Irritable bowel syndrome: Difference between revisions
CosineKitty (talk | contribs) m Reverted 1 edit by 71.22.184.81 identified as vandalism to last revision by Sciencewatcher. using TW |
No edit summary |
||
Line 39: | Line 39: | ||
[[Image:Wiki ibs cause figures.png|thumb|200px|right|Prevalence of protozoal infections in industrialized countries (United States and Canada) in 21st century.<ref name="CMAJ_2006" /><ref name="pmid12224595">{{cite journal |author=Amin OM |title=Seasonal prevalence of intestinal parasites in the United States during 2000 |journal=Am. J. Trop. Med. Hyg. |volume=66 |issue=6 |pages=799–803 |year=2002 |pmid=12224595 |doi=}}</ref>]] |
[[Image:Wiki ibs cause figures.png|thumb|200px|right|Prevalence of protozoal infections in industrialized countries (United States and Canada) in 21st century.<ref name="CMAJ_2006" /><ref name="pmid12224595">{{cite journal |author=Amin OM |title=Seasonal prevalence of intestinal parasites in the United States during 2000 |journal=Am. J. Trop. Med. Hyg. |volume=66 |issue=6 |pages=799–803 |year=2002 |pmid=12224595 |doi=}}</ref>]] |
||
NO YOU MAY NOT HAS COOKIES THE DINOSAUR SAYS NO U FATTY. F OFF. an as-yet undiscovered active infection. Most recently, a study found that the antibiotic [[Rifaximin]] provides sustained relief for IBS patients.<ref name="pmid17043337">{{cite journal |author=Pimentel M, Park S, Mirocha J, Kane SV, Kong Y |title=The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial |journal=Ann. Intern. Med. |volume=145 |issue=8 |pages=557–63 |year=2006 |pmid=17043337 |doi=}}</ref> While some researchers see this as evidence that IBS is related to an undiscovered agent, others believe IBS patients suffer from overgrowth of [[Gut flora|intestinal flora]] and the antibiotics are effective in reducing the overgrowth (known as ''[[Small bowel bacterial overgrowth syndrome|small intestinal bacterial overgrowth]]'').<ref name="pmid17148502">{{cite journal |author=Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M |title=Small intestinal bacterial overgrowth in patients with irritable bowel syndrome |journal=Gut |volume=56 |issue=6 |pages=802–8 |year=2007 |pmid=17148502 |doi=10.1136/gut.2006.108712}}</ref> Other researchers have focused on an unrecognized [[protozoa]]l infection as a cause of IBS<ref name=Stark7/> as certain protozoal infections occur more frequently in IBS patients.<ref name="YAKOOB_2004">{{cite journal |author=Yakoob J, Jafri W, Jafri N, ''et al.'' |title=Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis |journal=Am. J. Trop. Med. Hyg. |volume=70 |issue=4 |pages=383–5 |year=2004 |pmid=15100450 |doi=}}</ref><ref name="GIACOM_1999">{{cite journal |author=Giacometti A, Cirioni O, Fiorentini A, Fortuna M, Scalise G |title=Irritable bowel syndrome in patients with Blastocystis hominis infection |journal=Eur. J. Clin. Microbiol. Infect. Dis. |volume=18 |issue=6 |pages=436–9 |year=1999 |pmid=10442423|doi=10.1007/s100960050314}}</ref> 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<ref name="QADRI_1989">{{cite journal |author=Qadri SM, al-Okaili GA, al-Dayel F |title=Clinical significance of Blastocystis hominis |journal=J. Clin. Microbiol. |volume=27 |issue=11 |pages=2407–9 |year=1989 |pmid=2808664 |doi= |pmc=267045}}</ref> though these reports are contested by some physicians.<ref name="MARKELL_1986">{{cite journal |author=Markell EK, Udkow MP |title=Blastocystis hominis: pathogen or fellow traveler? |journal=Am. J. Trop. Med. Hyg. |volume=35 |issue=5 |pages=1023–6 |year=1986 |pmid=3766850 |doi=}}</ref> 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]],<ref name="WINDSOR_2007">{{cite journal |author=Windsor J |title=B. hominis and D. fragilis: Neglected human protozoa |journal=British Biomedical Scientist |pages=524–7 |year=2007|doi= |url=http://www.ibms.org/index.cfm?method=publications.biomedical_scientist&subpage=contents_2007_July}}{{Dead link|date=November 2009}}</ref> 47% reported from the Department of Gastroenterology at [[Aga Khan University]] in Pakistan<ref name="YAKOOB_2004" /> and 18.1% reported from the Institute of Diseases and Public Health at [[University of Ancona]] in Italy.<ref name="GIACOM_1999" /> 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,<ref name="STENSVOLD_2006">{{cite journal |author=Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC |title=Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction |journal=J. Parasitol. |volume=92 |issue=5 |pages=1081–7 |year=2006 |pmid=17152954|doi=10.1645/GE-840R.1}}</ref> and ''Blastocystis'' may not respond to treatment with common antiprotozoals.<ref name="MARKELL_1986"/><ref name="pmid15250669">{{cite journal |author=Yakoob J, Jafri W, Jafri N, Islam M, Asim Beg M |title=In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome |journal=Br. J. Biomed. Sci. |volume=61 |issue=2 |pages=75–7 |year=2004 |pmid=15250669 |doi=}}</ref><ref name="pmid10357863">{{cite journal |author=Haresh K, Suresh K, Khairul Anus A, Saminathan S |title=Isolate resistance of Blastocystis hominis to metronidazole |journal=Trop. Med. Int. Health |volume=4 |issue=4 |pages=274–7 |year=1999 |pmid=10357863|doi=10.1046/j.1365-3156.1999.00398.x}}</ref><ref name="pmid10566723">{{cite journal |author=Ok UZ, Girginkardeşler N, Balcioğlu C, Ertan P, Pirildar T, Kilimcioğlu AA |title=Effect of trimethoprim-sulfamethaxazole in Blastocystis hominis infection |journal=Am. J. Gastroenterol. |volume=94 |issue=11 |pages=3245–7 |year=1999 |pmid=10566723|doi=10.1111/j.1572-0241.1999.01529.x}}</ref> |
''[[Blastocystis]]'' is a single-celled organism which has been reported to produce symptoms of abdominal pain, constipation and diarrhea in patients<ref name="QADRI_1989">{{cite journal |author=Qadri SM, al-Okaili GA, al-Dayel F |title=Clinical significance of Blastocystis hominis |journal=J. Clin. Microbiol. |volume=27 |issue=11 |pages=2407–9 |year=1989 |pmid=2808664 |doi= |pmc=267045}}</ref> though these reports are contested by some physicians.<ref name="MARKELL_1986">{{cite journal |author=Markell EK, Udkow MP |title=Blastocystis hominis: pathogen or fellow traveler? |journal=Am. J. Trop. Med. Hyg. |volume=35 |issue=5 |pages=1023–6 |year=1986 |pmid=3766850 |doi=}}</ref> 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]],<ref name="WINDSOR_2007">{{cite journal |author=Windsor J |title=B. hominis and D. fragilis: Neglected human protozoa |journal=British Biomedical Scientist |pages=524–7 |year=2007|doi= |url=http://www.ibms.org/index.cfm?method=publications.biomedical_scientist&subpage=contents_2007_July}}{{Dead link|date=November 2009}}</ref> 47% reported from the Department of Gastroenterology at [[Aga Khan University]] in Pakistan<ref name="YAKOOB_2004" /> and 18.1% reported from the Institute of Diseases and Public Health at [[University of Ancona]] in Italy.<ref name="GIACOM_1999" /> 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,<ref name="STENSVOLD_2006">{{cite journal |author=Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC |title=Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction |journal=J. Parasitol. |volume=92 |issue=5 |pages=1081–7 |year=2006 |pmid=17152954|doi=10.1645/GE-840R.1}}</ref> and ''Blastocystis'' may not respond to treatment with common antiprotozoals.<ref name="MARKELL_1986"/><ref name="pmid15250669">{{cite journal |author=Yakoob J, Jafri W, Jafri N, Islam M, Asim Beg M |title=In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome |journal=Br. J. Biomed. Sci. |volume=61 |issue=2 |pages=75–7 |year=2004 |pmid=15250669 |doi=}}</ref><ref name="pmid10357863">{{cite journal |author=Haresh K, Suresh K, Khairul Anus A, Saminathan S |title=Isolate resistance of Blastocystis hominis to metronidazole |journal=Trop. Med. Int. Health |volume=4 |issue=4 |pages=274–7 |year=1999 |pmid=10357863|doi=10.1046/j.1365-3156.1999.00398.x}}</ref><ref name="pmid10566723">{{cite journal |author=Ok UZ, Girginkardeşler N, Balcioğlu C, Ertan P, Pirildar T, Kilimcioğlu AA |title=Effect of trimethoprim-sulfamethaxazole in Blastocystis hominis infection |journal=Am. J. Gastroenterol. |volume=94 |issue=11 |pages=3245–7 |year=1999 |pmid=10566723|doi=10.1111/j.1572-0241.1999.01529.x}}</ref> |
Revision as of 15:16, 3 February 2010
This article needs attention from an expert in Medicine. Please add a reason or a talk parameter to this template to explain the issue with the article.(January 2009) |
Irritable bowel syndrome | |
---|---|
Specialty | Gastroenterology |
Irritable bowel syndrome (IBS or spastic colon) is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause.[1] In some cases, the symptoms are relieved by bowel movements.[2] 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), a stressful life event, or 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.[2]
Several conditions may present as IBS including celiac disease, mild infections, parasitic infections like giardiasis[3], 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.[4][5]
IBS does not lead to more serious conditions in most patients.[6][7][8][9][10] But it is a source of chronic pain, fatigue, and other symptoms, and it increases a patient's medical costs,[11][12] and contributes to work absenteeism.[13][14] Researchers have reported that the high prevalence of IBS,[15][16][17] in conjunction with increased costs produces a disease with a high societal cost.[18] It is also regarded as a chronic illness and can dramatically affect the quality of a sufferer's life.
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[19]). 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).
Symptoms
The primary symptoms of IBS are abdominal pain or discomfort in association with frequent diarrhea or constipation, a change in bowel habits.[20] There may also be urgency for bowel movements, a feeling of incomplete evacuation (tenesmus), bloating or abdominal distention.[21] People with IBS more commonly than others have gastroesophageal reflux, symptoms relating to the genitourinary system, psychiatric symptoms such as depression and anxiety, fibromyalgia, chronic fatigue syndrome, headache and backache.[21][22]
Causes
The cause of IBS is unknown, 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.[23]. 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.[24] A 1997 study published in Gut magazine suggested that IBS was associated with a "derailing of the brain-gut axis."[25] Psychological factors may be important in the etiology of IBS [22].
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.
Active infections
NO YOU MAY NOT HAS COOKIES THE DINOSAUR SAYS NO U FATTY. F OFF. an as-yet undiscovered active infection. Most recently, a study found that the antibiotic Rifaximin provides sustained relief for IBS patients.[28] 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).[29] Other researchers have focused on an unrecognized protozoal infection as a cause of IBS[5] as certain protozoal infections occur more frequently in IBS patients.[30][31] 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[32] though these reports are contested by some physicians.[33] 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,[34] 47% reported from the Department of Gastroenterology at Aga Khan University in Pakistan[30] and 18.1% reported from the Institute of Diseases and Public Health at University of Ancona in Italy.[31] 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,[35] and Blastocystis may not respond to treatment with common antiprotozoals.[33][36][37][38]
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.[26][39] 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.[40] Researchers have noted that methods used clinically may fail to detect some Dientamoeba fragilis infections.[39] It is also found in people without IBS.[41]
Diagnosis
There is no specific laboratory or imaging test which can be performed to diagnose irritable bowel syndrome. Diagnosis of IBS involves excluding conditions which produce IBS-like symptoms, and then following a procedure to categorize the patient's symptoms. Ruling out parasitic infections, lactose intolerance, small intestinal bacterial overgrowth and celiac disease is recommended for all patients before a diagnosis of irritable bowel syndrome is made. In patients over 50 years old it is recommended that they undergo a screening colonoscopy. .[42]
Differential diagnosis
Because there are many causes of diarrhea that give IBS-like symptoms, the American Gastroenterological Association 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.[42] 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.[43] 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.[43]
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.[44] On this line is a recent study,[45] which showed that constipation and/or diarrhea seems to be different manifestations of the same underlying condition, that is a build-up of fecal retention reservoirs in the colon. Abdominal X-rays were analyzed for colon transit time and fecal distribution, which correlated significantly with bloating and abdominal pain. Thus a group of patients were identified with an increased fecal loading compared to controls, but having a colon transit time equal or less to the controls. This suggest that defecation patterns do not reflect the amount of feces in the colon and is called hidden constipation. This phenomenon may be linked to bacterial overgrowth.
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, coeliac disease,[46] helicobacter pylori,[47][48] parasites.[5][49][50] See the 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.[51] 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.[52]
Comorbidities
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.[53] 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.[22]
- Inflammatory bowel disease (IBD): Some researchers have suggested that IBS is a type of low-grade inflammatory bowel disease.[6] Researchers have suggested that IBS and IBD are interrelated diseases,[7] noting that patients with IBD experience IBS-like symptoms when their IBD is in remission.[8][9] A 3-year study found that patients diagnosed with IBS were 16.3 times more likely to develop IBD during the study period.[10] 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.[54] A 2005 study reported that IBS patients are 87% more likely to undergo abdominal and pelvic surgery, and three times more likely to undergo gallbladder surgery.[55] A study published in Gastroenterology came to similar conclusions, and also noted IBS patients were twice as likely to undergo hysterectomy.[56]
- Endometriosis: One study reported a statistically significant link between migraine headaches, IBS, and endometriosis.[57]
- 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.[58]
Management
A number of treatments have been found to be better than placebo including: fiber, antispasmodics, and peppermint oil.[59]
Diet
Some people with IBS likely have food intolerances but at present the evidence base is not strong enough to restrictive diets.[60] 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]
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.[62]
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.[63]
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.[64][65]
It also appears that some foods are more difficult for the gut as evidenced by elevated food-specific IgG4 antibodies being present,[66][67] while others increase colonic contractions, which may be painful, due to increased visceral sensitivity in IBS sufferers.[68]
- Fiber
There is convincing evidence that soluble fiber supplementation (e.g. psyllium) is effective in the general IBS population but insoluble fiber (e.g. bran) has not been found to be effective for IBS.[69] However, in some people fiber supplementation may even aggravate symptoms.[60] Fiber might be beneficial in those who have a predominance of constipation. 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] One meta-analysis found that only soluble fiber improved global symptoms of irritable bowel, but neither type of fiber reduced pain.[70] However, an updated meta-analysis by the same authors found that soluble fiber reduced symptoms .[71] Positive studies have used 10-30 grams per day of psyllium seed.[72][73] 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[74] An uncontrolled study noted increased symptoms with insoluble fibers.[75] It is unclear if these symptoms are truly increased compared with a control group. If the symptoms are increased, it is unclear if these patients were diarrhea predominant (which can be exacerbated by insoluble fiber[76][77]), or if the increase is temporary before benefit occurs.
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.[78][79][80]
Drugs affecting serotonin (5-HT) in the intestines can help reduce symptoms.[81] Serotonin stimulates the gut motility and so agonists can help constipation-predominate irritable bowel, while antagonists can help diarrhea-predominant irritable bowel.
- Laxatives
For patients who do not adequately respond to dietary fiber, osmotic laxatives such as polyethylene glycol, sorbitol, and lactulose can help avoid 'cathartic colon' which has been associated with stimulant laxatives.[82] 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.
- Antispasmodics
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.[78] 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]
- Tricyclic antidepressants
There is strong evidence that low doses of tricyclic antidepressants can be effective for irritable bowel syndrome. There is little evidence of effectiveness of other antidepressant classes such as the SSRIs.[60][69]
- 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.[83]
- 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[84] and randomized controlled trials[85][86][87] support this role.
- Serotonin antagonists
- Alosetron, a selective 5-HT3 antagonist for IBS-D and cilansetron, also a selective 5-HT3 antagonist were trialed for irritable bowel syndrome but due to severe adverse effects namely ischemic colitis and severe constipation are not available or recommended for irritable bowel syndrome.[60]
- Other agents
Magnesium Aluminum Silicates and alverine citrate drugs can be effective for irritable bowel syndrome.[60]
There is conflicting evidence about the benefit of antidepressants in IBS. Some meta-analysis have found a benefit while others have not.[88] A meta-analysis of randomized controlled trials of mainly TCAs found 3 patients have to be treated with TCAs for one patient to improve.[89] A separate randomized controlled trial found that TCAs are best for patients with diarrhea-predominant IBS.[90]
Recent studies have suggested that rifaximin can be used as an effective treatment for abdominal bloating and flatulence,[28][91] giving more credibility to the potential role of bacterial overgrowth in some patients with IBS.[92]
Domperidone, a dopamine receptor blocker and a parasympathomimetic, has been shown to reduce bloating and abdominal pain as a result of an accelerated colon transit time and reduced faecal load, that is a relief from hidden constipation; defecation was similarly improved.[93].
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.[94]
Psychotherapy
The mind-body or brain-gut interactions has been proposed for irritable bowel syndrome and is gaining increasing research attention.[69] For some patients psychological therapies may help with symptoms. Cognitive behavioural therapy and hypnosis have been found to be the most benefitial. Hypnosis can improve mental wellbeing and cognitive behavioural therapy can provide psychological coping strategies for dealing with distressing symptoms as well as help suppress thoughts and behaviours which increase the symptoms of irritable bowel syndrome.[60][69] Cognitive behavioral therapy has been found to improve symptoms in a number of studies.[95][96] Relaxation therapy has also been found to be helpful.[97]
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.[98]
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%).
Alternative treatments
Due to often unsatisfactory results from medical treatments for IBS up to 50 percent of people turn to complementary alternative medicine.[69]
- Probiotics
Probiotics can be beneficial in the treatment of IBS, taking 10 billion to 100 billion beneficial bacteria per day is recommended for beneficial results. However, further research is needed on individual strains of beneficial bacteria for more refined recommendations.[69][99] Many different type have be found to be effective including: Lactobacillus plantarum[100] and Bifidobacteria infantis;[101] however, one review found that only Bifidobacteria infantis showed efficacy.[102] Some yoghurt is made using probiotics that may help ease symptoms of irritable bowel syndrome.[103]
- 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.[104]
- Peppermint oil
Enteric coated peppermint oil capsules has been advocated for IBS symptoms in adults and children.[105] There is good evidence of a beneficial effect of and it is recommended that peppermint is trialed in all irritable bowel syndrome patients. Safety during pregnancy has not been established however and caution is required not to chew or break the enteric coating otherwise gastroesophageal reflux may occur as a result of lower esophageal sphincter relaxation. Occasionally nausea and perianal burning occur as side effects.[69]
- Yoga
Yoga may be effective for some sufferers of irritable bowel syndrome.[60]
- Herbal remedies
There is little evidence for the effectiveness of herbal remedies for irritable bowel syndrome. They also have the potential for adverse effects and are therefore not recommended.[69]
- Acupuncture
Acupuncture may be worth a trial in select patients but the evidence base for effectiveness is weak.[69] 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.[106]
Epidemiology
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:
Percentage of Population Reporting Symptoms of IBS in Various Studies from Various Geographic Areas | |||
---|---|---|---|
Country | Prevalence | Author/Year | Notes |
Canada | 6%[15] | Boivin,2001 | |
Japan | 10%[107] | Quigley,2006 | Study measured prevalence of GI abdominal pain/cramping |
United Kingdom | 8.2%[108]
10.5%[16] |
Ehlin,2003
Wilson,2004 |
Prevalence increased substantially 1970-2004 |
United States | 14.1%[109] | Hungin, 2005 | Most undiagnosed |
United States | 15%[15] | Boivin,2001 | Estimate |
Pakistan | 14%[110] | Jafri, 2007 | Much more common in 16-30 age range. Of IBS patients, 56% male, 44% female |
Pakistan | 34%[111] | Jafri,2005 | College students |
Mexico City | 35%[17] | Schmulson, 2006 | n=324. Also measured functional diarrhea and functional vomiting. High rates attributed to "stress of living in a populated city." |
Brazil | 43%[107] | Quigley,2006 | Study measured prevalence of GI abdominal pain/cramping |
Mexico | 46%[107] | Quigley,2006 | Study measured prevalence of GI abdominal pain/cramping |
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.[112]
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.
Economics
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.[18] 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.[12] 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.[11] 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.[13] 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.[114] 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.[115]
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.
See also
References
- ^ "irritable bowel syndrome" at Dorland's Medical Dictionary
- ^ a b Mayer EA (2008). "Clinical practice. Irritable bowel syndrome". N. Engl. J. Med. 358 (16): 1692–9. doi:10.1056/NEJMcp0801447. PMID 18420501.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help) - ^ Intestinal Infection[dead link]
- ^ Yang CM, Li YQ (2007). "[The therapeutic effects of eliminating allergic foods according to food-specific IgG antibodies in irritable bowel syndrome]". Zhonghua Nei Ke Za Zhi (in Chinese). 46 (8): 641–3. 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): 11–20. doi:10.1016/j.ijpara.2006.09.009. PMID 17070814.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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): 235–45, vi–vii. doi:10.1016/j.gtc.2005.02.007. PMID 15862932.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Quigley EM (2005). "Irritable bowel syndrome and inflammatory bowel disease: interrelated diseases?". Chinese journal of digestive diseases. 6 (3): 122–32. doi:10.1111/j.1443-9573.2005.00202.x. PMID 16045602.
- ^ a b Simrén M, Axelsson J, Gillberg R, Abrahamsson H, Svedlund J, Björnsson 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): 389–96. doi:10.1111/j.1572-0241.2002.05475.x. PMID 11866278.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ 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): 469–74. doi:10.1023/B:DDAS.0000020506.84248.f9. PMID 15139501.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b García Rodríguez LA, Ruigómez 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): 306–11. doi:10.1080/003655200750024191. PMID 10766326.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Nyrop KA, Palsson OS, Levy RL, Korff MV, Feld AD, Turner MJ, Whitehead WE (2007). [www3.interscience.wiley.com/cgi-bin/fulltext/117987809/HTMLSTART "Costs of health care for irritable bowel syndrome, chronic constipation, functional diarrhoea and functional abdominal pain"]. Aliment Pharmacol Ther. 26 (2): 237–48. doi:10.1111/j.1365-2036.2007.03370.x. PMID 17593069.
{{cite journal}}
: Check|url=
value (help)CS1 maint: multiple names: authors list (link) - ^ a b 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): 3122–9. doi:10.1111/j.1572-0241.2001.05258.x. PMID 11721759.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Paré 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): 1726–35, discussion 1710–1. doi:10.1016/j.clinthera.2006.10.010. PMID 17157129.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Maxion-Bergemann S, Thielecke F, Abel F, Bergemann R (2006). "Costs of irritable bowel syndrome in the UK and US". PharmacoEconomics. 24 (1): 21–37. doi:10.2165/00019053-200624010-00002. PMID 16445300.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c
Boivin M (2001). "Socioeconomic impact of irritable bowel syndrome in Canada". Can. J. Gastroenterol. 15 (Suppl B): 8B–11B. PMID 11694908.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help) - ^ a b Wilson S, Roberts L, Roalfe A, Bridge P, Singh S (2004). "Prevalence of irritable bowel syndrome: a community survey". Br J Gen Pract. 54 (504): 495–502. PMC 1324800. PMID 15239910.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Schmulson M, Ortiz O, Santiago-Lomeli M, Gutierrez-Reyes G, Gutierrez-Ruiz MC, Robles-Diaz G, Morgan D (2006). "Frequency of functional bowel disorders among healthy volunteers in Mexico City" (PDF). Dig Dis. 24 (3–4): 342. doi:10.1159/000092887. PMID 16849861.
{{cite journal}}
: Unknown parameter|oissue=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Hulisz D (2004). "The burden of illness of irritable bowel syndrome: current challenges and hope for the future". J Manag Care Pharm. 10 (4): 299–309. PMID 15298528.
- ^ Holten KB, Wetherington A, Bankston L (2003). "Diagnosing the patient with abdominal pain and altered bowel habits: is it irritable bowel syndrome?". Am Fam Physician. 67 (10): 2157–62. PMID 12776965.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Schmulson MW, Chang L (1999). "Diagnostic approach to the patient with irritable bowel syndrome". Am. J. Med. 107 (5A): 20S–26S. doi:10.1016/S0002-9343(99)00278-8. PMID 10588169.
- ^ a b Talley NJ (2006). "Irritable bowel syndrome". Intern Med J. 36 (11): 724–8. doi:10.1111/j.1445-5994.2006.01217.x. PMC 1761148. PMID 17040359.
- ^ a b c Whitehead WE, Palsson O, Jones KR (2002). "Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?". Gastroenterology. 122 (4): 1140–56. doi:10.1053/gast.2002.32392. PMID 11910364.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Thabane M, Kottachchi DT, Marshall JK (2007). [www3.interscience.wiley.com/cgi-bin/fulltext/117987841/HTMLSTART "Systematic review and meta-analysis: The incidence and prognosis of post-infectious irritable bowel syndrome"]. Aliment Pharmacol Ther. 26 (4): 535–44. doi:10.1111/j.1365-2036.2007.03399.x. PMID 17661757.
{{cite journal}}
: Check|url=
value (help); Unknown parameter|doi_brokendate=
ignored (|doi-broken-date=
suggested) (help)CS1 maint: multiple names: authors list (link) - ^ Fukudo S, Nomura T, Muranaka M, Taguchi F (1993). "Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study". J. Clin. Gastroenterol. 17 (2): 133–41. doi:10.1097/00004836-199309000-00009. PMID 8031340.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Orr WC, Crowell MD, Lin B, Harnish MJ, Chen JD (1997). "Sleep and gastric function in irritable bowel syndrome: derailing the brain-gut axis". Gut. 41 (3): 390–3. PMC 1891498. PMID 9378397.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Lagacé-Wiens PR, VanCaeseele PG, Koschik C (2006). "Dientamoeba fragilis: an emerging role in intestinal disease". CMAJ : Canadian Medical Association journal = Journal De l'Association Medicale Canadienne. 175 (5): 468–9. doi:10.1503/cmaj.060265. PMC 1550747. PMID 16940260.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Amin OM (2002). "Seasonal prevalence of intestinal parasites in the United States during 2000". Am. J. Trop. Med. Hyg. 66 (6): 799–803. PMID 12224595.
- ^ a b Pimentel M, Park S, Mirocha J, Kane SV, Kong Y (2006). "The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial". Ann. Intern. Med. 145 (8): 557–63. PMID 17043337.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) Cite error: The named reference "pmid17043337" was defined multiple times with different content (see the help page). - ^ Posserud I, Stotzer PO, Björnsson ES, Abrahamsson H, Simrén M (2007). "Small intestinal bacterial overgrowth in patients with irritable bowel syndrome". Gut. 56 (6): 802–8. doi:10.1136/gut.2006.108712. PMID 17148502.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Yakoob J, Jafri W, Jafri N; et al. (2004). "Irritable bowel syndrome: in search of an etiology: role of Blastocystis hominis". Am. J. Trop. Med. Hyg. 70 (4): 383–5. PMID 15100450.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ a b Giacometti A, Cirioni O, Fiorentini A, Fortuna M, Scalise G (1999). "Irritable bowel syndrome in patients with Blastocystis hominis infection". Eur. J. Clin. Microbiol. Infect. Dis. 18 (6): 436–9. doi:10.1007/s100960050314. PMID 10442423.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Qadri SM, al-Okaili GA, al-Dayel F (1989). "Clinical significance of Blastocystis hominis". J. Clin. Microbiol. 27 (11): 2407–9. PMC 267045. PMID 2808664.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Markell EK, Udkow MP (1986). "Blastocystis hominis: pathogen or fellow traveler?". Am. J. Trop. Med. Hyg. 35 (5): 1023–6. PMID 3766850.
- ^ Windsor J (2007). "B. hominis and D. fragilis: Neglected human protozoa". British Biomedical Scientist: 524–7.[dead link]
- ^ Stensvold R, Brillowska-Dabrowska A, Nielsen HV, Arendrup MC (2006). "Detection of Blastocystis hominis in unpreserved stool specimens by using polymerase chain reaction". J. Parasitol. 92 (5): 1081–7. doi:10.1645/GE-840R.1. PMID 17152954.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Yakoob J, Jafri W, Jafri N, Islam M, Asim Beg M (2004). "In vitro susceptibility of Blastocystis hominis isolated from patients with irritable bowel syndrome". Br. J. Biomed. Sci. 61 (2): 75–7. PMID 15250669.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Haresh K, Suresh K, Khairul Anus A, Saminathan S (1999). "Isolate resistance of Blastocystis hominis to metronidazole". Trop. Med. Int. Health. 4 (4): 274–7. doi:10.1046/j.1365-3156.1999.00398.x. PMID 10357863.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Ok UZ, Girginkardeşler N, Balcioğlu C, Ertan P, Pirildar T, Kilimcioğlu AA (1999). "Effect of trimethoprim-sulfamethaxazole in Blastocystis hominis infection". Am. J. Gastroenterol. 94 (11): 3245–7. doi:10.1111/j.1572-0241.1999.01529.x. PMID 10566723.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Stensvold CR, Arendrup MC, Mølbak K, Nielsen HV (2007). "The prevalence of Dientamoeba fragilis in patients with suspected enteroparasitic disease in a metropolitan area in Denmark". Clin. Microbiol. Infect. 13 (8): 839–42. doi:10.1111/j.1469-0691.2007.01760.x. PMID 17610603.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Borody T, Warren E, Wettstein A; et al. (2002). "Eradication of Dientamoeba fragilis can resolve IBS-like symptoms". J Gastroenterol Hepatol. 17 (Suppl, pages=A103).
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Missing pipe in:|issue=
(help)CS1 maint: multiple names: authors list (link) - ^
Windsor JJ, Macfarlane L (2005). "Irritable bowel syndrome: the need to exclude Dientamoeba fragilis". Am. J. Trop. Med. Hyg. 72 (5): 501, author reply 501–2. PMID 15891119. Retrieved 2009-11-04.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b Yawn BP, Lydick E, Locke GR, Wollan PC, Bertram SL, Kurland MJ (2001). "Do published guidelines for evaluation of irritable bowel syndrome reflect practice?". BMC gastroenterology. 1: 11. doi:10.1186/1471-230X-1-11. PMC 59674. PMID 11701092.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Fass R, Longstreth GF, Pimentel M; et al. (2001). "Evidence- and consensus-based practice guidelines for the diagnosis of irritable bowel syndrome". Arch. Intern. Med. 161 (17): 2081–8. doi:10.1001/archinte.161.17.2081. PMID 11570936.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Talley NJ (2006). "A unifying hypothesis for the functional gastrointestinal disorders: really multiple diseases or one irritable gut?". Reviews in gastroenterological disorders. 6 (2): 72–8. PMID 16699476.
- ^ name="RAAHAVE D, Christensen E, Loud FB, Knudsen LL.Correlation of bowel symptoms with colonic transit, length, and fecal load in functional fecal retention. Dan Med Bull 2009;56:83-8
- ^ Spiegel BM, DeRosa VP, Gralnek IM, Wang V, Dulai GS (2004). "Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost-effectiveness analysis". Gastroenterology. 126 (7): 1721–32. doi:10.1053/j.gastro.2004.03.012. PMID 15188167.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Su YC, Wang WM, Wang SY; et al. (2000). "The association between Helicobacter pylori infection and functional dyspepsia in patients with irritable bowel syndrome". Am. J. Gastroenterol. 95 (8): 1900–5. doi:10.1111/j.1572-0241.2000.02252.x. PMID 10950033.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Gerards C, Leodolter A, Glasbrenner B, Malfertheiner P (2001). "H. pylori infection and visceral hypersensitivity in patients with irritable bowel syndrome". Dig Dis. 19 (2): 170–3. doi:10.1159/000050673. PMID 11549828.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Grazioli B, Matera G, Laratta C; et al. (2006). "Giardia lamblia infection in patients with irritable bowel syndrome and dyspepsia: a prospective study". World J. Gastroenterol. 12 (12): 1941–4. PMID 16610003.
{{cite journal}}
: Explicit use of et al. in:|author=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Vernia P, Ricciardi MR, Frandina C, Bilotta T, Frieri G (1995). "Lactose malabsorption and irritable bowel syndrome. Effect of a long-term lactose-free diet". The Italian journal of gastroenterology. 27 (3): 117–21. PMID 7548919.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^
American College of Gastroenterology Task Force on Irritable Bowel Syndrome (2009). [www.nature.com/ajg/journal/v104/n1s/pdf/ajg2008122a.pdf "An Evidence-Based Systematic Review on the Management of Irritable Bowel Syndrome"] (PDF). Am J Gastroenterology. pp. S1–S35. doi:10.1038/ajg.2008.122.
{{cite web}}
: Check|url=
value (help); Unknown parameter|month=
ignored (help) - ^ Professor C Heather Ashton (1987). "Benzodiazepine Withdrawal: Outcome in 50 Patients". British Journal of Addiction. 82: 655–671.
- ^ Cole JA, Rothman KJ, Cabral HJ, Zhang Y, Farraye FA (2006). "Migraine, [[fibromyalgia]], and depression among people with IBS: a prevalence study". BMC gastroenterology. 6: 26. doi:10.1186/1471-230X-6-26. PMC 1592499. PMID 17007634.
{{cite journal}}
: URL–wikilink conflict (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Corazziari E, Attili AF, Angeletti C, De Santis A (2008). "Gallstones, cholecystectomy and irritable bowel syndrome (IBS) MICOL population-based study". Dig Liver Dis. 40 (12): 944–50. doi:10.1016/j.dld.2008.02.013. PMID 18406218.
{{cite journal}}
:|first2=
missing|last2=
(help);|first3=
missing|last3=
(help);|first4=
missing|last4=
(help)CS1 maint: multiple names: authors list (link) - ^ Cole JA, Yeaw JM, Cutone JA; et al. (2005). "The incidence of abdominal and pelvic surgery among patients with irritable bowel syndrome". Dig. Dis. Sci. 50 (12): 2268–75. doi:10.1007/s10620-005-3047-1. PMID 16416174.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Longstreth GF, Yao JF (2004). "Irritable bowel syndrome and surgery: a multivariable analysis". Gastroenterology. 126 (7): 1665–73. doi:10.1053/j.gastro.2004.02.020. PMID 15188159.
- ^ Tietjen GE, Bushnell CD, Herial NA, Utley C, White L, Hafeez F (2007). "Endometriosis is associated with prevalence of comorbid conditions in migraine". Headache. 47 (7): 1069–78. doi:10.1111/j.1526-4610.2007.00784.x. PMID 17635599.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ "Interstitial cystitis: Risk factors". Mayo Clinic. January 20, 2009.
- ^ Ford AC, Talley NJ, Spiegel BM; et al. (2008). "Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis". BMJ. 337: a2313. doi:10.1136/bmj.a2313. PMC 2583392. PMID 19008265.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ a b c d e f g Ducrotté, P. (2007). "[Irritable bowel syndrome: current treatment options]". Presse Med. 36 (11 Pt 2): 1619–26. doi:10.1016/j.lpm.2007.03.008. PMID 17490849.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Böhmer CJ, Tuynman HA (2001). "The effect of a lactose-restricted diet in patients with a positive lactose tolerance test, earlier diagnosed as irritable bowel syndrome: a 5-year follow-up study". Eur J Gastroenterol Hepatol. 13 (8): 941–4. doi:10.1097/00042737-200108000-00011. PMID 11507359.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ Atkinson W, Sheldon TA, Shaath N, Whorwell PJ (2004). "Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial". Gut. 53 (10): 1459–64. doi:10.1136/gut.2003.037697. PMC 1774223. PMID 15361495.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Sjölund K, Ekman R, Lindgren S, Rehfeld J (1996). "Disturbed motilin and cholecystokinin release in the irritable bowel syndrome". Scand J Gastroenterol. 31 (11): 1110–4. doi:10.3109/00365529609036895. PMID 8938905.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Caldarella MP, Milano A, Laterza F, Sacco F, Balatsinou C, Lapenna D, Pierdomenico SD, Cuccurullo F, Neri M (2005). "Visceral sensitivity and symptoms in patients with constipation- or diarrhea-predominant irritable bowel syndrome (IBS): effect of a low-fat intraduodenal infusion". Am J Gastroenterol. 100 (2): 383–9. doi:10.1111/j.1572-0241.2005.40100.x. PMID 15667496.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Choi, Y. Fats, Fructose May Contribute to IBS Symptoms. ACG 68th Annual Scientific Meeting: Abstract 21, presented October 13, 2003; Abstract 547, presented October 14, 2003.
- ^ Zar S, Benson MJ, Kumar D (2005). "Food-specific serum IgG4 and IgE titers to common food antigens in irritable bowel syndrome". Am J Gastroenterol. 100 (7): 1550–7. doi:10.1111/j.1572-0241.2005.41348.x. PMID 15984980.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Zar S, Mincher L, Benson MJ, Kumar D (2005). "Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome". Scand J Gastroenterol. 40 (7): 800–7. doi:10.1080/00365520510015593. PMID 16109655.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Mayer EA, Berman S, Suyenobu B, Labus J, Mandelkern MA, Naliboff BD, Chang L (2005). "Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis". Pain. 115 (3): 398–409. doi:10.1016/j.pain.2005.03.023. PMID 15911167.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c d e f g h i Shen, YH.; Nahas, R. (2009). "Complementary and alternative medicine for treatment of irritable bowel syndrome". Can Fam Physician. 55 (2): 143–8. PMC 2642499. PMID 19221071.
{{cite journal}}
: Unknown parameter|month=
ignored (help) - ^ a b Bijkerk C, Muris J, Knottnerus J, Hoes A, de Wit N (2004). "Systematic review: the role of different types of fiber in the treatment of irritable bowel syndrome". Aliment Pharmacol Ther. 19 (3): 245–51. doi:10.1111/j.0269-2813.2004.01862.x. PMID 14984370.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Bijkerk C, de Wit N, Muris JW; et al. (2009). "Systematic Soluble or insoluble fiber in irritable bowel syndrome in primary care? Randomised placebo controlled trial". BMJ. 339 (b): 3154-. PMID 19713235.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Prior A, Whorwell P (1987). "Double blind study of ispaghula in irritable bowel syndrome". Gut. 28 (11): 1510–3. doi:10.1136/gut.28.11.1510. PMC 1433676. PMID 3322956.
- ^ Jalihal A, Kurian G (1990). "Ispaghula therapy in irritable bowel syndrome: improvement in overall well-being is related to reduction in bowel dissatisfaction". J Gastroenterol Hepatol. 5 (5): 507–13. doi:10.1111/j.1440-1746.1990.tb01432.x. PMID 2129822.
- ^ Kumar A, Kumar N, Vij J, Sarin S, Anand B (1987). "Optimum dosage of ispaghula husk in patients with irritable bowel syndrome: correlation of symptom relief with whole gut transit time and stool weight". Gut. 28 (2): 150–5. doi:10.1136/gut.28.2.150. PMC 1432983. PMID 3030900.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Francis CY, Whorwell PJ (1994). "Bran and irritable bowel syndrome: time for reappraisal". Lancet. 344 (8914): 39–40. doi:10.1016/S0140-6736(94)91055-3. PMID 7912305.
- ^ Cann P, Read N, Holdsworth C, Barends D (1984). "Role of loperamide and placebo in management of irritable bowel syndrome (IBS)". Dig Dis Sci. 29 (3): 239–47. doi:10.1007/BF01296258. PMID 6365490.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Cann P, Read N, Holdsworth C (1984). "What is the benefit of coarse wheat bran in patients with irritable bowel syndrome?". Gut. 25 (2): 168–73. doi:10.1136/gut.25.2.168. PMC 1432266. PMID 6319244.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b Quartero A, Meineche-Schmidt V, Muris J, Rubin G, de Wit N (2005). "Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome". Cochrane Database Syst Rev (2): CD003460. doi:10.1002/14651858.CD003460.pub2. PMID 15846668.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum A (2004). "Meta-analysis: The treatment of irritable bowel syndrome". Aliment Pharmacol Ther. 20 (11–12): 1253–69. doi:10.1111/j.1365-2036.2004.02267.x. PMID 15606387.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Jailwala J, Imperiale T, Kroenke K (2000). "Pharmacologic treatment of the irritable bowel syndrome: a systematic review of randomized, controlled trials". Ann Intern Med. 133 (2): 136–47. PMID 10896640.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Talley N (2001). "Serotoninergic neuroenteric modulators". Lancet. 358 (9298): 2061–8. doi:10.1016/S0140-6736(01)07103-3. PMID 11755632.
- ^ Joo J, Ehrenpreis E, Gonzalez L, Kaye M, Breno S, Wexner S, Zaitman D, Secrest K (1998). "Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited". J Clin Gastroenterol. 26 (4): 283–6. doi:10.1097/00004836-199806000-00014. PMID 9649012.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Evans B, Clark W, Moore D, Whorwell P (2004). "Tegaserod for the treatment of irritable bowel syndrome". Cochrane Database Syst Rev (1): CD003960. doi:10.1002/14651858.CD003960.pub2. PMID 14974049.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Tack J, Broekaert D, Fischler B, Oudenhove L, Gevers A, Janssens J (2006). "A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome". Gut. 55 (8): 1095–103. doi:10.1136/gut.2005.077503. PMC 1856276. PMID 16401691.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Vahedi H, Merat S, Rashidioon A, Ghoddoosi A, Malekzadeh R (2005). "The effect of fluoxetine in patients with pain and constipation-predominant irritable bowel syndrome: a double-blind randomized-controlled study". Aliment Pharmacol Ther. 22 (5): 381–5. doi:10.1111/j.1365-2036.2005.02566.x. PMID 16128675.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B (2003). "The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome". Gastroenterology. 124 (2): 303–17. doi:10.1053/gast.2003.50055. PMID 12557136.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Tabas G, Beaves M, Wang J, Friday P, Mardini H, Arnold G (2004). "Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial". Am J Gastroenterol. 99 (5): 914–20. doi:10.1111/j.1572-0241.2004.04127.x. PMID 15128360.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ "UpToDate Inc" (subscription required).
- ^ Jackson J, O'Malley P, Tomkins G, Balden E, Santoro J, Kroenke K (2000). "Treatment of functional gastrointestinal disorders with antidepressant medications: a meta-analysis". Am J Med. 108 (1): 65–72. doi:10.1016/S0002-9343(99)00299-5. PMID 11059442.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Drossman D, Toner B, Whitehead W, Diamant N, Dalton C, Duncan S, Emmott S, Proffitt V, Akman D, Frusciante K, Le T, Meyer K, Bradshaw B, Mikula K, Morris C, Blackman C, Hu Y, Jia H, Li J, Koch G, Bangdiwala S (2003). "Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders". Gastroenterology. 125 (1): 19–31. doi:10.1016/S0016-5085(03)00669-3. PMID 12851867.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I (2006). "A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence". Am J Gastroenterol. 101 (2): 326–33. doi:10.1111/j.1572-0241.2006.00458.x. PMID 16454838.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Quigley EM (2006). "Germs, gas and the gut; the evolving role of the enteric flora in IBS". Am J Gastroenterol. 101 (2): 334–5. doi:10.1111/j.1572-0241.2006.00445.x. PMID 16454839.
- ^ Raahave D, Christensen E, Loud FB, Knudsen LL. Correlation of bowel symptoms with colonic transit, length, and faecal load in functional faecal retention 2009;56:83-8
- ^ Warfield, Carol A. (2003). Principles and Practice of Pain Medicine. McGraw-Hill Professional. ISBN 0071443495.
{{cite book}}
: Unknown parameter|coauthors=
ignored (|author=
suggested) (help) - ^ Kennedy T, Jones R, Darnley S, Seed P, Wessely S, Chalder T (2005). "Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial". BMJ. 331 (7514): 435. doi:10.1136/bmj.38545.505764.06. PMC 1188111. PMID 16093252.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Heymann-Mönnikes I, Arnold R, Florin I, Herda C, Melfsen S, Mönnikes H (2000). "The combination of medical treatment plus multicomponent behavioral therapy is superior to medical treatment alone in the therapy of irritable bowel syndrome". Am J Gastroenterol. 95 (4): 981–94. doi:10.1111/j.1572-0241.2000.01937.x. PMID 10763948.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ van der Veek PP, van Rood YR, Masclee AA (2007). [www3.interscience.wiley.com/cgi-bin/fulltext/117987882/HTMLSTART "Clinical trial: short- and long-term benefit of relaxation training for irritable bowel syndrome"]. Aliment. Pharmacol. Ther. 26 (6): 943–52. doi:10.1111/j.1365-2036.2007.03437.x. PMID 17767479.
{{cite journal}}
: Check|url=
value (help); Unknown parameter|doi_brokendate=
ignored (|doi-broken-date=
suggested) (help)CS1 maint: multiple names: authors list (link) - ^ Halpert AD, Thomas AC, Hu Y, Morris CB, Bangdiwala SI, Drossman DA (2006). "A survey on patient educational needs in irritable bowel syndrome and attitudes toward participation in clinical research". J Clin Gastroenterol. 40 (1): 37–43. doi:10.1097/01.mcg.0000190759.95862.08. PMID 16340632.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Nikfar S, Rahimi R, Rahimi F, Derakhshani S, Abdollahi M (2008). "Efficacy of probiotics in irritable bowel syndrome: a meta-analysis of randomized, controlled trials". Dis. Colon Rectum. 51 (12): 1775–80. doi:10.1007/s10350-008-9335-z. PMID 18465170.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Niedzielin K, Kordecki H, Birkenfeld B (2001). "A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome". Eur J Gastroenterol Hepatol. 13 (10): 1143–7. doi:10.1097/00042737-200110000-00004. PMID 11711768.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ "New Studies Examine the Evidence on Probiotics in IBS" (PDF) (Press release). American College of Gastroenterology. October 31, 2005.
- ^ Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS (2009). "The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review". Am. J. Gastroenterol. 104 (4): 1033–49, quiz 1050. doi:10.1038/ajg.2009.25. PMID 19277023.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ "IBS diet: Can yogurt ease symptoms?". Mayo Clinic. May 21, 2008.
- ^ Madisch A, Holtmann G, Plein K, Holz J (2004). "Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial". Aliment Pharmacol Ther. 19 (3): 271–9. doi:10.1111/j.1365-2036.2004.01859.x. PMID 14984373.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Hadley SK, Gaarder SM (2005). "Treatment of irritable bowel syndrome". Am Fam Physician. 72 (12): 2501–6. PMID 16370407.
- ^ Lim B, Manheimer E, Lao L, Ziea E, Wisniewski J, Liu J, Berman B (2006). "Acupuncture for treatment of irritable bowel syndrome". Cochrane Database Syst Rev (4): CD005111. doi:10.1002/14651858.CD005111.pub2. PMID 17054239.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ a b c
Quigley EM, Locke GR, Mueller-Lissner S, Paulo LG, Tytgat GN, Helfrich I, Schaefer E (2006). "Prevalence and management of abdominal cramping and pain: a multinational survey". Aliment. Pharmacol. Ther. 24 (2): 411–9. doi:10.1111/j.1365-2036.2006.02989.x. PMID 16842469.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Ehlin AG, Montgomery SM, Ekbom A, Pounder RE, Wakefield AJ (2003). "Prevalence of gastrointestinal diseases in two British national birth cohorts". Gut. 52 (8): 1117–21. doi:10.1136/gut.52.8.1117. PMC 1773740. PMID 12865268.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^
Hungin AP, Chang L, Locke GR, Dennis EH, Barghout V (2005). "Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact". Aliment. Pharmacol. Ther. 21 (11): 1365–75. doi:10.1111/j.1365-2036.2005.02463.x. PMID 15932367.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Jafri W, Yakoob J, Jafri N Islam M, Ali QM (2007). "Irritable bowel syndrome and health seeking behaviour in different communities of Pakistan". J Pak Med Assoc. 57 (6): 285–7. PMID 17629228.
{{cite journal}}
:|access-date=
requires|url=
(help); Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Jafri W, Yakoob J, Jafri N, Islam M, Ali QM (2005). "Frequency of irritable bowel syndrome in college students". J Ayub Med Coll Abbottabad. 4 (17): 9–11. PMID 16599025.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Tuteja AK, Talley NJ, Gelman SS, Alder SC, Adler SC, Thompson C, Tolman K, Hale DC (2008). "Development of Functional Diarrhea, Constipation, Irritable Bowel Syndrome, and Dyspepsia During and After Traveling Outside the USA". Dig. Dis. Sci. 53 (1): 271–6. doi:10.1007/s10620-007-9853-x. PMID 17549631.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Brown PW (1950). "The irritable bowel syndrome". Rocky Mountain medical journal. 47 (5): 343–6. PMID 15418074.
- ^ Leong SA, Barghout V, Birnbaum HG; et al. (2003). "The economic consequences of irritable bowel syndrome: a US employer perspective". Arch. Intern. Med. 163 (8): 929–35. doi:10.1001/archinte.163.8.929. PMID 12719202.
{{cite journal}}
: Explicit use of et al. in:|author=
(help)CS1 maint: multiple names: authors list (link) - ^ Martin B, Ganguly R, Pannicker S, Feride F, Barghout V (2003). "Utilization Patterns and Net Direct Medical Costs Medicaid of Irritable Bowel Syndrome". Curr Med Res Opin. 19 (8): 771–80. doi:10.1185/030079903125002540. PMID 12719202.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)