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Niels Keiding

Publications and source records attributed to Niels Keiding.

13 recordsLinked to original sources
PubMed2003

Consequences of exposure measurement error for confounder identification in environmental epidemiology.

Non-differential measurement error in the exposure variable is known to attenuate the dose-response relationship. The amount of attenuation introduced in a given situation is not only a function of the precision of the exposure measurement but also depends on the conditional variance of the true exposure given the other independent variables. In addition, confounder effects may also be affected by the exposure measurement error. These difficulties in statistical model development are illustrated by examples from a epidemiological study performed in the Faroe Islands to investigate the adverse health effects of prenatal mercury exposure.

Bias↗
PubMed2003

Intensification of mercaptopurine/methotrexate maintenance chemotherapy may increase the risk of relapse for some children with acute lymphoblastic leukemia.

PURPOSE: Thioguanine nucleotides (TGNs) mediate the cytotoxicity of mercaptopurine (MP). Methylated MP metabolites (formed by thiopurine methyltransferase [TPMT]) and methotrexate (MTX) polyglutamates can inhibit de novo purine synthesis. We explored whether dose adjustment of MP and MTX by erythrocyte (E) levels of TGN and MTX (including polyglutamates) could improve outcome in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: A total of 538 children with ALL were randomly assigned to have their oral MP/MTX maintenance therapy adjusted by white cell counts (WBC), E-TGN, and E-MTX (pharmacology group), or by WBC only (control group). RESULTS: After a median follow-up of 7.8 years, 79 patients had relapsed. Cox regression analysis showed an increased risk of relapse for boys (P =.00003), high WBC at diagnosis (P =.03), pharmacology arm (6.6 times increased relapse hazard for girls), high TPMT activity (P =.002), and high average neutrophil counts during maintenance therapy (P =.0009), with a significant interaction between sex and randomization group (P =.0007). For girls, the relapse risk was 5% in the control group and 19% in the pharmacology group (P =.001) because of an increased relapse hazard during the first year after cessation of therapy. TPMT activity was the most significant predictor of relapses among girls in the pharmacology arm (P <.0001). Overall, the TPMT activity was higher for patients who relapsed after cessation of therapy compared with those who stayed in remission (girls 19.5 v 17.4 U/mL, P =.03; boys 19.3 v 18.0 U/mL, P =.04). CONCLUSION: Adding pharmacologically guided treatment intensification to dose adjustments by blood counts may not be warranted for girls, whereas new approaches to optimize maintenance therapy are needed for boys.

Administration, Oral↗
PubMed2003

[Environmental epidemiology research leads to a decrease of the exposure limit for mercury].

The central nervous system is particularly vulnerable to prenatal exposure to methylmercury. Due to the widespread exposure to methylmercury from fish, several prospective environmental epidemiology studies have been initiated, in which the maternal exposure during the pregnancy is related to the neurobehavioural development of the children. We have studied a Faroese birth cohort prenatally exposed to methylmercury from maternal intake of contaminated pilot whale meat. At seven years of age, clear dose-response relationships were observed for deficits in attention, language, and memory. An increase in blood pressure was also associated with the prenatal exposure level. The exposure limit for mercury has therefore been decreased.

Animals↗
PubMed2002

Estimation of health effects of prenatal methylmercury exposure using structural equation models.

BACKGROUND: Observational studies in epidemiology always involve concerns regarding validity, especially measurement error, confounding, missing data, and other problems that may affect the study outcomes. Widely used standard statistical techniques, such as multiple regression analysis, may to some extent adjust for these shortcomings. However, structural equations may incorporate most of these considerations, thereby providing overall adjusted estimations of associations. This approach was used in a large epidemiological data set from a prospective study of developmental methyl-mercury toxicity. RESULTS: Structural equation models were developed for assessment of the association between biomarkers of prenatal mercury exposure and neuropsychological test scores in 7 year old children. Eleven neurobehavioral outcomes were grouped into motor function and verbally mediated function. Adjustment for local dependence and item bias was necessary for a satisfactory fit of the model, but had little impact on the estimated mercury effects. The mercury effect on the two latent neurobehavioral functions was similar to the strongest effects seen for individual test scores of motor function and verbal skills. Adjustment for contaminant exposure to poly chlorinated biphenyls (PCBs) changed the estimates only marginally, but the mercury effect could be reduced to non-significance by assuming a large measurement error for the PCB biomarker. CONCLUSIONS: The structural equation analysis allows correction for measurement error in exposure variables, incorporation of multiple outcomes and incomplete cases. This approach therefore deserves to be applied more frequently in the analysis of complex epidemiological data sets.

Biomarkers↗
PubMed2002

Preventive home visits to older people in Denmark: methodology of a randomized controlled study.

BACKGROUND AND AIMS: Preventive home visits were introduced by legislation in Denmark in 1998. This ongoing randomized controlled intervention study introduces a model where preventive home visits to elderly people are carried out in a standardized way, focusing on early signs of disability and on physical activity. The study includes general practitioners (GPs) in relevant parts of the assessment and endeavors coordinated interdisciplinary follow-up. Our main aim was to investigate whether this model gives enhanced active life expectancy, but the focus of the present paper is the design of the study. METHODS: The design was a prospective, controlled, follow-up study conducted over a 3-year period (1999-2001) with randomization and intervention at the community level, and outcomes measured at an individual level among people living in those communities. The study included 17 pairs of intervention and control communities (34 in total), including 2104 persons aged 75-80 years in the intervention communities (participation rate, 70.8%) and 1956 persons in the control communities (p.r. 70.3%). The main outcome measure is change in functional ability after 1.5 and 3 years. Other outcomes are mortality, and hospital and nursing home admissions. Intervention communities received systematic education and written materials; two key representatives from each community also attended bi-annual follow-up meetings. Control communities did not receive any intervention but were allowed to conduct a preventive program completely on their own. RESULTS: Baseline characteristics were similar in the intervention and control communities with regard to size, rural and urban characteristics and geriatric services, and the individual characteristics of participating persons living in these communities were also comparable. The intervention was well accepted and feasible. CONCLUSIONS: When results become available, the study should reveal the most important factors for preventive home visits to elderly people.

Aged↗
PubMed2002

Effect of ethnic background on Danish hospital utilisation patterns.

The aim of the study is to examine possible ethnic differences in the utilisation patterns of hospitalised immigrants versus patients born in Denmark. Data were obtained from the Register of Prevention at Statistics Denmark. This register includes both clinical and socio-demographic data. All patients discharged as inpatients during 1997 at Bispebjerg Hospital (a major hospital in Copenhagen) were identified through the Register of Prevention and linked to data concerning diagnosis, place of birth, age and gender. To compare immigrants with patients born in Denmark, a study group and a reference group were formed. The final study group consisted of all patients characterised by 22 major diagnostic categories and born outside the five Nordic countries (altogether 858 persons accounting for 976 inpatient contacts). The reference group consisted of 2004 patients accounting for 2432 inpatient contacts characterised by the same diagnostic categories among a random sample of 10,000 patients born in Denmark. The measure of utilisation employed was length of inpatient stay determined by the total number of days that each admission lasted. Data were analysed by a multiple regression analysis controlling for age, gender, diagnosis and place of birth. The results show that for some diagnostic groups, native Danes have longer inpatient stay compared to immigrants, whereas for other diagnostic groups immigrants have longer inpatient stay than native Danes. There was no overall effect of ethnicity on duration of hospital stay and consequently the utilisation patterns of inpatient care seem to reflect equal care for equal needs.

Age Distribution↗
PubMed2002

Estimating time to pregnancy from current durations in a cross-sectional sample.

A new design for estimating the distribution of time to pregnancy is proposed and investigated. The design is based on recording current durations in a cross-sectional sample of women, leading to statistical problems similar to estimating renewal time distributions from backward recurrence times. Non-parametric estimation is studied in some detail and a parametric approach is indicated. The results are illustrated on Monte Carlo simulations and on data from a recent European collaborative study. The role and applicability of this approach is discussed.

Journal Article↗
PubMed2002

Poor semen quality may contribute to recent decline in fertility rates.

During past decades, we have witnessed a remarkable decline in fertility rates (number of births per 1000 women of reproductive age) in the industrialized world. It seems beyond doubt that the enormous social changes of our societies play the major role in this decline, but can it be attributed to changing social structures alone or is a reduced fecundity in the population also a factor? To address this we have focused on trends in teenage pregnancies (which to a large extent are unplanned). During the period in question fertility rates among 15-19 year old Danish women have been falling and the decline in fertility rate is not counterbalanced by an increase in the rate of induced abortion. When seen together with recent results from Denmark, which have shown that more than 30% of 19 year old men from the general population now have sperm counts in the subfertile range, we argue that this fall may not be attributable to social factors, changes in conception practices or diminished sexual activity alone. It seems reasonable also to consider widespread poor semen quality among men as a potential contributing factor to low fertility rates among teenagers. Due to the concern caused by the low sperm count among younger Danish men, the Danish Ministries of Health and Environment have launched a surveillance programme which includes an annual examination of the semen quality in 600 young Danes from the general population. We propose that researchers in other countries with low and falling fertility rates among young women should consider the possibility that semen quality of their younger male cohorts may also have deteriorated.

Adolescent↗
PubMed2002

Multi-state models for event history analysis.

An introduction to event history analysis via multi-state models in given. Examples include the two-state model for survival analysis, the competing risks and illness-death models, and models for bone marrow transplantation. Statistical model specification via transition intensities and likelihood inference is introduced. Consequences of observational patterns are discussed, and a real example concerning mortality and bleeding episodes in a liver cirrhosis trial is discussed.

Biometry↗
PubMed2002

Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls.

OBJECTIVE: To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty. DESIGN: Following analysis for PCB in their umbilical cords, 196 boys from a Faroese birth cohort were examined for the development of puberty at 14 years of age. METHODS: Physical examination included determination of Tanner stages and testicular size. A morning urine sample was centrifuged and examined for the presence of sperm. Serum was analyzed for sex hormones. RESULTS: twenty boys (10.2%) had abnormalities in testicular development, mainly cryptorchidism. only three of them had a positive spermaturia test, but the level of exposure to pcbs in this group had not been increased. occurrence of spermaturia in 58 of the remaining 176 boys was also not associated with pcb exposure but showed highly significant associations with tanner stages and testicular size. serum concentrations of testosterone, fsh and lh were higher in boys with spermaturia, while sex hormone-binding globulin was lower and no difference occurred in inhibin b. serum hormone parameters showed only weak associations with the level of prenatal pcb exposure. CONCLUSIONS: These findings support the validity of spermaturia as a useful indicator of puberty, although a substantial rate of false negatives must be taken into account. Despite the wide range of exposure to PCB, the findings did not reveal any definite associations with the development of puberty. However, because of the limited size of the cohort, small effects cannot be excluded.

Adolescent↗
PubMedDate not supplied

Depression as a prognostic factor for breast cancer mortality.

It is unclear if depression or depressive symptoms have an effect on mortality in breast cancer patients. In this population-based, nationwide, retrospective cohort study in Denmark, depression was defined as affective or anxiety disorders that necessitated psychiatric hospital admission. All the affective and anxiety disorders were divided and categorized into five ordinal diagnostic groups. Early-stage (N=10382) and late-stage (N=10211) breast cancer patients were analyzed separately with Cox's regression adjusted for well-documented somatic prognostic variables. The authors used survival analysis of data from three central registers and found that breast cancer patients with depression had a modestly but significantly higher risk of mortality depending on stage of breast cancer and time of depression. The same result was found after censoring unnatural causes of death such as accident, suicide, or homicide.

Adult↗