Risk of hospitalization resulting from upper gastrointestinal bleeding among patients taking corticosteroids: a register-based cohort study.

PURPOSE: We assessed the risk of hospitalization for upper gastrointestinal bleeding among patients using systemic corticosteroids, accounting for the use of other drugs that may increase the risk of bleeding. SUBJECTS AND METHODS: We conducted a population-based cohort study in North Jutland County, Denmark. Data on the use of corticosteroids, nonsteroidal anti-inflammatory drugs, aspirin, and anticoagulants during 1991 to 1995 were obtained from a countywide prescription database. All hospitalizations because of upper gastrointestinal bleeding were identified through the Hospital Discharge Registry. The observed numbers of patients with gastrointestinal bleeding in various exposure categories among corticosteroid users were compared with the expected number based on the North Jutland population who did not receive prescriptions for any of the drugs under study. RESULTS: A total of 45,980 patients accrued 18,379 person-years of corticosteroid use. There were 109 hospital admissions for gastrointestinal bleeding among corticosteroid users, compared with 26 expected, yielding a relative risk of 4.2 [95% confidence interval (CI): 3.4 to 5.0]. Among corticosteroid users who did not use other drugs associated with gastrointestinal bleeding, the relative risk was 2.9 (95% CI: 2.2 to 3.7). The relative risk decreased further to 1.9 (95% CI: 1.4 to 2.5) when current corticosteroid usage was compared with former usage. CONCLUSION: We observed an increased risk of hospitalization because of upper gastrointestinal bleeding among patients prescribed corticosteroids, especially among those who use other medications. Confounding from the underlying disease may also have contributed to the observed increase in risk.

Population-based study of the risk and short-term prognosis for bacteremia in patients with liver cirrhosis.

We examined the risk of bacteremia in patients with liver cirrhosis (compared with the risk for all Danish citizens >20 years of age who were living in North Jutland County, Denmark), as well as the type of bacteremia and the 30-day case-fatality rate. We used the Danish National Registry of Patients to identify 1339 patients with liver cirrhosis, and we used the North Jutland County Bacteremia Database to identify episodes of bacteremia. We observed 117 cases of bacteremia in patients with liver cirrhosis (11.0 cases were expected), which yielded a standardized incidence ratio of 10.5 (95% confidence interval [CI], 8.8-12.7). Sixty-two cases of bacteremia were nosocomial infections. There were 53 cases of gram-positive bacteremia, 55 cases of gram-negative bacteremia, and 8 cases of polymicrobial bacteremia (1 case of candidemia was excluded from the analysis). The most common cause of death was bleeding from gastroesophageal varices; the second most common cause of death was infection in the respiratory system. The 30-day case-fatality rate was 0.53 (95% CI, 0.39-0.73). Patients with liver cirrhosis had an increased risk of bacteremia and a poor prognosis.

Birth outcome following maternal use of metoclopramide. The Euromap study group.

AIMS: Metoclopramide is an antiemetic drug used widely during pregnancy for nausea and vomiting. Because of its frequent use any adverse effects on infant health would have major public health implications. We therefore examined the safety of metoclopramide during pregnancy. METHODS: Using the Pharmaco-Epidemiological Prescription Database of North Jutland County, we identified 309 women with singleton pregnancies who had prescriptions for metoclopramide fom 1 January 1991 to 31 December 1996. Information on malformations, birth weight, preterm deliveries and stillbirth were compared with 13 327 references who did not receive prescriptions of any kind during pregnancy. RESULTS: Mean birth weight among exposed women was 3480 g compared with 3470 g among nonexposed. Based on logistic regression models no major differences in the risk were found concerning malformations (OR= 1.11; 95% confidence interval (CI): 0.6-2.1); low birth weight (OR= 1.79; 95% CI: 0.8-3.9) or preterm delivery (OR= 1.02; 95 CI: 0.6-1.7). CONCLUSIONS: We could not document any association between the use of metoclopramide during pregnancy and adverse pregnancy outcome. Because of the limited power of our study further research is required.

[Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography]. / Detektion af kolangiokarcinom ved primaer skleroserende cholangitis ved hjaelp af positron-emissionstomografi.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC). PET scanning can assess metabolism in vivo. The glucose analogue [18 F]fluoro-2-deoxy-D-glucose (FDG) accumulates in malignant tumours because of high glucose metabolism. PET scanning of the liver was performed after intravenous FDG in nine patients with PSC, six with PSC + CC, and five controls. "Hot spots" with radioactivity accumulation were seen in each PSC + CC patient, but not in the two other groups. Values of net metabolic clearance of FDG, K (ml min-1 100 ml-1 tissue), was in CC hot spots 1.59 to 4.17 (median, 2.34; n = 6); in reference liver tissues of these patients 0.40 to 0.69 (0.49); in PSC 0.23 to 0.53 (0.36); in controls 0.20 to 0.34 (0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < 0.001). FDG-PET may detect small CC tumours and be useful in therapeutic management of PSC.

The safety of proton pump inhibitors in pregnancy.

AIM: To assess the safety of proton pump inhibitors during pregnancy. METHODS: Fifty-one pregnant women exposed to proton pump inhibitors around the time of conception or during pregnancy were compared with 13 327 controls without exposure to any prescribed drug in a population-based study based on The Pharmaco-Epidemiological Prescription Database of North Jutland and the Danish Hospital Discharge Registry. RESULTS: Three babies with malformations were found among 38 women exposed to proton pump inhibitors from 30 days before conception to the end of the first trimester. No cases of stillbirth were recorded. Crude relative risks of malformation, low birth weight and preterm delivery were 1.6 (95% CI: 0.5-5.1), 1.8 (95% CI: 0.2-13.0) and 2.3 (95% CI: 0.9-6.0), respectively. CONCLUSIONS: In this population-based follow-up study, we found no substantially elevated risk in terms of malformations, low birth weight or number of preterm deliveries in pregnancies exposed to proton pump inhibitors. However, further monitoring is warranted in order to establish or rule out a potential association between the use of proton pump inhibitors and increased risk of either cardiac malformations or preterm birth.

Detection of cholangiocarcinoma in primary sclerosing cholangitis by positron emission tomography.

Primary sclerosing cholangitis (PSC) predisposes to cholangiocarcinoma (CC), which usually is widespread in the liver at the time of the diagnosis and which has a median survival of approximately 6 months. Positron emission tomography (PET) is a noninvasive scanning method that allows the assessment of metabolism in vivo by means of positron-emitting radiolabeled tracers. [18F]Fluoro-2-deoxy-D-glucose (FDG) is a glucose analogue that accumulates in various malignant tumors because of their high glucose metabolic rates. The purpose of the study was to develop a PET method to detect small CC tumors in patients with PSC. PET scanning of the liver was performed after intravenous injection of 200 MBq FDG in 9 patients with PSC, 6 patients with PSC + CC, and 5 controls. The scanning was performed at successive time intervals for a total of 90 minutes with simultaneous successive arterial blood sampling for radioactivity concentration determination. In each of the PSC + CC patients, 2 to 7 "hot spots" were seen, with volumes of 1.0 to 45 mL (median, 4.4 mL). There were no hot spots in the two other patient groups. The localization of hot spots was confirmed by single-blind evaluation. Data were analyzed by the Gjedde-Patlak plot, yielding values of the net metabolic clearance of FDG, K [mL min(-1) 100 mL(-1) tissue]. In the CC hot spots, maximum K values were 1.59 to 4.17 (median, 2.34; n = 6); in the reference liver tissues of these patients, K values were 0.40 to 0.69 (median, 0.49); in PSC patients, they were 0.23 to 0.53 (median, 0.36); and in controls, they were 0.20 to 0.34 (median, 0.31). The difference between K in CC hot spots and the other groups was statistically significant (P < .001). We conclude that FDG-PET seems to be able to detect small CC tumors and may be useful in the therapeutic management of PSC.

Hepatobiliary dysfunction and primary sclerosing cholangitis in patients with Crohn's disease.

BACKGROUND: Only a few studies have attempted to determined the prevalence of long-standing abnormal liver function and primary sclerosing cholangitis (PSC) in patients with Crohn's disease (CD). The aim of the study was to determine the prevalence of long-standing abnormal liver function test results and to describe the clinical, biochemical, and histologic findings in patients with large-duct classic PSC and small-duct PSC (that is, normal cholangiogram) in patients with CD during a 15-year period. METHODS: Patients with CD and long-standing abnormal liver function results were investigated individually with endoscopic retrograde cholangiography and liver biopsy. RESULTS: Of 262 consecutive patients with CD, 38 (15%) had long-standing increased alkaline phosphatase (ALP) values (mean, 1065 U/l; range, 321-4165 U/l). Of these, 10 patients were classified as having hepatic disease (4%), of which 9 had PSC and 1 had a non-specific reactive hepatitis. Of nine patients with PSC (3.4%), three were classified as having large-duct PSC; five, small-duct PSC; and one, unclassified. In patients with large-bowel CD (n = 102) the prevalence of PSC was 9%. Mean age at diagnosis of PSC was 35 years (22-46 years), and the female to male ratio, 7:2. All PSC patients had large-bowel involvement (P < 0.00015), and two of them developed colonic carcinoma of the large bowel (P < 0.01). All cases of small-duct PSC were stage 1, whereas large-duct PSC were stage 2-3. During the observation period (mean, 5.4 years) no PSC patients died. CONCLUSIONS: The results of our study indicate that PSC is the major hepatic disease in patients with CD and long-standing abnormal liver function tests and is approximately as prevalent as in ulcerative colitis. Patients with PSC and CD may have a milder liver disease than patients with PSC and ulcerative colitis, perhaps because large-duct PSC is less common in patients with CD. Cholangiograms and liver biopsies are both needed to evaluate the extent of the disease.

[Euricterus. A European database on icterus with emphasis on the Danish contribution]. / Euricterus. En europaeisk icterusdatabase med fokus på den danske andel.

Clinical and biochemical data were collected prospectively from 8032 jaundiced patients to form a database as part of a EU-supported project on computer-aided diagnosis. Patients were recruited prospectively from centres in all EU-countries and some other countries as well. Five hundred and twenty-eight jaundiced patients were collected from four centres in Denmark. Alcoholic cirrhosis, acute alcoholic liver disease and malignancy of the pancreas or the biliary tract were more common in the Danish data base: 49% of cases in Denmark as compared to 30% of cases in the international database. Viral hepatitis was underrepresented in Denmark, 16% as compared to 23% in the international group. A crude Bayesian diagnostic programme on the total database with 17 diagnostic groups achieved 63% accuracy. For the 528 Danish cases the diagnostic accuracy was 64% when the European data base was used, whereas it increased to 81% when only the Danish data base was taken as basis for the calculations. In conclusion, we found a drop in diagnostic accuracy for the Danish patients when using the large European data base instead of the national one.

Experimental pain in the stomach: a model based on electrical stimulation guided by gastroscopy.

BACKGROUND: Abdominal pain is often variable in intensity and difficult to characterise due to its referred pain pattern. Clinical pain is furthermore confounded by various emotional and cognitive factors. AIMS: To develop and apply an experimental model to induce localised gastric pain. SUBJECTS: Twelve healthy male volunteers. METHODS: Stimulating electrodes were mounted on a biopsy forceps and electric stimuli were delivered during gastroscopy. Single, five repeated, and continuous stimuli were given at four locations in the stomach. Pain detection thresholds and pain intensities were assessed together with localisation of the referred pain area. RESULTS: Pain detection thresholds were higher in the prepyloric region compared with those obtained at the lesser and greater curvature. Increasing stimulus intensity resulted in augmented pain perception and repeated stimuli elicited pain at a lower stimulus intensity than single stimuli. Continuous stimuli evoked constant (33%), increasing (33%), or decreasing (33%) pain. The localisation of referred pain varied considerably in the subjects. CONCLUSIONS: The model seems relevant to study basic pain mechanisms elicited by localised stimuli in the stomach. The experimental data support the premise that a gastric focus should always be suspected in patients referred with different kinds of abdominal pain.

Interferon-alpha 2b therapy in low-activity hepatitis C: a pilot study.

BACKGROUND: Many patients with chronic hepatitis C have long periods of normal or near-normal liver enzyme levels, even though histologic alterations have been confirmed. The recommendation today is not to treat this patient group. METHODS: In a pilot study 23 hepatitis C virus (HCV) RNA-positive patients with alanine aminotransferase (ALAT) levels less than 1.5 times upper normal limits for at least 6 months on more than three occasions and with histologic liver abnormalities compatible with chronic hepatitis C were treated with 3 MU of interferon-alpha 2b three times a week for 6 months. RESULTS: Nine patients (39%) became HCV RNA-negative in serum during treatment, but only two (8.7%) remained so after 6 months' follow-up. Significantly more patients with genotype other than type 1 became HCV RNA-negative than patients with genotype 1 during treatment (P = 0.005). CONCLUSIONS: Patients with low-activity chronic hepatitis C have a response to interferon-alpha treatment similar to that of patients with increased ALAT levels. Genotype seems to influence the rate of response.

[Recommendations for treatment of paracetamol poisoning. Danish Medical Society, Study of the Liver]. / Rekommandation for behandling af paracetamolforgiftning.

Based on recent reports concerning the efficacy of N-acetylcysteine (NAC) in paracetamol (acetaminophen) poisoning, guidelines for treatment and control of these patients are reviewed by a study group under the Danish Association for the Study of the Liver. It is recommended that NAC-treatment is initiated immediately after referral and continued for 36 hours in all cases. Further NAC-treatment should not be discontinued before a decrease in INR has been observed.

[Transmission of hepatitis B from an adopted child to an adult]. / Hepatitis B-smitte fra et adoptivbarn til en voksen.

A case of acute hepatitis B infection in a 43 year-old male is presented. Seven months before admission the family had adopted a two year-old boy from India, and the child was later found to be seropositive for HBsAg. The patient had no other risk factors of hepatitis B infection and transmission of hepatitis B virus from the adopted child is suspected. It is recommended that children who are adopted from countries with high hepatitis B virus prevalence should be examined for HBsAg, and adoptive family members be vaccinated if the child is found to be HBsAg seropositive.

[Sclerosing cholangitis and ulcerative colitis. Regional prevalence]. / Skleroserende cholangitis og colitis ulcerosa. Et regionalt materiale.

The aim of the study was to determine the prevalence of primary sclerosing cholangitis (PSC) in a regional population of patients with ulcerative colitis (UC). Three hundred and five patients with UC followed over a 12 year period were examined for elevations of serum alkaline phosphatase (> 280 U/l). Twenty four such patients were found. If no cause of these elevations were found by initial investigations, endoscopic retrograde cholangiography was performed in order to determine whether they had PSC. Eleven patients were found to have PSC (3.6%), of whom five had progressive disease, including two deaths from cholangio-carcinoma, during a six-year observation period. We found no certain relation between the extent, duration or activity of ulcerative colitis and the presence of PSC. Alkaline phosphatases were elevated up to 3.7 times the upper reference level, the aminotransferases were only found to be mildly elevated.

Primary sclerosing cholangitis in patients with ulcerative colitis.

The prevalence of primary sclerosing cholangitis (PSC) in patients with ulcerative colitis (UC) attending the Depts. of Medical and Surgical Gastroenterology, Aalborg Hospital, during a 12-year period, was determined. All patients with an alkaline phosphatase (ALP) value above the normal range were investigated. Of 305 patients with UC, 24 patients had elevated ALP values, and 11 of these (3.6% of the study population), 4 males and 7 females, were found to have PSC by direct cholangiography. In five patients the disease worsened (two patients died of cholangiocarcinoma), in four it was stationary, and in two patients the disease improved during a mean observation period of 6 years. No differences in location of disease, disease activity, or duration of disease were found between patients with UC and PSC and patients with UC without PSC. The ALP values were raised to a mean of 3.7 times the upper normal limit (observed range, 1.5-5.5 times the upper normal limit). Aspartate aminotransferase was moderately elevated in most patients, but no other abnormal biochemical liver test results were observed at onset. The results of our study indicate that PSC is the major cause of raised ALP values in patients with UC; thus cholangiography should be performed in UC patients with unexplained elevated ALP levels. A prognostic indicator is needed to predict the individual prognosis and to determine the optimal timing of liver transplantation.

[Autoimmune hepatitis. Forms of manifestation, diagnosis and treatment]. / Autoimmun hepatitis. Fremtroedelsesformer, diagnostik og behandling.

A retrospective study concerning ten patients with autoimmune hepatitis (AiH), diagnosed during a 2 1/2-year period is presented. The age of the patients ranged from 25 to 82 years and nine of the patients were women. Their symptoms included jaundice, pruritus, fever, anorexia and fatigue during a few weeks to years. Seven patients had increased serum aspartate aminotransferase (ASAT) levels. The three patients with normal ASAT levels had hypoalbuminaemia, decreased level of prothrombin or high levels of serum immunoglobulin G. Moderate or high levels of smooth muscle antibody titer were detected in nine patients, while none had increased levels of anti-nuclear antibody titer. Histological features of moderate or severe chronic active hepatitis were demonstrated in nine patients. One patient presented with clinical and histological features of acute hepatitis. Prednisolone therapy was followed by biochemical improvement in all the patients. In one patient, maintenance therapy with prednisolone was combined with azathioprine.

[Primary sclerosing cholangitis]. / Primaer skleroserende cholangitis.

Primary sclerosing cholangitis (PSC) is an uncommon disorder of unknown etiology, characterized by chronic inflammation and fibrosis of the intra- and extrahepatic bile ducts. PSC is commonly associated with chronic inflammatory bowel disease, especially ulcerative colitis, and often in younger men with an extensive colitis. The diagnosis is made by endoscopic retrograde cholangiography. The characteristic findings are multiple strictures and dilatations of the intra- and extrahepatic bile ducts. Patients with PSC usually have a cholestatic biochemical profile. The liver biopsy findings are often non-specific. Different survivals in these patients have been described. However, asymptomatic patients seems to have a more favorable prognosis. The only curative treatment is liver transplantation.