Gunnar Lauge Nielsen

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.

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.

Risk of adverse birth outcome and miscarriage in pregnant users of non-steroidal anti-inflammatory drugs: population based observational study and case-control study

Abstract Objective: To estimate the risk of adverse birth outcome in women who take non-steroidal anti-inflammatory drugs during pregnancy. Design and setting: Population based cohort study and a case-control study, both based on data from a prescription registry, the Danish birth registry, and one countys hospital discharge registry. Participants: Cohort study: 1462 pregnant women who had taken up prescriptions for non-steroidal anti-inflammatory drugs in the period from 30 days before conception to birth and 17 259 pregnant women who were not prescribed any drugs during pregnancy. Case-control study: 4268 women who had miscarriages, of whom 63 had taken non-steroidal anti-inflammatory drugs, and 29 750 primiparous controls who had live births. Main outcome measures: Incidences of congenital abnormality, low birth weight, preterm birth, and miscarriage. Results: Odds ratios for congenital abnormality, low birth weight, and preterm birth among women who took up prescriptions for non-steroidal anti-inflammatory drugs were 1.27 (95% confidence interval 0.93 to 1.75), 0.79 (0.45 to 1.38), and 1.05 (0.80 to 1.39) respectively. Odds ratios for the taking up of prescriptions in the weeks before miscarriage ranged from 6.99 (2.75 to 17.74) when prescriptions were taken up during the last week before the miscarriage to 2.69 (1.81 to 4.00) when taken up between 7 and 9 weeks before. The risk estimates were no different when the analysis was restricted to missed abortions. Conclusions: Use of non-steroidal anti-inflammatory drugs during pregnancy does not seem to increase the risk of adverse birth outcome but is associated with increased risk of miscarriage.

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.

Disease Activity in Pregnant Women With Crohn's Disease and Birth Outcomes: A Regional Danish Cohort Study

OBJECTIVES: CD is associated with increased risk of adverse birth outcomes, but existing studies have not assessed the impact of disease activity during pregnancy. We examined the impact of disease activity on birth outcomes: LBW, preterm birth, LBW at term, and CAs.METHODS: All births by CD women in North Jutland County, Denmark, from January 1, 1977 to December 31, 2005, were evaluated in a cohort study based on linkage between the Danish National Registry of Patients and the Medical Birth Registry. After identification of all births by CD women, review of medical records allowed collection of clinical details (including disease activity and drug therapy during pregnancy). The exposed cohort (N = 71) constituted pregnancies with low/moderate-high disease activity during pregnancy, and the unexposed cohort (N = 86) those with inactive disease. Logistic regression analyses were used to estimate the adjusted relative risks (with 95% confidence intervals) for adverse birth outcomes associated with disease activity in CD pregnancies. In subanalysis, we examined the impact of moderate-high activity.RESULTS: In women with disease activity, the adjusted risks of LBW, LBW at term, preterm birth, and CAs were 0.2 (0.0–2.6), 0.4 (0.0–3.7), 2.4 (0.6–9.5), and 0.8 (0.2–3.8), respectively. The crude risk of preterm birth was 3.4 (1.1–10.6) in those with moderate-high disease activity.CONCLUSIONS: Disease activity during pregnancy only increased the risk of preterm birth (especially in those with high disease activity). Further research is needed to assess the critical impact of disease activity in larger cohorts of CD women.

Do pregnant women report use of dispensed medications

Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health interview survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40–46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure. Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.

Angiotensin-converting enzyme inhibitors and the risk of cancer: a population-based cohort study in Denmark.

A recent observational study suggested that the use of angiotensin‐converting enzyme (ACE) inhibitors protects against cancer in general and against breast and female reproductive tract cancers in particular. To explore these hypotheses, the authors examined cancer risk among users of ACE inhibitors in North Jutland County, Denmark.

Increase in incidence and prevalence of inflammatory bowel disease in northern Denmark: A population-based study, 1978-2002

Objectives Although incidence rates of inflammatory bowel disease have been reported worldwide, few long-term population-based studies with current time-trend analyses exist. We therefore examined time trends in the incidence rate of inflammatory bowel disease in a 25-year study period, and estimated the prevalence in 2002. All patients diagnosed between 1978 and 2002 were included as incident cases (n=2326) and all patients living in North Jutland County on 31 December 2002 were used to estimate prevalent cases (n=2205). Methods Medical records of all patients diagnosed with ulcerative colitis and Crohns disease in the North Jutland County Hospital Discharge Registry were reviewed to examine if the diagnostic criteria were fulfilled. Age-specific and gender-specific standardized incidence rates were calculated. Results For ulcerative colitis, incidence rates in women increased from 8.3 (95% confidence interval (CI): 6.7–9.9) in 1978–1982 to 17.0 (95% CI: 14.7–19.3) per 100 000 person-years in 1998–2002. The corresponding figures for men were 7.7 (95% CI: 6.1–9.3) and 16.7 (95% CI: 14.4–18.8) per 100 000 person-years. For Crohns disease, the incidence rates in women increased from 4.1 (95% CI: 3.0–5.2) in 1978–1982 to 10.7 (95% CI: 8.8–12.5) per 100 000 person-years in 1998–2002. The corresponding figures for men were 3.2 (95% CI: 2.1–4.2) and 8.5 (95% CI: 6.9–10.2) per 100 000 person-years. The prevalence of ulcerative colitis and Crohns disease was 294 and 151 per 100 000 inhabitants, respectively. Conclusions A marked and parallel increase was seen in both ulcerative colitis and Crohns disease in both genders during the last 25 years, with a corresponding high prevalence of both 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.