Checking for completeness of 24-h urine collection using para-amino benzoic acid not necessary in the Observing Protein and Energy Nutrition study.

BACKGROUND/OBJECTIVES: The orally administered para-amino benzoic acid (PABA) is known to have near 100% excretion in urine and is used as a measure of 24-h urine collection completeness (referred to as PABAcheck). The purpose was to examine the effect of including urine collections deemed incomplete based on PABAcheck in a dietary measurement error study. SUBJECTS/METHODS: The Observing Protein and Energy Nutrition (OPEN) study was conducted in 1999-2000 and included 484 men and women aged 40-69 years. A food frequency questionnaire and 24-h dietary recalls were evaluated using recovery biomarkers that included urinary nitrogen and potassium from two 24-h urine collections. Statistical modeling determined the measurement error properties of dietary assessment instruments. In the original analyses, PABAcheck was used as a measure of complete urine collection; incomplete collections were either excluded or adjusted to acceptable levels. The OPEN data were reanalyzed including all urine collections and by using criteria based on self-reported missing voids to assess the differences. RESULTS: Means and coefficients of variation for biomarker-based protein and potassium intakes, and measurement error model-based correlations and attenuation factors were similar regardless of whether PABAcheck or missed voids were considered. CONCLUSION: PABAcheck may not be required in large population-based biomarker studies. However, until there are more analyses evaluating the necessity of a PABAcheck, it is recommended that PABA be given to all participants, but not necessarily analyzed. Then, PABAcheck could be used selectively as a marker of completeness among the collections in which low levels of biomarker are detected or for which noncompliance is suspected.

Associations between food patterns defined by cluster analysis and colorectal cancer incidence in the NIH-AARP diet and health study.

BACKGROUND/OBJECTIVES: To examine associations between food patterns, constructed with cluster analysis, and colorectal cancer incidence within the National Institutes of Health-AARP Diet and Health Study. SUBJECTS/METHODS: A prospective cohort, aged 50-71 years at baseline in 1995-1996, followed until the end of 2000. Food patterns were constructed, separately in men (n=293,576) and women (n=198,730), with 181 food variables (daily intake frequency per 1000 kcal) from a food frequency questionnaire. Four large clusters were identified in men and three in women. Cox proportional hazards regression examined associations between patterns and cancer incidence. RESULTS: In men, a vegetable and fruit pattern was associated with reduced colorectal cancer incidence (multivariate hazard ratio, HR: 0.85; 95% confidence interval, CI: 0.76, 0.94), when compared to less salutary food choices. Both the vegetable and fruit pattern and a fat-reduced foods pattern were associated with reduced rectal cancer incidence in men. In women, a similar vegetable and fruit pattern was associated with colorectal cancer protection (age-adjusted HR: 0.82; 95% CI: 0.70, 0.95), but the association was not statistically significant in multivariate analysis. CONCLUSIONS: These results, together with findings from previous studies support the hypothesis that micronutrient dense, low-fat, high-fiber food patterns protect against colorectal cancer.

Index-based dietary patterns and risk of colorectal cancer: the NIH-AARP Diet and Health Study.

The authors compared how four indexes-the Healthy Eating Index-2005, Alternate Healthy Eating Index, Mediterranean Diet Score, and Recommended Food Score-are associated with colorectal cancer in the National Institutes of Health-AARP Diet and Health Study (n = 492,382). To calculate each score, they merged data from a 124-item food frequency questionnaire completed at study entry (1995-1996) with the MyPyramid Equivalents Database (version 1.0). Other variables included energy, nutrients, multivitamins, and alcohol. Models were stratified by sex and adjusted for age, ethnicity, education, body mass index, smoking, physical activity, and menopausal hormone therapy (in women). During 5 years of follow-up, 3,110 incident colorectal cancer cases were ascertained. Although the indexes differ in design, a similarly decreased risk of colorectal cancer was observed across all indexes for men when comparing the highest scores with the lowest: Healthy Eating Index-2005 (relative risk (RR) = 0.72, 95% confidence interval (CI): 0.62, 0.83); Alternate Healthy Eating Index (RR = 0.70, 95% CI: 0.61, 0.81); Mediterranean Diet Score (RR = 0.72, 95% CI: 0.63, 0.83); and Recommended Food Score (RR = 0.75, 95% CI: 0.65, 0.87). For women, a significantly decreased risk was found with the Healthy Eating Index-2005, although Alternate Healthy Eating Index results were similar. Index-based dietary patterns that are consistent with given dietary guidelines are associated with reduced risk.

OPEN about obesity: recovery biomarkers, dietary reporting errors and BMI.

OBJECTIVE: Obesity-related under-reporting of usual dietary intake is one of the most persistent sources of bias in nutrition research. The aim of this paper is to characterize obese and non-obese individuals with respect to reporting errors observed with two common dietary instruments, using energy and protein recovery biomarkers as reference measures. POPULATION AND METHODS: This report employs data from the Observing Protein and Energy Nutrition (OPEN) study. Analyses are based on stratified samples of 211 (57 obese) men and 179 (50 obese) women who completed 24-h recalls (24HR), food frequency questionnaires (FFQ), doubly labelled water (DLW) and urinary nitrogen (UN) assessments. RESULTS: In obese and non-obese subgroups, FFQ yielded lower energy and protein intake estimates than 24HR, although biomarker-based information indicated under-reporting with both dietary instruments. Gender differences in obesity-related bias were noted. Among women, the DLW-based energy requirement was 378 kcal greater in obese than in non-obese groups; the FFQ was able to detect a statistically significant portion of this extra energy, while the 24HR was not. Among men, the DLW-based energy requirement was 485 kcal greater in the obese group; however, neither FFQ nor 24HR detected this difference in energy requirement. Combining protein and energy estimates, obese men significantly over-reported the proportion of energy from protein using the 24HR, but not with the FFQ. In obese women, no significant reporting error for energy percent protein was observed by either method. At the individual level, correlations between energy expenditure and reported energy intake tended to be weaker in obese than non-obese groups, particularly with the 24HR. Correlations between true and reported protein density were consistently higher than for protein or energy alone, and did not vary significantly with obesity. CONCLUSION: This work adds to existing evidence that neither of these commonly used dietary reporting methods adequately measures energy or protein intake in obese groups. The 24HR, while capturing more realistic energy distributions for usual intake, may be particularly problematic in the obese.

Precision of the doubly labeled water method in a large-scale application: evaluation of a streamlined-dosing protocol in the Observing Protein and Energy Nutrition (OPEN) study.

OBJECTIVE: To evaluate whether the doubly labeled water (DLW) method is precise under conditions required for a large-scale evaluation of dietary intake instruments. DESIGN: Energy expenditure was measured in 484 subjects (main study). Subjects received one of five different weight DLW dose bottles prepared in advance of the study. A repeat energy expenditure measure was obtained in a subset of 24 subjects (substudy). DLW measures of energy expenditure were performed over a 2-week interval with urine collection at the beginning and end. SETTING: Free-living environment with three clinic visits in the Maryland suburban area of Washington, DC. SUBJECTS: A total of 484 subjects (261 men and 223 women) aged 40-69 y, 24 of whom (13 men and 11 women) participated in a substudy in which DLW was administered a second time. RESULTS: The coefficient of variation of the DLW energy expenditure measurement was 5.1%. This included a 2.9% analytical and a 4.2% physiologic variation. Based on observed initial isotopic enrichment, the preweighed dosages were optimal in 70% of the main study subjects, and 9% received a dose that was less than optimal. Only six subjects (1%) were excluded because the final isotopic enrichment was too low to conduct precise measurement. CONCLUSIONS: Use of preweighed DLW dosages did not compromise the precision of the DLW method. The DLW method is a reliable measure of energy expenditure for large-scale evaluations of dietary intake instruments.

Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires : the Eating at America's Table Study.

Researchers at the National Cancer Institute developed a new cognitively based food frequency questionnaire (FFQ), the Diet History Questionnaire (DHQ). The Eating at America's Table Study sought to validate and compare the DHQ with the Block and Willett FFQs. Of 1,640 men and women recruited to participate from a nationally representative sample in 1997, 1,301 completed four telephone 24-hour recalls, one in each season. Participants were randomized to receive either a DHQ and Block FFQ or a DHQ and Willett FFQ. With a standard measurement error model, correlations for energy between estimated truth and the DHQ, Block FFQ, and Willett FFQ, respectively, were 0.48, 0.45, and 0.18 for women and 0.49, 0.45, and 0.21 for men. For 26 nutrients, correlations and attenuation coefficients were somewhat higher for the DHQ versus the Block FFQ, and both were better than the Willett FFQ in models unadjusted for energy. Energy adjustment increased correlations and attenuation coefficients for the Willett FFQ dramatically and for the DHQ and Block FFQ instruments modestly. The DHQ performed best overall. These data show that the DHQ and the Block FFQ are better at estimating absolute intakes than is the Willett FFQ but that, after energy adjustment, all three are more comparable for purposes of assessing diet-disease risk.

Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study.

In 1995-1996, the authors mailed a food frequency questionnaire to 3.5 million American Association of Retired Persons members who were aged 50-69 years and who resided in one of six states or two metropolitan areas with high-quality cancer registries. In establishing a cohort of 567,169 persons (340,148 men and 227,021 women), the authors were fortunate in that a less-than-anticipated baseline response rate (threatening inadequate numbers of respondents in the intake extremes) was offset by both a shifting and a widening of the intake distributions among those who provided satisfactory data. Reported median intakes for the first and fifth intake quintiles, respectively, were 20.4 and 40.1 (men) and 20.1 and 40.0 (women) percent calories from fat, 10.3 and 32.0 (men) and 8.7 and 28.7 (women) g per day of dietary fiber, 3.1 and 11.6 (men) and 2.8 and 11.3 (women) servings per day of fruits and vegetables, and 20.7 and 156.8 (men) and 10.5 and 97.0 (women) g per day of red meat. After 5 years of follow-up, the cohort is expected to yield nearly 4,000 breast cancers, more than 10,000 prostate cancers, more than 4,000 colorectal cancers, and more than 900 pancreatic cancers. The large size and wide intake range of the cohort will provide ample power for examining a number of important diet and cancer hypotheses.

Empirical evidence of correlated biases in dietary assessment instruments and its implications.

Multiple-day food records or 24-hour recalls are currently used as "reference" instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. The common adjustment is based on the critical requirements that errors in the reference instrument be independent of those in the FFQ and of true intake. When data on urinary nitrogen level, a valid reference biomarker for nitrogen intake, are used, evidence suggests that a dietary report reference instrument does not meet these requirements. In this paper, the authors introduce a new model that includes, for both the FFQ and the dietary report reference instrument, group-specific biases related to true intake and correlated person-specific biases. Data were obtained from a dietary assessment validation study carried out among 160 women at the Dunn Clinical Nutrition Center, Cambridge, United Kingdom, in 1988-1990. Using the biomarker measurements and dietary report measurements from this study, the authors compare the new model with alternative measurement error models proposed in the literature and demonstrate that it provides the best fit to the data. The new model suggests that, for these data, measurement error in the FFQ could lead to a 51% greater attenuation of true nutrient effect and the need for a 2.3 times larger study than would be estimated by the standard approach. The implications of the results for the ability of FFQ-based epidemiologic studies to detect important diet-disease associations are discussed.

Efficient regression calibration for logistic regression in main study/internal validation study designs with an imperfect reference instrument.

An extension to the version of the regression calibration estimator proposed by Rosner et al. for logistic and other generalized linear regression models is given for main study/internal validation study designs. This estimator combines the information about the parameter of interest contained in the internal validation study with Rosner et al.'s regression calibration estimate, using a generalized inverse-variance weighted average. It is shown that the validation study selection model can be ignored as long as this model is jointly independent of the outcome and the incompletely observed covariates, conditional, at most, upon the surrogates and other completely observed covariates. In an extensive simulation study designed to follow a complex, multivariate setting in nutritional epidemiology, it is shown that with validation study sizes of 340 or more, this estimator appears to be asymptotically optimal in the sense that it is nearly unbiased and nearly as efficient as a properly specified maximum likelihood estimator. A modification to the regression calibration variance estimator which replaces the standard uncorrected logistic regression coefficient variance with the sandwich estimator to account for the possible misspecification of the logistic regression fit to the surrogate covariates in the main study, was also studied in this same simulation experiment. In this study, the alternative variance formula yielded results virtually identical to the original formula. A version of the proposed estimator is also derived for the case where the reference instrument, available only in the validation study, is imperfect but unbiased at the individual level and contains error that is uncorrelated with other covariates and with error in the surrogate instrument. Replicate measures are obtained in a subset of study participants. In this case it is shown that the validation study selection model can be ignored when sampling into the validation study depends, at most, only upon perfectly measured covariates. Two data sets, a study of fever in relation to occupational exposure to antineoplastics among hospital pharmacists and a study of breast cancer incidence in relation to dietary intakes of alcohol and vitamin A, adjusted for total energy intake, from the Nurses' Health Study, were analysed using these new methods. In these data, because the validation studies contained less than 200 observations and the events of interest were relatively rare, as is typical, the potential improvements offered by this new estimator were not apparent.

Evaluation of alternative approaches to assign nutrient values to food groups in food frequency questionnaires.

Although every food frequency questionnaire (FFQ) requires a nutrient database to produce nutrient intake estimates, it is often unclear how a particular database has been generated. Moreover, alternative methods for constructing a database have not been rigorously evaluated. Using 24-hour recalls from the 1994-1996 Continuing Survey of Food Intake by Individuals, the authors categorized 5,261 individual foods reported by 10,019 adults into 170 food groups consistent with line items on an FFQ. These food groups were used to generate 10 potential nutrient databases for a FFQ that varied by whether the authors 1) used means or medians, 2) did or did not consider age, 3) incorporated collapsing strategies for small age-gender-portion size cells, 4) excluded outliers in a regression, and 5) used weighted median nutrient density x age-gender-portion size-specific median gram weights (Block method). Mean error, mean squared error, and mean absolute error were calculated and compared across methods, with error being the difference in total observed (from recalls for each individual) and total estimated intake (from each of the 10 methods) for seven nutrients. Mean methods for assigning nutrients to food groups were superior to median approaches for all measurements. Among the mean methods, no single variation was consistently better.

Evaluation of 2 brief instruments and a food-frequency questionnaire to estimate daily number of servings of fruit and vegetables.

BACKGROUND: Measurement of fruit and vegetable intake is important in the surveillance of populations and in epidemiologic studies that examine the relations between diet and disease. Some situations require the use of brief dietary assessment tools. OBJECTIVE: Our objective was to evaluate the performance of 2 brief dietary assessment instruments, a 7-item standard screener and a new 16-item screener, and a complete food-frequency questionnaire (FFQ) in measuring total fruit and vegetable consumption. DESIGN: About 800 men and women from the National Institutes of Health-AARP Diet and Health Study completed an FFQ, 1 of the 2 screeners, and two 24-h dietary recalls. Fruit and vegetable intakes as measured by each screener and the FFQ were compared with estimated true usual intake by using a measurement-error model. RESULTS: Median daily servings of fruit and vegetables were underestimated by both screeners. The estimated agreement between true intake and the screener was higher for the new screener than for the standard screener and was higher for women than for men. The estimated agreement between true intake and the FFQ was higher than that for both screeners. Attenuation coefficients for the FFQ and screeners were comparable. CONCLUSIONS: For estimating median intakes of fruit and vegetables and the prevalence of recommended intakes being met, the use of screeners without appropriate adjustment is suboptimal. For estimating relative risks in the relations between fruit and vegetable intake and disease, screeners and this FFQ are similar in performance.

Implications of a new dietary measurement error model for estimation of relative risk: application to four calibration studies.

Food records or 24-hour recalls are currently used to calibrate food frequency questionnaires (FFQs) and to correct disease risks for measurement error. The standard regression calibration approach requires that these reference measures contain only random within-person errors uncorrelated with errors in FFQs. Increasing evidence suggests that records/recalls are likely to be also flawed with systematic person-specific biases, so that for any individual the average of multiple replicate assessments may not converge to her/his true usual nutrient intake. The authors propose a new measurement error model to accommodate person-specific bias in the reference measure and its correlation with systematic error in the FFQ. Sensitivity analysis using calibration data from four studies demonstrates that failure to account for person-specific bias in the reference measure can often lead to substantial underestimation of the relative risk for a nutrient. These results indicate that in the absence of information on the extent of person-specific biases in reference instruments and their relation to biases in FFQs, the adequacy of the standard methods of correcting relative risks for measurement error is in question, as is the interpretation of negative findings from nutritional epidemiology such as failure to detect an important relation between fat intake and breast cancer.

Measurement error and dietary intake.

This chapter reviews work of Carroll, Freedman, Kipnis, and Li (1998) on the statistical analysis of the relationship between dietary intake and health outcomes. In the area of nutritional epidemiology, there is some evidence from biomarker studies that the usual statistical model for dietary measurements may break down due to two causes: (a) systematic biases depending on a person's body mass index; and (b) an additional random component of bias, so that the error structure is the same as a one-way random effects model. We investigate this problem, in the context of (1) the estimation of the distribution of usual nutrient intake; (2) estimating the correlation between a nutrient instrument and usual nutrient intake; and (3) estimating the true relative risk from an estimated relative risk using the error-prone covariate. While systematic bias due to body mass index appears to have little effect, the additional random effect in the variance structure is shown to have a potentially important impact on overall results, both on corrections for relative risk estimates and in estimating the distribution usual of nutrient intake. Our results point to a need for new experiments aimed at estimation of a crucial parameter.

Effect of measurement error on energy-adjustment models in nutritional epidemiology.

The use and interpretation of energy-adjustment regression models in nutritional epidemiology has been vigorously debated recently. There has been little discussion, however, regarding the effect of dietary measurement error on the performance of such models. Contrary to conventional assumptions invoked in the standard treatment of the effect of measurement error in regression analysis, reporting errors in dietary studies are usually biased, correlated with true nutrient intakes and with each other, heteroscedastic, and nonnormally distributed. Methods developed in this paper allow for this more complex error structure and are therefore more appropriate for dietary data. For practical illustration, these methods are applied to data from the Women's Health Trial Vanguard Study. The results demonstrate considerable shrinkage in the magnitude of the estimated main exposure effect in energy-adjustment models due to attenuation of the true effect and contamination from the effect of an adjusting covariate. In most cases, this shrinkage causes a sharply reduced statistical power of the corresponding significance test in comparison with measurement without error. These results emphasize the need to understand the measurement error properties of dietary instruments through validation/calibration studies and, where possible, to correct for the impact of measurement error when applying energy-adjustment models.

Relationship between static chemical and cyclic mechanical fatigue in a feldspathic porcelain.

OBJECTIVES: The goal of this study was to determine if static chemical and cyclic mechanical fatigue are independent, or if they interact to produce greater than additive strength loss in a feldspathic porcelain. METHODS: A blunt indentation technique was used to investigate the response of a feldspathic dental porcelain to cyclic mechanical fatigue and static chemical fatigue. All specimens were fabricated in a dry inert environment and then mechanically fatigued by cyclic loading and strength-tested in dry inert nitrogenous, ambient or wet environments. A series of experiments were performed to evaluate the effects of chemical and mechanical fatigue, and their interaction on strength loss; to determine the effects of, and interaction between, the factors of cyclic fatigue environment and strength test environment on strength; to ascertain if the type of environment during strength testing influenced specimen strength; and to distinguish between chemical damage caused by exposure to moisture alone and stress corrosion damage resulting from the strength testing environment, using a pair of two-way analysis of variance, a single one-way analysis of variance and a t-test (p < 0.05). RESULTS: These experiments indicated that both static chemical fatigue and cyclic mechanical fatigue significantly reduced specimen strength, but they did not interact to produce greater than summative effects. It was also learned that chemical fatigue was not detected on initial exposure to moisture and that it occurred to a small extent during mechanical fatigue cycling, and primarily occurred during strength testing through a stress-corrosion phenomenon. Micrographs visually evaluated the effects of mechanical and chemical fatigue on surface contact damage. SIGNIFICANCE: As both static chemical and cyclic mechanical fatigue influenced porcelain strength, they should both be considered in future evaluations. However, because they largely acted independently, they can be studied separately.

Approached to monitoring the results of long-term disease prevention trials: examples from the Women's Health Initiative.

We contrast monitoring therapeutic trials with monitoring prevention trails. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simply on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of others. We describe one approach, illustrated by the Women's Health Initiative. For each of several sets of hypothetical interim results ("scenarios"), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that are based on (1) the primary targeted disease, (2) a combination of various disease outcomes, or (3) a mixture of both were applied to these scenarios. One objective was to find a statistical approach that mirrors the majority view of the DSMC. A second objective was to stimulate discussion among DSMC members in preparation for their task of monitoring the trial as the real data become available. We found that no single method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the global index to be "supportive," with separate monitoring of adverse effects, corresponded with the majority vote quite well. This approach maintains the emphasis on the primary hypothesis while assuring that broader safety and ethical issues of multiple diseases are incorporated.

Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1.

A Siberian kindred with spinocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CAG triplet expansion within the coding region of the SCA1 gene. The kindred includes 1,484 individuals, 225 affected and 656 at risk, making this collection the largest spinocerebellar ataxia type 1 (SCA1) pedigree known. Each of the studied 78 SCA1 patients carried an expanded allele containing a stretch of 39 to 72 uninterrupted CAG repeats. Normal alleles had 25 to 37 trinucleotide repeats. Expanded alleles containing 40 to 55 repeats were found in 26 at-risk relatives. The number of CAG repeats in the mutated allele was inversely correlated with age at disease onset. Cerebellar deficiency was present in each patient and its severity was moderately affected by the number of CAG repeats. In contrast, the associated signs, dysphagia, diffuse skeletal muscle atrophy with fasciculations, and tongue atrophy were absent or mild in patients with low CAG repeat numbers, but severely complicated the course of illness in patients with a larger number of repeat units. One female mutation carrier was asymptomatic at age 66, more than 2 standard deviations beyond the average age of risk, suggesting incomplete penetrance. In 2 symptomatic individuals who had an expanded number of CAG repeats on both chromosomes, age at onset, rate of progression, and clinical manifestation corresponded to the size of the larger allele.

Effect of dynamic loading methods on cement film thickness in vitro.

PURPOSE: Reduced cement flm thicknesses can improve crown seating and decrease marginal discrepancies. Improved marginal adaptation has the potential to reduce plaque accumulation, periodontal disease, and cement dissolution. Studies have indicated that dynamic seating methods can reduce seating discrepancies associated with zinc phosphate and resin cements. However, other types of cements and other dynamic techniques have not yet been studied or compared, nor has the mechanism for improved seating been fully explained. Therefore, the purpose of this study was to investigate the effect of a variety of loading methods on the film thicknesses of current types of crown and fixed partial denture cements compressed between glass plates. MATERIALS AND METHODS: This study investigated the effect of three dynamic loading methods on film thickness of six representative fixed prosthodontic cements. These included zinc phosphate, resin-modified glass ionomer, encapsulated glass ionomer, adhesive composite resin, composite resin, and polycarboxylate. The method was derived from American Dental Association specifications for cement film thickness. In control groups, the cements were placed between two glass glass plates and statically loaded with a 15-kg weight. The test groups were initially similarly loaded, and then for 30 seconds further subjected to simulated repeated patient opening and closing, vibrations from an electromallet, or an ultrasonic device. RESULTS: Mean film thicknesses ranged from 7.4 micrometers for polycarboxylate / ultrasound up to 40.3 micrometers for composite resin / static. Two-way analysis of variance revealed that the effects of material type and cementation method and their interaction all significantly affected film thickness (P < .0001). Multiple range analysis showed that dynamic methods were generally superior to static loading and that the ultrasonic method was the best overall. CONCLUSIONS: The different dynamic loading methods all significantly decreased cement film thicknesses between glass plates. The ultrasonic method was the most effective. The type of cement used also influenced film thickness. Composite resins were more affected than other materials.