Smoking prevalence and its influence on disease course and surgery in Crohn's disease and ulcerative colitis.

BACKGROUND: Smoking demonstrates divergent effects in Crohn's disease (CD) and ulcerative colitis (UC). Smoking frequency is greater in CD and deleterious to its disease course. Conversely, UC is primarily a disease of nonsmokers and ex-smokers, with reports of disease amelioration in active smoking. AIM: To determine the prevalence of smoking and its effects on disease progression and surgery in a well-characterised cohort of inflammatory bowel diseases (IBD) patients. METHODS: Patients with smoking data of the Sydney IBD Cohort were included. Demographic, phenotypic, medical, surgical and hospitalisation data were analysed and reported on the basis of patient smoking status. RESULTS: 1203 IBD patients were identified comprising 626 CD and 557 UC with 6725 and 6672 patient-years of follow-up, respectively. CD patients were more likely to smoke than UC patients (19.2% vs. 10.2%, P < 0.001). A history of smoking in CD was associated with an increased proportional surgery rate (45.8% vs. 37.8%, P = 0.045), requirement for IBD-related hospitalisation (P = 0.009) and incidence of peripheral arthritis (29.8% vs. 22.0%, P = 0.027). Current smokers with UC demonstrated reduced corticosteroid utilisation (24.1% vs. 37.5%, P = 0.045), yet no reduction in the rates of colectomy (3.4% vs. 6.6%, P = 0.34) or hospital admission (P = 0.25) relative to nonsmokers. Ex-smokers with UC required proportionately greater immunosuppressive (36.2% vs. 26.3%, P = 0.041) and corticosteroid (43.7% vs. 34.5%, P = 0.078) therapies compared with current and never smokers. CONCLUSIONS: This study confirms the detrimental effects of smoking in CD, yet failed to demonstrate substantial benefit from smoking in UC. These data should encourage all patients with IBD to quit smoking.

An objective study of acid reflux and cough in children using an ambulatory pHmetry-cough logger.

OBJECTIVE: There are no objective ambulatory studies on the temporal relationship between reflux and cough in children. Commercial pHmetry loggers have slow capture rates (0.25 Hz) that limit objective quantification of reflux and cough. The authors aimed to evaluate if there is a temporal association between cough and acid pH in ambulatory children with chronic cough. DESIGN, SETTING AND PATIENTS: The authors studied children (aged <14 years) with chronic cough, suspected of acid reflux and considered for pHmetry using a specifically built ambulatory pHmetry-cough logger that enabled the simultaneous ambulatory recording of cough and pH with a fast (10 Hz) capture rate. MAIN OUTCOME MEASURES: Coughs within (before and after) 10, 30, 60 and 120 s of a reflux episode (pH<4 for >0.5 s). RESULTS: Analysis of 5628 coughs in 20 children. Most coughs (83.9%) were independent of a reflux event. Cough-reflux (median 19, IQR 3-45) and reflux-cough (24.5, 13-51) sequences were equally likely to occur within 120 s. Within the 10 and 30 s time frame, reflux-cough (10 s=median 2.5, IQR 0-7.25; 30 s=6.5, 1.25-22.25) sequences were significantly less frequent than reflux-no cough (10 s=27, IQR 15-65; 30 s=24.5, 14.5-55.5) sequences, (p=0.0001 and p=0.001, respectively). No differences were found for 60 and 120 s time frame. Cough-reflux sequence (median 1.0, IQR 0-8) within 10 s was significantly less (p=0.0001) than no cough-reflux sequences (median 29.5, 15-67), within 30 s (p=0.006) and 60 s (p=0.048) but not within 120 s (p=0.47). CONCLUSIONS: In children with chronic cough and suspected of having gastro-oesophageal reflux disease, the temporal relationship between acid reflux and cough is unlikely causal.

Who needs colonoscopy to identify colorectal cancer? Bowel symptoms do not add substantially to age and other medical history.

BACKGROUND: Many bodies advise that people with bowel symptoms undergo colonoscopy to detect colorectal cancer. AIM: To determine which bowel symptoms predict cancer on colonoscopy. METHODS: Information was collected on symptoms, demographics and medical history from patients subsequently undergoing colonoscopy. Multiple logistic regression modelling was used to identify predictors of colorectal cancer. An ROC curve was estimated for each model, and the area under the curve (AUC) was computed. RESULTS: Cancer was found in 159 patients and no cancer or adenoma in 7577 patients. Bowel symptoms that predicted cancer were rectal bleeding, change in bowel habit and rectal mucus. Prediction was the strongest in patients who had symptoms at least weekly and commencing within the previous 12 months; abdominal pain was predictive only in such patients. The odds ratios never exceeded 4.27. A model based on age, gender, and medical history was highly predictive (AUC = 0.79). Adding symptoms to this model increased the AUC to 0.85. CONCLUSIONS: This model predicts patients in whom colonoscopy will have the highest yield. Conversely, colonoscopy can be avoided in people at low risk: in our study, 95% of cancers could have been detected by doing only 60% of the colonoscopies.

Clinical trial: the treatment of gastro-oesophageal reflux disease in primary care--prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg.

BACKGROUND: A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care. AIM: To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg. METHODS: In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0-7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8-27. RESULTS: Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes. CONCLUSIONS: In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.

The effectiveness of rifabutin triple therapy for patients with difficult-to-eradicate Helicobacter pylori in clinical practice.

BACKGROUND: Failure of first line and subsequent Helicobacter pylori eradication therapy is a significant problem and alternative treatments are few. AIMS: To evaluate the efficacy of a rifabutin-based triple therapy in clinical practice and determine the optimal strategy for its use. METHODS: Patients referred after first or subsequent treatment failure were prescribed rifabutin triple therapy consisting of standard dose proton pump inhibitor, amoxicillin 1 g and rifabutin 150 mg each b.d. for 10 days. RESULTS: In 67 patients, the main indications for treatment were dyspepsia (55%), peptic ulcer disease (24%) and increased gastric cancer risk (18%). The median number of previous treatments was 2 (range: 1-9). Eradication of Helicobacter pylori was achieved in 76% (48/63) per protocol and 72% (48/67) on an intention-to-treat basis. When used as second line therapy, 95% (18/19) achieved eradication compared with 68% (30/44) when two or more previous treatments had been used (P = 0.03). Outcome was independent of age, ethnicity, gender or indication for treatment. Adverse events were reported in 10%. CONCLUSION: Rifabutin triple therapy is a well tolerated and effective second line therapy in the treatment of persistent Helicobacter pylori; however, its efficacy decreases with increasing number of failed previous therapies.

The C-caffeine breath test distinguishes significant fibrosis in chronic hepatitis B and reflects response to lamivudine therapy.

BACKGROUND: The 13C-caffeine breath test is a non-invasive, quantitative test of liver function. AIM: To determine the utility of the 13C-caffeine breath test in chronic hepatitis B virus and its ability to monitor response to lamivudine. METHODS: Forty-eight chronic hepatitis B virus patients and 24 controls underwent the 13C-caffeine breath test. In 28 patients commenced on lamivudine, 13C-caffeine breath tests were performed at 1 week (n = 12) and after 1 year of therapy. RESULTS: Patients with Metavir F0-1 fibrosis (2.30 +/- 1.02 Delta per thousand per 100 mg caffeine) had a 13C-caffeine breath test similar to controls (2.31 +/- 0.85, P = 0.96). However, patients with F2-3 fibrosis (1.59 +/- 0.78, P = 0.047) and cirrhotic patients (0.99 +/- 0.33, P = 0.001) had a decreased 13C-caffeine breath test. Fibrosis correlated best with the 13C-caffeine breath test (r(s) = -0.62, P < 0.001). The 13C-caffeine breath test independently predicted significant (F > or = 2) and advanced (F > or = 3) fibrosis and yielded the greatest area under the receiver operating characteristic curve (0.91 +/- 0.04) for predicting advanced fibrosis. The 13C-caffeine breath test was unaltered by 1 week of lamivudine but improved by 61% (P < 0.001) in responders to long-term lamivudine, whereas in those with viraemia and elevated alanine aminotransferase, values remained stable or deteriorated. CONCLUSION: The 13C-caffeine breath test distinguishes chronic hepatitis B virus-related fibrosis and detects improvement in liver function in response to long-term lamivudine.

Review article: oesophageal complications and consequences of persistent gastro-oesophageal reflux disease.

The major oesophageal complications associated with persistent gastro-oesophageal reflux disease (GERD) include erosive oesophagitis, ulceration, strictures and gastrointestinal (GI) bleeding. Although the causes of these complications are uncertain, studies indicate that erosive oesophagitis may progress to the development of ulcers, strictures and GI bleeding. Pharmacological treatment with proton pump inhibitors is favoured over that with H(2)-receptor antagonists for the treatment of strictures. The treatment of strictures is accomplished with dilation and many favour the concomitant use of proton pump inhibitors. Most gastroenterologists are seeing far fewer oesophageal strictures these days since the introduction of proton pump inhibitors. In addition, research has shown that oesophageal complications have a greater impact on patients suffering from night-time GERD than on those suffering from daytime GERD. Barrett's oesophagus is a significant complication associated with persistent GERD and those at risk generally experience a longer duration of symptoms, especially those with a high degree of severity. In addition, there is a strong relationship between Barrett's oesophagus and oesophageal adenocarcinoma. This is in part due to the association of obesity and the development of hiatal hernias. Furthermore, endoscopic screening is being used to detect Barrett's oesophagus and oesophageal adenocarcinoma in persons suffering from chronic GERD, even though screening may not have an impact on outcomes (Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett's esophagus: The AGA Chicago Workshop. Gastroenterology 2004; 127: 310-30.).

Gastro-oesophageal reflux disease and Helicobacter pylori.

The interaction between gastro-oesophageal reflux disease (GERD) and Helicobacter pylori (H. pylori) infection has been the subject of intense scrutiny in recent years. Although the evidence base is incomplete it is now sufficient to clarify a number of key questions. H. pylori is not a risk factor for reflux disease. Similarly, H. pylori infection, in most patients, is not ''protective'' against the risk of developing reflux and oesophagitis. Furthermore, reflux and oesophagitis are not more likely to develop or to worsen after H. pylori eradication therapy and eradication does not make control of reflux symptoms with proton pump inhibitor (PPI) therapy more difficult. Long term PPI therapy in the presence of H. pylori infection does increase the rate at which gastric mucosal atrophy and intestinal metaplasia develop. Eradication therapy has been shown to reduce this risk. In the uninfected stomach, PPIs are associated with a low likelihood of these adverse histological changes. PPI therapy reduces the accuracy of diagnostic tests for H. pylori. The decision to test for and treat H. pylori infection in the context of reflux must be individualised based on patient factors including co-morbidity, age, gastric histology, family history and informed choice. Distinction must be made between treating symptoms and potentially reducing risks. A decision not to test for and treat H. pylori is now just as active a choice as is the decision to test and treat. Recent international consensus statements recommend eradication of H. pylori prior to long term PPI therapy in reflux disease, although there is not a universal agreement on this. Further research to clarify the risk and benefits of such an approach is required.

Chest pain. Differentiating GIT from cardiac causes.

BACKGROUND: Chest pain is a common presenting symptom in general practice. Although a cardiac cause is not the commonest origin, a high index of suspicion is needed. When the diagnosis is not clear, a cardiac cause should be considered until proven otherwise. A gastrointestinal origin of chest pain is not infrequent and may be due to oesophageal, gastric or biliary disease. Oesophageal causes are most common and include reflux, hypersensitivity or dysmotility. OBJECTIVE: This paper reviews the main gastrointestinal causes that may present with acute chest pain. DISCUSSION: Clinical history taking is the key to decision making and guides the choice of prompt or routine investigation or a therapeutic trial. When reflux is suspected as the cause, a therapeutic trial of high dose antisecretory therapy is appropriate. Investigations may be helpful when typical reflux symptoms are not present or there is a poor response to this approach. Investigations may include endoscopy, ambulatory pH monitoring, barium swallow or oesophageal manometry.

Randomized trial of omeprazole and metronidazole with amoxycillin or clarithromycin for Helicobacter pylori eradication, in a region of high primary metronidazole resistance: the HERO study.

BACKGROUND: The efficacy of omeprazole-based eradication therapies has been determined mostly in populations with low to moderate prevalence of metronidazole resistant Helicobacter pylori, yet resistance is high in many regions. AIM AND METHODS: The H. pylori eradication and duodenal ulcer healing rates after 1 week of either omeprazole 40 mg mane, amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. (OAM) or omeprazole 20 mg b.d., metronidazole 400 mg b. d. and clarithromycin 250 mg b.d. (OMC) were compared in a randomized trial in Australia and New Zealand. Patients had a further 1 week of omeprazole 20 mg. Outcome was assessed at 6 weeks with stringent criteria (endoscopy, biopsies and 13C-urea breath test). RESULTS: Of 220 subjects randomized, the H. pylori eradication rates (all patients treated/per protocol) were 82%/85% for OMC and 58%/63% for OAM (P= 0.001). Pre-treatment metronidazole resistance was present in 56% and clarithromycin resistance in 6%. The eradication rate for primary metronidazole resistance isolates treated with OMC was 80% (CI: 65-90%) compared with 45% (CI: 29-62%) for OAM, whereas for sensitive organisms, the eradication rates were 94% (CI: 79-99%) and 79% (CI: 62-91%), respectively. Duodenal ulcer healing was 96% for OMC and 87% for OAM. Compliance was excellent and both treatments were well-tolerated. CONCLUSIONS: OMC is a well-tolerated, effective therapy for H. pylori eradication and duodenal ulcer healing in this region despite the high metronidazole resistance rate. OAM is less effective, largely due to the impact of metronidazole resistance.

Aspartate aminotransferase: alanine aminotransferase ratio in chronic hepatitis C infection: is it a useful predictor of cirrhosis?

BACKGROUND: The clinical usefulness of the ratio of serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) has been explored in several liver disorders. It has been suggested that in patients with chronic hepatitis C virus (HCV) infection an AST:ALT > or = 1 has 100% specificity and positive predictive value in distinguishing cirrhotic from non-cirrhotic patients. Such statistical certainty attached to a simple biochemical test merits further evaluation. The present study, therefore, assessed the AST:ALT in patients with chronic HCV infection to determine the validity of the ratio in predicting cirrhosis and to correlate the ratio with the histological grade of necroinflammatory activity and fibrosis. METHODS: A retrospective analysis of 153 patients with chronic HCV infection was conducted. Serum biochemistry had been obtained within a mean of 4 weeks of liver biopsy. The histology was scored in terms of activity and fibrosis as described by Scheuer and correlated with AST:ALT. RESULTS: In 30 patients with cirrhosis, the mean AST:ALT (0.99 +/- 0.06) was higher than in 123 patients without cirrhosis (0.60 +/- 0.02; P < 0.001). A ratio > or = 1 had 95.9% specificity and 73.7% positive predictive value in distinguishing cirrhotic from non-cirrhotic patients, with a 46.7% sensitivity and 88.1% negative predictive value. The ratio also parallelled the Scheuer score with respect to fibrosis but not with respect to inflammation. CONCLUSION: Although relatively insensitive, an AST:ALT > or = 1 is highly specific but not diagnostic for the presence of cirrhosis in patients with chronic HCV infection. The ratio reflects the grade of fibrosis in these patients.

Treating Helicobacter pylori.

BACKGROUND: The treatment for Helicobacter pylori infection has changed continuously during the past decade and recommended treatments have not always been readily available in primary care. These factors have contributed to confusion and considerable variation in prescribing. OBJECTIVE: This short review outlines the key aspects of current treatment of H pylori. DISCUSSION: With the advent of single script, effective therapies, there should be more uniformity in treating this common infection. With appropriate choice of therapy and patient counselling to maximise compliance, excellent H pylori eradication rates are achievable in general practice.

The impact of short-term ranitidine use on the precision of the 13C-urea breath test in subjects infected with Helicobacter pylori.

BACKGROUND: The 13C-urea breath test (13C-UBT) is a very accurate method of Helicobacter pylori diagnosis with a false-negative rate of 1-3%. However, the accuracy of the 13C-UBT is affected by potent acid inhibition with proton-pump inhibitors, which may suppress H. pylori and cause false-negative results. It is not known whether this occurs with less potent acid inhibition by H2-antagonists and any effect may be important clinically. OBJECTIVE: To determine the kinetics of 13CO2 excretion in H. pylori infected subjects during and after short-term ranitidine use. METHODS: Volunteers underwent a baseline 13C-UBT (positive: delta13CO2 > or = 5.0; negative: < or = 3.5; indeterminate: > 3.5 to < 5.0). Infected subjects took ranitidine 300 mg each evening for up to 28 days. 13C-UBTs were performed at weekly intervals and then every other day after ranitidine was ceased. If the 13C-UBT remained positive after 14 days, ranitidine was continued for a further 14 days. RESULTS: Thirty-one subjects were studied (mean age 40.4 +/- 2.1 years; 23 female/8 male; mean baseline delta13CO2 27.3 +/- 2.5). In 28 subjects the 13C-UBT remained positive during ranitidine use. The mean delta13CO2 rose to 124% (P< 0.06) and 121% (P < 0.05) of baseline at 14 and 28 days respectively. In two subjects, the delta13CO2 became indeterminate at day 7 (delta13CO2 4.3 and 3.8). In one of these, return to a positive value (delta13CO2 13.6; 103% of baseline) occurred while still on ranitidine. The other subject became positive again by day 3 off ranitidine (17.8; 119% of baseline). One subject had a transiently negative test after 21 days and this became positive again while still taking ranitidine. CONCLUSIONS: Ranitidine has a minimal effect on the 13C-UBT. The rate of indeterminate or false-negative tests is no greater than in patients on no anti-secretory medication.

The effect of dosing with omeprazole on the accuracy of the 13C-urea breath test in Helicobacter pylori-infected subjects.

BACKGROUND: The 13C-urea breath test (13C-UBT) is an accurate means of Helicobacter pylori diagnosis. However, proton pump inhibitors may suppress H. pylori and cause false negative results. AIM: To study the kinetics of H. pylori suppression by omeprazole during and after short-term use. METHODS: Volunteers underwent a baseline 13C-UBT (13C-urea 100 mg). H. pylori-positive subjects took omeprazole 20 mg daily for 14 days. Those who remained 13C-UBT positive (delta13CO2 >/= 5) continued omeprazole for a further 14 days. 13C-UBTs were performed weekly on omeprazole and then every second day after it was stopped. False negatives occurred when delta13CO2 fell to < 5. RESULTS: In 25 H. pylori-positive subjects (mean age 43.9 +/- 2.4 years; 21 females, 4 males) the mean baseline delta13CO2 was 28.1 +/- 3.4. False negative breath tests occurred in three subjects after 7 days of omeprazole and in a further four subjects after 14 days. A further six subjects developed negative tests between Days 14 and 28. Following cessation of omeprazole, the 13C-UBT became positive again in 12/13 subjects within 4 days and in all within 6 days, with a mean recovery to 99.9 +/- 18.6% of baseline delta13CO2. CONCLUSIONS: False negative 13C-UBTs are common during treatment with omeprazole and occur after as little as 7 days. Return to positive test results is rapid after cessation of omeprazole. These findings are relevant to the timing of testing in clinical practice.

The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach.

BACKGROUND: Vitamin C may be protective against gastric cancer though infection with Helicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C. AIMS: To examine the effects of H pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations. PATIENTS: One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia. METHODS: High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis. RESULTS: Gastric juice ascorbic acid concentration was significantly lower in patients infected with H pylori compared with those uninfected (19.3 mumol/l (interquartile range (IQR) 10.7-44.5) versus 66.9 mumol/l (IQR 24.4-94.2), p = 0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p = 0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 mumol/1 (IQR 7.9-52.2) versus 39 mumol/l (IQR 19.9-142.2), p = 0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p = 0.04). CONCLUSIONS: The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pylori associated carcinogenesis.