Risk prediction rule for advanced neoplasia on screening colonoscopy for average-risk individuals.

BACKGROUND: In resource-limited countries, risk stratification can be used to optimize colorectal cancer screening. Few prospective risk prediction models exist for advanced neoplasia (AN) in true average-risk individuals. AIM: To create and internally validate a risk prediction model for detection of AN in average-risk individuals. METHODS: Prospective study of asymptomatic individuals undergoing first screening colonoscopy. Detailed characteristics including diet, exercise and medications were collected. Multivariate logistic regression was used to elucidate risk factors for AN (adenoma ≥1 cm, villous histology, high-grade dysplasia or carcinoma). The model was validated through bootstrapping, and discrimination and calibration of the model were assessed. RESULTS: 980 consecutive individuals (51% F; 49% M) were enrolled. Adenoma and AN detection rates were 36.6% (F 29%: M 45%; P < 0.001) and 5.1% (F 3.8%; M 6.5%) respectively. On multivariate analysis, predictors of AN [OR (95%CI)] were age [1.036 (1.00-1.07); P = 0.048], BMI [overweight 2.21 (0.98-5.00); obese 3.54 (1.48-8.50); P = 0.018], smoking [< 40 pack-years 2.01 (1.01-4.01); ≥ 40 pack-years 3.96 (1.86-8.42); P = 0.002], and daily red meat consumption [2.02 (0.92-4.42) P = 0.079]. Nomograms of AN risk were developed in terms of risk factors and age separately for normal, overweight and obese individuals. The model had good discrimination and calibration. CONCLUSION: The prevalence of adenoma and AN in average-risk Lebanese individuals is similar to the West. Age, smoking, and BMI are important predictors of AN, with obesity being particularly powerful. Though external validation is needed, this model provides an important platform for improved risk-stratification for screening programs in regions where universal screening is not currently employed.

Fecal Microbiota Transplant Decreases Mortality in Patients with Refractory Severe or Fulminant Clostridioides difficile Infection.

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for recurrent Clostridioides difficile infection (CDI). FMT cures nearly 80% of patients with severe or fulminant CDI (SFCDI) when utilized in a sequential manner. We compared outcomes of hospitalized patients before and after implementation of an FMT program for SFCDI and investigated whether the changes could be directly attributed to the FMT program. METHODS: We performed a retrospective analysis of characteristics and outcomes of patients hospitalized for SFCDI (430 hospitalizations) at a single center, from January 2009 through December 2016. We performed subgroup analyses of 199 patients with fulminant CDI and 110 patients with refractory SFCDI (no improvement after 5 or more days of maximal anti-CDI antibiotic therapy). We compared CDI-related mortality within 30 days of hospitalization, CDI-related colectomy, length of hospital stay, and readmission to the hospital within 30 days before (2009-2012) vs after (2013-2016) implementation of the inpatient FMT program. RESULTS: CDI-related mortality and colectomy were lower after implementation of the FMT program. Overall, CDI-related mortality was 10.2% before the FMT program was implemented vs 4.4% after (P = .02). For patients with fulminant CDI, CDI-related mortality was 21.3% before the FMT program was implemented vs 9.1% after (P = .015). For patients with refractory SFCDI, CDI-related mortality was 43.2% before the FMT program vs 12.1% after (P < .001). The FMT program significantly reduced CDI-related colectomy in patients with SFCDI (6.8% before vs 2.7% after; P = .041), in patients with fulminant CDI (15.7% before vs 5.5% after; P = .017), and patients with refractory SFCDI (31.8% vs 7.6%; P = .001). The effect of FMT program implementation on CDI-related mortality remained significant for patients with refractory SFCDI after we accounted for the underlying secular trend (odds ratio, 0.09 for level change; P = .023). CONCLUSIONS: An FMT program significantly decreased CDI-related mortality among patients hospitalized with refractory SFCDI.

Educational Intervention Improves Proton Pump Inhibitor Stewardship in Outpatient Gastroenterology Clinics.

BACKGROUND: Improper chronic proton pump inhibitor (PPI) use has risen significantly in the last few decades. In our gastroenterology trainees' clinics, we aimed to optimize PPI usage. METHODS: We collected baseline data on patients' PPI use for 8 weeks. Based on gastroenterology society guidelines, we determined conditions for appropriate PPI use. If the indication could not be determined, it was categorized as "unknown". Generated from the three most frequent causes for inappropriate PPI use, interventions were developed to correct each issue. Following a brief educational session, trainees implemented these interventions over a subsequent 8-week interval. RESULTS: During our pre-intervention period, trainees evaluated 263 patients who were prescribed a PPI. In 49% of the cases, the use of PPI was deemed inappropriate. The most common reasons were: gastroesophageal reflux disease (GERD) which was never titrated to the lowest effective dose, twice daily dosing for Barrett's esophagus (BE) chemoprevention and unknown indication. During our intervention period, trainees evaluated 145 patients prescribed a PPI for GERD with well-controlled symptoms in 101 cases. PPI had not been titrated to lowest effective dose in 37 cases prompting intervention which was successful in 23 cases. PPI indication was unknown in 17 cases prompting a message to the prescribing provider to review appropriateness. Two cases of BE chemoprevention with twice daily dosing were appropriately reduced to daily dosing. Ultimately, after intervention, PPI use was deemed appropriate after intervention in 172 (77%) cases. CONCLUSIONS: Improper chronic PPI use was significant. Focusing intervention efforts on PPI use for GERD, BE and unknown indications substantially increased appropriateness of PPI use.

Improving Colorectal Cancer Screening Rates in Patients Referred to a Gastroenterology Clinic.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in the United States. Colonoscopy and fecal immunochemistry testing (FIT) are the primary recommended CRC screening modalities. The purpose of this study is to improve rates of CRC screening in Veterans and County hospital patients referred to gastroenterology fellow's clinics. A total of 717 patients between ages of 49 and 75 years were seen. Previous CRC screening was not performed in 109 patients (15.2%) because of not being offered (73.4%) or declining (26.6%) screening. Patients who received previous CRC screening compared with no previous screening were older (mean age 62.3 years vs. 60.3 years, p < .003), white (88.6% vs. 78.3%, p < .027), and more likely to be Veterans patients (90.8% vs. 77.5%, p < .001). After systematically discussing options for screening with 78 of the 109 unscreened patients, 56 of them (71.8%) underwent screening with either colonoscopy (32) or FIT (24). Patients seen by fellows in their last year of training agreed to undergo screening more often than those seen by other fellows (100% vs. 66.2%, p < .033). Systematic discussions about both colonoscopy and FIT can improve the overall rates of CRC screening.

Defining adenoma detection rate benchmarks in average-risk male veterans.

BACKGROUND AND AIMS: Veterans have higher prevalence of colorectal neoplasia than non-veterans; however, it is not known whether specific Veterans Affairs (VA) adenoma detection rate (ADR) benchmarks are required. We compared ADRs of a group of endoscopists for colonoscopies performed at a VA center with their ADRs at a non-VA academic medical center. METHODS: This was a retrospective review of screening colonoscopies performed by endoscopists who practice at the Indianapolis VA and Indiana University (IU). Patients were average-risk men aged 50 years or older. ADR, proximal ADR, advanced ADR, and adenomas per colonoscopy were compared between IU and the VA groups. RESULTS: Six endoscopists performed screening colonoscopies at both locations during the study period (470 at IU vs 608 at the VA). The overall ADR was not significantly different between IU and the VA (58% vs 61%; P = .21). Advanced neoplasia detection rate (13% vs 17%; P = .46), proximal ADR (46% vs 47%; P = .31), and adenomas per colonoscopy (1.59 vs 1.84; P = .24) were not significantly different. There were no significant differences in cecal intubation rate (100% vs 99%; P = .13) or withdrawal time (10.9 vs 11.1 min; P = .28). In regression analysis, there was significant correlation between the attending-specific ADRs at IU and the VA (P = .041, r2 = 0.69). CONCLUSIONS: In this study of average-risk men undergoing screening colonoscopies by the same group of endoscopists, the ADRs of VA and non-VA colonoscopies were not significantly different. This suggests that a VA-specific ADR target is not required for endoscopists with high ADRs.

Should We Measure Adenoma Detection Rate for Gastroenterology Fellows in Training?

BACKGROUND: Adenoma detection rate (ADR) is a proven quality metric for colonoscopy. The value of ADR for the evaluation of gastroenterology fellows is not well established. The aim of this study is to calculate and evaluate the utility of ADR as a measure of competency for gastroenterology fellows. METHODS: Colonoscopies for the purposes of screening and surveillance, on which gastroenterology fellows participated at the Richard L. Roudebush VAMC (one of the primary training sites at Indiana University), during a 9-month period, were included. ADR, cecal intubation rate, and indirect withdrawal time were measured. These metrics were compared between the levels of training. RESULTS: A total of 591 screening and surveillance colonoscopies were performed by 14 fellows. This included six, four and four fellows, in the first, second and third year of clinical training, respectively. Fellows were on rotation at the VAMC for a mean of 1.9 months (range 1 to 3 months) during the study period. The average ADR was 68.8% (95% CI 65.37 - 72.24). The average withdrawal time was 27.59 min (95% CI 23.45 - 31.73). The average cecal intubation rate was 99% (95% CI 98-100%). There was no significant difference between ADRs, cecal intubation rates, and withdrawal times at different levels of training; however, a trend toward swifter withdrawal times with advancing training was noted. CONCLUSIONS: ADR appears not to be a useful measure of competency for gastroenterology fellows. Consideration should be given to alternative metrics that could avoid bias and confounders.

Under-diagnosing and under-treating iron deficiency in hospitalized patients with gastrointestinal bleeding.

AIM: To determine whether patients hospitalized with gastrointestinal (GI) blood loss anemia are being checked and treated for iron deficiency. METHODS: Retrospective chart review was conducted for all patients admitted to a single tertiary care hospital between 11/1/2011 and 1/31/2012 for any type of GI bleeding. The primary endpoint was the percentage of patients who had their iron studies checked during a hospitalization for GI blood loss anemia. Secondary outcomes included percentage of anemic GI bleeders who had adequate documentation of anemia and iron deficiency, and those who were treated for their iron deficiency. Then we tried to identify possible predictors of checking iron studies in an attempt to understand the thought process that physicians go through when managing these patients. Iron deficiency was defined as Iron saturation less than 15% or ferritin level less than 45 µg/L. Anemia was defined as hemoglobin level less than 13 g/dL for males and 12 g/dL for females. RESULTS: Three hundred and seven GI bleeders were hospitalized during the study period, and 282 of those (91.9%) had anemia during their hospital stay. Ninety-five patients (30.9%) had iron studies performed during hospitalization, and 45 of those (47.4%) were actually found to be iron deficient. Only 29 of those 45 iron deficient patients were discharged home on iron supplements. Of the 282 patients that had anemia during hospitalization, 50 (17.7%) had no documentation of the anemia in their hospital chart. Of the 45 patients that had lab proven iron deficiency anemia (IDA), only 22 (48.5%) had documentation of IDA in at least one note in their chart. Predictors of checking iron studies in anemic GI bleeders were lower mean corpuscular volume, documentation of anemia, having fecal occult blood testing, not having hematemesis or past history of GI bleeding. There were no significant differences between the teaching and non-teaching services in any patient characteristics or outcomes. CONCLUSION: Iron deficiency is under-diagnosed, under-recognized even when iron studies were checked, and under-treated in hospitalized patients with GI bleeding.

Challenging the dogma: a randomized trial of standard vs. half-dose concomitant nonbismuth quadruple therapy for Helicobacter pylori infection.

BACKGROUND: Current treatment of Helicobacter pylori consists of three or four drugs for 7-14 days with important associated cost and adverse events. AIMS: This study compared efficacy and safety of standard dose vs. half-dose concomitant nonbismuth quadruple therapy (NBQT) for 7 days. The standard dose consisted of twice daily rabeprazole 20 mg, amoxicillin 1 g, metronidazole 500 mg, and clarithromycin 500 mg. METHODS: This was a prospective randomized trial. (14)C-urea breath test was performed ≥4 weeks after treatment and ≥2 weeks off acid suppressive therapy. Compliance and adverse events were monitored during treatment. RESULTS: A total of 200 consecutive treatment-naïve patients were enrolled. Baseline characteristics were similar between groups, with 15.5% of subjects reporting prior macrolide use. Eradication occurred in 78% (95% CI 68.6-85.7%) in both groups on intention-to-treat analysis. Per-protocol rates were 82.1 vs. 83.9% for standard-dose patients vs. half-dose patients, respectively (p = NS). Adverse events (only mild) were reported in 57 vs. 41% of standard-dose patients vs. half-dose patients (p = 0.024), with metallic taste and nausea notably less frequent in the latter (36 vs. 12% and 18 vs. 7%, respectively; p < 0.05 for both). Overall, eradication failed in 38.7% of prior macrolide users vs. 18.9% without such exposure (p = 0.019). On multivariate logistic regression, prior macrolide exposure was the only factor associated with failed eradication (OR 2.60, 95% CI 1.06-6.39; p = 0.038). Treatment was cheaper with the half-dose regimen. INTERPRETATION: A 50% reduction in antibiotic dosage does not diminish efficacy of concomitant nonbismuth quadruple therapy but leads to significant reduction in cost and adverse events. Seven-day concomitant NBQT is suboptimal for H. pylori independent of prior macrolide exposure.

Colon cancer metastasis to mediastinal lymph nodes without liver or lung involvement: A case report.

Colon cancer is the second most common type of cancer in females and the third in males, worldwide. The most common sites of colon cancer metastasis are the regional lymph nodes, liver, lung, bone and brain. In this study, an extremely rare case of colon adenocarcinoma with extensive metastasis to the mediastinal lymph nodes without any other organ involvement is presented. A 44-year-old Caucasian male presented with abdominal pain, a change in bowel habits, melena and weight loss. Colonoscopy revealed a large friable, ulcerated, circumferential mass in the ascending colon. Biopsies were consistent with the diagnosis of invasive moderately differentiated adenocarcinoma. Subsequently, right colon resection was performed, and pathological analysis revealed moderately differentiated adenocarcinoma of the right colon with extensive regional lymph node involvement. Computed tomography (CT) scans of the chest, abdomen and pelvis were performed preoperatively as part of routine staging for colon cancer. No liver or lung pathology was identified; however, multiple pathologically enlarged mediastinal lymph nodes were observed. Endoscopic ultrasound with fine needle aspiration of the largest mediastinal lymph node, which measured 5.2×3.5 cm on CT scans, was performed. The pathology was again consistent with the diagnosis of metastatic colorectal primary adenocarcinoma. At present, no optimum treatment has been identified for metastatic colon cancer to the mediastinal lymph nodes. The patient in the current case received chemotherapy with folinic acid, fluorouracil and oxaliplatin (FOLFOX), as well as with bevacizumab. Initial follow-up CT scans of the chest revealed a positive response to treatment. Physicians, in particular, radiologists, must consider the mediastinum during the first evaluation and further follow-up of patients with colorectal carcinoma even in the absence of metastasis.

Sugar-free menthol candy drops improve the palatability and bowel cleansing effect of polyethylene glycol electrolyte solution.

BACKGROUND: Colon preparations are generally poorly tolerated. OBJECTIVE: To study the efficacy of sugar-free candy drops in improving palatability and tolerability of polyethylene glycol electrolyte solution (PEG-E). DESIGN: Single-blind, randomized, controlled trial. SETTING: University medical center. PATIENTS: Ambulatory patients scheduled for elective colonoscopy. INTERVENTION: Menthol candy drops. Patients were randomly assigned to split-dose, 4-L, PEG-E ± cough drops. Palatability was assessed on a linear scale of 1 to 5 (1 = disgusting; 5 = tasty). Quality of preparation, remaining unconsumed volume, and side effects were secondary outcomes. MAIN OUTCOME MEASUREMENTS: Palatability and tolerability of PEG-E. RESULTS: A total of 99 patients were enrolled (50 control group, 49 candy drops-added group). The mean (± standard deviation) palatability score was significantly better in candy drop users versus controls (3.9 ± 0.7 vs 2.8 ± 1.2, respectively; P < .001) as were the preparations scored as excellent (63.3% vs 34% of controls; P = .004). Side effects were similar except for nausea (24.5% candy drops vs 44% controls; P = .04). The amount of unconsumed PEG-E was not different between candy drop and control groups (128 [± 361 mL] versus 69 [± 194 mL], respectively; P = .32) but was significantly lower in excellent grade preparations versus other grades (31 [± 103 mL] versus 162 [± 384 mL], respectively; P = .024). On multivariate logistic regression, an excellent preparation was associated with candy drops (odds ratio [OR] 3.3, 95% confidence interval [CI], 1.4-7.8; P = .006) and smaller unconsumed volume of same-day PEG-E [OR 0.996, 95% CI, 0.992-1.000; P = .044). LIMITATIONS: Single-center study. CONCLUSION: Sugar-free menthol candy drops are a safe and effective addition to split-dose PEG-E, resulting in improved tolerability and patient compliance, which appears to translate into improved bowel cleansing. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01541683.).

Association of Streptococcus bovis endocarditis and advanced colorectal neoplasia: a case-control study.

OBJECTIVE: To study the association between Streptococcus bovis (S. bovis) endocarditis and advanced colorectal neoplasia. METHODS: This was a case-control study of patients with S. bovis endocarditis undergoing colonoscopic evaluation. Patients were matched 1:20 with controls by gender and age (±2 years) from a large screening colonoscopy database. The baseline, colonoscopic and clinicopathological characteristics of patients with S. bovis endocarditis were analyzed. RESULTS: From 1996 to 2010, 18 adult patients with S. bovis bacteremia were identified, of whom 10 with infective endocarditis (IE) underwent colonoscopic evaluation. Endocarditis involved a native or prosthetic valve in six and four of those patients, respectively. All 10 patients recovered without recurrence of IE (mean follow-up duration 49.6 months). None had a concurrent or preceding history of colon disease and only one had subclinical chronic liver disease. Advanced neoplasia, defined as the presence of polyps ≥1 cm (n = 6), villous histology (n = 3), high-grade focal dysplasia (n = 1) or cancer (n = 1), was found under colonoscopy in 6 of the 10 cases (60.0%) compared with 13/200 (6.5%) matched controls (OR 21.6, 95% CI 5.4-86.1, P < 0.0001). CONCLUSIONS: S. bovis endocarditis is strongly associated with the presence of advanced colorectal neoplasia. In the absence of any contraindication, colonoscopic examination is strongly recommended in patients with endocarditis. The exact pathophysiological mechanisms underlying this association and the predilection for S. bovis bacteremia in patients with advanced colonic neoplasia remain unclear.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

Proton pump inhibitors have no measurable effect on calcium and bone metabolism in healthy young males: a prospective matched controlled study.

OBJECTIVES: Proton pump inhibitors (PPIs) are associated with an increased risk of bone fractures. This study sought to evaluate the effect of PPIs on biochemical markers of calcium and bone metabolism. METHODS: Prospective matched controlled study involving healthy adult males (age 18-50years) suffering from frequent heartburn. Patients received standard-dose PPI for 12weeks and were matched by age with healthy controls. Blood studies were taken at 0, 1 and 3months for biochemical markers of mineral and bone metabolism. Two-way (time and PPI treatment) repeated measures analysis of variance (RM-ANOVA) and multiple linear regression were used for analysis. RESULTS: A total of 58 participants (29 per group) completed the study. Mean age of participants was 33.2±7.5years. Baseline characteristics and biomarkers were similar for both groups except for higher BMI (28.6 vs. 25.6kg/m(2), p=0.008) and serum C-terminal cross linked telopeptides of type I collagen [CrossLaps, (300 vs. 228pg/ml, p=0.028)] in the PPI group. There was no difference in parathormone (PTH), ionized calcium, vitamin D, osteocalcin and CrossLaps between the PPI and control subjects (all non-significant; 2-way RM-ANOVA). Multiple linear regression modeling showed no effect of PPIs on any of the studied calcium or bone metabolism biomarkers. CONCLUSION: PPI intake for 12weeks has no measurable effect on calcium or bone metabolism in healthy young males.

Alcohol consumption is a risk factor for colonic diverticulosis.

BACKGROUND AND AIM: The exact factors predisposing to colonic diverticulosis other than age are unknown. METHODS: Cross-sectional study of asymptomatic subjects undergoing screening colonoscopy. A detailed dietary and social questionnaire was completed on all participants. A worldwide review of the literature was performed to further investigate any association between identified risk factors and diverticulosis. RESULTS: Seven hundred forty-six consecutive individuals were enrolled (mean age, 61.1±8.3 y; female: male=0.98). Overall, the prevalence of diverticulosis was 32.8% (95% CI, 29.5-36.2). Diverticula were left-sided, right-sided, or both in 71.5%, 5.8%, and 22.7% of affected subjects, respectively. On univariate analysis, age, sex, adenomatous polyps, advanced neoplasia (adenoma≥1 cm, villous histology, or cancer), aspirin, and alcohol use were significantly associated with diverticulosis. Diet, body mass index, physical activity, and bowel habits were not associated with the disease. On multivariate analysis, increasing age (P<0.001), advanced neoplasia (P=0.021), and alcohol consumption (P<0.001) were significantly associated with diverticulosis. The adjusted odds ratio for diverticulosis in alcohol users was 1.91 (1.36 to 2.69), with increasing prevalence with higher alcohol consumption (P-value for trend=0.001). When the prevalence of diverticulosis reported from 18 countries was analyzed against alcohol use, there was a strong correlation with national per-capita alcohol consumption rates (Pearson correlation coefficient r=0.68; P=0.002). CONCLUSIONS: Alcohol use is a significant risk factor for colonic diverticulosis and may offer a partial explanation for the existing East-West paradox in disease prevalence and phenotype. Further studies are needed to investigate this association and its putative pathophysiological mechanisms.

A randomized trial of standard-dose versus half-dose rabeprazole, clarithromycin, and amoxicillin in the treatment of Helicobacter pylori infection.

OBJECTIVES: To evaluate the efficacy and safety of a standard-dose versus half-dose 10-day triple regimen for the eradication of Helicobacter pylori infection. METHODS: A total of 115 consecutive patients with documented infection were enrolled in this open-label trial. Group A (standard dose) received rabeprazole (20 mg), amoxicillin (1 g), and clarithromycin (500 mg), all twice daily for 10 days. Group B (half dose) received rabeprazole (10 mg), amoxicillin (500 mg), and clarithromycin (250 mg), all twice daily for 10 days. (14)C urea breath tests were performed a minimum of 4 weeks after treatment and a minimum of 2 weeks off any acid-suppressive therapy. Compliance and adverse effects were evaluated throughout the treatment period. RESULTS: A total of 115 patients were enrolled (59 women and 56 men; mean age 47.1±14.0 years). Eradication occurred in 45 of 58 patients [77.6%; 95% confidence interval (CI): 66.9-88.3%] in the standard-dose group versus 44 of 57 in the half-dose group (77.2%; 95% CI: 66.3-88.1%) on an intent-to-treat (ITT) analysis (P=1.00). Per protocol eradication rates were 45 of 57 (78.9%; 95% CI: 68.4-85.9%) and 44 of 54 (81.5%; 95% CI: 71.1-91.8%), respectively (P=0.81). The number of patients reporting any adverse effect was significantly higher in the standard-dose group (64.9 vs. 40.4%; P=0.014). The cost of treatment was significantly less in patients receiving the half-dose regimen (ITT analysis; P<0.05). The number needed to harm to suffer one additional failure in the half-dose over the standard-dose arm was 250 (ITT analysis). CONCLUSION: A half-dose 10-day regimen of rabeprazole, amoxicillin, and clarithromycin is equally effective but cheaper and better tolerated than its standard-dose regimen in the treatment of Helicobacter pylori. Eradication rates of both regimens are, however, suboptimal compared with accepted standards.

Severe hepatotoxicity associated with the combination of spiramycin plus metronidazole.

Drug-induced liver injury (DILI) is a leading cause of acute liver failure and is the most frequent reason for post-marketing drug withdrawal. The spectrum of liver injury is wide, ranging from mild and subclinical injury, noticeable only on routine biochemical testing, to fulminant liver failure and death. Antibiotics, as a group, are a leading cause of DILI. We herein describe 4 patients who developed moderate to severe hepatotoxicity after exposure to a commercially - available combination of two antibiotics - spiramycin and metronidazole - commonly used for the treatment and prevention of periodontal infections. No other aetiology for liver injury could be identified in all cases. Two patients recovered spontaneously, and two had a more severe course, one responding to corticosteroids and mycophenolate mofetil and the other requiring liver transplantation for subacute massive necrosis.

Investigational agents for the irritable bowel syndrome.

IMPORTANCE OF THE FIELD: Irritable bowel syndrome (IBS) is a common disorder with significant health and economic consequences. The etiology of IBS is complex and appears to be multifactorial. Traditional IBS therapies have been directed primarily at the relief of individual symptoms but have been largely disappointing. This has triggered the search for newer treatment strategies with improved patient outcomes. AREAS COVERED IN THIS REVIEW: Enhanced knowledge about the putative pathophysiology of IBS has allowed the identification of new mechanistic targets for treatment. Our aim is to review emerging and promising drugs in the treatment of IBS based on disease pathophysiology. Data were extracted using Medline and PubMed search engines until January 2010. Abstracts were identified through 'Web of Science' and abstract supplements of major gastrointestinal scientific meetings. Drugs were classified according to mechanism of action and those with efficacy in trials involving human subjects examined. WHAT THE READER WILL GAIN: Additional insight into the pathophysiology as well as current and prospective treatments of IBS. TAKE HOME MESSAGE: A multitude of putative drug targets have been identified and some novel treatments have progressed through to human clinical trials, but very few will be approved for the market in the near future. Moreover, and in keeping with the complex and multifactorial nature of this syndrome, it is unlikely that there will be one dominant and universally effective form of therapy for all IBS patients.

Duration of pain is correlated with elevation in liver function tests in patients with symptomatic choledocholithiasis.

BACKGROUND & AIMS: We assessed the temporal relationship between abdominal pain and elevation in liver function tests (LFTs) in patients with acute symptomatic choledocholithiasis. METHODS: Retrospective study of patients that presented within 12 hours of pain onset and were subsequently found to have choledocholithiasis. RESULTS: We identified 40 patients with complete medical records. Levels of aspartate and alanine aminotransferases (AST and ALT) correlated with duration of pain (Pearson correlation, r = 0.633 and 0.622 respectively, P < .001 for both); the correlation was not as strong for γ-glutamyl transpeptidase (GGT) (r = 0.326, P = .046) and was not significant for alkaline phosphatase or bilirubin. This temporal association was stronger in patients that had undergone cholecystectomy versus those with intact gallbladders (for ALT, r = 0.603 vs r = 0.311, respectively). Eighteen patients, evaluated within 6 hours of pain, had normal or minimal alterations in LFTs; transabdominal ultrasound was abnormal in 6 (sensitivity 33.3%). All had repeat LFTs within 24 hours (mean 10.3 ± 6.9 hours later) and large increases in ALT and aspartate aminotransferase levels (mean 10.5- and 6.8-fold respectively; P < .01 for both), intermediate increases in glutamyl transpeptidase levels, (mean 4-fold, P < .05), and no changes in alkaline phosphatase levels. This significant increase in LFTs was the only indication of biliary pathology before endoscopy in 11/18 patients. CONCLUSIONS: Increasing duration of pain is associated with increasing LFTs (particularly transaminases) in patients with acute symptomatic choledocholithiasis. Patients with normal LFTs and ultrasound upon presentation should have repeat LFTs if biliary pain is suspected. The absence of significant biochemical abnormalities within the first 24 hours makes the diagnosis of symptomatic choledocholithiasis unlikely.