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The ACG’s 2007 treatment guideline on the management of H. pylori infection (26) listed the following as established indications for diagnosis and treatment:
===Indications===
*Active PUD (gastric or duodenal).
*Confirmed history of PUD (not previously treated for H. pylori)
*Gastric MALT lymphoma (low grade)
*After endoscopic resection of EGC


'''To go back to the main page, click [[microchapter templates|here]]'''
Recommended  first-line treatment for Helicobacter pylori


{{CMG}} {{AE}} {{MKK}}
{| class="wikitable"
!Regimen
!Drug dose
!Dosing frequency
!Duration(days)
!FDA approval
|-
|Clarithromycin triple
|PPI(standard or double dose
Clarithromycin(500mg)


==Introduction to the Historical Perspective Page==
Amoxicillin(1gm)or Metronidazole(500mg TID)
* The page name should be '''"(Disease name) historical perspective"''', with only the first letter of the title capitalized.
|BID
* '''Goal:''' to provide the background on the history of how the disease/condition was discovered, and the developments in the study of the disease over time.
|14 days
* As with all microchapter pages linking to the main page, at the top of the edit box put <nowiki>{{CMG}}</nowiki>, your name template , and the microchapter navigation template you created at the beginning.
|YES<sup></sup>
* Remember to create links within Wikidoc by placing <nowiki>[[square brackets]]</nowiki> around key words which you want to link to other pages. Make sure you makes your links as specific as possible. For example if a sentence contained the phrase anterior spinal artery syndrome, the link should be to [[anterior spinal artery syndrome]] not [[anterior]] or [[artery]] or [[syndrome]].  For more information on how to create links click [[Help:Links|here]].
|-
* Remember this is not the page for patient history, or the natural history of the disease.
|Bismuth Quadruple
* Remember to follow the same format and capitalization of letters  as outlined in the template below
|PPI(standard dose)
* You should include the name of the disease in the first sentence of every subsection.
Bismuth subcitrate (120-300mg)or Subsalicylate (300mg)


==Overview==
Tetracyclin(500mg)
* This section should include the name of the disease in the first sentence, and give a brief description of the important aspects of the information that is relayed in the rest of the page.
* For an example of the overview section of the historical perspective page, click [[Chronic stable angina historical perspective#overview|here]].
===Template===
*'''First Sentence:'''
:[Disease name] was first discovered by [scientist] in [year] during/following [event].
:OR
:[Disease name] was first described by [scientist] in [year].
*'''Examples:'''
:Example 1:''Shigella'' was first discovered by Dr. Kiyoshi Shiga following a bacillary dysentery outbreak in Japan in 1896.
:Example 2: Melanoma was first described by Hippocrates in the 5th century BC.
<br>
*'''Additional Sentences:'''
:Additional Sentence 1: In [year], the first [event] occurred/was first reported following/during [event].
:Additional Sentence 2: In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
:Additional Sentence 3: There have been several outbreaks of [disease] which are summarized below.
:Additional Sentence 4: [Disease name] was first described in [year] by [scientist].
:Additional Sentence 5: [Risk factor or cause] was first discovered to be associated with [disease] in [year].
:Additional Sentence 6: In [year], [scientist] was the first to discover the association between [risk factor] and development of [disease].
:Additional Sentence 7: In [year], [gene] mutations were first identified in the pathogenesis of [disease].
*'''Examples:'''
:Example 1: In 1918, the first major human influenza pandemic occurred.
:Example 2: In 2003, human-to-human transmission of avian influenza was first reported during the influenza A H5N1 outbreaks in Southeast and Central Asia.
:Example 3: In 1978, the first cell-cytotoxicity assay was developed by Te-Wen Chang to diagnose ''C. difficile'' infection based on fecal toxins A and B.
:Example 4: There have been several outbreaks of avian influenza which are summarized below.
:Example 5: In 1956, Henry Lancaster, an Australian mathematician, was the first to discover the association between UV radiation exposure and development of melanoma.
:Example 6:  In 2003, ''BRAF'' mutations were first identified in the pathogenesis of melanoma.


==Preferred Template Statements==
Metronidazole(250-500mg)
IF the circumstances under which the disease was discovered are known:
|BID
*Gastric ulcer was first discovered by Goldstein, a [nationality + occupation], in [year]/during/following [event].
QID


Other sentences may describe the development of diagnostic techniques or therapies to treat the disease, outbreaks or epidemics throughout history, discoveries relating to the pathogenesis or causes of the disease, etc. A non-comprehensive list of additional template statements is below.
QID
*In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
*There have been several outbreaks of [disease name], which are summarized below. 
*The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
*In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
*In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
*The following are a few famous cases of [disease name].
Spiral-shaped microorganism described by Polish clinical researcher  Professor W.Jaworski at Cracow Jagiellonian University 100 years ago but it was confirmed in the animal by G.Bizzazero.In late 1970, J.R Warren, a pathologist in Perth, Australia found the appearance of spiral bacteria overlying gastric mucosa.
In 1982 Warren and B.J marshall cultured the organism and demonstrate a strong association between Helicobacter pylori and inflammation of gastric mucosa ,it is not due to spicy food and stress <ref name="pmid15075463">{{cite journal |vauthors=Konturek JW |title=Discovery by Jaworski of Helicobacter pylori and its pathogenetic role in peptic ulcer, gastritis and gastric cancer |journal=J. Physiol. Pharmacol. |volume=54 Suppl 3 |issue= |pages=23–41 |year=2003 |pmid=15075463 |doi= |url=}}</ref><ref name="urlHome | CDC Ulcer">{{cite web |url=https://www.cdc.gov/ulcer/index.htm |title=Home &#124; CDC Ulcer |format= |work= |accessdate=}}</ref>
1994
A National Institutes of Health Consensus Development Conference concludes that there is a strong association between H. pylori and ulcer disease, and recommends that ulcer patients with H. pylori infection be treated with antibiotics.


==Discovery==
TID to QID (500mg)
* This section should describe how the disease was initially discovered, when it was discovered, and who discovered it.
|10-14 days
* For an example of the discovery section within a historical perspective page, click [[Appendicitis historical perspective#Discovery|here]].
|NO<sup>‡</sup>
|-
|Concomitant
|PPI (standard dose)
Clarithromycin (500mg)


==Landmark Events in the Development of Treatment Strategies==
Amoxicillin(1gm)
* Include notable scientists who studied the condition.
* Include landmark changes in approaches to studying the disease.
* This is a good place to include pictures of treatments, such as the "iron lung" for polio. For more information on adding pictures, click [[Help:Images and other Media|here]].
* For an example of a development of treatment strategies section within a historical perspective page, click [[Appendicitis historical perspective#Development of Treatment Strategies|here]].


==Impact on Cultural History==
Nitroimidazole(500mg)
* Here you can include the impact the disease has had over time from a cultural aspect.
|BID
* Include pandemics, epidemics, outbreaks, and initial mortality.
|10 -14 days
* Include the impact of the disease on society, such as the devastation, the way the sick were treated, and the impacts of the treatments that were used at the time.
|NO
* For an example of an impact on cultural history section within a historical perspective page, click [[Appendicitis historical perspective#Impact on Cultural History|here]].
|-
|Sequential
|PPI(standard dose)+Amoxicillin(1gm)
PPI,Clarithromycin(500mg)+Nitroimidazole(500mg)
|BID


==Famous Cases==
BID
* Include prominent cases of the condition in history (eg. Typhoid Mary).
|5-7 days
* Include famous people who were afflicted by the condition.
* Include famous cases that defined the condition in history.


==References==
5-7 days
* References should be cited for the material that you have put on your page. Type in <nowiki>{{reflist|2}}</nowiki>. This will generate your references in small font, in two columns, with links to the original article and abstract.
|NO
* For information on how to add references into your page, click [[Help:Adding References to Articles|here]].
|-
|Hybrid
|PPI(standard)+Amoxicillin(1gm)
PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg)
|BID
BID
|7 days
7 days
|NO
|-
|Levofloxacin triple
|PPI(standard dose)
Levofloxacin(500mg)


[[Category:Help]]
Amoxicillin(1gm)
[[Category:Templates]]
|BID
QID


{{WikiDoc Help Menu}}
BID
{{WikiDoc Sources}}
 
|10-14 days
|NO
|-
|Levofloxacin sequential
|PPI(standard or double dose)+Amoxicillin(1 gm)
PPI,Amoxicillin,Levofloxacin(500mg QD),Nitroimidazole(500mg)
|BID
BID
|5-7 days
|NO
|-
|LOAD
|Levofloxacin(250mg)
PPI(double dose)
 
Nitazoxanide(500mg)
 
Doxycycline(100mg)
|QD
QD
 
BID
 
QD
|7-10 days
|NO
|}
 
'''†''': Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval ,PPI, Clarithromycin, Metronidazole is not an FDA approved treatment regimen.
 
'''‡:''' PPI, Bismuth, Tetracycline and metronidazole prescribed separately is not an FDA approved treatment regimen.However ,Pylera, a combination product containing Bismuth subcitrate,Tetracycline , Metronidazole combination with PPi for 10 days is an FDA approved regimen.
 
'''Adjuvant therapy in the treatment of H. pylori infection:'''
 
Emerging evidence suggests an inhibitory effect of Lactobacillus
and Bifidobacterium species on H. pylori. Furthermore,
these probiotic strains may also help to reduce the side effects
of eradication therapies and improve compliance with therapy.
 
== Selection of firstline Treatment==
 
{{familytree/start}}
{{familytree |boxstyle=text-align: left; | | | | | | | | | A01 | | | |A01=•Is there a penicillin (PCN) allergy?<br> •Previous macrolide (MCL) exposure for any reason ?<br>}}
{{familytree | | |,|-|-|-|-|v|-|^|-|v|-|-|-|.| ||}} 
{{familytree |boxstyle=text-align: left; | | B01 | | | B02 | | B03 | | B04||B01=•PCN allergy: '''No'''<br> •MCL exposure: '''No'''<br> |B02=•PCN allergy: '''No'''<br> •MCL exposure: '''Yes'''<br> |B03=•PCN allergy: '''Yes'''<br> •MCL exposure: '''No'''<br> |B04=•PCN allergy: '''Yes'''<br> •MCL exposure: '''Yes'''<br> }}
{{familytree | | |!| | | | |!| | | |!| | | |!| ||}} 
{{familytree |boxstyle=text-align: left; | | B01 | | | B02 | | B03 | | B04||B01='''Recomended treatment:'''<br> •Bismuth quadruple <br> •Clarithromycin triple with amoxicillin<br> '''Other options''':<br> •Sequential<br> •HYBRID<br> •Levofloxacin triple<br> •Levofloxacin sequential <br>•LOAD<br> |B02='''Recomended treatment:'''<br>•Bismuth quadruple <br>•Levofloxacin sequential<br>'''Other options''':<br>•Concomitant therapy<br>•Sequential therapy <br>• HYBRID<br> •LOAD<br>|B03='''Recomended treatment:'''<br> •Bismuth quadruple <br> •Clarithromycin triple <br> with metronidazole<br> •Bismuth quadruple<br>|B04= '''Recomended treatment:''' <br> •Bismuth quadruple <br> •Clarithromycin triple with metronidazole<br> •Bismuth quadruple<br>}}
{{Familytree/end}}
 
 
 
{{familytree/start}}
{{familytree| | | | | | | | | | | | | | | | | | A01 | | | | | |A01=Persistent Helicobacter pylori infection }}
{{familytree| | | | | | | | | |,|-|-|-|-|-|-|-|-|^|-|-|-|-|-|-|-|-|.| |}}
{{familytree| | | | | | | | | B01 | | | | | | | | | | | | | | | | B02 ||B01=Patient recieved clarithromycin triple therapy|B02=Patient received Bismuth quadriple therapy }}
{{familytree| | |,|-|-|-|v|-|-|^|-|-|v|-|-|-|.| | | |,|-|-|-|v|-|-|^|-|-|v|-|-|-|.|}}
{{familytree|boxstyle=text-align: left; | C01 | | C02 | | | | C03 | | C04 | | C05 | | C06 | | | | C07 | | C08 | |C01= •No previous Quinolone exposure<br>•No PCN allergy<br>'''Recomended treatment:'''<br> •Bismuth quadruple<br> •Levofloxacin<br> •Rifabutin triple<br> •High dose dual|C02= •Previous Quinolone exposure<br> •No PCN Allergy<br>'''Recomended treatment:'''<br> •Bismuth quadruple therapy<br> •Rifabutin triple<br> •High dose dual<br>|C03= •No previous Quinolone exposure<br> •PCN Allergy<br> '''Recomended treatment:'''<br>•Bismuth quadruple| C04=•Previous Quinolone exposure<br> •PCN Allergy<br>'''Recomended treatment:'''<br> •Bismuth quadruple<br>|C05=•No previous Quinolone exposure<br>•No PCN allergy<br>'''Recomended treatment:'''<br>•Levofloxacin triple concomitant<br>•Rifabutin triple<br>•High dose triple<br>|C06=•Previous Quinolone exposure<br> •No PCN Allergy<br>'''Recomended treatment:'''<br>•Concomitant Rifabutin triple <br>•High dose dual<br>|C07=•No previous Quinolone<br> exposure<br> •PCN Allergy<br> '''Recomended treatment:'''<br>•PPI,Clarithromycin<br>,Metronidazole<br>•PPI,Levofloxacin,<br>Metronidazole|C08=•Previous Quinolone exposure<br> •No PCN Allergy<br>'''Recomended treatment:'''<br> •PPI,Clarithromycin,<br>Metronidazole<br>•Bismuth quadruple }}
{{familytree/end}}
 
 
===Diagnostic testing===
The American Journal of Gastroenterology guidelines recommend that '''endoscopy''' should be performed to rule out [[peptic ulcer disease]], esophagogastric [[malignancy]], and other rare upper gastrointestinal tract disease in the following settings:
* [[Dyspeptic]] patients <u>more than 55 years old</u> {{or2}}
* [[Dyspeptic]] patients with <u>alarm features</u>
:* [[Bleeding]]
:* [[Anemia]]
:* [[Early satiety]]
:* Unexplained [[weight loss]] (> 10% body weight)
:* Progressive [[dysphagia]]
:* [[Odynophagia]]
:* Persistent [[vomiting]]
:* A family history of gastrointestinal cancer
:* Previous esophagogastric [[malignancy]]
:* Previous documented [[peptic ulcer]], [[lymphadenopathy]], or an abdominal mass
 
In patients aged 55 years or younger with no alarm features, two management options may be considered:
* '''Test-and-treat strategy''' using a validated noninvasive test (urea breathing test or stool antigen test) for ''[[H. pylori]]'' and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of ''[[H. pylori]]'' infection (≥ 10%)
* '''Empiric trial of acid suppression''' with a [[proton pump inhibitor]] for 4–8 weeks – preferable in low prevalence situations
 
Repeat [[endoscopy]] is not recommended once a firm diagnosis of functional [[dyspepsia]] has been established, unless new symptoms or alarm features develop.<ref>{{Cite journal| doi = 10.1111/j.1572-0241.2005.00225.x| issn = 0002-9270| volume = 100| issue = 10| pages = 2324–2337| last1 = Talley| first1 = Nicholas J.| last2 = Vakil| first2 = Nimish| last3 = Practice Parameters Committee of the American College of Gastroenterology| title = Guidelines for the management of dyspepsia| journal = The American Journal of Gastroenterology| date = 2005-10| pmid = 16181387}}</ref>  Testing to prove ''[[H. pylori]]'' eradication is most accurate if performed 4 weeks after the completion of therapy.<ref>{{Cite journal| doi = 10.1136/gutjnl-2012-302084| issn = 1468-3288| volume = 61| issue = 5| pages = 646–664| last1 = Malfertheiner| first1 = Peter| last2 = Megraud| first2 = Francis| last3 = O'Morain| first3 = Colm A.| last4 = Atherton| first4 = John| last5 = Axon| first5 = Anthony T. R.| last6 = Bazzoli| first6 = Franco| last7 = Gensini| first7 = Gian Franco| last8 = Gisbert| first8 = Javier P.| last9 = Graham| first9 = David Y.| last10 = Rokkas| first10 = Theodore| last11 = El-Omar| first11 = Emad M.| last12 = Kuipers| first12 = Ernst J.| last13 = European Helicobacter Study Group| title = Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report| journal = Gut| date = 2012-05| pmid = 22491499}}</ref>

Latest revision as of 14:48, 30 October 2017

The ACG’s 2007 treatment guideline on the management of H. pylori infection (26) listed the following as established indications for diagnosis and treatment:

Indications

  • Active PUD (gastric or duodenal).
  • Confirmed history of PUD (not previously treated for H. pylori)
  • Gastric MALT lymphoma (low grade)
  • After endoscopic resection of EGC

Recommended first-line treatment for Helicobacter pylori

Regimen Drug dose Dosing frequency Duration(days) FDA approval
Clarithromycin triple PPI(standard or double dose

Clarithromycin(500mg)

Amoxicillin(1gm)or Metronidazole(500mg TID)

BID 14 days YES
Bismuth Quadruple PPI(standard dose)

Bismuth subcitrate (120-300mg)or Subsalicylate (300mg)

Tetracyclin(500mg)

Metronidazole(250-500mg)

BID

QID

QID

TID to QID (500mg)

10-14 days NO
Concomitant PPI (standard dose)

Clarithromycin (500mg)

Amoxicillin(1gm)

Nitroimidazole(500mg)

BID 10 -14 days NO
Sequential PPI(standard dose)+Amoxicillin(1gm)

PPI,Clarithromycin(500mg)+Nitroimidazole(500mg)

BID

BID

5-7 days

5-7 days

NO
Hybrid PPI(standard)+Amoxicillin(1gm)

PPI,Amoxicillin,Clarithromycin(500mg),Nitroimidazole(500mg)

BID

BID

7 days

7 days

NO
Levofloxacin triple PPI(standard dose)

Levofloxacin(500mg)

Amoxicillin(1gm)

BID

QID

BID

10-14 days NO
Levofloxacin sequential PPI(standard or double dose)+Amoxicillin(1 gm)

PPI,Amoxicillin,Levofloxacin(500mg QD),Nitroimidazole(500mg)

BID

BID

5-7 days NO
LOAD Levofloxacin(250mg)

PPI(double dose)

Nitazoxanide(500mg)

Doxycycline(100mg)

QD

QD

BID

QD

7-10 days NO

: Several PPI, Clarithromycin, and Amoxicillin combinations have achieved FDA approval ,PPI, Clarithromycin, Metronidazole is not an FDA approved treatment regimen.

‡: PPI, Bismuth, Tetracycline and metronidazole prescribed separately is not an FDA approved treatment regimen.However ,Pylera, a combination product containing Bismuth subcitrate,Tetracycline , Metronidazole combination with PPi for 10 days is an FDA approved regimen.

Adjuvant therapy in the treatment of H. pylori infection:

Emerging evidence suggests an inhibitory effect of Lactobacillus and Bifidobacterium species on H. pylori. Furthermore, these probiotic strains may also help to reduce the side effects of eradication therapies and improve compliance with therapy.

Selection of firstline Treatment

 
 
 
 
 
 
 
 
•Is there a penicillin (PCN) allergy?
•Previous macrolide (MCL) exposure for any reason ?
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•PCN allergy: No
•MCL exposure: No
 
 
•PCN allergy: No
•MCL exposure: Yes
 
•PCN allergy: Yes
•MCL exposure: No
 
•PCN allergy: Yes
•MCL exposure: Yes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Recomended treatment:
•Bismuth quadruple
•Clarithromycin triple with amoxicillin
Other options:
•Sequential
•HYBRID
•Levofloxacin triple
•Levofloxacin sequential
•LOAD
 
 
Recomended treatment:
•Bismuth quadruple
•Levofloxacin sequential
Other options:
•Concomitant therapy
•Sequential therapy
• HYBRID
•LOAD
 
Recomended treatment:
•Bismuth quadruple
•Clarithromycin triple
with metronidazole
•Bismuth quadruple
 
Recomended treatment:
•Bismuth quadruple
•Clarithromycin triple with metronidazole
•Bismuth quadruple


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Persistent Helicobacter pylori infection
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient recieved clarithromycin triple therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient received Bismuth quadriple therapy
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
•No previous Quinolone exposure
•No PCN allergy
Recomended treatment:
•Bismuth quadruple
•Levofloxacin
•Rifabutin triple
•High dose dual
 
•Previous Quinolone exposure
•No PCN Allergy
Recomended treatment:
•Bismuth quadruple therapy
•Rifabutin triple
•High dose dual
 
 
 
•No previous Quinolone exposure
•PCN Allergy
Recomended treatment:
•Bismuth quadruple
 
•Previous Quinolone exposure
•PCN Allergy
Recomended treatment:
•Bismuth quadruple
 
•No previous Quinolone exposure
•No PCN allergy
Recomended treatment:
•Levofloxacin triple concomitant
•Rifabutin triple
•High dose triple
 
•Previous Quinolone exposure
•No PCN Allergy
Recomended treatment:
•Concomitant Rifabutin triple
•High dose dual
 
 
 
•No previous Quinolone
exposure
•PCN Allergy
Recomended treatment:
•PPI,Clarithromycin
,Metronidazole
•PPI,Levofloxacin,
Metronidazole
 
•Previous Quinolone exposure
•No PCN Allergy
Recomended treatment:
•PPI,Clarithromycin,
Metronidazole
•Bismuth quadruple
 


Diagnostic testing

The American Journal of Gastroenterology guidelines recommend that endoscopy should be performed to rule out peptic ulcer disease, esophagogastric malignancy, and other rare upper gastrointestinal tract disease in the following settings:

In patients aged 55 years or younger with no alarm features, two management options may be considered:

  • Test-and-treat strategy using a validated noninvasive test (urea breathing test or stool antigen test) for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve – preferable in populations with a moderate to high prevalence of H. pylori infection (≥ 10%)
  • Empiric trial of acid suppression with a proton pump inhibitor for 4–8 weeks – preferable in low prevalence situations

Repeat endoscopy is not recommended once a firm diagnosis of functional dyspepsia has been established, unless new symptoms or alarm features develop.[1] Testing to prove H. pylori eradication is most accurate if performed 4 weeks after the completion of therapy.[2]

  1. Talley, Nicholas J.; Vakil, Nimish; Practice Parameters Committee of the American College of Gastroenterology (2005-10). "Guidelines for the management of dyspepsia". The American Journal of Gastroenterology. 100 (10): 2324–2337. doi:10.1111/j.1572-0241.2005.00225.x. ISSN 0002-9270. PMID 16181387. Check date values in: |date= (help)
  2. Malfertheiner, Peter; Megraud, Francis; O'Morain, Colm A.; Atherton, John; Axon, Anthony T. R.; Bazzoli, Franco; Gensini, Gian Franco; Gisbert, Javier P.; Graham, David Y.; Rokkas, Theodore; El-Omar, Emad M.; Kuipers, Ernst J.; European Helicobacter Study Group (2012-05). "Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report". Gut. 61 (5): 646–664. doi:10.1136/gutjnl-2012-302084. ISSN 1468-3288. PMID 22491499. Check date values in: |date= (help)