Alexander C. Ford

Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis

BACKGROUND & AIMS Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. METHODS MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. RESULTS Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. CONCLUSIONS The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described.

The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review

Introduction Probiotics may benefit irritable bowel syndrome (IBS) symptoms, but randomised controlled trials (RCTs) have been conflicting; therefore a systematic review was conducted. Methods MEDLINE (1966 to May 2008), EMBASE (1988 to May 2008) and the Cochrane Controlled Trials Register (2008) electronic databases were searched, as were abstracts from DDW (Digestive Diseases Week) and UEGW (United European Gastroenterology Week), and authors were contacted for extra information. Only parallel group RCTs with at least 1 week of treatment comparing probiotics with placebo or no treatment in adults with IBS according to any acceptable definition were included. Studies had to provide improvement in abdominal pain or global IBS symptoms as an outcome. Eligibility assessment and data extraction were performed by two independent researchers. Data were synthesised using relative risk (RR) of symptoms not improving for dichotomous data and standardised mean difference (SMD) for continuous data using random effects models. Results 19 RCTs (18 papers) in 1650 patients with IBS were identified. Trial quality was generally good, with nine reporting adequate methods of randomisation and six a method of concealment of allocation. There were 10 RCTs involving 918 patients providing outcomes as a dichotomous variable. Probiotics were statistically significantly better than placebo (RR of IBS not improving=0.71; 95% CI 0.57 to 0.88) with a number needed to treat (NNT)=4 (95% CI 3 to 12.5). There was significant heterogeneity (χ2=28.3, p=0.001, I2=68%) and possible funnel plot asymmetry. Fifteen trials assessing 1351 patients reported on improvement in IBS score as a continuous outcome (SMD=−0.34; 95% CI −0.60 to −0.07). There was statistically significant heterogeneity (χ2=67.04, p<0.001, I2=79%), but this was explained by one outlying trial. Conclusion Probiotics appear to be efficacious in IBS, but the magnitude of benefit and the most effective species and strain are uncertain.

Efficacy of Antidepressants and Psychological Therapies in Irritable Bowel Syndrome: Systematic Review and Meta-analysis.

Objective: Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder. Evidence for treatment of the condition with antidepressants and psychological therapies is conflicting. Design: Systematic review and meta-analysis of randomised controlled trials (RCTs). MEDLINE, EMBASE and the Cochrane Controlled Trials Register were searched (up to May 2008). Setting: RCTs based in primary, secondary and tertiary care. Patients: Adults with IBS. Interventions: Antidepressants versus placebo, and psychological therapies versus control therapy or “usual management”. Main outcome measures: Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. Results: The search strategy identified 571 citations. Thirty-two RCTs were eligible for inclusion: 19 compared psychological therapies with control therapy or “usual management”, 12 compared antidepressants with placebo, and one compared both psychological therapy and antidepressants with placebo. Study quality was generally good for antidepressant but poor for psychological therapy trials. The RR of IBS symptoms persisting with antidepressants versus placebo was 0.66 (95% CI, 0.57 to 0.78), with similar treatment effects for both tricyclic antidepressants and selective serotonin reuptake inhibitors. The RR of symptoms persisting with psychological therapies was 0.67 (95% CI, 0.57 to 0.79). The NNT was 4 for both interventions. Conclusions: Antidepressants are effective in the treatment of IBS. There is less high-quality evidence for routine use of psychological therapies in IBS, but available data suggest these may be of comparable efficacy.

Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis.

Objective To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane controlled trials register up to April 2008. Review methods Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. Results 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients (0.43, 0.32 to 0.59). Conclusion Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome.

Efficacy of Biological Therapies in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis

OBJECTIVES:Crohns disease (CD) and ulcerative colitis (UC) are inflammatory disorders of the gastrointestinal tract of unknown etiology. Evidence for treatment of the condition with biological therapies exists, but no systematic review and meta-analysis has examined this issue in its entirety.METHODS:MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (through to December 2010). Trials recruiting adults with active or quiescent CD or UC and comparing biological therapies (anti-tumor necrosis factor-α (TNFα) antibodies or natalizumab) with placebo were eligible. Dichotomous symptom data were pooled to obtain relative risk (RR) of failure to achieve remission in active disease and RR of relapse of activity in quiescent disease once remission had occurred, with a 95% confidence interval (CI).RESULTS:The search strategy identified 3,061 citations, 27 of which were eligible. Anti-TNFα antibodies and natalizumab were both superior to placebo in inducing remission of luminal CD (RR of no remission=0.87; 95% CI 0.80–0.94 and RR=0.88; 95% CI 0.83–0.94, respectively). Anti-TNFα antibodies were also superior to placebo in preventing relapse of luminal CD (RR of relapse=0.71; 95% CI 0.65–0.76). Infliximab was superior to placebo in inducing remission of moderate to severely active UC (RR=0.72; 95% CI 0.57–0.91).CONCLUSIONS:Biological therapies were superior to placebo in inducing remission of active CD and UC, and in preventing relapse of quiescent CD.

Antibiotic Therapy in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

The etiology of inflammatory bowel disease (IBD) is unknown but may relate to an unidentified bacterial pathogen or an immunological reaction to gut microbiota. Antibiotics have therefore been proposed as a therapy for Crohns disease (CD) and ulcerative colitis (UC) to induce remission in active disease to prevent relapse. Current data are conflicting and we therefore conducted a systematic review of randomized controlled trials (RCTs) evaluating antibiotics in IBD. Only parallel group RCTs were considered eligible. Studies with adult patients receiving any dose of therapy for at least 7 days and up to 16 weeks for active disease, or at least 6 months of follow-up for preventing relapse in quiescent disease were analyzed. We included any antibiotics alone or in combination using predefined definitions of remission and relapse. Two reviewers independently assessed eligibility and extracted data. The primary outcome was remission or relapse using an intention-to-treat methodology. The data were summarized using relative risk (RR) and pooled using a random effects model. For active CD, there were 10 RCTs involving 1,160 patients. There was a statistically significant effect of antibiotics being superior to placebo (RR of active CD not in remission=0.85; 95% confidence interval (CI)=0.73–0.99, P=0.03). There was moderate heterogeneity between results (I2=48%) and a diverse number of antibiotics were tested (anti-tuberculosis therapy, macrolides, fluroquinolones, 5-nitroimidazoles, and rifaximin) either alone or in combination. Rifamycin derivatives either alone or in combination with other antibiotics appeared to have a significant effect at inducing remission in active CD. In perianal CD fistula there were three trials evaluating 123 patients using either ciprofloxacin or metronidazole. There was a statistically significant effect in reducing fistula drainage (RR=0.8; 95% CI=0.66–0.98) with no heterogeneity (I2=0%) and an number needed to treat 5 (95% CI=3–20). For quiescent CD, there were 3 RCTs involving 186 patients treated with different antibiotics combinations (all including antimycobacterials) vs. placebo. There was a statistically significant effect in favor of antibiotics vs. placebo (RR of relapse=0.62; 95% CI=0.46–0.84), with no heterogeneity (I2=0%). In active UC, there were 9 RCTs with 662 patients and there was a statistically significant benefit for antibiotics inducing remission (RR of UC not in remission=0.64; 95% CI=0.43–0.96). There was moderate heterogeneity (I2=69%) and antibiotics used were all different single or combination drugs. Antibiotic therapy may induce remission in active CD and UC, although the diverse number of antibiotics tested means the data are difficult to interpret. This systematic review is a mandate for further trials of antibiotic therapy in IBD.

Prevalence of, and Risk Factors for, Chronic Idiopathic Constipation in the Community: Systematic Review and Meta-analysis

OBJECTIVES:Chronic idiopathic constipation (CIC) is a common functional gastrointestinal disorder in the community, yet no previous systematic review and meta-analysis has estimated the global prevalence, or potential risk factors for the condition.METHODS:MEDLINE, EMBASE, and EMBASE Classic were searched (up to December 2010) to identify population-based studies reporting the prevalence of CIC in adults (≥15 years), according to self-report, questionnaire, or specific symptom-based criteria. The prevalence of CIC was extracted for all studies, and according to country, age, gender, socioeconomic status, and presence or absence of irritable bowel syndrome (IBS) where reported. Pooled prevalence overall, and according to study location and certain other characteristics, as well as odds ratios (ORs), with 95% confidence intervals (CIs) were calculated.RESULTS:Of the 100 papers evaluated, 45 reported the prevalence of CIC in 41 separate study populations, containing 261,040 subjects. Pooled prevalence of CIC in all studies was 14% (95% CI: 12–17%). The prevalence of CIC was lower in South East Asian studies, and in studies using the Rome II or III criteria. The prevalence of CIC was higher in women (OR: 2.22; 95% CI: 1.87–2.62), and increased with age and lower socioeconomic status. The prevalence was markedly higher in subjects who also reported IBS (OR: 7.98; 95% CI: 4.58–13.92), suggesting common pathogenic mechanisms.CONCLUSIONS:Pooled prevalence of CIC in the community was 14%, and of similar magnitude in most geographical regions. Rates were higher in women, older individuals, and those of lower socioeconomic status. Presence of IBS was strongly associated with CIC.

Efficacy of Prebiotics, Probiotics, and Synbiotics in Irritable Bowel Syndrome and Chronic Idiopathic Constipation: Systematic Review and Meta-analysis

OBJECTIVES:Irritable bowel syndrome (IBS) and chronic idiopathic constipation (CIC) are functional bowel disorders. Evidence suggests that disturbance in the gastrointestinal microbiota may be implicated in both conditions. We performed a systematic review and meta-analysis to examine the efficacy of prebiotics, probiotics, and synbiotics in IBS and CIC.METHODS:MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to December 2013). Randomized controlled trials (RCTs) recruiting adults with IBS or CIC, which compared prebiotics, probiotics, or synbiotics with placebo or no therapy, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). Continuous data were pooled using a standardized or weighted mean difference with a 95% CI.RESULTS:The search strategy identified 3,216 citations. Forty-three RCTs were eligible for inclusion. The RR of IBS symptoms persisting with probiotics vs. placebo was 0.79 (95% CI 0.70–0.89). Probiotics had beneficial effects on global IBS, abdominal pain, bloating, and flatulence scores. Data for prebiotics and synbiotics in IBS were sparse. Probiotics appeared to have beneficial effects in CIC (mean increase in number of stools per week=1.49; 95% CI=1.02–1.96), but there were only two RCTs. Synbiotics also appeared beneficial (RR of failure to respond to therapy=0.78; 95% CI 0.67–0.92). Again, trials for prebiotics were few in number, and no definite conclusions could be drawn.CONCLUSIONS:Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear. Further evidence is required before the role of prebiotics or synbiotics in IBS is known. The efficacy of all three therapies in CIC is also uncertain.

American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation.

Irritable bowel syndrome (IBS) and chronic idiopathic constipation ((CIC) also referred to as functional constipation) are two of the most common functional gastrointestinal disorders worldwide. IBS is a global problem, with anywhere from 5 to 15 % of the general population experiencing symptoms that would satisfy a defi nition of IBS ( 1,2 ). In a systematic review on the global prevalence of IBS, Lovell and Ford ( 1 ) documented a pooled prevalence of 11 % with all regions of the world suff ering from this disorder at similar rates. Given its prevalence, the frequency of symptoms, and their associated debility for many patients and the fact that IBS typically occurs in younger adulthood, an important period for furthering education, embarking on careers, and / or raising families, the socioeconomic impact of IBS is considerable. Th ese indirect medical costs are frequently compounded by the direct medical costs related to additional medical tests and the use of various medical and nonmedical remedies that may have limited impact. CIC is equally common; in another systematic review, Suares and Ford ( 3 ) reported a pooled prevalence of 14 % , and also noted that constipation was more common in females, in older subjects, and those of lower socioeconomic status ( 3 ). Chronic constipation has also been linked to impaired quality of life ( 4 ), most notably among the elderly ( 5 ). Neither IBS nor CIC are associated with abnormal radiologic or endoscopic abnormalities, nor are they associated with a reliable biomarker; diagnosis currently rests entirely, therefore, on clinical grounds. Although a number of clinical defi nitions of both IBS and CIC have been proposed, the criteria developed through the Rome process, currently in its third iteration, have been those most widely employed in clinical trials and, therefore, most relevant to any review of the literature on the management of these disorders. According to Rome III, IBS is defi ned on the basis of the presence of:

Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: Systematic Review and Meta-analysis

BACKGROUND & AIMS Small intestinal bacterial overgrowth (SIBO) has been proposed as an etiologic factor in irritable bowel syndrome (IBS), but evidence is conflicting. We conducted a systematic review and meta-analysis of the prevalence of SIBO in IBS. METHODS MEDLINE and EMBASE were searched up to November 2008. Case series and case-control studies applying diagnostic tests for SIBO in unselected adults meeting diagnostic criteria for IBS were eligible. Prevalence of a positive test for SIBO was extracted and pooled for all studies, and compared between cases and controls using an odds ratio and 95% confidence interval (CI). RESULTS Twelve studies were identified containing 1921 subjects meeting criteria for IBS. Pooled prevalence of a positive lactulose or glucose hydrogen breath test was 54% (95% CI, 32%-76%) and 31% (95% CI, 14%-50%), respectively, with statistically significant heterogeneity between study results. Prevalence of a positive jejunal aspirate and culture was 4% (95% CI, 2%-9%). The pooled odds ratio for any positive test for SIBO in cases compared with healthy asymptomatic controls was 3.45 (95% CI, 0.9-12.7) or 4.7 (95% CI, 1.7-12.95), depending on the criteria used to define a positive test, with statistically significant heterogeneity for both. CONCLUSIONS Prevalence of SIBO in individuals meeting diagnostic criteria for IBS was highest with breath testing. The prevalence in cases with IBS compared with controls varied according to criteria used to define a positive test. The role of testing for SIBO in individuals with suspected IBS remains unclear.