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## Complete Summary

#### GUIDELINE TITLE

American Gastroenterological Association medical position statement:
perianal Crohn´s disease.

#### BIBLIOGRAPHIC SOURCE(S)

American Gastroenterological Association medical position statement:
perianal Crohn\'s disease. Gastroenterology 2003 Nov;125(5):1503-7. \[2
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14598267)

#### GUIDELINE STATUS

This is the current release of the guideline.

According to the guideline developer, the Clinical Practice Committee
meets three times a year to review all American Gastroenterological
Association Institute (AGAI) guidelines. This review includes new
literature searches of electronic databases followed by expert committee
review of new evidence that has emerged since the original publication
date.

### \*\* REGULATORY ALERT \*\*

#### FDA WARNING/REGULATORY ALERT

**Note from the National Guideline Clearinghouse (NGC)**: This guideline
references a drug(s) for which important revised regulatory and/or
warning information has been released.

-   [July 08, 2008, Fluoroquinolones (ciprofloxacin, norfloxacin,
    ofloxacin, levofloxacin, moxifloxacin,
    gemifloxacin)](http://www.fda.gov/medwatch/safety/2008/safety08.htm#Fluoroquinolone):
    A BOXED WARNING and Medication Guide are to be added to the
    prescribing information to strengthen existing warnings about the
    increased risk of developing tendinitis and tendon rupture in
    patients taking fluoroquinolones for systemic use.

### COMPLETE SUMMARY CONTENT

 \*\* REGULATORY ALERT \*\*\
 SCOPE\
 METHODOLOGY - including Rating Scheme and Cost Analysis\
 RECOMMENDATIONS\
 EVIDENCE SUPPORTING THE RECOMMENDATIONS\
 BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS\
 CONTRAINDICATIONS\
 QUALIFYING STATEMENTS\
 IMPLEMENTATION OF THE GUIDELINE\
 INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT
CATEGORIES\
 IDENTIFYING INFORMATION AND AVAILABILITY\
 DISCLAIMER

### SCOPE

#### DISEASE/CONDITION(S)

Perianal Crohn´s disease

#### GUIDELINE CATEGORY

Diagnosis\
Management\
Treatment

#### CLINICAL SPECIALTY

Colon and Rectal Surgery\
Gastroenterology

#### INTENDED USERS

Physicians

#### GUIDELINE OBJECTIVE(S)

-   To present the official recommendations of the American
    Gastroenterological Association (AGA) on perianal Crohn´s disease

-   To summarize epidemiology, diagnosis, medical and surgical
    treatments, and approaches to treatment of perianal Crohn´s disease

#### TARGET POPULATION

Patients who have Crohn´s disease with perianal lesions

#### INTERVENTIONS AND PRACTICES CONSIDERED

**Diagnosis**

1.  Classification systems

    -   Cardiff classification

    -   Crohn´s Disease Activity Index

    -   Parks classification

    -   Empiric classification (in clinical practice)

    -   Simple or complex fistulas

2.  Examination/Imaging

    -   Examination under anesthesia (EUA)

    -   Anorectal endoscopic ultrasonography (EUS)

    -   Pelvic magnetic resonance imaging (MRI)

**Medical Treatments**

1.  Antibiotics: ciprofloxacin; metronidazole

2.  Azathioprine and 6-mercaptopurine

3.  Infliximab

4.  Cyclosporine

5.  Tacrolimus

**Surgical Treatments**

1.  Skin tags: excision (not recommended)

2.  Hemorrhoids: simple hemorrhoidectomy (usually contraindicated)

3.  Anal fissures: fissurectomy (contraindicated); lateral
    sphincterectomy

4.  Anorectal strictures: dilations

5.  Perianal abscess: surgical drainage

6.  Perianal fistulas:

    -   Fistulotomy

    -   Noncutting seton

    -   Endorectal advancement flap

    -   Temporary diverting ileostomy (rarely performed)

7.  Rectovaginal fistulas; fistulotomy (rarely indicated); primary
    closure; advancement flaps

8.  Obstetrical surgical procedures: cesarean section recommended during
    active disease); vaginal delivery and episiotomy

**General Treatment of Crohn´s Disease**

1.  Active proximal luminal disease: budesonide, conventional
    corticosteroids, azathioprine, 6-mercaptopurine, methotrexate,
    infliximab, surgical resection

2.  Postoperative bile salt diarrhea or steatorrhea: loperamide,
    diphenoxylate and atropine, codeine, cholestyramine, low-fat diet

#### MAJOR OUTCOMES CONSIDERED

**Diagnosis**

Accuracy of examination/imaging studies

**Treatment**

-   Fistula closure

-   Healing rate

-   Number of draining fistulas

-   Quantity of fistula drainage

-   Relapse rates

-   Adverse events

### METHODOLOGY

#### METHODS USED TO COLLECT/SELECT EVIDENCE

Hand-searches of Published Literature (Primary Sources)\
Hand-searches of Published Literature (Secondary Sources)\
Searches of Electronic Databases

#### DESCRIPTION OF METHODS USED TO COLLECT/SELECT THE EVIDENCE

A search of the online bibliographic databases MEDLINE (1966 to August
2002) and Current Contents/ Science Edition (1996 to August 2002) was
performed to identify potentially relevant English-language articles.
The Medical Subject Heading terms \"Crohn´s disease\" or \"inflammatory
bowel disease\" or \"regional enteritis\" AND \"fistulas\" or
\"perianal\" were used to perform keyword searches of the database.
Manual searches of the reference lists from the potentially relevant
papers and the proceedings from annual meetings of the American
Gastroenterological Association, American College of Gastroenterology,
and American Society of Colon and Rectal Surgeons from 1990 to 2003 were
performed to identify additional studies that may have been missed using
the computer-assisted search strategy.

Studies selected were retrospective or prospective studies reporting on
the classification, epidemiology, diagnosis with magnetic resonance
imaging (MRI) or anorectal endoscopic ultrasonography (EUS), treatment
with medical therapy, and surgical treatment of perianal Crohn´s
disease. This technical review is not based solely on level 1 studies
(population-based natural history studies and randomized, double-blind,
placebo-controlled trials of diagnostic modalities and therapeutic
interventions), because only 5 level 1 studies were identified and they
do not provide a sufficient basis for an \"evidence-based\" technical
review and medical position statement.

#### NUMBER OF SOURCE DOCUMENTS

Not stated

#### METHODS USED TO ASSESS THE QUALITY AND STRENGTH OF THE EVIDENCE

Expert Consensus

#### RATING SCHEME FOR THE STRENGTH OF THE EVIDENCE

Not applicable

#### METHODS USED TO ANALYZE THE EVIDENCE

Systematic Review with Evidence Tables

#### DESCRIPTION OF THE METHODS USED TO ANALYZE THE EVIDENCE

Not stated

#### METHODS USED TO FORMULATE THE RECOMMENDATIONS

Expert Consensus

#### DESCRIPTION OF METHODS USED TO FORMULATE THE RECOMMENDATIONS

Not stated

#### RATING SCHEME FOR THE STRENGTH OF THE RECOMMENDATIONS

Not applicable

#### COST ANALYSIS

A formal cost analysis was not performed and published cost analyses
were not reviewed.

#### METHOD OF GUIDELINE VALIDATION

Internal Peer Review

#### DESCRIPTION OF METHOD OF GUIDELINE VALIDATION

The paper was approved by the Committee on May 18, 2003, and by the
American Gastroenterological Association (AGA) Governing Board on July
25, 2003.

### RECOMMENDATIONS

#### MAJOR RECOMMENDATIONS

**Diagnosis**

To plan appropriate medical or surgical therapy, patients with perianal
Crohn´s disease must be classified as having simple or complex perianal
disease (refer to the original guideline document for details).
Diagnosis of simple fistulas or complex perianal disease by physical
examination and rectosigmoid endoscopy may be sufficient for many
patients when medical therapy is the initial treatment strategy.
Additional diagnostic evaluation by examination under anesthesia (EUA)
and either anorectal endoscopic ultrasonography (EUS) or pelvic magnetic
resonance imaging (MRI) is indicated in those patients with pain,
fluctuation, or stricture on digital rectal examination, in those
patients in whom surgical therapy is the initial treatment strategy
(because up to 10% of patients with perianal fistulas will be
misclassified by EUA alone and fistulotomy of a high fistula
misclassified as a low fistula may lead to incontinence and/or poor
wound-healing and in some instances subsequent proctectomy), and in
those failing medical or surgical therapy. It is recognized that this
recommendation represents a change in practice, even for
gastroenterologists and colorectal surgeons with great expertise in the
management of perianal Crohn´s disease, but acknowledges that EUA is not
100% accurate and that inaccurate diagnosis before surgical intervention
may lead to irreversible functional consequences.

**General Treatment of Crohn´s Disease**

In addition to the specific medical and surgical treatments outlined as
follows, any active proximal luminal disease should also be treated as
appropriate with budesonide, conventional corticosteroids, azathioprine,
6-mercaptopurine, methotrexate, infliximab, and surgical resection.

Postoperative bile salt diarrhea or steatorrhea should be treated as
indicated with loperamide, diphenoxylate and atropine, codeine,
cholestyramine, and low-fat diet. These measures are all aimed at
reducing stool liquidity, with the goal of decreasing the quantity of
fistula drainage.

**Treatment of Simple Perianal Fistulas**

Potential treatments for simple fistulas include antibiotics,
fistulotomy, and possibly azathioprine or 6-mercaptopurine and
infliximab. Antibiotics are widely used to treat simple fistulas and are
recommended in practice guidelines and previous treatment algorithms but
have not been evaluated in placebo-controlled trials. Fistulotomy is
widely used by surgeons to treat simple fistulas, resulting in a high
rate of healing that is often sustained. The prevailing view among
surgeons is that those patients with a simple fistula who do not respond
to a short course of antibiotics are best treated with fistulotomy.
However, reported surgical series have been small, there are no
controlled trials comparing fistulotomy with sham operation or medical
therapy, and some patients fail to heal and may require proctectomy. The
immunosuppressive medications azathioprine and 6-mercaptopurine can be
used to treat simple fistulas and are recommended in practice guidelines
but have not been evaluated in placebo-controlled trials in which
fistula reduction or closure was the primary end point. These agents are
slow acting and thus may be of more utility for maintaining fistula
closure than for the initial induction of fistula closure. Infliximab
has been proven effective in placebo-controlled trials for the
indications of both reduction in the number of draining fistulas and
maintenance of that reduction, and a 3-dose induction regimen and a
maintenance regimen every 8 weeks are approved by the U.S. Food and Drug
Administration (FDA) for treatment of fistulas; however, infliximab is
expensive, concomitant immunosuppressive therapy is probably required to
counteract the formation of human antichimeric antibodies that may lead
to infusion reactions and loss of efficacy, and rarely serious
infections may occur. There are insufficient high-quality data (level 1
evidence \[population-based natural history studies and randomized,
double-blind, placebo-controlled trials of diagnostic modalities and
therapeutic interventions\]) to make a clear recommendation as to
whether antibiotics, fistulotomy, azathioprine or 6-mercaptopurine, or
infliximab is the preferred strategy for simple fistulas. Tacrolimus and
cyclosporine are not appropriate treatment for simple fistulas because
of toxicity.

**Treatment of Complex Perianal Fistulas**

Potential treatments for complex fistulas include antibiotics,
azathioprine and 6-mercaptopurine, infliximab, tacrolimus and
cyclosporine, and surgery (dilation of anal strictures, placement of
noncutting setons, endorectal advancement flap, repair of rectovaginal
fistulas, fecal diversion, and proctectomy). Antibiotics are widely used
to treat complex fistulas and are recommended in practice guidelines and
treatment algorithms but have not been evaluated in placebo-controlled
trials. Relapse rates are high after antibiotic therapy for complex
fistulas is discontinued, and their use should probably be adjunctive in
combination with other medical agents or surgery in this setting.
Similarly, the immunosuppressive medications azathioprine and
6-mercaptopurine are used to treat complex fistulas and are recommended
in practice guidelines but have not been evaluated in placebo-controlled
trials in which fistula reduction or closure was the primary end point.
Furthermore, these agents are slow acting and thus are of more utility
for maintaining fistula closure than for the initial reduction in the
number of draining fistulas.

In contrast to antibiotics and immunosuppressive medications, infliximab
has been proven to be effective in placebo-controlled trials for
reduction in the number of draining fistulas and maintenance of that
reduction and treatment of fistulas with a 3-dose induction regimen and
a maintenance regimen every 8 weeks is approved by the U.S. Food and
Drug Administration (FDA). Finally, tacrolimus or cyclosporine can
rarely be considered in selected patients who fail multimodality
treatment with other medical and surgical therapies, including
infliximab. This practice is based on uncontrolled case series with
cyclosporine and a single short-term placebo-controlled trial with
tacrolimus that showed a reduction in the number of draining fistulas;
however, nephrotoxicity and other side effects occur frequently and
these agents should be used with caution. The trials examining
tacrolimus and cyclosporine have been of short duration, without
determining whether maintenance therapy after initial fistula closure is
safe and effective.

Surgical therapy for complex perianal disease is largely palliative.
Perianal abscesses should be drained and anal strictures dilated.
Noncutting setons can be placed in fistula tracts in patients with
macroscopic rectal inflammation, and endorectal advancement flap
procedures for high perianal fistulas and rectovaginal fistulas can be
performed in patients without rectal inflammation. The recurrence rates
following removal of noncutting setons and following endorectal
advancement flap procedures are both relatively high. Setons can be left
in place indefinitely; however, given the alternative of suppressive
medical therapy, patients may not prefer this option. Because infliximab
therapy can completely close all fistula tracks in many patients with
complex fistulas, most gastroenterologists now believe that infliximab
is the initial treatment of choice in this setting (it is debated by
surgeons whether infliximab or noncutting setons is the initial
treatment of choice for the subgroup of patients with complex perianal
fistulas who do not have active rectal disease, because there are no
data on patient acceptance of long-term noncutting setons versus
treatment with infliximab). Azathioprine, 6-mercaptopurine, or
methotrexate should be coadministered routinely both to counteract an
immunogenic reaction to infliximab and as maintenance of remission
therapy. Some patients will require combination maintenance therapy with
azathioprine, 6-mercaptopurine, or methotrexate and infliximab.
Temporary adjunctive therapy with antibiotics may be considered. Routine
EUA and seton placement before initiating infliximab therapy is not
mandatory.

Patients with complex fistulas who initially fail treatment with
infliximab should undergo anorectal endoscopic ultrasonography or pelvic
MRI as well as EUA with placement of setons as indicated while
continuing treatment with infliximab, azathioprine or 6-mercaptopurine,
and antibiotics. Tacrolimus or cyclosporine can be considered in
patients who fail this multimodality approach. As a last resort, fecal
diversion or proctectomy may be undertaken.

**Specific Treatment of Rectovaginal Fistulas**

Potential treatments for rectovaginal fistulas include both medical
therapy and surgery. 6-Mercaptopurine, infliximab, cyclosporine, and
tacrolimus have all been used to treat rectovaginal fistulas in
uncontrolled series. A controlled trial of maintenance infliximab
infusions in patients with fistulas who responded to infliximab included
a subgroup of patients with rectovaginal fistulas. Surgical treatment of
rectovaginal fistulas can only be performed when there is endoscopic
healing of the rectosigmoid mucosa. Standard medical therapy with
conventional corticosteroids, azathioprine, 6-mercaptopurine,
methotrexate, or infliximab should be administered as indicated to
control active luminal inflammatory disease in the rectosigmoid colon.
If the rectovaginal fistula persists after the patient has received
medical therapy to treat both the fistula itself and the rectosigmoid
mucosa, and there is no evidence of an anorectal stricture or active
rectal disease, then surgical repair with transanal or transvaginal
advancement flaps, or laparotomy with primary closure or sleeve
advancement flap can be performed. Advancement flap surgery should be
reserved for patients with disabling symptoms because of the risk of
worsening symptoms in those patients in whom the operation fails. As a
last resort, fecal diversion or proctectomy may be undertaken. Some
women may choose to accept residual fistula drainage over proctectomy
with an ostomy to optimize their overall quality of life.

#### CLINICAL ALGORITHM(S)

A treatment algorithm for managing patients with Crohn´s perianal
fistulas is provided in the Technical Review that accompanies the
guideline (see the \"Companion Documents\" field).

### EVIDENCE SUPPORTING THE RECOMMENDATIONS

#### TYPE OF EVIDENCE SUPPORTING THE RECOMMENDATIONS

The type of evidence supporting the recommendations is not explicitly
stated.

### BENEFITS/HARMS OF IMPLEMENTING THE GUIDELINE RECOMMENDATIONS

#### POTENTIAL BENEFITS

Improved treatment of perianal Crohn´s disease, with greater potential
for disease cure; or with reduced need for maintenance therapy and
prolonged periods of remission

#### POTENTIAL HARMS

**Medication-related Adverse Events**

-   Adverse events associated with **metronidazole** include metallic
    taste, glossitis, nausea, and a distal peripheral sensory
    neuropathy.

-   Adverse events associated with **ciprofloxacin** are uncommon but
    include headache, nausea, diarrhea, and rash.

-   Adverse events associated with **azathioprine and 6-mercaptopurine**
    include leukopenia, allergic reactions, infection, pancreatitis,
    drug-induced hepatitis, and possibly non-Hodgkin´s lymphoma.
    Patients treated with these medications should have regular
    monitoring of leukocyte counts and liver transaminase levels.

-   Adverse events observed in patients treated with **infliximab**
    include infusion reactions, delayed hypersensitivity reactions,
    formation of human antichimeric antibodies, formation of antinuclear
    antibodies and anti-double-stranded deoxyribonucleic acid (DNA)
    antibodies, and drug-induced lupus. Concomitant immunosuppressive
    therapy with azathioprine, 6-mercaptopurine, or methotrexate is
    recommended to reduce the frequency of these reactions, which are
    largely due to an immunogenic response to the murine component of
    the chimeric antibody. There is also an increased overall rate of
    infections and, rarely, serious infections including pneumonia,
    sepsis, tuberculosis, histoplasmosis, coccidioidomycosis,
    listeriosis, *Pneumocystis carinii* pneumonia, and aspergillosis
    occur. It is recommended that patients undergo purified protein
    derivative skin testing before treatment with infliximab.

-   Adverse events observed in patients treated with **cyclosporine**
    include renal insufficiency, hirsutism, hypertension, paresthesias,
    headache, seizure, tremor, gingival hyperplasia, hepatotoxicity, and
    an increased incidence of infection (including *P. carinii*
    pneumonia).

-   Adverse events observed in patients treated with **tacrolimus\***
    include headache, increased serum creatinine level, insomnia, leg
    cramps, paresthesias, and tremor, typically resolved with dose
    reduction. The major toxicity observed in patients treated with
    tacrolimus\* was an increase in serum creatinine level from baseline
    to a value [\>]{.underline}1.5 mg/dL (designated before the study as
    nephrotoxicity requiring tacrolimus dose reduction), which occurred
    in 8 of 21 patients (38%) treated with tacrolimus compared with 0 of
    25 (0%) placebo-treated patients (*P* = 0.008).

### CONTRAINDICATIONS

#### CONTRAINDICATIONS

-   Simple hemorrhoidectomy, the newer procedure for prolapsing
    hemorrhoids, or banding of hemorrhoids in patients with Crohn´s
    disease are usually contraindicated due to the frequent occurrence
    of postoperative complications, including poor wound healing,
    anorectal stenosis, and a high rate of proctectomy.

-   Fissurectomy is contraindicated.

### QUALIFYING STATEMENTS

#### QUALIFYING STATEMENTS

-   The guideline has been developed under the aegis of the Clinical
    Practice Committee of the American Gastroenterological Association
    (AGA). It provides preferred approaches to specific medical problems
    or issues. The statements herein are derived from the data available
    at the time of their creation and may need to be modified as new
    information is generated. Unless otherwise stated, these statements
    are intended for adult patients. The strength of the evidence upon
    which the statements are based is noted, with prospective,
    randomized, controlled trials being the strongest. When adequate
    data are absent, expert consensus may be used and will be identified
    as such. This document is not to be construed as a standard of care.
    All decisions regarding the care of a patient should be made by the
    physician in consideration of all aspects of the patient´s specific
    medical circumstances.

-   Although descriptions of surgical therapy are provided in the
    accompanying Technical Review, along with the indications, outcomes,
    and complications of surgical intervention, the reader is cautioned
    that this review is not meant to provide the details of how to
    perform the specific individual surgical procedures.

### IMPLEMENTATION OF THE GUIDELINE

#### DESCRIPTION OF IMPLEMENTATION STRATEGY

An implementation strategy was not provided.

#### IMPLEMENTATION TOOLS

Clinical Algorithm

For information about
[availability](#identifying-information-and-availability), see the
\"Availability of Companion Documents\" and \"Patient Resources\" fields
below.

### INSTITUTE OF MEDICINE (IOM) NATIONAL HEALTHCARE QUALITY REPORT CATEGORIES

#### IOM CARE NEED

Getting Better\
Living with Illness

#### IOM DOMAIN

Effectiveness

### IDENTIFYING INFORMATION AND AVAILABILITY

#### BIBLIOGRAPHIC SOURCE(S)

American Gastroenterological Association medical position statement:
perianal Crohn\'s disease. Gastroenterology 2003 Nov;125(5):1503-7. \[2
references\]
[PubMed](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14598267)

#### ADAPTATION

Not applicable: The guideline was not adapted from another source.

#### DATE RELEASED

2003 Nov

#### GUIDELINE DEVELOPER(S)

American Gastroenterological Association Institute - Medical Specialty
Society

#### SOURCE(S) OF FUNDING

American Gastroenterological Association Institute

#### GUIDELINE COMMITTEE

American Gastroenterological Association Clinical Practice Committee

#### COMPOSITION OF GROUP THAT AUTHORED THE GUIDELINE

Not stated

#### FINANCIAL DISCLOSURES/CONFLICTS OF INTEREST

Not stated

#### GUIDELINE STATUS

This is the current release of the guideline.

According to the guideline developer, the Clinical Practice Committee
meets three times a year to review all American Gastroenterological
Association Institute (AGAI) guidelines. This review includes new
literature searches of electronic databases followed by expert committee
review of new evidence that has emerged since the original publication
date.

#### GUIDELINE AVAILABILITY

Electronic copies: Available from the [American Gastroenterological
Association Institute (AGAI) *[Gastroenterology]{.underline}* journal
Web
site](http://www.gastrojournal.org/article/S0016-5085(03)01366-0/fulltext).

Print copies: Available from the American Gastroenterological
Association Institute, 4930 Del Ray Avenue, Bethesda, MD 20814.

#### AVAILABILITY OF COMPANION DOCUMENTS

The following is available:

-   W.J. Sandborn, V.W. Fazio, B.G. Feagan, S.B. Hanauer. AGA technical
    review on perianal Crohn´s disease. Gastroenterology. 2003
    Nov;125(5):1508-1530.

Electronic copies: Available from the [American Gastroenterological
Association Institute (AGAI) Gastroenterology journal Web
site](http://www.gastrojournal.org/article/S0016-5085(03)01367-2/fulltext).

Print copies: Available from the American Gastroenterological
Association Institute, 4930 Del Ray Avenue, Bethesda, MD 20814.

#### PATIENT RESOURCES

None available

#### NGC STATUS

This NGC summary was completed by ECRI on May 19, 2004. This summary was
updated by ECRI on March 15, 2005 following release of a public health
advisory from the U.S. Food and Drug Administration regarding the use of
Elidel. This summary was updated by ECRI Institute on July 28, 2008
following the U.S. Food and Drug Administration advisory on
fluoroquinolone antimicrobial drugs.

#### COPYRIGHT STATEMENT

This NGC summary is based on the original guideline, which is subject to
the guideline developer\'s copyright restrictions.

### DISCLAIMER

#### NGC DISCLAIMER

The National Guideline Clearinghouse™ (NGC) does not develop, produce,
approve, or endorse the guidelines represented on this site.

All guidelines summarized by NGC and hosted on our site are produced
under the auspices of medical specialty societies, relevant professional
associations, public or private organizations, other government
agencies, health care organizations or plans, and similar entities.

Guidelines represented on the NGC Web site are submitted by guideline
developers, and are screened solely to determine that they meet the NGC
Inclusion Criteria which may be found at
<http://www.guideline.gov/about/inclusion.aspx> .

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Readers with questions regarding guideline content are directed to
contact the guideline developer.

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© 1998-2008 National Guideline Clearinghouse

Date Modified: 11/3/2008