Opioid use disorder during pregnancy: An overview.

Women with opioid use disorder who become pregnant are a particularly vulnerable population and require a comprehensive treatment approach for mother and fetus. Research is continuing on opioid use disorder, effects of opioid use on the fetus, and best treatment approaches. This article reviews current recommendations and guidelines for treatment.

A New Source of Nonprofit Neurosurgical Funding.

The purpose of this paper is to propose and qualify a novel funding mechanism for international neurosurgical nonprofits. The article first identifies and explains neurosurgeons' means for practicing in the developing world through a literature review. After this examination of the current funding methods for surgical care in low-income regions, the work transitions to an explanation of the applications and limitations of a new resource: the internal wealth of a developing country. This wealth may be leveraged by way of a for-profit hospital to create sustainable and domestic funding for nonprofit neurosurgical training. The applicability of the proposed mechanism extends beyond the field of neurosurgery to nonprofits in any health-related discipline. Factors influencing the viability of this mechanism (including local disease burden, economic trajectory, and political stability) are examined to create a baseline set of conditions for success.

Aberrant Behaviors and Co-occurring Conditions as Predictors of Psychotropic Polypharmacy among Children with Autism Spectrum Disorders.

OBJECTIVES: The purpose of this study was to identify rates and predictors of psychotropic medication polypharmacy among Medicaid-eligible children in South Carolina with autism spectrum disorder (ASD) from 2000 to 2008. METHODS: Population-based surveillance data were linked with state Medicaid records to obtain a detailed demographic, behavioral, educational, clinical, and diagnostic data set for all Medicaid-eligible 8-year-old children (n=629) who were identified and diagnosed with ASD using standardized criteria. Polypharmacy was defined as having interclass psychotropic medication claims overlapping for ≥30 consecutive days at any time during the 2-year study period. Multivariable logistic regression was used to model predictors of any polypharmacy, and for the three most common combinations. RESULTS: Overall, 60% (n=377) used any psychotropic medication, and 41% (n=153) of those had interclass polypharmacy. Common combinations were attention-deficit/hyperactivity disorder (ADHD) medications with an antidepressant (A/AD), antipsychotic (A/AP) or a mood stabilizer (A/MS). Black children had lower odds of any polypharmacy, as did those eligible for Medicaid because of income or being foster care versus those eligible because of disability. There were no significant associations between polypharmacy and social deficits in ASD for any combination, although children with communication deficits diagnostic of ASD had lower odds of any polypharmacy and A/AP polypharmacy. Children with argumentative, aggressive, hyperactive/impulsive, or self-injurious aberrant behaviors had higher odds of polypharmacy, as did children with diagnosed co-occurring ADHD, anxiety or mood disorders, or conduct/oppositional defiant disorder (ODD) in Medicaid records. CONCLUSIONS: Future research is warranted to investigate how child-level factors impact combination psychotropic medication prescribing practices and outcomes in ASD.

Isolated left homonymous hemianopia secondary to a pericatheter cyst-a rare presentation of a ventriculoperitoneal shunt failure.

A 26-year-old woman developed a left homonymous hemianopia 1 week after placement of a ventriculoperitoneal shunt through a right parieto-occipital approach. Computed tomography demonstrated a parenchymal cyst in the right occipital lobe. After shunt revision, there was concomitant resolution of the cyst and visual field defect over 1 month. The literature is reviewed regarding this unusual complication of ventriculoperitoneal shunt failure.

Neurosurgical capacity building in the developing world through focused training.

OBJECT: In Tanzania, there are 4 neurosurgeons for a population of 46 million. To address this critical shortage of neurosurgical care, the authors worked with local Tanzanian health care workers, neurosurgeons, the Ministry of Health and Social Welfare, and the Office of the President of Tanzania to develop a train-forward method for sustainable, self-propagating basic and emergency neurosurgery in resource-poor settings. The goal of this study was to assess the safety and effectiveness of this method over a 6-year period. METHODS: The training method utilizes a hands-on bedside teaching technique and was introduced in 2006 at a remote rural hospital in northern Tanzania. Local health care workers were trained to perform basic and emergency neurosurgical procedures independently and then were taught to train others. Outcome information was retrospectively collected from hospital records for the period from 2005 (1 year before method implementation) through 2010. Analysis of de-identified data included descriptive statistics and multivariable assessment of independent predictors of complications following a patient's first neurosurgical procedure. RESULTS: By 2010, the initial Tanzanian trainee had trained a second Tanzanian health care worker, who in turn had trained a third. The number of neurosurgical procedures performed increased from 18 in 2005 to an average of 92 per year in the last 3 years of the study period. Additionally, the number of neurosurgical cases performed independently by Tanzanian health care providers increased significantly from 44% in 2005 to 86% in 2010 (p < 0.001), with the number of complex cases independently performed also increasing over the same time period from 34% to 83% (p < 0.001). Multivariable analysis of clinical patient outcome information to assess safety indicated that postoperative complications decreased significantly from 2005 through 2010, with patients who had been admitted as training progressed being 29% less likely to have postoperative complications (OR 0.71, 95% CI 0.52-0.96, p = 0.03). CONCLUSIONS: The Madaktari Africa train-forward method is a reasonable and sustainable approach to improving specialized care in a resource-poor setting.

Rates and predictors of adherence to psychotropic medications in children with autism spectrum disorders.

Medication adherence in children is poor, particularly among those with chronic or mental health disorders. However, adherence has not been fully assessed in autism spectrum disorders (ASDs). The validated proportion of days covered method was used to quantify adherence to psychotropic medication in Medicaid-eligible children who met diagnostic criteria for ASD between 2000 and 2008 (N = 628). Among children prescribed attention deficit hyperactivity disorder (ADHD) medications, antidepressants, or antipsychotics, 44, 40 and 52 % were adherent respectively. Aggressive behaviors and abnormalities in eating, drinking, and/or sleeping, co-occurring ADHD, and the Medication Regimen Complexity Index were the most significant predictors of adherence rather than demographics or core deficits of ASD. Identifying barriers to adherence in ASD may ultimately lead to improved treatment outcomes.

A double-blind placebo-controlled trial of N-acetylcysteine in the treatment of cocaine dependence.

BACKGROUND: There remains no FDA approved medication for the treatment of cocaine dependence. Preclinical studies and early pilot clinical investigations have suggested that N-acetylcysteine (NAC) may be useful in the treatment of the disorder. OBJECTIVE: The present report assessed the efficacy of NAC in the treatment of cocaine dependence. METHODS: Cocaine-dependent volunteers (n = 111) were randomized to receive daily doses of 1,200 mg of NAC, 2,400 mg of NAC, or placebo. Participants were followed for 8 weeks (up to three visits weekly). At each of these visits, urine samples were collected, along with self-reports of cocaine use. Urine samples were assessed for quantitative levels of benzoylecognine (ie, cocaine metabolite). RESULTS: Overall, the primary results for the clinical trial were negative. However, when considering only subjects who entered the trial having already achieved abstinence, results favored the 2,400 mg NAC group relative to placebo, with the 2,400 mg group having longer times to relapse and lower craving ratings. CONCLUSION: While the present trial failed to demonstrate that NAC reduces cocaine use in cocaine-dependent individuals actively using, there was some evidence it prevented return to cocaine use in individuals who had already achieved abstinence from cocaine. SCIENTIFIC SIGNIFICANCE: N-acetylcysteine may be useful as a relapse prevention agent in abstinent cocaine-dependent individuals.

Frequency and pattern of documented diagnostic features and the age of autism identification.

OBJECTIVE: The DSM-IV-TR specifies 12 behavioral features that can occur in hundreds of possible combinations to meet diagnostic criteria for autism spectrum disorder (ASD). This paper describes the frequency and variability with which the 12 behavioral features are documented in a population-based cohort of 8-year-old children under surveillance for ASD, and examines whether documentation of certain features, alone or in combination with other features, is associated with earlier age of community identification of ASD. METHOD: Statistical analysis of behavioral features documented for a population-based sample of 2,757 children, 8 years old, with ASD in 11 geographically-defined areas in the US participating in the Autism and Developmental Disabilities Monitoring Network in 2006. RESULTS: The median age at ASD identification was inversely associated with the number of documented behavioral features, decreasing from 8.2 years for children with only seven behavioral features to 3.8 years for children with all 12. Documented impairments in nonverbal communication, pretend play, inflexible routines, and repetitive motor behaviors were associated with earlier identification, whereas impairments in peer relations, conversational ability, and idiosyncratic speech were associated with later identification. CONCLUSIONS: The age dependence of some of the behavioral features leading to an autism diagnosis, as well as the inverse association between age at identification and number of behavioral features documented, have implications for efforts to improve early identification. Progress in achieving early identification and provision of services for children with autism may be limited for those with fewer ASD behavioral features, as well as features likely to be detected at later ages.

Utilization of CT perfusion patient selection for mechanical thrombectomy irrespective of time: a comparison of functional outcomes and complications.

BACKGROUND: Patient selection for acute ischemic stroke has been largely driven by time-based criteria, although emerging data suggest that image-based criteria may be useful. The purpose of this study was to directly compare outcomes of patients treated within a traditional time window with those treated beyond this benchmark when CT perfusion (CTP) imaging was used as the primary selection tool. METHODS: A prospectively collected database of all patients with acute ischemic stroke who received intra-arterial therapy at the Medical University of South Carolina was retrospectively analyzed, regardless of time from symptom onset. At presentation, CTP maps were qualitatively assessed. Selected patients underwent intra-arterial therapy. Functional outcome according to the modified Rankin scale (mRS) score at about 90 days was documented. RESULTS: 140 patients were included in the study. The median time from symptom onset to groin access was 7.0 h. Overall, 28 patients (20%) had bleeding complications, but only 10 (7.1%) were symptomatic. The average National Institute of Health Stroke Scale (NIHSS) score for patients treated ≤ 7 h from symptom onset was 17.3 and 30.2% had a mRS score of 0-2 at 90 days. Patients treated >7 h from symptom onset had an average NIHSS score of 15.1 and 45.5% achieved a mRS score of 0-2 at 90 days (p=0.104). Patients in the two groups had similar rates of symptomatic intracerebral hemorrhage (8.5% and 5.8%, respectively; p=0.745). CONCLUSIONS: No difference was found in the rates of good functional outcome between patients treated ≤ 7 h and those treated >7 h from symptom onset. These data suggest that imaging-based patient selection is a safe and viable methodology.

Completeness of case ascertainment for surveillance of autism spectrum disorders using the autism developmental disabilities monitoring network methodology.

BACKGROUND: The Autism and Developmental Disabilities Monitoring Network (ADDM), sponsored by the Centers for Disease Control and Prevention, is the largest-scale project ever undertaken to identify the prevalence of Autism Spectrum Disorders (ASD) in the United States. OBJECTIVE: The objective of the present study was to examine the accuracy of the ADDM methodology in terms of completeness of case ascertainment; that is, to assess the success of the ADDM Network in identifying and accurately classifying all existing cases of ASD among 8-year-old children in the target study areas. METHODS: To accomplish this objective, the ADDM methodology was applied to a selected region of South Carolina for 8-year olds in 2000 (birth year 1992) and again seven years later for the same region and birth year. RESULTS: For this region and birth year, completeness of case ascertainment was high, with prevalence estimates of 7.6 per 1000 at both ages 8- and 15-years. For children common to both surveillance years, concordance in case status was also high (82%). CONCLUSIONS: Given that prevalence did not change within this region and birth year, continued research is needed to better understand the changes in prevalence estimates being found by the ADDM network across surveillance groups.

Maternal smoking during pregnancy and the prevalence of autism spectrum disorders, using data from the autism and developmental disabilities monitoring network.

BACKGROUND: Reported associations between gestational tobacco exposure and autism spectrum disorders (ASDs) have been inconsistent. OBJECTIVE: We estimated the association between maternal smoking during pregnancy and ASDs among children 8 years of age. METHODS: This population-based case-cohort study included 633,989 children, identified using publicly available birth certificate data, born in 1992, 1994, 1996, and 1998 from parts of 11 U.S. states subsequently under ASD surveillance. Of these children, 3,315 were identified as having an ASD by the active, records-based surveillance of the Autism and Developmental Disabilities Monitoring Network. We estimated prevalence ratios (PRs) of maternal smoking from birth certificate report and ASDs using logistic regression, adjusting for maternal education, race/ethnicity, marital status, and maternal age; separately examining higher- and lower-functioning case subgroups; and correcting for assumed under-ascertainment of autism by level of maternal education. RESULTS: About 13% of the source population and 11% of children with an ASD had a report of maternal smoking in pregnancy: adjusted PR (95% confidence interval) of 0.90 (0.80, 1.01). The association for the case subgroup autistic disorder (1,310 cases) was similar: 0.88 (0.72, 1.08), whereas that for ASD not otherwise specified (ASD-NOS) (375 cases) was positive, albeit including the null: 1.26 (0.91, 1.75). Unadjusted associations corrected for assumed under-ascertainment were 1.06 (0.98, 1.14) for all ASDs, 1.12 (0.97, 1.30) for autistic disorder, and 1.63 (1.30, 2.04) for ASD-NOS. CONCLUSIONS: After accounting for the potential of under-ascertainment bias, we found a null association between maternal smoking in pregnancy and ASDs, generally. The possibility of an association with a higher-functioning ASD subgroup was suggested, and warrants further study.

Brief report: Association between behavioral features and gastrointestinal problems among children with autism spectrum disorder.

Recent reports suggest certain behaviors among children with autism spectrum disorders (ASD) may indicate underlying gastro-intestinal (GI) problems, and that the presence of these behaviors may help alert primary care providers to the need to evaluate a child with ASD for GI problems. The purpose of this population-based study of 487 children with ASD, including 35 (7.2%) with a medically documented history of GI problems, was to compare behavioral features of children with and without a history of GI problems. Unusual sleeping or eating habits and oppositional behavior were significantly associated with GI problems. These behaviors, however, were frequent in both children with and without GI problems, suggesting they may have limited utility in a screening capacity for GI problems.

Comparison of Methods for Identifying Phenotype Subgroups Using Categorical Features Data With Application to Autism Spectrum Disorder.

We evaluate the performance of the Dirichlet process mixture (DPM) and the latent class model (LCM) in identifying autism phenotype subgroups based on categorical autism spectrum disorder (ASD) diagnostic features from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision. A simulation study is designed to mimic the diagnostic features in the ASD dataset in order to evaluate the LCM and DPM methods in this context. Likelihood based information criteria and DPM partitioning are used to identify the best fitting models. The Rand statistic is used to compare the performance of the methods in recovering simulated phenotype subgroups. Our results indicate excellent recovery of the simulated subgroup structure for both methods. The LCM performs slightly better than DPM when the correct number of latent subgroups is selected a priori. The DPM method utilizes a maximum a posteriori (MAP) criterion to estimate the number of classes, and yielded results in fair agreement with the LCM method. Comparison of model fit indices in identifying the best fitting LCM showed that adjusted Bayesian information criteria (ABIC) picks the correct number of classes over 90% of the time. Thus, when diagnostic features are categorical and there is some prior information regarding the number of latent classes, LCM in conjunction with ABIC is preferred.

Enhanced cortisol response to stress in children in autism.

Children with Autism often show difficulties in adapting to change. Previous studies of cortisol, a neurobiologic stress hormone reflecting hypothalamic-pituitary-adrenal (HPA) axis activity, in children with autism have demonstrated variable results. This study measured cortisol levels in children with and without Autism: (1) at rest; (2) in a novel environment; and (3) in response to a blood draw stressor. A significantly higher serum cortisol response was found in the group of children with autism. Analysis showed significantly higher peak cortisol levels and prolonged duration and recovery of cortisol elevation following the blood-stick stressor in children with autism. This study suggests increased reactivity of the HPA axis to stress and novel stimuli in children with autism.

High prescription drug use and associated costs among Medicaid-eligible children with autism spectrum disorders identified by a population-based surveillance network.

PURPOSE: We assessed medication use and associated costs among 8- and 15-year-old children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network. METHODS: All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n = 263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder-not otherwise specified were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data. RESULTS: All 263 SCADDM-identified children had Medicaid data available; 56% (n = 147) had a prescription of any type, 40% (n = 105) used psychotropic medication, and 20% (n = 52) used multiple psychotropic classes during the study period. Common combinations were (1) attention deficit hyperactivity disorder medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age. CONCLUSIONS: Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age.

The prevalence of youth with autism spectrum disorders in the criminal justice system.

Past surveys have reported high rates of youth with disabilities in the juvenile justice system, however, little research has examined the frequency with which youth with Autism spectrum disorders (ASD) are in contact with law enforcement. Using records linkage with the Department of Juvenile Justice and the South Carolina Law Enforcement Division and the South Carolina Autism and Developmental Disabilities Monitoring Program (SC ADDM), this study compares the frequency, type, and outcome of criminal charges for youth with ASD and non-ASD youth. Youth with ASD had higher rates of crimes against persons and lower rates of crimes against property. Youth with ASD were more likely to be diverted into pre-trial interventions and less likely to be prosecuted than comparison youth. When compared to the overall SC ADDM sample, charged youth were less likely to have comorbid intellectual disability.

Application of beta regression to analyze ischemic stroke volume in NINDS rt-PA clinical trials.

BACKGROUND AND PURPOSE: Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes. METHODS: The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis. RESULTS: Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes. CONCLUSIONS: Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes.

Risk for cognitive deficit in a population-based sample of U.S. children with autism spectrum disorders: variation by perinatal health factors.

BACKGROUND: From 30% to 60% of children with an autism spectrum disorder (ASD) have an IQ measure that falls in the intellectual disability (ID) range. It is not well studied whether, for children within this ASD subgroup, there is variation in the risk for low IQ based on a child's perinatal risk factors. OBJECTIVE/HYPOTHESES: We assessed whether preterm delivery and term small-for-gestational-age (tSGA) were associated with various measures of cognitive deficit among children with ASDs. METHODS: A sample of 1129 singleton children born in 1994 and identified through school and health record review as having an ASD by age 8 years were selected from a U.S. population-based surveillance network. Mean IQ and dichotomous IQ outcomes indicating various levels of ID were examined according to whether a child was preterm (<37 weeks' gestation) or tSGA (term delivery and birth weight <10th percentile for gestational age of a U.S. referent). Results for the total sample and within race-ethnicity/maternal education strata were adjusted for child sex and ASD subtype classification. RESULTS: Mean IQ was significantly (p < .05) lower in children delivered preterm (69.5) than term (74.5) and tSGA (69.3) than term appropriate-for gestational age (75.3). In stratified analyses, the preterm-IQ association was significant only among non-Hispanic white (NHW) children with maternal education at birth of high school or less; adjusted mean IQ was 8 points lower among those delivered preterm (65.4) than term (73.8). Term-SGA was associated with a significant 8-point deficit in adjusted mean IQ (75.5 vs. 83.8) in NHW children with maternal education greater than high school and a 6-point deficit that approached significance (68.4 vs. 74.5, p=0.10) in NHW children with maternal education of high school or less. Non-Hispanic black children in both maternal education groups had significantly lower mean IQs than NHW children with little variation by preterm or tSGA. CONCLUSIONS: In children with ASDs, the risk for concurrent ID or IQ deficit is associated with both preterm delivery and tSGA; these associations may vary by race-ethnicity and SES. Further studies of ASD-ID co-occurrence and the effectiveness of intervention strategies should consider both perinatal and sociodemographic factors.

Association of medically attended traumatic brain injury and in-prison behavioral infractions: a statewide longitudinal study.

This study examined the association between medically attended traumatic brain injury (TBI) and in-prison behavioral infractions in a statewide population by comparing rate ratios of infractions in inmates with and without TBI over an 11.5-year period (16,299 males and 1,270 females). The in-prison behavioral infraction rate was significantly increased in males with TBI compared with no TBI for all infractions (RR = 1.32, 95% CI: 1.12, 1.55), violent infractions (RR = 1.86, 95% CI: 1.54, 2.24), and nonviolent infractions (RR = 1.19, 95% CI: 1.00, 1.41). The violent behavioral infraction rate was significantly increased in females with TBI compared with no TBI (RR = 2.44, 95% CI: 1.45, 4.12). A clearer understanding of inmates with a history of TBI and further examination of the association of TBI and behavioral infractions are needed.