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Plasma leptin measurements in epidemiological investigation: comparison of two commonly used assays and estimate of regression dilution bias.

BACKGROUND AND AIM: As leptin is the object of intensive clinical research, we compared the radio-immunological assay (RIA) and enzyme-linked immunosorbent assay (ELISA) commercially available for measuring its plasma concentration in humans (Study 1), and sought to determine the power of a single plasma leptin measurement to characterise adequately a subject within a population on the basis of its intra- and inter-individual variations (Study 2). METHODS AND RESULTS: Study 1--Plasma leptin concentrations were determined by means of RIA and ELISA in a sample of 80 males. The measurements obtained using the two methods were closely correlated (r = 0.942), but the bias of the means was 21.1 +/- 73.5% (M +/- SD, p < 0.001) and indicated that the two assays were not in agreement with each other. As expected, there were strong statistical associations between plasma leptin and a number of anthropometric indices, but the slopes of the regression of leptin concentration was significantly steeper when measured by ELISA. Study 2--ELISA was used to measure plasma leptin concentrations in three different samples obtained from 12 males and 12 females at two-week intervals. The inter-individual variation in plasma leptin was much greater than its intra-individual variation (the ratio of intra-to inter-individual variance = 0.05 and 0.04 in males and females, respectively), thus suggesting that a single fasting measurement is sufficient to characterise an individual's plasma leptin level within a population. CONCLUSIONS: ELISA is at least as effective as RIA in measuring plasma leptin, and is fully suitable for epidemiological investigations. A single measurement made in the morning and under fasting conditions is sufficient to characterise an individual within a population.

Adult↗

Blood pressure measurement in epidemiological investigations in teenagers.

BACKGROUND: The use of sphygmomanometers may lead to problems in investigations on health of young people. The purpose of this paper is to present the validation of the blood pressure (BP) collected during the survey 'Youth Heart Health' in Hainaut by using second sample of young people in Hainaut for which BP was measured by a manual taking of tension and by an electronic device. METHODS: Validation was done with a control sample of 343 young with five successive BP measures: twice with the mercury sphygmomanometer and three with DXL. We compared the manual and the electronic measures in order to study the correlation between the two methods. The control sample was used in order to compare the BP measurements with the results of the survey on the health of young people in Hainaut. RESULTS: The differences between manual systolic BP and Dinamap measures are significant (differences in averages 3.6 mmHg; d.s. 7.8; 95% CI: 2.8-4.4 mmHg; p < 0.001) and the regression coefficient is -0.015. Diastolic BP is significantly higher with the manual method than with Dinamap (differences in means: 8.2 mmHg; d.s. 7.0; 95% CI: 7.4-8.9 mmHg; p < 0.001) and the coefficient of regression is 0.096. We observe a difference in BP between the general survey and the control group (10.3 mmHg for systolic manual control and of 10.9 mmHg for systolic electronic control; 3.3 mmHg for diastolic manual control and of 11.5 mmHg for diastolic electronic control). CONCLUSIONS: The values of BP of the 'Youth Heart Health' are significantly higher. These observations indicate the difficulties in the choice of the tool for measurements of BP in epidemiological investigations in the teenagers. In order to decrease skews of observations in the measurement of BP, it is recommended to use a valid electronic instrument. Dinamap XL is an instrument of choice in such studies of young people. Environmental and organisational factors may also explain the observed difference, which means that survey's protocols should address this issue carefully.

Adolescent↗

Comparison of two epidemiological protocols for measuring airway responsiveness and allergic sensitivity in adults.

In recent years, airway responsiveness has commonly been measured in epidemiological studies using one of two methods. In one method, histamine is administered via a handheld DeVilbiss nebulizer and in the other, methacholine is administered via a dosimeter. Allergic sensitivity has commonly been measured by either the allergen droplet method or by Phazet. We wanted to assess the comparability of airway responsiveness and of allergic sensitivity measured by both methods. A total of 48 volunteers, including normal and asthmatic subjects, participated in the study. Subjects first underwent one of the two tests of airway responsiveness and allergic sensitivity, and then returned within 10 days to undergo tests using the second protocol. Commencement protocol was allocated in random order. There was good agreement between both methods for assessing airway responsiveness and for assessing allergic sensitivity. The difference for dose response ratio (DRR) between histamine and methacholine was a 1.19 (95% (CI) 0.78, 1.82) fold changes, which was not statistically significant. Agreement between allergic sensitivity methods was perfect for Alternaria tenuis, good for rye-grass (kappa = 0.71) and moderate for cat and Dermatophagoides pteronyssinus (kappa approximately 0.5). It is possible to compare data from epidemiological studies which use these methods.

Adolescent↗

Blood pressure measurements in epidemiological surveys--time to change?

Blood pressure recordings in epidemiological surveys are usually obtained by non-ambulatory, multiple one-occasion, manual sphygmomanometric measurements by trained observers in study participants subjected to standardized examination conditions. High validity and reliability of blood pressure measurements ensure the comparability of study results obtained in different places and at different times, and have a major impact on the detection of correlates and determinants of blood pressure and hypertension. A blood pressure measurement quality assessment was performed within the multi-center collaborative WHO-MONICA Project investigating results of 47 surveys from various geographic regions of the world. In an overall summary assessment, six out of these 47 surveys were found to have had major measurement problems which prohibited their further inclusion in collaborative analyses. Most of the problems were associated with observer-related factors. Therefore, it was contended that automatic blood pressure measurement devices might be able to reduce and abolish most of these "nuisance" factors. In 1995, we had the opportunity to simultaneously study two independent random samples of men and women, aged 45 to 64 years, from the city of Augsburg in Southern Germany. One sample was examined by 16 observers with a random zero sphygmomanometer (MONICA Augsburg), the other sample (J.A.P. Study) was examined by two observers with an invasively validated, automatic oscillometric device (boso Oscillomat). In both surveys, blood pressure was measured three times under similarly standardized conditions. comparing the blood pressure results of the two surveys, the intra-individual measurement variation tended to be slightly higher with the Oscillomat than the random zero, and the population mean blood pressures and hypertension prevalences were found to be significantly lower with the Oscillomat. We conclude that manual measurements of blood pressure by sphygmomanometer should not be indiscriminately replaced externally validated automatic devices. The imponderabilities of automatic devices with varying technical principles have to be assessed in epidemiological settings weighed against recognized disadvantages of sphygmomanometry before any recommendations can be given as to changing the present epidemiological practice.

Bias↗

Relative-risk-estimate bias and loss of power in the Mantel test for trend resulting from the use of magnetic-field point-in-time ("spot") measurements in epidemiological studies based on an ordinal exposure scale.

We assessed the merits of various point-in-time ("spot") measurement protocols in case-control studies based on an ordinal exposure scale. After classifying a number of houses on the basis of prolonged monitoring of the ambient, extremely low frequency (ELF) magnetic field, we determined the probability of misclassification for each "spot" measurement protocol. We calculated the effect of this misclassification on the relative risk estimates and on the Mantel test for trend. We found that classification based on a small group of point-in-time measurements allows an adequate estimate of the relative risk, although the statistical significance of the dose-response gradient may be seriously underestimated. However, the use of automated ambient-field monitors, which results in loss of information on spatial variability, can lead to similar consequences. Therefore, manually collected point-in-time measurements remain a viable option for exposure assessment.

Air Pollution, Indoor↗

[Correlation measures in epidemiology].

When a significant correlation has been noted between the occurrence of a disease and exposure to a risk factor, it becomes necessary to measure the strength of the correlation. This can be done using either relative risk or odds ratio techniques depending on the type of study. The purpose of article this article is to present guidelines for calculation and interpretation of these indicators using examples taken from the Médecine Tropicale journal.

Confidence Intervals↗

Blood pressure measurement in childhood epidemiological studies.

BACKGROUND: Accurate measurement of blood pressure in childhood epidemiological studies requires standardized conditions, valid instruments, and multiple measurements. METHODS AND RESULTS: We used published literature and our own data to make recommendations on the reduction of biases caused by various technical factors, to discuss the advantages and disadvantages of selected measurement devices, and to evaluate the optimal number of visits and measurements per visit for accurate estimation of a child's blood pressure level. The conditions under which blood pressure is measured should be standardized. This includes training and certification to minimize observer biases; equipment factors such as use of an appropriate cuff bladder size, subject factors such as minimizing activities before and during the reading, environmental factors such as accounting for the time of day and ambient temperature, and technique factors such as recording both the fourth and fifth Korotkoff sounds. The choice of instrument for measuring blood pressure depends on the goals of the study and the resources available to the investigators. CONCLUSIONS: Although relatively economical and easy to use, the standard mercury sphygmomanometer is subject to the bias resulting from knowledge of earlier readings. The random-zero sphygmomanometer overcomes this bias, but it is more expensive and difficult to use and may underestimate blood pressure levels. In contrast to auscultatory devices, automated oscillometric devices are not subject to observer biases. They are gaining wider use and may be especially appropriate for younger children. However, they are expensive, and each model requires validation before use in epidemiological studies. Ambulatory blood pressure monitoring represents a potentially useful technique for future epidemiological studies. Multiple measurements are vital in estimating a child's blood pressure, and the number of visits, days or weeks apart, is at least as important as the number of measurements per visit.

Blood Pressure Determination↗

Chronic low-dose lesion equilibrium along genes: measurement, molecular epidemiology, and theory of the minimal relevant dose.

Spontaneous mutations seem to be caused almost entirely by endogenous lesions. The pattern of these lesions along a gene represents an equilibrium between damage and repair. A pattern can be measured using ligation-mediated PCR (polymerase chain reaction) and a large chronic dose of a suspected endogenous mutagen. A study using dimethylsulfate-induced 7meGuanine lesions indicates that the exogenously induced pattern depends on how methyl purine glycosylase recognizes sequence context and, for this lesion, the pattern may be independent of the mutagen's dose.

DNA Adducts↗

A re-analysis of caries rates in a preventive trial using Poisson regression models.

The analysis of caries incidence in clinical trials has several challenging features: (1) The distribution of the number of caries onsets per patient is skewed, with the majority of patients having few or no cavities; (2) the number of surfaces at risk varies (i) over time and (ii) between patients, due to eruption and exfoliation patterns, dental diseases, and treatments; (3) surfaces within a patient differ in their caries susceptibility, and (4) caries onsets within a patient are correlated due to shared host factors. Recent statistical developments in the area of correlated data analyses permit incorporation of some of these characteristics into the analyses. With Poisson regression models, the expected number of caries onsets can be related to the number of surfaces at risk, the time they have been at risk, and surface- and subject-specific explanatory variables. The parameter estimated in these models is an epidemiological measure of disease occurrence: the disease incidence rate (caries rate) or the rate of change from healthy (sound) to diseased (carious). Differences and ratios of these rates provide standard epidemiological measures of excess risk. To illustrate, Poisson regression models were used for exploratory analyses of the Ylivieska xylitol study.

Age Factors↗

Quality control of lipid measurements in epidemiological studies: the U.S. Air Force HEART program.

A special standardization and quality assurance program, similar to that created for the Lipid Research Clinics Program (LRC), was developed for the American Health Foundation Laboratory by the Centers for Disease Control (CDC) to assure the quality of lipid measurements in the U.S. Air Force Health Evaluation and Risk Tabulation (HEART) Program. This study was designed to test the feasibility of reducing the incidence of heart disease in active-duty U.S. Air Force personnel through life-study intervention. During the 18-month study, CDC provided serum calibrators and reference materials for internal control and an external surveillance program for measurements of total cholesterol (TC) and high-density-lipoprotein cholesterol (HDLC). The Laboratory, using an automated enzymic method to measure cholesterol, achieved an overall goal for accuracy of less than 2% error (av systematic error, -30.6 mg/L) for TC, as measured on nine reference pools for which values were assigned by CDC. The average bias of measurements of HDLC with heparin-manganese to separate the lipoproteins in five CDC reference pools was -4.6 mg/L. Bias was estimated relative to the values assigned to the reference materials by the CDC reference methods for TC and HDLC. The average CV for TC was 0.89%, for HDLC 2.66%. Accuracy of cholesterol measurements can be assured over time with a standardization and quality-assurance program that incorporates accurately labeled reference materials for calibration, internal quality control, and external surveillance.

Cholesterol↗

Prioritization MICA: a Web-based application to prioritize public health resources.

Although setting priorities is an important step in making public health policy, the benefit of using epidemiology to prioritize scarce public health resources has not been fully recognized. This situation is mostly due to the complexity of proposed models for setting priorities. We describe a public health priority setting model, Missouri Information for Community Assessment Priority Setting Model (Priority MICA), which uses epidemiologic measures available in most surveillance systems across the United States. Priority MICA uses data from birth and death certificates, hospital discharges, emergency departments, risk factors from the Behavioral Risk Factors Surveillance System, and eight epidemiologic measures to construct six priority criteria: size (the number of emergency department visits, hospitalizations, and deaths), severity (number of deaths of people younger than 65), urgency (trends in deaths and hospital morbidity), preventability (evidence-based score), community support (score of social support for preventive action), and racial-disparity (race comparison through death and morbidity rate ratio). Priority MICA is part of a Web-based interactive tool that makes available data from a wide variety of surveillance systems (http://www.dhss.mo.gov/MICA). The top 10 priority diseases determined by Priority MICA were compared to a more traditional method of ranking diseases by mortality rates. Using the additional criteria in Priority MICA identified four more priority diseases than were identified using just mortality while the ranking of the other six priority diseases differed between methods.

Health Care Rationing↗

Development of an integrated method of skin phenotype measurement using the melanins.

Different types of melanin pigments have recently been identified and recognized as critical determinants of the photosensitivity of individuals. Eumelanin, the black to brown melanin pigments, are believed to protect against ultraviolet-induced cell damage, while phaeomelanin, the reddish brown variant, is thought to be photosensitizing. The relative, qualitative and absolute amount of melanin production under stimulation of solar radiation is likely to be genetically determined. The hypothesis of this study is that determination of these values can help in identifying those people who are less protected. However, these techniques must be evaluated at a population level and against traditional epidemiological measures. We assessed the amount and type of melanin in 195 subjects in four centres across Europe, relating the results to epidemiological measures such as skin characteristics, history of sunburns and number of naevi. The most important finding was that eumelanin and phaeomelanin have very different distributions in the population, being associated with other phenotype characteristics with different patterns. The relationship between phaeomelanin and eumelanin is linearly inverse in the range from black to dark blonde hair colour, while it is weakly directly proportional in the range from dark blonde to light blonde, with people with red hair showing a peculiar pattern. Phaeomelanin rather than eumelanin seemed to be independent of other skin characteristics. The results show the feasibility of a further study with an appropriate case-control design and accurate determination of melanin.

Chromatography, High Pressure Liquid↗

Integrating exposure measurements into epidemiologic studies in agriculture.

Agricultural epidemiology studies frequently rely on questionnaires to assess pesticide exposure. Farmers can provide accurate information regarding their pesticide use history. However, pesticide exposure is influenced not only by the pesticide, but also by factors related to pesticide application and behavior; estimates of exposure can be improved by incorporating data on these factors. Exposure measurement studies help to elucidate influential factors with regard to pesticide dose. These factors can be incorporated into exposure estimates to reduce measurement error and allow for better resolution of the exposure distribution. In the Agricultural Health Study, two exposure algorithms were developed to evaluate exposure intensity; this exposure intensity score was used to modify the lifetime days of pesticide application. This metric, along with additional refinement as a result of on-going field studies, will allow better assignment of exposure levels in the cohort. Future work to develop exposure metrics that incorporate both chemical and behavior characteristics for all farmworkers and farm residents will further improve epidemiologic studies in agriculture.

Agricultural Workers' Diseases↗

Careful use of pseudo R-squared measures in epidemiological studies.

Many epidemiological research problems deal with large numbers of exposed subjects of whom only a small number actually suffers the adverse event of interest. Such rare events data can be analysed by employing an approximate Poisson model. The objective of this study is to challenge the interpretability of the corresponding Poisson pseudo R-squared measure. It will lack sensible interpretation whenever the approximate Poisson outcome is generated by counting the number of events within covariate patterns formed by cross-tabulating categorical covariates. The failure is caused by the immanent arbitrariness in the definition of the covariate patterns, that is, independent Bernoulli events, B(1,pi), are arbitrarily combined into binomially distributed ones, B(n,pi), which are then approximated by the Poisson model.

Adult↗

Intercomparison of five PM10 monitoring devices and the implications for exposure measurement in epidemiological research.

Five different instruments for the determination of the mass concentration of PM10 in air were compared side-by-side for up to 33 days in an undisturbed indoor environment: a tripod mounted BGI Inc. PQ100 gravimetric sampler with a US EPA certified Graseby Andersen PM10 inlet; an Airmetrics Minivol static gravimetric sampler; a Casella cyclone gravimetric personal sampler; an Institute of Occupational Medicine gravimetric PM10 personal sampler; and two TSI Inc. Dustrak real-time optical scattering personal samplers. For 24 h sampling of ambient PM10 concentrations around 10 microg m(-3), the estimated measurement uncertainty for the two gravimetric personal samplers was larger (approximately +/- 20%) compared with estimated measurement uncertainty for the PQ100/Graseby Andersen sampler (< +/- 5%). Measurement uncertainty for the Dustraks was lower (approximately +/- 15% on average) but calibration of the optical response against a reference PM10 method is essential since the Dustraks systematically over-read PM10 determined gravimetrically by a factor approximately 2.2. However, once calibrated, the Dustrak devices demonstrated excellent functionality in terms of ease of portability and real-time data acquisition. Estimated measurement uncertainty for PM10 concentrations determined with the Minivol were +/- 5%. The Minivol data correlated well with PQ100/Graseby Andersen data (r= 0.97, n = 18) but were, on average, 23% greater. The reason for the systematic discrepancy could not be traced. Intercomparison experiments such as these are essential for assessing measurement error and revealing systematic bias. Application of two Dustraks demonstrated the spatial and temporal variability of exposure to PM10 in different walking and transport microenvironments in the city of Edinburgh, UK. For example, very large exposures to PM10 were identified for the lower deck of a double-decker tour bus compared with the open upper deck of the same vehicle. The variability observed emphasises the need to determine truly personal exposure profiles of PM10 for quantifying exposure response relationships for epidemiological studies.

Air Pollution, Indoor↗

The use of 'spot' measurements in epidemiological studies of the health effects of magnetic field exposure.

In several countries, epidemiological studies are being planned, or are in progress, to test the hypothesis that a causal relation exists between exposure to extremely low frequency magnetic fields and cancer incidence. One of the major difficulties in these studies is the development of valid and efficient protocols to assess magnetic field exposure. In studies focusing on residential magnetic fields, many researchers are turning to recently developed stationary automated magnetic field monitors to characterize exposure. We argue that a relatively small number of manually collected 'spot' measurements may be an adequate alternative which has several advantages. We compared a dichotomous exposure classification based on continuous magnetic field monitoring of 40 houses with that obtained through 'spot' measurements randomly sampled from the continuous records. We found that a single spot measurement had at least an 80% chance of classifying houses correctly and that this probability did not increase significantly as the number of readings was increased. We also calculated the sensitivity and specificity of various simulated measurement protocols and, from these, the effect of misclassification on estimates of relative risk. Since relatively large spatial variations in background magnetic field exist in many homes, we suggest that a small number of readings collected manually at several points within a residence may characterize the magnetic field better than continuous monitoring at one fixed location.

Australia↗