Prenatal alcohol exposure and cognition at midlife: Evidence of fluid cognition deficits in two cohorts.

BACKGROUND: Prenatal alcohol exposure (PAE) impacts cognition in childhood and early adulthood. Here we evaluate the cognitive abilities of middle-aged adults with and without a history of PAE. METHODS: Participants (N = 200) were recruited from longitudinal cohorts in the Atlanta and Seattle metropolitan areas and completed measures comprising the National Institutes of Health Toolbox's Fluid Cognition Composite. RESULTS: We found that individuals with PAE had lower Fluid Cognition Summary scores and lower Dimensional Change Card Sort and Flanker task subtest scores than non-PAE controls, after accounting for both potentially confounding demographic variables using propensity scores and the effects of study site. When we evaluated the effects of PAE with and without dysmorphic physical features, we found that middle-aged adults in both groups had lower fluid cognition scores than non-PAE controls. However, only the presence of PAE with dysmorphic features was associated with lower performance on the Dimensional Change Card Sort Test and Flanker tasks. CONCLUSION: While all participants with PAE had lower fluid cognition, those with PAE and dysmorphic features also exhibited specific deficits in their performance on measures of inhibition, attention, and cognitive flexibility. Thus, PAE is associated with ongoing cognitive deficits in middle adulthood, which can be observed most clearly among individuals with dysmorphic features.

Phosphorus removal from municipal wastewater by hydrous ferric oxide reactive filtration and coupled chemically enhanced secondary treatment: part II--mechanism.

The removal mechanism of a hydrous ferric oxide (HFO) reactive filtration (RF) process with coupled chemically enhanced secondary treatment (RECYCLE) for phosphorus removal from municipal wastewater (HFO-RF-RECYCLE) was examined. A 0.95-ML/d (0.25-mgd) demonstration of HFO-RF-RECYCLE was performed at a municipal wastewater treatment plant equipped with oxidation ditches and secondary clarifiers. Influent to the plant averaged 6.0 mg/L phosphorus, with a 3-month tertiary effluent average of 0.011 mg/L phosphorus. In addition to aqueous geochemical modeling, experiments with surface charge, scanning electron microscopy, adsorptive capacity, thermal desorption, and most probable number of iron(III)-reducing bacteria were performed on samples from the system, to determine the major phosphorus-removal pathways. Results suggest that, in addition to filtration of particulate phosphorus, the low tertiary effluent total phosphorus result was achieved by adsorption.

Development of the ICD-10 procedure coding system (ICD-10-PCS).

The International Classification of Diseases 10th Revision Procedure Classification System (ICD-10-PCS) has been developed as a replacement for Volume 3 of the International Classification of Diseases 9th Revision. The development of ICD-10-PCS was funded by the U.S. Health Care Financing Administration. ICD-10-PCS has a multi-axial seven character alphanumerical code structure, which provides a unique code for all substantially different procedures and which allows new procedures to be easily incorporated as new codes. ICD-10-PCS was under development for over five years and the initial draft was formally tested and evaluated by an independent contractor. The final version of the ICD-10-PCS was released in the spring of 1998. The design, development and testing of ICD-10-PCS are discussed.

Development of the ICD-10 Procedure Coding System (ICD-10-PCS).

The ICD-10 Procedure Coding System (ICD-10-PCS) has been developed as a replacement for Volume 3 of ICD-9-CM. This article will describe the development and structure of ICD-10-PCS--as well as describe the modifications that have been made to the system as a result of extensive review and testing.

When case management isn't enough: a model of paraprofessional advocacy for drug- and alcohol-abusing mothers.

The Seattle Birth to 3 Project is a paraprofessional advocacy model of enhanced case management designed to effectively intervene with high-risk, drug-dependent mothers. Postpartum women were enrolled based on their heavy use of drugs or alcohol during pregnancy and lack of connection to community services, including prenatal care. Each participant was assigned a paraprofessional advocate who worked intensively on a one-to-one basis with her and her family for 3 years postpartum. Six components of the model advocacy program are identified: establishing the relationship; identifying client goals; establishing linkages with service providers; using written agreements; role modeling and teaching of basic skills; and evaluating the outcome. Results for 51 women assessed after 1 year indicate significant areas of improvement including increased involvement with drug/alcohol treatment agencies, decreased drug use, increased use of birth control, and increased involvement with supportive and skill-building groups such as parenting classes.

Disposition of heroin and its metabolites in heroin-related deaths.

Although many deaths occur annually from heroin intoxication, the presence of heroin has not been reported in postmortem tissues. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, extraction procedures were developed for the efficient recovery of heroin, 6-acetylmorphine, and morphine from postmortem tissue utilizing solid-phase extraction coupled with gas chromatography/mass spectrometry. From heroin-related deaths, 21 sets of blood and urine specimens were collected. The mode of death in these cases was categorized as rapid, delayed, or undetermined. Compared with delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine, and total opiates in blood; a higher ratio of free morphine concentrations to total opiate concentrations in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood of 6-acetylmorphine detection in blood; and lesser likelihood of heroin detection in urine. The study also included analysis of multiple tissue specimens from two subjects who died of heroin intoxication. Heroin was identified in urine and injection-site tissue. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen, and brain were substantially higher than in blood, liver, lung, and kidney. All specimens were positive for morphine. Heroin metabolites were detected in hair specimens. The identification of heroin and 6-acetylmorphine in biological tissues effectively established the presence of heroin in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information for the differential diagnosis of heroin-related deaths.

Pharmacokinetics and pharmacodynamics of intranasal "snorted" heroin.

The purity of illicit heroin in the United States has increased steadily over the last several years, while prices have fallen. Associated with this trend, there has been a recent shift among heroin addicts from intravenous injection to intranasal use ("snorting"). Because of the lack of information on this route of administration, we evaluated the pharmacokinetic and pharmacodynamic properties of intranasal heroin. Results were compared to the effects of heroin by the intramuscular route. Six healthy, male volunteers were administered single doses of intranasal heroin hydrochloride (6 and 12 mg), intramuscular heroin hydrochloride (6 mg), and placebo. Blood levels of heroin, 6-acetylmorphine, and morphine were measured by gas chromatography/mass spectrometry. Simultaneous physiological, behavioral, and performance measures were obtained. Peak blood levels of heroin were attained within 5 min of heroin administration by the intranasal route, similar to those observed for intramuscular administration. Generally, the pharmacokinetic profile of intranasal heroin was equivalent to that for the intramuscular route. Physiological, behavioral, and performance effects following intranasal administration were similar to the effects following intramuscular administration. The relative potency of intranasal heroin was estimated to be approximately one-half that of intramuscular administration. The efficacy of the intranasal route, combined with decreased heroin cost, reduced fear of infection, and the lack of requirements for additional drug paraphernalia, could make this an attractive route of drug administration to naive or infrequent drug users.

Measurement of heroin and its metabolites by isotope-dilution electron-impact mass spectrometry.

A solid-phase extraction procedure was developed for the isolation of heroin, 6-acetylmorphine, and morphine from blood, plasma, saliva, and urine with subsequent assay by gas chromatography/mass spectrometry. Aprotic solvents, mild elution conditions, and an enzyme inhibitor were used to ensure maximum analyte stability. Samples were extracted and the extract was divided into two equal portions. One portion was assayed directly for heroin; detector response was linear over a concentration range of 1.0 to 250 micrograms/L. The second part of the extract was reacted with N-methyl-bis-trifluoroacetamide and assayed for the trifluoroacetyl derivatives of 6-acetylmorphine and morphine; detector response was linear over a concentration range of 1.0 to 500 micrograms/L. The limit of sensitivity was 1.0 microgram/L for each analyte. Hydrolysis of heroin to 6-acetylmorphine during extraction and analysis was < 5%. The method can be used to corroborate heroin use and to study the pharmacological effects of heroin and its metabolites.

The analysis of cocaine and benzoylecgonine in meconium.

We describe an assay for measuring cocaine and benzoylecgonine in meconium of infants born to mothers suspected of using cocaine during their pregnancy. The assay involves the use of fluorescence polarization immunoassay (FPIA) to screen for benzoylecgonine in a methanolic extract of the meconium. The FPIA is sensitive to 0.6 microgram benzoylecgonine per gram meconium. Confirmation of the presence (or absence) of benzoylecgonine and cocaine in meconium samples was performed by solid phase extraction of a second methanolic extract of the meconium, derivatizing using BSTFA, followed by a gas chromatographic/mass spectrometric (GC/MS) analysis, which can detect both cocaine and benzoylecgonine. The GC/MS confirmation was sensitive to less than 0.25 microgram cocaine or 0.5 microgram benzoylecgonine per gram meconium. FPIA, which is commonly used in many toxicology laboratories, is advantageous because it precludes the need to use radioimmunoassays for the initial screen. The confirmation step provides greater certainty for the presence of cocaine and/or benzoylecgonine in meconium.

Measurement of gestational cocaine exposure: sensitivity of infants' hair, meconium, and urine.

We studied the sensitivity of testing the newborn infant's hair, meconium, and urine in detecting gestational cocaine exposure. The infants were born to 59 women who were interviewed to determine their use of cocaine during pregnancy and whose hair was analyzed for the presence of cocaine. Regression analysis was used to evaluate the relationship between cocaine in newborn hair and in maternal hair. Radioimmunoassay of infants' hair and gas chromatography-mass spectrometry of meconium were more sensitive than immunoassay of urine (p less than 0.02), which failed to identify 60% of cocaine-exposed infants. The quantity of benzoylecgonine in the newborn infant's hair correlated best with the proximal-segment maternal hair, representing the last 12 weeks of antepartum hair growth (R = less than R less than 0.83). Approximately half (52%) of the variation in infants' hair was explained by variation in the proximal maternal hair segment. Correlation (R = 0.77) and explained variation (59%) improved slightly when premature infants (n = 9) were excluded. We conclude that analysis of the newborn infant's hair by radioimmunoassay or of meconium by gas chromatography-mass spectrometry is more sensitive than analysis by immunoassay of urine, and can detect fetal cocaine exposure that occurred during the last two trimesters of pregnancy.

Cocaine and the use of alcohol and other drugs during pregnancy.

Recent reports of adverse pregnancy outcomes associated with prenatal cocaine exposure have raised questions about the actual numbers of infants who are exposed to cocaine in utero. Whereas toxicologic urine screens obtained at delivery can detect cocaine use in the preceding few days, they fail to yield a comprehensive picture of use during and immediately before pregnancy. According to postpartum self-report, 15% of a teaching hospital sample and 3% of a private hospital sample of mothers had used cocaine during pregnancy or in the previous month (total = 876). Rates at the teaching hospital reflect a fifteenfold increase over the past 12-year period, when compared with previously obtained data. Cocaine users were significantly more likely to report that they drank alcohol, smoked cigarettes, and took other illicit drugs during pregnancy than women who denied using cocaine. Mothers at highest risk for cocaine use were those who were black (20%), were single-separated-divorced (24% to 33%), and had less than a high school education (21%).