Faculty Bibliography

In a longitudinal population-based study of 2,905 children, we investigated if infants' neuromotor development was associated with autistic traits in childhood. Overall motor development and muscle tone were examined by trained research assistants with an adapted version of Touwen's Neurodevelopmental Examination between ages 2 and 5 months. Tone was assessed in several positions and items were scored as normal, low, or high tone. Parents rated their children's autistic traits with the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist at 6 years. We defined clinical PDP if scores were >98th percentile of the norm population. Diagnosis of autism spectrum disorder (ASD) was clinically confirmed in 30 children. We observed a modest association between overall neuromotor development in infants and autistic traits. Low muscle tone in infancy predicted autistic traits measured by SRS (adjusted beta = 0.05, 95% CI for B: 0.00-0.02, P = 0.01), and PDP (adjusted beta = 0.08, 95% CI for B: 0.04-0.10, P < 0.001). Similar results emerged for the association of low muscle tone and clinical PDP (adjusted OR = 1.36, 95% CI: 1.08-1.72, P = 0.01) at age 6 years. Results remained unchanged if adjusted for child intelligence. There was no association between high muscle tone and SRS or PDP. Exclusion of children with ASD diagnosis did not change the association. This large study showed a prospective association of infant muscle tone with autistic traits in childhood. Our findings suggest that early detection of low muscle tone might be a gateway to improve early diagnosis of ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Background: There is little data on presentation of and care for oncology patients in the ED. Our goal was to describe the characteristics and dispositions of patients with active cancer who present to EDs of the Comprehensive ONCologic Emergencies Research Network. Methods: Prospective, observational study of patients >=18 years of age with active cancer in 19 US tertiary-care EDs. A patient survey was administered in the ED, and a 30-day chart review identified ED course, comorbidities, revisits, and outcomes. Descriptive statistics were calculated. Results: We enrolled 616 patients, with 364 having complete 30 day chart reviews. The population was 50% female, 13% African-American, 3% Asian, and 7% Hispanic. Mean age was 63 years with 291 >=65. The most common cancer types were gastrointestinal (22%), breast (12%), and lung (10%). Almost half (47%) had no living will or advanced directive. In the week prior to ED visit, symptoms reported as present "quite a bit" or "very much" included pain (47%), shortness of breath (24%), and nausea (20%). ED symptom-related complaints were common including pain (69%), shortness of breath (38%), and nausea (34%). Ten percent reported fever >=100.4degree F prior to ED arrival. In the 364 subjects with completed chart reviews, 52% received pain medication and 31% nausea medication in the ED. Antibiotics were administered to 28% (n=99). ED disposition included admission in 64% (12% to step-down or ICU), observation in 7%, and discharge in 28%. 30-day mortality was 5.7% (95% CI 3.4-8.7%). 30-day ED revisit and hospital readmission rates were 27% and 23%.< Conclusion: ED patients with active cancer present with high acuity and substantial symptom burden including pain, nausea, and shortness of breath. Infection is a frequent concern in the ED with high rates of antibiotic administration. These patients have high admission, mortality, and revisit rates. Additional studies to identify optimal ED care and disposition practices for this population are warranted

Background: Cocaine is commonly involved in unintentional drug poisoning (overdose) deaths, accounting for 41% of overdose in New York City (NYC) in 2014. However, little research exists regarding cocaine use by middle-aged and older adults, who are more likely than younger individuals to have underlying cardiovascular disease and other chronic conditions and therefore may be at increased risk for adverse health consequences of cocaine use including death.
Objective(s): To describe demographic characteristics of middle-and-older-aged NYC adults who died of a cocaine-involved overdose death, and to identify potential associations by age, race, borough of residence, and concomitant drugs among deaths involving cocaine compared with overdose deaths not involving cocaine.
Method(s): We conducted a retrospective analysis of unintentional drug overdose deaths of adults aged 45 to 84 in New York City (NYC) from 2000 to 2014 using 2 linked sources, NYC death certificates and toxicology results from the Office of the Chief Medical Examiner. We described demographic characteristics and drugs involved in overdoses, by age ranges 45 to 54, 55 to 64, and 65 to 84. Data were stratified and compared by cocaine involvement using bivariable analysis. The multivariable analysis included age, race, gender, and borough of residence to determine associations between demographic characteristics and cocaine-involved overdoses.
Result(s): From 2000 to 2014, there were 5339 unintentional drug overdose deaths among adults aged 45 to 84 in NYC. Of those, cocaine was involved in 54% (n = 2856). Co-occurring opioid involvement (heroin, methadone, or opioid analgesics) and alcohol use among deaths involving cocaine was common. Compared with decedents of noncocaine-involved overdose, decedents of cocaine-involved overdose were more likely to be younger (52.5-53.0 years, P = 0.002), male (75% vs 72%, P = 0.005), and non-Hispanic black (47% vs 26%, P < 0.001). Multivariate analysis showed that male gender (AOR=1.34, 95% CI 1.17-1.52), Bronx residence (AOR= 1.278, 95% CI 1.04-1.57), and non-Hispanic black race/ethnicity (AOR = 2.31, 95% CI 1.98-2.69) were independently associated with cocaine-involved overdose compared with none cocaine-involved overdose.
Conclusion(s): Cocaine was involved in over half of unintentional drug overdose deaths in NYC for adults aged 45 to 84. It remains unclear what the role of cocaine was in the setting of adults with underlying cardiovascular disease. Studies that examine autopsy data may be able to elucidate the underlying impact of cocaine in drug-related overdose deaths

Significance: Limited data exist regarding tobacco and nicotine containing product (TNCP) use and their association with other drugs of abuse in high-risk settings. The purpose of this study was to examine the associations between TNCP use and other common illicit drug use among adults attending Electronic Dance Music (EDM) parties at nightclubs and festivals in New York City (NYC).
Method(s): Adults (age 18-40) were recruited outside of EDM events in NYC between May and August 2016 and completed a computer-assisted personal interview on a tablet. The survey took approximately 10 minutes and queried sociodemographic characteristics, and self-reported use of TNCPs (e-cigarettes, hookah, and "tobacco") and other drugs. Among recent (12-month) TNCP users, we compared illicit drug use according to the number of TNCPs reportedly used with the use of 1 TNCP representing mono-use, any 2 representing dual-use, and all 3 representing poly-use.
Result(s): More than half the overall sample (54%; N = 524 of 965) reported past year use of a TNCP. Participants' mean age was (25.1+4.5) years, and 55.2% were male. Almost half (46%) were mono users, 27% were dual TNCP users, and 27% were poly TNCP users. Sociodemographic characteristics were not associated with a number of TNCPs used; however, a number of products was significantly different regarding the past-year use of marijuana, powder cocaine, ecstasy (MDMA, "Molly"), LSD, and psilocybin ("magic mushrooms"). Poly users were more likely to report use of marijuana (94.4% vs 87.9% dual and 68.3% mono; P < 0.001), cocaine (69.2% vs 56.7% dual and 32.1% mono; P < 0.001), ecstasy (65.0% vs 61.0% dual and 49.6% mono; P = 0.007), LSD (46.9% vs 34.8% dual and 19.6% mono; P< 0.001), and psilocybin (44.8% vs 31.2% dual and 16.7% mono; P< 0.001).
Conclusion(s): Among this sample of EDM attendees in NYC, past-year use of TNCPs was strongly associated with the use of illicit drugs suggesting the use of more TNCPs is associated with risky behavior in high-risk settings. A limitation was that "tobacco" included all other TNCPs other than e-cigarettes and hookah. Adults' TNCP use patterns might be indicative of the extent of illicit drug use, especially among those frequenting high-risk settings. Future research needs to probe in the reasons behind the patterns of TNCP use among those in high-risk settings

HapMap imputed genome-wide association studies (GWAS) have revealed >50 loci at which common variants with minor allele frequency >5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel loci that have been missed by previous efforts. To investigate the value of such a more complete variant catalog, we conducted a GWAS meta-analysis of kidney function based on the estimated glomerular filtration rate (eGFR) in 110,517 European ancestry participants using 1000 Genomes imputed data. We identified 10 novel loci with p-value < 5 × 10^-8 previously missed by HapMap-based GWAS. Six of these loci (HOXD8, ARL15, PIK3R1, EYA4, ASTN2, and EPB41L3) are tagged by common SNPs unique to the 1000 Genomes reference panel. Using pathway analysis, we identified 39 significant (FDR < 0.05) genes and 127 significantly (FDR < 0.05) enriched gene sets, which were missed by our previous analyses. Among those, the 10 identified novel genes are part of pathways of kidney development, carbohydrate metabolism, cardiac septum development and glucose metabolism. These results highlight the utility of re-imputing from denser reference panels, until whole-genome sequencing becomes feasible in large samples.

BACKGROUND:As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate. METHODS:In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines. RESULTS:Friedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25-39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to 0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation. CONCLUSIONS:Estimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.

BACKGROUND: The objective of the current study was to improve colorectal cancer (CRC) screening uptake with the fecal immunochemical test (FIT). The current study investigated the differential impact of a multicomponent, targeted, low-literacy educational intervention compared with a standard, nontargeted educational intervention. METHODS: Patients aged 50 to 75 years who were of average CRC risk and not up-to-date with CRC screening were recruited from either a federally qualified health center or a primary care community health clinic. Patients were randomized to the intervention condition (targeted photonovella booklet/DVD plus FIT kit) or comparison condition (standard Centers for Disease Control and Prevention brochure plus FIT kit). The main outcome was screening with FIT within 180 days of delivery of the intervention. RESULTS: Of the 416 participants, 54% were female; the participants were racially and ethnically diverse (66% white, 10% Hispanic, and 28% African American), predominantly of low income, and insured (the majority had county health insurance). Overall, the FIT completion rate was 81%, with 78.1% of participants in the intervention versus 83.5% of those in the comparison condition completing FIT (P = .17). In multivariate analysis, having health insurance was found to be the primary factor predicting a lack of FIT screening (adjusted odds ratio, 2.10; 95% confidence interval, 1.04-4.26 [P = .04]). CONCLUSIONS: The multicomponent, targeted, low-literacy materials were not found to be significantly different or more effective in increasing FIT uptake compared with the nontargeted materials. Provision of a FIT test plus education may provide a key impetus to improve the completion of CRC screening. The type of educational material (targeted vs nontargeted) may matter less. The findings of the current study provide a unique opportunity for clinics to adopt FIT and to choose the type of patient education materials based on clinic, provider, and patient preferences. Cancer 2017;123:1390-1400. (c) 2016 American Cancer Society.

BACKGROUND:Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001-2009 period, but data on recent incidence trends are lacking. METHODS:We ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health-plan member counts. After the calculation of annual incidence rates for the 2002-2012 period, we analyzed trends using generalized autoregressive moving-average models with 2-year moving averages. RESULTS:A total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002-2003 to 21.7 cases per 100,000 youths per year in 2011-2012, P=0.03). In adjusted pairwise comparisons, the annual rate of increase was greater among Hispanics than among non-Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths per year in 2002-2003 to 12.5 cases per 100,000 youths per year in 2011-2012, P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted pairwise comparisons showed that the relative annual increase in the incidence of type 2 diabetes among non-Hispanic whites (0.6%) was lower than that among non-Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for all comparisons) and that the annual rate of increase among Hispanics differed significantly from that among Native Americans (3.1% vs. 8.9%, P=0.01). After adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2 diabetes was 4.8% (P<0.001). CONCLUSIONS:The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002-2012 period, particularly among youths of minority racial and ethnic groups. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Centers for Disease Control and Prevention.).