Quantitative bias analysis in an asthma study of rescue-recovery workers and volunteers from the 9/11 World Trade Center attacks.

Purpose: When learning bias analysis, epidemiologists are taught to quantitatively adjust for multiple biases by correcting study results in the reverse order of the error sequence. To understand the error sequence for a particular study, one must carefully examine the health study's epidemiologic data-generating process. In this article, we describe the unique data-generating process of a man-made disaster epidemiologic study.

Adjusting for multiple-misclassified variables in a study using birth certificates.

Purpose: Birth certificates are a convenient source of population data for epidemiologic studies. It is well documented, however, that birth certificate data can be highly inaccurate. Nonetheless, studies based on birth certificates are routinely analyzed without accounting for sources of data errors.

Pesticide exposure and neurodevelopmental outcomes: review of the epidemiologic and animal studies.

Assessment of whether pesticide exposure is associated with neurodevelopmental outcomes in children can best be addressed with a systematic review of both the human and animal peer-reviewed literature. This review analyzed epidemiologic studies testing the hypothesis that exposure to pesticides during pregnancy and/or early childhood is associated with neurodevelopmental outcomes in children. Studies that directly queried pesticide exposure (e.

Adjusting for outcome misclassification: the importance of accounting for case-control sampling and other forms of outcome-related selection.

Purpose: Special care must be taken when adjusting for outcome misclassification in case-control data. Basic adjustment formulas using either sensitivity and specificity or predictive values (as with external validation data) do not account for the fact that controls are sampled from a much larger pool of potential controls. A parallel problem arises in surveys and cohort studies in which participation or loss is outcome related.

Self-report versus medical record - perinatal factors in a study of infant leukaemia: a study from the Children's Oncology Group.

In a case-control study of infant leukaemia, we assessed agreement between medical records and mother's self-reported pregnancy-related conditions and procedures and infant treatments. Interview and medical record data were available for 234 case and 215 control mothers. Sensitivity, specificity and predictive values for maternal report were estimated for case and control mothers separately, taking the medical record as correct.

Evaluation of newborn screening bloodspot-based genetic testing as second tier screen for bedside newborn hearing screening.

Purpose: : Bedside newborn hearing screening is highly successful in identifying deaf or hard-of-hearing infants. However, newborn hearing screening protocols have high loss to follow-up rates. We propose that bloodspot-based genetic testing for GJB2 alleles can provide a means for rapid confirmation in a subset of infants who fail bedside newborn hearing screening.

The inborn errors of metabolism information system: A project of the Region 4 Genetics Collaborative Priority 2 Workgroup.

The Region 4 Genetics Collaborative has brought together metabolic clinicians and follow-up specialists from state departments of health in the region (Illinois, Indiana, Kentucky, Michigan, Minnesota, Ohio, and Wisconsin) in a workgroup to create a dynamic registry, the Inborn Errors of Metabolism Information System, to facilitate gathering information about long-term follow-up for individuals identified by newborn blood spot screening. With the concept that by developing a core series of agreed-on data elements and general treatment strategies, differences in treatment plans could yield evidence about optimal treatment choices, data elements for initial intake, and interval follow-up were selected based on a paradigm condition, medium-chain acyl-CoA dehydrogenase deficiency. Demographic elements that will be used as a common data set for all conditions were identified along with condition-specific elements and general information to be obtained at intervals.

Maternal dietary patterns during early pregnancy and the odds of childhood germ cell tumors: A Children's Oncology Group study.

Maternal diet during pregnancy may be associated with cancer in offspring. Intake of individual foods, as well as dietary patterns, can be used when examining these relations. Here, the authors examined associations between maternal dietary intake patterns and pediatric germ cell tumors (GCTs) using principal components analysis and logistic regression.

The association between atopy and childhood/adolescent leukemia: a meta-analysis.

Atopic disease is hypothesized to be protective against several malignancies, including childhood/adolescent leukemia. To summarize the available epidemiologic evidence, the authors performed a meta-analysis of associations between atopy/allergies, asthma, eczema, hay fever, and hives and childhood/adolescent leukemia, acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). They searched MEDLINE literature (1952-March 2009) and queried international experts to identify eligible studies.

Socioeconomic predictors of cognition in Ugandan children: implications for community interventions.

Background: Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions.

Detection of cytomegalovirus DNA in dried blood spots of Minnesota infants who do not pass newborn hearing screening.

Background: Up to 15% of infants with asymptomatic congenital cytomegalovirus (CMV) infection will experience some degree of sensorineural hearing loss. Many infants who fail newborn hearing screening (NHS) are likely to have congenital CMV infection, but may escape definitive virologic identification because diagnostic evaluation may not commence until several weeks or months of age, making differentiation between congenital and postnatal CMV infection difficult. Early diagnosis linking virologic identification of congenital CMV infection to infants failing NHS may improve diagnostic precision and enhance opportunities for therapeutic intervention.

Specifying exposure classification parameters for sensitivity analysis: family breast cancer history.

One of the challenges to implementing sensitivity analysis for exposure misclassification is the process of specifying the classification proportions (eg, sensitivity and specificity). The specification of these assignments is guided by three sources of information: estimates from validation studies, expert judgment, and numerical constraints given the data. The purpose of this teaching paper is to describe the process of using validation data and expert judgment to adjust a breast cancer odds ratio for misclassification of family breast cancer history.

Sexual identity and tobacco use in a venue-based sample of adolescents and young adults.

Background: Tobacco use has been found to be more prevalent among lesbian, gay, bisexual, and transgender (LGBT) adults than among the general population, but there is little information about LGBT youth. This study examined tobacco use in relation to sexual identity in a community venue-based sample of youth.

Methods: Time-space sampling was used to select individuals aged 13-24 years visiting venues frequented by both LGBT and non-LGBT youth, including drop-in and recreational centers, cafes, bars, and a park.

Cerebral malaria in children is associated with long-term cognitive impairment.

Objective: Cerebral malaria affects >785000 African children every year. We previously documented an increased frequency of cognitive impairment in children with cerebral malaria 6 months after their initial malaria episode. This study was conducted to determine the long-term effects of cerebral malaria on the cognitive function of these children.

Cerebrospinal fluid cytokine levels and cognitive impairment in cerebral malaria.

Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-alpha (TNF-alpha), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF.

How far from non-differential does exposure or disease misclassification have to be to bias measures of association away from the null?

A well-known heuristic in epidemiology is that non-differential exposure or disease misclassification biases the expected values of an estimator toward the null value. This heuristic works correctly only when additional conditions are met, such as independence of classification errors. We present examples to show that, even when the additional conditions are met, if the misclassification is only approximately non-differential, then bias is not guaranteed to be toward the null.

Uncertainty analysis: an example of its application to estimating a survey proportion.

Uncertainty analysis is a method, established in engineering and policy analysis but relatively new to epidemiology, for the quantitative assessment of biases in the results of epidemiological studies. Each uncertainty analysis is situation specific, but usually involves four main steps: (1) specify the target parameter of interest and an equation for its estimator; (2) specify the equation for random and bias effects on the estimator; (3) specify prior probability distributions for the bias parameters; and (4) use Monte-Carlo or analytic techniques to propagate the uncertainty about the bias parameters through the equation, to obtain an approximate posterior probability distribution for the parameter of interest. A basic example is presented illustrating uncertainty analyses for four proportions estimated from a survey of the epidemiological literature.

Cognitive impairment after cerebral malaria in children: a prospective study.

Objective: This study was conducted to assess prospectively the frequency of cognitive deficits in children with cerebral malaria.

Methods: Cognitive testing in the areas of working memory, attention, and learning was performed for Ugandan children 5 to 12 years of age with cerebral malaria (n = 44), children with uncomplicated malaria (n = 54), and healthy community children (n = 89) at admission and 3 and 6 months later.

Results: Six months after discharge, 21.

Exposure-measurement error is frequently ignored when interpreting epidemiologic study results.

Introduction: One important source of error in study results is error in measuring exposures. When interpreting study results, one should consider the impact that exposure-measurement error (EME) might have had on study results.

Methods: To assess how often this consideration is made and the form it takes, journal articles were randomly sampled from original articles appearing in the American Journal of Epidemiology and Epidemiology in 2001, and the International Journal of Epidemiology between December 2000 and October 2001.

Risk factors for work-related assaults on nurses.

Background: Work-related homicides have been the subject of considerable study, but little is known about nonfatal violence and relevant risk factors.

Methods: We surveyed 6300 Minnesota nurses who were selected randomly from the 1998 licensing database and determined their employment and occupational violence experience. In a nested case-control study, we examined environmental exposures and physical assault.

Proper interpretation of non-differential misclassification effects: expectations vs observations.

Background: Many investigators write as if non-differential exposure misclassification inevitably leads to a reduction in the strength of an estimated exposure-disease association. Unfortunately, non-differentiality alone is insufficient to guarantee bias towards the null. Furthermore, because bias refers to the average estimate across study repetitions rather than the result of a single study, bias towards the null is insufficient to guarantee that an observed estimate will be an underestimate.