Low-level lead exposure and mortality in US adults: a population-based cohort study.

BACKGROUND: Lead exposure is a risk factor for cardiovascular disease mortality, but the number of deaths in the USA attributable to lead exposure is poorly defined. We aimed to quantify the relative contribution of environmental lead exposure to all-cause mortality, cardiovascular disease mortality, and ischaemic heart disease mortality. METHODS: Our study population comprised a nationally representative sample of adults aged 20 years or older who were enrolled in the Third National Health and Nutrition Examination Survey (NHANES-III) between 1988 and 1994 and followed up to Dec 31, 2011. Participants had completed a medical examination and home interview and had results for concentrations of lead in blood, cadmium in urine, and other relevant covariates. Individuals were linked with the National Death Index. This study presents extended follow-up of an earlier analysis. FINDINGS: We included 14 289 adults in our study. The geometric mean concentration of lead in blood was 2·71 µg/dL (geometric SE 1·31). 3632 (20%) participants had a concentration of lead in blood of at least 5 µg/dL (≥0·24 µmol/L). During median follow-up of 19·3 years (IQR 17·6-21·0), 4422 people died, 1801 (38%) from cardiovascular disease and 988 (22%) from ischaemic heart disease. An increase in the concentration of lead in blood from 1·0 µg/dL to 6·7 µg/dL (0·048 µmol/L to 0·324 µmol/L), which represents the tenth to 90th percentiles, was associated with all-cause mortality (hazard ratio 1·37, 95% CI 1·17-1·60), cardiovascular disease mortality (1·70, 1·30-2·22), and ischaemic heart disease mortality (2·08, 1·52-2·85). The population attributable fraction of the concentration of lead in blood for all-cause mortality was 18·0% (95% CI 10·9-26·1), which is equivalent to 412 000 deaths annually. Respective fractions were 28·7% (15·5-39·5) for cardiovascular disease mortality and 37·4% (23·4-48·6) for ischaemic heart disease mortality, which correspond to 256 000 deaths a year from cardiovascular disease and 185 000 deaths a year from ischaemic heart disease. INTERPRETATION: Low-level environmental lead exposure is an important, but largely overlooked, risk factor for cardiovascular disease mortality in the USA. A comprehensive strategy to prevent deaths from cardiovascular disease should include efforts to reduce lead exposure. FUNDING: The Artemis Fund and Simon Fraser University.

Utility of Pediatric Appendicitis Score in Female Adolescent Patients.

OBJECTIVES: Acute appendicitis is common in the pediatric population and is difficult to diagnose in adolescent females. The validated Pediatric Appendicitis Score (PAS) has unclear utility in female adolescents. The purpose of this study is to determine the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of the PAS for female adolescents compared to all other patients. METHODS: This study examined a retrospective observational cohort of patients ages 3 to 21 years in a pediatric emergency department with prospectively assigned PAS from an existing database. We compared the sensitivity, specificity, PPV, and NPV of the PAS for acute appendicitis among female adolescent patients (13 to 21 years) and all other patients. RESULTS: Of the 1,228 patients enrolled, 901 (73.4%) had a complete PAS. Among the 901 patients, 249 (27.6%) had pathology-proven appendicitis, 494 (54.8%) were female, and 272 (30.2%) were adolescent females. At a cutoff of ≥8, the PAS showed a specificity of 89% for adolescent females and 78% for all other patients (p < 0.001), although the specificities did not differ at a cutoff of ≥7. At both cutoffs, the PPVs were poor in both groups. At a cutoff of ≥3, the PAS showed similar sensitivities in both groups. At a cutoff of <3, the NPVs did not significantly differ between groups. CONCLUSION: At a cutoff of ≥8 (although not ≥7), the PAS demonstrated a higher specificity among female adolescents compared to all other patients. The PPV for both cutoffs in both groups were poor. At a cutoff of ≥3, sensitivities were equivalent. The NPV for a cutoff of <3 was acceptable but similar in both groups. While sensitivities were similar to previously reported, specificities in both groups were lower. This highlights the need for further investigation of the PAS's performance in specific subpopulations.

Prenatal Exposure to Organophosphorous Pesticides and Fetal Growth: Pooled Results from Four Longitudinal Birth Cohort Studies.

BACKGROUND: Organophosphorous (OP) pesticides are associated with reduced fetal growth in animals, but human studies are inconsistent. OBJECTIVES: We pooled data from four cohorts to examine associations of prenatal OP exposure with birth weight (n = 1,169), length (n = 1,152), and head circumference (n = 1,143). METHODS: Data were from the CHAMACOS, HOME, Columbia, and Mount Sinai birth cohorts. Concentrations of three diethyl phosphate (ΣDEP) and three dimethyl phosphate (ΣDMP) metabolites of OP pesticides [summed to six dialkyl phosphates (ΣDAPs)] were measured in maternal urine. Linear regression and mixed-effects models were used to examine associations with birth outcomes. RESULTS: We found no significant associations of ΣDEP, ΣDMP, or ΣDAPs with birth weight, length, or head circumference overall. However, among non-Hispanic black women, increasing urinary ΣDAP and ΣDMP concentrations were associated with decreased birth length (ß = -0.4 cm; 95% CI: -0.9, 0.0 and ß = -0.4 cm; 95% CI: -0.8, 0.0, respectively, for each 10-fold increase in metabolite concentration). Among infants with the PON1192RR genotype, ΣDAP and ΣDMP were negatively associated with length (ß = -0.4 cm; 95% CI: -0.9, 0.0 and ß = -0.5 cm; 95% CI: -0.9, -0.1). CONCLUSIONS: This study confirms previously reported associations of prenatal OP exposure among black women with decreased infant size at birth, but finds no evidence of smaller birth weight, length, or head circumference among whites or Hispanics. Contrary to our hypothesis, we found stronger inverse associations of DAPs and birth outcome in infants with the less susceptible PON1192RR genotype. The large pooled data set facilitated exploration of interactions by race/ethnicity and PON1 genotype, but was limited by differences in study populations. CITATION: Harley KG, Engel SM, Vedar MG, Eskenazi B, Whyatt RM, Lanphear BP, Bradman A, Rauh VA, Yolton K, Hornung RW, Wetmur JG, Chen J, Holland NT, Barr DB, Perera FP, Wolff MS. 2016. Prenatal exposure to organophosphorous pesticides and fetal growth: pooled results from four longitudinal birth cohort studies. Environ Health Perspect 124:1084-1092; http://dx.doi.org/10.1289/ehp.1409362.

Prenatal Organophosphorus Pesticide Exposure and Child Neurodevelopment at 24 Months: An Analysis of Four Birth Cohorts.

BACKGROUND: Organophosphorus pesticides (OPs) are used in agriculture worldwide. Residential use was common in the United States before 2001. OBJECTIVES: We conducted a pooled analysis of four birth cohorts (children's centers; n = 936) to evaluate associations of prenatal exposure to OPs with child development at 24 months. METHODS: Using general linear models, we computed site-specific and pooled estimates of the association of total dialkyl (ΣDAP), diethyl (ΣDEP), and dimethylphosphate (ΣDMP) metabolite concentrations in maternal prenatal urine with mental and psychomotor development indices (MDI/PDI) and evaluated heterogeneity by children's center, race/ethnicity, and PON1 genotype. RESULTS: There was significant heterogeneity in the center-specific estimates of association for ΣDAP and ΣDMP and the MDI (p = 0.09, and p = 0.05, respectively), as well as heterogeneity in the race/ethnicity-specific estimates for ΣDAP (p = 0.06) and ΣDMP (p = 0.02) and the MDI. Strong MDI associations in the CHAMACOS population per 10-fold increase in ΣDAP (ß = -4.17; 95% CI: -7.00, -1.33) and ΣDMP (ß = -3.64; 95% CI: -5.97, -1.32) were influential, as were associations among Hispanics (ß per 10-fold increase in ΣDAP = -2.91; 95% CI: -4.71, -1.12). We generally found stronger negative associations of ΣDAP and ΣDEP with the 24-month MDI for carriers of the 192Q PON1 allele, particularly among blacks and Hispanics. CONCLUSIONS: Data pooling was complicated by center-related differences in subject characteristics, eligibility, and changes in regulations governing residential use of OPs during the study periods. Pooled summary estimates of prenatal exposure to OPs and neurodevelopment should be interpreted with caution because of significant heterogeneity in associations by center, race/ethnicity, and PON1 genotype. Subgroups with unique exposure profiles or susceptibilities may be at higher risk for adverse neurodevelopment following prenatal exposure. CITATION: Engel SM, Bradman A, Wolff MS, Rauh VA, Harley KG, Yang JH, Hoepner LA, Barr DB, Yolton K, Vedar MG, Xu Y, Hornung RW, Wetmur JG, Chen J, Holland NT, Perera FP, Whyatt RM, Lanphear BP, Eskenazi B. 2016. Prenatal organophosphorus pesticide exposure and child neurodevelopment at 24 months: an analysis of four birth cohorts. Environ Health Perspect 124:822-830; http://dx.doi.org/10.1289/ehp.1409474.

Uncertainties in estimating health risks associated with exposure to ionising radiation.

The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.

Can the reduction of pediatric injury rates be sustained using a community-based approach?

BACKGROUND: Injuries are the leading cause of morbidity and mortality in US residents aged 1 to 44 years. Community-based interventions are effective in reducing injuries. Using this approach, investigators significantly reduced injuries in Avondale, Ohio, between 1999 and 2004 compared with three control communities (42 vs. 15%, respectively). The objective of this study was to determine if injury reduction was sustained through the 5 years after initial implementation of injury prevention (IP) efforts in Avondale compared with the same three control communities. DESIGN/METHODS: Injury prevention interventions implemented in Avondale, Ohio, during previous study years were sustained. Two new playgrounds were built, but no other new interventions were introduced. Control communities had no programs introduced by the team during the study period. Data were obtained from the Hamilton County Injury Surveillance System from 2005 to 2009 for deaths, hospitalizations, and emergency department visits due to injury for children 0 to 19 years old. Data from the study community were compared with those of the same three control communities as in our previous work, with similar demographics and socioeconomic characteristics, as well as with data obtained previously from 1999 to 2004. Census data based on annual estimates were used to calculate injury rates. RESULTS: The injury rate in Avondale decreased from 17,073 to 11,284 injuries per 100,000 children per year during the 11-year period (33.9% reduction). The injury rate in the control communities decreased from 14,436 to 12,381 injuries per 100,000 children per year in the same period (14.2% reduction). The difference in the injury rate decrease between the intervention and control communities was statistically significant, p < 0.001. From 2005 to 2009, the lower injury rate was sustained in Avondale, p = 0.58. CONCLUSIONS: Community-based strategies to prevent injuries to children in high-risk communities can be successful in reducing overall injury rates. These efforts can result in sustained injury reduction over time despite no new interventions being introduced.

Determining the effectiveness of the pentavalent rotavirus vaccine against rotavirus hospitalizations and emergency department visits using two study designs.

The objective of this study is to determine the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) for preventing rotavirus-related hospitalizations and emergency department (ED) visits during the 2006-07 and 2007-08 rotavirus seasons using two study designs. Active, prospective population-based surveillance was conducted to identify cases of laboratory-confirmed rotavirus-related hospitalizations and ED visits to be used in case-cohort and case-control designs. VE was calculated using one comparison group for the case-cohort method and two comparison groups for the case-control method. The VE estimates produced by the three analyses were similar. Three doses of RV5 were effective for preventing rotavirus-related hospitalizations and ED visits in each analysis, with VE estimated as 92% in all three analyses. Two doses of RV5 were also effective, with VE ranging from 79% to 83%. A single dose was effective in the case-cohort analysis, but was not significant in either of the case-control analyses. The case-cohort and the case-control study designs produced the same VE point estimates for completion of the three dose series. Two and three doses of RV5 were effective in preventing rotavirus-related hospitalizations and ED visits.

Mortality and ionising radiation exposures among workers employed at the Fernald Feed Materials Production Center (1951-1985).

OBJECTIVES: To examine mortality patterns and dose-response relations between ionising radiation and mortality outcomes of a priori interest in 6409 uranium workers employed for at least 30 days (1951-1985), and followed through 2004. METHODS: Cohort mortality was evaluated through standardised mortality ratios (SMR). Linear excess relative risk (ERR) regression models examined associations between cause-specific mortality and exposures to internal ionising radiation from uranium deposition, external gamma and x-ray radiation, and radon decay products, while adjusting for non-radiologic covariates. RESULTS: Person-years at risk totalled 236 568 (mean follow-up 37 years), and 43% of the cohort had died. All-cause mortality was below expectation only in salaried workers. Cancer mortality was significantly elevated in hourly males, primarily from excess lung cancer (SMR=1.25, 95% CI 1.09 to 1.42). Cancer mortality in salaried males was near expectation, but lymphohaematopoietic malignancies were significantly elevated (SMR=1.52, 95% CI 1.06 to 2.12). A positive dose-response relation was observed for intestinal cancer, with a significant elevation in the highest internal organ dose category and a significant dose-response with organ dose from internal uranium deposition (ERR=1.5 per 100 µGy, 95% CI 0.12 to 4.1). CONCLUSIONS: A healthy worker effect was observed only in salaried workers. Hourly workers had excess cancer mortality compared with the US population, although there was little evidence of a dose-response trend for any cancer evaluated except intestinal cancer. The association between non-malignant respiratory disease and radiation dose observed in previous studies was not apparent, possibly due to improved exposure assessment, different outcome groupings, and extended follow-up.

Effects of HEPA air cleaners on unscheduled asthma visits and asthma symptoms for children exposed to secondhand tobacco smoke.

OBJECTIVE: The goal was to test the effects of high-efficiency, particulate-arresting (HEPA) air cleaners on unscheduled asthma visits and symptoms among children with asthma exposed to secondhand smoke. METHODS: We enrolled 225 eligible children who were 6 to 12 years of age, had physician-diagnosed asthma, and were exposed to ≥5 cigarettes per day. We conducted a double-blind, randomized trial. Children were assigned randomly to receive 2 active or inactive HEPA air cleaners. RESULTS: Of 225 enrolled children, 110 (49%) were assigned to the intervention group and 115 (51%) to the control group; 215 (95%) completed the trial. During the trial, there were 42 fewer unscheduled asthma visits among children in the intervention group (18.5% [95% confidence interval: 1.25%-82.75%]; P = .043), compared with those in the control group, after adjustment for baseline differences. There was a significant difference in the reductions of levels of particles of >0.3 µm according to group assignment; there was a 25% reduction in particle levels in the intervention group, compared with a 5% reduction in the control group (P = .026). There were no significant differences in parent-reported asthma symptoms, exhaled nitric-oxide levels, air nicotine levels, or cotinine levels according to group assignment. CONCLUSIONS: These results hold promise for using HEPA air cleaners as part of a multifaceted strategy to reduce asthma morbidity, but further research is necessary before they can be recommended routinely for the medical management of asthma.

Dietary patterns associated with fat and bone mass in young children.

BACKGROUND: Obesity and osteoporosis have origins in childhood, and both are affected by dietary intake and physical activity. However, there is little information on what constitutes a diet that simultaneously promotes low fat mass and high bone mass accrual early in life. OBJECTIVE: Our objective was to identify dietary patterns related to fat and bone mass in children during the age period of 3.8-7.8 y. DESIGN: A total of 325 children contributed data from 13 visits over 4 separate study years (age ranges: 3.8-4.8, >4.8-5.8, >5.8-6.8, and >6.8-7.8 y). We performed reduced-rank regression to identify dietary patterns related to fat mass and bone mass measured by dual-energy X-ray absorptiometry for each study year. Covariables included race, sex, height, weight, energy intake, calcium intake, physical activity measured by accelerometry, and time spent viewing television and playing outdoors. RESULTS: A dietary pattern characterized by a high intake of dark-green and deep-yellow vegetables was related to low fat mass and high bone mass; high processed-meat intake was related to high bone mass; and high fried-food intake was related to high fat mass. Dietary pattern scores remained related to fat mass and bone mass after all covariables were controlled for (P < 0.001-0.03). CONCLUSION: Beginning at preschool age, diets rich in dark-green and deep-yellow vegetables and low in fried foods may lead to healthy fat and bone mass accrual in young children.

Determinants of serum cotinine and hair cotinine as biomarkers of childhood secondhand smoke exposure.

Understanding the determinants of childhood secondhand smoke (SHS) exposure is important in measuring and preventing exposure to this widespread environmental contaminant. We evaluated the ability of a broad set of factors to explain variability in serum cotinine, reflecting recent exposure, and hair cotinine, reflecting longer-term exposure. We included repeated measures from 223 elementary-school-age asthmatic children residing with a smoker. We used a manual model-building approach and likelihood ratio tests to select a model predicting each biomarker, and also compared the predictive ability of determinants using Akaike Information Criteria. Potential determinants included a comprehensive parent questionnaire, household nicotine, home ventilation characteristics, exposure in vehicles and others' homes, child demographics, and family social class. Variables in each of these categories remained in the final model for both serum (R(2) of 0.61) and hair cotinine (R(2) of 0.45). A comprehensive set of factors was required to best predict cotinine. Studies should use biomarkers for the best quantitative assessment of SHS exposure. Hair cotinine may be a problematic measure because it was highly influenced by racial differences that were unexplained by SHS exposure. When biospecimen collection is not possible, a household nicotine measurement is warranted. If only questionnaires are available, multiple questions are required to best characterize exposure, such as number of cigarettes, hours spent in a room with concurrent smoking, maternal smoking, and approximate home size.

Mortality from lymphohematopoietic malignancies and brain cancer among embalmers exposed to formaldehyde.

BACKGROUND: Excess mortality from lymphohematopoietic malignancies, in particular myeloid leukemia, and brain cancer has been found in surveys of anatomists, pathologists, and funeral industry workers, all of whom may have worked with formaldehyde. We investigated the relation of mortality to work practices and formaldehyde exposure levels among these professionals to address cancer risk in the funeral industry. METHODS: Professionals employed in the funeral industry who died between January 1, 1960, and January 1, 1986, from lymphohematopoietic malignancies (n = 168) or brain tumors (n = 48) (ie, case subjects) were compared with deceased matched control subjects (n = 265) with regard to lifetime work practices and exposures in the funeral industry, which were obtained by interviews with next of kin and coworkers, and to estimated levels of formaldehyde exposure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by use of logistic regression. All statistical tests were two-sided. RESULTS: Mortality from myeloid leukemia increased statistically significantly with increasing number of years of embalming (P for trend = .020) and with increasing peak formaldehyde exposure (P for trend = .036). Compared with subjects who performed fewer than 500 lifetime embalmings, mortality from myeloid leukemia was elevated among those who performed embalmings for more than 34 years (OR = 3.9, 95% CI = 1.2 to 12.5, P = .024), who performed more than 3068 embalmings (OR = 3.0, 95% CI = 1.0 to 9.2, P = .057), and those whose estimated cumulative formaldehyde exposure exceeded 9253 parts per million-hours (OR = 3.1; 95% CI = 1.0 to 9.6, P = .047). These exposures were not related to other lymphohematopoietic malignancies or to brain cancer. CONCLUSION: Duration of embalming practice and related formaldehyde exposures in the funeral industry were associated with statistically significantly increased risk for mortality from myeloid leukemia.

Age of greatest susceptibility to childhood lead exposure: a new statistical approach.

BACKGROUND: Susceptibility to lead toxicity is often assumed to be greatest during early childhood (e.g., 2 years of age), but recent studies suggest that blood lead concentrations (BPb) taken at 5-7 years of age are more strongly associated with IQ. OBJECTIVE: We aimed to determine the age of greatest susceptibility to lead exposure using an innovative statistical approach that avoids the problem of correlated serial BPb measurements. METHODS: We analyzed two cohorts of children that were followed from infancy to 6 years of age in Rochester, New York (n = 211), and Cincinnati, Ohio (n = 251). Serial BPb levels were measured and IQ tests were done when children were 6 years of age. After adjustment for relevant covariates, the ratio of 6-year BPb to 2-year BPb was added to the multiple regression model to test whether the pattern of BPb profiles during childhood had additional effect on IQ. RESULTS: The ratio of BPb at 6 years to the BPb at 2 years showed a strong effect on IQ (p < .001) when added to the multiple regression model that included the average childhood BPb. IQ decreased by 7.0 points for children whose BPb at 6 years of age was 50% greater than that at 2 years compared with children whose 6-year BPb was 50% less than their 2-year BPb. Similarly, criminal arrest rates were a factor of 3.35 higher for those subjects whose 6-year BPb was 50% higher than their 2-year BPb. CONCLUSIONS: We conclude that 6-year BPb is more strongly associated with cognitive and behavioral development than is BPb measured in early childhood.

Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children.

Exhaled nitric oxide (FeNO), a measure of airway inflammation, is being explored as a tool to guide asthma management in children. Investigators have identified associations of genetic polymorphisms in nitric oxide synthase genes (NOS1 and NOS3) with FeNO levels; however, none have explored whether these polymorphisms modify the relationship of environmental exposures with FeNO. The objective of this project was to evaluate the association of NOS polymorphisms and environmental exposures with FeNO levels among children with asthma. We conducted a 12-month prospective cohort study of 225 tobacco-smoke exposed children (6-12 years) with doctor-diagnosed asthma. We assessed environmental exposures (tobacco, indoor allergens, & airborne particulates), polymorphisms in NOS1 (an intronic AAT tandem repeat) and NOS3 (G894T), and FeNO levels. There was no association of NOS1 or NOS3 polymorphisms with FeNO levels. There were no significant interactions of environmental exposures and the NOS1 polymorphism with FeNO levels. In contrast, there was an interaction of the NOS3 polymorphism and airborne nicotine concentration with FeNO levels (P = 0.01). Among GG genotype individuals, nicotine exposure did not affect FeNO levels; however, among individuals with at least one T allele, higher nicotine exposure was associated with lower FeNO levels (approximately 5 ppb decrease from the lowest to the highest quartile). We conclude that genetic differences may explain some of the conflicting results in studies of the effects of tobacco smoke exposure on FeNO levels and may make FeNO interpretation difficult for a subset of children with asthma.

Epidemiology of necrotizing enterocolitis temporal clustering in two neonatology practices.

OBJECTIVE: To develop a statistical method for defining clusters of necrotizing enterocolitis (NEC) cases in the neonatal intensive care unit (NICU). STUDY DESIGN: The study group included 2782 infants weighing 401 to 1500 g at birth born between 1996 and 2004. NEC was defined as Bell stage II or III. Two statistical methods were used to define "disease clusters": a modified scan test and a comparison of observed and expected incidence density rates (IDRs) of NEC at each NICU. RESULTS: The proportion of infants with NEC was similar in the 2 NICUs (7.1% vs 7.7%; P = .6), as was the expected IDR of NEC (1.39/1000 patient-days vs 1.32/1000 patient-days; P = .72). Twelve temporal clusters of NEC were identified in the 2 NICUs, representing 18% of 203 total NEC cases during the study period. No seasonal/secular trends were noted for NEC rates or identified clusters. Potential NEC clusters of > or =3 cases at either NICU had a >75% likelihood of being a true NEC cluster. CONCLUSIONS: No operational definition of NEC cluster exists. This study introduces methods to use in prospective surveillance and to guide studies investigating etiologic relevance. Using the proposed methods, statistically significant clusters (ie, potential outbreaks) of NEC within NICUs can be identified early, providing an opportunity for early implementation of cluster investigation protocols.

Genome screen to detect linkage to common susceptibility genes for intracranial and aortic aneurysms.

BACKGROUND AND PURPOSE: Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study. METHODS: Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable). RESULTS: Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively. CONCLUSIONS: Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.

Views of treatment decision making from adolescents with chronic illnesses and their parents: a pilot study.

OBJECTIVE: Shared decision making may increase satisfaction with health care and improve outcomes, but little is known about adolescents' decision-making preferences. The primary purpose of this study is to describe the decision-making preferences of adolescents with chronic illnesses and their parents, and the extent to which they agree. DESIGN: Survey. SETTING AND PARTICIPANTS: Participants were 82 adolescents seen at one of four paediatric chronic illness subspecialty clinics and 62 of their parents. MAIN VARIABLES: Predictor variables include sociodemographics, health parameters, risk behaviour, and physical and cognitive development. The main outcome variable is preferences for decision-making style. RESULTS AND CONCLUSIONS: When collapsed into three response categories, nearly equal percentages of adolescents (37%) and parents (36%) preferred shared decision making. Overall, the largest proportion of adolescents (46%) and parents (53%) preferred passive decision making compared to active or shared decision making. Across five response choices, 33% of pairs agreed. Agreement was slight and not significant. Improved general health perceptions (OR=0.76, 95% CI=0.59-0.99) and improved behaviour (OR=0.75, 95% CI=0.56-0.99) were significantly associated with parents' preferences for less active decision making. Older age was significantly associated with agreement (OR 1.58, 95% CI=1.09-2.30) between parents and adolescents. The paucity of significant predictor variables may indicate physicians need to inquire directly about patient and parent preferences.

Patient-specific decision modeling to guide the use of drotrecogin alpha (activated) in patients with severe sepsis.

PURPOSE: The expected benefit of treating severe sepsis with drotrecogin alpha (activated) for an individual patient may depend upon several clinical factors including disease severity. Our objective was to create a decision support tool incorporating patient-specific inputs to estimate the balance between treatment risks and benefits for individual patients with severe sepsis. MATERIALS AND METHODS: Logistic regression models were developed to calculate patient-specific mortality risk with and without treatment, which were then used as inputs into a 75-state Markov model. Patient-specific inputs included patient age, sex, and 12 readily available clinical characteristics. RESULTS: The expected benefit from drotrecogin alpha (activated) treatment was most dependent upon the underlying disease severity. For example, for a 56-year-old white man with severe sepsis and a 28-day mortality risk of 29%, the model predicted a treatment-related gain of 1.2 quality-adjusted life years (17.3 vs 16.1). Probabilistic sensitivity analyses demonstrated that this patient would benefit from therapy 85% of the time. CONCLUSIONS: A customizable decision model using patient-specific inputs can be used to inform the treatment decision when considering the use of drotrecogin alpha (activated) therapy by weighing the risks vs the benefits of therapy in the treatment of severe sepsis.

Influenza vaccine effectiveness among children 6 to 59 months of age during 2 influenza seasons: a case-cohort study.

OBJECTIVE: To measure vaccine effectiveness (VE) in preventing influenza-related health care visits among children aged 6 to 59 months during 2 consecutive influenza seasons. DESIGN: Case-cohort study estimating effectiveness of inactivated influenza vaccine in preventing inpatient/outpatient visits (emergency department [ED] and outpatient clinic). We compared vaccination status of laboratory-confirmed influenza cases with a cluster sample of children from a random sample of practices in 3 counties (subcohort) during the 2003-2004 and 2004-2005 seasons. SETTING: Counties encompassing Rochester, New York, Nashville, Tennessee, and Cincinnati, Ohio. PARTICIPANTS: Children aged 6 to 59 months seen in inpatient/ED or outpatient clinic settings for acute respiratory illnesses and community-based subcohort comparison. Main Exposure Influenza vaccination. MAIN OUTCOME MEASURES: Influenza vaccination status of cases vs subcohort using time-dependent Cox proportional hazards models to estimate VE in preventing inpatient/ED and outpatient visits. RESULTS: During the 2003-2004 and 2004-2005 seasons, 165 and 80 inpatient/ED and 74 and 95 outpatient influenza cases were enrolled, while more than 4500 inpatient/ED and more than 600 outpatient subcohorts were evaluated, respectively. In bivariate analyses, cases had lower vaccination rates than subcohorts. However, significant influenza VE could not be demonstrated for any season, age, or setting after adjusting for county, sex, insurance, chronic conditions recommended for influenza vaccination, and timing of influenza vaccination (VE estimates ranged from 7%-52% across settings and seasons for fully vaccinated 6- to 59-month-olds). CONCLUSION: In 2 seasons with suboptimal antigenic match between vaccines and circulating strains, we could not demonstrate VE in preventing influenza-related inpatient/ED or outpatient visits in children younger than 5 years. Further study is needed during years with good vaccine match.