Baseline findings of the population-based, randomized, multifaceted Danish cardiovascular screening trial (DANCAVAS) of men aged 65-74 years.

BACKGROUND: The challenge of managing age-related diseases is increasing; routine checks by the general practitioner do not reduce cardiovascular mortality. The aim here was to reduce cardiovascular mortality by advanced population-based cardiovascular screening. The present article reports the organization of the study, the acceptability of the screening offer, and the relevance of multifaceted screening for prevention and management of cardiovascular disease. METHODS: Danish men aged 65-74 years were invited randomly (1 : 2) to a cardiovascular screening examination using low-dose non-contrast CT, ankle and brachial BP measurements, and blood tests. RESULTS: In all, 16 768 of 47 322 men aged 65-74 years were invited and 10 471 attended (uptake 62·4 per cent). Of these, 3481 (33·2 per cent) had a coronary artery calcium score above 400 units. Thoracic aortic aneurysm was diagnosed in the ascending aorta (diameter 45 mm or greater) in 468 men (4·5 per cent), in the arch (at least 40 mm) in 48 (0·5 per cent) and in the descending aorta (35 mm or more) in 233 (2·2 per cent). Abdominal aortic aneurysm (at least 30 mm) and iliac aneurysm (20 mm or greater) were diagnosed in 533 (5·1 per cent) and 239 (2·3 per cent) men respectively. Peripheral artery disease was diagnosed in 1147 men (11·0 per cent), potentially uncontrolled hypertension (at least 160/100 mmHg) in 835 (8·0 per cent), previously unknown atrial fibrillation confirmed by ECG in 50 (0·5 per cent), previously unknown diabetes mellitus in 180 (1·7 per cent) and isolated severe hyperlipidaemia in 48 men (0·5 per cent). In all, 4387 men (41·9 per cent), excluding those with potentially uncontrolled hypertension, were referred for additional cardiovascular prevention. Of these, 3712 (35·5 per cent of all screened men, but 84·6 per cent of those referred) consented and were started on medication. CONCLUSION: Multifaceted cardiovascular screening is feasible and may optimize cardiovascular disease prevention in men aged 65-74 years. Uptake is lower than in aortic aneurysm screening.

The DanCavas Pilot Study of Multifaceted Screening for Subclinical Cardiovascular Disease in Men and Women Aged 65-74 Years.

OBJECTIVE/BACKGROUND: This pilot study of a large population based randomised screening trial investigated feasibility, acceptability, and relevance (prevalence of clinical and subclinical cardiovascular disease [CVD] and proportion receiving insufficient prevention) of a multifaceted screening for CVD. METHODS: In total, 2060 randomly selected Danish men and women aged 65-74 years were offered (i) low dose non-contrast computed tomography to detect coronary artery calcification (CAC) and aortic/iliac aneurysms; (ii) detection of atrial fibrillation (AF); (iii) brachial and ankle blood pressure measurements; and (iv) blood levels of cholesterol and hemoglobin A1c. Web based self booking and data management was used to reduce the administrative burden. RESULTS: Attendance rates were 64.9% (n = 678) and 63.0% (n = 640) for men and women, respectively. In total, 39.7% received a recommendation for medical preventive actions. Prevalence of aneurysms was 12.4% (95% confidence interval [CI] 9.9-14.9) in men and 1.1% (95% CI 0.3-1.9) in women, respectively (p < .001). A CAC score > 400 was found in 37.8% of men and 11.3% of women (p < .001), along with a significant increase in median CAC score with age (p = .03). Peripheral arterial disease was more prevalent in men (18.8%, 95% CI 15.8-21.8) than in women (11.2%, 95% CI 8.7-13.6). No significant differences between the sexes were found with regard to newly discovered AF (men 1.3%, women 0.5%), potential hypertension (men 9.7%, women 11.5%), hypercholesterolemia (men 0.9%, women 1.1%) or diabetes mellitus (men 2.1%, women 1.3%). CONCLUSION: Owing to the higher prevalence of severe conditions, such as aneurysms and CAC ≥ 400, screening for CVD seemed more prudent in men than women. The attendance rates were acceptable compared with other screening programs and the logistical structure of the screening program proved successful.

Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

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.

Third generation oral contraceptives and heritable thrombophilia as risk factors of non-fatal venous thromboembolism.

Third generation oral contraceptives (OCs) are apparently stronger risk factors for venous thromboembolism (VTE) than other OCs, however, the increased risk may be due to confounding by indication related to differences in prescription behaviour. We estimated the risk of VTE associated with use of OCs with and without the presence of Factor V Leiden mutation, protein C-, protein S- or antithrombin deficiency. Sixty-seven cases with VTE were compared with 134 controls. The risk of VTE in the presence of thrombophilia was of the same magnitude for third generation OC users as for users of other OCs; OR: 52.5 (95% CI: 3.7-738.1) and OR: 63.3 (95% CI: 6.2-648.4), respectively. It is unlikely that confounding by indication entirely explains the risk of VTE associated with third generation OCs since the combined effect exceeds what could be explained if this source of error was the only determinant of the association.

Outcome of pre-hospital antibiotic treatment of meningococcal disease.

OBJECTIVE: To assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. DESIGN: A 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark. SUBJECTS: 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. MAIN OUTCOME MEASURES: Death. RESULTS: 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae, and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio (OR) for death in patients treated with antibiotics was high (OR = 3.2; 95% CI, 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. If skin bleeding was replaced in the models by the presence of disseminated intravascular coagulation on admission, the OR for death in patients with pre-hospital antibiotic treatment was 35.9 (95% CI, 2.9-441.8) in the presence of disseminated intravascular coagulation and 1.9 (95% CI, 0.2-19.5) in its absence. CONCLUSIONS: Pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings but provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

Lipid-lowering medication and risk of cancer.

Low or declining levels of serum cholesterol have been associated with increased mortality from cancer. We conducted a population-based cohort study of 1882 patients from one Danish county who received lipid-lowering drugs between January 1, 1991 and December 31, 1994. During the follow-up period of up to 4 years, 41 cancers were observed among users of lipid-lowering drugs, with 42.9 expected, to yield an age- and sex-standardized incidence ratio of 1.0 (95% confidence interval, 0.7-1.3). Although limited by small numbers and short follow-up period, examination by site of cancer and type of drug provided no evidence of an association. Further research is needed, however, with longer follow-up to assess more fully any potential cancer risk with these medications.

A population-based study of antibiotic prescriptions for Danish children.

BACKGROUND: The aim of the study was to examine the use of systemic and topical antibiotics in relation to age and sex in Danish children. METHODS: We used the Pharmacoepidemiological Prescription Database to identify the individual prescriptions of antibiotics provided for all 0-to 15-year-old children in North Jutland County, Denmark, during 1997. The population was approximately 95000 children. RESULTS: We identified 44640 prescriptions for systemic antibiotics. The annual prescription rate was highest in the 1- to 2-year-olds, with 945 prescriptions/1000 children/year. One-half of these children received at least 1 prescription, and 12% received 3 or more prescriptions. Among the 11- to 15-year-old children 17% received one or more prescriptions. Overall 88% of the prescriptions were penicillins and 10% were macrolides. In children younger than 3 years 57% of prescriptions were for broad spectrum penicillins, but in children older than 6 years penicillin V was the most frequently used antibiotic. We identified 12 661 prescriptions for topical antibiotics used in eye infections. The prescription rate peaked in the 1- to 2-year-old children, one-third of whom received at least 1 prescription. CONCLUSIONS: Almost two-thirds of the 0- to 2-year-old children in the population were treated with either systemic or topical antibiotics during 1 year. Physicians prescribe mostly penicillins, but the proportion of broad spectrum penicillins for young children was so high, however, that enforcement of national guidelines should be reconsidered.

Alcohol consumption and serum liver-derived enzymes in a Danish population aged 30-50 years.

BACKGROUND: Based on the increased consumption of alcohol in Denmark the aim of this study was to measure prevalence of abnormal liver-derived enzymes in a homogeneous Danish population and possible associations with alcohol consumption, smoking and body mass index (BMI). METHOD: In a representative population sample of 905 people (aged 30-50) from the baseline survey of the Ebeltoft Health Promotion Project in Denmark, we examined prevalence of abnormal liver-derived enzymes and its possible association with self-reported alcohol consumption, smoking and BMI, applying logistic regression analyses. RESULTS: In a significant proportion, 12% (women 8%; men 16%) of the cohort we found raised levels of liver-derived enzymes associated with moderate self-reported alcohol intake adjusted for BMI and smoking. If the intake was higher than moderate, i.e. > 28 units per week (one unit equals 12 g of alcohol), the odds ratio (OR) for raised liver enzymes increased further; S-gamma-glutamyltransferase (GGT) (OR: for women 24.4; men 18.4). S-aspartate-aminotransferase (ASAT) (24.2; 5.8) and S-alanine-aminotransferase (ALAT) (27.2; 3.0). Furthermore, daily smoking increased the risk of raised liver enzymes in women (OR: 3.4-4.2), and obesity (BMI > or = 30 kg/m2) in men showed a positive association with all three enzymes (OR: 3.0-9.0). CONCLUSIONS: The occurrence of raised liver-derived enzymes was frequent in the Danish population sample and associated with moderate self-reported alcohol consumption adjusted for BMI and smoking.

A population-based cohort study of birth and neonatal outcome in older primipara.

OBJECTIVES: To examine the risk of adverse birth outcome in older primiparous women. METHODS: We identified 14,676 primiparae of 20 years of age or more from 1991 to 1996 using the Birth Registry in the North Jutland County, Denmark. We evaluated the risk of adverse birth outcome in the primiparous women aged 30-34 years and above 35 years using the primiparae aged 20-29 years at time of birth as reference. RESULTS: The risks of induced labor, perineotomy, stimulating contraction and vacuum extraction were significantly higher (adjusted odds ratio: 1.3 to 1.7) in the primiparae of 35 years or more. The odds ratio for cesarean section delivery was 2.1 (95% confidence interval: 1.7-2.6) and the odds ratio for delivering a low birth weight child among the primiparae of 35 years or more was 2.2 (95% confidence interval: 1.4-3.3) compared with the primiparae of 20-29 years of age. These risk estimates were independent of women's infertility treatment history. CONCLUSIONS: A negative effect of maternal age on birth and neonatal outcome may be seen even after 30 years of age and is partly related to chronic diseases. However, it is impossible to rule out selection bias, but the actual risk must be taken into consideration in antenatal care.

[Incidence of cancer after primary deep venous thrombosis or pulmonary embolism]. / Incidens af cancer efter påvist primaer dyb venetrombose eller lungeemboli.

We report a nationwide study based on a cohort of patients with a thromboembolic event (TE) defined as deep venous thrombosis and/or pulmonary embolism identified from the Danish National Registry of Patients from 1977 to 1993. Cancer occurrence in the cohort was determined by linkage to the Danish Cancer Registry. Expected number of cancer cases was estimated from age, sex and site-specific incidence rates. A total of 26,653 TE-cases were identified. We observed 1737 cases of cancer versus 1371 expected (SIR 1.3; 95% CI, 1.21 to 1.33). The risk was particularly high during the first months of follow-up, but declined rapidly hereafter to a constant level slightly above 1.0 one year after the TE. Forty percent of patients diagnosed with cancer within one year from the hospitalization for TE had distant metastases at the time of cancer diagnosis. The observed risk pattern provides evidence that most often a preclinical cancer gives rise to a subsequent TE. An aggressive search for hidden cancer in patients with TE is not warranted.

[Implementation of research results. Are physicians interested in reference programs?]. / Implementering af forskningsresultater. Er loegerne interesserede i referenceprogrammer?

In a questionnaire we investigated whether 315 general practitioners (GPs), 79 heads of departments of medicine and 20 heads of departments of neuromedicine were aware of new national guidelines for oral anticoagulation in atrial fibrillation issued by the Danish Society of Internal Medicine. The guidelines were only known to 22% of the GPs, 6% of the neurological consultants and 64% of the medical consultants, but nevertheless only 4-7% of the doctors did not want distribution of guidelines. Fifty-four percent of the GPs and 12% of the specialists preferred the Danish College of General Practitioners to in some way participate in the development of guidelines. Our study suggests that guidelines are met with a positive response, but to obtain optimal use a powerful implementation effort must be recommended.

[Alcohol consumption and liver enzymes in persons 30-50 years of age. Cross-sectional study from Ebeltoft]. / Alkoholforbrug og leverenzymer hos 30-50-årige. En tvaersnitsundersøgelse fra Ebeltoft.

In a representative population sample of 905 persons we examined the prevalence of raised levels of liver-derived enzymes and its possible association with self-reported alcohol consumption adjusted for smoking and BMI applying logistic regression analyses. A large proportion of 12% (women 8%; men 16%) presented raised liver-derived enzymes. Below 21 units per week (one unit equals 12 grams of alcohol) there was no association with self-reported alcohol consumption. However, the risk of abnormal liver enzymes increased with higher consumption for both sexes; if the intake was above 28 units per week, the odds ratio for raised liver enzymes increased dramatically. Whether this subclinical biochemical liver condition is an early marker of alcohol-related liver damage remains to be seen, but the long-term consequences of the reported alcohol consumption and the frequency of raised liver enzymes require follow-up.

[Antibiotic pre-hospital treatment and the course of meningococcal disease]. / Antibiotisk behandling før indlaeggelse og forløbet af meningokoksygdom.

The aim of the study was to assess the effect of pre-hospital antibiotic treatment given by general practitioners to patients with meningococcal disease. It was carried out as a 16-year population-based historical follow-up study based on referral letters and hospital records in the County of North Jutland, Denmark, and included 320 patients with meningococcal disease, of whom 302 were examined by a general practitioner before admission to hospital. The main outcome measure was death. We found that 44 patients (14.6%) were given antibiotic treatment by the referring general practitioner. Nine of these (20.5%) died, compared with 16 (6.2%) patients who did not receive pre-hospital antibiotic treatment. The presence of skin bleeding, petechiae and impaired consciousness were strongly associated with case fatality. Even after adjustment for these variables the odds ratio for death in patients treated with antibiotics was high (3.2; 95% CI 0.9-10.6). In the 15 patients with skin bleeding (ecchymoses, suggillations) the case fatality rate was 100% in patients treated with antibiotics, and 50% in patients who did not receive antibiotics before hospitalization. It is concluded that pre-hospital treatment is mainly given to the most severe cases with expected high case fatality, and this confounding by indication was probably not fully adjusted for with the available data. The results contradict previous findings and provide reason to doubt the benefit of pre-hospital antibiotic treatment in patients with meningococcal disease.

[Registration in medical journals of prescriptions for strong analgesics prescribed by general practitioners]. / Praktiserende laegers journalregistrering af recepter udstedt på staerke analgetika.

The use of strong analgesics was continuously registered in 90 patients throughout 12 months via the public health authorities, who are responsible for the control of prescription of strong analgesics. After the 12 months, questionnaires were sent to the prescribing doctors about the treatment during that period. Twenty-five patients were excluded mainly due to incomplete data and non-responding GPs. Analysis of validity of the GPs' registration, with the public health authorities' registration used as the reference standard, showed 90% (95% confidence limits (CL):68-99%) agreement concerning continuing treatment with strong analgesics and 98% (CL:88-100%) regarding GPs' registration of patients not being treated with strong analgesics. In all, misclassification occurred in 5% (CL:1-13%) of the patients. Our study suggests that the GPs' information about prescriptions of strong analgesics is valid, and that it can be used in research.

Variation in antibiotic prescribing costs in Danish general practice: an epidemiological pharmaco-economic analysis.

Based on 49,621 prescriptions during a period of 6 months we analysed factors relevant to the use of antibiotics among 137 general practitioners based on the reimbursement by the Danish Health Service. The background population constituted 167,105 adults and 42,392 children. The Danish Health Service refunds either 50 or 75% of the costs of antibiotics. The mean reimbursement per prescription was 96.45 DKK ranging between 56.10 DKK and 141.95 DKK. The total prescribed amount of antibiotics per GP measured in defined daily dose (DDD), the reimbursement per prescription for all other drugs than antibiotics, the proportion of patients above the age of 65 years and the number of cultures per 1,000 patients were positively associated with the reimbursement per prescription of antibiotics. The four variables explained 29% of the variation. The number of cultures and consultations per general practitioner were positively associated with the total reimbursement for antibiotics per general practitioner, while the number of throat swabs per general practitioner was negatively associated. The prescribed amount of DDD per prescription and the reimbursement per DDD of antibiotics contributed almost equally to the variation in reimbursement for each prescription. The study thus shows that the doctors prescribing the highest amounts of antibiotics measured as DDD also choose the most expensive drugs and that this choice of expensive drugs seems to be a general trend independent of the ATC group.

Research in the Danish health service system: completeness and validity of prescription data, illustrated by analysis of utilization of oral anticoagulants.

We studied the utilization of oral anticoagulants and the degree of completeness and validity of some key research variables from the Danish health service in the county of North Jutland (482 000 inhabitants), studying the records of 12 855 prescriptions of oral anticoagulants during 1991 and 1992. The utilization of oral anticoagulants showed an increase of 16% from 1991 to 1992, when 0.3% of all women and 0.4% of all men were treated during one year. The increase was less than expected based on newly introduced indications for treatment of atrial fibrillation. The following variables were studied: the name (ATC commodity number) and amount of the prescribed drug, the defined daily dose, the personal registration number of the patient, type of prescription (e.g. in writing or by telephone), number of repeat prescriptions, date of prescription issued by the doctor, the registration number of the GP or hospital department (if the prescription is made by a hospital doctor) and date of expedition from the pharmacy. The number of wrong and missing data was less than 1%. The study suggests that Danish prescription information is of such quality that it can be used for pharmacoepidemiological studies.

The Pharmacoepidemiologic Prescription Database of North Jutland - a valid tool in pharmacoepidemiological research.

In this paper we describe the options of a pharmacoepidemiologic database comprising data on all reimbursed prescriptions taken up at pharmacies in the County of Northern Jutland since 1991 including precise identification of the individual person for whom the medicin was prescribed. The County comprises 487,000 inhabitants equal to approximately 10% of the total Danish population.