Predictors of antiviral treatment initiation in hepatitis C virus-infected patients: a Danish cohort study.

Predictive factors for initiation of antiviral therapy in chronically infected hepatitis C virus (HCV) patients are not fully elucidated. The aim of this study was to determine predictive factors for initiation of treatment with standard or pegylated interferon either alone or combined with ribavirin. A Danish cohort of individuals chronically infected with HCV was used and observation time was calculated from the date of inclusion in the cohort to date of death, last clinical observation, 1 January 2007, or start of HCV antiviral treatment in treatment-naïve patients. Kaplan-Meier survival analysis was used to construct time to event curves. Cox regression was used to determine the incidence rate ratios as estimates of relative risk (RR) and 95% confidence intervals (CI). A total of 1780 patients were enrolled in the study. The cumulative chance of treatment initiation over 5 years was 33.0%. We found several strong predictors of treatment initiation: elevated alanine aminotransferase [>2 times upper limit (RR = 2.17, 95% CI 1.64-2.87), >3 times upper limit (RR = 3.64, 95% CI 2.75-4.81)], genotype 2 or 3 (RR = 1.86, 95% CI 1.49-2.31) and HIV co-infection (RR = 0.28, 95% CI 0.15-0.53). To our knowledge, this study is the first to estimate factors predicting initiation of antiviral treatment in patients with chronic HCV infection on a nationwide scale. We found that several of the factors predicting initiation of antiviral treatment correlate with factors known to predict a better response to treatment and factors known to increase the progression of liver disease.

Duodenal ulcer healing on 2 g of sucralfate daily at bedtime compared to 1 g four times daily.

Seventy-seven patients with endoscopically verified duodenal ulcers were randomized to treatment with either 2 g sucralfate daily at bedtime or 1 g sucralfate q.d.s. in a controlled double-blind comparative study. After a 4-week treatment period, the healing rate was 68% for the former and 69% for the latter treatment.

[Hepatic toxicity of nitrofurantoin. Cases reported to the Center for Monitoring Adverse Drug Reactions 1968-1998]. / Nitrofurantoin-levertoksicitet. Tilfaelde indberettet til Bivirkningsnaevnet 1968-1998.

Forty-four cases of nitrofurantoin-associated hepatic injury were reported to the Danish Center for Monitoring of Adverse Drug reactions from 1968 to 1998. Forty-one were women with a median age of 69 years. They had been treated with nitrofurantoin for median one year (two days-seven years), and all had biochemical and clinical signs of hepatitis. In five cases the injury had been provoked by a rechallenge. Twenty-seven liver biopsies showed an equal amount of acute and chronic histopathological changes. Cirrhosis was diagnosed in seven cases. Four died in liver failure; the others apparently recovered without long-term symptoms. In rare cases, nitrofurantoin can cause toxic hepatitis. Apparently elderly women in long-term treatment are more sensitive to develop this adverse reaction. The drug should be withdrawn if the patient shows any signs of hepatitis during treatment and the patient should be informed about the possible relationship to nitrofurantoin exposure. Rechallenge should not be performed.

[Treatment of irritable colon with the food additive Appital]. / Behandling af colon irritabile med kosttilskuddet Appital.

Appital is a herbal medicine. The aim was to examine its effect in patients with irritable bowel syndrome (IBS). Other diseases were excluded by physical examination, rectoscopy, blood tests and in patients older than 35 years X-ray of the colon or colonoscopy. The study was designed as a double-blind placebo-controlled trial. The patients were randomized to either Appital or placebo. Following two weeks without medicine, the patient had Appital or placebo for eight weeks. Fifty-nine patients were randomized, 47 completed the study. The results were based on symptom scores registered by the patients. The symptom score was significantly reduced in patients treated with Appital (p = 0.002), but when compared to placebo, the difference was insignificant (p = 0.081). We concluded that Appital has no effect in relieving symptoms of IBS compared to placebo, although due to the possibility of type two error we cannot exclude a small, but hardly clinically relevant effect.

Fatal adverse drug reactions reported in Denmark 1968-1988.

During the period 1968-88 a total of 27,938 reports on adverse drug reactions (ADR) were received through the voluntary reporting system in Denmark, of which 713 concerned fatal reactions. Excluding cases of overdosage, congenital malformations and unclassifiable reactions, 590 reports were selected for analysis. Of 215 drugs involved, 41% were marketed before 1968. When corrected for drug consumption figures no significant differences in incidence were found with age and gender. The most frequently reported drug groups were antirheumatics (92), cytostatics (54), antibiotics (53) and oral contraceptives (50). Over-the-counter drugs were involved in 13 reports. Fatal drug interactions were reported in 17 cases. In general the duration of treatment was longer in cases of fatal ADR than the average for ADR as a whole. The diagnoses most frequently reported were bone marrow depression (105), "sudden unexpected death" (57), anaphylactic shock (30) and malignant disease (23). The incidence of fatal thromboembolism involving oral contraceptives was halved following the withdrawal of high-estrogen preparations resulting in an incidence over the period 1983-88 of 1 per 141, 000 user years. The corresponding figure concerning non-steroidal antiinflammatory agents was 1 fatal ADR per 26,000 treatment years. Halothane-induced hepatic damage was reported in 33 cases during 1968-83, but only in 2 cases over the period 1983-88. The number of fatal ADR following use of inhaled adrenergic antiasthmatics was 19 during 1968-83, but 0 during 1983-88 despite a sale corresponding to 360,000 treatment years. Lactate acidosis following oral antidiabetics was reported in 18 cases during 1968-78, but only in 1 during 1978-88 following the withdrawal of phenformin. The annual number of reported fatal ADR remained fairly constant throughout the period despite the introduction of numerous potent drugs. Subject to reservations reflecting the shortcomings inherent in a retrospective analysis of data from a voluntary ADR reporting system, the risk of a fatal ADR is considered extremely low, being estimated at 6 per million inhabitants per year and 1 per 180,000 treatment years.

Reported adverse reactions to and consumption of nonsteroidal anti-inflammatory drugs in Denmark over a 17-year period.

Over the 17-year period 1969-1985, 2,721 reports of 3,521 suspected adverse drug reactions (ADRs) associated with non-steroidal anti-inflammatory drugs (NSAIDs) were submitted to the Danish Committee on ADRs. The results are presented together with the consumption of each drug during the same period. The total sale of NSAIDs showed a four-fold increase during the 17 years, the average corresponding to a permanent intake by 2.2% of the population. The number of reported ADRs per defined daily dose (DDD) sold was markedly lower for "older" drugs like the butazones, indomethacin, ibuprofen, naproxen, ketoprofen, and fenoprofen than for the drugs marketed during the last decade. These differences could not be accounted for by the well-known biases attached to spontaneous ADR reporting. Of 67 fatal reactions, 25 were due to bleeding or perforation of a gastric ulcer, mostly during treatment with indomethacin and naproxen, and in elderly people, and 27 were caused by bone marrow depression or leukaemia, begun mostly during treatment with butazones, but some with indomethacin and naproxen as well. It is pointed out that all reports on fatal bone marrow depression associated with butazones were submitted before 1976 and that the fact that none have been received since that time could be a result of better understanding of the proper dosage of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Yellow nail syndrome--the triad of yellow nails, lymphedema and pleural effusions. A review of the literature and a case report.

The yellow nail syndrome, combination of yellow discoloured nails, lymphedema and pleural effusions, is a rare clinical condition. A review of the literature, including 97 patients, is presented. Most patients developed yellow nail syndrome in early middle age, and the overall male:female ratio was 1.1.6. The etiology of the syndrome is obscure, while the pathogenesis seems to involve impaired lymphatic drainage. A patient, whose recurrent pleural effusions were effectively controlled by chemical pleurodesis, is also presented.

Drug related hospital admissions. Results from an intervention program.

As part of a high-intensity monitoring study of drug events as the cause of admission to departments of internal medicine, the effect of an educational intervention programme was studied. Two departments were included, one specialising in geriatrics and one that received patients by non-selected referral. The series consisted of 607 consecutive admissions studied before and 703 after the intervention. The drug events considered were adverse drug reactions and dose-related therapeutic failures, mainly due to non-compliance. A modest, statistically non-significant decrease in drug related hospital admissions (DRH) was seen, from 14% before to 13% after the intervention period. However, DRHs classified as definitely avoidable showed the significant decrease of 83%. There was no apparent relationship between the topics selected for the intervention programme and changes in the pattern of DRHs. No relationship between alterations in sales data and hospital admissions caused by a given drug could be demonstrated. A blinded external evaluation of case abstracts did not disclose any significant shift in the investigators' assessments. The intervention may have had an non-specific effect on avoidable DRHs.

Eradication of Helicobacter pylori compared with long-term acid suppression in duodenal ulcer disease. A randomized trial with 2-year follow-up. The Danish Ulcer Study Group.

BACKGROUND: Trials evaluating long-term management of duodenal ulcer disease have mainly been focused on recurrence of ulcers, disregarding effects on dyspeptic and reflux symptoms. Profound acid inhibition with a proton pump inhibitor is the gold standard therapy in acid-related diseases. We aimed to compare the symptomatic effects of eradication therapy with those of long-term omeprazole treatment in a design with periods both with and without acid inhibition. METHODS: Patients with active duodenal ulcer were randomized either to omeprazole, 20 mg twice daily until healing, followed by omeprazole, 20 mg/ day for 1 year, or to eradication therapy (metronidazole, amoxicillin, and omeprazole for 2 weeks) followed by placebo for 1 year. All patients were followed up passively for an additional year. Clinical controls were performed every 2 months the 1st year (maintenance phase) and every 6 months during the passive follow-up phase. The study was multicentric and double-blind. The primary end-point was discontinuation of treatment, irrespective of reason. RESULTS: Two hundred and seventy-six patients were randomized (139 in the eradication treatment group). In the maintenance phase there were no differences in the reporting of dyspeptic symptoms or in premature withdrawal. In the passive follow-up phase only five patients in the eradication therapy group discontinued owing to relapse of dyspeptic symptoms or ulcer, compared with 51 patients initially randomized to long-term omeprazole. There were no differences in reflux symptoms or in the development of reflux oesophagitis. CONCLUSIONS: Eradication therapy and long-term omeprazole are equally effective in controlling dyspeptic symptoms and reflux in duodenal ulcer patients with healed ulcers. One-quarter of the duodenal ulcer patients who start eradication therapy continue to be symptomatic or fail therapy for other reasons over a 2-year period. Eradication therapy does not increase the risk of reflux in ulcer patients.