Flemming Hald Steffensen

The Risk of a Diagnosis of Cancer after Primary Deep Venous Thrombosis or Pulmonary Embolism

BACKGROUND Several small studies have indicated an association between deep venous thrombosis or pulmonary embolism and a subsequent diagnosis of cancer, but the subject is controversial. METHODS We conducted a nationwide study of a cohort of patients with deep venous thrombosis or pulmonary embolism that was drawn from the Danish National Registry of Patients for the years 1977 through 1992. The occurrence of cancer in the cohort was determined by linkage to the Danish Cancer Registry. The expected number of cancer cases was estimated on the basis of national age-, sex-, and site-specific incidence rates. RESULTS A total of 15,348 patients with deep venous thrombosis and 11,305 patients with pulmonary embolism were identified. We observed 1737 cases of cancer in the cohort with deep venous thrombosis, as compared with 1372 expected cases (standardized incidence ratio, 1.3; 95 percent confidence interval, 1.21 to 1.33). Among the patients with pulmonary embolism, the standardized incidence ratio was 1.3, with a 95 percent confidence interval of 1.22 to 1.41. The risk was substantially elevated only during the first six months of follow-up and declined rapidly thereafter to a constant level slightly above 1.0 one year after the thrombotic event. Forty percent of the patients given a diagnosis of cancer within one year after hospitalization for thromboembolism had distant metastases at the time of the diagnosis of cancer. There were strong associations with several cancers, most pronounced for those of the pancreas, ovary, liver (primary hepatic cancer), and brain. CONCLUSIONS An aggressive search for a hidden cancer in a patient with a primary deep venous thrombosis or pulmonary embolism is not warranted.

Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure

BACKGROUND The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT). METHODS In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death. RESULTS After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval [CI], 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29). CONCLUSIONS In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).

Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin

OBJECTIVE:Aspirin products are known to cause irritation and injury to the gastric mucosa. We examined the risk of hospitalization for upper gastrointestinal bleeding with use of low-dose aspirin.METHODS:This was a cohort study based on record linkage between a population-based prescription database and a hospital discharge registry in North Jutland County, Denmark, from January 1, 1991, to December 31, 1995. Incidence rates of upper gastrointestinal bleeding in 27,694 users of low-dose aspirin were compared with the incidence rates in the general population in the county.RESULTS:A total of 207 exclusive users of low-dose aspirin experienced a first episode of upper gastrointestinal bleeding with admission to the hospital during the study period. The standardized incidence rate ratio was 2.6 (95% confidence interval, 2.2–2.9), 2.3 in women and 2.8 in men. The standardized incidence rate ratio for combined use of low-dose aspirin and other nonsteroidal anti-inflammatory drugs was 5.6 (95% confidence interval, 4.4–7.0). The risk was similar among users of noncoated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 1.8–3.5) and coated low-dose aspirin (standardized incidence rate ratio, 2.6; 95% confidence interval, 2.2–3.0).CONCLUSIONS:Use of low-dose aspirin was associated with an increased risk of upper gastrointestinal bleeding, with still higher risks when combined with other nonsteroidal anti-inflammatory drugs. Enteric coating did not seem to reduce the risk. The findings from this observational study raise the possibility that prophylactic use of low-dose aspirin may convey an increased risk of gastrointestinal bleeding, which may offset some of its benefits.

The cumulative incidence of venous thromboembolism during pregnancy and puerperium

OBJECTIVES The aim of the study was to estimate the cumulative incidence of venous thromboembolism during pregnancy and the puerperium. METHODS All diagnoses concerning venous thromboembolism in the Hospital Discharge Registry from a Danish County in women less than 49 years of age from 1984 to 1994 were included. The number of deliveries in the County during this period was obtained from The Medical Registry of Birth. RESULTS The cumulative incidence of venous thromboembolism during pregnancy and puerperium was 0.85 (95% CI: 0.64-1.11) per 1000 deliveries. The cumulative incidence was 0.49 (95% CI: 0.28-04).80) in 1984-89 but increased to 1.23 (95% CI: 0.87-1.69) after the introduction of ultrasound. CONCLUSION The risk of diagnosed venous thromboembolism is low but estimates of the incidence are probably procedure dependent.

Drug use in first pregnancy and lactation : a population-based survey among Danish women

AbstractObjective: To examine the drug prescription pattern in Danish women from 12 weeks prior to conception until 12 weeks post-partum. Method: A drug utilization study based on The North Jutland Prescription Database. The Danish pharmacies use a computerized accounting system for all subsidized drugs and this was linked to the Danish Medical Birth Registry concerning prescription patterns for all women who had given birth in the county of North Jutland from 1991 to 1996. Results: The analysis included 16 001 primiparous women, who had redeemed 34 834 prescriptions prior to, during and after pregnancy. During pregnancy 44.2% of the women received prescriptions for at least one drug. Users received 2.6 prescriptions on average during pregnancy; 5% of the users redeemed 24.2% of all prescriptions. The proportion of women who redeemed prescriptions for more than three different drugs was 2.7%. The majority of prescriptions were for antibiotics (28.7%), gynaecological drugs (13.3%) and anti-asthma drugs (7.6%). The post-partum prescription proportion was 34.0% and the majority of the prescriptions during this period were for penicillins (20.1%), opthalmologicals (15.5%) and corticosteroids for dermatological use (5.7%). Conclusion: A high proportion of the women received drugs during pregnancy. The pattern of drug use within the Anatomical Therapeutical Chemical (ATC) groups changed, i.e. the amount of broad spectrum antibiotics decreased and the proportion of prescriptions for local use increased. A small proportion of women redeemed prescriptions for more than three different drugs during pregnancy.

Low birth weight and preterm delivery as risk factors for asthma and atopic dermatitis in young adult males.

Gestational factors have been hypothesized to play a role in the susceptibility to asthma and atopic dermatitis. We examined whether fetal growth was associated with asthma and atopic dermatitis separately in a population of 4,795 male conscripts born between 1973 and 1975 in Denmark. The prevalence of asthma was 4.7%. The prevalence odds ratio of asthma in conscripts with a birth weight below 2,501 g was 1.5 (95% confidence interval = 0.7-3.1) compared with conscripts with a birth weight of 3,001-3,500 g, adjusted for gestational age and potential confounders. The adjusted prevalence odds ratio among conscripts born before 34 gestational weeks was 0.8 (95% confidence interval = 0.3-2.0) compared with conscripts born at term. The prevalence of atopic dermatitis was 1.0%. The prevalence odds ratio of atopic dermatitis among those with a birth weight below 2,501 g was 3.0 (95% confidence interval = 0.8-11.9) compared with those whose birth weight was between 3,001 and 3,500 g. Men whose gestational age had been below 34 weeks had an adjusted prevalence odds ratio of 0.3 (95% confidence interval = 0.0-3.1). These findings indicate that fetal growth retardation rather than preterm delivery of male infants is the main gestational factor underlying the associations but does not explain the apparent increase over time of asthma or atopic diseases.

Cancer Risk in Users of Calcium Channel Blockers

Ca2+ channel blockers may cause cancer by inhibiting apoptosis or reducing intracellular Ca2+ in certain tissues. Recent findings suggest that drug users are at increased risk for cancer in general and for colon cancer in particular. We conducted a study in one Danish county of 17911 patients who received at least one prescription of Ca2+ channel blockers between 1 January 1991 and 31 December 1993. The patients were identified from records in the National Health Insurance Program, which refunds part of the price of such drugs. Cancer occurrence and rate were determined by use of the files of the Danish Cancer Registry and compared with county-specific incidence rates for various categories of cancer. During the follow-up period of up to 3 years, 412 cancers were observed among users of Ca2+ channel blockers, compared with 414 expected, to yield an age- and sex-standardized incidence ratio (SIR) of 1.00 (95% confidence interval, 0.90 to 1.10). There was no indication of an excess risk in the subgroup of likely long-term users or users of specific drugs. The SIR of colon cancer, a site of a priori interest, was 0.8 (95% confidence interval, 0.5 to 1.1) on the basis of 34 cases. Although the results are reassuring, the lack of association could reflect the relatively short follow-up after registration in the prescription database. Continued monitoring of cancer risk is planned.

Pregnancy Outcome Following Prescription for Sumatriptan

Background.– Some 2.5% of fertile Danish women use sumatriptan, and the drug is also taken during pregnancy. Although sumatriptan reacts selectively in brain vessels, the possibility of reactions with placental blood flow and uterotonic activity cannot be ruled out. The aim of our study was to examine the association between sumatriptan exposure during pregnancy and the risk of preterm delivery and low birth weight.

Major haemorrhagic complications during oral anticoagulant therapy in a Danish Population‐based cohort

Abstract. Steffensen FH, Kristensen K, Ejlersen E, Dahlerup JF, S~rensen HT (University of Aarhus and Aarhus University Hospital, Arhus, and Aalborg Hospital, Aalborg, Denmark). Major haemorrhagic complications during oral anticoagulant therapy in a Danish population‐based cohort. 1 Intern Med 199 7; 242: 497‐503.

Risk of acute pancreatitis in patients with chronic inflammatory bowel disease: A Danish 16-year nationwide follow-up study

Background: There are few epidemiologic data about the risk of acute pancreatitis in chronic inflammatory bowel diseases; we therefore wanted to estimate the risk of a first episode of acute pancreatitis in patients with Crohns disease and ulcerative colitis in the total Danish population. Methods: The study included all patients discharged from Danish hospitals with a diagnosis of Crohns disease or ulcerative colitis registered in the Danish National Registry of Patients in the period from 1977 to 1992. The first episode of acute pancreatitis was identified in the cohort. The observed number of patients with acute pancreatitis was compared with expected numbers on the basis of age, sex, and calendar-specific incidence rates in the general population. Results: Overall, 15,526 patients were discharged and followed up for 112,824 person-years. The standardized incidence ratio (SIR) for acute pancreatitis was increased both in patients with Crohns disease (SIR = 4.3; 95% confidence interval (CI), 2.9-6.1)...