rs11670527 Upstream of ZNF264 Associated with Body Mass Index in the Coriell Personalized Medicine Collaborative.

INTRODUCTION: the effects of obesity on health are a concern for the military as they affect the fitness to serve of active service members, increase costs to the Military Health System, and reduce quality of life for veterans and beneficiaries. Although obesity can be influenced by behavioral and environmental factors, it has also been shown to be associated with genetic risk factors that are not fully understood. MATERIALS AND METHODS: we performed a genome-wide association study of 5,251 participants in the Coriell Personalized Medicine Collaborative, which includes 2,111 Air Force participants. We applied a generalized linear model, using principal component analysis to account for population structure, and analyzed single-variant associations with body mass index (BMI) as a continuous variable, using a Bonferroni-corrected P-value threshold to account for multiplicity. RESULTS: we identified one genome-wide significant locus, rs11670527, upstream of the ZNF264 gene on chromosome 19, associated with BMI. CONCLUSIONS: the finding of an association between rs11670527 and BMI adds to the growing body of literature characterizing the complex genetics of obesity. These efforts may eventually inform personalized interventions aimed at achieving and maintaining healthy weight.

Individuals with CYP2C8 and CYP2C9 reduced metabolism haplotypes self-adjusted ibuprofen dose in the Coriell Personalized Medicine Collaborative.

OBJECTIVES: The objectives of this study were to determine whether differences in CYP2C8 and CYP2C9 haplotype influence the dose of ibuprofen self-administered by individuals, and to examine the potential relationship between CYP2C8 and CYP2C9 reduced metabolism haplotypes and adverse events. PARTICIPANTS AND METHODS: We investigated relationships between genetic variations in CYP2C8 and CYP2C9 and ibuprofen use, dose, and side effects (reported by questionnaire) in 445 participants from the Coriell Personalized Medicine Collaborative. RESULTS: Carriers of reduced metabolism haplotypes for CYP2C8 (*2, *3, *4) and CYP2C9 (*2, *3) were significantly (P=0.0171) more likely than those lacking these variants to take less than the recommended dose of ibuprofen, after controlling for sex, age, race, and cohort. In contrast to ibuprofen dose, there were no differences in ibuprofen use frequency or reported side effects based on haplotype. However, there are often no early signs of acute kidney injury, the most serious side effect of elevated ibuprofen exposure. CONCLUSION: These results suggest a subset of individuals with genetic variation in CYP2C8 and CYP2C9 recognize that they obtain adequate drug efficacy with lower ibuprofen doses, or take lower doses due to prior side effects. However, most (82.6%) individuals with reduced metabolism haplotypes nonetheless took recommended or higher doses, potentially putting them at increased risk for side effects.

Precision Military Medicine: Conducting a multi-site clinical utility study of genomic and lifestyle risk factors in the United States Air Force.

Following several years enrolling disease-specific and otherwise healthy cohorts into the Coriell Personalized Medicine Collaborative, a prospective study aimed at evaluating the clinical utility of personal genomic information for common complex disease and pharmacogenomics, the Coriell Personalized Medicine Collaborative expanded to create a military cohort, specifically, the United States Air Force. Initial recruitment focused on Air Force Medical Service personnel and later expanded to include all Active Duty Air Force members and beneficiaries. Now in its 6th year, the study has produced a wide variety of insights, including optimal study design for military-sponsored genomic research, and discussion on genetic information sharing between and amongst Air Force study participants, civilian and military researchers, and the United States Department of Defense. Over the longer term, analyses will further contribute to the development of policies and processes relevant to clinical decision support and data sharing within the US military, and on-going work with the Air Force Medical Service sub-cohort will generate critical insights into how best to deploy useful genomic information in clinical care. Here we discuss challenges faced and critical success factors for military-civilian collaborations around genomic research.

Multilevel Provider-Based Sampling for Recruitment of Pregnant Women and Mother-Newborn Dyads.

OBJECTIVE: In 2010, the National Children's Study launched 3 alternative recruitment methods to test possible improvements in efficiency compared with traditional household-based recruitment and participant enrollment. In 2012, a fourth method, provider-based sampling (PBS), tested a probability-based sampling of prenatal provider locations supplemented by a second cohort of neonates born at a convenience sample of maternity hospitals. METHODS: From a sampling frame of 472 prenatal care provider locations and 59 maternity hospitals, 49 provider and 7 hospital locations within or just outside 3 counties participated in study recruitment. During first prenatal care visits or immediately postdelivery at these locations, face-to-face contact was used to screen and recruit eligible women. RESULTS: Of 1450 screened women, 1270 were eligible. Consent rates at prenatal provider locations (62%-74% by county) were similar to those at birth locations (64%-77% by county). During 6 field months, 3 study centers enrolled a total prenatal cohort of 530 women (the majority in the first trimester) and during 2 months enrolled a birth cohort of an additional 320 mother-newborn dyads. As personnel became experienced in the field, the time required to enroll a woman in the prenatal cohort declined from up to 200 hours to 50 to 100 hours per woman recruited. CONCLUSIONS: We demonstrated that PBS was feasible and operationally efficient in recruiting a representative cohort of newborns from 3 diverse US counties. Our findings suggest that PBS is a practical approach to recruit large pregnancy and birth cohorts across the United States.

Genomic medicine in the military.

The announcement of the Precision Medicine Initiative was an important step towards establishing the use of genomic information as part of the wider practice of medicine. The US military has been exploring the role that genomic information will have in health care for service members (SMs) and its integration into the continuum of military medicine. An important part of the process is establishing robust protections to protect SMs from genetic discrimination in the era of exome/genome sequencing.

Overview of 'Omics Technologies for Military Occupational Health Surveillance and Medicine.

Systems biology ('omics) technologies are emerging as tools for the comprehensive analysis and monitoring of human health. In order for these tools to be used in military medicine, clinical sampling and biobanking will need to be optimized to be compatible with downstream processing and analysis for each class of molecule measured. This article provides an overview of 'omics technologies, including instrumentation, tools, and methods, and their potential application for warfighter exposure monitoring. We discuss the current state and the potential utility of personalized data from a variety of 'omics sources including genomics, epigenomics, transcriptomics, metabolomics, proteomics, lipidomics, and efforts to combine their use. Issues in the "sample-to-answer" workflow, including collection and biobanking are discussed, as well as national efforts for standardization and clinical interpretation. Establishment of these emerging capabilities, along with accurate xenobiotic monitoring, for the Department of Defense could provide new and effective tools for environmental health monitoring at all duty stations, including deployed locations.

Impact of preconception enrollment on birth enrollment and timing of exposure assessment in the initial vanguard cohort of the U.S. National Children's Study.

BACKGROUND: The initial vanguard cohort of the U.S. National Children's Study was a pregnancy and birth cohort study that sought to enroll some women prior to pregnancy, and to assess exposures early in pregnancy. METHODS: During the recruitment phase (2009-2010), geographically based sampling was used to recruit women early in pregnancy and women not currently pregnant, not using contraception and heterosexually active. We assessed the following outcomes for women enrolled preconception and early in pregnancy: yield of births; demographic characteristics of births for different enrollment groups; time to pregnancy for preconception women; and the timing of study visits for exposure assessment. RESULTS: 1399 women were recruited into the initial vanguard cohort: 429 preconception (198 trying for pregnancy, and 231 not trying) and 970 already pregnant. There were 1135 pregnancies (81% of women) and 922 newborns enrolled (81% of pregnancies) through September 2012. Preconception women represented 30.6% of women enrolled, and contributed 14.5% of births. Among women who gave birth, and who had enrolled preconception trying for pregnancy, 67.3% were white non-Hispanic, compared to 50.0% of preconception women not trying for pregnancy, and 61.5% of pregnant women. Women enrolled preconception who were trying for pregnancy had higher cumulative probability of pregnancy at one year compared to women not trying (adjusted 86% versus 56%). Of 165 women enrolled preconception who became pregnant, 19% had a study visit within 30 days of conception. By 10.5 weeks after conception, 75% of women enrolled preconception had completed a pregnancy study visit; for women enrolled pregnant, the 75% threshold was reached at 28.4 weeks. CONCLUSIONS: There were demographic differences in births from women enrolled preconception trying for pregnancy, preconception not trying for pregnancy, or during pregnancy. Time to pregnancy was shorter for women actively trying for pregnancy. Most women enrolled preconception did not have exposure assessment within 30 days of conception, but they did have exposure assessment much earlier during pregnancy than women who enrolled during pregnancy.

Recruitment of women in the National Children's Study Initial Vanguard Study.

The initial Vanguard Study of the National Children's Study was conducted during 2009-2010 in 7 locations in the United States. A goal was to evaluate the feasibility and yield of a household-based sampling design to recruit pregnant women. A multistage area probability sampling design was used to identify study locations (generally, counties) that were subsequently divided into smaller geographical units, termed segments. Between 7 and 18 segments were selected in each location, and dwelling units within segments were listed. A household-based recruitment process was implemented, which included enumeration of households to identify age-eligible women, pregnancy screening to identify pregnant women eligible for immediate enrollment and nonpregnant women for telephone follow-up, and administration of informed consent to eligible women. After a recruitment period of 17-20 months, 67,181 (89%) households were enumerated, which identified 34,172 (88%) age-eligible women to whom the pregnancy screener was administered. Among those who completed the screener, 2,285 women became eligible for enrollment, of whom 1,399 (61%) enrolled. Although response rates were fairly high at initial contact and among pregnant women, the overall yield was lower than anticipated. In particular, telephone follow-up of nonpregnant women was not a practicable strategy for prospective recruitment of newly pregnant women.

Unintentional injuries among youth with developmental disabilities in the United States, 2006-2007.

We examined unintentional injury among youth with and without developmental disabilities. Our nationally representative sample included 6369 injured youth, aged 0-17 years, who were seen in one of the 63 US hospital emergency rooms that participated in the National Electronic Injury Surveillance System - All Injury Program (NEISS-AIP) in 2006-2007. Parents or guardians of injured youth were interviewed by telephone after the hospital visit to ascertain disability status. Denominator data were obtained from the National Health Interview Survey. Leading causes of injury were comparable for youth with and without disability. Injury rates (per 100 youth per year) were also comparable [10.4; 95% confidence interval (CI) 7.8, 13.0 and 10.5; 95% CI 8.2, 12.9, for youth with and without disability, respectively]. When examined by specific disability, the rate ratio for youth with learning disabilities versus youth without learning disability was 1.57 (95% CI 1.04, 2.10), which may represent a subgroup for targeted interventions.

Preventing young children's injuries: analysis of data from a population-based surveillance.

The objective of this study is to determine prevention strategies for potentially serious injury events among children younger than 3 years of age based upon circumstances surrounding injury events. Surveillance was conducted on all injuries to District of Columbia (DC) residents less than 3 years old that resulted in an Emergency Department (ED) visit, hospitalization, or death for 1 year. Data were collected through abstraction of medical records and interviews with a subset of parents of injured children. Investigators coded injury-related events for the potential for death or disability. Potential prevention strategies were then determined for all injury events that had at least a moderate potential for death or disability and sufficient detail for coding (n = 425). Injury-related events included 10 deaths, 163 hospitalizations, and 2,868 ED visits (3,041 events in total). Of the hospitalizations, 88% were coded as moderate or high potential for disability or death, versus only 21% of the coded ED visits. For potentially serious events, environmental change strategies were identified for 47%, behavior change strategies for 77%, and policy change strategies for 24%. For 46% of the events more than one type of prevention strategy was identified. Only 8% had no identifiable prevention strategy. Prevention strategies varied by specific cause of injury. Potential prevention strategies were identifiable for nearly all potentially serious injury events, with multiple potential prevention strategies identified for a large fraction of the events. These findings support developing multifaceted prevention approaches informed by community-based injury surveillance.

Association between swimming lessons and drowning in childhood: a case-control study.

OBJECTIVE: To estimate the association between swimming lessons and the risk of drowning among children aged 1 to 19 years. DESIGN: Case-control study. SETTING: Cases were identified from medical examiners'/coroners' offices between mid-2003 and mid-2005. Jurisdictions included the states of Maryland and North Carolina, 14 districts (33 counties) in Florida, 3 counties in California, 1 county in Texas, and 1 county in New York. PARTICIPANTS: Cases were children and adolescents aged 1 to 19 years who died of unintentional drowning. Interviews were conducted with 88 families of children who drowned and 213 matched controls. Main Exposure Swimming lessons. Main Outcome Measure Death due to unintentional drowning. Drownings that were intentional, of undetermined intent, or that occurred under conditions in which swimming ability was unlikely to impact risk (eg, in ice water or bathtubs) were excluded. RESULTS: Of the 61 cases in the 1- to 4-year age group, 2 (3%) had participated in formal swimming lessons vs 35 of 134 matched controls (26%) (adjusted odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97). Among the 27 cases aged 5 to 19 years, 7 (27%) had ever taken formal swimming lessons vs 42 of 79 matched controls (53%) (adjusted OR, 0.36; 95% CI, 0.09-1.51). In adjusted analyses, there was no statistically significant association between informal instruction and drowning risk. CONCLUSIONS: Participation in formal swimming lessons was associated with an 88% reduction in the risk of drowning in the 1- to 4-year-old children, although our estimates were imprecise and 95% CIs included risk reductions ranging from 3% to 99%.

Effectiveness of a mentor-implemented, violence prevention intervention for assault-injured youths presenting to the emergency department: results of a randomized trial.

OBJECTIVE: The goal was to assess the impact of a mentor-implemented, violence prevention intervention in reducing aggression, fighting, and reinjury among assault-injured youths. METHODS: In a randomized, controlled trial performed in the emergency departments of 2 large urban hospitals, 10- to 15-year-old youths who presented with peer assault injuries were recruited and randomly assigned to intervention and comparison groups. In the intervention group, youths received a mentor, who implemented a 6-session problem-solving curriculum, and parents received 3 home visits with a health educator, to discuss family needs and to facilitate service use and parental monitoring. The comparison group received a list of community resources, with 2 follow-up telephone calls to facilitate service use. Youths and parents were interviewed at baseline and at 6 months, for assessment of attitudes about violence, risk factors, fighting, and repeat injury. RESULTS: A total of 227 families were recruited, with 23% refusing participation and 4% providing partial interview completion. A total of 166 families were enrolled, with 87 assigned to the intervention group and 79 to the comparison group; 118 (71%) completed both youth and parent follow-up interviews, and 113 had usable data. The intervention and comparison groups were not significantly different at baseline with respect to demographic features or risk factors, except for increased knife-carrying and fewer deviant peers in the intervention group. After adjustment for baseline differences, there was a trend toward significant program effects, including reduced misdemeanor activity and youth-reported aggression scores and increased youth self-efficacy. Program impact was associated with the number of intervention sessions received. CONCLUSIONS: A community-based, mentor-implemented program with assault-injured youths who presented to the emergency department trended in the direction of decreased violence, with reduced misdemeanors and increased self-efficacy.

Participation of next of kin in research following sudden, unexpected death of a child.

OBJECTIVE: To assess parents' perceptions of their experience being interviewed after the sudden, unexpected death of their child. DESIGN: Case-control study in which cases were victims of unintentional drowning. SETTING: Households of recent drowning victims in 6 states in the United States. PARTICIPANTS: Caregivers (primarily parents) of 87 cases and 491 matched controls were interviewed via telephone about their child. MAIN EXPOSURE: Recent death of a child by unintentional drowning. MAIN OUTCOME MEASURES: Degree of stress related to interview, perception of interview length, and participants' views about their willingness to participate in this type of interview again, given their experience with the current interview. RESULTS: Although case participants were more likely than controls to perceive the interview as somewhat or very stressful (odds ratio, 3.64; 95% confidence interval, 1.67-7.96), most of the case participants (87.2%) and controls (96.1%) perceived the interview to be not at all or a little stressful. A greater percentage of controls (37.8%) found the interview to be too long, compared with case participants (20.9%). Among case participants, perceived stress during the interview and the perceived length of the interview were not associated with willingness to participate again. Both of these associations were significant (P<.001) for controls. CONCLUSIONS: Caregivers who chose to participate in the study generally rated their experiences as not very stressful. Most of the caregivers indicated that they would be willing to participate again in a similar study.

Beliefs about the appropriate age for initiating toilet training: are there racial and socioeconomic differences?

OBJECTIVE: To examine racial and socioeconomic differences in parental beliefs about the appropriate age at which to initiate toilet training. STUDY DESIGN: A cross-sectional survey of 779 parents visiting child health providers in 3 clinical sites in Washington, DC and the surrounding metropolitan area completed a self-report survey. The main outcome variable was parental beliefs about the appropriate age at which to initiate toilet training. Using multiple linear regression, differences in beliefs were assessed in relation to race, family income, parental education, parental age, and age of the oldest and youngest children. RESULTS: Among respondents, parents felt that the average age at which toilet training should be initiated was 20.6 months (+/-7.6 months), with a range of 6 to 48 months. Caucasian parents believed that toilet training should be initiated at a significantly later age (25.4 months) compared with both African-American parents (18.2 months) and parents of other races (19.4 months). In the multiple regression model, factors predicting belief in when to initiate toilet training were Caucasian race and higher income. CONCLUSIONS: Race and income were independent predictors of belief in age at which to initiate toilet training. More research is needed to determine what factors contribute to toilet training practices in diverse populations.

Assault-injured adolescents presenting to the emergency department: causes and circumstances.

OBJECTIVES: To describe the causes and circumstances of conflict leading to assault injury among urban youth seeking care in the emergency department. METHODS: The authors conducted in-person and telephone interviews with a convenience sample of 143 youth aged 12-19 years presenting to two urban emergency departments with an interpersonal assault injury. Patients were interviewed about the nature and circumstances of their injury. Descriptive analysis was performed, including stratified analysis by gender, age (12-15 vs. 16-19 years), and weapon use. RESULTS: Seventy percent of patients knew or knew of the person(s) who injured them; most were friends, classmates, or acquaintances. More than half of the injuries (56%) were related to a past disagreement. Among assaults related to a past disagreement, 33% of patients had previous arguments with their assailant, 16% had previous fights, and 14% had previous weapons threats. Twenty-nine percent had been previously threatened, and 11% had previously threatened their assailant. Twenty-eight percent of patients believed they helped to cause the injury by provoking a fight or letting down their guard. Nearly two thirds (64%) believed there were things they could change to prevent future injury, including staying away from dangerous situations and bad influences or controlling their tempers. CONCLUSIONS: Most assault injuries among adolescents involved past disagreements with people they knew. Many injured youth were mutually involved in conflict before their injury. Over time, many victims and perpetrators may be interchangeable. These data may help inform emergency department-based interventions to prevent assault injury.

Swimming pool drownings among US residents aged 5-24 years: understanding racial/ethnic disparities.

OBJECTIVE: We examined circumstances surrounding swimming pool drownings among US residents aged 5 to 24 years to understand why Black males and other racial/ethnic groups have high drowning rates. METHODS: We obtained data about drowning deaths in the United States (1995-1998) from death certificates, medical examiner reports, and newspaper clippings collected by the US Consumer Product Safety Commission. RESULTS: During the study period, 678 US residents aged 5 to 24 years drowned in pools. Seventy-five percent were male, 47% were Black, 33% were White, and 12% were Hispanic. Drowning rates were highest among Black males, and this increased risk persisted after we controlled for income. The majority of Black victims (51%) drowned in public pools, the majority of White victims (55%) drowned in residential pools, and the majority of Hispanic victims (35%) drowned in neighborhood pools (e.g., an apartment complex pool). Foreign-born males also had an increased risk for drowning compared with American-born males. CONCLUSIONS: Targeted interventions are needed to reduce the incidence of swimming pool drownings across racial/ethnic groups, particularly adult supervision at public pools.

Flammability of common ocular lubricants in an oxygen-rich environment.

PURPOSE: Approximately 100 surgical fires take place in the United States each year. Recently, an ophthalmic lubricant was blamed for burning a child's eye while oxygen was administered during surgery. This study sought to determine whether four common ocular lubricants would ignite and sustain combustion in an oxygen-rich or standard room air environment. METHODS: A model head was modified to allow placement of a cow eye and marked with 1-inch gradations from the eye. A nasal cannula supplied room air and 100% oxygen at flow rates of 0, 2, 4, and 6 L/minute. Four common ocular lubricants were chosen and placed on the eye before attempted ignition. The ignition source (an AccuTemp disposable electrocautery unit and unipolar and bipolar cautery set at 10, 20, and 30 watts) was brought down from the hairline toward the cannula. Each lubricant was tested with each ignition source and each room air/oxygen flow rate. RESULTS: None of the ocular lubricants ignited under any of the experimental environments tested. A small surface flame was noted with the AccuTemp electrocautery unit, but it did not create a flash fire during the experiment. CONCLUSIONS: The ocular lubricants in this experiment showed no detectable tendency to ignite, even with direct application of the ignition source. Factors such as body hair or oxygen pooling likely provided the conditions necessary for the surgical fire. Most importantly, the ophthalmic lubricants tested actually protected the corneal epithelium and decreased damage to the conjunctiva and lids.

Level of maternal IgG anti-group B streptococcus type III antibody correlated with protection of neonates against early-onset disease caused by this pathogen.

The present study estimates the level of maternal immunoglobulin (Ig) G anti-group B streptococcus (GBS) type III required to protect neonates against early-onset disease (EOD) caused by this pathogen. Levels of maternal serum IgG anti-GBS type III, measured by enzyme-linked immunosorbent assay, in 26 case patients (neonates with EOD caused by GBS type III) and 143 matched control subjects (neonates colonized by GBS type III who did not develop EOD) of > or = 34 weeks gestation were compared. The probability of EOD decreased with increasing levels of maternal IgG anti-GBS type III (P = .01). Neonates whose mothers had > or = 10 microg/mL IgG anti-GBS type III had a 91% lower risk for EOD, compared with those whose mothers had levels of < 2 microg/mL. A vaccine that induces IgG anti-GBS type III levels of > or = 10 microg/mL in mothers can be predicted to offer a significant degree of protection against EOD caused by this pathogen.