The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families.

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6 months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR = 2.8, CI[1.004, 7.617], p = 0.049) and maintained higher objective understanding over time (OR = 1.1, CI[1.004, 1.127], p = 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR = 3.9, CI[1.603, 9.254], p = 0.003), confidence (OR = 2.7, CI[1.021, 7.277], p = 0.046), and objective understanding (OR = 1.1, CI[1.009, 1.212], p = 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

Prenatal and childhood exposure to phthalates and motor skills at age 11 years.

BACKGROUND: Previous reports suggest that prenatal phthalate exposure is associated with lower scores on measures of motor skills in infants and toddlers. Whether these associations persist into later childhood or preadolescence has not been studied. METHODS: In a follow up study of 209 inner-city mothers and their children the concentrations of mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), monomethyl phthalate (MEP), mono-carboxy-isooctyl phthalate (MCOP), and four di-2-ethylhexyl phthalate metabolites (ΣDEHP) were measured in spot urine sample collected from the women in late pregnancy and from their children at ages 3, 5, and 7 years. The Bruininks-Oseretsky Test of Motor Proficiency short form (BOT-2) was administered at child age 11 to assess gross and fine motor skills. RESULTS: The total number of children included in the study was 209. Of the 209 children, 116(55.5%) were girls and 93 were (45%) boys. Among girls, prenatal MnBP(b=-2.09; 95%CI: [-3.43, -0.75]), MBzP (b=-1.14; [95%CI: -2.13, -0.14]), and MiBP(b=-1.36; 95%CI: [-2.51, -0.21] and MEP(b=-1.23 [95%CI: -2.36, -0.11]) were associated with lower total BOT-2 composite score. MnBP (b= -1.43; 95% CI: [-2.44, -0.42]) was associated with lower fine motor scores and MiBP(b = -0.56; 95% CI: [-1.12, -0.01]) and MEP (b = -0.60; 95% CI: [-1.14, -0.06])was associated with lower gross motor scores. Among boys, prenatal MBzP (b = -0.79; 95% CI: [-1.40, -0.19]) was associated with lower fine motor composite score. The associations between MEP measured at age 3 and the BOT-2 gross motor, fine motor and total motor score differed by sex. In boys, there was an inverse association between ΣDEHP metabolites measured in childhood at ages 3 (b = -1.30; 95% CI: [-2.34, -0.26]) and 7 years (b = -0.96; 95% CI: [-1.79, -0.13]), and BOT-2 fine motor composite scores. CONCLUSIONS: Higher prenatal exposure to specific phthalates was associated with lower motor function among 11- year old girls while higher postnatal exposure to ΣDEHP metabolites was associated with lower scores among boys. As lower scores on measures of motor development have been associated with more problems in cognitive, socioemotional functioning and behavior, the findings of this study have implications related to overall child development.

Prepregnancy obesity is associated with cognitive outcomes in boys in a low-income, multiethnic birth cohort.

BACKGROUND: Maternal obesity and high gestational weight gain (GWG) disproportionally affect low-income populations and may be associated with child neurodevelopment in a sex-specific manner. We examined sex-specific associations between prepregnancy BMI, GWG, and child neurodevelopment at age 7. METHODS: Data are from a prospective low-income cohort of African American and Dominican women (n = 368; 44.8% male offspring) enrolled during the second half of pregnancy from 1998 to 2006. Neurodevelopment was measured using the Wechsler Intelligence Scale for Children (WISC-IV) at approximately child age 7. Linear regression estimated associations between prepregnancy BMI, GWG, and child outcomes, adjusting for race/ethnicity, marital status, gestational age at delivery, maternal education, maternal IQ and child age. RESULTS: Overweight affected 23.9% of mothers and obesity affected 22.6%. At age 7, full-scale IQ was higher among girls (99.7 ± 11.6) compared to boys (96.9 ± 13.3). Among boys, but not girls, prepregnancy overweight and obesity were associated with lower full-scale IQ scores [overweight ß: - 7.1, 95% CI: (- 12.1, - 2.0); obesity ß: - 5.7, 95% CI: (- 10.7, - 0.7)]. GWG was not associated with full-scale IQ in either sex. CONCLUSIONS: Prepregnancy overweight and obesity were associated with lower IQ among boys, but not girls, at 7 years. These findings are important considering overweight and obesity prevalence and the long-term implications of early cognitive development.

Mood disorders in familial epilepsy: A test of shared etiology.

OBJECTIVE: Mood disorders are the most common comorbid conditions in epilepsy, but the cause remains unclear. One possible explanation is a shared genetic susceptibility to epilepsy and mood disorders. We tested this hypothesis by evaluating lifetime prevalence of mood disorders in relatives with and without epilepsy in families containing multiple individuals with epilepsy, and comparing the findings with rates from a general population sample. METHODS: The Composite International Diagnostic Interview was administered to 192 individuals from 60 families, including 110 participants with epilepsy of unknown cause (50 focal epilepsy [FE], 42 generalized epilepsy [GE], 6 FE and GE, 12 unclassifiable) and 82 relatives without epilepsy (RWOE). Odds ratios (ORs) for lifetime prevalence of mood disorders in participants with versus without epilepsy were computed through logistic regression, using generalized estimation equations to account for familial clustering. Standardized prevalence ratios (SPRs) were used to compare prevalence in family members with general population rates. RESULTS: Compared with RWOE, ORs for mood disorders were significantly increased in participants with FE (OR = 2.4, 95% confidence interval [CI] = 1.1-5.2) but not in those with GE (OR = 1.0, 95% CI = 0.4-2.2). In addition, prevalence of mood disorders was increased in individuals with epilepsy who had ≥1 relative with FE. Compared with general population rates, mood disorders were significantly increased in individuals with FE but not in those with GE. Rates were also increased in RWOE, but not significantly so (SPR = 1.4, P = .14). SIGNIFICANCE: These findings are consistent with the hypothesis of shared genetic susceptibility to epilepsy and mood disorders, but suggest (1) the effect may be restricted to FE, and (2) the shared genetic effect on risk of mood disorders and epilepsy may be restricted to individuals with epilepsy, that is, to those in whom the genetic risk for epilepsy is "penetrant."

Evaluating parental personal utility of pediatric genetic and genomic testing in a diverse, multilingual population.

There is increasing evidence of the clinical utility of genetic and genomic testing (GT); however, factors influencing personal utility of GT, especially in diverse, multilingual populations, remain unclear. We explored these factors in a diverse cohort of parents/guardians (participants) whose children received clinical GT through the NYCKidSeq program. A total of 847 participants completed surveys at baseline, post-results disclosure, and 6 months (6m) post-results. The largest population groups were Hispanic/Latino(a) (48%), White/European American (24%), and Black/African American (16%). Personal utility was assessed using the Personal Utility (PrU) scale, adapted for pediatric populations and included on the surveys. Three PrU subscales were identified using factor analysis: practical, educational, and parental psychological utility. Overall personal utility summary score and the three subscales significantly decreased after receiving results and over time. Hispanic/Latino(a) participants identified greater overall personal utility than European American and African American participants at all time points (p < 0.001) as did participants whose children received positive/likely positive results compared with those with negative and uncertain results (post-results: p < 0.001 and p < 0.001; 6m post-results: p = 0.002 and p < 0.001, respectively). Post-results, higher subscale scores were associated with lower education levels (practical, parental psychological: p ≤ 0.02) and higher levels of trust in the healthcare system (practical, parental psychological: p ≤ 0.04). These findings help to understand the perspectives of diverse parents/guardians, which is critical to tailoring pre- and post-test counseling across a variety of populations and clinical settings.

Chemotherapy use in elderly patients with soft tissue sarcoma: a population-based study.

Adjuvant chemotherapy for soft tissue sarcoma (STS) remains controversial while improvement in survival has never been conclusively demonstrated for metastatic STS. We identified individuals in SEER-Medicare with resected or metastatic STS, 1991-2007. Of 2,382 patients with resected STS, 106 (4.5%) received chemotherapy. High tumor grade, larger tumor size, and malignant fibrous histiocytoma subtype were associated with chemotherapy receipt. Of 365 patients with metastatic STS, 118 (32.4%) received chemotherapy. Younger age, fewer comorbidities, and being married were associated with chemotherapy receipt. Consistent with clinical trials, we found minimal use of chemotherapy. Clinical factors were associated with chemotherapy receipt in nonmetastatic STS.

Uptake and patterns of use of gemcitabine for metastatic pancreatic cancer: a population-based study.

Gemcitabine was approved for advanced pancreatic cancer in 1996. We investigated uptake and predictors of its use. We identified 3,231 individuals > 65 years in the SEER-Medicare database with stage IV pancreatic adenocarcinoma, diagnosed between 1998-2005, who survived > 30 days. Of these, 54% received chemotherapy, 93% with gemcitabine. Gemcitabine nonreceipt was associated with advanced age and unmarried (OR: 0.65, 95% CI: 0.55-0.76). Diagnosis in 2004-2005 versus 1998-2000 was more likely to receive gemcitabine (OR: 1.51, 95% CI: 1.23-1.84) as were higher SES patients (highest versus lowest quintile, OR: 2.14, 95% CI: 1.60-2.85). Gemcitabine was rapidly adopted among elderly advanced pancreatic cancer patients; several factors are associated with use.

Shortened surveillance intervals following suboptimal bowel preparation for colonoscopy: results of a national survey.

PURPOSE: Suboptimal bowel preparation can result in decreased neoplasia detection, shortened surveillance intervals, and increased costs. We assessed bowel preparation recommendations and the relationship to self-reported proportion of suboptimal bowel preparations in practice; and evaluated the impact of suboptimal bowel preparation on colonoscopy surveillance practices. A random sample of a national organization of gastroenterologists in the U.S. was surveyed. METHODS: Demographic and practice characteristics, bowel preparation regimens, and proportion of suboptimal bowel preparations in practice were ascertained. Recommended follow-up colonoscopy intervals were evaluated for optimal and suboptimal bowel preparation and select clinical scenarios. RESULTS: We identified 6,777 physicians, of which 1,354 were randomly selected; 999 were eligible, and 288 completed the survey. Higher proportion of suboptimal bowel preparations/week (≥10 %) was associated with hospital/university practice, teaching hospital affiliation, >25 % Medicaid insured patients, recommendation of PEG alone and sulfate-free. Those reporting >25 % Medicare and privately insured patients, split dose recommendation, and use of MoviPrep® were associated with a <10 % suboptimal bowel preparations/week. Shorter surveillance intervals for three clinical scenarios were reported for suboptimal preparations and were shortest among participants in the Northeast who more often recommended early follow-up for normal findings and small adenomas. Those who recommended 4-l PEG alone more often advised <1 year surveillance interval for a large adenoma. CONCLUSIONS: Our study demonstrates significantly shortened surveillance interval recommendations for suboptimal bowel preparation and that these interval recommendations vary regionally in the United States. Findings suggest an interrelationship between dietary restriction, purgative type, and practice and patient characteristics that warrant additional research.

Racial disparities in the use of palliative therapy for ureteral obstruction among elderly patients with advanced prostate cancer.

OBJECTIVES: Palliative issues are an important but understudied issue for patients with advanced cancer. Ureteral obstruction is a complication of advanced prostate cancer, usually relieved with placement of retrograde ureteral stent (RUS) or percutaneous nephrostomy (PCN) to palliate symptoms associated with obstructive uropathy and/or renal failure. We investigated predictors of receipt of RUS and PCN and their association with survival for older advanced prostate cancer patients. METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified patients aged 65 or older with stage IV (n = 10,848) or recurrent (n = 7,872) prostate cancer. We used multivariable analysis to compare those with ureteral obstruction treated with RUS or PCN to those not treated and to analyze the association between RUS, PCN, and survival. RESULTS: Sixteen percent (n = 2,958) of the sample developed ureteral obstruction. Compared to no treatment, African Americans were more likely to undergo placement of PCN [odds ratio 1.48, 95 % confidence intervals (CI) 1.03-2.13] than Whites, but equally likely to receive a stent. Subjects of >80 years were less likely to undergo RUS (ages 80-84, 0.41, 95 % CI 0.27-0.63; ages ≥85, 0.30, 95 % CI 0.16-0.54) compared to patients 65-69 years. Subjects who received a PCN were 55 % more likely to die than those who were untreated. There was no difference in survival among those receiving RUS vs untreated. Nine percent of subjects received RUS or PCN within 30 days of dying. CONCLUSIONS: This is the first population-based study to demonstrate a racial disparity in the palliative treatment of advanced prostate cancer. Reasons for disparate care need to be determined so that interventions may be developed.

Phase II study of glucosamine with chondroitin on aromatase inhibitor-associated joint symptoms in women with breast cancer.

PURPOSE: Many women with hormone receptor-positive breast cancer discontinue effective aromatase inhibitor (AI) treatment due to joint symptoms. METHODS: We conducted a single-arm, open-label, phase II study evaluating glucosamine-sulfate (1,500 mg/day) + chondroitin-sulfate (1,200 mg/day) for 24 weeks to treat joint pain/stiffness in postmenopausal women with early stage breast cancer who developed moderate-to-severe joint pain after initiating AIs. The primary endpoint was improvement in pain/stiffness at week 24 assessed by the Outcome Measure in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Secondary endpoints assessed changes in pain, stiffness, and function using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) Index for hips/knees and the Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) for hands/wrists. The Brief Pain Inventory (BPI) assessed pain interference, severity, and worst pain. RESULTS: Of 53 patients enrolled, 39 were evaluable at week 24. From baseline to week 24, 46 % of patients improved according to OMERACT-OARSI criteria. At week 24, there were improvements (all P < 0.05) in pain and function as assessed by WOMAC and M-SACRAH, and in pain interference, severity, and worst pain as assessed by BPI. Estradiol levels did not change from baseline. The most commonly reported side effects were headache (28 %), dyspepsia (15 %), and nausea (17 %). CONCLUSIONS: In this single-arm study, 24 weeks of glucosamine/chondroitin resulted in moderate improvements in AI-induced arthralgias, with minimal side effects, and no changes in estradiol levels. These results suggest a need to evaluate efficacy in a placebo-controlled trial.

Computerized cognitive and social cognition training in schizophrenia for impulsive aggression.

BACKGROUND: Schizophrenia is associated with an elevated risk for impulsive aggression for which there are few psychosocial treatment options. Neurocognitive and social cognitive deficits have been associated with aggression with social cognitive deficits seemingly a more proximal contributor. The current study examined the effects of combining cognitive and social cognition treatment on impulsive aggression among inpatients with chronic schizophrenia and schizoaffective disorder and a history of aggression compared to cognitive remediation treatment alone. METHODS: The two-center study randomized 130 participants to receive 36 sessions of either a combination of cognitive remediation and social cognition treatment or cognitive remediation plus a computer-based control. Participants had at least one aggressive incident within the past year or a Life History of Aggression (LHA) score of 5 or more. Participants completed measures of neurocognition, social cognition, symptom severity, and aggression at baseline and endpoint. RESULTS: Study participants were mostly male (84.5 %), had a mean age 34.9 years, and 11.5 years of education. Both Cognitive Remediation Training (CRT) plus Social Cognition Training (SCT) and CRT plus control groups were associated with significant reductions in aggression measures with no group differences except on a block of the Taylor Aggression Paradigm (TAP), a behavioral task of aggression which favored the CRT plus SCT group. Both groups showed significant improvements in neurocognition and social cognition measures with CRT plus SCT being associated with greater improvements. CONCLUSION: CRT proved to be an effective non-pharmacological treatment in reducing impulsive aggression in schizophrenia inpatient participants with a history of aggressive episodes. The addition of social cognitive training did not enhance this anti-aggression treatment effect but did augment the CRT effect on cognitive functions, on emotion recognition and on mentalizing capacity of our participants.

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic counseling in racially and ethnically diverse families.

Background: Digital solutions are needed to support rapid increases in the application of genetic and genomic tests (GT) in diverse clinical settings and patient populations. We developed GUÍA, a bi-lingual web-based platform that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial evaluated GUÍA's impact on understanding of GT results. Methods: NYCKidSeq enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GT. Families were randomized to genetic counseling with GUÍA (intervention) or standard of care (SOC) genetic counseling for results disclosure. Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6-months later. Survey measures assessed the primary study outcomes of perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. We used regression models to evaluate the association between the intervention and the study outcomes. Results: The analysis included 551 participants, 270 in the GUÍA arm and 281 in SOC. Participants' mean age was 41.1 years and 88.6% were mothers. Most participants were Hispanic/Latino(a) (46.3%), White/European American (24.5%), or Black/African American (15.8%). Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR=2.8, CI[1.004,7.617], P=0.049) and maintained higher objective understanding over time (OR=1.1, CI[1.004, 1.127], P=0.038) compared to those in the SOC arm. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR=3.9, CI[1.6, 9.3], P=0.003), confidence (OR=2.7, CI[1.021, 7.277], P=0.046), and objective understanding (OR=1.1, CI[1.009, 1.212], P=0.032) compared to SOC . Conclusions: This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions. These findings build a case for utilizing GUÍA to deliver complex and often ambiguous genetic results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics. Trial Registration: Clinicaltrials.gov identifier NCT03738098.

Gastroenterologists' perceived barriers to optimal pre-colonoscopy bowel preparation: results of a national survey.

Poor quality bowel preparation has been reported in almost one third of all colonoscopies. To better understand factors associated with poor bowel preparation, we explored perceived patient barriers to optimal pre-colonoscopy bowel preparation from the perspective of the gastroenterologist. A random sample of physician members of the American College of Gastroenterology was surveyed via the internet and postal mailing. Demographic and practice characteristics and practice-related and perceived patient barriers to optimal bowel preparation were assessed among 288 respondents. Lack of time, no patient education reimbursement, and volume of information were not associated with physician level of suboptimal bowel preparation. Those reporting ≥ 10 % suboptimal bowel preparations were more likely to believe patients lack understanding of the importance of following instructions, have problems with diet, and experience trouble tolerating the purgative. Bowel preparation instruction communication and unmet patient educational needs contribute to suboptimal bowel preparation. Educational interventions should address both practice and patient-related factors.

Psychiatric genetic essentialism and stigma in child custody proceedings: public views.

The introduction of behavioral, including psychiatric, genetic information in American courts has gained traction but raises concerns of undue influence on judicial outcomes. We conducted a vignette-based survey of a nationally representative sample of US adults to assess how evidence about a parent's psychiatric genetic makeup and explicit and implicit stigmatizing beliefs about psychiatric conditions may affect key decisions in child custody proceedings. Psychiatric genetic evidence did not affect public perspectives on custody decisions, but it increased the genetic essentialist understanding of psychiatric conditions (regardless of a diagnosis). Explicit stigma was associated with a preference to deny parents with a (or with an alleged) psychiatric condition joint custody. Our newly created Implicit Association Test identified an association between psychiatric conditions and perceived bad parenting. Research to identify effective interventions and educational programs to address genetic essentialism and to reduce bias against people, including parents, with psychiatric conditions is urgently needed.

Effects of Clozapine on Neurocognitive Functions in Schizophrenia: A Naturalistic Comparison to Non-clozapine Antipsychotics.

OBJECTIVE: While clozapine is recognized as the most effective antipsychotic for individuals with treatment-resistant schizophrenia, its effects on neurocognition remain unclear. This study aimed to compare the neurocognitive effects of clozapine treatment to those of non-clozapine antipsychotics in patients with schizophrenia and to examine the role of anticholinergic burden on cognitive impairments. DESIGN: This was a naturalistic study. Cross-sectional data were drawn from participants with chronic schizophrenia in two clinical trials assessing cognition. Cognition was evaluated using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Anticholinergic burden was calculated for each medication using the Anticholinergic Cognitive Burden (ACB) scoring system. We stratified the participants treated with non-clozapine antipsychotics into high ACB score versus low ACB score groups. RESULTS: One hundred and seventy participants were enrolled and treated with clozapine (n=58) or non-clozapine antipsychotics (n=112). We observed no significant differences in the MCCB T-scores between the clozapine and the total non-clozapine groups for the cognitive composite score and the seven domain scores. However, the non-clozapine high ACB group showed significant impairments in processing speed and attention/vigilance, in contrast to the non-clozapine low ACB group (p<0.05). CONCLUSION: Our results show that cognitive effects of clozapine might be no different from other antipsychotics. Negative effects on neurocognition in participants treated with antipsychotics with a high ACB score were related to their total ACB score.

The double helix at school: Behavioral genetics, disability, and precision education.

The prospect of using behavioral genetic data in schools is gaining momentum in the U.S., with some scholars advocating for the tailoring of educational interventions to students' genetic makeup ("precision education"). Public perspectives on testing for and using behavioral genetic data in schools can affect policies but are unknown. We explored public views in the U.S. (n = 419) on key issues in precision education. The introduction of a child's behavioral genetic information regarding Attention-Deficit/Hyperactivity-Disorder was associated with beliefs that such data should be considered in educational planning for the child and increased medicalization, but also a belief in treatment efficacy. Most participants expressed interest in learning about children's behavioral genetic predispositions but would disapprove of testing without parental consent. Differences by participants' race, ethnicity and educational attainment were observed. Our findings indicate the public's complex understanding of genetic information and the challenges for wide implementation of precision education in the U.S.

The Psychiatric Genetic Data of Children in Proceedings to Terminate Parental Rights.

The introduction of psychiatric genetic evidence in court proceedings to terminate parental rights raises concerns that such information will result in misconceived assumptions about the child's mental health trajectory and unjust rulings on termination of parental rights. We conducted an online vignette-based survey with a nationally representative sample of adults from the general public (n = 300 respondents) to assess their views on how evidence about a child's psychiatric genetic makeup may affect key decisions in termination proceedings. Our findings indicate that genetic evidence increased the child's labeling as having a psychiatric disorder, regardless of the presence of symptoms, treatment recommendations, evaluation of prescription medication, and beliefs in treatment efficacy. Genetic evidence alone did not affect whether participants would terminate parental rights, but participants who thought that the child did not have a psychiatric disorder were more likely to terminate in the presence of genetic test results. We conclude that psychiatric genetic evidence in termination proceedings may have unintended consequences, and that measures should be taken to ensure that it does not unfairly affect outcomes.

Adolescent varicocele: influence of Tanner stage at presentation on the presence, development, worsening and/or improvement of testicular hypotrophy without surgical intervention.

PURPOSE: Testicular asymmetry in adolescents with varicocele can worsen, remain unchanged or decrease on followup. We determined the incidence of testicular asymmetry at presentation by Tanner stage and the correlation between Tanner stage at presentation and subsequent changes in percent asymmetry (ability for catch-up growth or progressive asymmetry) without surgical intervention. MATERIALS AND METHODS: We retrospectively studied the records of 115 boys with a mean age of 14.1 years (range 9.2 to 20.0) with grade 2 or 3 left varicocele who underwent testicular volume measurement at 2 visits at least that were a minimum of 6 months apart. Of the patients 92% and 8% underwent Doppler duplex ultrasound and orchidometry, respectively. Patients were divided into 2 groups, including those with less than 15% and those with 15% or greater asymmetry. Catch-up growth was defined as less than 15% asymmetry at any subsequent visit. RESULTS: At presentation 58%, 64%, 67%, 35% and 39% of Tanner 1 to 5 cases showed 15% or greater testicular asymmetry, respectively. When Tanner 1 to 3 cases were combined and compared with Tanner 4 and 5 cases, the difference in initial asymmetry was significant (64% vs 38%, p = 0.007). Although it was not statistically significant, there was a trend toward more catch-up growth for the later Tanner stages, including 27% for Tanner 1 to 3 vs 53% for Tanner 4 and 5 (p = 0.06). CONCLUSIONS: Slightly more than 50% of children and adolescents referred with varicocele have 15% or greater testicular asymmetry at presentation. Initial asymmetry is statistically more common in cases of earlier Tanner stages (1 to 3). Adolescents with 15% or greater testicular asymmetry who present at higher Tanner stages (4 and 5) show a trend toward a higher incidence of catch-up growth, although it is not significant.

Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort.

Whether maternal obesity and gestational weight gain (GWG) are associated with early-childhood development in low-income, urban, minority populations, and whether effects differ by child sex remain unknown. This study examined the impact of prepregnancy BMI and GWG on early childhood neurodevelopment in the Columbia Center for Children's Environmental Health Mothers and Newborns study. Maternal prepregnancy weight was obtained by self-report, and GWG was assessed from participant medical charts. At child age 3 years, the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Intelligence were completed. Sex-stratified linear regression models assessed associations between prepregnancy BMI and pregnancy weight gain z-scores with child PDI and MDI scores, adjusting for covariates. Of 382 women, 48.2% were normal weight before pregnancy, 24.1% overweight, 23.0% obese, and 4.7% underweight. At 3 years, mean scores on the PDI and MDI were higher among girls compared to boys (PDI: 102.3 vs. 97.2, P = 0.0002; MDI: 92.8 vs. 88.3, P = 0.0001). In covariate-adjusted models, maternal obesity was markedly associated with lower PDI scores in boys [b = -7.81, 95% CI: (-13.08, -2.55), P = 0.004], but not girls. Maternal BMI was not associated with MDI in girls or boys, and GWG was not associated with PDI or MDI among either sex (all-P > 0.05). We found that prepregnancy obesity was associated with lower PDI scores at 3 years in boys, but not girls. The mechanisms underlying this sex-specific association remain unclear, but due to elevated obesity exposure in urban populations, further investigation is warranted.