Director's Report to Council - Research Findings Excerpts

February, 2006

Basic Neurosciences Research

Prenatal Cocaine Exposure and Brain Development

It has been demonstrated that exposure to cocaine increases cell death (i.e., apoptosis) in the fetal brain. To examine the molecular mechanisms of this effect, Dr. Michael Lidow and his group conducted studies in a mouse model of prenatal cocaine exposure. These studies demonstrate that maternal cocaine use is capable of interfering with a range of apoptosis-related genes in the cells of the fetal cerebral wall making these brain cells more sensitive to death-inducing signals. However, this increase in potential for apoptosis is likely to result in actual cell death only when and where the affected cells are subjected to a death-promoting local environment, with the distribution and harshness of such tissue environment depending not only on the cocaine exposure itself but also on fetal developmental stage, maternal health, nutritional status, etc. Consequently, the severity and scope of structural and functional impacts of the pro-apoptotic gene alterations in the offspring of cocaine-abusing mothers should be prone to significant variability due to idiosyncratic use of cocaine and a great diversity in the quality of prenatal care. Furthermore, apoptosis represents just one of several potentially negative influences of cocaine exposure on fetal corticogenesis, with proliferation, migration, and differentiation of cortical cells also being affected by this drug. Novikova, S.I., He, F., Bai, J., Badan, I., Lidow, I.A. and Lidow, M.S. Cocaine-induced Changes in the Expression of Apoptosis-related Genes in the Fetal Mouse Cerebral Wall. Neurotoxicology and Teratology, 27, pp. 3-14, 2005.

Melanocortin-1 Receptor Gene Variants Affect Pain and -Opioid Analgesia in Mice And Humans

Melanocortin-1 receptor (MCR1) was recently found to mediate -opioid receptor analgesia, especially in female mice and human volunteers. This was an unexpected finding because MCR1 is thought to be primarily involved in skin/hair pigmentation and immunomodulation. Mogil and colleagues tested MCR1 mutant mice and humans of various hair color for sensitivity to pain and -opioid analgesia. Mice were tested for their basal sensitivity on six different assays of acute and tonic nociception. Human volunteers were also tested for tolerance to acute pain. For both mice and humans, morphine and its derivative, morphine-6-glucuronide (M6G), were assessed for their effectiveness in reducing pain. In mice, mutants for MCR1 displayed reduced nociceptive responses to morphine and M6G and this effect was significant for both sexes. Studies in human volunteers with two or more variant alleles of the MCR1 gene in amino acids known to abolish MCR1 functionality, compared to volunteers with no or one variant, showed that baseline tolerance differed significantly between genotypes, with greater tolerance for pain in volunteers with the MCR1 variant. In addition, analgesic responses after M6G were greater in MCR1 variant subjects compared to controls. In contrast to the -opioid receptor analgesia, the effect on the -opioid receptor is not sex-dependent. This study eloquently demonstrates the power of direct mouse to human translation in genetic studies. Mogil and colleagues show a significant link between MCR1 gene variants, pain tolerance, and potential efficacy of analgesics acting on the -opioid receptor. Larger human studies are needed to validate these findings in this important area of pain research. Mogil, J.S., Ritchie, J., Smith S.B., Strasburg, K., Kaplan, L., Wallace, M.R., Romberg, R.R., Bijl, H., Sarton, E.Y., Fillingim, R.B. and Dahan, A. Melanocortin-1 Receptor Gene Variants Affect Pain and Mu-opioid Analgesia in Mice and Humans. Journal of Medical Genetics, 42, pp. 583-587, 2005.

Basic Behavioral Research

Sex and Estrous Cycle Phase Influence Conditioned Cue-Induced Reinstatement of Cocaine-Seeking Behavior in Rats

Studies comparing cocaine self-administration in male and female rats have found that females exhibit greater sensitivity in a variety of outcomes; for example, they acquire self-administration more quickly, a greater percentage of females acquire self-administration, females exhibit greater disruption in the diurnal control over cocaine intake, and they exhibit greater motivation for cocaine. Additionally, females exhibit greater cocaine-primed reinstatement of cocaine-seeking behavior. Dr. Ron See and colleagues at the Medical University of South Carolina now report sex differences in reinstatement of cocaine seeking behavior using a conditioned-cue procedure. Separate groups of rats were trained to bar press for varying doses of i.v. cocaine (0.25, 0.4, 0.5, 0.6, and 1.0 mg/kg per infusion). Each infusion was paired with a compound conditioned stimulus (CS) consisting of a light and tone. Following the establishment of stable cocaine self-administration, cocaine responding was extinguished and during reinstatement, the ability of the CS alone (without cocaine) was assessed. During the extinction period, females exhibited more extinction responses (i.e., greater resistance to extinction) than males, perhaps reflecting greater cocaine motivation. During the reinstatement period in which bar-presses produced the CS, but not cocaine, both males and females in all the training dose groups exhibited increased bar-pressing relative to the extinction responding. At intermediate training doses (0.4, 0.5, 0.6 mg/kg) there were no sex differences in reinstatement. Females trained at the lowest dose (0.25 mg/kg) and the highest dose (1.0mg/kg), however, exhibited less bar pressing for the CS than did males. Analysis of reinstatement by females tested during the estrous phase (versus non-estrous) indicated that those trained on the 0.25 mg/kg dose did not show reinstatement, although estrous status did not affect reinstatement at the other training doses. In summary, sex differences in reinstatement occurred at the highest and lowest training dose wherein reinstatement was greater in males than females and at the lowest training dose reinstatement was not observed in estrous females. Given that prior research has shown greater cocaine-primed reinstatement in females than males, the authors suggest that there are sex differences in the variables that control reinstatement. Specifically, females may be more vulnerable to pharmacologically induced reinstatement, whereas males may be more vulnerable to conditioned cue-induced reinstatement. Further research on these sex differences, including hormonal control, and their implications for relapse in humans is warranted. Fuchs, R.A., Evans, A., Mehta, R.H., Case, J. M. and See, R.E. Influence of Sex and Estrous Cyclicity on Conditioned Cue-induced Reinstatement of Cocaine-seeking Behavior in Rats. Psychopharmacology, 179, pp. 662-672, 2005.

Exogenous Progesterone Attenuates the Subjective Effects of Smoked Cocaine in Women, But Not In Men

Several preclinical studies have shown greater sensitivity to cocaine in females as compared to males. Further, many of these behavioral effects are modulated by the estrous cycle, and are eliminated by ovariectomy and subsequently restored by administration of estradiol, suggesting a role for estradiol in male-female differences in cocaine sensitivity. On the other hand, there is suggestive evidence from both preclinical and clinical studies that progesterone may also play a role in cocaine's subjective effects and may contribute to male-female differences in cocaine sensitivity. Drs. Suzette Evans and Richard Foltin of the New York State Psychiatric Institute and Columbia University pursued this possibility by comparing the subjective effects of exogenously administered progesterone in males and in females. In inpatient sessions, each female was studied in the mid-luteal phase (when both progesterone and estradiol were elevated), in the follicular phase (when progesterone was negligible and estradiol was elevated), and in a follicular phase in which progesterone was administered. A dose of 150 mg oral micronized progesterone was given so that the progesterone levels approximated those of the mid-luteal phase. Each male was studied under progesterone administration and under placebo. For each subject a full cocaine dose-response curve (0, 6, 12, and 25 mg cocaine) was obtained in each session. Replicating prior studies, cocaine's subjective effects were greater in the follicular phase than the luteal. Progesterone administration during the follicular phase resulted in an attenuation of the positive subjective effects, but did not alter the subjective effects in males. Drs. Evans and Foltin are now conducting a study to determine whether the administration of progesterone will attenuate cocaine self-administration. Evans, S.M. and Foltin, R.W. Exogenous Progesterone Attenuates the Subjective Effects of Smoked Cocaine in Women, But Not in Men. Neuropsychopharmacology, 31(3), pp. 659-674, 2006.

Behavioral and Brain Development Research

Maternal Cocaine Use during Pregnancy and Physiological Regulation in 4- to 8-Week-Old Infants

In their report on associations between maternal cocaine use during pregnancy and physiological regulation in infants at 4 to 8 weeks of age, Drs. Schuetze and Eiden provided data for 141 mother-infant dyads (77 cocaine-exposed and 64 nonexposed) recruited at birth. Physiological measures of regulation included heart rate (HR) and respiratory sinus arrhythmia (RSA), assessed during a 15-minute period of sleep. Results indicated a dose-dependent relationship between prenatal exposure to cocaine and RSA. The analyses found no evidence that fetal growth or other prenatal exposure to substances mediated this association or that fetal growth or maternal age moderated this association. Analyses did indicate that birth weight (BW), but not birth length (BL), head circumference (HC) or other substance use mediated the association between prenatal exposure to cocaine and HR. In their conclusions, the researchers note that the findings highlight the importance of considering level of exposure when assessing infant outcomes. Schuetze, P. and Eiden, R.D. The Association Between Maternal Cocaine Use During Pregnancy and Physiological Regulation in 4- to 8-Week-Old Infants: An Examination of Possible Mediators and Moderators. Journal of Pediatric Psychology, 31, pp. 15-26, 2006.

Prenatal Drug Exposure and Mother-Infant Interaction

Based on data from the Maternal Lifestyle Study, a multi-site investigation of development following prenatal drug exposure, this report provides findings for mother-infant interactions observed at 4 months infant age. Specifically, the face-to-face still-face (FFSF) paradigm was used, a standardized procedure in which infants engage in face-to-face interaction with the caregiver, and also have to deal with a stressful interaction during which the caregiver becomes poker-faced as well as vocally and gesturally unresponsive. The sample involved 236 cocaine-exposed and 459 non-cocaine-exposed infants (49 were opiate-exposed and 646 non-opiate-exposed). No opiate exposure effects were observed. Mothers of cocaine-exposed infants showed more negative engagement than other mothers. The cocaine-exposed dyads also showed higher overall levels of mismatched engagement states than other dyads, including more maternal negative engagement when the infants were in states of neutral engagement. Infants exposed to heavier levels of cocaine showed more passive-withdrawn negative engagement and engaged in more negative affective matching with their mothers than other infants. The study authors conclude that although effect sizes were small, cocaine exposure, especially heavy cocaine exposure, was associated with subtly negative interchanges, which may have a cumulative impact on infants' later development and their relationships with their mothers. Tronick, E.Z., Messinger, D.S., Weinberg, M.K., et al. Cocaine Exposure is Associated with Subtle Compromises of Infants' and Mothers' Social-Emotional Behavior and Dyadic Features of Their Interaction in the Face-to-Face Still-Face Paradigm. Developmental Psychology, 41, pp. 711-722, 2005.

Prenatal Cocaine/Polydrug Use and Maternal-Infant Feeding Interactions during the First Year of Life

In research conducted at Case Western Reserve University, relationships between prenatal cocaine use and quality of maternal-infant interactions were examined. The Nursing Child Assessment Feeding Scale (NCAFS) was used with a sample of 341 mothers (155 with prenatal cocaine use and 186 without prenatal cocaine use) and their infants at 6.5 and 12 months infant age. Analyses included a number of sociodemographic and maternal covariates, including postnatal substance use. Women who used cocaine during pregnancy were found to be less sensitive to infant cues at 6.5 and 12 months than were non-cocaine-using women. At 6.5 months, heavier prenatal cocaine use was related to less maternal responsiveness to infants. In infants, prenatal cocaine exposure was related to poorer clarity of cues. The investigators found no significant cocaine effects on maternal social-emotional growth fostering, cognitive growth fostering, or infant responsiveness to mother. The study authors note implications of the findings for clinicians and intervention programs. Minnes, S., Singer, L.T., Arendt, R. and Satayathum, S. Effects of Prenatal Cocaine/Polydrug Use on Maternal-Infant Feeding Interactions During the First Year of Life. Developmental and Behavioral Pediatrics, 26, pp. 194-200, 2005.

Cocaine Use during Pregnancy and Preschool Development at 3 Years of Age

In this University of Florida longitudinal cohort study, 154 pregnant cocaine users were recruited and were matched on race, parity, socioeconomic status, and perinatal risk with 154 noncocaine users. The study protocol involves examining development of the children at multiple ages. This report presents findings for the children at 3 years of age based on two measures, the Bayley Scales of Infant Development, and the Vineland Adaptive Behavior Scales (the latter involving caregiver report). A preschool development variable was created, using the Bayley Mental and Psychomotor Development Indices, and the Communication and Motor Skills subscales of the Vineland. Based on structural equation modeling analyses, the researchers concluded that environmental factors accounted for most of the variance in the preschool development variable, and that prenatal cocaine exposure exerted an indirect effect on preschool development through its effect on birth head circumference. Behnke, M., Eyler, F.D., Warner, T.D., et al. Outcome from a Prospective, Longitudinal Study of Prenatal Cocaine Use: Preschool Development at 3 Years of Age. Journal of Pediatric Psychology, 31, pp. 41-49, 2006.

Aggression at Age 5 Years Relative to Prenatal Cocaine Exposure, Gender, and Environmental Risk

In a project conducted by researchers from Robert Wood Johnson Medical School, childhood aggression at age 5 years was examined using a multiple risk model that included prenatal cocaine exposure, environmental risk, and gender as predictors. Aggression was assessed in 206 children using multiple methods, including teacher report, parent report, child's response to hypothetical provocations, and child's observed behavior. Also examined was a composite score that reflected high aggression across contexts. Multiple aspects of the environment were assessed and quantified using a cumulative environmental risk score. Analyses indicated that a significant amount of variance in each of the aggression measures and the composite was explained by the predictors. The factors that were independently related differed depending on the outcome. Prenatal cocaine exposure, gender, and environmental risk were all related to the composite aggression score. The investigators concluded that prenatal cocaine exposure, being male, and living in a high-risk environment were all predictive of aggressive behavior at 5 years. They also suggested that it is this group of exposed boys at high environmental risk that is most likely to show continued aggression over time. Bendersky, M., Bennett, D. and Lewis, M. Aggression at Age 5 as a Function of Prenatal Exposure to Cocaine, Gender, and Environmental Risk. Journal of Pediatric Psychology, 31, pp. 71-84, 2006.

Prenatal Cocaine Exposure and Language Functioning at 6 and 9.5 Years: Moderating Effects of Child Age, Birthweight, and Gender

In this report from an ongoing longitudinal cohort study of development following prenatal drug exposure, results are presented for language functioning at 6 and 9.5 years relative to prenatal cocaine exposure (PCE) and other individual and environmental variables. Analyses involved data for 160 low-income, urban children who completed a standardized language assessment. Based on multivariate longitudinal analyses using generalized estimating equations (GEE), the authors concluded that age, birthweight, and gender moderated the relation between PCE and school-aged children's language. For example, children with PCE had lower receptive language than unexposed children at 6 but not at 9.5 years, lower expressive language if they had lower birthweight, and lower expressive and total language if they were female. Other risk (e.g., violence exposure) and protective factors (e.g., preschool experience) were related to language outcomes regardless of PCE status. Beeghly, M., Martin, B., Rose-Jacobs, R., et al. Prenatal Cocaine Exposure and Children's Language Functioning at 6 and 9.5 Years: Moderating Effects of Child Age, Birthweight, and Gender. Journal of Pediatric Psychology, 31, 98-115, 2006.

fMRI Reveals Alterations in Spatial Working Memory Networks Across Adolescence

Dr. Susan Tapert and her colleagues at the University of California - San Diego have used functional neuroimaging to characterize the development of spatial working memory in adolescents. Their findings show that the frontal and parietal networks that are involved in working memory change over the course of adolescence, with activation of the left prefrontal and bilateral inferior posterior parietal regions increasing with age and activation of bilateral superior parietal cortex decreasing. Their data also demonstrate gender differences, with males showing greater activation of the anterior cingulate cortex and frontopolar cortex than females. Over the age range tested, there were no differences in performance on the working memory task, suggesting that the alterations in activation patterns with age represent the evolution of the strategies used in the task. Schweinsburg, A.D., Nagel, B.J. and Tapert, S.F. J. Int. Neuropsych. Soc. 11, pp. 631-644, 2005.

Clinical Neuroscience Research

Frontal Glucose Hypometabolism in Abstinent Methamphetamine Users

Renshaw and colleagues at McLean Hospital and in Korea examined changes in relative regional cerebral glucose metabolism (rCMRglc) and potential gender differences in abstinent methamphetamine (METH) users. Relative rCMRglc was measured by 18F-fluorodeoxyglucose PET. Frontal executive functions, as assessed by Wisconsin card sorting test (WCST), were compared between 35 abstinent METH users and 21 healthy comparison subjects. In addition, male and female METH users and their gender-matched comparison subjects were compared to investigate potential gender differences. METH users had lower rCMRglc levels in the right superior frontal white matter and more perseveration and nonperseveration errors in the WCST, relative to healthy comparison subjects. Relative rCMRglc in the frontal white matter correlated with number of errors in the WCST in METH users. In the subanalysis for gender differences, lower rCMRglc in the frontal white matter and more errors in the WCST were found only in male METH users, not in female METH users, relative to their gender-matched comparison subjects. The current findings suggest that METH use causes persistent hypometabolism in the frontal white matter and impairment in frontal executive function. These findings also suggest that the neurotoxic effect of METH on frontal lobes of the brain might be more prominent in men than in women. Kim, S.J., Lyoo, I.K, Hwang, J., Young, H.S., Lee, H.L, Lee, D.S., Jeong, D. and Renshaw P. Neuropsychopharmacology, 30, pp. 1383-1391, 2005.

Increased White Matter Hyperintensities in Male Methamphetamine Abusers

Renshaw and colleagues at McLean Hospital and in Korea used structural MRI to compare the prevalence, severity, and location of white matter signal hyperintensities (WMH) in methamphetamine (METH) abusers. Thirty-three METH abusers and 32 age- and gender-matched healthy comparison subjects were studied. Axial T-2 weighted images and fluid attenuated inversion recovery axial images were obtained using a 3.0 T MR scanner. The severity of WMH was assessed separately for deep and periventricular WMH. Ordinal logistic regression models were used to assess the odds ratio for WMH. The METH abusers had greater severity of WMH than the healthy comparison subjects (odds ratio: 7.06, 8.46, and 4.56 for all, deep, and periventricular WMH, respectively). Severity of deep WMH correlated with total cumulative dose of METH. Male METH abusers had greater severity of WMH than female METH abusers. Although male METH abusers had greater severity of WMH than male comparison subjects, there was no significant difference in WMH severity between female METH abusers and female comparison subjects. The current study reports increased WMH in METH abusers, which may be related to METH-induced cerebral perfusion deficits. In addition, female METH abusers had less severe WMH than male METH abusers, possibly due to estrogen's protective effect against ischemic or neurotoxic effects of METH. Bae, C.S, Lyoo, I.K., Sung, Y.H., Yoo, J., Yoon, C.S.J., Kimd, D-J., Hwang, D.W., Kime, S.J. and Renshaw, P. Drug and Alcohol Dependence, 81, pp. 83-88, 2006.

Epidemiology and Etiology Research

Differentiating Risk Factors for Drug Use and Drug Abuse/Dependence

This study asked whether there are risk factors that associate specifically with illicit drug use or illicit drug abuse/dependence, and whether the magnitude of the association is the same for use and abuse/dependence, across different categories of drugs. Data from 1943 female adult twins in a population-based Virginia sample were used to assess the association of 26 putative risk factors with use and abuse/dependence of six illicit psychoactive drugs. These factors, which include socio-demographic variables, religiosity, personality measures, childhood factors, and psychiatric diagnoses, were each examined in relation to drug use, abuse/dependence, or both. Several findings are notable: First, factors associate in similar patterns with different drug categories; second, there is a stronger association of significant socio-demographic factors with drug use, while the psychiatric diagnoses are more strongly associated with progression to abuse/dependence. Third, childhood sexual abuse was associated with drug use and with progression to abuse/dependence. This suggests complex, interacting pathways that determine drug habits in individuals. These results are hypothesis generating. Future studies of causal relationships may draw from the outcomes presented in these analyses. Agrawal, A., Gardner, C., Prescott, C. and Kendler, K. The Differential Impact of Risk Factors on Illicit Drug Involvement in Females. Soc Psychiatry Psychiatr Epidemiol, 40(6), pp. 454-466, 2005.

Risk of Becoming Cocaine Dependent 24 Months after First Use

This study explores estimates for the risk of becoming cocaine dependent within 24 months after first use of the drug, and study subgroup variation in this risk. The study estimates are based on the National Household Survey on Drug Abuse conducted during 2000-2001, with a representative sample of US residents aged 12 years and older (n=114 241). A total of 1081 respondents were found to have used cocaine for the first time within 24 months prior to assessment. Between 5 and 6% of these recent-onset users had become cocaine dependent since onset of use. Less [corrected] risk of recent cocaine dependence soon after onset of cocaine use was found for female subjects, young adults aged 21-25 years, and non-Hispanic Black/African-Americans. Use of crack-cocaine and taking cocaine by injection were associated with having become cocaine dependent soon after onset of use. These epidemiologic findings help to quantify the continuing public health burden associated with new onsets of cocaine use in the 21st century. O 'Brien, M., and Anthony, J. Risk of Becoming Cocaine Dependent: Epidemiological Estimates for the United States, 2000-2001. Neuropsychopharmacology, 30(5), pp. 1006-1018, 2005.

Receptive Syringe Sharing among IDUs during ESAP

Effective January 1, 2001, New York State enacted the Expanded Syringe Access Demonstration Program (ESAP), which allows syringes to be sold in pharmacies without a prescription or dispensed through doctors, hospitals, and clinics to persons 18 years of age or older and permits the possession of those syringes for the purposes of injecting drugs. In this study, researchers assessed changes in receptive syringe sharing since the inception of the ESAP. Sociodemographic characteristics and syringe use data regarding the last injection episode were combined from 3 projects (n = 1181) recruiting injection drug users in ongoing studies in Harlem and the Bronx in New York City from January 2001 through June 2003. These data were analyzed as serial cross sections by calendar quarter. Findings showed that receptive sharing decreased significantly over time, from 13.4% in the first quarter to 3.6% in the last quarter. Obtaining the last injection syringe from an ESAP source (mostly pharmacies) increased significantly over time, from 7.5% in the first quarter to 25.0% in the last quarter. In multiple logistic regression analysis, variables that were significantly associated with less receptive sharing were syringe exchange and ESAP syringe source as well as time since ESAP inception. Female gender and white race/ethnicity were significantly associated with greater receptive sharing. These data show that the increase in the use of pharmacies and other ESAP syringe sources in this sample has been accompanied by a decline in receptive sharing. Pouget, E., Deren, S., Fuller, C., Blaney, S., McMahon, J., Kang, S., Tortu, S., Andia, J., Des Jarlais, D. and Vlahov, D. Receptive Syringe Sharing Among Injection Drug Users in Harlem and the Bronx During the New York State Expanded Syringe Access Demonstration Program. J Acquir Immune Defic Syndr, 39(4), pp. 471-477, 2005.

Influences of Early Attachment, Depression, Illicit Drug Use, and Perceived Support on Drug-dependent Mothers' Parenting

In this study, the authors used an attachment framework to examine how drug-dependent mothers' early bonding experience, depression, illicit drug use, and perceived support work together to influence the family environment. The authors hypothesized that (a) depression and drug use function as proxies for a stronger risk factor, the perceived absence of support available in everyday life, and (b) associations between mothers' early bonding experience and family environment are mediated by perceptions of support and nurture available in everyday life. The authors used a "building block" analytic approach and data collected from 125 mothers enrolled in methadone maintenance to test hypotheses. They expected that associations between mothers' early bonding experience and their perceptions of relationships with their children would be mediated by their perceptions of support and nurture available in their everyday life. Each of these hypotheses was supported for the first outcome, mothers' perceptions of family adaptability. Few psychosocial factors were associated with the second outcome, mothers' perceptions of family cohesion, and a majority of mothers (87.2%) in the sample reported no cohesion in their relationships with their children. Although preliminary, the findings suggest that perceptions of relationships in everyday life play a critical role in the etiology of drug-dependent mothers' parenting. Suchman, N., McMahon, T., Slade, A. and Luthar, S. How Early Bonding, Depression, Illicit Drug Use, and Perceived Support Work Together to Influence Drug-Dependent Mothers' Care Giving. Am J Orthopsychiatry, 75(3), pp. 431-445, 2005.

Prevention Research

Assertiveness and Alcohol Use in Rural Adolescents

There is evidence of higher prevalence rates for alcohol use among rural adolescents relative to urban adolescents. Strategies aimed at preventing adolescent alcohol use typically include the development of social skills to resist peer pressure; among the social skills frequently targeted is assertiveness. Self-report data were collected from a sample of rural adolescents (N-470) participating in a longitudinal preventive intervention study. Five hypothesized dimensions of assertiveness were validated with confirmatory factor analysis: specific substance refusal, individual rights, transaction, justice and social approach. Using gender as a between-subject factor, plus time and assertiveness as within-subject factors to predict an alcohol use composite index, repeated measures analysis revealed a number of significant findings. Several assertiveness dimensions were found to have significant effects on the alcohol use index (specific substance refusal, individual rights, and justices associate lower alcohol involvement; social assertiveness was associated with higher involvement). Moreover, there were significant two and three way interaction effects with time and gender. Goldberg-Lillehoj, C.J., Spoth, R. and Trudeau, L. Assertiveness Among Young Rural Adolescents: Relationship to Alcohol Abuse. J. Child and Adol Sub Abuse, 14(3), pp. 39-67, 2005.

Rural Youth Attitudes towards Substance Use and Violence

To determine the effectiveness of multi-component prevention campaigns (media and other community wide interventions) the authors conducted 15 focus groups with 169 male and female 6th-, 7th-, and 8th- graders. Participants were recruited from small to mid-size communities across the US. The focus groups examined youth attitudes towards their own use and their peers'' use of alcohol, tobacco, drugs, and violence. Several key findings emerged that may be utilized in future multi-component campaigns. First, youth value spending unstructured time with their friends. In terms of tobacco use, both boys and girls are worried about getting caught by their parents; but girls are more concerned about the physical effects of smoking in terms of their attractiveness to members of the opposite sex. In terms of alcohol use, girls were concerned about the dangers of drinking and driving (especially girls in 8th grade) and the pressure to have sex if a date is inebriated. Hispanic youth were more concerned about being a good role model for younger siblings than Caucasian youth. In terms of violence, girls were more likely to spread rumors while boys were more likely to engage in verbal and or physical violence. Finally, both boys and girls preferred prevention and intervention campaigns that were based on real situations and experiences, reflected their culture, were positive, and stress the capabilities of an individual to take action. Kelly, K.J., Comelle, M.G. and Edwards, R.W. Attitudes of Rural Middle-School Youth Toward Alcohol, Tobacco, Drugs, and Violence. The Rural Educator, 25(3), pp. 19-24, 2004.

Which Comes First in Adolescence - Sex and Drugs or Depression

The notion that adolescents self-medicate for depression with substance use and sexual behaviors is widespread, but the temporal ordering of depression and these risk behaviors is not clear. This study tests whether gender-specific patterns of substance use and sexual behavior precede and predict depression or vice versa. Data from the National Longitudinal Study of Adolescent Health were weighted to produce population estimates. The sample includes 13,491 youth, grades 7 to 11, interviewed in 1995 and again one year later. Multivariate logistic regression analyses, conducted in 2004, tested temporal ordering, controlling for covariates. The main outcome measures were depression, as measured by a modified Center for Epidemiological Studies-Depression Scale (CES-D), and three behavior patterns: (1) abstaining from sexual intercourse and drug use, (2) experimental behavior patterns, and (3) high-risk behavior patterns. Results showed that overall, sex and drug behaviors predicted an increased likelihood of depression, but depression did not predict sex and drug behaviors. Among girls, both experimental and high-risk behavior patterns predicted depression. Among boys, only high-risk behavior patterns increased the odds of later depression. Depression did not predict behavior in boys, or experimental behavior in girls; but it decreased the odds of high-risk behavior among abstaining girls (RRR=0.14) and increased the odds of high-risk behavior (RRR=2.68) among girls already experimenting with substance use. Engaging in sex and drug behaviors placed adolescents, especially girls, at risk for future depression. Mechanisms of these relationships are yet to be determined. Hallfors, D.D., Waller, M.W., Bauer, D. and Ford, C.A. Which Comes First in Adolescence - Sex and Drugs or Depression? Am J Prev Med, 29(3), pp. 163-170, 2005.

Consistent Predictors of Substance Use in Emerging Adulthood are Male Gender and Previous Use

This 5-year longitudinal study followed a group of 848 adolescents attending an alternative high school in the emerging adulthood years and measured their adult role taking and substance use. Psychological factors at baseline, and adult role taking at the follow-up were examined as correlates of substance use during emerging adulthood. At this stage of life 74% of subjects were employed, 30% were married or engaged, and 53% had at least one child. One third of subjects were daily cigarette smokers, and 24% had used marijuana in the past 30 days. Forty-seven percent had experienced negative consequences of alcohol or drug use in the last year. The most consistent positive predictors of substance use in emerging adulthood were male gender and previous drug use. Addiction concern was a consistent negative predictor. After controlling for baseline psychosocial variables, attending school and being married at the five-year follow-up were negative correlates of both personal consequences and problems related to alcohol or drug use. Pentz, M.A., Mares, D., Schinke, S. and Rohrbach, L.A. Tobacco, Alcohol, and Other Drug Use Among High-risk Young People: A Five-year Longitudinal Study From Adolescence to Emerging Adulthood. Journal of Drug Issues, 35(2), pp. 333-356, 2005.

Coping Strategies and Mental Health Services

This study examined the relationship among trauma, coping, depression, and mental health service seeking in a probability sample of sheltered homeless and low-income housed women. Results highlight the diversity of trauma. In a longitudinal analysis, women who lived in shelters or experienced major violence had a twofold increase in their risk of depression over the 6-month follow-up. In a cross-sectional analysis, childhood sexual abuse, living in a shelter, physical violence, childhood physical abuse, and death or injury of a friend or relative predicted avoidant coping and symptoms of depression. Active coping and depression predicted mental health service seeking among traumatized women. Modifying coping strategies may ameliorate some of the negative impact of trauma and potentially enhance mental health service use among at-risk women. Rayburn, N.R., Wenzel, S.L., Elliott, M.N., Hambarsoomians, K., Marshall, G.N. and Tucker, J.S. Trauma, Depression, Coping, and Mental Health Service Seeking Among Impoverished Women. J Consult Clin Psychol, 73(4), pp. 667-677, 2005.

American Indian Girls Exceed American Indian Boys, White Girls and White Boys in Cigarette, Marijuana, Alcohol and Inhalant Use

This article documents the prevalence of self-reported substance use among White and American Indian adolescents enrolled in 7th grade in 1997 in a Northern Plains state. Data were collected by self-administered questionnaire preceding adolescents' participation in a randomized field trial of Project Alert (a 7th and 8th grade prevention curriculum). Rates of lifetime and past-month use of cigarettes and marijuana were higher among American Indians than among Whites of the same gender. American Indian girls exceeded American Indian boys as well as White girls and White boys on lifetime and past-month use of cigarettes, marijuana, alcohol and inhalants; differences in cigarette and inhalant use reached statistical significance. These findings add to the sparse literature on substance use among adolescents as young as 12 through 13 years old and underscore the importance of examining gender-specific substance use patterns early in adolescence. Spear, S., Longshore, D. and McCaffrey, D. Prevalence of Substance Use Among White and American Indian Young Adolescents in a Northern Plains State. Journal of Psychoactive Drugs, 37(1), pp. 1-16, 2005.

Research on Behavioral & Combined Treatments for Drug Abuse

Gamblers with Antisocial Personality Disorder (ASPD) Exhibit More Drug Problems

Nancy Petry and colleagues at University of Connecticut School of Medicine examined problems of 237 compulsive gamblers entering a treatment program and found that approximately 16.5% of participants met diagnostic criteria for ASPD. Male gender, history of illicit substance use, Addiction Severity Index Medical composite score, and the number of criteria for compulsive gambling diagnosis all were positive predictors of Antisocial Personality Disorder. These individuals were more likely to have had a history of substance abuse treatment and to have used a wider variety of substances at higher lifetime rates. The results add to the body of literature supporting a subtype of gambler characterized by high levels of other risk taking and illegal behavior such as substance abuse. Pietrzak R.H. and Petry N.M. Antisocial Personality Disorder is Associated with Increased Severity of Gambling, Medical, Drug and Psychiatric Problems among Treatment-seeking Pathological Gamblers. Addiction, 100, pp. 1183-1193, 2005.

Computer-based Brief Motivational Intervention for Perinatal Drug Use in Primary Care

Computer based brief motivational interventions may be able to reach a high proportion of at risk-individuals and thus have potential for significant population impact. Dr. Ondersma and colleagues at Wayne State University conducted a series of studies to determine the feasibility of delivering a computer-based brief motivational intervention, the Motivation Enhancement System (MES) for perinatal drug use. Overall, the women rated the MES as highly acceptable and easy to use and reported significant increases in state motivation at post-intervention and at one month follow up. These preliminary results suggest the feasibility of this approach. Ondersma, S.J., Chase, S.K., Svikis, D.S. and Schuster, C.R. Computer-based Brief Motivational Intervention for Perinatal Drug Use. Journal of Substance Abuse Treatment, 28, pp. 305-312, 2005.

Anxiety Disorders among Patients with Co-occurring Bipolar and Substance Use Disorders

Dr. Kolodziej and colleagues at Harvard and Boston University examined the prevalence and nature of anxiety disorder among treatment seeking patients diagnosed with current bipolar and substance use disorders, and investigated the association between anxiety disorders and substance use. Among 90 participants diagnosed with bipolar disorder I (n=75, 78%) or II (n=15, 22%), 43 (48%) had a lifetime anxiety disorder, with posttraumatic stress disorder (PTSD) occurring most frequently (n=21, 23%). They found that those with PTSD, but not with the other anxiety disorders assessed, began using drugs at an earlier age and had more lifetime substance use disorders, particularly cocaine and amphetamine use disorders, than those without PTSD. Most participants with PTSD were women, sexual abuse was the most frequently reported index trauma, and the mean age of the earliest index trauma occurred before the mean age of initiation of drug use. These findings highlight the heterogeneity of dually diagnosed patients, and the importance of further investigating the ramifications of a trauma history among those who are diagnosed with bipolar and substance use disorders. Kolodziej, M.E., Griffin, M.L., Najavits, L.M., Otto, M.W., Greenfield, S.F. and Weiss, R.D. Anxiety Disorders among Patients with Co-occurring Bipolar and Substance Use Disorders. Drug and Alcohol Dependence, 80(2), pp. 251-257, 2005.

Gender Differences among HIV-Positive Methadone Maintenance Patients Enrolled in a Medication Adherence Trial

Dr. Haug and colleagues at UCSF examined gender differences among HIV + methadone maintained patients on antiretroviral medications. Participants were enrolled in a larger clinical trial, which included a 4 week observation period using electronic monitors to track medication adherence. Contrary to previous literature, no significant differences were detected between men (n=42) and women (n=36) on medication adherence or depression. Both groups showed poor adherence during baseline (M=56% of doses taken on time), high overall prevalence of depression (47%) and illicit cocaine use (47%). Women reported significantly more medication side effects (M=21.4 vs.14.9), higher severity of ASI psychiatric problems (M=0.50 vs. 0.40), and lower SF-36 health related quality of life in physical (M=42.1 vs. 63.3) and emotional functioning (M=26.9 vs. 58.9) than men. Women tested positive for opioids at higher rates than men (53% vs. 29%, respectively, whereas men were more likely to be positive for benzodiazepines than women (26% vs. 6%, respectively). The findings suggest that gender differences between male and female methadone maintenance patients have relevance to treatment providers. Comprehensive assessment, specialized medical care and mental health services may be necessary in the treatment of HIV positive female drug abusers. Haug, N.A., Sorensen, J.L., Lollo, N.D., Gruber, C.A., Delucchi, K.L. and Hall, S.M. Gender Differences among HIV-positive Methadone Maintenance Patients Enrolled in a Medication Adherence Trial. AIDS Care, 17(8), pp. 1022-1029, 2005.

Research on Pharmacotherapies for Drug Abuse

Buprenorphine Versus Methadone in the Treatment of Pregnant Opioid-dependent Patients: Effects on the Neonatal Abstinence Syndrome

Buprenorphine may be shown to be an alternate medication to methadone in pregnant women. The purpose of this study was to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and provide preliminary safety and efficacy data for a larger multi-center trial. In this randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial, treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20-100 mg, respectively. Primary outcome measures were number of neonates treated for NAS; amount of opioid agonist medication used to treat NAS; length of neonatal hospitalization; and peak NAS score. Two of 10 buprenorphine-exposed and 5 of 11 methadone-exposed neonates were treated for NAS. Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates. Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates. Peak NAS total scores did not significantly differ between groups. Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy. Jones, H.E., Johnson, R.E., Jasinski, D.R., O'Grady, K.E., Chisholm, C.A., Choo, R.E., Crocetti, M., Dudas, R., Harrow, C., Huestis, M.A., Jansson, L.M., Lantz, M., Lester, B.M. and Milio, L. Buprenorphine Versus Methadone in the Treatment of Pregnant Opioid-dependent Patients: Effects on the Neonatal Abstinence Syndrome. Drug Alcohol Depend. 79(1), pp. 1-10, 2005. Males and Females Differ in Response to Opioid Agonist Medications Few clinical trials include sex as a factor. This analysis explored within-sex differences in response to opioid agonist medications. Males and females randomly assigned to buprenorphine, LAAM, or methadone were compared on opioid use and retention in treatment. Females receiving buprenorphine had less objective drug use than females receiving methadone, while males receiving LAAM had less objective drug use than males receiving buprenorphine. Retention in treatment was longer for both sexes receiving methadone versus LAAM. Within-subject change results indicate that all three medications benefit both sexes. Clinical trials should be designed to examine the impact of sex on outcomes. Jones, H.E., Fitzgerald, H.and Johnson, R.E. Males and Females Differ in Response to Opioid Agonist Medications. Am. J. Addict. 14(3) pp. 223-233, 2005.

Gender Effects Following Repeated Administration of Cocaine and Alcohol in Humans

Use of cocaine, alcohol, and the two drugs simultaneously is common and the risk of morbidity and mortality associated with these drugs is widely reported. This group carried out a double-blind, placebo-controlled, randomized study examining gender differences in response to administration of these drugs alone and in combination. Current users of cocaine and alcohol (n = 17) who met diagnostic criteria (DSM-IV) for cocaine dependence and alcohol abuse or dependence (not physiologically dependent on alcohol) and who were not seeking treatment for substance use disorders gave voluntary, written, informed consent to participate in three drug administration sessions:1) four doses of intranasal cocaine (1 mg/kg every 30 min) with oral alcohol (1 g/kg following the initial cocaine dose and a second drink at +60 min (120 mg/kg) calculated to maintain a plasma alcohol concentration of approximately 100 mg/dL; 2)four doses of cocaine and alcohol placebo; 3) cocaine placebo and alcohol. Pharmacokinetics were obtained by serial blood sampling, physiological measurements (heart rate and blood pressure) were obtained with automated equipment, and subjective effects were assessed using visual analog scales over 480 min. The results showed that responses to cocaine, alcohol, and cocaine-alcohol were equivalent by gender for most measurements. Women had higher heart rates following alcohol administration (p = .02). Women consistently reported higher ratings for "Feel Good", a measure of overall mental/physical well-being, for all study conditions, reaching statistical significance for cocaine (p = .05) and approaching significance for alcohol administration (p = .1). Women showed equivalent responses to drug administration with the exception of perception of well-being, which was significantly increased for women. These findings may have implications for differential risk for acute and chronic toxicity in women. McCance-Katz, E.F., Hart, C.L., Boyarsky, B., Kosten, T. and Jatlow, P. Gender Effects Following Repeated Administration of Cocaine and Alcohol in Humans. Subst. Use Misuse 40(4), pp. 511-528, 2005.

What Came First, Major Depression or Substance Use Disorder? Clinical Characteristics and Substance Use Comparing Teens in a Treatment Cohort

This study utilized data on a treatment cohort from a randomized clinical trial that recruited adolescents with co-occurring major depression and substance use disorder (N=126). The purpose of this study was to compare adolescents for whom the onset of depression was first versus those for whom the onset of substance use disorder was first or in the same year as depression. Intake clinical evaluations were abstracted to yield common stressors that included childhood abuse, early loss or death, exposure to violence, and attachment problems. Tobacco, alcohol, and cannabis initiation and dependence were compared for the depression first and substance use disorder first groups, and within those groups by gender. Among the substances studied, only cannabis dependence was significantly more prevalent among those with depression first. Comparisons suggest some differences in the developmental path toward comorbid depression and substance use disorders, but remarkable similarity in measures of dependence and severity. Although small samples limited statistical significance, observed differences suggest possible avenues for prevention or intervention. Libby, A M., Orton, H.D., Stover, S.K. and Riggs, P.D. What Came First, Major Depression or Substance Use Disorder? Clinical Characteristics and Substance Use Comparing Teens in a Treatment Cohort. Addict Behav., 30, pp. 1649-1662, 2005.

Services Research

Hospital and Outpatient Health Services Utilization among HIV-Infected Adults In Care: 2000-2002

Rapid changes in HIV epidemiology and antiretroviral therapy may have resulted in recent changes in patterns of healthcare utilization. The objective of this study was to examine sociodemographic and clinical correlates of inpatient and outpatient HIV-related health service utilization in a multi-state sample of patients with HIV. Demographic, clinical, and resource utilization data were collected from medical records for 2000, 2001, and 2002. The study was conducted at 11 U.S. HIV primary and specialty care sites in different geographic regions. Chosen for inclusion, for each year, were HIV-positive patients with at least one CD4 count and any use of inpatient, outpatient, or emergency room services. Sample sizes were 13,392 in 2000, 15,211 in 2001, and 14,403 in 2002. Main outcome measures were the number of hospital admissions, total days in the hospital, and the number of outpatient clinic/office visits per year. Inpatient and outpatient costs were estimated by applying unit costs to numbers of inpatient days and outpatient visits. Findings show that mean numbers of admissions per person per year decreased from 2000 (0.40) to 2002 (0.35), but this difference was not significant in multivariate analyses. Hospitalization rates were significantly higher among patients with greater immunosuppression, women, blacks, patients who acquired HIV through drug use, those 50 years of age and over, and those with Medicaid or Medicare. The mean annual outpatient visits decreased significantly between 2000 and 2002, from 6.06 to 5.66 visits per person per year. Whites, Hispanics, those 30 years of age and over, those on highly active antiretroviral therapy (HAART), and those with Medicaid or Medicare had significantly higher outpatient utilization. Inpatient costs per patient per month (PPPM) were estimated to be 514 dollars in 2000, 472 dollars in 2001, and 424 dollars in 2002; outpatient costs PPPM were estimated at 108 dollars in 2000, 100 dollars in 2001, and 101 dollars in 2002. In conclusion, changes in utilization over this 3-year period, although statistically significant in some cases, were not substantial. Hospitalization rates remain relatively high among minority or disadvantaged groups, suggesting persistent disparities in care. Combined inpatient and outpatient costs for patients on HAART were not significantly lower than for patients not on HAART. Fleishman, J., Gebo, K., Reilly, E., Conviser, R., Christopher Mathews, W., Todd Korthuis, P., Hellinger, J., Rutstein, R., Keiser, P., Rubin, H. and Moore, R. Hospital and Outpatient Health Services Utilization Among HIV-Infected Adults in Care 2000-2002. Med Care, 43(9), pp. 40-52, 2005.

HIV Intervention for Indigent Substance Abusing Women in the USVI

As the HIV/AIDS epidemic continues to expand and penetrate new communities around the globe, risk reduction intervention initiatives must continue to evolve and adapt to new challenges and populations. This is especially true in the Caribbean Basin, where the feminization of the HIV epidemic is tied to a cultural milieu characterized by pervasive gender inequality. HIV intervention programs in the Caribbean must treat women's risks as a function of the social context, standards, and meanings of sexual behaviors and practices in the local community. As such, this article describes an initiative to develop an HIV prevention-intervention protocol for the cultural context of substance abusing women in the US Virgin Islands. Through street-based survey research combined with focus groups and in-depth interviews with such "cultural insiders" as members of the substance-abusing target population, members of the local public health and social services system, and community leaders, a culturally sensitive HIV/AIDS protocol was developed which addresses the supports and barriers to risk reduction faced by substance abusing women in the Virgin Islands. Surratt, H.L. and Inciardi, J. A. Developing an HIV Intervention for Indigent Women Substance Abusers in the United States Virgin Islands. J Urban Health, 82(3-4), pp. iv74-iv83, 2005.

The Intersection of Violence with Culture and HIV Risk among Sex Workers

The Republic of South Africa has become an epicentre of heterosexual HIV transmission among Black women, and the interface between violence against women, substance abuse, and HIV risk is becoming evident. This article describes the characteristics of Black South African women who engage in sex work in Pretoria and examines their intersecting experiences of high-risk sexual behaviour, substance abuse, and victimization. Ninety-three women were recruited into the study. Field staff collected biological measures of drug use and administered a structured, self-report interview. Findings indicate that young South African women who engage in sex work and use drugs rely on this activity as their main source of income and are supporting other family members. The majority of sample women reported experiencing some victimization at the hand of men, either clients or boyfriends, with many reporting childhood abuse histories; young women also report great fear of future victimization. Findings also suggest that as a result of their decreased likelihood of using protection, women who reported any sexual or physical victimization are at increased risk for HIV and other STIs. Results support the critical need for targeted, comprehensive interventions that address substance abuse, sexual risk, and violence as interrelated phenomena. Wechsberg, W.M., Luseno, W.M. and Lam, W.K. Violence Against Substance-Abusing South African Sex Workers: Intersection with Culture and HIV Risk. AIDS Care, 17, Supplement 1, pp. s55-s64, 2005.

Women in Outpatient Treatment for Methamphetamine Improved Family Relationships and Their Medical Condition Relative to Men

This prospective longitudinal study examined treatment outcomes among 1,073 methamphetamine-abusing patients (567 women, 506 men) from 32 community-based outpatient and residential programs in 13 California counties. Data were collected at intake and at 3 months and 9 months after admission. With one exception, improvements from baseline to follow-up were observed in all areas measured by the Addiction Severity Index for both women and men in either modality. Compared to men, women demonstrated greater improvement in family relationships and medical problems, and similar improvement in all other areas, despite the fact that more women were unemployed, had childcare responsibilities, were living with someone who also used alcohol or drugs, had been physically or sexually abused, and reported more psychiatric symptoms. Implications for service improvement are discussed. Hser, Y., Evans, E. and Huang, Y. Treatment Outcomes Among Women and Men Methamphetamine Abusers in California. J Subst Abuse Treat, 28(1), pp. 775-785, 2005.

Patterns of Diagnoses In Hospital Admissions In A Multi-State Cohort of HIV-Positive Adults In 2001

Admissions for AIDS-related illnesses decreased soon after the introduction of highly active antiretroviral therapy (HAART), but it is unclear if the trends have continued in the current HAART era. The investigators examined the diagnoses for hospitalizations of patients with HIV in 2001. Demographic and healthcare data were collected for 8,376 patients from 6 U.S. HIV care sites. Diagnoses were categorized into 18 disease groups and Poisson regression was used to analyze the number of admissions for each of the 4 most common groups. Investigators also compared patients with admissions for AIDS-defining illnesses (ADI) with patients admitted for other diagnoses. Findings revealed that twenty-one percent of patients had at least 1 hospitalization. Among patients hospitalized at least once, 28% were hospitalized for an ADI. Comparing diagnosis categories, the most common hospitalizations were AIDS-defining illnesses (21.6%), gastrointestinal (GI) diseases (9.5%), mental illnesses (9.0%), and circulatory diseases (7.4%). In multivariate analysis, women had higher hospitalization rates than men for ADI (incidence rate ratio [IRR], 1.50; 95% confidence interval [CI], 1.25-1.79) and GI diseases (IRR, 1.52; 95% CI, 1.15-2.00). Compared with whites, blacks had higher admission rates for mental illnesses (IRR, 1.70; 95% CI, 1.22-2.36), but not for ADI. As expected, CD4 count and viral load were associated with ADI admission rates; CD4 counts were also related to hospitalizations for GI and circulatory conditions. Thus, five years after the introduction of HAART, AIDS-defining illnesses continue to have the highest hospitalization rate among the diagnosis categories examined. This result emphasizes the importance of vaccination for pneumonia and influenza, as well as prophylaxis for Pneumocystis jiroveci pneumonia. The relatively large number of mental illness admissions highlights the need for co-management of psychiatric disease, substance abuse, and HIV. Overall, the majority of patients were hospitalized for reasons other than ADI, illustrating the importance of managing comorbid conditions in this population. Data from this cohort of patients with HIV may help guide the allocation of healthcare resources by enhancing our understanding of factors associated with variation in inpatient utilization rates. An understanding of healthcare utilization patterns is important for optimization of care and resource allocation. Betz, M., Gebo, K., Barber, E., Sklar, P., Fleishman, J., Reilly, E. and Christopher Mathews, W. Patterns of Diagnoses in Hospital Admissions in a Multistate Cohort of HIV-Positive Adults in 2001. Med Care, 43(9), pp. 3-14, 2005.

High Rates of Primary Mycobacterium Avium Complex and Pneumocystis Jiroveci Prophylaxis In The U.S.

National data from the mid-1990s demonstrated that many eligible patients with HIV infection do not receive prophylaxis for opportunistic infections (OIs) and that racial and gender disparities existed in OI prophylaxis receipt. The investigative team examined whether demographic disparities in the use of OI prophylaxis persisted in 2001 and whether outpatient care was associated with OI prophylaxis utilization. Demographic, clinical, and pharmacy utilization data were collected from 10 U.S. HIV primary care sites in the HIV Research Network (HIVRN). This study consisted of adult patients (>or=18 years old) in longitudinal HIV primary care. Indications for Pneumocystis jiroveci pneumonia (PCP) or Mycobacterium avium complex (MAC) prophylaxis were 2 or more CD4 counts less than 200 or 50 cells/mm(3) during calendar year (CY) 2001, respectively. Using multivariate logistic regression, they examined demographic and clinical characteristics associated with receipt of PCP or MAC prophylaxis and the association of outpatient utilization with appropriate OI prophylaxis. As for findings, among eligible patients, 88.1% received PCP prophylaxis and 87.6% received MAC prophylaxis. Approximately 80% had 4 or more outpatient visits during CY 2001. Adjusting for care site, male gender (odds ratio [OR], 1.47), Medicare coverage (OR, 1.60), and having 4 or more outpatient visits in a year (OR, 2.34) were significantly associated with increased likelihood of PCP prophylaxis. Adjusting for care site, having 4 or more outpatient visits in a year (OR, 1.85) was associated with increased likelihood of receipt of MAC prophylaxis. There were no demographic or insurance characteristics associated with receipt of MAC prophylaxis. In conclusion, the overall prevalence of OI prophylaxis has increased since the mid-1990s, and previous racial and HIV risk factor disparities in receipt of OI prophylaxis were found to have waned. Integration into the healthcare system is considered an important correlate to receiving OI prophylaxis. Gebo, K., Fleishman, J., Reilly, E., Moore, R. and Moore, R. High Rates of Primary Mycobacterium Avium Complex and Pneumocystis Jiroveci Prophylaxis in the United States. Med Care, 43(9), pp. 23-30, 2005.

International Research

Interactive Skills of Infants With Their High-Risk Mothers

Savonlahti, E., Pajulo, M., Ahlqvist, S., Helenius, H., Korvenranta, H., Tamminen, T. and Piha J. Nord J Psychiatry. 59(2), pp. 139-147, 2005. (INVEST Fellow: Marjaterttu Pajulo, Finland, 2003-2004). In this pilot study, the interactive skills of infants with their high-risk, substance-dependent mothers were explored in residential treatment from pregnancy until the infant was 6 months of age. Fourteen mother-infant pairs were videotaped in feeding and free play situations at 6 months after birth. A comparison, low-risk group consisted of 12 ordinary Finnish mother-infant pairs with minimal clinical risks. The findings show significantly higher levels of dyadic interactive deficiencies among the high-risk mother-infant pairs compared to the low-risk pairs, displayed especially in the feeding situation as lack of mutuality and flat, empty, constricted affective tone of interaction. Also, more interactive deficiencies were found among the high-risk infants compared to the low-risk infants, but the differences were not significant. In this study, this finding might reflect the reduced amount of somatic complications and the benefits of treatment, the impacts of which were not explored. The differences between the high- and low-risk infants were displayed as more withdrawal, depressed mood and avoiding behavior and as less alertness and attentional abilities, robustness and focus on parent's emotional state among the high-risk group.