Claus Aalykke

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

Abstract 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.

Helicobacter pylori and risk of ulcer bleeding among users of nonsteroidal anti-inflammatory drugs: A case-control study

BACKGROUND & AIMS Peptic ulcer complications related to use of nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most common serious adverse drug reactions. Whether Helicobacter pylori infection potentiates this gastrointestinal toxicity of NSAIDs is still unresolved. In this study, we investigated the role of H. pylori as a cause of bleeding peptic ulcer among NSAID users. METHODS A case-control study of current users (n = 132) of NSAIDs (including acetylsalicylic acid), admitted because of bleeding peptic ulcer, was performed. Controls were 136 NSAID users without gastrointestinal complications. H. pylori was diagnosed by either increased levels of serum immunoglobulin G or by 13C-urea breath test. RESULTS Fifty-eight (44%) case subjects had a bleeding gastric ulcer, 54 (41%) had a bleeding duodenal ulcer, 12 (9%) had both gastric and duodenal ulcers, and 8 (6%) had hemorrhagic gastritis. H. pylori was present in 75 (57%) cases compared with 59 (43%) controls. The adjusted odds ratio of bleeding peptic ulcer among NSAID users associated with H. pylori infection was 1.81 (95% confidence interval, 1.02-3.21). H. pylori accounted for approximately 24% of bleeding peptic ulcers among elderly NSAID users. CONCLUSIONS NSAID users infected with H. pylori have an almost twofold increased risk of bleeding peptic ulcer compared with NSAID users without H. pylori.

Clinical characteristics of importance to outcome in patients with axial spondyloarthritis: protocol for a prospective descriptive and exploratory cohort study

Introduction Spondyloarthritis (SpA) is a heterogeneous spectrum of rheumatic diseases with either predominantly axial inflammatory symptoms of the spine and sacroiliac joints or predominantly peripheral arthritis. The two main entities of axial SpA (axSpA) are ankylosing spondylitis or non-radiographic axSpA (nr-axSpA). Tumour necrosis factor-α inhibitors have revolutionised the treatment of patients with axSpA who failed to respond to non-steroidal anti-inflammatory drugs and physical therapy. Chronic pain is common in patients with SpA and may still persist despite the lack of signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may play a role in the generation of chronic pain in SpA. The painDETECT Questionnaire (PDQ) is a screening tool developed to detect neuropathic pain components. The primary objective is to explore the prognostic value of the PDQ regarding treatment response in patients with axSpA 3 months after initiating a biological agent. Secondary aim is to evaluate the impact of extra-articular manifestations, comorbidities and patient-reported outcomes and elucidate if these factors influence treatment response. Method and analysis We will include 60 participants (≥18 years of age) diagnosed with axSpA independent of main entity, who initiate or switch treatment of a biologic. Data will be collected at baseline and at endpoint following Danish clinical practice (≥3 months) of treatment with biologics. We will explore whether the PDQ and other phenotypical patient characteristics are prognostically important for response to biological therapy according to established response criteria like 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (50%) and Ankylosing Spondylitis Disease Activity Score. Ethics and dissemination The study is approved by the Region of Southern Denmark’s Ethics committee (S-20160094) and has been designed in cooperation with patient representatives. The study is registered at clinicaltrials.gov (NCT02948608, pre-results). Dissemination will occur through publication(s) in international peer-reviewed journal(s).

Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate.

We present a case of a 56-year-old woman with Crohns disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated in patients treated with immunosuppressive drugs. Following vaccination, the patient fell ill with influenza-like illness. Elevated transaminase levels and YF viremia were detected. Despite being immunocompromised, the patient did not develop more severe adverse effects. Neutralising antibodies to YF virus were detected on day 14 following vaccination and remained protective at least 10 months after vaccination. Limited data is available on outcomes of YFV in patients receiving immunosuppressive therapy, including biologics, and we report this case as a reminder of vigilance of vaccine recommendations in this population.

Gastrointestinal (GI) symptoms, quality of life and endoscopic diagnoses in patients with upper GI symptoms

Gastrointestinal (GI) symptoms, quality of life and endoscopic diagnoses in patients with upper GI symptoms