Use of prokinetic agents in hospitalised adult patients: A scoping review.

BACKGROUND: Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations. METHODS: We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. RESULTS: We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents. CONCLUSIONS: In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Establishing a donor stool bank for faecal microbiota transplantation: methods and feasibility.

Faecal microbiota transplantation (FMT) is a promising treatment, but donor selection and implementation in clinical practice are difficult. Here, we describe the establishment of a donor stool bank based on the Tissue Act. Stool donors were recruited among blood donors and asked to donate five times in a month. A screening questionnaire, a medical interview and testing of blood and stool were conducted before and after donations. Donations were made at home and transported to the lab, where 50 g of stool was suspended and filtered in saline and 20-mL glycerol (final concentration of 10%) to a volume of 170 mL. The processed stool was assigned a batch number, frozen within 2 h after defecation and stored at - 80 °C for up to 1 year. All steps were documented and cross-checked before donor stool were released for clinical use. Thirteen donors were eligible at the first interview and started donations. Two donors were excluded due to a positive Helicobacter pylori test, two withdrew consent and one was lost to follow-up. One donor took a single dose of NSAIDs 2 days prior to a donation, which was discarded. There were no other excluding findings at the second interview or testing. Eight of the 13 donors were approved as stool donors. All donated five times with each donation yielding 1-6 portions. Eighty-four portions were released for clinical use. Recruiting stool donors among blood donors is safe and effective. The Tissue Act yields an appropriate regulative framework for FMT.

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide.

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment. Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon's diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances. Results: Ten LC patients, 10 CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p = .02), but not during and after treatment (p = .09 and p = .33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p < .05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p < .01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p = .06) with no effect of treatment. Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.

Systematic review with meta-analyses: does the pathogen matter in post-infectious irritable bowel syndrome?

Objective: Acute gastroenteritis (AGE) is a risk factor for post-infectious irritable bowel syndrome (PI-IBS). This systematic review evaluates the prevalence and risk-factors of PI-IBS after AGE by specific pathogens. Materials and methods: Medline (1966-2019) and Embase (1974-2019) were searched for studies evaluating PI-IBS minimum 3 months after AGE with Campylobacter spp., Salmonella spp., Shigella spp., Escherischia coli, Clostridium difficile, norovirus, rotavirus, Cryptosporidium spp. or Giardia intestinalis using validated criteria for IBS. Pooled prevalence (PP), odds ratios (OR) and risk factors were determined for single pathogens, groups of bacteria, viruses and parasites, and overall for AGE caused by any pathogen. Random-effect models were used for meta-analyses. Results: A total of 34 articles were included. PP of PI-IBS after Campylobacter spp. was 12% (confidence interval 95% [CI]: 10-15%), Salmonellosis 12% (CI: 9-15%), Shigellosis 11% (CI: 8-15%), C. difficile 14% (CI: 4-29%) and E. coli spp. 12% (CI: 5-20%). OR of PI-IBS after salmonellosis was 5.5 (CI: 2.3-12.8) and after shigellosis 13.8 (CI: 4.2-45.4). Bacterial AGE overall showed OR 5.8 (CI: 4.0-8.3) and AGE caused by any pathogen OR 4.9 (CI: 3.9-6.1). Few studies exist on viral and parasitic gastroenteritis. Conclusions: Current literature show similar risks for bacterial pathogens. Studies are limited for viral and parasitic pathogens. The evaluated risk-factors for PI-IBS varied among the included studies and the existing evidence is insufficient to identify pathogen-specific risk factors.

Antibiotics: a risk factor for irritable bowel syndrome in a population-based cohort.

OBJECTIVES: Use of antibiotics affects the composition of the gut microbiome. The microbiome is thought to play a role in development of irritable bowel syndrome (IBS), but antibiotics as a possible risk factor for IBS has not been clarified. We aimed to explore if antibiotics is a risk factor for IBS by investigating use of antibiotics and development of IBS in a cohort from the Danish background population. MATERIALS AND METHODS: An internet-based web panel representative of the Danish background population was invited to participate in a survey regarding the epidemiology of IBS in 2010, 2011 and 2013. A questionnaire based on the Rome III criteria for IBS were answered at all three occasions. In 2013, a question regarding use of antibiotics in the past year was included. RESULTS: In 2013, use of antibiotics was reported by 22.4% (624/2781) of the population. A higher proportion of individuals with IBS reported use of antibiotics compared with asymptomatic controls [29.0% (155/534) vs. 17.9% (212/1,184), p < .01]. For asymptomatic respondents in 2010 and 2011 (n = 1004), the relative risk of IBS in 2013 related with use of antibiotics was 1.9 [95% confidence interval (CI): 1.1-3.1]. Adjusting for sex by logistic regression, development of IBS was predicted by use of antibiotics with an odds ratio of 1.8 (95% CI: 1.0-3.2). CONCLUSIONS: Antibiotics is a risk factor for IBS in asymptomatic individuals. Possible mechanisms should be investigated in future studies.

Psychometric evaluation of a daily gastro-oesophageal reflux disease symptom measure.

OBJECTIVE: The objective of this study was to evaluate the validity of the Heartburn Reflux Dyspepsia Questionnaire (HRDQ), a newly developed measure of gastro-oesophageal reflux disease (GORD) symptoms. Specifically, the HRDQ was developed for patients, who still experience symptoms with proton pump inhibitor (PPI) treatment. MATERIAL AND METHODS: The psychometric properties of HRDQ were evaluated based on data from two clinical trials of patients with GORD with a partial response to PPIs, one from the UK and one from Denmark and Germany. RESULTS: The HRDQ had good internal consistency (Cronbach's alpha range .83-.88) and test-retest reliability (intraclass correlation coefficient range .71-.90). Convergent and discriminant validity were supported by high correlations with ReQuest™ and ability to differentiate between groups based on ReQuest™ cut-off values. Responsiveness of HRDQ was demonstrated by moderate to high correlations with ReQuest™ change scores and time with symptoms. An HRDQ cut-off value of 0.70 for definition of 'bad day' was also evaluated. CONCLUSIONS: Based on existing evidence, the HRDQ is a valid and reliable measure of GORD symptoms that can be used as a study outcome in clinical trials.

Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota.

The gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant's gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. We conducted a parallel, double-blind, randomised, placebo-controlled, HMO-supplementation study in 100 healthy, adult volunteers, consuming chemically produced 2'-O-fucosyllactose (2'FL) and/or lacto-N-neotetraose (LNnT) at various daily doses and mixes or placebo for 2 weeks. All participants completed the study without premature discontinuation. Supplementation of 2'FL and LNnT at daily doses up to 20 g was shown to be safe and well tolerated, as assessed using the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show that supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria.

The prevalence of intestinal parasites is not greater among individuals with irritable bowel syndrome: a population-based case-control study.

BACKGROUND & AIMS: The parasites Dientamoeba fragilis and Blastocystis have been detected in feces from patients with irritable bowel syndrome (IBS), therefore these parasites may be involved in IBS pathogenesis. We proposed that a higher prevalence of the parasites in IBS subjects compared with asymptomatic controls would support such a mechanism. We aimed to determine the prevalence of these parasites in IBS subjects (cases) and controls and to identify risk factors associated with parasite carriage. METHODS: We performed a population-based, case-control study of an adult population from an internet-based research institute in Denmark. In January 2010, subjects completed a questionnaire based on the Rome III criteria for IBS and answered questions on factors associated with parasite carriage. Respondents (n = 483) were asked to submit fecal samples for parasite testing; samples were analyzed from 124 cases and 204 controls. RESULTS: A greater proportion of controls than cases carried the parasites (50% vs 36%; P = .01). D fragilis was detected in a greater proportion of fecal samples from controls than cases (35% vs 23%; P = .03), as was Blastocystis (22% of controls vs 15% of cases; P = .09), and a greater percentage of controls carried more than 1 species of parasite (16% of controls vs 8% of cases; P = .05). D fragilis infection was associated with having children 5 to 18 years old in the household and Blastocystis infection was associated with high income (≥600,000 Danish Kroner/y, approximately $100,000 US dollars/y), no animals in the household, and drinking bottled water. CONCLUSIONS: D fragilis and Blastocystis were detected in a greater proportion of fecal samples from the asymptomatic background population in Denmark than from subjects with IBS symptoms. These findings indicate that these parasites are not likely to have a direct role in the pathogenesis of IBS. Longitudinal studies are required to understand their role in gastrointestinal health.

Use of proton pump inhibitors after antireflux surgery: a nationwide register-based follow-up study.

OBJECTIVE: Antireflux surgery (ARS) has been suggested as an alternative to lifelong use of proton pump inhibitors (PPI) in reflux disease. Data from clinical trials on PPI use after ARS have been conflicting. We investigated PPI use after ARS in the general Danish population using nationwide healthcare registries. DESIGN: A nationwide retrospective follow-up study of all patients aged ≥18 and undergoing first-time ARS in Denmark during 1996-2010. Two outcome measures were used: redemption of first PPI prescription after ARS (index prescription) and a marker of long-term use, defined by an average PPI use of ≥180 defined daily doses (DDDs) per year. Kaplan-Meier curves and Cox proportional hazards model were used for statistics. RESULTS: 3465 patients entered the analysis. 12.7% used no PPI in the year before surgery, while 14.2%, 13.4% and 59.7% used 1-89 DDD, 90-179 DDD and ≥180 DDD, respectively. Five-, 10- and 15-year risks of redeeming index PPI prescription were 57.5%, 72.4% and 82.6%, respectively. Similarly, 5-, 10- and 15-year risks of taking up long-term PPI use were 29.4%, 41.1% and 56.6%. Female gender, high age, ARS performed in most recent years, previous use of PPI and use of nonsteroidal anti-inflammatory drugs or antiplatelet therapy significantly increased the risk of PPI use. CONCLUSIONS: Risk of PPI use after ARS was higher than previously reported, and more than 50% of patients became long-term PPI users 10-15 years postsurgery. Patients should be made aware that long-term PPI therapy is often necessary after ARS.

Metronidazole therapy for treating dientamoebiasis in children is not associated with better clinical outcomes: a randomized, double-blinded and placebo-controlled clinical trial.

BACKGROUND: There is a paucity of evidence documenting the pathogenicity of Dientamoeba fragilis, an intestinal protozoan common in children. As case reports on successful treatment are numerous, many authors advocate treatment, despite no placebo-controlled trials being available. Metronidazole is often used for treatment, though eradication rates are relatively low (60%-80%). In the present study we determined the clinical and microbiological efficacy of metronidazole in Danish children. METHODS: In this parallel placebo-controlled double-blinded trial, children aged 3-12 years with >4 weeks of gastrointestinal symptoms were allocated using block randomization in a 1:1 ratio to a 10-day course of oral metronidazole or placebo. Primary outcome was change in level of gastrointestinal symptoms, measured on a visual-analog-scale (VAS), and secondary outcome was eradication of D. fragilis infection. Participants, caregivers, investigators, and sponsor were all blinded to group assignment. The trial was registered with clinicaltrials.gov (NCT01314976) prior to start. RESULTS: Of 96 participants, 48 were allocated to the metronidazole and placebo group each. Mean VAS change from pre- to post-treatment did not differ significantly (P = .8) between the metronidazole (-1.8 CI, [-2.5, -1.1]) and the placebo group (-1.6 CI, [-2.3, -.9]). Eradication of D. fragilis was significantly greater in the metronidazole group, although it declined rapidly from 62.5% 2 weeks after end of treatment to 24.9% 8 weeks after end of treatment. CONCLUSIONS: These findings do not provide evidence to support routine metronidazole treatment of D. fragilis positive children with chronic gastrointestinal symptoms. Study funded by Statens Serum Institut. CLINICAL TRIALS REGISTRATION: Trial was registered with clinicaltrials.gov (NCT01314976).

Use of antacids, alginates and proton pump inhibitors: a survey of the general Danish population using an internet panel.

OBJECTIVE: Both over-the-counter medicine, such as antacids or alginates, and proton pump inhibitors (PPI) are used for treating acid-related disorders. We sought to describe what characterizes users of these different medicines, including long-term PPI users within the general population. METHOD: A cross-sectional survey was conducted in an internet panel representative of the Danish adult population in 2012. Data queried included antacid/alginate and PPI use, reason for therapy, co-medication, and presence of upper gastrointestinal symptoms. Long-term PPI use was defined as using PPI ≥1/3 of the last year (∼120 days). Risk of long-term PPI use was estimated by logistic regression. RESULTS: A total of 18,223 people received the questionnaire, of which 52% (9390) responded. Antacid/alginate use was reported by 23%; 16% reported use of only antacid/alginate. PPI use was reported by 13.6%; 6.2% were defined as long-term PPI users. Antacid/alginate users were younger, used less co-medication, had most often started on therapy because of reflux symptoms, and had less often ongoing symptoms. Risk of long-term PPI use appeared to be increased in male gender, by renewing PPI prescription by phone/e-mail, using co-medication, and having started on PPI for several reasons. Combination of antacid/alginate and PPI was reported by approximately 50% of those on therapy with weekly or daily symptoms. CONCLUSION: 23% of Danish adults were using antacids or alginates and 14% were using PPI, of which one-half were on long-term therapy. Prescription renewal by phone or e-mail and use of other prescription medication were associated with long-term PPI use, indicating a behavioral pattern, in which unnecessary PPI therapy may be maintained.

Prevalence, incidence, and risk factors of intestinal parasites in Danish primary care patients with irritable bowel syndrome.

The gut microbiota may be involved in the aetiopathogenesis of irritable bowel syndrome (IBS). We studied the role of intestinal parasites by describing the epidemiology and risk factors for infection in primary care patients aged 18-50 y with IBS. One hundred and thirty-eight patients at baseline and 78/116 patients returning 1 y later, submitted faecal samples that were examined by microscopy, culture for Blastocystis, and real-time PCR for Dientamoeba fragilis, Entamoeba (dispar and histolytica), Cryptosporidium spp., and Giardia intestinalis. Overall, 42-45% of patients harboured intestinal parasites (baseline and follow-up, respectively): D. fragilis carriage was 35-41%; Blastocystis 14-20%. Incidence rates for D. fragilis and Blastocystis were 10 and 4 per 100 person-y, respectively. Blastocystis carriage increased the odds for carrying D. fragilis. Clinical comparisons showed D. fragilis to be associated with a low frequency of defecation. Further, D. fragilis was associated with having children aged 5-18 y and Blastocystis with increasing age.

Health-related quality of life scores changes significantly within the first three months after hernia mesh repair.

BACKGROUND: Patient-related outcome measures (PROM) such as quality of life (QoL) after hernia repair are important to monitor, since QoL is an important indication of a hernia repair. Carolinas Comfort Scale (CCS) is a hernia-specific questionnaire regarding health-related QoL after a mesh hernia repair. The primary objective of this study was to monitor changes in health-related QoL over time after different mesh hernia repair procedures using the CCS. METHODS: We performed a prospective study with an exploratory, intraobserver design enrolling consecutive patients who were to undergo elective mesh hernia repair. Four different hernia repair techniques were included and analyzed specifically for each surgical group. Patients scored themselves using CCS preoperatively and at several fixed times postoperatively. Since no gold standard exists for either hernia-specific QoL questionnaires or change of scores on PROMs as a function of time after hernia repair, we compared the CCS scores with the visual analog scale (VAS) scores reflecting the subdomains of the CCS. RESULTS: A total of 166 patients completed the study. CCS scores for QoL, pain, sensation of mesh, and activity limitations changed significantly with time during the 90-day study period. Furthermore, CCS and VAS showed significant agreement and correlation (ρ = 0.52-0.82, P < 0.001). CONCLUSIONS: The present study is the first to demonstrate significant changes over time in health-related QoL using the CCS after four different types of hernia repair with mesh.

Analysis of upper gastrointestinal adverse events among patients given dabigatran in the RE-LY trial.

BACKGROUND & AIMS: Dabigatran is an oral and direct inhibitor of thrombin. In a study of patients with atrial fibrillation (the RE-LY trial), twice as many subjects given dabigatran reported dyspepsia-like symptoms compared with those given warfarin (controls). We analyzed data from this trial to quantify upper gastrointestinal nonbleeding adverse events (NB-UGI AEs). METHODS: We analyzed the AE database from the RE-LY trial (18,113 subjects) and assigned NB-UGI AEs to 4 groups: those associated with gastroesophageal reflux (GERD), upper abdominal pain and dyspepsia, dysmotility, or gastroduodenal injury. We analyzed frequency, timing, and severity, and clinical variables associated with NB-UGI AEs. RESULTS: NB-UGI AEs occurred in 16.9% of subjects given dabigatran and in 9.4% of controls (relative risk [RR], 1.81; 95% confidence interval [CI], 1.66%-1.97%; P < .001). Rates of AEs were not associated with the dose of dabigatran. Among subjects with any UGI symptom who were given dabigatran (n = 2045), symptoms were rated as mild in 46.3%, moderate in 44.8%, and severe in 8.9%; these values were similar to those of controls. GERD-associated NB-UGI AEs were most frequent among the 4 groups (compared with controls, RR, 3.71; 95% CI, 2.98%-4.62%; P < .001). Four percent of subjects stopped taking dabigatran because of NB-UGI AEs (most within 3 months of starting therapy), compared with 1.7% of controls (RR, 2.34; 95% CI, 1.90%-2.88%; P < .001). NB-UGI AEs slightly increased risk of major GI bleeding among subjects given dabigatran and controls (6.8% vs 2.3%, P < .001). CONCLUSIONS: Among patients given dabigatran for atrial fibrillation, NB-UGI AEs are generally mild or moderate; 4% stopped taking the drug over a median of 21.7 months. The greatest increase was in GERD-type NB-UGI AEs. These observations should guide management and prevention strategies.

A positive diagnostic strategy is noninferior to a strategy of exclusion for patients with irritable bowel syndrome.

BACKGROUND & AIMS: Guidelines recommend a positive strategy based on symptom criteria to diagnose patients with irritable bowel syndrome (IBS). We conducted a randomized noninferiority trial to determine whether a positive diagnostic strategy is noninferior to a strategy of exclusion, with regard to patients' health-related quality of life (HRQOL). METHODS: We studied 302 patients (18-50 years old) from primary care who were suspected of having IBS and referred by general practitioners. Patients who fulfilled the Rome III criteria for IBS with no alarm signals were randomly assigned to groups assessed by a strategy of exclusion (analyses of blood, stool samples for intestinal parasites, and sigmoidoscopies with biopsies) or a positive strategy (analyses of blood cell count and C-reactive protein). Patients were followed for 1 year. The primary end point was difference in change of HRQOL from baseline to 1 year between groups (on the basis of the Short Form 36 health survey, physical component summary, and noninferiority margin of 3 points). Secondary outcomes were change in gastrointestinal symptoms, satisfaction with management, and use of resources. Findings of diagnostic misclassification were registered. RESULTS: A positive strategy was noninferior to a strategy of exclusion (difference, 0.64; 95% confidence interval, -2.74 to 1.45). The positive diagnostic strategy had lower direct costs. Each approach had similar effects on symptoms, satisfaction, and subsequent use of health resources. No cases of inflammatory bowel disease, colorectal cancer, or celiac disease were found. CONCLUSIONS: In diagnosing IBS in primary care, use of a positive diagnostic strategy is noninferior to using a strategy of exclusion with regard to the patients' HRQOL. Our findings support the current guideline recommendations.

Patients suspected of irritable bowel syndrome--cross-sectional study exploring the sensitivity of Rome III criteria in primary care.

OBJECTIVES: The Rome III criteria for irritable bowel syndrome (IBS) are recommended by guidelines to help identify the syndrome. The majority of IBS patients are managed in primary care, where a pragmatic approach to diagnosis is usually adopted, using clinical judgment and knowledge about the patient. Many general practitioners (GPs) have no or limited knowledge of the diagnostic criteria, few use them, and many consider IBS a diagnosis of exclusion. The aim of this study is to explore the sensitivity of the Rome III criteria in relation to a GP-based clinical diagnosis of IBS, to identify differences between Rome III-positive and -negative patients, and to describe the agreement between the various symptom-based criteria. METHODS: Patients aged 18-50 years, presenting in primary care with gastrointestinal complaints and identified as IBS patients by their GP, were referred for enrollment. The Manning and Rome I-III criteria were evaluated through interviews and patients completed the questionnaires The Gastrointestinal Symptom Rating Scale (GSRS)/The Gastrointestinal Symptom Rating Scale modified for use in patients with IBS (GSRS-IBS), Short Form 36, Irritable Bowel Syndrome Quality of Life measurement, Work Productivity and Activity Impairment questionnaire-irritable bowel version, and a questionnaire on use of health-care resources. RESULTS: A total of 604 patients were referred and 499 were included (mean age 32.8 (s.d. 9.5) years, 75% were female). The Rome III criteria were fulfilled by 376 patients (sensitivity 0.75, 95% CI 71-79%). Rome III-positive patients more frequently reported disturbed defecation, had a higher symptom burden, and lower disease-specific health-related quality of life compared with Rome III-negative patients. The various symptom-based criteria identified slightly different subpopulations with the highest agreement between the Rome II and III criteria. CONCLUSIONS: The Rome III criteria identified three in four patients labeled with IBS in primary care. The relevance of the Rome III for IBS in primary care is supported.

The epidemiology of irritable bowel syndrome in Denmark. A population-based survey in adults ≤50 years of age.

OBJECTIVE: Our aims were to investigate the prevalence and subtype distribution of irritable bowel syndrome (IBS) according to the Rome III criteria in Denmark, to describe the difference in symptom reporting between those with gastrointestinal (GI) symptoms not fulfilling Rome III for IBS compared to those classified as IBS, and furthermore to describe the proportion of consulters and formally diagnosed subjects. MATERIAL AND METHODS: A web-based survey was carried out in January 2010. Questionnaires were emailed to a web panel (n = 19,567) representative of the general Danish population aged 18-50 years on gender, age, and geography. IBS and subtypes were estimated by the Rome III criteria. RESULTS: Of 6112 responders, 979 (16%) fulfilled the Rome III criteria for IBS and had no organic diagnosis likely to explain their symptoms. Subtypes were: mixed IBS 36%, IBS with diarrhea 33%, IBS with constipation 18%, and unsubtyped IBS 11%. Those with GI symptoms, not fulfilling Rome III for IBS, had symptoms very similar to those classified as IBS, but symptoms were less frequent and of shorter duration. Of IBS subjects, 180/978 (18.4%) had consulted a doctor for GI symptoms within the past 3 months, but only 7.9% were diagnosed with IBS. CONCLUSION: Symptoms compatible with IBS according to Rome III are highly prevalent in Denmark. A high proportion of sufferers are undiagnosed.