Activation of RAAS in a rat model of liver cirrhosis: no effect of losartan on renal sodium excretion.

BACKGROUND: Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis. METHODS: Bile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured. RESULTS: The renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p < 0.001) which indicated hemodynamic impairment. CONCLUSIONS: Losartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.

The continuous reaction time test for minimal hepatic encephalopathy validated by a randomized controlled multi-modal intervention-A pilot study.

BACKGROUND: Minimal hepatic encephalopathy (MHE) is clinically undetectable and the diagnosis requires psychometric tests. However, a lack of clarity exists as to whether the tests are in fact able to detect changes in cognition. AIM: To examine if the continuous reaction time test (CRT) can detect changes in cognition with anti-HE intervention in patients with cirrhosis and without clinically manifest hepatic encephalopathy (HE). METHODS: Firstly, we conducted a reproducibility analysis and secondly measured change in CRT induced by anti-HE treatment in a randomized controlled pilot study: We stratified 44 patients with liver cirrhosis and without clinically manifest HE according to a normal (n = 22) or abnormal (n = 22) CRT. Each stratum was then block randomized to receive multimodal anti-HE intervention (lactulose+branched-chain amino acids+rifaximin) or triple placebos for 3 months in a double-blinded fashion. The CRT is a simple PC-based test and the test result, the CRT index (normal threshold > 1.9), describes the patient's stability of alertness during the 10-minute test. Our study outcome was the change in CRT index in each group at study exit. The portosystemic encephalopathy (PSE) test, a paper-and-pencil test battery (normal threshold above -5), was used as a comparator test according to international guidelines. RESULTS: The patients with an abnormal CRT index who were randomized to receive the active intervention normalized or improved their CRT index (mean change 0.92 ± 0.29, p = 0.01). Additionally, their PSE improved (change 3.85 ± 1.83, p = 0.03). There was no such effect in any of the other study groups. CONCLUSION: In this cohort of patients with liver cirrhosis and no manifest HE, the CRT identified a group in whom cognition improved with intensive anti-HE intervention. This finding infers that the CRT can detect a response to treatment and might help in selecting patients for treatment.

The use of selective serotonin receptor inhibitors (SSRIs) is not associated with increased risk of endoscopy-refractory bleeding, rebleeding or mortality in peptic ulcer bleeding.

BACKGROUND: Observational studies have consistently shown an increased risk of upper gastrointestinal bleeding in users of selective serotonin receptor inhibitors (SSRIs), probably explained by their inhibition of platelet aggregation. Therefore, treatment with SSRIs is often temporarily withheld in patients with peptic ulcer bleeding. However, abrupt discontinuation of SSRIs is associated with development of withdrawal symptoms in one-third of patients. Further data are needed to clarify whether treatment with SSRIs is associated with poor outcomes, which would support temporary discontinuation of treatment. AIM: To identify if treatment with SSRIs is associated with increased risk of: (1) endoscopy-refractory bleeding, (2) rebleeding or (3) 30-day mortality due to peptic ulcer bleeding. METHODS: A nationwide cohort study. Analyses were performed on prospectively collected data on consecutive patients admitted to hospital with peptic ulcer bleeding in Denmark in the period 2006-2014. Logistic regression analyses were used to investigate the association between treatment with SSRIs and outcome following adjustment for pre-defined confounders. Sensitivity and subgroup analyses were performed to evaluate the validity of the findings. RESULTS: A total of 14 343 patients were included. Following adjustment, treatment with SSRIs was not associated with increased risk of endoscopy-refractory bleeding (odds ratio [OR] [95% Confidence Interval (CI)]: 1.03 [0.79-1.33]), rebleeding (OR [95% CI]: 0.96 [0.83-1.11]) or 30-day mortality (OR [95% CI]: 1.01 [0.85-1.19]. These findings were supported by sensitivity and subgroup analyses. CONCLUSIONS: According to our data, treatment with SSRIs does not influence the risk of endoscopy-refractory bleeding, rebleeding or 30-day mortality in peptic ulcer bleeding.

Minimal hepatic encephalopathy characterized by parallel use of the continuous reaction time and portosystemic encephalopathy tests.

Minimal hepatic encephalopathy (MHE) is a frequent complication to liver cirrhosis that causes poor quality of life, a great burden to caregivers, and can be treated. For diagnosis and grading the international guidelines recommend the use of psychometric tests of different modalities (computer based vs. paper and pencil). To compare results of the Continuous Reaction time (CRT) and the Portosystemic Encephalopathy (PSE) tests in a large unselected cohort of cirrhosis patients without clinically detectable brain impairment and to clinically characterize the patients according to their test results. The CRT method is a 10-minute computerized test of a patient's motor reaction time stability (CRTindex) to 150 auditory stimuli. The PSE test is a 20-minute paper-pencil test evaluating psychomotor speed. Both tests were performed at the same occasion in 129 patients. Both tests were normal in only 36% (n = 46) of the patients and this group had the best quality of life, a normal CRP, a low risk of subsequent overt HE, and a low short term mortality. Either the CRT or the PSE test was abnormal in a total of 64% of the patients (n = 83), the CRT in 53% (n = 69) and the PSE in 34% (n = 44). All these patients had a poorer quality of life, low-grade CRP elevation, moderate risk for subsequent overt HE, and a higher than 20% short term mortality. Both tests were abnormal in 23% (n = 30) of the patients and this group had more advanced cirrhosis and a 40 % short-term mortality. One of the tests was abnormal in the majority of the patients but concordant in only 60%. Most cirrhosis patients seem to have impairments of different cognitive domains and more domains with advancing disease. Two abnormal tests identified patients with an increased risk of overt HE and death.

Review article: the efficacy of biomarkers in chronic fibroproliferative diseases - early diagnosis and prognosis, with liver fibrosis as an exemplar.

BACKGROUND: Nearly 45% of all deaths are associated with chronic fibroproliferative diseases, of which the primary characteristic is altered remodelling of the extracellular matrix. A major difficulty in developing anti-fibrotic therapies is the lack of accurate and established techniques to estimate dynamics of fibrosis, regression or progression, in response to therapy. AIM: One of the most pressing needs in modern clinical chemistry for fibroproliferative disorders is the development of biomarkers for early diagnosis, prognosis, and early efficacy for the benefit of patients and to facilitate improved drug development. The aim of this article was to review the serological biomarkers that may assist in early diagnosis of patients, separate fast from slow- or nonprogressors, and possibly assist in drug development for fibroproliferative diseases, exemplified by liver fibrosis. The lack of success of biochemical markers and the possible reasons for this is discussed in the context of other fields with biomarker success. METHOD: This is a personal opinion review article. RESULTS: Biochemical markers, originating from the fibrotic structure, may have increased specificity and sensitivity for disease. Assessment of the tissue turnover balance by measurement of tissue formation and tissue degradation separately by novel technologies may provide value. CONCLUSIONS: Novel technologies focused on the protein fingerprint in addition to biomarker classification, may increase the quality of biomarker development and provide the much needed biomarkers to further the fibroproliferative field. This is in direct alignment with the Food and Drug Administration and European Medicinal Agencies initiatives of personal health care.

Re-prescribing of causative drugs in persons discharged after serious drug-induced upper gastrointestinal bleeding.

BACKGROUND: Several drug classes are known to be associated with serious upper gastrointestinal bleeding (UGIB), among others NSAID, low-dose acetylsalicylic acid (ASA), vitamin K antagonists (VKA), clopidogrel and selective serotonin reuptake inhibitors (SSRIs). There are few data on how and to what extent these drugs are reintroduced in patients who have been discharged after a bleeding episode related to any of them. AIM: To assess if physicians re-prescribed potential causative drugs after an episode of UGIB and to explore whether drugs with antihaemostatic action (DAHA) are re-prescribed without a gastro-protective agent. METHODS: By use of the Kaplan-Meyer method, we estimated the time from UGIB to re-prescribing for 3652 cases who were all admitted to hospital with a diagnosis of serious upper gastrointestinal bleeding from 1995 to 2006. Data on drug exposure were retrieved from a Danish prescription database, a recent study on drug-related UGIB, and The National Board of Health in Denmark. RESULTS: One-year rates of re-prescribing after UGIB were; 82%, 25%, 43%, 68%, 55%, 71% for SSRIs, NSAID, low-dose ASA, VKA, clopidogrel and dipyridamol, respectively. However, re-prescribing rates without proton pump inhibitors (PPIs) were markedly lower 25%, 3%, 5%, 1%, 17% and 6%, respectively. Non-users of DAHA had a prevalence of PPI use of about 30% a few months after an UGIB. CONCLUSIONS: Drugs with antihaemostatic action are re-prescribed to a large extent after an episode of upper gastrointestinal bleeding, but usually covered by PPIs. This use of PPI is specific for users of drugs with antihaemostatic action.

There is an association between selective serotonin reuptake inhibitor use and uncomplicated peptic ulcers: a population-based case-control study.

BACKGROUND: Persons who use serotonin reuptake inhibitors (SSRIs) seem to be at increased risk of having serious upper gastrointestinal bleeding. In vitro studies have shown that SSRIs inhibit platelet aggregation. It remains unknown if SSRIs have a direct ulcerogenic effect. AIM: To investigate if there is a possible association between use of SSRIs and uncomplicated peptic ulcers. METHODS: A population-based case-control study was conducted in the county of Funen, Denmark, using local prescription database and patient register. The 4862 cases all had a first diagnosis of uncomplicated peptic ulcers from 1995 to 2009. Controls (n = 19 448), matched for age and gender, were selected by risk-set sampling. RESULTS: The adjusted odds ratios (OR) of uncomplicated peptic ulcers among current, recent and past users of SSRIs were 1.50 (95% CI 1.18-1.90), 1.56 (95% CI 0.98-2.49) and 1.32 (95% CI 1.08-1.61). There was no association with tricyclic antidepressants [OR 0.94 (95% CI 0.65-1.35)]. The adjusted OR for the SSRI-uncomplicated peptic ulcers association was 0.76 (95% CI 0.46-1.25) among users of proton pump inhibitors. CONCLUSIONS: Use of SSRI is associated with uncomplicated peptic ulcers, possibly by some effect on the healing process. We cannot exclude some effects of residual confounding or bias by frequent physician contact.

Helicobacter pylori test and eradicate versus prompt endoscopy for management of dyspeptic patients: 6.7 year follow up of a randomised trial.

BACKGROUND: Dyspepsia is a chronic disease with significant impact on the use of health care resources. A management strategy based on Helicobacter pylori testing has been recommended but the long term effect is unknown. AIM: To investigate the long term effect of a test and treat strategy compared with prompt endoscopy for management of dyspeptic patients in primary care. PATIENTS: A total of 500 patients presenting in primary care with dyspepsia were randomised to management by H pylori testing plus eradication therapy (n = 250) or by endoscopy (n = 250). Results of 12 month follow up have previously been presented. METHODS: Symptoms, quality of life, and patient satisfaction were recorded during a three month period, a median 6.7 years after randomisation (range 6.1-7.3 years). Number of endoscopies, antisecretory medication, H pylori treatments, and hospital visits were recorded from health care databases for the entire follow up period. RESULTS: Median age was 45 years; 28% were H pylori infected. Use of resources was registered in all 500 patients (3084 person years) of whom 312 completed diaries. We found no difference in symptoms between the two groups. Median proportion of days without symptoms was 0.52 (interquartile range 0.10-0.88) in the test and eradicate group versus 0.64 (0.14-0.90) in the prompt endoscopy group (p = 0.27) (mean difference 0.05 (95% confidence interval (CI) -0.03 to 0.14)). Compared with the prompt endoscopy group, the test and eradicate group underwent fewer endoscopies (mean difference 0.62 endoscopies/person (95% CI 0.38-0.86)) and used less antisecretory medication (mean difference 102 defined daily doses/person (95% CI -1 to 205)). CONCLUSION: On a long term basis, a H pylori test and eradicate strategy is as efficient as prompt endoscopy for management of dyspeptic patients in primary care and reduces the use of endoscopy and antisecretory medication.

Use of anti-secretory medication: a population-based cohort study.

BACKGROUND: Total use of anti-secretory medication (H2 blockers and proton pump inhibitors) is increasing rapidly, but knowledge of factors related to the increasing use is sparse. AIM: To describe development in the use of anti-secretory medication between 1993 and 2002 at a population level. METHODS: We extracted data on use of anti-secretory medication (H2-blockers and proton pump inhibitors) and ulcerogenic drugs, demographic data, and data on gastroscopy and endoscopically verified oesophagitis and peptic ulcer diagnoses, from three large population-based databases covering the County of Funen, Denmark 1990-2002 (population 470,000). RESULTS: Between 1993 and 2002 incidence of first time users was stable at 16.7/1000 persons/year. Total amount of consumed anti-secretory medication increased from 10.5 DDD/1000 persons/day to 25.2 DDD/1000 persons/day. Ninety per cent of the increase was related to long-term use of anti-secretory medication (> or = 180 DDD/patient/year). In 1993 21% of the anti-secretory medication was used by patients with oesophagitis, this increased to 28% in 2002. The proportion of medication used by peptic ulcer patients decreased from 29% in 1993 to 19% in 2002. CONCLUSIONS: Total use of anti-secretory medication increased as a result of more extensive long-term use, and most of the medication was used by patients without diagnosed peptic ulcer or oesophagitis.

Prediction of therapy in primary endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: It seems rational to perform endoscopic retrograde cholangiopancreatography (ERCP) if the probability of endoscopic therapy is high, but to carry out magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) first if this probability is moderate or low. The aim of the present study was to develop a model describing the probability of endoscopic therapy in patients without previous biliary imaging. PATIENTS AND METHODS: The development of the model was based on stepwise multiple logistic regression applied to 2470 prospectively registered first-time ERCP procedures. The model was evaluated by application to 442 prospectively registered first-time ERCP procedures entered in the database in the following 2 years. RESULTS: Predictors selected were: age, gender, p-amylase >/= 400 U/l, ln(s-bilirubin), ln(s-alkaline phosphatase), common bile duct (CBD) stone seen on transabdominal ultrasonography, gallbladder stone seen on transabdominal ultrasonography, interaction of dilated bile ducts seen on transabdominal ultrasonography with ln(s-bilirubin), and interaction between age and male gender. The area under the receiver operating characteristic (ROC) curve was 0.875 and there was good fit of the model. A test with a probability cutoff value of 80 % had a positive predictive value (PPV) of 92.8 %. Specificity was 87.1 % and, using this test, 52.4 % of patients would have been selected for primary ERCP. In the application cohort, the frequency of therapy was higher than in the development cohort. The area under the ROC curve was 78.7 %. When used in the evaluation cohort, with a cutoff probability of 80 %, the test had sensitivity 84.0 %, specificity 49.5 %, negative predictive value (NPV) 46.6 % and PPV 85.6 %. Of the patients, 76.7 % would have been selected for ERCP. This would have identified 85.5 % of individuals needing therapeutic ERCP without use first of MRCP or EUS. Test-positive cases constituted 90.3 % of stent insertions and 86.3 % of stone extractions. CONCLUSIONS: The model is useful for selection of patients for ERCP at our center.

The cystic fibrosis transmembrane conductance regulator is not a base transporter in isolated duodenal epithelial cells.

Duodenal epithelial bicarbonate secretion has previously been shown to be greatly impaired in mice deficient of the cystic fibrosis transmembrane conductance regulator (CFTR). It has been proposed that transmembranal bicarbonate transport occurs through the CFTR channel itself. In the present study, the transport of acid/base equivalents across the plasma membrane of proximal duodenal epithelial cells from CFTR deficient mice was compared with that of cells from normal littermates. Mixed epithelial cells from both villi and crypts were isolated from proximal duodenum and intracellular pH was assessed by cuvette-based fluorescence spectrometry using the pH sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. The steady state intracellular pH, the acid extrusion rate and the alkaline extrusion rate were unaffected by CFTR deficiency in the presence of CO(2)/HCO(-)(3). Forskolin had no effect on acid extrusion or alkaline extrusion rates. In control experiments without CO(2)/HCO(-)(3), the intrinsic buffering capacities, the steady state intracellular pH and the acid extrusion rates were equivalent in the cells from CFTR deficient mice and normal littermates. The results are consistent with a model where acid/base transport is almost exclusively mediated by the previously described transporters in the murine duodenum (i.e. Na+/H+ exchange, Cl(-)/HCO(-)(3). exchange and Na+:HCO(-)(3). cotransport). There were no evidence for significant CFTR dependent HCO(-)(3). transport in proximal duodenal epithelial cells of mixed villus and crypt origin.

The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease.

BACKGROUND: Mutations in the PRSS1 gene explain most occurrences of hereditary pancreatitis (HP) but many HP families have no PRSS1 mutation. Recently, an association between the mutation N34S in the pancreatic secretory trypsin inhibitor (SPINK1 or PSTI) gene and idiopathic chronic pancreatitis (ICP) was reported. It is unclear whether the N34S mutation is a cause of pancreatitis per se, whether it modifies the disease, or whether it is a marker of the disease. PATIENTS AND METHODS: A total of 327 individuals from 217 families affected by pancreatitis were tested: 152 from families with HP, 108 from families with ICP, and 67 with alcohol related CP (ACP). Seven patients with ICP had a family history of pancreatitis but no evidence of autosomal dominant disease (f-ICP) compared with 87 patients with true ICP (t-ICP). Two hundred controls were also tested for the N34S mutation. The findings were related to clinical outcome. RESULTS: The N34S mutation was carried by five controls (2.5%; allele frequency 1.25%), 11/87 (13%) t-ICP patients (p=0.0013 v controls), and 6/7 (86%) affected (p<0.0001 v controls) and 1/9 (11%) unaffected f-ICP cases. N34S was found in 4/108 affected HP patients (p=0.724 v controls), in 3/27 (11%) with wild-type and in 1/81 (1%) with mutant PRSS1, and 4/67 ACP patients (all p>0.05 v controls). The presence of the N34S mutation was not associated with early disease onset or disease severity. CONCLUSIONS: The prevalence of the N34S mutation was increased in patients with ICP and was greatest in f-ICP cases. Segregation of the N34S mutation in families with pancreatitis is unexplained and points to a complex association between N34S and another putative pancreatitis related gene.

Collagen metabolites in the peripheral and splanchnic circulation of patients with Crohn disease.

BACKGROUND: Fragments of collagen arising during synthesis and breakdown have been suggested as markers of fibrous tissue remodelling in Crohn disease. We compared serum concentrations of the C-terminal propeptide of collagen I (PICP), the N-terminal propeptide of collagen III (PIIINP) and the C-terminal telopeptide of type I collagen (ICTP) in the splanchnic and systemic circulation in Crohn disease requiring segmental intestinal resection. METHOD: 15 consecutive patients undergoing surgery due to strictures or continuous inflammation. Male:female ratio was 6:9. Blood was drawn from a peripheral vein prior to surgery. Immediately before intestinal resection, additional samples were drawn from the antecubital vein and from a mesenteric vein draining the affected intestinal segment. PIIINP, PICP and ICTP were measured with radioimmunoassays. RESULTS: Pre-surgery S-ICTP (median 5.5 microg/L; range 3.2-17.2 microg/L) was significantly increased in peripheral blood compared with healthy controls (median 2.6 microg/L; range 0.6-5.7 microg/L), P < or = 0.05. By contrast, S-PICP (median 98 microg/L; range 62-137 microg/L) and S-PIIINP (median 2.5 microg/L; range 1.2-7.4 microg/L) were significantly lower than S-PICP (median 133 microg/L; range 66-284 microg/L) and S-PIIINP (median 3.4 microg/L; range 1.0-7.1 microg/L) in healthy controls, P < or = 0.05. During surgery. no difference in S-PICP and S-PIIINP was documented between peripheral blood and splanchnic blood. In contrast, S-ICTP was increased in splanchnic blood (median 6.2 microg/L; range 2.7-17.4) compared to peripheral blood (median 5.0 microg/L; range 3.1-13.4) (P=0.05). CONCLUSION: The present study provides further evidence that the altered intestinal collagen metabolism in Crohn disease is reflected in the local and systemic circulation.

Secretin in plasma: ups and downs.

The establishment of a reliable radioimmunoassay for secretin in plasma enabled studies on the physiology of secretin. It was shown that secretin, i.e. the heptacosapeptide isolated by Jorpes and Mutt, is in fact responsible for the phenomena observed by Starling and Bayliss in 1902 when studying the stimulation of pancreatic bicarbonate secretion in response to duodenal acidification. Secretin is released in amounts considerably lower than anticipated, but these amounts are nevertheless sufficient to drive pancreatic and biliary secretion of bicarbonate. Whereas secretin in the fasting state is the most important stimulus to pancreatic secretion of water and bicarbonate, other hormones and nervous factors are essential for the majority of pancreatic postprandial secretion.

Outbreak of Hepatitis B among injecting drug users in Denmark.

BACKGROUND: The incidence of hepatitis B is low in Denmark, but injecting drug users (IDUs) remains a high-risk group for this infection. OBJECTIVES: The aim of the study was to describe a hepatitis B outbreak among IDUs by comparing existing registers. Additionally, we wanted to analyze the genetic variation of the hepatitis B virus involved in the outbreak. STUDY DESIGN: In the County of Funen, registers of laboratory diagnosis, hospital records and reports from clinicians to the Medical Officer of Health (MOH) were compared between 1992 and 1998. HBsAg positive sera recovered from the epidemic were sequenced and compared to known HBV strains. RESULTS: We identified 648 cases of hepatitis B of which 51% (332) were acute infections. The laboratory database identified 96% (319/332) of these, 45% (150/332) were admitted to hospital and 38% (127/332) were reported to public health. By capture-recapture analysis based on MOH reports and hospital records the estimated total number of acute cases were 334 (95% C.I. 283-385). We sequenced 75 HBsAg positive samples and identified two very similar strains of genotype D (serotype ayw3) among IDUs involved in the outbreak. CONCLUSIONS: The current surveillance system did not detect the majority of acute hepatitis B cases in County of Funen. We suggest laboratory-based surveillance of hepatitis B to be implemented at a national level as this may identify new outbreaks faster and more complete than the current surveillance system.

Identifying responders to acid suppression in dyspepsia using a random starting day trial.

BACKGROUND: Functional dyspepsia is a heterogeneous condition and a uniform response to drug treatment is not likely. This may be the reason for the general failure of acid suppression in clinical trials in these patients. It may be more rewarding to identify true responders to drug treatment by a single subject trial. AIM: To develop and to test a novel single subject trial design (random starting day trial) in dyspeptic patients. PATIENTS AND METHODS: A total of 301 dyspeptic patients entered a 16-day trial. All patients received placebo for the first 4 days and switched to omeprazole at a randomized and blinded day between day 5 and day 14. Response was defined as a sustained >/= 50% decrease in symptom score occurring in relation to drug shifting. RESULTS: Spontaneous response varied between 0.3% and 10.6% per day, uniformly distributed over time. Overall, 53-61% of patients with organic dyspepsia had a symptom response in relation to shifting to active treatment, compared to only 23% of patients with functional dyspepsia. The only predictor of response was symptoms suggesting gastro-oesophageal reflux. CONCLUSIONS: A random starting day trial may be a valuable tool to identify response to acid suppression in dyspeptic patients.

Helicobacter pylori test-and-eradicate versus prompt endoscopy for management of dyspeptic patients: a randomised trial.

BACKGROUND: Strategies based on screening for Helicobacter pylori to manage dyspeptic patients in primary care have been proposed, but the clinical consequences are unclear. We did a randomised trial to assess the efficacy and safety of a test-and-eradicate strategy compared with prompt endoscopy in the management of patients with dyspepsia. METHODS: 500 patients presenting in primary care with dyspepsia (> or = 2 weeks of epigastric pain, no alarm symptoms) were assigned H. pylori testing plus eradication therapy or endoscopy. Symptoms, quality of life, patients' satisfaction, and use of resources were recorded during 1 year of follow-up. FINDINGS: 250 patients were assigned test-and-eradicate, and 250 prompt endoscopy. The median age was 45 years and 28% were H. pylori infected. 1 year follow-up was completed by 447 patients. We found no differences in symptoms between the two groups (median registered days without dyspeptic symptoms=0.63 [IQR 0.27-0.81] in the test-and-eradicate group vs 0.67 [0.36-0.86] in the prompt endoscopy group; mean difference 0.04 [95% CI -0.01-0.10], p=0.12). Nor did we find any difference in quality of life or numbers of sick-leave days, visits to general practitioners, or hospital admissions. In the test-and-eradicate group, 27 (12%) of the patients were dissatisfied with management, compared with eight (4%) in the endoscopy group (p=0.013). After 1 year, the use of endoscopies in the test-and-eradicate group was 0.40 times (95% CI 0.31-0.51) the use in the endoscopy group, the use of H. pylori tests increased by a factor of 8.1 (5.7-13.1), the use of eradication treatments increased by a factor of 1.5 (0.9-2.7), and the use of proton-pump inhibitors was 0.89 (0.59-1.33) times the use in the endoscopy group. 43 (91% [80-98%]) of 47 peptic-ulcer patients would have been identified by endoscopy or treated by eradication therapy. INTERPRETATION: A H. pylori test-and-eradicate strategy is as efficient and safe as prompt endoscopy for management of dyspeptic patients in primary care, although fewer patients are satisfied with their treatment.

[Diagnosis of Helicobacter pylori infections--how, when and in whom?]. / Helicobacter pylori-diagnostik--hvordan, hvornår og hos hvem?

Recognition of Helicobacter pylori (Hp) as the major cause of peptic ulcer disease has profoundly changed treatment and prognosis of this disease. The diagnostic tests are invasive (i.e. via the endoscopy) or non-invasive. The invasive tests are: urease test, histology, culture and PCR. Non invasive tests are: breath test, serology and Hp-antigens in faeces. The performance of the tests are almost similar. Sensitivities and specificities usually are > 90%, however the sensitivities and specificities of serological tests may be lower. Choice of diagnostic test depends on the clinical situation, sensitivity and specificity of test and the prevalence of Hp. Patients who should be examined for Hp: 1. The peptic ulcer patient who has used ASA/NSAID (urease test). 2. MALT-lymphoma, (histology). 3: The young (< 45 years) dyspeptic patient with no alarm symptoms and not taking NSAID/ASA (breath test). 4. Recurrence of upper dyspepsia after former eradication of Hp in peptic ulcer patients (if malignancy is not suspected breath test is first choice). 5. Verification of Hp eradication is necessary only in patients with MALT-lymphoma (histology) or patients with complicated peptic ulcer. Breath test will be the first choice in patients with complicated peptic ulcer when endoscopy is not performed. When endoscopy is performed, the urease test is the first choice. Diagnosis of Hp status not indicated: 1. There is no documentation that Hp eradication is of benefit in patients with non organic dyspepsia. Therefore, there is no indication for diagnosis of Hp. 2. Although there is some association between Hp positivity and chronic active gastritis and carcinoma of the stomach, there is at present no indication for diagnosis of Hp, as treatment of the infection has not proved effective in reversing atrophy or dysplasia. 3. The relationship between Hp and ASA/NSAIDs in peptic ulcer disease is far from clear. There is no indication for diagnosis and treatment of the infection prior to treatment with these medications. 4. For patients treated with longterm proton pump inhibitors there is no indication for diagnosis and treatment.

Survival and incidence of colorectal cancer in patients with ulcerative colitis in Funen county diagnosed between 1973 and 1993.

BACKGROUND: The aim of the study was to determine the death rate and the risk of developing colorectal cancer in patients with ulcerative colitis in Funen County. METHODS: The medical records of 801 patients with ulcerative colitis diagnosed in 1973-93 in Funen County were scrutinized with regard to colectomy, survival, and colorectal cancer, and in 1998 a follow-up was carried out. RESULTS: The patients were managed at nine different hospitals: one university hospital, one central hospital, and seven smaller hospitals. The mean age at diagnosis was 41 years, and the mean duration of disease was 10.11 years. Sixty-one per cent of the patients were classified as having proctosigmoiditis, 21% as having left-sided colitis, and 18% as having pancolitis. In 127 patients who underwent proctocolectomy during the study period lethal complications occurred in 8 cases: 5 of 110 in Odense University hospital and 3 of 17 in the other hospitals. One hundred and twenty patients in the cohort died during the period of observation, nine of them of colitis-related causes. There was a slightly increased risk of early death in the cohort after 15 years of disease. Six colorectal cancers were found, whereas four were expected, giving a standard incidence ratio of 1.665. The cumulative cancer risk after 20 years' disease duration was 5.3% in the observed group, contrasting with an expected rate of 0.49%, and 10.1% after 25 years. CONCLUSION: In this cohort of ulcerative colitis patients the mortality and the risk of developing colorectal cancer were slightly higher than expected compared with the background population.