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PubMed2001

Bayesian haplotype inference for multiple linked single-nucleotide polymorphisms.

Haplotypes have gained increasing attention in the mapping of complex-disease genes, because of the abundance of single-nucleotide polymorphisms (SNPs) and the limited power of conventional single-locus analyses. It has been shown that haplotype-inference methods such as Clark's algorithm, the expectation-maximization algorithm, and a coalescence-based iterative-sampling algorithm are fairly effective and economical alternatives to molecular-haplotyping methods. To contend with some weaknesses of the existing algorithms, we propose a new Monte Carlo approach. In particular, we first partition the whole haplotype into smaller segments. Then, we use the Gibbs sampler both to construct the partial haplotypes of each segment and to assemble all the segments together. Our algorithm can accurately and rapidly infer haplotypes for a large number of linked SNPs. By using a wide variety of real and simulated data sets, we demonstrate the advantages of our Bayesian algorithm, and we show that it is robust to the violation of Hardy-Weinberg equilibrium, to the presence of missing data, and to occurrences of recombination hotspots.

Algorithms↗
PubMed2002

Appropriate time frames for data collection in quality of life research among cancer patients at the end of life.

Longitudinal research has been recommended as the most appropriate research design to ensure the validity of quality of life assessments. However, high attrition and non-random missing data in quality of life studies for terminal cancer patients raise questions about generalizability of the study, and at worst they may jeopardize interpretation of the results. Appropriate time frames for eliciting information directly from terminal cancer patients can ensure the internal and external validity of quality of life research in end-of-life care, allow health care professionals to detect sensitively the effects of end-of-life care within the shortest intervention period, and make comparisons across studies possible. From a review of the literature, it is recommended that the appropriate time frame for interviewing terminal cancer patients about their quality of life be a weekly assessment schedule based on the following factors: (a) the median survival of terminal cancer patients enrolling in a hospice/palliative care program is approximately 30 days and there are substantial number of patients who die in each week; (b) at the final weeks of life, quality of life and symptoms of some terminal cancer patients change dramatically; and (c) the shortest intervention period that is likely to give a clinically significant effect of end-of-life care management is 1 week after the enrollment in end-of-life care.

Humans↗
PubMed1999

Longitudinal data analysis (repeated measures) in clinical trials.

Longitudinal data is often collected in clinical trials to examine the effect of treatment on the disease process over time. This paper reviews and summarizes much of the methodological research on longitudinal data analysis from the perspective of clinical trials. We discuss methodology for analysing Gaussian and discrete longitudinal data and show how these methods can be applied to clinical trials data. We illustrate these methods with five examples of clinical trials with longitudinal outcomes. We also discuss issues of particular concern in clinical trials including sequential monitoring and adjustments for missing data. A review of current software for analysing longitudinal data is also provided. Published in 1999 by John Wiley & Sons, Ltd. This article is a US Government work and is the public domain in the United States.

Clinical Trials as Topic↗
PubMed2002

A limited dependent variable model for heritability estimation with non-random ascertained samples.

In a questionnaire study, a random sample of Dutch families was asked whether they suffered from asthma and related symptoms. From these families, a selected sample was invited to come to the hospital for further phenotyping. Families were selected if at least one family member reported a history of asthma and the twins were 18 years of age or older. Not all families that were thus selected volunteered, leaving us with a fraction of the original sample. The aim of this paper is to describe a limited dependent variable model that can be used in such situations in order to obtain estimates that are representative of the population from which the sample was originally drawn. The model is a linear (DeFries-Fulker) regression model corrected for sample selection. This correction is possible when (some of) the characteristics that determine whether subjects volunteer (or not) are known for all subjects, including those that did not volunteer. The questionnaire study is of interest by itself but serves mainly to provide a concrete illustration of our method. The present model is used to analyze the data and the results are compared to those obtained with other methods: raw (or direct) likelihood estimation, multiple imputation, and sample weighting. Throughout, Rubin's general theory of inference with missing data serves as an integrating framework.

Adolescent↗
PubMed1999

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for prevention of stroke.

OBJECTIVE: To determine if 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in preventing fatal and nonfatal strokes in patients at increased risk of coronary artery disease. DESIGN: Meta-analysis of randomized controlled trials. Clinical trials were identified by a computerized search of MEDLINE (1983 to June 1996), by an assessment of the bibliographies of published studies, meta-analyses and reviews, and by contacting pharmaceutical companies that manufacture statins. Trials were included in the analysis if their patients were randomly allocated to a statin or placebo group, and reported data on stroke events. Thirteen of 28 clinical trials were selected for review. Data were extracted for details of study design, patient characteristics, interventions, duration of therapy, cholesterol measurements, and the number of fatal and nonfatal stroke events in each arm of therapy. Missing data on stroke events were obtained by contacting the investigators of the clinical trials. MAIN RESULTS: Among 19,921 randomized patients, the rate of total stroke in the placebo group was 2.38% (90% nonfatal and 10% fatal). In contrast, patients who received statins had a 1.67% stroke rate. Using an exact stratified analysis, the pooled odds ratio (OR) for total stroke was 0.70 (95% confidence interval [CI] 0.57, 0.86; p =.0005). The pooled OR for nonfatal stroke was 0.64 (95% CI 0.51, 0.79; p =.00001), and the pooled OR for fatal stroke was 1.25 (95% CI 0.71, 2.24; p =.4973). In separate analyses, reductions in total and nonfatal stroke risk were found to be significant only for trials of secondary coronary disease prevention. Regression analysis showed no statistical association between the magnitude of cholesterol reduction and the relative risk for any stroke outcome. CONCLUSIONS: The available evidence clearly shows that HMG-CoA reductase inhibitors reduce the morbidity associated with strokes in patients at increased risk of cardiac events. Data from 13 placebo-controlled trials suggest that on average one stroke is prevented for every 143 patients treated with statins over a 4-year period.

Aged↗
PubMed2006

A comparison of phasing algorithms for trios and unrelated individuals.

Knowledge of haplotype phase is valuable for many analysis methods in the study of disease, population, and evolutionary genetics. Considerable research effort has been devoted to the development of statistical and computational methods that infer haplotype phase from genotype data. Although a substantial number of such methods have been developed, they have focused principally on inference from unrelated individuals, and comparisons between methods have been rather limited. Here, we describe the extension of five leading algorithms for phase inference for handling father-mother-child trios. We performed a comprehensive assessment of the methods applied to both trios and to unrelated individuals, with a focus on genomic-scale problems, using both simulated data and data from the HapMap project. The most accurate algorithm was PHASE (v2.1). For this method, the percentages of genotypes whose phase was incorrectly inferred were 0.12%, 0.05%, and 0.16% for trios from simulated data, HapMap Centre d'Etude du Polymorphisme Humain (CEPH) trios, and HapMap Yoruban trios, respectively, and 5.2% and 5.9% for unrelated individuals in simulated data and the HapMap CEPH data, respectively. The other methods considered in this work had comparable but slightly worse error rates. The error rates for trios are similar to the levels of genotyping error and missing data expected. We thus conclude that all the methods considered will provide highly accurate estimates of haplotypes when applied to trio data sets. Running times differ substantially between methods. Although it is one of the slowest methods, PHASE (v2.1) was used to infer haplotypes for the 1 million-SNP HapMap data set. Finally, we evaluated methods of estimating the value of r(2) between a pair of SNPs and concluded that all methods estimated r(2) well when the estimated value was >or=0.8.

Algorithms↗
PubMed2004

Bayesian analysis, pattern analysis, and data mining in health care.

PURPOSE OF REVIEW: To discuss the current role of data mining and Bayesian methods in biomedicine and heath care, in particular critical care. RECENT FINDINGS: Bayesian networks and other probabilistic graphical models are beginning to emerge as methods for discovering patterns in biomedical data and also as a basis for the representation of the uncertainties underlying clinical decision-making. At the same time, techniques from machine learning are being used to solve biomedical and health-care problems. SUMMARY: With the increasing availability of biomedical and health-care data with a wide range of characteristics there is an increasing need to use methods which allow modeling the uncertainties that come with the problem, are capable of dealing with missing data, allow integrating data from various sources, explicitly indicate statistical dependence and independence, and allow integrating biomedical and clinical background knowledge. These requirements have given rise to an influx of new methods into the field of data analysis in health care, in particular from the fields of machine learning and probabilistic graphical models.

Bayes Theorem↗
PubMed2006

Usefulness of the Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire in patients with diabetes in a multi-ethnic Asian country.

INTRODUCTION: Asia will be at the forefront of the current epidemic of diabetes mellitus. Quality of life (QOL) is an important outcome measure in the assessment of diabetes care. However, few QOL instruments are culturally suitable for use in Asian countries. The Audit of Diabetes-Dependent Quality-of-Life (ADDQoL) questionnaire is a third-generation individualised QOL instrument. Individualised instruments such as the ADDQoL have the potential to be useful and less costly alternatives to computerised adaptive testing (CAT), which may not be practical in developing countries. OBJECTIVE: To evaluate and validate the ADDQoL questionnaire in English-speaking patients with diabetes in Singapore, a multi-ethnic Asian country. METHODS: The ADDQoL and EQ-5D were administered to English-speaking respondents with type 1 or 2 diabetes (aged > or =18 years) recruited from a tertiary acute-care referral hospital by convenience sampling. The usefulness of the key design features of the ADDQoL were assessed by measuring the number of zero-importance responses, the change in item ranking with and without weighting for importance, and the frequency of utilisation of the 'not applicable' (NA) options. The acceptability, factor structure and internal consistency (Cronbach's alpha) of the ADDQoL were also assessed. Data were subjected to unforced factor analysis with oblimin rotation and then the condition was set to force a one-factor solution. The validity of the ADDQoL was tested with the following hypotheses: those with moderate or severe problems on the EQ-5D would have worse ADDQoL average weighted impact (AWI) scores than those with a perfect health rating on the EQ-5D; those with better Present QOL scores on the ADDQoL would have better EQ-5D utility and visual analogue scale (VAS) scores; on the ADDQoL, AWI scores would correlate better with diabetes-dependent QOL than with Present QOL scores; and female respondents, those who required insulin or had longer duration of known diabetes would have worse ADDQoL AWI scores (known-group validity). RESULTS: We analysed data from 152 respondents (49% Chinese, 34% Indian; 45% female; mean age 52 years, range 18-80; mean duration of known diabetes 10 years, range 0-62). There were few missing data. Weighted scoring and NA options were shown to be necessary, thus supporting the usefulness of individualised health-related QOL measures. Factor structure of the ADDQoL was supported and internal consistency was high (alpha = 0.94). All hypotheses were fulfilled except for one that was partially fulfilled; respondents with longer duration of known diabetes did not report worse ADDQoL AWI scores. CONCLUSIONS: The ADDQoL is culturally appropriate, valid, reliable and well accepted among Singaporean patients with diabetes. Individualised measures such as the ADDQoL allow one to obtain precise score estimates and may offer developing countries a useful alternative to CAT.

Adolescent↗
PubMed1994

Application of multistage Markov modeling to malignant melanoma progression.

BACKGROUND: A fundamental research goal in clinical melanoma studies is to understand the natural history of melanoma and its relationship with prognostic factors. The current understanding of melanoma progression and the relationship of risk factors is based on two-stage modeling. METHODS: The authors propose a multistage Markov model for melanoma progression. This model is applied to a data set consisting of approximately 3900 follow-up staging visits of patients with melanoma. The approach takes into account the heavy censoring encountered in this data set and all chronic, subclinically progressive disease. The Markov transition parameters are expressed as Cox regression functions of the relevant prognostic variables. Parameter estimation is achieved by using a missing-data approach. RESULTS: Tumor thickness, level, and site and patient gender and age at diagnosis are independent risk factors in the transition from local to nodal disease. Tumor thickness and level of invasion and patient age are factors in the transition from local disease to dissemination (without intervening involvement of the nodes). Tumor thickness, patient age, primary site, and the number of involved lymph nodes are factors in the transition from nodal disease to dissemination. Transition from dissemination to death is affected by primary thickness, patient gender, number of nodes involved, and site of metastases. CONCLUSION: This multistage analysis contributes to a more accurate understanding of the progress of melanoma and is likely to be applicable to the study of other progressive diseases. Graphic goodness-of-fit results suggest satisfactory predictability of the model to other data sets.

Female↗
PubMed1998

Tests of data quality, scaling assumptions, and reliability of the SF-36 in eleven countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population samples in 11 countries (n = 1483 to 9151) were used to assess data quality and test the assumptions underlying the construction and scoring of multi-item scales from the SF-36 Health Survey. Across all countries, the rate of item-level missing data generally was low, although slightly higher for items printed in the grid format. In each country, item means generally were clustered as hypothesized within scales. Correlations between items and hypothesized scales were greater than 0.40 with one exception, supporting item internal consistency. Items generally correlated significantly higher with their own scale than with competing scales, supporting item discriminant validity. Scales could be constructed for 93-100% of respondents. Internal consistency reliability of the eight SF-36 scales was above 0.70 for all scales, with two exceptions. Floor effects were low for all except the two role functioning scales; ceiling effects were high for both role functioning scales and also were noteworthy for the Physical Functioning, Bodily Pain, and Social Functioning scales in some countries. These results support the construction and scoring of the SF-36 translations in these 11 countries using the method of summated ratings.

Cross-Cultural Comparison↗
PubMed1999

French survey of anesthesia in 1996.

BACKGROUND: To identify the growth in the number of anesthetic procedures since 1980 and the changes in the practice of anesthesia, the present survey was designed to collect and analyze the anesthetic activity performed in France in 1996, from a representative sample collected in all French hospitals and clinics. METHODS: This study, initiated by the French Society of Anesthesia and Intensive Care, collected information that included the characteristics of patients (age, sex, American Society of Anesthesiologists status), the techniques of anesthesia, and the nature of the procedure for which anesthesia was required. All French private, public, and military hospitals were asked to participate in the survey. In each hospital in the country, all anesthetic procedures were documented and collected during 3 consecutive days, chosen at random during a 12-month period, to obtain a representative sample of the annual activity. All data were analyzed at the INSERM (National Institute of Health and MEDICAL RESEARCH: At the conclusion of the study, 5% of hospitals were randomly assigned to be audited to check for missing data and errors. The rate of anesthetic activity was calculated as the ratio between the annual number of anesthetic procedures and the number of the general population in the same age group. RESULTS: The participation rate of hospitals was 98%. The analysis of the 62,415 collected questionnaires allowed extrapolation of the anesthetic activity to 7,937,000 anesthetic procedures (95% confidence interval, +/- 387,000) performed in France in 1996. Thus, the annual rate of anesthetic procedures was 13.5 per 100 population, varying between 5.4 per 100 in girls aged 5-14 yr and 30.2 per 100 in men aged 75-84 yr. Surgery was involved in 71% of anesthesia cases. Regional anesthesia alone was performed in 20% of all surgical cases and was combined with general anesthesia in 3% of additional cases. Anesthesia for obstetric procedures represented 9% of all cases. Seventy-six percent of all anesthetic procedures started between 12:00 A.M. and 7:00 A.M. were related to obstetric activities. CONCLUSION: In comparison with a previous study, the present survey shows that the number of anesthetic procedures has increased by 120% since 1980, and the rate of anesthetic procedures increased from 6.6 to 13.5 per 100 population, the major changes being observed in patients aged > or = 75 yr and in those with an American Society of Anesthesiologists physical status of 3. In the same time period, the number of regional anesthetic procedures increased 14-fold. In obstetrics, the practice of epidural analgesia extended from 1.5% to 51% of all deliveries of the country.

Adolescent↗
PubMed2003

Community pharmaceutical care: an 8-month critical review of two pharmacies in Kampala.

BACKGROUND: The concept of pharmaceutical care is neither well developed nor adequately documented in Uganda. OBJECTIVES: This study is therefore an attempt to identify and quantify the various service components of community pharmacy practice in Kampala, Uganda's capital city. SETTING: Two pharmacies operating retail outlets were chosen out of about 110 in Kampala. The city itself is fairly small with a rather congested population. It is Uganda's economic hub with the greatest number of private sector health facilities and pharmacy outlets. METHODS: This study involved an 8-month observation period at the two pharmacies, combined with a data collection form to record demographic characteristics of respondents and parameters such as self-medication, pharmacy initiated therapy, prescription filling, patient/non-patient clients and treatment received. RESULTS: 567 observations were made. Missing data for parameters studied were omitted during analysis, thus yielding different totals for the various sets of variables. Just less than half of 564 respondents (44.3%), were females compared to males (55.7%). The study found that clients over the age of 12 years seeking pharmaceutical services were 8-fold (93.1%) more likely to be the very patients compared to children (OR = 8.3; 95% CI, 3.7-18.7). Slightly over thirty percent of respondents (32.3%) were third party patients. About fifteen percent (14.7%) of respondents came to fill prescriptions, 28.8% to receive pharmacy-initiated therapy and 56.5% came for self-medication with all drugs including antibiotics at 22.4%. Most clients (75.2%) received treatment. The availability of a drug at the pharmacy was found to be a significant predictor of whether treatment was received, with the client age acting as a confounding variable (OR = 59.7; 95% CI 25.9-137.6).

Adolescent↗
PubMed1996

The Bristol Female Lower Urinary Tract Symptoms questionnaire: development and psychometric testing.

OBJECTIVE: To develop a questionnaire that is sensitive to changes in the symptomatology of the female lower urinary tract, particularly urinary incontinence, providing an instrument that can characterize symptom severity, impact on quality of life and evaluate treatment outcome. PATIENTS, SUBJECTS AND METHODS: Items covering as wide a range of urinary symptoms as possible were devised after consultation with clinicians and a health scientist, a literature review and discussion with patients. Additional items assessed the degree of 'bother' that symptoms were causing. Eighty-five women with clinical symptoms attending for urodynamic assessment and 20 women with none were asked to self-complete the questionnaire. The instrument's validity was assessed by interviewing patients and measuring levels of missing data, comparing symptom scores between clinical and non-clinical populations and comparison with frequency/volume charts and data from pad tests. The instrument's reliability was assessed by measuring both internal consistency and stability, using a 2-week test-retest analysis. RESULTS: The questionnaire was completed by the patients with a mean of only 2% of items missing; most questions were easily understood. Construct validity was good, with the instrument easily differentiating clinical and non-clinical populations. Criterion validity, as tested against frequency/volume charts and pad-test data, was acceptable, with Kappa coefficients of 0.29-0.79 for frequency/volume data and Spearman rank correlations of 0.50-0.97 and 0.31-0.67 for frequency/volume and pad-test data, respectively. The reliability of the instrument was good; a Cronbach's alpha of 0.78 indicated that the symptom questions had high internal consistency, while stability was excellent, with 78% of symptoms and problems answered identically on two occasions, and Spearman rank correlations of 0.86 and 0.90, respectively. CONCLUSION: The instrument has good psychometric validity and reliability. The stability demonstrated at baseline and the ability to differentiate clearly between community and clinical populations suggest that it should be ideal for measuring changes following therapeutic intervention. The addition of life-impact items and a 'bother' factor may provide the opportunity to identify those women who wish treatment for their symptoms; this dimension requires further exploration.

Adult↗
PubMed2005

Exact family-based association tests for biallelic data.

Family-based study designs have an important role in the search for association between disease phenotypes and genetic markers. Unlike traditional case-control methods, family-based tests use within-family data to avoid identification of spurious associations that may result from population admixture. Many family-based association tests have been proposed to accommodate a variety of ascertainment schemes and patterns of missing data. In this report, we describe exact family-based association tests for biallelic data. Specifically, we discuss test of the null hypotheses "no linkage and no association" and "linkage, but no association". These tests, which are valid under various models for inheritance and patterns of missingness, utilize the procedure proposed by Rabinowitz and Laird [2000: Hum Hered 50:211-223] that provides a unified framework for family based association testing (FBAT). The conditioning approach implemented in FBAT makes an exact test conceptually straightforward, but computationally difficult since the minimum sufficient statistics upon which we condition do not have a conventional form. An exact test may be especially critical when accurate computation of the extreme area of the FBAT statistic is needed, such as when the study design necessitates multiple comparisons adjustments. We describe the exact approach as a useful alternative to the asymptotic test and show that the exact tests for biallelic data may be most useful for the recessive disease model.

Algorithms↗
PubMed2005

Assessing the effects of the dating violence prevention program "safe dates" using random coefficient regression modeling.

The Safe Dates Project is a randomized trial for evaluating a school-based adolescent dating violence prevention program. Five waves of data were used to examine the effects of Safe Dates over time including primary and secondary prevention effects, moderators, and mediators of program effects. Using random coefficients models, with multiple imputation of missing data, significant program effects were found at all four follow-up periods on psychological, moderate physical, and sexual dating violence perpetration and moderate physical dating violence victimization. Marginal effects were found on sexual victimization. Effects on severe physical perpetration at all four follow-up periods were moderated by prior involvement in that type of violence. Primary and secondary prevention effects were found and the program was equally effective for males and females and for whites and non-whites. Program effects were mediated by changes in dating violence norms, gender-role norms, and awareness of community services.

Adolescent↗
PubMed2006

A brief measure of perceived understanding of informed consent in a clinical trial was validated.

BACKGROUND AND OBJECTIVE: To develop and evaluate an Informed Consent Questionnaire (ICQ) for measuring self-reported perceived understanding of informed consent in a randomized clinical trial. METHODS: The study was embedded in a Department of Veterans Affairs randomized clinical trial of Gulf War veterans' illnesses (CSP#470). The trial was initiated in May 1999 at 20 hospitals and concluded in September 2001; 1,092 participants were enrolled and followed for 12 months. The reliability and validity sample included 1,086 participants evaluated at baseline, 906 at 3 months, 929 at 6 months, and 910 at 12 months. The psychometric evaluations included tests of acceptability (based on missing data, endorsement frequencies, and floor/ceiling effects), item reduction, internal consistency, and construct validity (based on Cronbach's alpha coefficients, item-total correlations, and principal components analysis). RESULTS: The ICQ had >5% missing information on some questions at baseline, indicating poor acceptability prior to the initiation of the trial; however, the scale had good acceptability at each of the follow-up visits. Psychometric evaluation following standard item reduction techniques confirmed the reliability and validity of a four-item subscale of the ICQ (ICQ-4). CONCLUSIONS: The ICQ-4 is a simple and psychometrically sound self-report measure of perceived understanding of informed consent.

Adult↗
PubMed2000

Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach: application to African-American populations.

We describe a novel method for analysis of marker genotype data from admixed populations, based on a hybrid of Bayesian and frequentist approaches in which the posterior distribution is generated by Markov chain simulation and score tests are obtained from the missing-data likelihood. We analysed data on unrelated individuals from eight African-American populations, genotyped at ten marker loci of which two (FY and AT3) are linked (22 cM apart). Linkage between these two loci was detected by testing for association of ancestry conditional on parental admixture. The strength of this association was consistent with European gene flow into the African-American population between five and nine generations ago. To mimic the mapping of an unknown gene in an 'affecteds- only' analysis, a binary trait was constructed from the genotype at the AT3 locus and a score test was shown to detect linkage of this 'trait' with the FY locus. Mis-specification of the ancestry-specific allele frequencies - the probabilities of each allelic state given the ancestry of the allele - was detected at three of the ten marker loci. The methods described here have wide application to the analysis of data from admixed populations, allowing the effects of linkage and population structure (variation of admixture between individuals) to be distinguished. With more markers and a more complex statistical model, genes underlying ethnic differences in disease risk could be mapped by this approach.

Bayes Theorem↗
PubMed2005

Biomarkers of exposure to passive smoking of school children: frequency and determinants.

UNLABELLED: This study aims to assess the extent of children' exposure to ETS and quantify potential determinants. A total of 2767 children aged 5-14 years participated in an environmental survey in East Germany in 1998-1999 (participation rate 75.9%). A subgroup of 979 children between the ages of 11 and 14 years with complete data on nicotine and cotinine in urine were selected for this analysis. This study population consisted of 73 self-reported smokers (7.5%), 793 non-smokers (81%) and 113 children with missing data on smoking status (11.5%). Nicotine and cotinine concentrations in spontaneous urine sample were determined by high-performance liquid chromatography methods with ultraviolet-detection and corrected for creatinine. Approximately 40% of self-reported non-smokers were exposed to environmental tobacco smoke (ETS) at home. Non-smoking children exposed to parental tobacco smoke at home compared with not exposed showed in average higher nicotine and cotinine concentration (geometric mean 4.7 microg/l vs. 1.4 microg/l and 8.1 microg/l vs. 2.7 microg/l) and the adjusted odds ratio (OR) for detectable biomarkers ranged between 17 and 22. There were increased rates of detectable biomarkers in urine with increasing numbers of smoked cigarettes in the household (adjusted OR increased from 8 to 54). Maternal smoking showed a stronger effect than paternal smoking. Furthermore, low parental education, cold season, height of dwelling (<or=2.40), urine collected on Monday were statistically significant associated with high nicotine and cotinine excretion levels. Children exposed to parental smoke showed much higher biomarker levels than the non-smoking spouse of an adult smoker. Therefore, children need specifically protection from ETS at home. PRACTICAL IMPLICATIONS: As children showed a higher internal exposure compared with adults the health hazards association with passive smoking might have a more serious effect in children. Children are unable to complain and unable to remove themselves from tobacco smoke exposure. Thus, parents should make sure that their children live in a smoke free environment. Each country should take all necessary legislative and regulatory measures which forbids smoking in public places and the home environment even if it requires sacrifices by the parents.

Adolescent↗