Anne M. Jurek

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. METHODS. Children who were 5 to 12 years of age and presented to Mulago Hospital, Kampala, Uganda, with cerebral malaria (n = 44) or uncomplicated malaria (n = 54), along with healthy, asymptomatic community children (n = 89), were enrolled in a prospective cohort study of cognition. Cognitive testing was performed at enrollment and 2 years later. The primary outcome was presence of a deficit in ≥1 of 3 cognitive areas tested. RESULTS. At 2-year follow-up testing, 26.3% of children with cerebral malaria and 12.5% with uncomplicated malaria had cognitive deficits in ≥1 area, as compared with 7.6% of community children. Deficits in children with cerebral malaria were primarily in the area of attention (cerebral malaria, 18.4%, vs community children, 2.5%). After adjustment for age, gender, nutrition, home environment, and school level, children with cerebral malaria had a 3.67-fold increased risk for a cognitive deficit compared with community children. Cognitive impairment at 2-year follow-up was associated with hyporeflexia on admission and neurologic deficits 3 months after discharge. CONCLUSIONS. Cerebral malaria is associated with long-term cognitive impairments in 1 of 4 child survivors. Future studies should investigate the mechanisms involved so as to develop interventions aimed at prevention and rehabilitation.

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, 21.4% of children with cerebral malaria had cognitive deficits, compared with 5.8% of community children. Deficits were seen in the areas of working memory (11.9% vs 2.3%) and attention (16.7% vs 2.3%). Children with cerebral malaria had a 3.7-fold increased risk of a cognitive deficit, compared with community children, after adjustment for age, gender, nutritional status, school level, and home environment. Among children with cerebral malaria, those with a cognitive deficit had more seizures before admission (mean: 4.1 vs 2.2) and a longer duration of coma (43.6 vs 30.5 hours), compared with those without a deficit. Children with uncomplicated malaria did not have an increased frequency of cognitive deficits. CONCLUSIONS. Cerebral malaria may be a major cause of cognitive impairment in children in sub-Saharan Africa. Cognitive deficits in children with cerebral malaria are more likely for those who have multiple seizures before effective treatment for cerebral malaria.

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. Cases of assault in the previous 12 months and controls randomly selected from assault-free months were surveyed about prior-month exposures. Results: After adjustment by multiple logistic regression, incidence of physical assault was 13.2 per 100 persons per year (95% confidence interval = 12.2–14.3). Among 310 cases and 946 control subjects, odds ratios for assault were increased: in nursing homes or long-term care facilities (2.6; 1.9–3.6), emergency departments (4.2; 1.3–12.8), and psychiatric departments (2.0; 1.1–3.7); in environments not “bright as daylight” (2.2; 1.6–2.8); and for each additional hour of shift duration (1.05; 0.99–1.11). Risks were decreased when carrying cellular telephones or personal alarms (0.3; 0.2–0.7). Conclusions: These results may guide in-depth investigation of ways protective and risk factors can control violence against nurses.

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. In light of such examples, we advise that evaluation of misclassification should not be based on the assumption of exact non-differentiality unless the latter can be deduced logically from the facts of the situation.

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

IntroductionOne 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.MethodsTo 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.ResultsTwenty-two (39%) of the 57 articles surveyed mentioned nothing about EME. Of the 35 articles that mentioned something about EME, 16 articles described qualitatively the effect EME could have had on study results. Only one study quantified the impact of EME on study results; the investigators used a sensitivity analysis. Few authors discussed the measurement error in their study in any detail.ConclusionsOverall, the potential impact of EME on error in epidemiologic study results appears to be ignored frequently in practice.

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. Ten case-control studies were included. Summary odds ratios and 95% confidence intervals were computed via random-effects models. Odds ratios for atopy/allergies were 1.42 (95% confidence interval (CI): 0.60, 3.35) for 3 studies of leukemia overall, 0.69 (95% CI: 0.54, 0.89) for 6 studies of ALL, and 0.87 (95% CI: 0.62, 1.22) for 2 studies of AML, with high levels of heterogeneity detected for leukemia overall and ALL. Inverse associations were observed for ALL and asthma (odds ratio (OR) = 0.79, 95% CI: 0.61, 1.02), eczema (OR = 0.74, 95% CI: 0.58, 0.96), and hay fever (OR = 0.55, 95% CI: 0.46, 0.66) examined separately. Odds ratios for ALL differed by study design, exposure data source, and latency period, indicating that these factors affect study results. These results should be interpreted cautiously given the modest number of studies, substantial heterogeneity, and potential exposure misclassification but are useful in designing future research.

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. Methods A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, childs educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months. Results A higher childs education level was associated with better memory (p = 0.03), attention (p = 0.005) and spatial learning scores over the 24 months (p = 0.05); higher nutrition scores predicted better visual spatial processing (p = 0.002) and spatial learning scores (p = 0.008); and a higher home environment score predicted a better memory score (p = 0.03). Conclusion Cognition in Ugandan children is predicted by childs education, nutritional status and the home environment. Community interventions to improve cognition may be effective if they target multiple socioeconomic variables.

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. Methods: The goal of this study was to compare newborn dried blood spots from Minnesota infants who had failed NHS, and were designated for referral, with control infants who passed NHS, for the presence of CMV DNA by real-time PCR, using hybridization probes for the CMV gene UL54. Results: Of 479 infants with a failed NHS (bilateral failure), 13 had CMV DNA present in the blood spot (2.7%). This compared with only 2/479 positive results from a control group of infants who passed the NHS (0.4%; P = 0.007, Fisher exact test). Comparisons of the glycoprotein B (gB) genotype as well as direct DNA sequencing of selected positives revealed that PCR positive samples represented unique clinical isolates. The mean viral load among the 15 positive samples was 1.6 × 103 genomes/microgram of total DNA. Conclusions: Newborn bloodspot CMV screening by real-time PCR may be a useful and rapid adjunct to functional NHS and may enable more rapid etiologic diagnosis of sensorineural hearing loss in newborns.

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. ORs for the association between LGBT identity and tobacco use were estimated using logistic regression models with adjustment for demographic covariates and venue selection. The two main outcomes were lifetime and last-30-day cigarette smoking. Sixteen secondary outcomes pertained to the type, initiation, frequency, and quantity of tobacco use; symptoms of dependence; and cessation. RESULTS Seventy-seven percent (500/653) of eligible participants completed surveys by interview in 2005-2006. Sixty-three percent smoked in the last 30 days, 22% smoked more than 30 days ago, and 17% reported no prior cigarette smoking. LGBT identity predicted any prior cigarette use (OR 2.2, 95% CI=1.7, 3.2), but not recent use. Compared to non-LGBT youth, LGBT participants were less likely to use smokeless tobacco (OR 0.6, 95% CI=0.5, 0.7) and to want to quit smoking cigarettes (OR 0.6, 95% CI=0.5, 0.8). Other tobacco-related attitudes and behaviors were similar. CONCLUSIONS Few meaningful differences in tobacco use were related to sexual identity. The remarkably high levels of cigarette smoking in the sample highlights the need for prevention and cessation resources.

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.Methods: We performed a case-control study comparing the prevalence of common GJB2 mutations from deidentified bloodspots designated as “refer” by newborn hearing screening and contemporaneously selected randomly chosen controls designated as “pass.” Between March 2006 and December 2007, 2354 spots were analyzed for common alleles, c.35delG, c.167delT, c.235delC, and p.V37I in GJB2 with a subset reanalyzed by conventional Sanger sequencing to search for additional alleles.Results: The prevalence of biallelic GJB2 mutations in bloodspots from infants who referred by newborn hearing screening is approximately 1 in 50 (23/1177). In contrast, one bloodspot from an infant who passed newborn hearing screening was identified to harbor biallelic GJB2 mutations.Conclusions: These findings show that when a newborn refers by newborn hearing screening, there is a significant chance that GJB2-related hearing loss is present. Bloodspot-based genetic testing for common GJB2 alleles should be considered as second tier testing for bedside newborn hearing screening.