N. C. Suares

BACKGROUND: There has been no definitive systematic review and meta-analysis to date examining the effect of laxatives and pharmacological therapies in chronic idiopathic constipation (CIC). OBJECTIVE: To assess efficacy of these therapies systematically in CIC. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). DATA SOURCES: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched (up to September 2010). ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Placebo-controlled trials of laxatives or pharmacological therapies in adult CIC patients were eligible. Minimum duration of therapy was 1 week. Trials had to report either a dichotomous assessment of overall response to therapy at last point of follow-up in the trial, or mean number of stools per week during therapy. STUDY APPRAISAL AND SYNTHESIS METHODS: Symptom data were pooled using a random effects model. Effect of laxatives or pharmacological therapies compared to placebo was reported as RR of failure to respond to therapy, or a weighted mean difference (WMD) in mean number of stools per week, with 95% CIs. RESULTS: Twenty-one eligible RCTs were identified. Laxatives (seven RCTs, 1411 patients, RR=0.52; 95% CI 0.46 to 0.60), prucalopride (seven trials, 2639 patients, RR=0.82; 95% CI 0.76 to 0.88), lubiprostone (three RCTs, 610 patients, RR=0.67; 95% CI 0.56 to 0.80), and linaclotide (three trials, 1582 patients, RR=0.84; 95% CI 0.80 to 0.87) were all superior to placebo in terms of a reduction in risk of failure with therapy. Treatment effect remained similar when only RCTs at low risk of bias were included in the analysis. Diarrhoea was significantly more common with all therapies. LIMITATIONS: Only two RCTs were conducted in primary care, and total adverse events data for laxatives and linaclotide were sparse. CONCLUSIONS: Laxatives, prucalopride, lubiprostone and linaclotide are all more effective than placebo for the treatment of CIC.

BACKGROUND: Patients with chronic idiopathic constipation are often told to increase dietary fibre intake. Whether this is of any benefit remains unclear. AIM: To conduct a systematic review of the efficacy of soluble and insoluble fibre supplementation in the management of chronic idiopathic constipation. METHODS: MEDLINE, EMBASE, and the Cochrane central register of controlled trials were searched to identify randomised controlled trials (RCTs) comparing fibre with placebo or no therapy in adult chronic idiopathic constipation patients. Studies had to report dichotomous data assessing response to therapy, or continuous data examining either effect of therapy on mean number of stools per week, or mean symptom scores. Adverse events data were extracted where reported. RESULTS: Six RCTs were eligible. Four used soluble fibre and two used insoluble fibre. Formal meta-analysis was not undertaken due to concern about methodological quality of identified studies. Compared with placebo, soluble fibre led to improvements in global symptoms (86.5% vs. 47.4%), straining (55.6% vs. 28.6%), pain on defaecation, and stool consistency, an increase in the mean number of stools per week (3.8 stools per week after therapy compared with 2.9 stools per week at baseline), and a reduction in the number of days between stools. Evidence for any benefit of insoluble fibre was conflicting. Adverse events data were limited, with no RCT reporting total numbers. CONCLUSIONS: Soluble fibre may be of benefit in chronic idiopathic constipation, but data for insoluble fibre are conflicting. More data from high quality RCTs are required before the true efficacy of either fibre type in the treatment of chronic idiopathic constipation is known.

BACKGROUND: Prevalence of, and risk factors for, noncardiac chest pain in the community have not been well studied. AIMS: To conduct a systematic review and meta-analysis to examine these issues. METHODS: MEDLINE, EMBASE and EMBASE Classic were searched (up to March 2011) to identify population-based studies reporting prevalence of noncardiac chest pain in adults (≥15 years) according to self-report, questionnaire or specific symptom-based criteria. Prevalence of noncardiac chest pain was extracted for all studies, and according to study location and certain other characteristics including presence or absence of gastro-oesophageal reflux disease (GERD) symptoms, where reported. Pooled prevalence overall, as well as odds ratios (OR), with 95% confidence intervals (CIs) were calculated. RESULTS: Of 18 articles evaluated, 16 reported prevalence of noncardiac chest pain in 14 separate populations, containing 24 849 subjects. Pooled prevalence of noncardiac chest pain in all studies was 13% (95% CI 9-16). The prevalence of noncardiac chest pain was higher in Australian studies and in studies using a questionnaire to define its presence, compared with those using Rome I or II criteria. Prevalence was no different in women vs. men (OR 0.99; 95% CI 0.82-1.20). The prevalence was markedly higher in subjects who also reported GERD (OR 4.71; 95% CI 3.32-6.70) and increased according to frequency of GERD symptoms. CONCLUSIONS: Pooled prevalence of noncardiac chest pain in the community was 13%, but there were few studies. Rates did not appear to differ according to gender or age. Presence of GERD was strongly associated with noncardiac chest pain.

BACKGROUND: Infliximab is effective for induction and maintenance of remission in patients with Crohn's disease. There are few data, however, examining effect of infliximab therapy on management costs of Crohn's disease. AIM: To assess Crohn's disease-related costs of care and resource use in a single-centre cohort of patients with Crohn's disease 12 months pre- and post-infliximab therapy. METHODS: Data on 100 consecutive patients receiving infliximab were collected. Crohn's disease-related resource use was collected 12 months pre- and post-infliximab. National Health Service reference costs were applied to these data and the total Crohn's disease-related health service costs per patient were calculated (£UK). The cost of infliximab therapy was not included in our analysis. RESULTS: Cost savings were demonstrated in all areas of Crohn's disease-related resource use following infliximab therapy. Mean total Crohn's disease-related cost reduction, 12 months following commencement of infliximab therapy, was £2750 per patient. Mean costs at 12 months post-infliximab in responders were lower than in nonresponders (£1656 vs. £3608, P = 0.02). The number of hospitalizations was reduced. Requirements for examination under anaesthesia were also significantly decreased. CONCLUSION: Infliximab use resulted in Crohn's disease-related cost savings and hospital resource use, although this was not sufficient to cover the cost of therapy.

BACKGROUND: Randomised controlled trials demonstrate that methotrexate is effective in inducing remission and preventing relapse of Crohn's disease (CD) as a first-line immunosuppressant, but efficacy data after failure with, or intolerance to, thiopurines are limited. AIMS: To report efficacy of methotrexate in a cohort of refractory CD patients, most of whom had not responded to, or were intolerant of, thiopurines. METHODS: Data were collected for patients receiving methotrexate for active CD. Response to methotrexate induction therapy at 4 months, and sustained clinical benefit at last point of follow-up with maintenance therapy, were assessed via physician's global assessment. Demographic and disease factors predicting response, or sustained clinical benefit, were examined by univariate and multivariate analysis. RESULTS: Sixty-six [38 (54%) female patients, mean age at diagnosis 29.4 years] patients received methotrexate between 2001 and 2010, 61 (92%) of whom received the drug parenterally. Sixty patients had failed, or were intolerant of, thiopurines. Response to therapy at 4 months occurred in 54 (82%) patients. However, sustained clinical benefit occurred in only 19 (29%) patients at last point of follow-up, including six patients who discontinued the drug for family planning reasons. No predictors of response or sustained clinical benefit were identified. Adverse events occurred in 20 (30%) patients. CONCLUSIONS: These data suggest that methotrexate is effective in terms of initial response in Crohn's disease patients who have failed, or are intolerant of, thiopurines. However, efficacy is not sustained in the long term.