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

A Scandcleft randomised trials of primary surgery for unilateral cleft lip and palate:1. Planning and management

<p><b>Background and aims:</b> Longstanding uncertainty surrounds the selection of surgical protocols for the closure of unilateral cleft lip and palate, and randomised trials have only rarely been performed. This paper is an introduction to three randomised trials of primary surgery for children born with complete unilateral cleft lip and palate (UCLP). It presents the protocol developed for the trials in CONSORT format, and describes the management structure that was developed to achieve the long-term engagement and commitment required to complete the project.</p> <p><b>Method:</b> Ten established national or regional cleft centres participated. Lip and soft palate closure at 3–4 months, and hard palate closure at 12 months served as a common method in each trial. Trial 1 compared this with hard palate closure at 36 months. Trial 2 compared it with lip closure at 3–4 months and hard and soft palate closure at 12 months. Trial 3 compared it with lip and hard palate closure at 3–4 months and soft palate closure at 12 months. The primary outcomes were speech and dentofacial development, with a series of perioperative and longer-term secondary outcomes.</p> <p><b>Results:</b> Recruitment of 448 infants took place over a 9-year period, with 99.8% subsequent retention at 5 years.</p> <p><b>Conclusion:</b> The series of reports that follow this introductory paper include comparisons at age 5 of surgical outcomes, speech outcomes, measures of dentofacial development and appearance, and parental satisfaction. The outcomes recorded and the numbers analysed for each outcome and time point are described in the series.</p> <p><b>Trial registration:</b> ISRCTN29932826.</p