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Biomedical subjects

N Keiding

Publications and source records attributed to N Keiding.

At least 19 recordsLinked to original sources

The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.

UNLABELLED: Randomised clinical trials find no protection against development of ischaemic heart disease by use of Hormone Therapy (HT) after the age of 50 years. Observational studies suggest that early menopause is a risk factor for ischaemic heart disease. Yet, a clinical very relevant question is whether HT reduces this risk associated with early menopause. OBJECTIVE: To analyse whether early menopause based on various causes are independent risk factors for ischaemic heart disease, and to investigate whether the risks are modified by use of HT. METHODS: In a prospective cohort study questionnaires were mailed to Danish female nurses above 44 years of age in 1993. Information on menopause, use of HT and lifestyle was obtained. In total 19,898 (86%) nurses fulfilled the questionnaire, among them 10.533 were postmenopausal with definable menopausal age, free of previous ischaemic heart disease, stroke or cancer. Through individual linkage to national register incident cases of ischaemic heart disease were identified until end of 1998. RESULTS: Menopause below both age 40 and 45 was associated with an increased risk of ischaemic heart disease, seeming most pronounced for women who had an early ovariectomy but also among spontaneous menopausal women. Generally HT did not reduce the risk except for the early-ovariectomised women, where no increased risk of ischaemic heart disease for HT users was found. CONCLUSION: We found an increased risk of ischaemic heart disease associated with early removal of the ovaries that might be reduced with HT. The present study need confirmation from other studies but suggests that early ovariectomised women could benefit from HT.

Adult↗

Individual survival time prediction using statistical models.

Doctors' survival predictions for terminally ill patients have been shown to be inaccurate and there has been an argument for less guesswork and more use of carefully constructed statistical indices. As statisticians, the authors are less confident in the predictive value of statistical models and indices for individual survival times. This paper discusses and illustrates a variety of measures which can be used to summarise predictive information available from a statistical model. The authors argue that models and statistical indices can be useful at the group or population level, but that human survival is so uncertain that even the best statistical analysis cannot provide single-number predictions of real use for individual patients.

Carcinoma, Non-Small-Cell Lung↗

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy.

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.

Aged↗

Relation between hormone replacement therapy and ischaemic heart disease in women: prospective observational study.

OBJECTIVE: To investigate the risk of ischaemic heart disease and myocardial infarction among women using hormone replacement therapy, especially the potential modifying effect of cardiovascular risk factors. DESIGN: Prospective observational study. SETTING: Denmark. PARTICIPANTS: 19 898 nurses aged 45 and over completing a questionnaire on lifestyle and use of hormone replacement therapy in 1993. MAIN OUTCOME MEASURES: All cases of death and incident cases of ischaemic heart disease and myocardial infarction until the end of 1998. RESULTS: Current users of hormone replacement therapy smoked more, consumed more alcohol, had lower self rated health, but were slimmer and had a lower prevalence of diabetes than never users. In current users compared with never users, hormone replacement therapy had no protective effect on ischaemic heart disease (hazard ratio 1.2, 0.9 to 1.7) or myocardial infarction (1.0, 0.6 to 1.7), whereas current users with diabetes had an increased risk of death (3.2, 1.4 to 7.5), ischaemic heart disease (4.2, 1.4 to 12.5), and myocardial infarction (9.2, 2.0 to 41.4) compared with never users with diabetes. CONCLUSION: Hormone replacement therapy showed no protective effect on ischaemic heart disease, but there was a significantly increased risk of death from all causes and ischaemic heart disease among women with diabetes.

Aged↗

Increased incidence of affective disorders, anxiety disorders, and non-natural mortality in women after breast cancer diagnosis: a nation-wide cohort study in Denmark.

OBJECTIVE: To investigate whether breast cancer patients have increased incidence of psychiatric admission with affective disorders, anxiety disorders, or non-natural mortality compared with the general female population. METHOD: Register-linkage between nation-wide registries: The Danish Psychiatric Central Register, The Danish Cancer Registry, and The Danish National Register of Causes of Death. A total of 61 709 women registered with primary invasive breast cancer between 1970 and 1993 were included and 356 023 person-years were accrued. RESULTS: The standardized incidence ratio of first-ever psychiatric admission with affective disorder was 1.49 (95% CI: 1.35-1.63) and with anxiety disorder 1.25 (95% CI: 1.06-1.46). The standardized non-natural mortality ratio during the first year after breast cancer diagnosis was 1.54 (95% CI: 1.27-1.87). All analyses were adjusted for age, calendar period, and place of residence. CONCLUSION: Breast cancer patients have significantly increased incidence of psychiatric admission with affective disorders, anxiety disorders, and non-natural mortality.

Adolescent↗

An epidemiological survey of hemiplegic migraine.

The objective of the present study was to use systematic nation-wide case-finding methods to establish the prevalence and sex ratio of hemiplegic migraine (HM) in the entire Danish population of 5.2 million inhabitants. Affected patients were identified from three different recruitment sources: the National Patient Register, case records from private practising neurologists and advertisements. Based on the observed number of affected patients from each case-finding method, it was attempted to estimate the total number of affected patients by means of the statistical method known as capture-recapture. Two hundred and ninety-one affected patients were identified; 147 were familial HM from 44 different families, 105 were sporadic HM and 39 were unclassifiable HM. The HM sex ratio (M:F) was 1:3. Based on the identified number of affected patients the prevalence of HM at the end of 1999 was estimated to be 0.01% in Denmark, where the familial and sporadic form were equally frequent.

Advertising↗

Time to pregnancy and semen parameters: a cross-sectional study among fertile couples from four European cities.

BACKGROUND: In fertile populations, little is known about the association between semen parameters and time to pregnancy (TTP). METHODS: Pregnant women from Copenhagen, Edinburgh, Paris and Turku who conceived without medical intervention were asked for their TTP (942 couples), and their partners provided a semen sample. The proportion of morphologically normal sperm and the multiple anomalies index (MAI, ratio of the total number of anomalies to the number of abnormal sperm) were centrally estimated. We estimated rate ratios for the occurrence of a pregnancy by a discrete survival model, adjusted for sexual activity and female factors affecting fecundity. RESULTS: Increasing sperm concentration influenced TTP up to 55 x 10(6)/ml. The proportion of morphologically normal sperm influenced TTP up to 39% according to David's criteria, and this association held among the subjects with a sperm concentration >55 x 10(6)/ml. For strict criteria, the threshold value was 19% normal sperm. An increase of 0.5 in MAI was associated with an adjusted rate ratio for the occurrence of a pregnancy of 0.68 (95% confidence interval: 0.54-0.85). CONCLUSIONS: These results highlight the importance of sperm morphology parameters and indicate that the effect of proportion of normal sperm on TTP may be independent of sperm concentration.

Cross-Sectional Studies↗

Long term mortality trends behind low life expectancy of Danish women.

STUDY OBJECTIVE: To examine the long time mortality trends of women in Denmark. DESIGN: Age-period-cohort analysis. SETTING: To search for possible causes we analysed mortality rates for all Danish women and men aged 40-84 during 1960-1999. Age-period-cohort modelling was used, handling the well known indeterminacy in a sensitivity analysis. MAIN RESULTS: The results indicate that the high risk of dying among Danish women is associated with being born between the two world wars. A similar pattern was not seen for men. CONCLUSION: The rather simple descriptive exploration in the framework of age-period-cohort modelling used, revealed a pattern not reflected by the commonly used life expectancy calculation. It is suggested that future studies on the low life expectancy of Danish women focus on the "between wars" generations identified with a high risk of dying in this study.

Adult↗

Multi-state models and outcome prediction in bone marrow transplantation.

Multi-state models have proved versatile and useful in the statistical analysis of the complicated course of events after bone marrow transplantation. Working from data from the International Bone Marrow Transplant Registry, we show that summary probability calculations may be useful to explore hypothetical scenarios where some transition intensities are set by the researcher. A multi-state Markov process model is specified with six states: the initial state 0; acute; chronic and both acute and chronic graft-versus-host disease A, C and AC; relapse R and death in remission D. Transition rates between the states are estimated using Nelson-Aalen estimators and Cox regression models and combined to transition probability estimators using Aalen-Johansen product integration. Besides the estimated transition probabilities to D and R we explore hypothetical probabilities obtained by artificially changing certain transition intensities, with the general purposes of getting summary views of the development for actual patients 'in this world' and of exploring the intrinsic information from real patients about consequences of various changed conditions.

Bone Marrow Transplantation↗

Correlations between the incidence of childhood-onset type I diabetes in Europe and HLA genotypes.

There are large variations in the incidence of Type I (insulin-dependent) diabetes mellitus within Europe, ranging from 3.2 cases per 100,000 person-years in the Republic of Macedonia to more than 40 new cases per 100,000 person-years in Finland. This variation could be caused by differences in the distribution of genetic susceptibility markers, by differences in the distribution of environmental disease determinants or by a combination of both. To assess how much genes contribute to this variation, we correlated the level of incidence of Type I diabetes with the prevalence in the general population of genetic susceptibility and protective markers encoded by the human leukocyte antigen (HLA)-DQ loci. Positive association was found for the combined group of genotypes associated with Type I diabetes risk (p < 0.001). The whole positive effect was, however, accounted for by the HLA-DQ2/ DQ8 (DQA1*0501-DQB1*0201/DQA1*0301-DQB1*0302) and HLA-DQ4/DQ8 (DQA1*0401-DQB1*0402/DQA*0301-DQB1*0302) genotypes (p < 0.001 and p < 0.004, respectively). No correlation was found between incidence of Type I diabetes and population prevalence of genotypes not encoding for aspartate on position 57 on the HLA-DQbeta chain. It was not possible to detect any negative correlation between Type I diabetes incidence and the prevalence of HLA-genotypes conferring protection against Type I diabetes in a population (HLA-DQA1*0102-DQB1*0602/X). The results suggest that a substantial part of the transnational variation in the incidence of childhood-onset Type I diabetes in Europe is explained by variations between populations in the distribution of particular DQ genotypes which confer a high risk of Type I diabetes in the general population.

Age of Onset↗

Use of isokinetic muscle strength as a measure of severity of rheumatoid arthritis: a comparison of this assessment method for RA with other assessment methods for the disease.

The aim of this study was to study the association between isokinetic muscle strength (IMS) and other clinical indicators of disability and disease activity in patients with rheumatoid arthritis (RA). A cohort of 36 RA patients was followed over a 1-year period with five measurements of disease activity at regular intervals during this time. IMS was measured at seven angular velocities in both knees, on five separate occasions. The measurement was expressed by the level of the fitted line of the seven peak torque values--IMS30. The association between IMS30 and clinical indicators was stated. As an indicator of disability the score from the Stanford Health Assessment Questionnaire (HAQ) was used. As indicators of disease activity morning stiffness, an index of swelling and pain in the joint, erythrocyte sedimentation rate (ESR) and haemoglobin (Hb) were chosen. Larsen's X-ray score was used as an indicator of bone destruction due to longer-lasting disease activity. IMS was significantly associated with the HAQ score, but not with indicators of disease activity or radiological findings. IMS was significantly associated with changes in indicators of disease activity, but not with the changes in the HAQ score, or in the X-ray-score. IMS showed the strongest association with changes in the degree of arthritis of the knee. In conclusion, IMS was associated with the HAQ score and can therefore be used when measuring outcome in a specific group of RA patients. Changes in IMS were associated with indicators of changes in disease activity, and are therefore usable as a measure of patient outcome. Of particular importance is that IMS decreased if a patient developed active arthritis in the knee, and normalised again when the inflammation decreased.

Adult↗

Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis.

In this paper, we describe modern statistical methods for presentation of the results of studies of bone marrow transplantation. We focus here on 'univariate' or unadjusted techniques to describe the outcomes of such studies. In another paper we will discuss multivariate methods. We discuss the type of data one may have available to make inference about outcomes. We explain the differences between the Kaplan-Meier estimator of the survival function and the cumulative incidence curve, how these curves should be interpreted and when each is the appropriate summary statistic. We discuss the weighted log rank statistic and show how different weights can be used to put emphasis on detecting differences between groups in different time periods. We also present a simple estimate of current leukemia-free survival which is useful in summarizing post-transplant events.

Analysis of Variance↗

Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part 2: Regression modeling.

In this paper, we address methods of multivariate regression. We discuss the value of regression compared to matched pairs analysis, methods of coding variables, basic concepts of the Cox model and interpretation of results of the Cox model. We present methods of handling variables whose effect changes with time. We present methods to check the assumptions of the Cox regression. Finally, and perhaps most importantly, we provide suggestions for presenting the results in clear and thorough tables and graphs.

Bone Marrow Transplantation↗

Regional differences in waiting time to pregnancy among fertile couples from four European cities.

BACKGROUND: A previous European study found a longer time to pregnancy (TTP) among fertile women from Paris compared with women from other Western European countries. A co-ordinated, cross-sectional study of pregnant couples from Denmark (Copenhagen), France (Paris), Scotland (Edinburgh) and Finland (Turku) was therefore undertaken to assess differences in waiting TTP among couples from these cities. METHODS: Pregnant women were invited to participate when they showed up for their first antenatal visit in one of the four centres. Inclusion criteria included that their partner was 20-45 years of age and born in the country in which he was currently living and that the pregnancy was achieved without fertility treatment. Both partners filled in a questionnaire and the man underwent a physical examination and delivered a semen sample (Turku: n = 237, Copenhagen: n = 302, Edinburgh: n = 212, Paris: n = 191). RESULTS: French couples had a decreased probability of conception compared with couples from the other three countries, although only after adjustment for confounders. No significant differences between couples from the three other countries were found. CONCLUSION: The observed geographical differences in TTP remain unexplained and were not due to differences in semen quality, but may be caused by varying exposures to environmental factors or psychological distress. In addition, selection bias due to the low participation rates cannot be ruled out. Future studies examining the causes for geographical differences in TTP are needed.

Adult↗

Regional differences in semen quality in Europe.

Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, inter-laboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (x 10(6)/ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Adult↗

Benchmark dose calculation from epidemiological data.

A threshold for dose-dependent toxicity is crucial for standards setting but may not be possible to specify from empirical studies. Crump (1984) instead proposed calculating the lower statistical confidence bound of the benchmark dose, which he defined as the dose that causes a small excess risk. This concept has several advantages and has been adopted by regulatory agencies for establishing safe exposure limits for toxic substances such as mercury. We have examined the validity of this method as applied to an epidemiological study of continuous response data associated with mercury exposure. For models that are linear in the parameters, we derived an approximative expression for the lower confidence bound of the benchmark dose. We find that the benchmark calculations are highly dependent on the choice of the dose-effect function and the definition of the benchmark dose. We therefore recommend that several sets of biologically relevant default settings be used to illustrate the effect on the benchmark results and to stimulate research that will guide an a priori choice of proper default settings.

Animals↗

Selection bias in determining the age dependence of waiting time to pregnancy.

Many studies have found decreased fecundability, that is, the ability to conceive in a menstrual cycle, with increasing female age. To evaluate the effect of maternal age on waiting time to pregnancy, the authors reviewed hospital charts of all pregnant women attending prophylactic antenatal care at Odense University Hospital, Denmark, during 1972-1987. Only the first pregnancy of each woman and only planned pregnancies were included (n = 14,754). The fecundability odds ratio (FR) was calculated as the odds of a conception in a menstrual cycle among the older women divided by the odds among women aged 15-24 years. The FR for women aged 25-29 years was 1.12 (95% confidence interval (CI): 1.04, 1.20), for women aged 30-34 years it was 1.15 (95% CI: 1.01, 1.30), and for women above 34 years the FR was 2.44 (95% CI: 1.84, 3.22) after adjustment for confounders. The increased fecundability with age is contrary to previous studies and may be explained by selection bias, as sterile women were not included. In addition, some very fertile young women who became pregnant by accident before efficient birth control methods were available and therefore were excluded from time to pregnancy studies may now use oral contraceptives until they plan a pregnancy later in life and are included.

Adolescent↗