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1.
J Clin Psychiatry ; 79(2)2018.
Article in English | MEDLINE | ID: mdl-29489078

ABSTRACT

OBJECTIVE: To examine whether sluggish cognitive tempo (SCT) symptomatology moderates dose response to methylphenidate and whether the impact of SCT on medication response is distinct from attention-deficit/hyperactivity disorder (ADHD) subtype effects. METHODS: Stimulant-naive children with ADHD predominantly inattentive type (ADHD-I; n = 126) or ADHD combined type (ADHD-C; n = 45) aged 7-11 years were recruited from the community from September 2006 to June 2013 to participate in a prospective, randomized, double-blind, 4-week crossover trial of long-acting methylphenidate. ADHD diagnosis and subtype were established according to DSM-IV criteria using a structured interview and teacher ADHD symptom ratings. SCT symptoms were assessed using a teacher-rated scale with 2 factors (Sluggish/Sleepy and Daydreamy). Primary outcomes included (1) categorization of children as methylphenidate responders, methylphenidate nonresponders, or placebo responders by 2 blinded physicians and (2) parent and teacher ratings of child behavior on the Vanderbilt ADHD Diagnostic Rating Scales while subjects were on treatment with placebo or 1 of 3 methylphenidate dosages (low, medium, high). RESULTS: Increased SCT Sluggish/Sleepy factor scores were associated with being a methylphenidate nonresponder or placebo responder rather than a methylphenidate responder (P = .04). Sluggish/Sleepy factor scores were also linked to diminished methylphenidate dose response for parent- and teacher-rated inattention symptoms (Sluggish/Sleepy factor × dose P = .004). SCT Daydreamy symptoms and ADHD subtype (ADHD-I vs ADHD-C) were not associated with methylphenidate responder status and did not moderate methylphenidate dose response for inattention symptoms. CONCLUSIONS: SCT Sluggish/Sleepy symptoms, but not SCT Daydreamy symptoms or ADHD subtype, predicted methylphenidate nonresponse. This novel finding, if replicated, may have important implications for assessing SCT as part of ADHD care. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01727414.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Child Behavior/drug effects , Cognition/drug effects , Fantasy , Methylphenidate , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/psychology , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/adverse effects , Child , Child, Preschool , Diagnostic and Statistical Manual of Mental Disorders , Dose-Response Relationship, Drug , Double-Blind Method , Drug Monitoring/methods , Female , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Psychiatric Status Rating Scales , Treatment Outcome
2.
J Pediatr Health Care ; 32(2): e37-e44, 2018.
Article in English | MEDLINE | ID: mdl-29455855

ABSTRACT

OBJECTIVE: Obese youth are more likely to report difficulties with sleep, depression, and quality of life (QOL). This study aims to characterize sleep problems, QOL, and symptoms of depression by degree of obesity. METHOD: The cross-sectional study was conducted in a specialized obesity clinic. Obese youth and their caregivers (N = 150) were evaluated with the Child Sleep Habits Questionnaire and Pediatric Quality of Life. Youth completed the Children's Depression Inventory. Regression models and correlations were calculated. RESULTS: Degree of obesity was predictive of increased sleep difficulties and decreased QOL scores. Children's Depression Inventory scores showed that children with more symptoms of depression had more sleep problems, and these were not associated with the degree of obesity. Adolescents with more difficulties sleeping also reported more symptoms of depression and lower QOL. CONCLUSIONS: Degree of obesity negatively affected QOL and sleep variables. Patients with greater sleeping difficulties reported more symptoms of depression.


Subject(s)
Depression/etiology , Obesity/psychology , Quality of Life/psychology , Sleep Wake Disorders/etiology , Body Weight , Child , Cross-Sectional Studies , Female , Humans , Male , Obesity/complications , Psychiatric Status Rating Scales , Sleep Hygiene , Surveys and Questionnaires
3.
J Head Trauma Rehabil ; 32(2): 125-133, 2017.
Article in English | MEDLINE | ID: mdl-26709583

ABSTRACT

OBJECTIVE: To (1) identify groups of persons with traumatic brain injury (TBI) who differ on 12 dimensions of cognitive function: cognitive, emotional, and physical symptoms; personal strengths; physical functioning; environmental supports; and performance validity; and (2) describe patterns of differences among the groups on these dimensions and on participation outcome. SETTING: Three centers for rehabilitation of persons with TBI. PARTICIPANTS: A total of 504 persons with TBI living in the community who were an average (standard deviation) of 6.3 (6.8) years postinjury and who had capacity to give consent, could be interviewed and tested in English, and were able to participate in an assessment lasting up to 4 hours. DESIGN: Observational study of a convenience sample of persons with TBI. MAIN MEASURES: Selected scales from the Traumatic Brain Injury Quality of Life measures, Neurobehavioral Symptom Inventory, Economic Quality of Life Scale, Family Assessment Device General Functioning Scale, measures of cognitive function, Word Memory Test, and Participation Assessment with Recombined Tools-Objective (PART-O) scale. RESULTS: Cluster analysis identified 5 groups of persons with TBI who differed in clinically meaningful ways on the 12 dimension scores and the PART-O scale. CONCLUSION: Cluster groupings identified in this study could assist clinicians with case conceptualization and treatment planning.


Subject(s)
Brain Injuries, Traumatic/classification , Brain Injuries, Traumatic/rehabilitation , Patient Care Planning , Patient Selection , Psychotherapy, Group/organization & administration , Adolescent , Adult , Brain Injuries, Traumatic/physiopathology , Cluster Analysis , Cohort Studies , Continuity of Patient Care , Female , Follow-Up Studies , Humans , Injury Severity Score , Male , Middle Aged , Neuropsychological Tests , Prospective Studies , Risk Assessment , Time Factors , Treatment Outcome , Young Adult
4.
Pediatr Emerg Care ; 32(8): 508-13, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27490724

ABSTRACT

OBJECTIVE: In 2006, the National Institute of Allergy and Infectious Disease established evidence-based treatment guidelines for anaphylaxis. The purpose of our study was to evaluate provider adherence to guidelines-based management for anaphylaxis in a tertiary care pediatric emergency department (ED). METHODS: Retrospective chart review was conducted of patients (0-18 years) presenting to the Arkansas Children Hospital ED from 2004 to 2011 for the treatment of anaphylaxis using International Classification of Diseases, Ninth Edition, codes. Multiple characteristics including demographics, clinical features, allergen source, and anaphylaxis management were collected. Fisher exact or χ tests were used to compare proportion of patients treated with intramuscular (IM) epinephrine in the preguideline versus postguideline period. Relative risk (RR) statistics were computed to estimate the ratio of patients who received self-injectable epinephrine prescription and allergy follow-up in the preguideline and postguideline groups. RESULTS: A total of 187 patients (median [range] age, 7 [1-18] years; 67% male; 48% African American) were evaluated. Food (44%) and hymenoptera stings (22%) were commonly described culprit allergens, whereas 29% had no identifiable allergen. Only 47% (n = 87) received epinephrine in the ED and 31% (n = 27) via the preferred IM route. Comparing postguideline (n = 126) versus preguideline (n = 61) periods demonstrated increase in the usage of the IM route (46% postguideline vs 6% preguideline; risk ratio (RR), 7.64; 95% confidence interval [CI], 2.04-46.0; P < 0.001). Overall, 61% (n = 115) of the patients received self-injectable epinephrine upon discharge, and there were no significant differences between the groups (64% postguideline vs 56% preguideline, P = 0.30). Postguideline patients were more likely to receive a prescription compared with preguideline patients (64% postguideline vs 56% preguideline; RR, 1.15; 95% CI, 0.89-1.55; P = 0.30). Only 45% (n = 85) received an allergy referral. Postguideline patients were more likely to receive an allergy referral than preguideline patients (48% postguideline vs 41% preguideline; RR, 1.16; 95% CI, 0.81-1.73; P = 0.40). CONCLUSIONS: Provider use of IM epinephrine has improved since anaphylaxis guidelines were published. However, more provider education is needed to improve overall adherence of guidelines in a tertiary care pediatric ED.


Subject(s)
Anaphylaxis/drug therapy , Epinephrine/administration & dosage , Sympathomimetics/administration & dosage , Adolescent , Anaphylaxis/etiology , Child , Child, Preschool , Emergency Medical Services/statistics & numerical data , Epinephrine/therapeutic use , Female , Guideline Adherence , Humans , Infant , Injections, Intramuscular/statistics & numerical data , Male , Practice Guidelines as Topic , Retrospective Studies , Risk , Sympathomimetics/therapeutic use
5.
Rehabil Psychol ; 60(2): 138-46, 2015 May.
Article in English | MEDLINE | ID: mdl-26120740

ABSTRACT

PURPOSE/OBJECTIVES: To determine key dimensions relevant to recovery in the postacute period for persons with traumatic brain injury (TBI) and to determine the ability of scores on these dimensions to predict participation outcomes for persons with TBI. RESEARCH METHOD/DESIGN: This was a prospective cohort, observational study of 504 persons with medically documented TBI. Participants completed a comprehensive battery of measures including cognitive tests; questionnaires assessing self-report of physical, cognitive, and emotional symptoms and strengths; environmental supports; and a measure of participation outcome. RESULTS: Participants were a predominantly male, ethnically/racially diverse sample of persons with complicated mild, moderate, and severe TBI. Variable cluster analysis identified 12 key dimensions of cognitive function, neurobehavioral complaints, personal strengths, physical symptoms and function, environmental supports, and performance validity. In unadjusted analyses, all 12 dimensions were predictive of participation outcome. In multivariable regression analysis with adjustment of all predictors for all other predictors, dimensions measuring memory, independence and self-esteem, resilience, emotional distress, physical functioning, and economic and family support made unique contributions to predicting participation outcome. CONCLUSIONS/IMPLICATIONS: Findings add to our understanding of key aspects of functioning and self-perception for persons with TBI. Knowledge of the profile of an individual patient on these 12 dimensions may assist with development of a treatment approach for the person with TBI. (PsycINFO Database Record


Subject(s)
Brain Injuries/psychology , Brain Injuries/rehabilitation , Health Services Accessibility/statistics & numerical data , Self Report , Social Support , Adolescent , Adult , Cohort Studies , Environment , Female , Humans , Male , Middle Aged , Prospective Studies , Surveys and Questionnaires , Young Adult
6.
Clin Neuropsychol ; 29(4): 522-41, 2015.
Article in English | MEDLINE | ID: mdl-26063081

ABSTRACT

OBJECTIVES: (1) To examine the rate of poor performance validity in a large, multicenter, prospectively accrued cohort of community dwelling persons with medically documented traumatic brain injury (TBI), (2) to identify factors associated with Word Memory Test (WMT) performance in persons with TBI. METHOD: This was a prospective cohort, observational study of 491 persons with medically documented TBI. Participants were administered a battery of cognitive tests, questionnaires on emotional distress and post-concussive symptoms, and a performance validity test (WMT). Additional data were collected by interview and review of medical records. RESULTS: One hundred and seventeen participants showed poor performance validity using the standard cutoff. Variable cluster analysis was conducted as a data reduction strategy. Findings revealed that the 10 cognitive tests and questionnaires could be summarized as 4 indices of emotional distress, speed of cognitive processing, verbal memory, and verbal fluency. Regression models revealed that verbal memory, emotional distress, age, and injury severity (time to follow commands) made unique contribution to prediction of poor performance validity. CONCLUSIONS: Poor performance validity was common in a research sample of persons with medically documented TBI who were not evaluated in conjunction with litigation, compensation claims, or current report of symptoms. Poor performance validity was associated with poor performance on cognitive tests, greater emotional distress, lower injury severity, and greater age. Many participants expected to have residual deficits based on initial injury severity showed poor performance validity.


Subject(s)
Brain Injuries/psychology , Cognition , Memory , Mental Recall , Post-Concussion Syndrome/psychology , Adult , Brain Injuries/complications , Emotions , Female , Humans , Male , Middle Aged , Neuropsychological Tests , Post-Concussion Syndrome/etiology , Prospective Studies , Reproducibility of Results , Surveys and Questionnaires
7.
Am J Med Genet A ; 167(6): 1231-42, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25846410

ABSTRACT

Right-sided and left-sided obstructive heart defects (OHDs) are subtypes of congenital heart defects, in which the heart valves, arteries, or veins are abnormally narrow or blocked. Previous studies have suggested that the development of OHDs involved a complex interplay between genetic variants and maternal factors. Using the data from 569 OHD case families and 1,644 control families enrolled in the National Birth Defects Prevention Study (NBDPS) between 1997 and 2008, we conducted an analysis to investigate the genetic effects of 877 single nucleotide polymorphisms (SNPs) in 60 candidate genes for association with the risk of OHDs, and their interactions with maternal use of folic acid supplements, and pre-pregnancy obesity. Applying log-linear models based on the hybrid design, we identified a SNP in methylenetetrahydrofolate reductase (MTHFR) gene (C677T polymorphism) with a main genetic effect on the occurrence of OHDs. In addition, multiple SNPs in betaine-homocysteine methyltransferase (BHMT and BHMT2) were also identified to be associated with the occurrence of OHDs through significant main infant genetic effects and interaction effects with maternal use of folic acid supplements. We also identified multiple SNPs in glutamate-cysteine ligase, catalytic subunit (GCLC) and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) that were associated with elevated risk of OHDs among obese women. Our findings suggested that the risk of OHDs was closely related to a combined effect of variations in genes in the folate, homocysteine, or glutathione/transsulfuration pathways, maternal use of folic acid supplements and pre-pregnancy obesity.


Subject(s)
Betaine-Homocysteine S-Methyltransferase/genetics , Cardiomyopathy, Hypertrophic/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , Glutamate-Cysteine Ligase/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Obesity/genetics , Adult , Betaine-Homocysteine S-Methyltransferase/metabolism , Cardiomyopathy, Hypertrophic/etiology , Cardiomyopathy, Hypertrophic/metabolism , Cardiomyopathy, Hypertrophic/pathology , DNA (Cytosine-5-)-Methyltransferases/metabolism , Dietary Supplements/adverse effects , Female , Folic Acid/adverse effects , Gene Expression , Gene-Environment Interaction , Glutamate-Cysteine Ligase/metabolism , Glutathione/metabolism , Homocysteine/metabolism , Humans , Infant , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , Models, Genetic , Obesity/etiology , Obesity/metabolism , Obesity/pathology , Polymorphism, Single Nucleotide , Pregnancy , Risk Factors , DNA Methyltransferase 3B
8.
Genetics ; 200(1): 69-78, 2015 May.
Article in English | MEDLINE | ID: mdl-25745024

ABSTRACT

Family-based study design is commonly used in genetic research. It has many ideal features, including being robust to population stratification (PS). With the advance of high-throughput technologies and ever-decreasing genotyping cost, it has become common for family studies to examine a large number of variants for their associations with disease phenotypes. The yield from the analysis of these family-based genetic data can be enhanced by adopting computationally efficient and powerful statistical methods. We propose a general framework of a family-based U-statistic, referred to as family-U, for family-based association studies. Unlike existing parametric-based methods, the proposed method makes no assumption of the underlying disease models and can be applied to various phenotypes (e.g., binary and quantitative phenotypes) and pedigree structures (e.g., nuclear families and extended pedigrees). By using only within-family information, it can offer robust protection against PS. In the absence of PS, it can also utilize additional information (i.e., between-family information) for power improvement. Through simulations, we demonstrated that family-U attained higher power over a commonly used method, family-based association tests, under various disease scenarios. We further illustrated the new method with an application to large-scale family data from the Framingham Heart Study. By utilizing additional information (i.e., between-family information), family-U confirmed a previous association of CHRNA5 with nicotine dependence.


Subject(s)
Genetic Association Studies/methods , Models, Genetic , Pedigree , Humans , Statistics, Nonparametric
9.
Arch Phys Med Rehabil ; 96(4): 652-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25461819

ABSTRACT

OBJECTIVE: To determine the accuracy of self-reported length of coma and posttraumatic amnesia (PTA) in persons with medically verified traumatic brain injury (TBI) and to investigate factors that affect self-report of length of coma and PTA duration. DESIGN: Prospective cohort study. SETTING: Specialized rehabilitation center with inpatient and outpatient programs. PARTICIPANTS: Persons (N=242) with medically verified TBI who were identified from a registry of persons who had previously participated in TBI-related research. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Self-reported length of coma and self-reported PTA duration. RESULTS: Review of medical records revealed that the mean medically documented length of coma and PTA duration was 6.9±12 and 19.2±22 days, respectively, and the mean self-reported length of coma and PTA duration was 16.7±22 and 106±194 days, respectively. The average discrepancy between self-report and medical record for length of coma and PTA duration was 8.2±21 and 64±176 days, respectively. Multivariable regression models revealed that time since injury, performance on cognitive tests, and medical record values were associated with self-reported values for both length of coma and PTA duration. CONCLUSIONS: In this investigation, persons with medically verified TBI showed poor accuracy in their self-report of length of coma and PTA duration. Discrepancies were large enough to affect injury severity classification. Caution should be exercised when considering self-report of length of coma and PTA duration.


Subject(s)
Amnesia/psychology , Brain Injuries/psychology , Coma/psychology , Self Report , Adult , Age Factors , Amnesia/etiology , Amnesia/rehabilitation , Brain Injuries/complications , Brain Injuries/rehabilitation , Coma/etiology , Coma/rehabilitation , Female , Glasgow Coma Scale , Humans , Male , Middle Aged , Prospective Studies , Rehabilitation Centers , Sex Factors , Socioeconomic Factors , Time Factors
10.
Matern Child Health J ; 19(1): 40-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24740726

ABSTRACT

Children with medical complexity (CMC) have multiple specialty need, technology dependence, and high health care utilization. The objective of this study is to profile types of pediatric health care utilization and costs by increasing levels of medical complexity. This is a cross-sectional study of the 2007, 2008 and 2009 Full-Year Data Sets from the Medical Expenditure Panel Survey. Medical complexity was defined by a higher number of positive items from the five question children with special health care needs (CSHCN) Screener. CMC were defined by ≥ 4 positive screener items. Outcomes included the number of inpatient, outpatient, and emergency department visits, associated costs and diagnoses, and reported satisfaction. ICD-9 codes were grouped by Clinical Classifications Software. Of 27,755 total study subjects ≤ 17 years, 4,851 had special needs and 541 were CMC. Older age, male gender, white/non-Hispanic race/ethnicity, and public insurance were all associated with medical complexity (all p < 0.001). CMC had an annual mean of 19 annual outpatient visits ($616) and 0.26 inpatient visits ($3,308), with other significant cost drivers including home health ($2,957) and prescriptions ($2,182). The most common reasons for non-CSHCN and less-complex CSHCN outpatient visits were viral illnesses, while the main reasons for CMC visits were for mental health. Compared to families without CSHCN, those with CMC have, on average, lower satisfaction with health care (8.4 vs. 8.9 out of 10, p < 0.001). Health care models for CMC should account for mental health conditions that may be driving high numbers of outpatient encounters.


Subject(s)
Child Health Services/economics , Child Health Services/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Hospitalization/statistics & numerical data , Outpatients/statistics & numerical data , Adolescent , Child , Child, Preschool , Chronic Disease/economics , Chronic Disease/epidemiology , Chronic Disease/therapy , Communicable Diseases/epidemiology , Cross-Sectional Studies , Disabled Children/statistics & numerical data , Emergency Service, Hospital/economics , Female , Hospitalization/economics , Humans , Infant , Infant, Newborn , Male , Professional-Family Relations , Sex Distribution , United States/epidemiology
11.
PLoS One ; 9(9): e108903, 2014.
Article in English | MEDLINE | ID: mdl-25275547

ABSTRACT

Conotruncal heart defects (CTDs) are among the most severe birth defects worldwide. Studies of CTDs indicate both lifestyle behaviors and genetic variation contribute to the risk of CTDs. Based on a hybrid design using data from 616 case-parental and 1645 control-parental triads recruited for the National Birth Defects Prevention Study between 1997 and 2008, we investigated whether the occurrence of CTDs is associated with interactions between 921 maternal and/or fetal single nucleotide polymorphisms (SNPs) and maternal obesity and tobacco use. The maternal genotypes of the variants in the glutamate-cysteine ligase, catalytic subunit (GCLC) gene and the fetal genotypes of the variants in the glutathione S-transferase alpha 3 (GSTA3) gene were associated with an elevated risk of CTDs among obese mothers. The risk of delivering infants with CTDs among obese mothers carrying AC genotype for a variant in the GCLC gene (rs6458939) was 2.00 times the risk among those carrying CC genotype (95% confidence interval: 1.41, 2.38). The maternal genotypes of several variants in the glutathione-S-transferase (GST) family of genes and the fetal genotypes of the variants in the GCLC gene interacted with tobacco exposures to increase the risk of CTDs. Our study suggests that the genetic basis underlying susceptibility of the developing heart to the adverse effects of maternal obesity and tobacco use involve both maternal and embryonic genetic variants. These results may provide insights into the underlying pathophysiology of CTDs, and ultimately lead to novel prevention strategies.


Subject(s)
Genetic Predisposition to Disease , Genetic Variation , Heart Defects, Congenital/epidemiology , Heart Defects, Congenital/genetics , Mothers , Obesity/complications , Tobacco Use/adverse effects , Case-Control Studies , Chromosomes, Human/genetics , Female , Gene-Environment Interaction , Humans , Polymorphism, Single Nucleotide/genetics , Signal Transduction/genetics , United States/epidemiology
12.
Am J Emerg Med ; 32(11): 1357-63, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25234796

ABSTRACT

OBJECTIVES: The goals of this study were to (1) identify valid variables that correlate with emergency department (ED) crowding and (2) determine a model that could be used to accurately reflect the degree of ED crowding. METHODS: A site sampling form was applied to convenience sampling of 13 community hospitals in California between April 6, 2011, and May 1, 2011. The outcome variable was average perception of crowding by the ED physician and charge nurse on a 100-mm visual analog scale. We focused on 20 candidate predictor variables that represented counts and times in the ED that were collected every 4 hours. A prediction model was developed using multivariable linear regression to determine the measures that predicted ED crowding. A parsimonious model was developed to allow for a clinical useful tool that that explained a significant amount of variability predicted by the full ED crowding model. RESULTS: A total of 2006 data sets were collected for each of the participating hospitals. A total of 1628 time entries for the hospitals were included in the study. Hospital EDs had censuses ranging from 18 000 to 98 000. Full evaluation was completed on 1489 data sets. Twenty variables were considered for the full model with 7 removed due to multicollinearity. The remaining 13 variables constituted the full model and explained 50.5% of the variability in the outcome variable. Five predictors were found to represent 92% of the variability represented by the full model. CONCLUSIONS: Five variables were highly correlated with community ED crowding and could be used to model the full set of all variables in explaining ED crowding.


Subject(s)
Crowding , Emergency Service, Hospital/statistics & numerical data , Hospitals, Community/organization & administration , California , Humans , Models, Organizational , Predictive Value of Tests
14.
Hum Genet ; 133(9): 1127-38, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24894164

ABSTRACT

The development of congenital heart defects (CHDs) involves a complex interplay between genetic variants, epigenetic variants, and environmental exposures. Previous studies have suggested that susceptibility to CHDs is associated with maternal genotypes, fetal genotypes, and maternal-fetal genotype (MFG) interactions. We conducted a haplotype-based genetic association study of obstructive heart defects (OHDs), aiming to detect the genetic effects of 877 SNPs involved in the homocysteine, folate, and transsulfuration pathways. Genotypes were available for 285 mother-offspring pairs with OHD-affected pregnancies and 868 mother-offspring pairs with unaffected pregnancies. A penalized logistic regression model was applied with an adaptive least absolute shrinkage and selection operator (lasso), which dissects the maternal effect, fetal effect, and MFG interaction effects associated with OHDs. By examining the association between 140 haplotype blocks, we identified 9 blocks that are potentially associated with OHD occurrence. Four haplotype blocks, located in genes MGMT, MTHFS, CBS, and DNMT3L, were statistically significant using a Bayesian false-discovery probability threshold of 0.8. Two blocks in MGMT and MTHFS appear to have significant fetal effects, while the CBS and DNMT3L genes may have significant MFG interaction effects.


Subject(s)
Carbon-Nitrogen Ligases/genetics , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Modification Methylases/genetics , DNA Repair Enzymes/genetics , Haplotypes , Heart Defects, Congenital/genetics , Tumor Suppressor Proteins/genetics , Adult , Case-Control Studies , Female , Fetus , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Logistic Models , Polymorphism, Single Nucleotide , Pregnancy , United States
15.
Am J Phys Med Rehabil ; 93(8): 687-702, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24743469

ABSTRACT

OBJECTIVE: This study examines the effect of preinjury depressive symptoms on outcomes 3 mos after complicated and uncomplicated cases of mild traumatic brain injury. DESIGN: Preinjury depressive symptoms, experienced in the 30 days before injury, as measured by retrospective self-report, were assessed within the first 2 wks after injury. The outcome measures assessed at 3 mos after injury included affective/behavioral, cognitive, and physical problems and health-related quality-of-life. RESULTS: There were 177 patients who completed both the baseline and 3-mo follow-up interviews. The sample was categorized by severity of depressive symptoms in the month before injury as normal, mild, or moderate-severe. Compared with those reporting no preinjury depressive symptoms, persons reporting moderate-severe depressive symptoms had significantly worse outcomes on the Affective and Behavioral and the Cognitive subscales of the Head Injury-Family Interview Problem Checklist and on the 36-item Short-Form Health Survey Mental Component Summary score. The group reporting mild preinjury depressive symptoms scored worse on a measure of cognitive symptoms compared with those with no preinjury depressive symptoms. There was no interaction between preinjury depressive symptoms and severity of the mild traumatic brain injury (complicated or uncomplicated) for any of the outcomes. CONCLUSION: Moderate to severe depressive symptoms in the month before injury seems to be a possible risk factor for poor affective/behavioral, cognitive, and mental health-related quality-of-life outcomes at 3 mos after mild traumatic brain injury. Clinicians and researchers should consider the impact of preinjury depression on the recovery process to provide at-risk patients adequate treatment soon after injury.


Subject(s)
Brain Injuries/psychology , Brain Injuries/rehabilitation , Checklist , Depression/epidemiology , Adolescent , Adult , Aged , Brain Injuries/complications , Comorbidity , Health Status Indicators , Humans , Linear Models , Middle Aged , Quality of Life , Risk Factors , Self Report , Treatment Outcome , Young Adult
16.
Genet Epidemiol ; 38(3): 198-208, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24585533

ABSTRACT

Nonsyndromic congenital heart defects (CHDs) develop during embryogenesis as a result of a complex interplay between environmental exposures, genetics, and epigenetic causes. Genetic factors associated with CHDs may be attributed to either independent effects of maternal or fetal genes, or the intergenerational interactions between maternal and fetal genes. Detecting gene-by-gene interactions underlying complex diseases is a major challenge in genetic research. Detecting maternal-fetal genotype (MFG) interactions and differentiating them from the maternal/fetal main effects has presented additional statistical challenges due to correlations between maternal and fetal genomes. Traditionally, genetic variants are tested separately for maternal/fetal main effects and MFG interactions on a single-locus basis. We conducted a haplotype-based analysis with a penalized logistic regression framework to dissect the genetic effect associated with the development of nonsyndromic conotruncal heart defects (CTD). Our method allows simultaneous model selection and effect estimation, providing a unified framework to differentiate maternal/fetal main effect from the MFG interaction effect. In addition, the method is able to test multiple highly linked SNPs simultaneously with a configuration of haplotypes, which reduces the data dimensionality and the burden of multiple testing. By analyzing a dataset from the National Birth Defects Prevention Study (NBDPS), we identified seven genes (GSTA1, SOD2, MTRR, AHCYL2, GCLC, GSTM3, and RFC1) associated with the development of CTDs. Our findings suggest that MFG interactions between haplotypes in three of seven genes, GCLC, GSTM3, and RFC1, are associated with nonsyndromic conotruncal heart defects.


Subject(s)
Haplotypes/genetics , Heart Defects, Congenital/genetics , Maternal-Fetal Exchange/genetics , Adult , Case-Control Studies , Epistasis, Genetic , Female , Fetus/embryology , Fetus/metabolism , Genetic Predisposition to Disease , Humans , Likelihood Functions , Logistic Models , Models, Genetic , Polymorphism, Single Nucleotide/genetics , Pregnancy , Quality Control , United States
17.
J Head Trauma Rehabil ; 29(2): E11-8, 2014.
Article in English | MEDLINE | ID: mdl-23535390

ABSTRACT

OBJECTIVES: To (1) determine factors associated with psychotic-type symptoms in persons with moderate or severe traumatic brain injury (TBI) during early recovery and (2) investigate the prognostic significance of early psychotic-type symptoms for patient outcome. SETTING: Acute neurorehabilitation inpatient unit. PARTICIPANTS: A total of 168 persons with moderate or severe TBI were admitted for inpatient rehabilitation. Of these, 107 had psychotic-type symptoms on at least 1 examination. One-year productivity outcome was available for 87 of the 107 participants. DESIGN: Prospective, inception cohort, observational study. MAIN MEASURES: Confusion Assessment Protocol, productivity outcome at 1 year postinjury. RESULTS: Presence of sleep disturbance, a shorter interval from admission to assessment, and greater cognitive impairment were associated with a greater incidence of psychotic-type symptoms. Younger age, more years of education, and lower frequency and severity of psychotic-type symptoms were associated with a greater likelihood of favorable productivity outcome. CONCLUSIONS: We identified risk factors for the occurrence of psychotic-type symptoms and extended previous findings regarding the significance of these symptoms for outcome after TBI. These findings suggest that improved sleep in early TBI recovery may decrease the occurrence of psychotic-type symptoms.


Subject(s)
Brain Injuries/psychology , Brain Injuries/rehabilitation , Confusion/physiopathology , Psychotic Disorders/physiopathology , Adolescent , Adult , Age Factors , Aged , Brain Injuries/complications , Cohort Studies , Confusion/etiology , Educational Status , Female , Follow-Up Studies , Glasgow Coma Scale , Humans , Injury Severity Score , Inpatients , Male , Middle Aged , Neuropsychological Tests , Predictive Value of Tests , Prevalence , Prospective Studies , Psychotic Disorders/epidemiology , Psychotic Disorders/etiology , Recovery of Function , Rehabilitation Centers , Risk Factors , Severity of Illness Index , Treatment Outcome , Young Adult
18.
J Head Trauma Rehabil ; 28(3): 186-94, 2013.
Article in English | MEDLINE | ID: mdl-23661070

ABSTRACT

OBJECTIVE: To investigate predictors of sexual functioning 1 year following traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Community. PARTICIPANTS: A total of 255 persons with TBI (187 males; 68 females) who had been treated at 1 of 6 TBI Model Systems inpatient rehabilitation units and were living in the community. MAIN MEASURES: Derogatis Interview for Sexual Functioning-Self-Report (DISF-SR); Global Satisfaction With Sexual Functioning (Global Sexual Satisfaction Index); Participation Assessment With Recombined Tools-Objective; Patient Health Questionnaire-9. RESULTS: Older age, female gender, and more severe injury were associated with greater sexual dysfunction 1 year following injury. As age increased from 24 to 49 years, the odds of sexual impairment increased more than 3-fold (95% confidence interval: 1.82-5.88). Females had a 2.5 increase in odds of sexual impairment compared with males (95% confidence interval: 1.23-5.26). Greater social participation was predictive of better sexual functioning. Dissatisfaction with sexual functioning was predicted by older age and depression. CONCLUSIONS AND IMPLICATIONS: Older persons and females appear to be at greater risk for sexual dysfunction after TBI and may benefit from specialized assessment and treatment services. Relationships were identified between social participation and sexual function and between depression and sexual satisfaction that may serve as clinical indicators for further assessment and intervention. Further research is needed to elucidate these relationships and identify effective clinical approaches.


Subject(s)
Brain Injuries/rehabilitation , Sexual Dysfunction, Physiological/epidemiology , Adult , Female , Health Status Indicators , Humans , Injury Severity Score , Logistic Models , Male , Middle Aged , Personal Satisfaction , Prospective Studies , Risk Assessment , Sex Factors , Sexual Behavior , Surveys and Questionnaires , Young Adult
19.
J Pediatr Orthop ; 33(2): 163-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23389571

ABSTRACT

BACKGROUND: The purpose of this study was to determine if digital enhancements could improve upon published and interobserver variability for Cobb angle measurements of idiopathic scoliosis using a commercially available PACS system. The study also sought to determine if experience of the observer affected overall variability and to evaluate the time required to measure Cobb angles using 3 different techniques. As the decision for scoliosis treatment requires serial radiographic measurements by 1 or more observers at different times, precise landmark identification and curve measurement should decrease variability and improve accuracy. METHODS: Fifty-four consecutive digital radiographs of 49 children with idiopathic scoliosis were collected and archived, yielding a total of 117 curves. Five observers, ranging from a PGY2 resident to a senior level faculty member, measured each radiograph in 3 different ways. Technique A involved measuring the curves as the image first appeared on the computer screen. Technique B consisted of 2 extra steps: enlarging the image until the spine filled the screen and using an edge enhancement tool. Technique C utilized the steps in B and further enlarging each vertebra to adjust each measurement. Each technique was timed for each observer. RESULTS: Technique C had the lowest variability that was significantly different from technique A. Technique B also had lower variability than technique A. The 2 observers with the greatest experience demonstrated the least intraobserver and interobserver variability. Techniques B and C decreased the variability of less experienced observers. The average time required for techniques A, B, and C was 25, 29, and 40 seconds, respectively. Confounding variables such as obesity did not affect the measurements, but curve location did, with thoracic curves causing greater variability for less experienced observers. DISCUSSION: The results demonstrate that less experienced observers using the relatively rapid technique A for digital radiographs are more likely to have clinically significant discrepancies in their measurements, which could affect treatment decisions. Taking 4 extra seconds using technique B significantly decreases variability and improves accuracy in the evaluation and management of scoliosis patients. LEVEL OF EVIDENCE: I (testing of previously developed diagnostic criteria).


Subject(s)
Image Interpretation, Computer-Assisted/methods , Scoliosis/diagnosis , Adolescent , Child , Humans , Observer Variation , Radiography , Reproducibility of Results , Scoliosis/diagnostic imaging , Scoliosis/pathology , Time Factors , Young Adult
20.
Burns ; 39(5): 866-75, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23312910

ABSTRACT

PURPOSE: Scar formation is one of the most functionally and cosmetically debilitating results of thermal injuries. Burn team members continuously search for new, cost effective, ways to prevent and treat hypertrophic scar formation. This study is a retrospective review of one facility's use of neoprene based products as an adjunct to, or in place of, traditional scar management techniques. METHODS: Records of all patients treated with neoprene patches or neoprene splints from March 2008 through April 2011 were retrospectively reviewed. Vancouver Scar Scores (VSS) were collected, photographs were reviewed and any documented problems reported by the patients were noted. RESULTS: Mean VSS scores were significantly lower at follow-up (5.3, SD 2.8) than at initial appointment (11.7, SD 1.4) with an estimated mean difference of 6.3 (P=0.0001). A 95% confidence interval for this mean difference is 3.9-8.7. CONCLUSIONS: In the reviewed cases, the use of neoprene inserts or splints resulted in a statistically significant reduction in hypertrophic scars with no secondary complications.


Subject(s)
Bandages , Cicatrix, Hypertrophic/therapy , Neoprene/therapeutic use , Adolescent , Adult , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Male , Regression Analysis , Retrospective Studies , Severity of Illness Index , Splints , Young Adult
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