Ove B. Schaffalitzky de Muckadell

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.

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.

Proton Pump Inhibitor or Testing for Helicobacter pylori as the First Step for Patients Presenting with Dyspepsia? A Cluster-Randomized Trial

OBJECTIVES:The optimal approach for management of patients with dyspepsia has not been determined. The aim of this study was to compare the efficacy of three strategies for management of dyspepsia: empirical antisecretory therapy, testing for Helicobacter pylori (H. pylori), or a combination of the two.METHODS:Cluster-randomized trial in general practices. Initial treatment with proton pump inhibitor (PPI) was performed in 222 patients, H. pylori test-and-eradicate in 250 patients, and PPI followed by H. pylori-testing if symptoms improved in 250 patients. Symptoms, quality of life, patient satisfaction, and use of resources were recorded during a 1-yr follow-up.RESULTS:The prevalence of H. pylori infection was 24%. We found no difference among the three strategies (p = 0.16) in terms of the proportion of days without dyspeptic symptoms. After 1 yr gastrointestinal symptom scores and quality-of-life scores had improved significantly and equally in the three groups (p < 0.001), but no statistically significant differences were found among the groups. The mean use of endoscopies per patient after 1 yr was higher in the PPI group (0.36 [95% CI 0.30–0.43]) than in the test-and-eradicate group (0.28 [95% CI 0.23–0.34]) and the combination group (0.22 [95% CI 0.17–0.27]), p = 0.02. H. pylori-positive patients given eradication therapy had more days without dyspeptic symptoms (p < 0.001), used less antisecretory therapy (p < 0.01), and were more satisfied (p < 0.001) than H. pylori-negative patients.CONCLUSION:The strategies based on H. pylori test enjoyed similar symptom resolution, but reduced endoscopic workload and lower 1-yr total costs compared with empirical antisecretory therapy.

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.

Rates of Dyspepsia One Year After Helicobacter pylori Screening and Eradication in a Danish Population

BACKGROUND & AIMS Helicobacter pylori (Hp) is strongly correlated with peptic ulcer and is a risk factor for gastric cancer. The aim of this study was to assess whether screening and eradication of Hp in a general population would reduce the prevalence of dyspepsia and the incidence of peptic ulcer and thus save health care resources and improve quality of life. METHODS Twenty thousand individuals aged 40 to 65 years were randomized to screening and eradication for Hp or to the control group. Hp status was assessed by a whole blood Hp test, a positive result confirmed by a (13)C-urea breath test. Hp-positive individuals were offered Hp eradication therapy. The prevalence of dyspepsia and the quality of life were assessed through a mailed questionnaire. Information on the use of endoscopies and the use of prescription medication was obtained from registers. RESULTS The response rate was 62.6%. The prevalence of Hp was 17.5%. The Hp eradication rate was 95%. In the intervention group, the prevalence of dyspepsia decreased from 24.3% at inclusion to 20.5% at 1-year follow-up. The reduction was similar in Hp-negative and Hp-positive persons. In the control group, dyspepsia increased from 20.3% to 21.5%. Gastroesophageal reflux symptoms improved slightly in Hp-eradicated participants. Except for a decreased consultation rate for dyspepsia, there were no visible savings in health care. CONCLUSIONS Dyspepsia was modestly reduced after the screening and treatment procedure, and the result was not sufficiently extensive to have an effect on the use of health care or to improve quality of life.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study

It is still controversial whether pre‐operative anti‐tumour necrosis factor‐alpha (anti‐TNF‐α) agents increase post‐operative complications in patients with ulcerative colitis (UC).

Placebo-controlled trial of cisapride and nizatidine in unselected Patients with functional dyspepsia

Objective:Patients in most trials of pharmacotherapy for nonorganic dyspepsia have been groups referred selectively for endoscopy, which could have led to a selection bias of nonresponders, explaining the negative outcome of most controlled treatment trials in nonorganic dyspepsia. The aim of this study was to evaluate the effects of cisapride and nizatidine in patients with nonorganic dyspepsia who were recruited directly from primary care settings, and to evaluate the therapeutic implications of dyspepsia subgrouping.Methods:A consecutive series of patients who consulted their general practitioner with dyspepsia were invited to an interview and endoscopy. Before endoscopy, symptoms were classified as reflux-like, dysmotility-like, ulcer-like, or unclassifiable. A total of 330 patients with either minor or no abnormalities at endoscopy were randomized to double blind treatment with cisapride 10 mg t.i.d., nizatidine 300 mg at night, or placebo for 2 wk.Results:A symptomatic response was found in 62% of patients on cisapride (therapeutic gain cisapride vs placebo: 0.1% [95% confidence interval –14% to 14%]) and in 54% of patients on nizatidine (therapeutic gain nizatidine vs placebo: –8% [95% confidence interval –22% to 7%]). Response to treatment was independent of symptom classification.Conclusions:The effects of a 2-wk course of cisapride or nizatidine in unselected patients with dyspepsia recruited from primary care were not superior to those of placebo. Symptom subgrouping was not predictive of response to therapy.

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.

Risk factors for dyspepsia in a general population: Non-steroidal anti-inflammatory drugs, cigarette smoking and unemployment are more important than Helicobacter pylori infection

Objective. Dyspepsia, a common condition in the community, affects quality of life and imposes costs on both the individual and the community. Several factors including Helicobacter pylori, acetylic salicylic acid (ASA)/non-steroidal anti-inflammatory drugs (NSAIDs) use, low-dose ASA use, alcohol consumption, cigarette smoking and social status might be responsible. Material and methods. A cross-sectional study from the inclusion (intervention group) of a general population study evaluating rates of dyspepsia after H. pylori screening and eradication was carried out. A total of 10,007 individuals aged 40–64 years received questionnaires and an invitation to take part in H. pylori screening. Information on dyspepsia (the gastrointestinal symptom rating scale (GSRS) and “most bothersome symptom”), use of ASA/NSAIDs, use of low-dose ASA, lifestyle factors and level of education and employment status was obtained from the questionnaire. Dyspepsia was defined as a score of ≥2 in the GSRS dimension abdominal pain syndrome (aps), allowing for a maximum of one light problem score in any of the 3 items in the dimension to be overlooked. Results. In all, 5749/10,007 individuals participated in the study; 24.9% reported dyspepsia. In a multiple logistic regression analysis H. pylori infection was found to be a risk factor for dyspepsia, odds ratio (OR) 1.21 (CI; 1.03–1.42). However, the highest ORs for dyspepsia were: for daily use of ASA/NSAIDs 2.33 (CI; 1.72–3.15), unemployment 2.18 (CI; 2.86–2.56) and cigarette smoking ≥20 g/day 1.55 (CI; 1.29–1.86). Conclusions. H. pylori infection is a significant risk factor for dyspepsia although of less importance than ASA/NSAIDs use, unemployment and heavy smoking.

Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery.

OBJECTIVES:The treatment of peptic ulcer bleeding (PUB) is complex, and mortality remains high. We present results from a nationwide initiative to monitor and improve the quality of care (QOC) in PUB.METHODS:All Danish hospitals treating PUB patients between 2004 and 2011 prospectively registered demographic, clinical, and prognostic data. QOC was evaluated using eight process and outcome indicators, including time to initial endoscopy, hemostasis obtainment, proportion undergoing surgery, rebleeding risks, and 30-day mortality.RESULTS:A total of 13,498 PUB patients (median age 74 years) were included, of which one-quarter were in-hospital bleeders. Preadmission use of anticoagulants, multiple coexisting diseases, and the American Society of Anesthesiologists scores increased between 2004 and 2011. Considerable improvements were observed for most QOC indicators over time. Endoscopic treatment was successful with primary hemostasis achieved in more patients (94% in 2010–2011 vs. 89% in 2004–2006, relative risk (RR) 1.06 (95% confidence intervals 1.04–1.08)), endoscopy delay for hemodynamically unstable patients decreased during this period (43% vs. 34% had endoscopy within 6 h, RR 1.33 (1.10–1.61)), and fewer patients underwent open surgery (4% vs. 6%, RR 0.72 (0.59–0.87)). After controlling for time changes in prognostic factors, rebleeding rates improved (13% vs. 18%, adjusted RR 0.77 (0.66–0.91)). Crude 30-day mortality was unchanged (11% vs. 11%), whereas adjusted mortality decreased nonsignificantly over time (adjusted RR 0.89 (0.78–1.00)).CONCLUSIONS:QOC in PUB has improved substantially in Denmark, but the 30-day mortality remains high. Future initiatives to improve outcomes may include earlier endoscopy, having fully trained endoscopists on call, and increased focus on managing coexisting disease.