Faculty Bibliography

OBJECTIVES: To analyse emergency department-based data on paediatric traumatic brain injury (TBI). METHODS: This study constructed a retrospective cohort of 493,890 children who were born in New York City between 1999-2007 and who were enrolled in the New York Medicaid programme at the time of their birth and followed these children from birth to the end of 2007. RESULTS: There were 62,089 injury-related emergency department visits, of which 1290 had ICD-9 codes consistent with TBI. Children with TBI were more likely to be male (59.4% vs 51.4%) and Hispanic (43.9% vs 26.3%) than those in the underlying birth cohort and were more than twice as likely to be admitted to the hospital for inpatient care (RR = 2.4, 95% CI = 2.2, 2.6). The most commonly listed cause of injury was falls (58.3%). Spatially-smoothed risk estimates indicated that some areas of the city are associated with a greater risk of paediatric TBI than others. CONCLUSIONS: Emergency department data can be used to describe paediatric TBI in ways not easily available through more routinely collected administrative health data. This information can be used to target prevention and control efforts.

BACKGROUND: Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induces neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been analyzed using existing data sets, and these studies produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at the Columbia University Medical Center (CUMC) and Children's Hospital of Boston (CHB) for the PANDA project. METHODS: The PANDA project uses an ambidirectional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs from 6 to 11 years of age. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair before the age of 36 months and the unexposed siblings had no anesthesia before the age of 36 months. All the sibling pairs were English speaking and were 36 weeks of gestational age or older. Each sibling pair underwent a direct testing using the Wechsler Abbreviated Scale of Intelligence (WASI) and the NEuroPSYchological Assessment, second edition (NEPSY II), and the parents completed questionnaires related to behavior using CBCL and Conners rating. Data are presented as means+/-SD. We conducted descriptive analyses of the demographic data. We compared both the exposed and the unexposed sibling groups on WASI and NEPSY II, and total and T scores from CBCL and Conners rating were analyzed as continuous data using the paired t test between the two groups. A P<0.05 was considered significant. RESULTS: After the Institutional Review Board approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. The scores for verbal IQ (exposed=106.1+/-16.3, unexposed=109.2+/-17.9), performance IQ (exposed=109.1+/-16.0, unexposed=113.9+/-15.9), and full IQ (exposed=108.2+/-14.0, unexposed=112.8+/-16.8) were comparable between the siblings. There were no differences between the two groups in T scores for any of the NEPSY II subdomains, CBCL, or Conners rating. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR). CONCLUSIONS: The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach and yielded pilot data from neuropsychological testing.

Experimental evidence of anesthesia-induced neurotoxicity has caused serious concern about the long-term effect of commonly used volatile anesthetic agents on young children. Several observational studies based on existing data have been conducted to address this concern with inconsistent results. We conducted a meta-analysis to synthesize the epidemiologic evidence on the association of anesthesia/surgery with neurodevelopmental outcomes in children. Using Bayesian meta-analytic approaches, we estimated the synthesized odds ratios (OR) and 95% credible interval (CrI) as well as the predictive distribution of a future study given the synthesized evidence. Data on 7 unadjusted and 6 adjusted measures of association were abstracted from 7 studies. The synthesized OR based on the 7 unadjusted measures for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.9 (95% CrI, 1.2-3.0). The most likely unadjusted OR from a future study was estimated to be 2.2 (95% CrI, 0.6-6.1). The synthesized OR based on the 6 adjusted measures for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.4 (95% CrI, 0.9-2.2). The most likely adjusted OR from a future study was estimated to be 1.5 (95% CrI, 0.5-4.0). We conclude that existent epidemiologic evidence suggests a modestly elevated risk of adverse behavioral or developmental outcomes in children who were exposed to anesthesia/surgery during early childhood. The evidence, however, is considerably uncertain.

BACKGROUND: Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. METHODS: We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. RESULTS: On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20-2.93, CELF-E: aRR, 1.72; 95% CI, 1.12-2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13-2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40-4.17, and CPM aRR, 1.73; 95% CI, 1.04-2.88). CONCLUSIONS: Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.

Since 1996, 16 states and the District of Columbia in the United States have enacted legislation to decriminalize marijuana for medical use. Although marijuana is the most commonly detected nonalcohol drug in drivers, its role in crash causation remains unsettled. To assess the association between marijuana use and crash risk, the authors performed a meta-analysis of 9 epidemiologic studies published in English in the past 2 decades identified through a systematic search of bibliographic databases. Estimated odds ratios relating marijuana use to crash risk reported in these studies ranged from 0.85 to 7.16. Pooled analysis based on the random-effects model yielded a summary odds ratio of 2.66 (95% confidence interval: 2.07, 3.41). Analysis of individual studies indicated that the heightened risk of crash involvement associated with marijuana use persisted after adjustment for confounding variables and that the risk of crash involvement increased in a dose-response fashion with the concentration of 11-nor-9-carboxy-delta-9-tetrahydrocannabinol detected in the urine and the frequency of self-reported marijuana use. The results of this meta-analysis suggest that marijuana use by drivers is associated with a significantly increased risk of being involved in motor vehicle crashes.

Changing the built environment is a sound, but often underutilized approach to injury control. The authors reviewed the literature and conducted a meta-analysis to synthesize the evidence on the association of roadway characteristics with risk of pediatric pedestrian injury. To synthesize the data, they converted results to odds ratios based on direct results or abstracted outcomes and used Bayesian meta-analytic approaches by modeling outcomes as the logit of a normally distributed set of outcomes with vague prior distributions for the central measure of effect and its variance. On the basis of 10 studies of roadway features restricted exclusively to pediatric populations, the synthesized effect estimate for the association of roadway characteristics with pedestrian injury risk was 2.5 (95% credible interval: 1.8, 3.2). The probability of a new study showing an association between the built roadway and pediatric pedestrian injury was nearly 100%. The authors concluded that the built environment is directly related to the risk of pedestrian injury. This review and meta-analysis suggests that even modest interventions to the built roadway environment may result in meaningful reductions in the risk of pediatric pedestrian injury.

BACKGROUND: In vitro and in vivo studies of anesthetics have demonstrated serious neurotoxic effects on the developing brain. However, the clinical relevance of these findings to children undergoing anesthesia remains unclear. Using data from a sibling birth cohort, we assessed the association between exposure to anesthesia in the setting of surgery in patients younger than 3 years and the risk of developmental and behavioral disorders. METHODS: We constructed a retrospective cohort of 10,450 siblings who were born between 1999 and 2005 and who were enrolled in the New York State Medicaid program. The exposed group was 304 children without a history of developmental or behavioral disorders who underwent surgery when they were younger than 3 years. The unexposed group was 10,146 children who did not receive any surgical procedures when they were younger than 3 years. Exposed children were entered into analysis at the date of surgery. Unexposed children were entered into analysis at age 10 months (the mean age at which exposed children underwent surgery). Both exposed and unexposed children were followed until diagnosis with a developmental or behavioral disorder, loss to follow-up, or the end of 2005. The association of exposure to anesthesia with subsequent developmental and behavioral disorders was assessed with both proportional hazards modeling, and pair-matched analysis. RESULTS: The incidence of developmental and behavioral disorders was 128.2 diagnoses per 1000 person-years for the exposed cohort and 56.3 diagnoses per 1000 person-years for the unexposed cohort. With adjustment for sex and history of birth-related medical complications, and clustering by sibling status, the estimated hazard ratio of developmental or behavioral disorders associated with any exposure to anesthesia when they were younger than 3 years was 1.6 (95% confidence interval [CI]: 1.4, 1.8). The risk increased from 1.1 (95% CI: 0.8, 1.4) for 1 operation to 2.9 (94% CI: 2.5, 3.1) for 2 operations and 4.0 (95% CI: 3.5, 4.5) for >/=3 operations. The relative risk in a matched analysis of 138 sibling pairs was 0.9 (95% CI: 0.6, 1.4). CONCLUSION: The risk of being subsequently diagnosed with developmental and behavioral disorders in children who were enrolled in a state Medicaid program and who had surgery when they were younger than 3 years was 60% greater than that of a similar group of siblings who did not undergo surgery. More tightly matched pairwise analyses indicate that the extent to which the excess risk is causally attributable to anesthesia or mediated by unmeasured factors remains to be determined.

OBJECTIVES: We estimated the number of deaths attributable to social factors in the United States. METHODS: We conducted a MEDLINE search for all English-language articles published between 1980 and 2007 with estimates of the relation between social factors and adult all-cause mortality. We calculated summary relative risk estimates of mortality, and we obtained and used prevalence estimates for each social factor to calculate the population-attributable fraction for each factor. We then calculated the number of deaths attributable to each social factor in the United States in 2000. RESULTS: Approximately 245,000 deaths in the United States in 2000 were attributable to low education, 176,000 to racial segregation, 162,000 to low social support, 133,000 to individual-level poverty, 119,000 to income inequality, and 39,000 to area-level poverty. CONCLUSIONS: The estimated number of deaths attributable to social factors in the United States is comparable to the number attributed to pathophysiological and behavioral causes. These findings argue for a broader public health conceptualization of the causes of mortality and an expansive policy approach that considers how social factors can be addressed to improve the health of populations.

AIMS: To assess the role of drug violations in aviation accidents. DESIGN: Case-control analysis. SETTING: Commercial aviation in the United States. PARTICIPANTS: Aviation employees who were tested for drugs during 1995-2005 under the post-accident testing program (cases, n = 4977) or under the random testing program (controls, n = 1 129 922). MEASUREMENTS: Point prevalence of drug violations, odds ratio of accident involvement and attributable risk in the population. A drug violation was defined as a confirmed positive test for marijuana (>/=50 ng/ml), cocaine (>/=300 ng/ml), amphetamines (>/=1000 ng/ml), opiates (>/=2000 ng/ml) or phencyclidine (>/=25 ng/ml). FINDINGS: The prevalence of drug violations was 0.64% [95% confidence interval (CI): 0.62-0.65%] in random drug tests and 1.82% (95% CI: 1.47-2.24%) in post-accident tests. The odds of accident involvement for employees who tested positive for drugs was almost three times the odds for those who tested negative (odds ratio 2.90, 95% CI: 2.35-3.57), with an estimated attributable risk of 1.2%. Marijuana accounted for 67.3% of the illicit drugs detected. The proportion of illicit drugs represented by amphetamines increased progressively during the study period, from 3.4% in 1995 to 10.3% in 2005 (P < 0.0001). CONCLUSIONS: Use of illicit drugs by aviation employees is associated with a significantly increased risk of accident involvement. Due to the very low prevalence, drug violations contribute to only a small fraction of aviation accidents.