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In Denmark, as in many other Western countries, a decline in mortality from ischaemic heart disease (IHD) has been observed. The present study assesses whether the decline in IHD mortality is due to a decrease in incidence and/or case-fatality, and whether parallel changes occurred in the various manifestations of IHD requiring hospitalization. The National Patient Register of hospital discharges and the Causes-of-Death Register were linked and all cases of first admission for IHD including acute myocardial infarction (AMI) and fatal first manifestation of IHD since 1977 in the entire Danish population were identified. Cases of AMI and IHD were considered as incident cases if no admission for these diagnoses had occurred during the preceding five years for the same person. Sex-specific, age-standardized annual mortality, incidence and case-fatality rates of AMI (ICD8 code 410), narrowly defined IHD (NIHD, ICD8 codes 410-4) and broadly defined IHD (BIHD, ICD8 codes 410-4, 427795-6) were calculated for the period 1982 through 1992. During the entire period the age-standardized mortality of AMI, NIHD and BIHD decreased in both men and women. The incidence of AMI and NIHD decreased, while the incidence of BIHD remained constant. Case-fatality of AMI decreased in both men and women, while case-fatality of NIHD and BIHD decreased in men and in women aged 0-64 years only. The declining mortality from IHD in Denmark may be partly due to declining incidence as well as declining case-fatality, but changes in disease manifestation or a diagnostic drift may also contribute, since more broadly defined diagnostic groups showed less or no decline in incidence.

Serologic studies (1–5) indicate that an epidemic of human herpesvirus 8 (HHV8) or Kaposi’s sarcoma (KS)associated herpesvirus, the viral etiologic agent of KS, occurred among homosexual men in the United States and in Europe concurrently with the human immunodeficiency virus-1 (HIV) epidemic in the early 1980s. However, studies from the United States (1,6) suggest that HHV8 possibly had become prevalent in some gay communities before the HIV epidemic. Thus, in the first decade of the U.S. HIV epidemic, the risk of acquired immunodeficiency syndrome (AIDS)-related KS in homosexual men was higher in HIV epicenters, such as New York, than elsewhere (6). Accordingly, the risk among homosexual men of being or becoming HHV8 infected from 1982 through 1990 was higher in New York than in Washington, DC (1). Little is known about the epidemiology of HHV8 in Europe before the HIV epidemic. Although studies (4,7) indicate that HHV8 was disseminated to the European gay communities from the United States or from KS-endemic regions, such as Africa, in conjunction with the introduction of HIV, it is not known whether HHV8 was already prevalent in the gay communities before the HIV epidemic. To study the prevalence of HHV8 infection before the HIV epidemic, we examined sera for HHV8 antibodies in individuals attending an outpatient clinic for a sexually transmitted disease (STD) in Copenhagen, Denmark, from March 1976 through February 1977. This study was approved by the Scientific Ethics Committees for Copenhagen and Frederiksberg Municipalities and by the Danish Data Protection Agency. The study population has been described in detail elsewhere (8). Briefly, from March 1976–February 1977, individuals attending the largest STD outpatient clinic in Copenhagen were invited to participate in a serologic study of gonorrhea. For all participants, information was recorded on age, sex, place of birth, and history of gonorrhea, including the outcome of actual clinical and microbiologic examinations. All participants had blood drawn, and since the original study, the sera have been stored at –20 °C. For the present study, we analyzed the sera from 641 anonymous individuals. The sera were analyzed for antibodies against HHV8 as described previously (9). Specifically, antibodies against the lytic phase glycoprotein K8.1 were detected with the use of a recombinant protein enzyme-linked immunosorbent assay (ELISA) (9). The samples that had an optical density of greater than 0.5 were further analyzed for antibodies against the HHV8 latencyassociated nuclear antigen by an indirect immunofluorescence assay that used the latently HHV8-infected BCP-1 cell line (9). Sera were classified as HHV8 positive if the optical density reading in the ELISA was greater than 1.0 or for samples with optical density readings between 0.5 and 1.0 if they were also positive by the indirect immunofluorescence assay (9). This testing algorithm is estimated to detect antibodies for HHV8, with a sensitivity of approximately 85% and a specificity of approximately 97% (9). We assessed ageand sex-specific HHV8 antibody prevalence and also evaluated the relevance of a diagnosis of gonorrhea (ever versus never) and country of origin (participants from classic KS-endemic areas [defined here as African countries, Italy, Israel, and Greece] versus all other countries). The relative risk of having HHV8 antibodies was estimated as the odds ratio (OR) ascertained by logistic regression analyses (SAS version 6.12; SAS Institute Inc., Cary, NC), with likelihood ratio-based 95% confidence intervals (CIs). All statistical tests were twosided. Overall, 27 (4.2%) of 641 individuals had HHV8 antibodies. The distribution by age, sex, country of origin, and history of gonorrhea is provided in Table 1. The prevalence was 5.1% (20 of 391) in men (4.1% [13 of 314] among Danish men only) and 2.8% (seven of 250) in women (3.2% [seven of 216] among Danish women only), a statistically nonsignificant difference (P .14) (Table 1). Overall, the prevalence of HHV8 antibodies increased with age (Table 1). Originating from a classic KS-endemic area was associated with a 15.7-fold (95% CI 5.0 to 45.5) increased likelihood of having HHV8 antibodies (Table 1). Because of the small number of women from KS-endemic areas, however, the increased risk associated with origin could be demonstrated only in men (OR 15.5; 95% CI 4.7 to 48.2) (Table 1). Overall, history of gonorrhea was associated with a 3.4-fold (95% CI 1.4 to 10.4) increased likelihood of having HHV8 antibodies (Table 1). The increased risk of having HHV8 antibodies was associated more strongly with a history of gonorrhea in men (crude OR 4.5 [95% CI 1.3 to 15.8]; adjusting for country of origin, OR 3.8 [95% CI 1.2 to 16.6]) than in women (OR 1.9; 95% CI 0.4 to 13.2). However, after adjusting for country of origin, the difference in risk estimates between men and women was not statistically significant (P .24). The application of different serologic assays makes it difficult to compare directly the prevalence of HHV8 antibodies in different populations (10). Still, the prevalence of HHV8 antibodies in this study of STD clinic attendees from 1976 through 1977, ranging from 3.2% in women to 4.1% in men, is of a similar order of magnitude to that reported in recent blood donor surveys in other

We studied the impact on survival of changes in breast cancer patients' distribution by lymph node status at the time of diagnosis. Our study included breast cancer patients diagnosed from 1978 to 1994 in Denmark, where the treatment schemes for breast cancer patients were fairly stable, and where mammography screening was limited. We measured lymph node status by the proportion of positive lymph nodes of all excised lymph nodes, as assessed by a pathologist. This measure was available for two-thirds of the breast cancer patients. The outcome was 5-year relative survival. Changes in lymph node status distribution explained half of the improvement in 5-year relative survival, and seem to be the single most important cause behind the improved survival of breast cancer patients in Denmark.

Udgivelsesdato: 2003-Oct-15 BACKGROUND: Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years. METHODS: Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. RESULTS: We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period. CONCLUSION: Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.

Introduction Many epidemiological methods for analysing follow-up studies require the calculation of rates based on accumulating person-time and events, stratified by various factors. Managing this stratification and accumulation is often the most difficult aspect of this type of analysis. Tutorial We provide a tutorial on accumulating person-time and events, stratified by various factors i.e. creating event-time tables. We show how to efficiently generate event-time tables for many different outcomes simultaneously. We also provide a new vocabulary to characterise and differentiate time-varying factors. The tutorial is focused on using a SAS macro to perform most of the common tasks in the creation of event-time tables. All the most common types of time-varying covariates can be generated and categorised by the macro. It can also provide output suitable for other types of survival analysis (e.g. Cox regression). The aim of our methodology is to support the creation of bug-free, readable, efficient, capable and easily modified programs for making event-time tables. We briefly compare analyses based on event-time tables with Cox regression and nested case-control studies for the analysis of follow-up data. Conclusion Anyone working with time-varying covariates, particularly from large detailed person-time data sets, would gain from having these methods in their programming toolkit.