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Niels Keiding

Publications and source records attributed to Niels Keiding.

At least 37 records · Page 2Linked to original sources
PubMed2004

Explained variation and predictive accuracy in general parametric statistical models: the role of model misspecification.

When studying a regression model measures of explained variation are used to assess the degree to which the covariates determine the outcome of interest. Measures of predictive accuracy are used to assess the accuracy of the predictions based on the covariates and the regression model. We give a detailed and general introduction to the two measures and the estimation procedures. The framework we set up allows for a study of the effect of misspecification on the quantities estimated. We also introduce a generalization to survival analysis.

Female↗
PubMed2004

Association between mercury concentrations in blood and hair in methylmercury-exposed subjects at different ages.

Mercury concentrations were measured in paired hair and blood samples from a cohort of about 1000 children examined at birth and at 7 and 14 years of age. The ratio between concentrations in maternal hair (in microg/g) and in cord blood (microg/L) was approximately 200, but samples from the children at age 14 years showed a ratio of about 250. These findings are in accordance with previous data from smaller studies. However, an even higher ratio of about 360 was seen at 7 years of age, suggesting that hair strands at this age retain more mercury. The 95th percentile of the hair-to-blood ratio was between five-fold and nine-fold greater than the 5th percentile. The results were examined in structural equation models to estimate the total imprecision of the individual biomarker results and the possibility that the ratio may not be constant. The hair-to-blood ratio was found to increase at lower mercury concentrations, a tendency that could not be explained by potential confounders, such as alcohol intake or number of amalgam fillings. The total imprecision (coefficient of variation) for the blood determinations averaged about 30%, thereby substantially exceeding normal laboratory imprecision. Yet hair-mercury results had an even greater imprecision, which suggested that preanalytical factors, such as variable sample characteristics, impacted the results. These findings are in accordance with other evidence that the cord blood concentration is a better predictor of neurobehavioral toxicity than is the maternal hair concentration. Although practical for field studies and monitoring purposes, hair-mercury concentration results, therefore, need to be calibrated and interpreted in regard to each specific study setting.

Adolescent↗
PubMed2004

Women's death in Scandinavia--what makes Denmark different?

OBJECTIVE: To compare the mortality for women in Sweden, Norway and Denmark in order to search for clues for the low life expectancy of Danish women. METHODS: Prospective age-period-cohort study covering 40 years for all Swedish, Norwegian and Danish women aged 40-84 during the period 1960-2000, and born 1900-1950. OUTCOME MEASURES: Relative risks and 95% confidence intervals for deaths. RESULTS: The high risk of dying among Danish women was associated with being born between the two World Wars, and that a similar pattern was not found for women in Norway and Sweden. A tendency of a cohort effect was observed for Swedish women born around 1940. CONCLUSIONS: The currently low life expectancy of Danish women compared with that of women in Norway and Sweden is partly a transitional phenomenon caused by excessive death rates for women born between the two World Wars. Data on smoking prevalence by birth cohort and age indicate that a high percentage of Danish women in these cohorts were smokers throughout their adult life.

Adult↗
PubMed2004

Structured home visits to older people. Are they only of benefit for women? A randomised controlled trial.

OBJECTIVE: To investigate whether education of primary care professionals improved functional ability in home-dwelling older people, with special focus on gender differences. DESIGN: A prospective controlled three-year follow-up study (1999-2001) with randomisation and intervention at municipality level and outcomes measured at individual level. Intervention municipality visitors received regular education and GPs were introduced to a short assessment programme. Control municipalities received no education but conducted the preventive programme in their own way. SETTING: Primary care, 34 municipalities. SUBJECTS: 5788 home-dwelling 75- and 80-year-olds were invited. 4060 (70.1%) participated: 2104 in 17 intervention- and 1956 in 17 matched control-municipalities. The main outcome measure was obtained from 3383 (95.6%) of 3540 surviving participants. MAIN OUTCOME MEASURE: Functional ability. RESULTS: Municipality intervention in coordination with GPs was associated with better functional ability in women (OR: 1.26; CI95: 1.08-1.47, p=0.004), but not in men (OR: 1.04; CI95: 1.85-1.27). Accepting and receiving free preventive home visits was associated with better functional ability among women (OR: 1.36; CI95: 1.16-1.60, p=0.0002), but not among men (OR: 0.98; CI95: 0.80-1.21). CONCLUSION: A brief, feasible educational intervention for primary care professionals and to accept and receive preventive home visits may have effect in older women, but not in older men.

Aged↗
PubMed2004

Emergency room utilization in Copenhagen: a comparison of immigrant groups and Danish-born residents.

BACKGROUND: The aim of the study was to investigate whether utilization of the emergency room differed between immigrant groups and Danish-born residents in Copenhagen, Denmark. METHODS: The authors compared the number of emergency room contacts during 1997 among different ethnic groups in the study population. Data were provided by the Statistical Office of the Municipality of Copenhagen. The study population consisted of 183,478 citizens residing in the catchment area of Bispebjerg Hospital in Copenhagen on 1 January 1998. "Contacts" included 22,026 visits made to the emergency room at Bispebjerg Hospital during 1997. Both the study population and "contacts" were characterized by gender, age, income, and country of birth. The immigrants comprised nine ethnic groups according to country of birth. Data were analysed by Poisson regression comparing rate ratios. RESULTS: Persons born in Somalia, Turkey, and ex-Yugoslavia had higher utilization rates of emergency room than Danish-born residents. All other non-Western-born residents had utilization rates similar to Danish-born residents. Persons born in other Western and European countries showed a tendency towards less utilization. CONCLUSION: Higher utilization rates among some immigrant groups may be explained by disparities in health or lack of knowledge about the Danish healthcare system as well as barriers to seeking primary care including language, fear of discrimination, and low satisfaction with primary care. The challenge remains to identify these causal relations, and to find out why utilization patterns vary between immigrant groups.

Adult↗
PubMed2004

How would a decline in sperm concentration over time influence the probability of pregnancy?

BACKGROUND: Reports have suggested a decline in sperm concentration during the second half of the 20th century. The effect of this decline on fecundability (the monthly probability of pregnancy) could be detected in principle by a study of time to pregnancy. In practice, the amplitude of this expected effect is not well known and the statistical power of time-to-pregnancy studies to detect it has not been explored. METHODS: We developed a nonparametric model to describe a temporal decline in sperm concentration using data on French semen donors. We then applied this model to 419 Danish couples planning a first pregnancy in 1992, to predict their time to pregnancy as if the pregnancy attempt had begun during earlier decades with higher sperm concentrations. Finally, we used bootstrap simulations to estimate the statistical power of prospective or retrospective studies that compared fecundability (estimated from time to pregnancy) across these time periods. We express the change in fecundability over time as a fecundability ratio (FR), with values less than 1 indicating decreased fecundability. RESULTS: We estimate that the median sperm concentration decreased by 21% from 1977 to 1992 and by 47% from 1947 to 1992. The estimated decline in fecundability with those semen changes was 7% from 1977 to 1992 (FR = 0.93, adjusted) and 15% from 1947 to 1992 (FR = 0.85, adjusted). The total numbers of couples that would be needed in prospective studies of time to pregnancy to detect these changes in fecundability (with a power of 80%) were 12,000 when comparing 1977 to 1992, and 2000 when comparing 1947 to 1992. Retrospective studies of the same size that excluded childless couples had much lower statistical power and were biased toward the null. CONCLUSION: The effect of realistic declines in sperm concentration on time to pregnancy may be observed only with studies that include several thousand couples.

Adult↗
PubMed2004

Effects of exposure imprecision on estimation of the benchmark dose.

In regression analysis failure to adjust for imprecision in the exposure variable is likely to lead to underestimation of the exposure effect. However, the consequences of exposure error for determination of safe doses of toxic substances have so far not received much attention. The benchmark approach is one of the most widely used methods for development of exposure limits. An important advantage of this approach is that it can be applied to observational data. However, in this type of data, exposure markers are seldom measured without error. It is shown that, if the exposure error is ignored, then the benchmark approach produces results that are biased toward higher and less protective levels. It is therefore important to take exposure measurement error into account when calculating benchmark doses. Methods that allow this adjustment are described and illustrated in data from an epidemiological study on the health effects of prenatal mercury exposure.

Algorithms↗
PubMed2004

Underestimation of risk due to exposure misclassification.

Exposure misclassification constitutes a major obstacle when developing dose-response relationships for risk assessment. A non-differentional error results in underestimation of the risk. If the degree of misclassification is known, adjustment may be achieved by sensitivity analysis. The purpose of this study was to examine the full magnitude of measurement error in determining the prenatal exposure to methylmercury. We used data from a prospective study of a Faroese birth cohort. Two biomarkers of methylmercury exposure were available, i.e., the mercury concentrations in cord blood and in maternal hair (sampled at the time of parturition). The laboratory imprecision on both chemical analyses was thought to be below 5% coefficient of variation (CV). As a third exposure parameter, we used the dietary questionnaire response on frequency of whale meat dinners. Factor analysis and structural equation analysis were applied to assess the full extent of the imprecision. The calculated total imprecision much exceeded the known laboratory variation: the CV was 28-30% for the cord-blood concentration and 52-55% for the maternal hair concentration. The dietary questionnaire response was even more imprecise. These findings illustrate that measurement error may be greatly underestimated if judged solely from reproducibility or laboratory quality data. Adjustment by sensitivity analysis is meaningful only if realistic measurement errors are applied. When exposure measurement errors are overlooked or underestimated, decisions based on the precautionary principle will not appropriately reflect the degree of precaution that was intended.

Biomarkers↗
PubMed2004

The Precautionary Principle and statistical approaches to uncertainty.

The central challenge from the Precautionary Principle to statistical methodology is to help delineate (preferably quantitatively) the possibility that some exposure is hazardous, even in cases where this is not established beyond reasonable doubt. The classical approach to hypothesis testing is unhelpful, because lack of significance can be due either to uninformative data or to genuine lack of effect (the Type II error problem). Its inversion, bioequivalence testing, might sometimes be a model for the Precautionary Principle in its ability to "prove the null hypothesis". Current procedures for setting safe exposure levels are essentially derived from these classical statistical ideas, and we outline how uncertainties in the exposure and response measurements affect the no observed adverse effect level, the Benchmark approach and the "Hockey Stick" model. A particular problem concerns model uncertainty: usually these procedures assume that the class of models describing dose/response is known with certainty; this assumption is, however, often violated, perhaps particularly often when epidemiological data form the source of the risk assessment, and regulatory authorities have occasionally resorted to some average based on competing models. The recent methodology of the Bayesian model averaging might be a systematic version of this, but is this an arena for the Precautionary Principle to come into play?

Bayes Theorem↗
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↗
PubMed2003

Increased risk of stroke in hypertensive women using hormone therapy: analyses based on the Danish Nurse Study.

BACKGROUND: Recent randomized clinical trials suggest an increased risk of stroke with hormone therapy (HT), whereas observational studies have suggested mixed results. Differences in design, definitions of HT exposure, and stroke outcome may explain these discrepancies. Little attention has been paid to identifying subgroups of women who are particularly sensitive to HT. OBJECTIVES: To investigate the risk of various stroke outcomes among women using HT based primarily on estradiol-17beta (unopposed or combined with norethisterone acetate) and to assess the potential modifying effect by presence of risk factors for stroke. DESIGN: Prospective cohort study. SETTING: In 1993, the Danish Nurse Study was established, and questionnaires on lifestyle and HT use were sent to all Danish nurses older than 44 years, of whom 19,898 (85.8%) replied. PARTICIPANTS: Postmenopausal women (n = 13,122) free of previous major cardiovascular and cerebrovascular disease and cancer. MAIN OUTCOME MEASURE: Ischemic or hemorrhagic stroke (n = 144) identified in the national registries of hospital discharges and cause of deaths in the total follow-up through December 31, 1998. RESULTS: In 1993, 28.0% of the 13 122 were current HT users, 14.3% were past users, and 57.7% were never users. Overall, HT exposure was not consistently associated with stroke. However, subdivision based on the presence of hypertension showed a significantly increased risk of stroke among hypertensive women. Compared with hypertensive never HT users, an increased risk of total stroke was found with current use (hazard ratio, 2.35; 95% confidence interval, 1.16-4.74) and especially with current use of estrogen-progestin (hazard ratio, 3.00; 95% confidence interval, 1.33-6.76). Normotensive women had no increased risk of stroke with HT. CONCLUSIONS: We found an increased risk of stroke among hypertensive but not normotensive women using HT. The present study suggests that HT should be avoided in hypertensive women.

Adult↗
PubMed2003

A changing relationship between disability and survival in the elderly population: differences by age.

BACKGROUND: Longitudinal studies estimating the association between disability and mortality in the elderly population have typically assumed disability constant through the follow-up study period. Current knowledge indicates that such assumptions may not be appropriate. Our purpose was to examine this association (disability and mortality) taking into account the transitions in the disablement process. METHODS: 1,294 participants (aged 65 and over) in the Health Interview Survey of Barcelona were followed up for a median of 8 years. Nine basic activities of daily living (ADLs) were measured at baseline and at the end of follow-up. Individuals were defined as "dependent" if they reported not being able to perform one or more of the activities without assistance. Survival analysis with delayed entry, age as the time variable, and disability as a time-dependent variable was performed. RESULTS: The rates of disability had increased by the end of the follow-up (from 42.0 to 60.0% among women and from 30.0 to 48.0%, among men); 7.5% of disabled women at baseline and 28.5% of men recovered from disability. The adjusted relative risk of dying for those with basic ADLs dependency varied with age: at 80 years of age it was 3.5 for women and 1.8 for men, while at 90 years it was 1.9 and 1.2, respectively. CONCLUSIONS: Disability increases monotonically over time while the risk of mortality associated with disability varies with gender and age. Elderly disabled women should be considered a target group for intervention because they show higher rates of disability and are less likely to recover from disability. Our results illustrate the need to consider disability status as a time-dependent variable, to avoid an underestimation of its association with mortality.

Activities of Daily Living↗
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↗