A model to predict the risk of aspirin/non-steroidal anti-inflammatory drugs-related upper gastrointestinal bleeding for the individual patient.

Upper gastrointestinal bleeding is a feared complication of using non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin. Studies predicting the incidence rate for individuals with a given set of characteristics are lacking. The aim of this study was to develop a risk model to predict the incidence rate of upper gastrointestinal bleeding (UGIB) in users of aspirin/NSAID based on presence of well-defined risk factors for the individual patient. METHODS: The model was developed from data from a case-control study, sampled from a well-defined source population, residents of the Funen County 1995-2006. All cases and controls were characterized in terms of factors known to affect the risk of UGIB. By using census data, we rescaled the control group, so their composition accurately reflected age and sex distribution of the source population. Only persons using NSAIDs or/and aspirin and no PPI were included in the analysis. As reference group, we chose 80- to 89-year-old women with no ulcer history, using NSAID, but neither aspirin, other platelet inhibitors, vitamin K antagonists, selective serotonin reuptake inhibitors nor corticosteroids. RESULTS: We identified 1388 cases among non-users of PPIs. We found a modelled baseline incidence rate of 10.7 per 1000 person-years for the reference group. The strongest associations were found for ADP inhibitors (OR 5.80), followed by anticoagulants treatment (OR 2.62) and prior ulcer (OR 2.68). The model performed well in terms of calibration and discriminatory power. CONCLUSION: This study is the first to describe a model, which estimates the incidence rate of UGIB for patients using aspirin/NSAID, based on the specific combination of risk factors. Risk of upper gastrointestinal bleeding for a given patient can be accurately estimated using this model.

Significant association between the use of different proton pump inhibitors and microscopic colitis: a nationwide Danish case-control study.

BACKGROUND: Microscopic colitis causes chronic watery diarrhoea and has previously been associated with the use of proton pump inhibitors. AIM: To explore the association between proton pump inhibitor use and microscopic colitis, including its dependency on timing, dose and choice of proton pump inhibitor. METHODS: Within a 10-year period, we identified 10 652 patients with a first-time diagnosis of microscopic colitis, including 6254 (59%) with collagenous colitis and 4398 (41%) with lymphocytic colitis. All microscopic colitis cases were histologically confirmed in the Danish Pathology Register. Information on proton pump inhibitor use was obtained from the Danish Prescription Register. In this case-control study, we estimated the adjusted odds ratios (aOR) for the association between proton pump inhibitor use and risk of microscopic colitis using conditional logistic regression while adjusting for potential confounders. RESULTS: We found strong associations between current proton pump inhibitor use and both collagenous colitis (aOR 6.98; 95% CI: 6.45-7.55) and lymphocytic colitis (aOR 3.95; 95% CI: 3.60-4.33). This association was observed with all PPIs. The strongest association was with the current use of lansoprazole for both collagenous colitis (aOR 15.74; 95% CI: 14.12-17.55) and lymphocytic colitis (aOR 6.87; 95% CI: 6.00-7.86). When considering timing, ORs were highest for current use of proton pump inhibitor and lower for recent or past exposure. No clear dose-response pattern was observed. CONCLUSIONS: We found a strong association between microscopic colitis and ongoing use of proton pump inhibitors, especially lansoprazole.

The association between use of serotonergic antidepressants and perioperative bleeding during total hip arthroplasty--a cohort study.

In vitro studies have shown that selective serotonin reuptake inhibitors inhibit platelet aggregation. It is well documented that SSRIs cause serious gastrointestinal bleeding, but studies on other bleeding manifestations have been equivocal. Our objective was to determine a possible association between use of serotonergic antidepressants (SA) and perioperative bleeding during hip replacements. We conducted a retrospective study between 1 January 2007 and 30 June 2012 among patients that underwent a primary unilateral uncemented total hip arthroplasty (THA). Information was collected on the observed blood loss and the need for blood transfusions among this group. We compared the blood loss between users of SA, users of non-serotonergic antidepressants (NSA) and non-users, while adjusting for potential confounders using multivariate linear regression. We indentified 1318 patients that underwent a THA in the study period. The average volume of surgical bleeding was 350 ml. The adjusted incremental blood loss associated with use of SA and NSA was 93, 95% confidence interval (38-147) ml and -50 (-125 to 25) ml compared with non-use. Only 48 subjects (3.6%) had transfusions. Use of SA was associated with an increased blood loss compared with non-users. The hypothesis that SA impairs haemostasis is supported by these results.

Helicobacter pylori and risk of upper gastrointestinal bleeding among users of selective serotonin reuptake inhibitors.

BACKGROUND: A number of studies have reported a possible association between use of selective serotonin reuptake inhibitors (SSRIs) and serious upper gastrointestinal bleeding (UGB). We conducted this case-control study to assess if Helicobacter pylori (H. pylori) potentiates the risk of serious UGB in SSRI users. MATERIAL AND METHODS: A population-based case-control study was conducted in the county of Funen, Denmark. Cases were 53 SSRI users with serious UGB whose H. pylori status on their bleeding date could be established. Controls (n = 723) were selected among subjects who participated in a population H. pylori screening study, and who were users of SSRIs. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by unconditional logistic regression. RESULTS: H. pylori infection increased the risk of serious UGB in patients using SSRI with an adjusted odds ratio (OR) of 2.73 (95% confidence interval (CI), 1.17-6.36). The adjusted OR for serious UGB among users of non-steroidal anti-inflammatory drugs (NSAIDs) and acetylsalicylic acid (ASA) were 3.91 (95% CI, 2.03-7.52) and 3.00 (95% CI, 0.94-9.54), respectively. CONCLUSION: H. pylori infection increases the risk of SSRI-related serious UGB.

An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding.

BACKGROUND & AIMS: In vitro studies have shown that selective serotonin reuptake inhibitors (SSRIs) inhibit platelet aggregation. It is controversial whether use of SSRIs is a cause of clinically important bleeding; results from observational studies have been equivocal. METHODS: A population-based case-control study was conducted in Denmark. The 3652 cases all had a first discharge diagnosis of serious upper gastrointestinal bleeding (UGB) from 1995 to 2006. Controls (n = 36,502), matched for age and sex, were selected by risk-set sampling. Data on drug exposure and medical history were retrieved from a prescription database and the county's patient register. Confounders were controlled for by conditional logistic regression and the case-crossover design. RESULTS: The adjusted odds ratio (OR) of UGB among current, recent, and past users of SSRIs was 1.67 (95% confidence interval [CI], 1.46-1.92), 1.88 (95% CI, 1.42-2.5), and 1.22 (95% CI, 1.07-1.39). The adjusted OR for concurrent use of SSRI and nonsteroidal anti-inflammatory drugs (NSAIDs) was 8.0 (95% CI, 4.8-13). The adjusted OR for the concurrent use of NSAID, aspirin, and SSRI was 28 (95% CI, 7.6-103). Of the UGB cases, 377 were current users of SSRI; the adjusted OR for UGB in the case crossover analysis was 2.8 (95% CI, 2.2-3.6). The adjusted OR among users of proton pump inhibitors was 0.96 (95% CI, 0.50-1.82). CONCLUSIONS: Use of SSRI was associated with UGB, consistent with its antiplatelet effects. SSRIs should be prescribed with caution for patients at high risk for UGB.

Do statins protect against upper gastrointestinal bleeding?

AIMS: Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other antithrombotic drugs. METHODS: A population-based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB from a hospital during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by a risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression. RESULTS: The adjusted odds ratios (ORs) associating use of statins with UGB were 0.94 (0.78-1.12) for current use, 1.40 (0.89-2.20) for recent use and 1.42 (0.96-2.10) for past use. The lack of effect was consistent across most patient subgroups, different cumulative or current statin doses and different statin substances. In explorative analyses, a borderline significant protective effect was observed for concurrent users of low-dose aspirin [OR 0.43 (0.18-1.05)]. CONCLUSION: Statins do not prevent UGB, except possibly in users of low-dose aspirin.

Spironolactone use and the risk of upper gastrointestinal bleeding: a population-based case-control study.

AIMS: Recent studies have suggested an increased risk of upper gastrointestinal bleeding (UGB) in spironolactone users. The aim was to confirm the association, identify the risk factors and quantify the absolute risk. METHODS: A population based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502) were selected by risk set sampling. Data on all subjects' drug exposure and past medical history were retrieved from a prescription database and from the County's patient register. Confounders were controlled by conditional logistic regression. RESULTS: The adjusted odds ratio (OR) associating current use of spironolactone with UGB was 2.7 [95% confidence interval (CI) 2.2, 3.2]. The risk increased with higher doses of spironolactone (5.4; 3.4, 8.6) for 100-mg tablets. No trend was found with increasing cumulative dose. The strongest association was found among users aged 55-74 years (OR 13.1; 6.5, 26.3). Current use of loop diuretics was also associated with an increased risk of UGB (1.9; 1.7, 2.1). CONCLUSION: The use of spironolactone is associated with increased risk of UGB. The risk increases with higher doses.

[Treatment of haemosuccus pancreaticus]. / Interventionel behandling af blødning gennem ductus pancreaticus.

With an upper gastrointestinal bleeding in patients diagnosed with chronic pancreatitis it's important to be aware of the possibility of bleeding from the pancreatic duct. This article describes three cases of haemosuccus pancreaticus which we have dealt with in our department over the last decade.

[Use of anti-thrombotic agents--monotherapy or combination and risk of upper gastrointestinal bleedings: a population-based case-control study. Secondary publication]. / Brug af antitrombotisk behandling i monoterapi eller kombination og risikoen for øvre gastrointestinal blødning. Et populationsbaseret case-kontrol-studie. Sekundaerpublikation.

The clinical use of anti-thrombotic agents has shifted towards more aggressive therapy and towards regimes with more than one drug. Data on the risk of upper gastrointestinal bleedings (UGB) with combined anti-thrombotic therapy are scarce. In the period 2000 through 2004, 1,443 cases of serious UGB and 57,720 control subjects were identified in Funen County. Anti-thrombotic therapy is becoming increasingly aggressive. Combined anti-thrombotic therapy confers particular risk and is associated with high incidence rates of GI bleeding.

[Peer tutorial programme as a part of the medical curriculum]. / Studieintroduktion som en del af curriculum.

This article shows the possible effects of an integrated intensive introduction to medical school using older students as tutors for first-year students. Our project resulted in a significant decrease in the average time to completion of the first five semesters of the medical bachelor' degree.

Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study.

OBJECTIVES: To assess the risk of serious upper gastrointestinal bleeding associated with the newer antithrombotic agents used alone or in combination with other antithrombotic drugs; to describe the trends in use of antithrombotic drugs in the background population. DESIGN: Population based case-control study. SETTING: Funen County, Denmark (population 470,000). SUBJECTS: 1443 cases of serious upper gastrointestinal bleeding identified during 2000-4; 57,720 age and sex matched controls. MAIN OUTCOME MEASURE: Exposure to low dose aspirin, clopidogrel, dipyridamole, vitamin K antagonists, and combined antithrombotic treatment. RESULTS: Adjusted odds ratios associating drug use with upper gastrointestinal bleeding were 1.8 (95% confidence interval 1.5 to 2.1) for low dose aspirin, 1.1 (0.6 to 2.1) for clopidogrel, 1.9 (1.3 to 2.8) for dipyridamole, and 1.8 (1.3 to 2.4) for vitamin K antagonists. Corresponding figures for combined use were 7.4 (3.5 to 15) for clopidogrel and aspirin, 5.3 (2.9 to 9.5) for vitamin K antagonists and aspirin, and 2.3 (1.7 to 3.3) for dipyridamole and aspirin. Other combinations were used too infrequently to allow estimation. The number of treatment years needed to produce one excess case varied from 124 for the clopidogrel-aspirin combination to 8800 for clopidogrel alone. During the study period, exposure to combined antithrombotic regimens increased by 425% in the background population. CONCLUSION: Antithrombotic treatment is becoming increasingly aggressive. Combined antithrombotic treatment confers particular risk and is associated with high incidence of gastrointestinal bleeding.

[Is the use of selective serotonin reuptake inhibitors associated with an increased risk of bleeding?]. / Er brug af selektive serotoningenoptagelseshaemmere associeret med en øget risiko for blødning?

Recent studies have shown that there may be an increased risk of upper gastrointestinal tract bleeding when patients use selective serotonin reuptake inhibitors (SSRIs). We have reviewed the available epidemiological papers on this subject. There is apparently an increased risk of clinically significant bleeding episodes in patients treated with SSRIs. Two papers report a multiplicative interaction for combined treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and SSRIs. We conclude that SSRIs should be used with caution in patients with an increased risk of bleeding.

[Plasmapheresis in the treatment of cholestasis-induced pruritus]. / Plasmaferese som led i behandlingen af kolestatisk udløst hudkløe.

This article describes a case of severe pruritus and intrahepatic cholestasis after injection with androgenic/anabolic steroid. A number of different treatments have been used in the last decade. This case history demonstrates the possible effect of plasmapheresis.