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Biomedical subjects

N Keiding

Publications and source records attributed to N Keiding.

At least 37 records · Page 2Linked to original sources
PubMed2000

Benchmark dose calculations of methylmercury-associated neurobehavioural deficits.

Prenatal methylmercury exposure is associated with neuropsychological deficits in Faroese children at age 7 years. Lower confidence bounds of benchmark doses (BMDLs) have now been calculated. With the cord-blood mercury concentration as the dose parameter, a logarithmic dose-response model tended to show a better fit than a linear dose model for the attention, language and verbal memory tests. The lowest BMDLs averaged approximately 5 microgram/l cord blood, which corresponds to a maternal hair concentration of approximately 1 microgram/g. However, most BMDLs for hair mercury concentrations were higher. Thus, the results of the benchmark calculations depend on the assumed dose-response model.

Biomarkers↗
PubMed2000

Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve.

A significant number of patients who relapse after allogeneic stem cell transplantation (SCT) for chronic myeloid leukaemia (CML) will achieve sustained molecular remissions after treatment with donor lymphocyte infusions (DLI) from the original stem cell donor. Leukaemia-free survival, defined as survival without evidence of relapse at any time after transplant does not account for patients who are successfully treated with DLI. To summarize adequately the response to treatment, a new summary probability, called the current leukaemia-free survival (CLFS), is proposed. This quantity is defined as the probability that a patient is alive and in remission at a given time after transplant. We discuss two statistical methods for estimating CLFS. The first is based on a multistate modelling approach. The second is based on an estimate constructed by looking at appropriate differences between Kaplan-Meier estimates. We compare these estimates using data on 189 consecutive patients who underwent SCT over a 7-year period.

Adoptive Transfer↗
PubMed2000

High frequency of sub-optimal semen quality in an unselected population of young men.

Male reproductive function seems to have deteriorated considerably during the past 4-5 decades. However, studies of the reproductive function in unselected populations have not previously been reported. As the large majority of young men in Denmark are subjected to a compulsory medical examination for military service, this provided a unique opportunity to study the reproductive function in an unbiased population. Altogether 891 young men delivered a blood sample in which reproductive hormones were measured. From 708 of these men data were also obtained on semen quality and testis size. The median sperm concentration was 41 x 10(6)/ml (mean 57.4 x 10(6)/ml). Men with ejaculation abstinence above 48 h had slightly higher sperm concentrations (median 45 x10(6)/ml, mean 63.2 x 10(6)/ml), but even in this subgroup, 21 and 43% respectively had sperm counts below 20 x 10(6)/ml and 40 x 10(6)/ml. Among men with no history of reproductive diseases and a period of abstinence above 48 h, as many as 18 and 40% respectively had concentrations below 20 and 40 x 10(6)/ml. Sperm counts were positively correlated with testis size, percentage normal spermatozoa and inhibin B, and negatively correlated with percentage immotile spermatozoa and follicle stimulating hormone. Possible causes for this high frequency of young men with suboptimal semen quality are obscure and need to be explored. Whether these findings apply for young male populations of comparable countries remains to be seen.

Analysis of Variance↗
PubMed2000

Retrospectively sampled time-to-pregnancy data may make age-decreasing fecundity look increasing. European Infertility and Subfecundity Study Group.

The retrospective study based on pregnancy samples is the most commonly used method for studying time to pregnancy. Using a simple Monte Carlo simulation, this note focuses on a particular selection bias problem associated with this design: even if each woman's fecundity decreases with age, estimation of the effect of age may show the opposite trend. We recommend exercising increased caution in interpreting findings from pregnancy-based time-to-pregnancy studies.

Adult↗
PubMed1999

Methylmercury exposure biomarkers as indicators of neurotoxicity in children aged 7 years.

The mercury concentration in blood or scalp hair has been widely used as a biomarker for methylmercury exposure. Because of the increased risks associated with exposures during prenatal and early postnatal development, biomarker results must be interpreted with regard to the age-dependent susceptibility. The authors compared regression coefficients for five sets of exposure biomarkers in 917 children from the Faroe Islands examined at birth, 1 year, and 7 years. Outcome variables were the results of neuropsychologic examination carried out in 1993-1994 at age 7 years. After adjustment for covariates, the cord-blood concentration showed the clearest associations with deficits in language, attention, and memory. Fine-motor function deficits were particularly associated with the maternal hair mercury at parturition. Mercury concentrations in the child's blood and hair at age 7 years were significant predictors only of performance on memory for visuospatial information. These findings emphasize the usefulness of the cord-blood mercury concentration as a main risk indicator. They also support the notion that the greatest susceptibility to methylmercury neurotoxicity occurs during late gestation, while early postnatal vulnerability is less, and they suggest that the time-dependent susceptibility may vary for different brain functions.

Biomarkers↗
PubMed1999

Reporting delay and corrected incidence of multiple sclerosis.

The incidence of multiple sclerosis can be adjusted for reporting delay in a way similar to that for AIDS incidence as described in this paper. Two models are applied to data from the Danish Multiple Sclerosis Registry. The first simply describes the delay distribution, the second is a regression model. For the latter it is shown how goodness-of-fit assessment for both time-dependent and time-independent covariates can be handled using ideas from the Cox proportional hazards model. The goodness-of-fit analysis shows that people with onset age below 40 years and people with onset age from 40 years and above should be analysed separately and this is done throughout the paper. The incidences are adjusted with the two estimated delays and an estimate of the variance for the adjusted incidence is given. Finally the crude incidences are compared with the adjusted ones. We find that the incidence has been increasing since 1965 but mostly for people with onset age below 40 years.

Adult↗
PubMed1999

Effect of active compression-decompression resuscitation (ACD-CPR) on survival: a combined analysis using individual patient data.

Active compression decompression resuscitation (ACD-CPR) has been developed as an alternative to standard cardiopulmonary resuscitation (S-CPR). To determine the effect of ACD-CPR on survival and neurologic outcome in patients with out-of-hospital cardiac arrest, this combined analysis involved individual patient data from 2866 patients from seven separate randomized prospective prehospital studies who had received ACD-CPR or S-CPR after out-of-hospital cardiac arrest in seven international sites. Significant improvement in 1-h survival (odds ratio (OR) = 0.83; confidence interval (CI): 0.695-0.99; P < 0.05) was found with ACD-CPR (n = 1410) versus S-CPR (n = 1456). The odds ratio for hospital discharge after ACD-CPR was similar (OR = 0.82; CI: 0.609-1.107, P = NS), but this finding was not statistically significant. Using the chi2-test for trend, there was a significant improvement in overall survival with ACD-CPR (P < 0.05) versus S-CPR. This improvement was largely due to the influence of results from one study site. Neurological outcome and complication rates were comparable between groups. Further study is needed to determine which emergency medical services systems may benefit from out-of-hospital use of ACD-CPR.

Aged↗
PubMed1999

Breast cancer risk among women with psychiatric admission with affective or neurotic disorders: a nationwide cohort study in Denmark.

There is a considerable interest in the possible relationship between psychosocial factors and the onset of breast cancer. This cohort study was based upon two nationwide and population-based central registers: The Danish Psychiatric Central Register, which contains all cases of psychiatric admissions, and The Danish Cancer Registry, which contains all cases of cancer. The register-linkage was accomplished by using a personal identification number. The study population comprised all women admitted to psychiatric departments or psychiatric hospitals in Denmark between 1969 and 1993 with an affective or a neurotic disorder. Overall, 66,648 women comprising 199,910 admissions and 775,522 person-years were included. The incidence of breast cancer in the cohort was compared with the national breast cancer incidence rates adjusted for age and calendar time. In all, 1270 women with affective or neurotic disorders developed breast cancer subsequent to the first admission as compared with the 1242 women expected, standardized incidence ratio (SIR) = 1.02 (95% confidence interval 0.97-1.08). None of the hypothetical risk factors: type of diagnosis, age or calendar period at cohort entry, age at breast cancer, alcohol abuse, alcohol/drug abuse without further specification, total number of admissions, total length of admissions, or time from first admission showed a statistically significant effect on the relative risk of breast cancer. We found no support for the hypothesis that women admitted to a psychiatric department with an affective or a neurotic disorder subsequently have an increased risk of breast cancer.

Adult↗
PubMed1999

Secular and seasonal changes in semen quality among young Danish men: a statistical analysis of semen samples from 1927 donor candidates during 1977-1995.

The objective of this study was to investigate whether semen quality has changed during the years 1977-1995 in a group of unselected semen donor candidates, and to determine whether semen quality is subject to seasonal variation, by analysis of time- and season-related changes in semen quality using multiple regression and ANOVA. The study was based on analysis of the first semen sample delivered by 1927 semen donor candidates in Copenhagen during the period 1977-1995, with determination of semen volume, sperm concentration, total sperm count, percentage motile spermatozoa, and a semiquantitative sperm motility score. Multiple linear regression analysis with year, sexual abstinence and season as covariates showed a significant increase in mean sperm concentration from 53.0 x 10(6)/mL in 1977 to 72.7 x 10(6)/mL in 1995 (p < 0.0001) and in mean total sperm count from 166.0 x 10(6) to 227.6 x 10(6) (p < 0.0001). Mean semen volume and percentage motile spermatozoa did not change. Sperm motility deteriorated, as the spermatozoa in 74.2% of the samples were of excellent motility in 1977-1980 compared to only 41.9% in 1993-1995 (chi 2 = 130.0, p < 0.0001). Analysis of variance showed significant variation between seasons regarding sperm concentration (p < 0.0001) and total sperm count (p < 0.0001). Highest sperm counts were found in spring, with a mean concentration (95% C.I.) of 77.6 x 10(6)/mL (71.9-83.7), and lowest in summer, with a mean of 57.5 x 10(6)/mL (50.1-65.4). No other semen parameter varied with season. It is concluded that sperm counts increased, whereas sperm motility decreased, in a group of Danish semen donor candidates, from 1977 to 1995. Due to the retrospective design and the anonymity of the donors, we were unable to control for variation in donor age, and we cannot exclude the possibility that some donor candidates were selected by being accepted as donors by other semen donor services in Copenhagen. With these limitations in mind, we suggest our results should be interpreted cautiously and regarded as a contribution to the ongoing dispute on whether or not there is a continuous decrease in sperm quality. The seasonal variations found in sperm concentration and total sperm count were pronounced and were not attributable to seasonal differences in the length of sexual abstinence. Additionally, the same seasonal pattern was observed in five successive year-intervals. These findings strongly indicate that human testicular function is influenced by season, a phenomenon well known in many lower mammals.

Adult↗
PubMed1999

Fecundability in relation to body mass and menstrual cycle patterns.

Few studies have investigated the association between body mass index and fecundability, that is, the ability to conceive in a menstrual cycle, among fertile women with normal menstrual cycle pattern. We examined the independent and combined effects of duration and regularity of the menstrual cycle, body mass index, and fecundability from records on pregnant women attending antenatal care at Odense University Hospital, Denmark, between 1972 and 1987. We included only the first birth of each woman who had planned pregnancies and no pre-pregnancy disease (N = 10,903). We estimated the fecundability odds ratio (FR) as the odds of conception in a menstrual cycle. After adjusting for confounders, the fecundability for women with a body mass index >25 kg/m2 was lower than for women with a body mass index of 20-25 kg/m2 [FR = 0.77; 95% confidence interval (CI) = 0.70-0.84]. FR was lower for women with long (>35 days) (FR = 0.74; 95% CI = 0.63-0.87) or irregular cycles (FR = 0.78; 95% CI = 0.70-0.87), even when their body mass index was within the normal range (20-25 kg/m2) and/or their cycles were regular.

Body Mass Index↗
PubMed1999

The graft versus leukemia effect after bone marrow transplantation: a case study using structural nested failure time models.

Over the last decade, J. M. Robins has developed a set of tools for assessing, from observational data, the causal effects of a time-dependent treatment or exposure in the presence of time-dependent covariates that may be simultaneously confounders and intermediate variables. This report concerns a case study of the application of one these techniques, G-estimation using structural nested failure time models, to the problem of assessing the effect of graft versus host disease on leukemia relapse after bone marrow transplantation.

Biometry↗
PubMed1999

Analysis of time-to-pregnancy data.

Statistical models for time-to-pregnancy data are usually formulated in discrete time. Two approaches were surveyed, including methods of accounting for both known heterogeneity (covariates, possibly time-dependent) and unknown heterogeneity (frailty). Delicate censoring and truncation patterns arose for prospective and, particularly, retrospective sampling designs. The inclusion of several pregnancies per couple presents new challenges and possibilities.

Cross-Sectional Studies↗
PubMed1999

Independent effects of stable and changing body weight on total mortality.

Most studies find that associations between mortality and either body mass index or weight change are U-shaped. Previous studies, however, have not considered independent effects of weight level and weight change while also controlling for confounding by diseases leading to weight change. We used follow-up data on average 10-year total mortality from a Danish population of 15,113 men and women, who had their weight measured at about 5-year intervals. We obtained information on preexisting disease at surveys and by linkage to hospital discharge registers. We defined subclinical disease as incident disease or death during the first 4 years of follow-up. We decomposed the mortality risk associated with weight change into a static effect, corresponding to the difference in mortality at stable weight at the initial and attained weight, and a dynamic effect, estimated as the difference between mortality after weight change and mortality at stable weight at the attained weight. Both weight level and weight change had independent effects on total mortality, with both these associations being U-shaped. Adjustment for smoking and the exclusion of subjects with preexisting and subclinical disease did not alter the associations.

Adult↗