Annmarie Touborg Lassen

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.

Complicated and uncomplicated peptic ulcers in a Danish county 1993-2002: a population-based cohort study.

Peptic ulcer epidemiology changes as the proportion of Helicobacter pylori infected people decreases, use of nonsteroidal anti-inflammatory drugs (NSAID) increases, and the proportion of elderly persons increases.OBJECTIVES:To describe incidence and prognosis of uncomplicated and complicated peptic ulcer patients in Funen County 1993–2002.METHODS:Data on endoscopies, gastric and duodenal operations, and related peptic ulcer diagnoses were extracted from four population-based databases covering a period from 1974 to 2002. All citizens of Funen County (population 470,000) who between 1993 and 2002 had a peptic ulcer diagnosed for the first time were identified.RESULTS:Between 1993 and 2002 the incidence of uncomplicated duodenal ulcer decreased from 0.55/1,000 person-years (95% CI 0.49–0.62) to 0.37 (0.31–0.43), uncomplicated gastric ulcer decreased from 0.56 (0.49–0.63) to 0.40 (0.34–0.46), and perforated ulcer decreased from 0.14 (0.11–0.18) to 0.08 (0.06–0.11). The incidence of bleeding peptic ulcer was stable with 0.55 (0.49–0.62) in 1993 and 0.57 (0.51–0.64) in 2002. The proportion of possible NSAID-related incident peptic ulcers increased from 320/827 (39%) in 1993 to 363/686 (53%) in 2002 (p < 0.01). A total of 3,233 patients with incident complicated peptic ulcer (9,927 person-years) and 4,421 patients with incident uncomplicated peptic ulcer (17,773 person-years) was followed for up to 10 yr. The first month following newly diagnosed complicated ulcer the standardized mortality rate was 37.1 (33.4–41.1) during the next 11 months it was 5.1 (4.6–5.6), and in the following years it was 2.6 (2.4–2.8). The corresponding figures for incident uncomplicated peptic ulcer was 11.6 (9.6–13.9), 4.0 (3.6–4.4), and 2.5 (2.3–2.7).CONCLUSION: During the period, incidence of peptic ulcers decreased and an increasing proportion was related to NSAID. Mortality is high.

Helicobacter pylori test and eradicate versus prompt endoscopy for management of dyspeptic patients: 6.7 year follow up of a randomised trial

Background: Dyspepsia is a chronic disease with significant impact on the use of health care resources. A management strategy based on Helicobacter pylori testing has been recommended but the long term effect is unknown. Aim: To investigate the long term effect of a test and treat strategy compared with prompt endoscopy for management of dyspeptic patients in primary care. Patients: A total of 500 patients presenting in primary care with dyspepsia were randomised to management by H pylori testing plus eradication therapy (n = 250) or by endoscopy (n = 250). Results of 12 month follow up have previously been presented. Methods: Symptoms, quality of life, and patient satisfaction were recorded during a three month period, a median 6.7 years after randomisation (range 6.1–7.3 years). Number of endoscopies, antisecretory medication, H pylori treatments, and hospital visits were recorded from health care databases for the entire follow up period. Results: Median age was 45 years; 28% were H pylori infected. Use of resources was registered in all 500 patients (3084 person years) of whom 312 completed diaries. We found no difference in symptoms between the two groups. Median proportion of days without symptoms was 0.52 (interquartile range 0.10–0.88) in the test and eradicate group versus 0.64 (0.14–0.90) in the prompt endoscopy group (p = 0.27) (mean difference 0.05 (95% confidence interval (CI) −0.03 to 0.14)). Compared with the prompt endoscopy group, the test and eradicate group underwent fewer endoscopies (mean difference 0.62 endoscopies/person (95% CI 0.38–0.86)) and used less antisecretory medication (mean difference 102 defined daily doses/person (95% CI −1 to 205)). Conclusion: On a long term basis, a H pylori test and eradicate strategy is as efficient as prompt endoscopy for management of dyspeptic patients in primary care and reduces the use of endoscopy and antisecretory medication.

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 countys 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.

Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial

BACKGROUND When used with standard diagnostic testing, point-of-care ultrasonography might improve the proportion of patients admitted with respiratory symptoms who are correctly diagnosed 4 h after admission to the emergency department. We therefore assessed point-of-care ultrasonography of the heart, lungs, and deep veins in addition to the usual initial diagnostic testing in this patient population. METHODS In a prospective, parallel-group trial in the emergency department at Odense University Hospital, Odense, Denmark, patients (≥18 years) with a respiratory rate of more than 20 per min, oxygen saturation of less than 95%, oxygen therapy, dyspnoea, cough, or chest pain were randomly assigned in a 1:1 ratio with a computer-generated list to a standard diagnostic strategy (control group) or to standard diagnostic tests supplemented with point-of-care ultrasonography of the heart, lungs, and deep veins (point-of-care ultrasonography group). The primary endpoint was the percentage of patients with a correct presumptive diagnosis 4 h after admission to the emergency department. Only the physicians doing the primary clinical assessment and the auditors were masked. Analyses were by intention to treat. The study is registered with ClinicalTrials.gov, number NCT01486394. FINDINGS Between Dec 7, 2011, and March 15, 2013, 320 patients were randomly assigned to the control group (n=160) and point-of-care ultrasonography group (n=160). 158 patients in the point-of-care ultrasonography group and 157 in the control group were analysed. 4 h after admission to the emergency department, 139 patients (88·0%; 95% CI 82·8-93·1) in the point-of-care ultrasonography group versus 100 (63·7%; 56·1-71·3) in the control group had correct presumptive diagnoses (p<0·0001). The absolute and relative effects were 24·3% (95% CI 15·0-33·1) and 1·38 (1·01-1·31), respectively. No adverse events were reported. INTERPRETATION Point-of-care ultrasonography is a feasible, radiation free, diagnostic test, which alongside standard diagnostic tests is superior to standard diagnostic tests alone for establishing a correct diagnosis within 4 h. It should therefore be considered for routine use as part of the standard diagnostic tests in the emergency department for patients admitted with respiratory symptoms. FUNDING University of Southern Denmark, Odense University Hospital, and Højbjerg Fund.

Randomized trial of stent placed above and across the sphincter of Oddi in malignant bile duct obstruction

BACKGROUND Placement of stents above an intact sphincter of Oddi might prevent migration of bacteria and deposition of organic material into the stent. In patients with malignant obstructive jaundice prolongation of function time of the stent would be expected if it is placed above the sphincter of Oddi. METHODS Thirty-four patients were randomized to stent placement either above (n = 17) or across (n = 17) the sphincter of Oddi. Straight 10F gauge Teflon stents were used. The patients were evaluated clinically and biochemically at monthly intervals during follow-up. RESULTS The median stent function time (i.e., the time from insertion of the stent until stent replacement, patient death, or study termination) were 110 days (25th to 75th percentiles, 61 to 320 days) for stents placed above the sphincter of Oddi and 126 days (25th to 75th percentiles, 89 to 175 days) for stents placed across the sphincter of Oddi (nonsignificant [NS]). Stent replacement rates were 58.8% (10 of 17) in patients with stents placed above the sphincter and 29.4% (5 of 17) in patients with stents placed across the sphincter (NS). Significantly more patients in the former group experienced stent migration (9 vs. 2, p = 0.026). The median time from stent insertion until replacement of the stents placed above and across the sphincter of Oddi were 82 days (25th to 75th percentiles, 31 to 185 days) and 89 days (25th to 75th percentiles, 13 to 150 days), respectively (NS). CONCLUSIONS No significant difference in overall stent performance between the two groups was found, although more stents placed above the sphincter of Oddi migrated. The time until dysfunction of the stent might be increased if migration of stents placed inside the common bile duct could be avoided.

Increasing incidence of pyogenic spondylodiscitis: a 14-year population-based study.

OBJECTIVES Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008. METHODS In a population-based study we identified all patients aged ≥18 years treated for pyogenic spondylodiscitis in Funen County, Denmark (population 483 123). Annual incidences were determined. Demographics, symptoms and diagnostic methods were recorded. RESULTS We found 192 cases: median age 66.6 years; 57.3% men; 76.6% culture positive cases. Staphylococcus aureus was the most common pathogen (55.1%). During 1995-2008 the overall incidence, incidence of culture negative cases, and incidence of cases due to S. aureus increased 2.2-5.8, 0.3-1.8, and 1.6-2.5 cases per 100 000 person years, respectively. The elderly had the highest incidence compared to those aged ≤70 years (rate ratio for men 5.9 (95% CI: 4.2-8.5) and for women 3.5 (95% CI: 2.3-5.3)). CONCLUSIONS During 1995-2008 the overall incidence of S. aureus and culture negative cases of spondylodiscitis increased and remained highest among the elderly. Whether the increase is real or is a result of improved diagnostic methods and workup remains unknown.

Esophagitis: Incidence and Risk of Esophageal Adenocarcinoma—A Population-Based Cohort Study

OBJECTIVES:Although symptoms of reflux are common, our knowledge of the epidemiology and natural history of gastroesophageal reflux disease is sparse. The risk of esophageal adenocarcinoma is increased among patients with acid reflux, but the contribution of Barretts lesions is unknown.METHODS:With the aim to estimate the incidence of diagnosed endoscopic esophagitis lesions and the risk of esophageal adenocarcinoma among patients with previously diagnosed esophagitis, we extracted data on endoscopies, esophagitis diagnoses, and gastroesophageal cancer diagnoses from five population-based databases covering the period from 1974 to 2002, and covering all citizens in Funen County (population 470,000).RESULTS:In 2002, the incidence of esophagitis lesions was 2.4 per 1,000 person-years (95% confidence interval 2.3–2.6), 18.3 per 1,000 persons (17.9–18.7) had previously diagnosed esophagitis. Incidence increased by calendar year and age, was higher among males than among females, and was closely related to rate of endoscopy. Among 11,129 patients with previously diagnosed esophagitis, 15 had esophageal adenocarcinoma during 58,322 person-years of follow-up (26 per 100,000 person-years). The expected number was 2.79 and the standardized incidence ratio was 5.38 (3.01–8.87). Ten of the 15 patients with esophageal adenocarcinoma had previously diagnosed Barretts esophagus.CONCLUSION:The risk of esophageal adenocarcinoma is increased fivefold in patients with previously diagnosed esophagitis, but most of the adenocarcinomas occurred among patients with Barretts esophagus.

Focused Sonography of the Heart, Lungs, and Deep Veins Identifies Missed Life-Threatening Conditions in Admitted Patients With Acute Respiratory Symptoms

BACKGROUND Patients with acute respiratory symptoms still remain a diagnostic challenge. The aim of the study was to evaluate whether focused sonography could potentially diagnose life-threatening conditions missed at the primary assessment in a patient population consisting of admitted patients with acute respiratory symptoms. METHODS A prospective blinded observational study was conducted in a medical ED. Inclusion criteria were the presence of one or more of the following: respiratory rate > 20/min, oxygen saturation < 95%, oxygen therapy initiated, dyspnea, cough, or chest pain. After the initial assessment, focused sonography of the heart, lungs, and deep veins was performed by a physician blinded to patient history and the results of the primary assessment. RESULTS One hundred thirty-nine patients were included. The focused sonographic examinations could be performed in 134 patients (96%). Focused sonography identified 19 patients (14%) with an acute life-threatening condition missed at the primary assessment. Diagnostic performance of focused sonography for the diagnosis of an acute life-threatening condition, when using audit as gold standard, was as follows: sensitivity, 100% (95% CI, 85.2%-100%); specificity, 93.3% (95% CI, 86.7%-97.3%); positive predictive value, 76.7% (95% CI, 57.7%-90.1%); and negative predictive value, 100% (95% CI, 96.3%-100%). CONCLUSIONS Focused sonography of the heart, lungs, and deep veins is fast, highly feasible, and able to diagnose life-threatening conditions missed at the primary assessment in admitted patients with acute respiratory symptoms. In an ED setting sonography can be used both for ruling in and ruling out acute life-threatening conditions in these patients.

Use of anti‐secretory medication: a population‐based cohort study

Background : Total use of anti‐secretory medication (H2 blockers and proton pump inhibitors) is increasing rapidly, but knowledge of factors related to the increasing use is sparse.