Declining Use of Corticosteroids for Crohn's Disease Has Implications for Study Recruitment: Results of a Pilot Randomized Controlled Trial.

BACKGROUND: Corticosteroids (CS) have been used extensively to induce remission in Crohn's disease (CD); however, they are associated with severe side effects. We hypothesized that the administration of an exclusive enteral nutrition (EEN) formula to CS would lead to increased CD remission rates and to decreased CS-related adverse events. We proposed to undertake a pilot study comparing EEN and CS therapy to CS alone to assess decrease symptoms and inflammatory markers over 6 weeks. AIM: The overall aim was to assess study feasibility based on recruitment rates and acceptability of treatment in arms involving EEN. METHODS: The pilot study intended to recruit 100 adult patients with active CD who had been prescribed CS to induce remission as part of their care. The patients were randomized to one of three arms: (i) standard-dose CS; (ii) standard-dose CS plus EEN (Modulen 1.5 kcal); or (iii) short-course CS plus EEN. RESULTS: A total of 2009 CD patients attending gastroenterology clinics were screened from October 2018 to November 2019. Prednisone was prescribed to only 6.8% (27/399) of patients with active CD attending outpatient clinics. Of the remaining 372 patients with active CD, 34.8% (139/399) started or escalated immunosuppressant or biologics, 49.6% (198/399) underwent further investigation and 8.8% (35/399) were offered an alternative treatment (e.g., antibiotics, surgery or investigational agents in clinical trials). Only three patients were enrolled in the study (recruitment rate 11%; 3/27), and the study was terminated for poor recruitment. CONCLUSION: The apparent decline in use of CS for treatment of CD has implications for CS use as an entry criterion for clinical trials.

Canadian association of gastroenterology clinical practice guideline for the management of Luminal Crohn's Disease

Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD. We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists. The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent. Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.

Deprescribing proton pump inhibitors: evidence-based clinical practice guideline

OBJECTIVE: To develop an evidence-based guideline to help clinicians make decisions about when and how to safely taper or stop proton pump inhibitors (PPIs); to focus on the highest level of evidence available and seek input from primary care professionals in the guideline development, review, and endorsement processes. METHODS: Five health professionals (1 family physician, 3 pharmacists, and 1 gastroenterologist) and 5 nonvoting members comprised the overall team; members disclosed conflicts of interest. The guideline process included the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, with a detailed evidence review in in-person, telephone, and online meetings. Uniquely, the guideline development process included a systematic review of PPI deprescribing trials and examination of reviews of the harm of continued PPI use. Narrative syntheses of patient preferences and resource-implication literature informed recommendations. The team refined guideline content and recommendation wording through consensus and synthesized clinical considerations to address common front-line clinician questions. The draft guideline was distributed to clinicians and then to health care professional associations for review and revisions made at each stage. A decision-support algorithm was developed in conjunction with the guideline. RECOMMENDATIONS: This guideline recommends deprescribing PPIs (reducing dose, stopping, or using "on-demand" dosing) in adults who have completed a minimum of 4 weeks of PPI treatment for heartburn or mild to moderate gastroesophageal reflux disease or esophagitis, and whose symptoms are resolved. The recommendations do not apply to those who have or have had Barrett esophagus, severe esophagitis grade C or D, or documented history of bleeding gastrointestinal ulcers. CONCLUSION: This guideline provides practical recommendations for making decisions about when and how to reduce the dose of or stop PPIs. Recommendations are meant to assist with, not dictate, decision making in conjunction with patients.

Derivation and validation of a diagnostic test for irritable bowel syndrome using latent class analysis.

BACKGROUND: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest. AIMS: To derive and validate a new test that utilises latent class analysis. METHODS: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models. RESULTS: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15. CONCLUSIONS: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin.

Poor predictive value of lower gastrointestinal alarm features in the diagnosis of colorectal cancer in 1981 patients in secondary care.

BACKGROUND: Clinicians are advised to refer patients with lower gastrointestinal (GI) alarm features for urgent colonoscopy to exclude colorectal cancer (CRC). However, the utility of alarm features is debated. AIM: To assess whether performance of alarm features is improved by using a symptom frequency threshold to trigger referral, or by combining them into composite variables, including minimum age thresholds, as recommended by the National Institute for Health and Care Excellence (NICE). METHODS: We collected data prospectively from 1981 consecutive adults with lower GI symptoms. Assessors were blinded to symptom status. The reference standard to define CRC was histopathological confirmation of adenocarcinoma in biopsy specimens from a malignant-looking colorectal lesion. Controls were patients without CRC. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values were calculated for individual alarm features, as well as combinations of these. RESULTS: In identifying 47 (2.4%) patients with CRC, individual alarm features had sensitivities ranging from 11.1% (family history of CRC) to 66.0% (loose stools), and specificities from 30.5% (loose stools) to 75.6% (family history of CRC). Using higher symptom frequency thresholds improved specificity, but to the detriment of sensitivity. NICE referral criteria also had higher specificities and lower sensitivity, with PPVs above 4.8%. More than 80% of those with CRC met at least one of the NICE referral criteria. CONCLUSIONS: Using higher symptom frequency thresholds for alarm features improved specificity, but sensitivity was low. NICE referral criteria had PPVs above 4.8%, but sensitivities ranged from 2.2% to 32.6%, meaning many cancers would be missed.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

An index with improved diagnostic accuracy for the diagnosis of Crohn's disease derived from the Lennard-Jones criteria.

BACKGROUND: The Lennard-Jones criteria are considered the gold standard for diagnosing Crohn's disease (CD) and include the items granuloma, macroscopic discontinuity, transmural inflammation, fibrosis, lymphoid aggregates and discontinuous inflammation on histology. The criteria have never been subjected to a formal validation process. AIM: To develop a validated and improved diagnostic index based on the items of Lennard-Jones criteria. METHODS: Included were 328 adult patients with long-standing CD (median disease duration 10 years) from three centres and classified as 'established', 'probable' or 'non-CD' by Lennard-Jones criteria at time of diagnosis. Controls were patients with ulcerative colitis (n = 170). The performance of each of the six diagnostic items of Lennard-Jones criteria was modelled by logistic regression and a new index based on stepwise backward selection and cut-offs was developed. The diagnostic value of the new index was analysed by comparing sensitivity, specificity and accuracy vs. Lennard-Jones criteria. RESULTS: By Lennard-Jones criteria 49% (n = 162) of CD patients would have been diagnosed as 'non-CD' at time of diagnosis (sensitivity/specificity/accuracy, 'established' CD: 0.34/0.99/0.67; 'probable' CD: 0.51/0.95/0.73). A new index was derived from granuloma, fibrosis, transmural inflammation and macroscopic discontinuity, but excluded lymphoid aggregates and discontinuous inflammation on histology. Our index provided improved diagnostic accuracy for 'established' and 'probable' CD (sensitivity/specificity/accuracy, 'established' CD: 0.45/1/0.72; 'probable' CD: 0.8/0.85/0.82), including the subgroup isolated colonic CD ('probable' CD, new index: 0.73/0.85/0.79; Lennard-Jones criteria: 0.43/0.95/0.69). CONCLUSION: We developed an index based on items of Lennard-Jones criteria providing improved diagnostic accuracy for the differential diagnosis between CD and UC.

No increase in prevalence of somatization in functional vs organic dyspepsia: a cross-sectional survey.

BACKGROUND: Psychological factors are associated with functional gastrointestinal (GI) disorders. Literature suggests that somatization is associated with functional dyspepsia (FD). However, the relationship between organic dyspepsia (OD), FD, and FD subtypes and somatization is poorly described. We aimed to examine this issue in a cross-sectional study of secondary care patients. METHODS: Demographic and GI symptom data were collected from 4224 adult patients via the Rome III questionnaire. Somatization data were collected using the patient health questionnaire-12. Mean somatization score and number of somatic symptoms were compared between patients with organic and FD, and between FD subtypes using analysis of variance. The same comparison was undertaken for the proportion of patients reporting individual somatic symptoms. KEY RESULTS: Exactly, 783 patients met criteria for dyspepsia, of whom 231 (29.5%) had organic disease following upper GI endoscopy. Mean somatization scores and number of somatic symptoms were no higher in functional vs OD (p = 0.23; p = 0.19). In addition, while the prevalence of somatization in FD was relatively high, there was no difference in severity of somatization in FD subgroups. CONCLUSIONS & INFERENCES: Somatization is associated with functional and OD to the same degree. Overall severity of somatization did not appear to vary according to FD subtype.

Irritable bowel syndrome is significantly associated with somatisation in 840 patients, which may drive bloating.

BACKGROUND: Psychological factors may influence persistence and perceived severity of symptoms in irritable bowel syndrome (IBS). Literature suggests that somatisation is associated with IBS. However, the relationship between IBS subtype, symptoms of IBS and somatisation is unclear. AIM: To examine this issue in a large cohort of secondary care patients. METHODS: Demographic and gastrointestinal (GI) symptom data were collected from 4224 adult patients via the Rome III questionnaire. Somatisation data were collected using the patient health questionnaire-12. Mean somatisation score and number of somatic symptoms were compared between IBS patients and controls with minimal GI symptoms, and between IBS subtypes using analysis of variance. Effect of level of somatisation on symptom frequency was compared according to IBS subtype using a χ(2) test. RESULTS: 840 patients met Rome III criteria for IBS, controls were 2137 patients with GI symptoms without IBS. Mean somatisation scores and number of somatic symptoms were higher in IBS vs. controls (P < 0.001), and in mixed stool pattern IBS (IBS-M), vs. IBS with constipation (IBS-C) or diarrhoea (IBS-D) (P < 0.001). High levels of somatisation were more prevalent in IBS-M (31.7%) vs. IBS-C (22.5%) or IBS-D (20.8%) (P = 0.003). For all IBS subtypes, high levels of somatisation were associated with a greater frequency of bloating or abdominal distension prior to logistic regression. CONCLUSIONS: IBS is strongly associated with higher levels of somatisation, particularly IBS-M. Bloating may be associated with higher levels of somatisation, perhaps explaining why it can be difficult to treat.

Bead study: a novel method to measure gastrointestinal transit in mice.

BACKGROUND: Intestinal transit assessment in mice using existing methods requires long recording periods or euthanization of animals to localize a tracer. We have developed a novel in vivo method to assess gastrointestinal (GI) transit in mice based on a clinically used 'shapes study'. METHODS: Mice (n = 70) were gavaged with 5 steel beads and barium 3 h before, with another dose of barium gavaged 10 min before imaging. Mice were fluoroscoped for 20-60 s, and then most of them were euthanized and the GI tract removed to confirm the localization of the beads fluoroscopically. The in vivo and postmortem recordings were analyzed and each bead was scored depending on its location; a total score was calculated by adding individual bead scores. Total scores obtained from the two methods were compared. A group of mice (n = 10) were examined on three occasions, before and after treatment with loperamide or prucalopride. KEY RESULTS: The stomach and cecum were consistently outlined by barium, serving as reference landmarks. There was an excellent overall correlation between in vivo and postmortem transit scores (r = 0.93). Analysis of scores for individual gut segments revealed high agreement for stomach, cecum, and expelled beads, and moderate agreement for the small bowel and colon. Gastrointestinal transit scores were decreased by loperamide and increased by prucalopride compared with baseline. CONCLUSIONS & INFERENCES: Metallic beads are reliably localized by videofluoroscopy in vivo within the GI tract. This novel imaging method enables repetitive measurements of GI transit in vivo and detects changes induced by motility-modifying agents.

British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett's oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett's oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as >80% agreement (A or A+), were revisited and modified until substantial agreement (>80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett's oesophagus and related neoplasia.

Characteristics of functional bowel disorder patients: a cross-sectional survey using the Rome III criteria.

BACKGROUND: There is some evidence that, despite attempts to classify them separately, functional bowel disorders are not distinct entities and that such divisions are artificial. AIM: To examine this issue in a large cohort of secondary care patients. METHODS: Consecutive, unselected adults with gastrointestinal (GI) symptoms attending out-patient clinics at two hospitals in Hamilton, Ontario were recruited. Demographic data, symptoms and presence of anxiety, depression or somatisation were collected prospectively. We used validated questionnaires, including the Rome III questionnaire, with patients categorised as having irritable bowel syndrome (IBS), functional diarrhoea or chronic idiopathic constipation (CIC). We compared data between these disorders, and measured degree of overlap between them by suspending their mutual exclusivity. RESULTS: Of 3656 patients providing complete lower GI symptom data, 1551 (42.4%) met criteria for a functional bowel disorder. Diarrhoea-predominant IBS (IBS-D) patients were younger, and more were female, met criteria for anxiety, and reported somatisation-type behaviour, compared with functional diarrhoea. Only loose, mushy or watery stools were more common in functional diarrhoea. When mutual exclusivity was suspended, overlap occurred in 27.6%. Constipation-predominant IBS (IBS-C) patients were younger, and more were female, had never married, reported anxiety type symptoms and exhibited somatisation-type behaviour. One in five CIC patients reported abdominal pain or discomfort. All constipation symptoms were more common in IBS-C. When the mutual exclusivity was suspended, overlap occurred in 18.1%. CONCLUSIONS: There were significant differences in demographics between individuals with functional bowel disorders. Despite this, the Rome III classification system falls short of describing unique entities.

Guide wire-assisted cannulation for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS: Cannulation techniques are recognized to be important in causing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, considerable controversy exists about the usefulness of the guide wire-assisted cannulation technique for the prevention of PEP. This systematic review of randomized controlled trials (RCTs) aimed to compare the guide wire-assisted cannulation technique with the contrast-assisted cannulation technique. METHODS: CENTRAL, MEDLINE, EMBASE, CINAHL, and abstracts from Digestive Disease Week and the United European Gastroenterology Week were searched up to February 2012 for RCTs comparing the guide wire-assisted ERCP cannulation technique with the conventional contrast-assisted ERCP cannulation technique. The risk of bias was assessed, and outcomes were pooled by meta-analysis (random-effects model). The primary outcome measure was PEP. Secondary outcome measures included severity of PEP, primary common bile duct (CBD) cannulation success, overall CBD cannulation success, precut sphincterotomy, and other ERCP-related complications. RESULTS: In total, 12 RCTs (3450 patients) were included. The guide wire-assisted cannulation technique significantly reduced PEP compared with the contrast-assisted cannulation technique (risk ratio [RR] 0.51, 95 % confidence interval [CI] 0.32 - 0.82). In addition, the guide wire-assisted cannulation technique was associated with greater primary cannulation success (RR 1.07, 95 %CI 1.00 - 1.15), fewer precut sphincterotomies (RR 0.75, 95 %CI 0.60 - 0.95), and no increase in other ERCP-related complications. Subgroup analyses indicated that this significant risk reduction in PEP with the guide wire-assisted cannulation technique existed only in "non-crossover" trials (RR 0.22, 95 %CI 0.12 - 0.42). The results were robust in sensitivity analyses. CONCLUSION: Compared with the contrast-assisted cannulation technique, the guide wire-assisted cannulation technique increases the primary cannulation rate and reduces the risk of PEP, and therefore appears to be the most appropriate first-line cannulation technique.

The impact of intensifying acid suppression on sleep disturbance related to gastro-oesophageal reflux disease in primary care.

BACKGROUND: Sleep disturbance is common in patients with GERD but there has been little evaluation of this problem in primary care in patients already taking therapy. AIM: To evaluate the impact of administering a questionnaire (PASS test) to identify patients with sleep problems and evaluate the efficacy of esomeprazole to improve sleep disturbance in patients with GERD. METHODS: This was a primary care based cluster-randomised, open-label study where practices were assigned to intervention or control groups. PASS test failures continued current therapy (control) or were switched to 4 weeks' once-daily esomeprazole 20 or 40 mg (intervention). Patients were evaluated at the end of 4 weeks and the outcomes that were assessed were the sleep questions from the Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire and the presence or absence of sleep disturbance from the PASS test questionnaire. RESULTS: A total of 1388 patients with evaluable data at 4 weeks were included in the analysis and 825 reported GERD-related sleep disturbance at baseline. At 4 weeks, 161 of 291 of control patients (55%) reported continued sleep disturbance compared to 120 of 534 (22.5%) of intervention patients [number needed to treat of 3: 95% confidence intervals (CI): 2.5-4]. There was a mean improvement in QOLRAD scores related to sleep in the intervention patients compared to control patients (mean improvement = 4.91; 95% CI: 3.73-6.09). CONCLUSION: A PASS strategy identifies GERD patients with sleep disturbance in primary care that will benefit from a change in acid-suppressive therapy. ClinicalTrials.gov identifier: NCT00392002; study code: D9612L00096.

The natural history of gastro-oesophageal reflux symptoms in the community and its effects on survival: a longitudinal 10-year follow-up study.

BACKGROUND: Gastro-oesophageal reflux symptoms (GERS) are common in the community. However, few studies have examined their long-term natural history, or impact on survival. AIM: To examine these issues in individuals recruited into a community-based screening programme for Helicobacter pylori in 1994. METHODS: Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, gastrointestinal symptoms and quality of life were recorded at study entry. The effect of all these factors on persistent and new-onset GERS, and 10-year mortality, were examined using univariate and multivariate analysis, with results expressed as odds ratios (ORs) or hazard ratios (HR) with 99% confidence intervals (CI). RESULTS: Of 3967 individuals providing complete GERS data at baseline and 10 years, 549 (13.8%) had GERS at baseline. Of these, 183 (33.3%) had persistent symptoms. Among 3418 individuals asymptomatic at baseline, approximately 0.8% per year developed new-onset GERS. No predictors of persistent GERS were identified. New-onset symptoms were associated with lower quality of life or presence of irritable bowel syndrome (IBS) at baseline, and higher body mass index (BMI) at 10 years. There were 8331 (99.1%) of 8407 subjects providing complete GERS data at baseline, 1289 (15.5%) of whom were symptomatic. Presence of GERS at baseline did not affect survival (HR: 0.84; 99% CI: 0.44-1.59). CONCLUSIONS: Gastro-oesophageal reflux symptoms persisted in one-third of individuals, whilst new-onset gastro-oesophageal reflux symptoms were associated with poor quality of life, irritable bowel syndrome and higher body mass index. Gastro-oesophageal reflux symptoms did not impact adversely on survival.

Review article: current treatment options and management of functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89-90%), postprandial fullness (75-88%), and early satiety (50-82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non-specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive. AIM: To present current management options for the treatment of FD (therapeutic gain/response rate noted when available). RESULTS: The utility of Helicobacter pylori eradication for the treatment of FD is modest (6-14% therapeutic gain), while the therapeutic efficacy of proton pump inhibitors (PPI) (7-10% therapeutic gain), histamine-type-2-receptor antagonists (8-35% therapeutic gain), prokinetic agents (18-45%), tricyclic antidepressants (TCA) (response rates of 64-70%), serotonin reuptake inhibitors (no better than placebo) is limited and hampered by inadequate data. This review discusses dietary interventions and analyses studies involving complementary and alternative medications, and psychological therapies. CONCLUSIONS: A reasonable treatment approach based on current evidence is to initiate therapy with a daily PPI in H. pylori-negative FD patients. If symptoms persist, a therapeutic trial with a tricyclic antidepressant may be initiated. If symptoms continue, the clinician can possibly initiate therapy with an anti-nociceptive agent, a prokinetic agent, or some form of complementary and alternative medications, although evidence from prospective studies to support this approach is limited.

Meta-analysis: factors affecting placebo response rate in the irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract with a significant placebo response. AIM: To conduct a systematic review and meta-analysis examining the magnitude of placebo response rate in treatment trials for IBS. METHODS: MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing pharmacological therapies with placebo in adult IBS patients. Studies reported either global assessment of IBS symptom cure or improvement or abdominal pain cure or improvement. Data were extracted as intention-to-treat analyses with drop-outs assumed to be treatment failures and pooled using a random-effects model. Proportion of placebo patients experiencing symptom improvement or resolution was reported with a 95% confidence interval (CI). Effect of trial characteristics on magnitude of placebo response was examined. RESULTS: In all, 73 RCTs were eligible, including 8364 patients with IBS allocated to placebo. Pooled placebo response rate across all RCTs was 37.5% (95% CI 34.4-40.6%). Rates were higher in European RCTs, RCTs that used physician-reported outcomes and RCTs using shorter duration of therapy. CONCLUSIONS: Placebo response rates across RCTs of pharmacological therapies in IBS were high. Future research should identify patient characteristics predicting placebo response.

Cost-utility analysis of proton pump inhibitors and other gastro-protective agents for prevention of gastrointestinal complications in elderly patients taking nonselective nonsteroidal anti-inflammatory agents.

BACKGROUND: The use of proton pump inhibitors (PPIs) among elderly patients using nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) has increased; the price of PPIs is higher than that of majority of alternative treatment strategies. AIM: To evaluate the cost-effectiveness of nsNSAIDS + PPIs relative to alternative gastroprotective regimens in the prevention of GI complications among elderly patients (aged > or = 65 years). METHODS: An incremental cost-utility analysis, comparing PPIs with alternative gastroprotective regimens was conducted using a decision analytical model. Clinical outcomes, costs and utilities were derived from recently published studies. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the results to variation in model inputs and assumptions. RESULTS: The incremental cost-utility ratio (ICUR) of PPIs, relative to nsNSAID alone, was $206,315 per QALY gained or were more costly and less effective. Other co-prescribed treatment options had higher costs per QALY gained. In patients with a history of a complicated or uncomplicated ulcer, PPIs had ICURs of $24,277 and $40,876, respectively. CONCLUSIONS: Use of PPIs in all elderly patients taking nsNSAIDs is unlikely to represent an efficient use of finite healthcare resources. Co-prescribing PPIs, however, to elderly patients taking nsNSAIDs who have a history of complicated or uncomplicated ulcers appears to be economically attractive.