancy (right>left) due to mono-articular JIA involving the right knee.

Figure 8. Joint inflammation affects the growth plates leading to longitudinal growth disturbances of the adjacent bones. This patient has a leg length discrepancy (right>left) due to mono-articular JIA involving the right knee.

Note the micrognathia as a result of stunted mandibular from TMJ arthritis.

Figure 9. Note the micrognathia as a result of stunted mandibular from TMJ arthritis.

A child with a leg length discrepancy may toe walk on the shorter leg, walk with the knee and hip of longer limb in flexion, or use the longer leg like a “pirate peg” and swivel around it.12 Inflammation may cause premature maturation of ossification centers, for example, advanced appearance of ossification centers in the bones of the hand affected with arthritis compared to the unaffected hand. The final result is premature fusion of growth plates and growth arrest.

Range of Motion

After inspection and palpation is performed, consecutive assessments of both active (AROM) and passive (PROM) range of motion is necessary to differentiate a muscle problem from a joint problem as a cause of the limitation. AROM is not practitioner-assisted whereas PROM is practitioner-assisted. Muscle weakness or tendon problems may result in a decrease in AROM without a decrease in PROM. A joint contracture, as seen with active arthritis, will result in loss of both AROM and PROM.13

AROM testing is geared for older children who can follow instructions; therefore, it may be a less reliable assessment in a younger child or infant. For younger children, observe them performing ADLs and notice how they modify them (see Figures 10 and 11) as an alternative way to assess AROM (see Table 1).14 This information is useful, particularly if there is a persistent change or regression.

Note how this patient with right wrist arthritis compensates while getting off the bed by (A) using his elbow and forearm to push himself off or (B) when using his hand, he keeps his wrist in neutral position to limit painful range of motion.

Figure 10. Note how this patient with right wrist arthritis compensates while getting off the bed by (A) using his elbow and forearm to push himself off or (B) when using his hand, he keeps his wrist in neutral position to limit painful range of motion.

(A) Due to active arthritis, this patient is having difficulty curling all fingers tightly and completely around to squeeze the examiner’s hand. (B) As a result, this patient will modify how he/she holds a writing and/or eating utensil. Note how this patient uses a loose and open grip on the pen.

Figure 11. (A) Due to active arthritis, this patient is having difficulty curling all fingers tightly and completely around to squeeze the examiner’s hand. (B) As a result, this patient will modify how he/she holds a writing and/or eating utensil. Note how this patient uses a loose and open grip on the pen.

Examples of How Activities of Daily Living May Be Affected by Age in a Patient with Arthritis

Table 1. Examples of How Activities of Daily Living May Be Affected by Age in a Patient with Arthritis

For infants or toddlers, the examiner can use a toy or jingle keys to coax them to follow directions. The parent can assist in the examination process by “racing” against the child to assess gait or, alternatively, have the child ambulate or crawl to the parent. The parent can “walk around” a younger child who will track the parent as the examiner assess the child’s neck ROM. Also, playing a modified game with younger children while examining their feet (such as the “little piggies”) or hands (such as “high fives”) is helpful to gain their cooperation while putting them through ROM testing.

With PROM, the patient does not have to follow a set of directions, so if it is a younger child, have them sit on the caretaker’s lap while the examiner performs the examination. Patients with active arthritis will naturally limit their movement to a ROM that is comfortable (so-called “comfort-zone”).16 The advantage of PROM is that the examiner will guide the patient toward the end ROM to assess if they exhibit guarding of the joint. This finding is usually detected by the patient wincing and withdrawing the involved joint from the examiner (see Figure 12); this should be reproducible, even when the patient is distracted.

PROM to assess internal rotation of the shoulder. This patient demonstrated pain when the shoulder was further rotated toward end PROM.

Figure 12. PROM to assess internal rotation of the shoulder. This patient demonstrated pain when the shoulder was further rotated toward end PROM.

Observation of these behavioral manifestations of pain at any age has been shown to be a reliable indicator of pain.17,18 Therefore, it is the authors’ opinion that PROM is a useful adjunct to uncover arthritis pain, especially in younger children and infants. As with AROM, it is important to compare sides for asymmetrical findings (Figure 13).

Assessing the hip and knee joints range of motion while prone allows the examiner to compare sides for asymmetrical findings. (A) This patient’s hip internal rotation (arrows) is worse on the left versus the right from midline (solid lines). The dashed line approximates normal internal rotation. (B) This patient is unable to flex the right knee as far as the left.

Figure 13. Assessing the hip and knee joints range of motion while prone allows the examiner to compare sides for asymmetrical findings. (A) This patient’s hip internal rotation (arrows) is worse on the left versus the right from midline (solid lines). The dashed line approximates normal internal rotation. (B) This patient is unable to flex the right knee as far as the left.

Some children may have hypermobile joints (that extend farther than normal), some may be “stiff” (not limber), but the child with normal physical exam should not be hypermobile on one side of the body and stiff on the other side.

Pediatric Gait, Arms, Legs, Spine (pGALS) Screening Examination

A validated musculoskeletal screening examination of school-aged children who present with musculoskeletal pain or dysfunction is known as the pediatric Gait, Arms, Legs, Spine screening examination, or the “pGALS.”19 It can be performed in a few minutes as a means to inspect, palpate, and assess range of motion of the main joints. It consists of asking three screening questions; observing the child’s gait; and performing some simple maneuvers of the upper extremities, lower extremities and spine (see Table 2). Any abnormalities should lead to a more detailed and focused examination of those areas.19 See Figure 14 (A-M) for corresponding abnormalities seen in JIA when using the pGALS screening maneuvers.

The components of the pGALS*

Table 2. The components of the pGALS

Laboratory Considerations

Although the diagnosis of inflammatory arthritis is a clinical one, laboratory markers can add value to differential diagnosis and prognosis. Careful interpretation of laboratory tests should be done in the context of the patient’s physical exam and history. Although JIA is an inflammatory condition, not all cases exhibit elevated markers of inflammation.

In active sJIA, one should expect to see a laboratory profile consistent with an acute phase response (elevated ESR, CRP and an inflammatory CBC with high WBC, anemia of chronic inflammation and thrombocytosis). In a severe polyarticular JIA with many active joints, the patient may have an elevated ESR or CRP or mild anemia of chronic inflammation, whereas in oligoarticular JIA, the ESR is usually normal in spite of active disease.11 In fact, if a patient has oligo JIA and has a persistently elevated ESR, then one should consider alternative differential diagnoses such as inflammatory bowel disease, leukemia, or infectious/post-infectious arthritis.8,9

Other markers of autoimmunity in JIA that are typically encountered include the antinuclear antibodies, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and HLA-B27. These tests are not diagnostic, but they have some prognostic value in patients who clinically meet criteria of JIA. If the ANA titer is positive in a patient with JIA, it may infer an increased risk of eye disease; especially in oligo-JIA.11 However, if the ANA titer is particularly elevated, then one should consider arthritis in the context of other systemic rheumatic diseases; mainly SLE or mixed connective tissue disease (MCTD).11

Patients with positive RF or anti-CCP (which is only about 5% to 10% of all JIA) tend to have more aggressive arthritis. The majority of JIA patients are RF negative and, therefore, the test does not exclude the diagnosis of JIA. The anti-CCP antibody has more recently come into use for JIA and corresponds with the RF, but is likely more specific because infection and other stressors often trigger RF.20,21 The HLA-B27 is a genetic test that confers an increased risk of sacroiliits or acute iritis in patients with enthesitis-related arthritis.11

Certain imaging modalities, when strategically used, are a useful adjunct to the physical exam. X-rays are not sensitive for the early changes of JIA and, therefore, offer little value other than confirming soft tissue swelling or evaluating for other conditions. Meanwhile, MRI with IV gadolinium contrast can show enhancement of inflamed synovium, cartilaginous erosions, or bone marrow edema as signs of active joint inflammation. In recent years, the use of musculoskeletal ultrasound has been gaining momentum as another imaging modality that may have an increasing role in aiding in the evaluation of active arthritis in JIA patients.

Conclusions

Evaluating and diagnosing a patient with juvenile arthritis can be challenging. The practitioner is further challenged because the patient may present while arthritis symptoms are evolving and the practitioner must be able to differentiate arthritic musculoskeletal complaints from non-arthritic ones. In the absence of diagnostic laboratory test for JIA, physical exam is essential in differentiating arthralgias from inflammatory arthritis. The pGALS may provide quick, effective and easy to use musculoskeletal screening examination for children with joint complaints.

References

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Examples of How Activities of Daily Living May Be Affected by Age in a Patient with Arthritis

Age Range Modification of Activity of Daily Living
Infancy Cries during diaper change when hips are flexed. Crawls on forearms instead of hands. Unable to use pincer grasp.
Toddler Limps. Delay or regression of milestones (eg, crawling or walking). Plays less or modifies play to accommodate for pain. Increases reliance on stroller/being carried. Looks up at parent with their eyes and avoids extending neck when wants to be picked up.
School aged Difficulty getting arms through sleeves, buttoning clothes, or using zippers. Difficulty using scissors, tying shoes, brushing teeth, toileting. Does not alternate feet on stairs.
Adolescence Difficulty writing, typing, opening doors or bottles, texting. Changes in ability to perform in sports or activities. Uses wheelchair.

The components of the pGALS *

pGALS Components Question or Maneuver See Figure 14 for illustrations of examples of abnormal physical examination findings.
Screening questions Do you have any pain or stiffness in your joints, muscles or your back? Do you have any difficulty getting yourself dressed without any help? Do you have any difficulty going up and down stairs?
Gait Observe the child walking. (Figure 14A) “Walk on your tip-toes/walk on your heels.” (Figure 14B)
Arms “Put your hands out in front of you.” (Figure 14C) “Turn your hands over and make a fist.” (Figure 14D) “Pinch your index finger and thumb together.” (Figure 14D) “Touch the tips of your fingers with your thumb.” (Figure 14D) Squeeze metacarpophalangeal joints. “Put your hands together.” (Figure 14E) “Put your hands back to back.” (Figure 14E) “Reach up and touch the sky.” (Figure 14F) “Look at the ceiling.” (Figure 14G) “Put your hands behind your neck.” (Figure 14H
Legs Feel for effusion at the knee. (Figure 14I) “Bend and then straighten your knee,” (active movement of knees and examiner feels for crepitus). (Figure 14J) Passive flexion (90 degrees) with internal rotation of the hip.
Spine “Open your mouth and put 3 of your (child’s own) fingers in your mouth.” (Figure 14K) Lateral flexion of cervical spine: “try to touch your shoulder with your ear.” (Figure 14L) Observe spine from behind. (Figure 14M) “Can you bend and touch your toes?” Observe from side and behind. (Figure 14M)
Authors

Renee F. Modica, MD, MSED, is Clinical Assistant Professor, University of Florida. Sukesh Sukumaran, MD, is Clinical Assistant Professor, Pediatric Rheumatology, University of Florida. Diana Milojevic, MD, is Associate Clinical Professor, Clinical Director, Pediatric Rheumatology, University of California San Francisco.

Address correspondence to: Renee F. Modica, MD, MSED, Pediatric Rheumatology, University of Florida, 1600 SW Archer Road, R118-G, Box 100296, Gainesville, FL 32610-0296; fax: 352-294-5248; email: modicar@peds.ufl.edu.

Disclosure: The authors have no relevant financial relationships to disclose.

10.3928/00904481-20121022-08

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