Irritable
bowel syndrome
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Irritable
bowel syndrome (IBS) is a blanket term for a variety of
diseases causing discomfort in the gastro-intestinal tract. Also called spastic
colon, it is a functional bowel disorder characterized
by chronic abdominal pain, discomfort, bloating, and alteration
of bowel habits in the absence of any organic cause. In some cases, the
symptoms are relieved by bowel movements.[1]
Diarrhea or constipation
may predominate, or they may alternate (classified as IBS-D, IBS-C
or IBS-A, respectively). IBS may begin after an infection
(post-infectious, IBS-PI) or a stressful
life event or may begin at onset of maturity without any other medical
indicators.
Although there
is no cure for IBS, there are treatments which attempt to relieve symptoms,
including dietary adjustments, medication and psychological
interventions. Patient education and a good doctor-patient relationship are also
important.[1]
Several
conditions may present as IBS including celiac
disease, mild infections, parasitic infections like giardiasis[2],
several inflammatory bowel diseases, functional chronic constipation, and chronic functional abdominal pain.
In IBS, routine clinical tests yield no abnormalities, though the bowels may be
more sensitive to certain stimuli, such as balloon insufflation testing. The
exact cause of IBS is unknown. The most common theory is that IBS is a disorder
of the interaction between the brain and the gastrointestinal tract, although there may
also be abnormalities in the gut flora or the immune
system.[3][4]
IBS does not
lead to more serious conditions in most patients.[5][6][7][8][9]
But it is a source of chronic pain, fatigue and other symptoms, and it
increases a patient's medical costs,[10][11]
and contributes to work absenteeism.[12][13]
Researchers have reported that the high prevalence of IBS,[14][15][16]
in conjunction with increased costs produces a disease with a high societal
cost.[17]
It is also regarded as a chronic illness and can dramatically affect the
quality of a sufferer's life.
[edit] Classification
IBS can be
classified as either diarrhea-predominant (IBS-D), constipation-predominant
(IBS-C) or IBS with alternating stool pattern (IBS-A or
pain-predominant[18]).
In some individuals, IBS may have an acute onset and develop after an infectious
illness characterized by two or more of the following: fever, vomiting, diarrhea, or
positive stool culture. This post-infective syndrome has
consequently been termed "post-infectious IBS" (IBS-PI).
[edit] Symptoms
The primary symptoms of IBS
are abdominal
pain or discomfort in association with frequent diarrhea or constipation,
a change in bowel habits.[19]
There may also be urgency for bowel movements, a feeling of incomplete
evacuation (tenesmus),
bloating or abdominal distention.[20]
People with IBS more commonly than others have gastroesophageal reflux, symptoms relating
to the genitourinary system, psychological symptoms, fibromyalgia,
chronic fatigue syndrome, headache and backache.[20][21]
A person with
irritable bowel syndrome could also experience lethargy, first
depression and disturbance when sleeping.
Digestive disorder can develop at any age, but usually first experienced
between ages 15 and 40.[22]
[edit] Diagnosis
There is no
specific laboratory or imaging test which can be performed to diagnose
irritable bowel syndrome.[23]
Diagnosis of IBS involves excluding conditions which produce IBS-like symptoms,
and then following a procedure to categorize the patient's symptoms.
[edit] Differential diagnosis
Because there
are many causes of diarrhea that give IBS-like
symptoms, the American Gastroenterological
Association has published a set of guidelines for tests to be performed to
rule out other causes for these symptoms. These include gastrointestinal
infections, lactose intolerance and Coeliac
disease. Research has suggested that these guidelines are not always
followed.[23]
Once other causes have been excluded, the diagnosis of IBS is performed using a
diagnostic algorithm.
Well-known algorithms
include the Manning Criteria, the obsolete Rome I
and II criteria, the Kruis Criteria, and studies have compared their
reliability.[24]
The more recent Rome III Process was published in 2006. Physicians may
choose to use one of these guidelines, or may simply choose to rely on their
own anecdotal experience with past patients. The algorithm may
include additional tests to guard against mis-diagnosis of other diseases as
IBS. Such "red flag" symptoms may include weight loss, GI bleeding,
anemia, or nocturnal symptoms. However, researchers have noted that red flag
conditions may not always contribute to accuracy in diagnosis for instance,
as many as 31% of IBS patients have blood in their stool.[24]
The diagnostic algorithm
identifies a name which can be applied to the patient's condition based on the
combination of the patient's symptoms of diarrhea,
abdominal pain, and constipation. For example, the statement "50% of
returning travelers had developed functional diarrhea while 25%
had developed IBS" would mean that half the travelers had diarrhea while
a quarter had diarrhea
with abdominal pain. While some researchers believe this categorization system
will help physicians understand IBS, others have questioned the value of the
system and suggested that all IBS patients have the same underlying disease but
with different symptoms.[25]
[edit] Misdiagnosis
Published research
has demonstrated that some poor patient outcomes are due to treatable causes of
diarrhea being mis-diagnosed as IBS. Common examples include infectious diseases, celiac
disease,[26]
helicobacter pylori,[27][28]
parasites.[4][29][30]
See List of causes of diarrhea for other
conditions which can cause diarrhea.
Celiac
disease in particular is often misdiagnosed as IBS. The American College of
Gastroenterology recommends that all patients with symptoms of IBS be tested
for celiac disease.[31]
Chronic use of certain sedative-hypnotic drugs especially the benzodiazepines
may cause irritable bowel like symptoms which can lead to a misdiagnosis of
irritable bowel syndrome.[32]
[edit] Medical
conditions that accompany IBS
Researchers have
identified several medical conditions, or comorbidities,
which appear with greater frequency in patients diagnosed with IBS.
Headache,
Fibromyalgia,
Chronic fatigue syndrome and Depression: A
study of 97,593 individuals with IBS identified comorbidities as headache, fibromyalgia,
and depression.[33]
A systematic review found that IBS occurs in 51% of chronic fatigue syndrome patients and 49%
of fibromyalgia
patients, and psychiatric disorders were found to occur in 94% of IBS patients.[21]
Inflammatory bowel disease: Some
researchers have suggested that IBS is a type of low-grade inflammatory bowel
disease.[5]
Researchers have suggested that IBS and IBD are interrelated diseases,[6]
noting that patients with IBD experience IBS-like symptoms when their IBD is in
remission.[7][8]
A 3-year study found that patients diagnosed with IBS were 16.3 times more
likely to develop IBD during the study period.[9]
Serum markers associated with inflammation have also been found in patients
with IBS (see Causes).
Abdominal
surgery:
A recent (2008) study found that IBS patients are at increased risk of having
unnecessary cholecystectomy (gall bladder removal surgery) not
due to an increased risk of gallstones, but rather to abdominal
pain, awareness of having gallstones, and inappropriate surgical indications.[34]
A 2005 study published in Digestive Disease Science reported that IBS
patients are 87% more likely to undergo abdominal and pelvic surgery, and three
times more likely to undergo gallbladder surgery.[35]
A study published in Gastroenterology came to similar conclusions,
and also noted IBS patients were twice as likely to undergo hysterectomy.[36]
Endometriosis: One
study has reported a statistically significant link between migraine
headaches, IBS, and endometriosis.[37]
Other
chronic disorders: Interstitial cystitis may be associated with
other chronic pain syndromes, such as irritable bowel syndrome and
fibromyalgia. The connection between these syndromes is unknown.[38]
[edit] Etiology
The cause of IBS
is not known, but several hypotheses have been proposed. The risk of developing
IBS increases sixfold after acute gastrointestinal infection. Post-infection,
further risk factors are young age, prolonged fever, anxiety and depression.[39]
[edit] Psychosomatic illness
Publications
suggesting the role of brain-gut "axis" appeared in the 1990s, such
as a study entitled Brain-gut response to stress and cholinergic stimulation
in IBS published in the Journal of Clinical Gastroenterology in
1993.[40]
A 1997 study published in Gut magazine suggested that IBS was associated
with a "derailing of the brain-gut axis."[41]
Psychological factors are still thought to be important in the etiology of IBS,[21]
and the symptoms defining the condition are referred to by some doctors as medically unexplained symptoms,[42]
a term some psychiatrists consider synonymous with somatoform disorder.
[edit] Immune reaction
From the late
1990s, research publications began identifying specific biochemical changes
present in tissue biopsies and serum samples from IBS patients. These studies
identified cytokines
and secretory products in tissues taken from IBS patients. The cytokines
identified in IBS patients produce inflammation
and are associated with the body's immune response.
[edit] Active infections
There is
research to support IBS being caused by an as-yet undiscovered active infection.
Most recently, a study has found that the antibiotic Rifaximin
provides sustained relief for IBS patients.[43]
While some researchers see this as evidence that IBS is related to an
undiscovered agent, others believe IBS patients suffer from overgrowth of intestinal
flora and the antibiotics are effective in reducing the overgrowth (known
as small intestinal bacterial
overgrowth).[44]
Other researchers have focused on an unrecognized protozoal
infection as a cause of IBS[4]
as certain protozoal infections occur more frequently in IBS patients.[45][46]
Two of the protozoa investigated have a high prevalence in industrialized
countries and infect the bowel, but little is known about them as they are
recently emerged pathogens.
Blastocystis is a
single-celled organism which has been reported to produce symptoms of abdominal
pain, constipation and diarrhea in patients, along with headaches and
depression,[47]
though these reports are contested by some physicians.[48]
Studies from research hospitals in various countries have identified high Blastocystis
infection rates in IBS patients, with 38% being reported from London School of
Hygiene & Tropical Medicine,[49]
47% reported from the Department of Gastroenterology at Aga Khan University in Pakistan[45]
and 18.1% reported from the Institute of Diseases and Public Health at University of Ancona in Italy.[46]
Reports from all three groups indicate a Blastocystis
prevalence of approximately 7% in non-IBS patients. Researchers have noted that
clinical diagnostics fail to identify infection,[50]
and Blastocystis may not respond to treatment with common
antiprotozoals.[51][52][53][54]
Prevalence of protozoal infections in industrialized
countries (United States and Canada) in 21st century.[55][56]
Dientamoeba fragilis is a single-celled
organism which produces abdominal pain and diarrhea. Studies have reported a
high incidence of infection in developed countries, and symptoms of patients
resolve following antibiotic treatment.[55][57]
One study reported on a large group of patients with IBS-like symptoms who were
found to be infected with Dientamoeba fragilis, and experienced
resolution of symptoms following treatment.[58]
Researchers have noted that methods used clinically may fail to detect some Dientamoeba fragilis infections.[57]
It is also found in people without IBS. [59]
[edit] Treatment
A questionnaire
in 2006 designed to identify patients perceptions about IBS, their preferences
on the type of information they need, as well as educational media and
expectations from health care providers, revealed misperceptions about IBS
developing into other conditions, including colitis, malnutrition,
and cancer.[60]
The survey found
IBS patients were most interested in learning about foods to avoid (60%),
causes of IBS (55%), medications (58%), coping strategies (56%), and
psychological factors related to IBS (55%). The respondents indicated that they
wanted their physicians to be available via phone or e-mail following a visit
(80%), have the ability to listen (80%), and provide hope (73%) and support
(63%).
[edit] Diet
Many different
dietary modifications have been attempted to improve the symptoms of IBS. Some
are effective in certain sub populations. As lactose intolerance and IBS have such similar
symptoms a trial of a lactose free diet is often recommended.[61]
Fiber supplements have not been found to be effective in the general IBS
population.[62]
They however might be beneficial in those who have a predominance of
constipation.
Definitive
determination of dietary issues can be accomplished by testing for the
physiological effects of specific foods. The ELISA food allergy
panel can identify specific foods to which a patient has a reaction. Other
testing can determine if there are nutritional deficiencies secondary to diet
that may also play a role. Removal of foods causing IgG immune response as
measured using the ELISA food panel has been shown to substantially decrease
symptoms of IBS in several studies.[63]
There is no evidence
that digestion of food or absorption of nutrients is problematic for those with
IBS at rates different from those without IBS. However, the very act of eating
or drinking can provoke an overreaction of the gastrocolic response in some patients with IBS
due to their heightened visceral sensitivity, and this can lead to abdominal
pain, diarrhea, and/or constipation.[64]
Several of the
most common dietary triggers are well-established by clinical studies at this
point; research has shown that IBS patients are hypersensitive to fats and fructose.[65][66]
It also appears
that some foods are more difficult for the gut as evidenced by elevated
food-specific IgG4 antibodies being present,[67][68]
while others increase colonic contractions, which may be painful, due to
increased visceral sensitivity in IBS sufferers.[69]
Fiber
In patients who
have constipation predominant irritable bowel, soluble fiber at doses of 20
grams per day can reduce overall symptoms but will not reduce pain. The
research supporting dietary fiber contains conflicting, small studies
that are complicated by the heterogeneity of types of fiber and doses used.[70]
The one meta-analysis that controlled for solubility found that
only soluble fiber improved global symptoms of irritable bowel and neither type
of fiber reduced pain[70]
Positive studies have used 20-30 grams per day of psyllium seed.[71][72]
One study specifically examined the effect of dose and found that 20 grams of
ispaghula husk was better than 10 grams and equivalent to 30 grams per day[73]
An uncontrolled study noted increased symptoms with insoluble fibers.[74]
It is unclear if these symptoms are truly increased compared to a control
group. If the symptoms are increased, it is unclear if these patients were
diarrhea predominant (which can be exacerbated by insoluble fiber[75][76]),
or if the increase is temporary before benefit occurs.
[edit] Medication
Medications may
consist of stool softeners and laxatives in constipation-predominant IBS, and antidiarrheals
(e.g., opiate, opioid or opioid analogs such as loperamide,
codeine, diphenoxylate)
in diarrhea-predominant IBS for mild symptoms.[77][78][79]
Drugs affecting serotonin
(5-HT) in the intestines can help reduce symptoms.[80]
Serotonin stimulates the gut motility and so agonists can help
constipation-predominate irritable bowel, while antagonists can help
diarrhea-predominant irritable bowel.
[edit] Laxatives
Main
article: Laxative
For patients who
do not adequately respond to dietary
fiber, osmotic agents such as polyethylene glycol, sorbitol, and lactulose can
help avoid 'cathartic colon' which has been associated with stimulant
laxatives.[81]
Among the osmotic laxatives, 17 to 26 grams/day of polyethylene glycol (PEG) has been well
studied.
- Lubiprostone
(Amitiza), is a gastrointestinal agent used for the treatment of idiopathic
chronic constipation
and constipation-predominant IBS. It is well-tolerated in adults,
including elderly patients. As of July 20, 2006, Lubiprostone had not been
studied in pediatric patients. Lubiprostone is a bicyclic fatty
acid (prostaglandin E1 derivative) which acts by
specifically activating ClC-2 chloride channels on the apical aspect of
gastrointestinal epithelial cells, producing a chloride-rich fluid
secretion. These secretions soften the stool, increase motility, and
promote spontaneous bowel movements (SBM). Unlike many laxative products,
Lubiprostone does not show signs of tolerance, dependency, or altered
serum electrolyte concentration.
[edit] Antispasmodics
Main
article: Antispasmodic
The use of
antispasmodic drugs (e.g. anticholinergics such as hyoscyamine
or dicyclomine)
may help patients, especially those with cramps or diarrhea. A meta-analysis
by the Cochrane Collaboration concludes that if 6
patients are treated with antispasmodics, 1 patient will benefit.[77]
Antispasmodics can be divided in two groups: neurotropics and musculotropics.
Neurotropics, such as atropine, act at the nerve fibre of the parasympathicus but
also affect other nerves and have side effects. Musculotropics such as mebeverine
act directly at the smooth muscle of the gastrointestinal tract, relieving
spasm without affecting normal gut motility.[citation needed] Since this
action is not mediated by the autonomic nervous system, the usual
anticholinergic side effects are absent.[citation needed]
[edit] Serotonin agonists
- Tegaserod
(Zelnorm), a selective 5-HT4 agonist for IBS-C, is available for relieving
IBS constipation in women and chronic idiopathic
constipation
in men and women. On March 30, 2007, the Food and Drug Administration
(FDA) requested that Novartis Pharmaceuticals voluntarily discontinue
marketing of tegaserod based on the recently identified finding of an
increased risk of serious cardiovascular adverse events (heart problems)
associated with use of the drug. Novartis agreed to voluntarily suspend
marketing of the drug in the United States and in many other countries. On
July 27, 2007 the Food and Drug Administration (FDA) approved a limited
treatment IND program for tegaserod in the USA to allow restricted access
to the medication for patients in need if no comparable alternative drug
or therapy is available to treat the disease. The USA FDA had issued two
previous warnings about the serious consequences of Tegaserod. In 2005,
tegaserod was rejected as an IBS medication by the European Union.
Tegaserod, marketed as Zelnorm in the United States, was the only agent
approved to treat the multiple symptoms of IBS (in women only), including
constipation, abdominal pain and bloating. A meta-analysis
by the Cochrane Collaboration concludes that
if 17 patients are treated with typical doses of tegaserod,
1 patient will benefit.[82]
- Selective serotonin
reuptake inhibitor anti-depressants (SSRIs), because of their
serotonergic effect, would seem to help IBS, especially patients who are
constipation predominant. Initial crossover studies[83]
and randomized controlled trials[84][85][86]
support this role.
[edit] Serotonin antagonists
- Alosetron,
a selective 5-HT3 antagonist for IBS-D, which is only available for women
in the United States under a restricted access program, due to severe
risks of side-effects if taken mistakenly by
IBS-A or IBS-C sufferers.[citation needed]
- Cilansetron,
also a selective 5-HT3 antagonist, is undergoing further clinical studies
in Europe for IBS-D sufferers. In 2005, Solvay Pharmaceuticals withdrew
Cilansetron from the United States regulatory approval process after
receiving a "not approvable" action letter from the FDA
requesting additional clinical trials.[citation needed]
[edit] Other agents
There is conflicting
evidence about the benefit of antidepressants in IBS. Some meta-analysis have
found a benefit while others have not.[87]
A meta-analysis
of randomized controlled trials of mainly
TCAs found 3 patients have to be treated
with TCAs for one patient to improve.[88]
A separate randomized controlled trial found that
TCAs are best for patients with diarrhea-predominant IBS.[89]
Recent studies
have suggested that rifaximin can be used as an effective treatment for
abdominal bloating and flatulence,[43][90]
giving more credibility to the potential role of bacterial overgrowth in some
patients with IBS.[91]
The use of opioids is
controversial due to the lack of evidence supporting their benefit and the
potential risk of tolerance, physical dependence and addiction.[92]
[edit] Psychotherapy
There is a
strong brain-gut component to IBS. Cognitive behavioral therapy has been
found to improve symptoms in a number of studies.[93][94]
Relaxation therapy has also been found to helpful.[95]
[edit] Alternative treatments
Probiotics
A 2008 review
has found probiotics
to be beneficial in the treatment of IBS.[96]
Many different type have be found to be effective including: Lactobacillus plantarum[97]
and Bifidobacteria infantis;[98]
however, one review found that only Bifidobacteria
infantis showed efficacy.[99]
Iberogast
The multi-herbal
extract Iberogast
was found to be significantly superior to placebo via both an abdominal pain
scale and an IBS symptom score after four weeks of treatment.[100]
Peppermint oil
Enteric coated peppermint
oil capsules has been advocated for IBS symptoms in adults and children;[101]
however, results from trials have been inconsistent.[102][103]
Acupuncture
Many sufferers
of IBS seek relief using acupuncture.[citation needed] A meta-analysis
by the Cochrane Collaboration however concluded
that most trials are of poor quality and that it is unknown whether acupuncture
is more effective than placebo.[104]
[edit] Epidemiology
Percentage of population with IBS reported in
various studies in different countries
By
Country:
Studies have reported that the prevalence of IBS varies by country and by age
range examined. The bar graph at right shows the percentage of the population
reporting symptoms of IBS in studies from various geographic regions (see table
below for references).
The following
table contains a list of studies performed in different countries that measured
the prevalence of IBS and IBS-like symptoms:
[hide]Percentage of Population
Reporting Symptoms of IBS in Various Studies from Various Geographic Areas **
Check the Rome criteria studies (eg, at PubMed) and see how the reported
prevalence rates drop! Also, one should be wary of trusting many of these
study results - ref. 'Havidol'.
|
Country
|
Prevalence
|
Author/Year
|
Notes
|
Canada
|
6%[14]
|
Boivin,2001
|
|
Japan
|
10%[105]
|
Quigley,2006
|
Study measured prevalence of GI
abdominal pain/cramping
|
United Kingdom
|
8.2%[106]
10.5%[15]
|
Ehlin,2003
Wilson,2004
|
Prevalence
increased substantially 1970-2004
|
United
States
|
14.1%[107]
|
Hungin,
2005
|
Most
undiagnosed
|
United
States
|
15%[14]
|
Boivin,2001
|
Estimate
|
Pakistan
|
14%[108]
|
Jafri,
2007
|
Much
more common in 16-30 age range. Of IBS patients, 56% male, 44% female
|
Pakistan
|
34%[109]
|
Jafri,2005
|
College
students
|
Mexico
City
|
35%[16]
|
Schmulson,
2006
|
n=324.
Also measured functional diarrhea and functional vomiting. High rates
attributed to "stress of living in a populated city."
|
Brazil
|
43%[105]
|
Quigley,2006
|
Study
measured prevalence of GI abdominal pain/cramping
|
Mexico
|
46%[105]
|
Quigley,2006
|
Study
measured prevalence of GI abdominal pain/cramping
|
Returning
Travelers:
A study of United States residents returning from international travel found a
high rate of IBS and persistent diarrhea which developed during travel and
persisted upon return. The study examined 83 subjects in Utah, most of whom
were returning missionaries. Of the 68 who completed the gastrointestinal questionnaire,
27 reported persistent diarrhea that developed while traveling, and 10 reported
persistent IBS that developed while traveling.[110]
[edit] Economic cost of IBS
The aggregate
cost of irritable bowel syndrome in the United States has been estimated at
$1.7-$10 billion in direct medical costs, with an additional $20 billion in
indirect costs, for a total of $21.7-$30 billion.[17]
A study by a managed care company comparing medical costs of IBS patients to
non-IBS controls identified a 49% annual increase in medical costs associated
with a diagnosis of IBS.[11]
A 2007 study from a managed care oganization found that IBS patients incurred
average annual direct costs of $5,049 and $406 in out-of-pocket expenses.[10]
A study of workers with IBS found that they reported a 34.6% loss in
productivity, corresponding to 13.8 hours lost per 40 hour week.[12]
A study of employer-related health costs from a Fortune 100 company conducted
with data from the 1990s found IBS patients incurred US $4527 in claims costs
vs. $3276 for controls.[111]
A study on Medicaid costs conducted in 2003 by the University of Georgia's
College of Pharmacy and Novartis found IBS was associated in an increase of $962 in Medicaid
costs in California, and $2191 in North Carolina. IBS patients had higher costs
for physician visits, outpatients visits, and prescription drugs. The study
suggested the costs associated with IBS were comparable to those found in
asthma patients.[112]
[edit] Research spending on
IBS
Further
information: NIH funding of IBS Research
The National Institutes of Health
provides a searchable database for grant awards since 1974 on its CRISP database, and
provides dollar amounts for recent awards on its Intramural
Grant Award Page. In 2006, the NIH awarded approximately 56 grants related
to IBS, totalling approximately $18.7 million.
[edit] History
One of the first
references to the concept of an "irritable bowel" appeared in the
Rocky Mountain Medical Journal in 1950.[113]
The term was used to categorize patients who developed symptoms of diarrhea,
abdominal pain, constipation, but where no well-recognized infective cause
could be found. Early theories suggested that the Irritable Bowel was caused by
a psychosomatic, or mental disorder.
[edit] See also
[edit] References
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b
Mayer EA (2008). "Clinical
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PMID 18420501. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18420501&promo=ONFLNS19.
- ^ Intestinal
Infection
- ^ Yang CM, Li YQ
(2007). "[The therapeutic effects of eliminating allergic foods
according to food-specific IgG antibodies in irritable bowel
syndrome]" (in Chinese). Zhonghua Nei Ke Za Zhi 46 (8):
6413. PMID 17967233.
- ^ a
b
c
Stark D, van Hal S, Marriott D, Ellis J, Harkness J (2007).
"Irritable bowel syndrome: a review on the role of intestinal
protozoa and the importance of their detection and diagnosis". Int.
J. Parasitol. 37 (1): 1120. doi:10.1016/j.ijpara.2006.09.009.
PMID 17070814.
- ^ a
b
Bercik P, Verdu EF, Collins SM (2005). "Is irritable bowel syndrome a
low-grade inflammatory bowel disease?". Gastroenterol. Clin. North
Am. 34 (2): 23545, vi-vii. doi:10.1016/j.gtc.2005.02.007.
PMID 15862932.
- ^ a
b
Quigley EM (2005). "Irritable bowel syndrome and inflammatory bowel
disease: interrelated diseases?". Chinese journal of digestive
diseases 6 (3): 12232. doi:10.1111/j.1443-9573.2005.00202.x.
PMID 16045602.
- ^ a
b
Simrιn M, Axelsson J, Gillberg R, Abrahamsson H, Svedlund J, Bjφrnsson ES
(2002). "Quality of life in inflammatory bowel disease in remission:
the impact of IBS-like symptoms and associated psychological
factors". Am. J. Gastroenterol. 97 (2): 38996. PMID 11866278.
- ^ a
b
Minderhoud IM, Oldenburg B, Wismeijer JA, van Berge Henegouwen GP, Smout
AJ (2004). "IBS-like symptoms in patients with inflammatory bowel
disease in remission; relationships with quality of life and coping
behavior". Dig. Dis. Sci. 49 (3): 46974. doi:10.1023/B:DDAS.0000020506.84248.f9.
PMID 15139501.
- ^ a
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Garcνa Rodrνguez LA, Ruigσmez A, Wallander MA, Johansson S, Olbe L (2000).
"Detection of colorectal tumor and inflammatory bowel disease during
follow-up of patients with initial diagnosis of irritable bowel
syndrome". Scand. J. Gastroenterol. 35 (3): 30611. doi:10.1080/003655200750024191.
PMID 10766326.
- ^ a
b
Nyrop KA, Palsson OS, Levy RL, Korff MV, Feld AD, Turner MJ, Whitehead WE.
(2007). "Costs of health care for irritable bowel syndrome, chronic
constipation, functional diarrhoea and functional abdominal pain.". Aliment
Pharmacol Ther 26 (2): 23748. PMID 17593069.
- ^ a
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Levy RL, Von Korff M, Whitehead WE, Stang P, Saunders K, Jhingran P,
Barghout V, Feld AD. (2001). "Costs of care for irritable bowel
syndrome patients in a health maintenance organization". Am J
Gastroenterol 96 (11): 31229. doi:10.1111/j.1572-0241.2001.05258.x.
PMID 11721759.
- ^ a
b
Parι P, Gray J, Lam S, et al. (2006). "Health-related quality
of life, work productivity, and health care resource utilization of
subjects with irritable bowel syndrome: baseline results from LOGIC
(Longitudinal Outcomes Study of Gastrointestinal Symptoms in Canada), a
naturalistic study". Clinical therapeutics 28 (10):
172635; discussion 17101. doi:10.1016/j.clinthera.2006.10.010.
PMID 17157129.
- ^ Maxion-Bergemann S,
Thielecke F, Abel F, Bergemann R (2006). "Costs of irritable bowel
syndrome in the UK and US". PharmacoEconomics 24 (1):
2137. doi:10.2165/00019053-200624010-00002.
PMID 16445300.
- ^ a
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