Efficacy of Low-Dose Buspirone for Restricted and Repetitive Behavior in Young Children with Autism Spectrum Disorder: A Randomized Trial.

OBJECTIVES: To determine safety and efficacy of the 5HT1A serotonin partial agonist buspirone on core autism and associated features in children with autism spectrum disorder (ASD). STUDY DESIGN: Children 2-6 years of age with ASD (N = 166) were randomized to receive placebo or 2.5 or 5.0 mg of buspirone twice daily. The primary objective was to evaluate the effects of 24 weeks of buspirone on the Autism Diagnostic Observation Schedule (ADOS) Composite Total Score. Secondary objectives included evaluating the effects of buspirone on social competence, repetitive behaviors, language, sensory dysfunction, and anxiety and to assess side effects. Positron emission tomography measures of tryptophan metabolism and blood serotonin concentrations were assessed as predictors of buspirone efficacy. RESULTS: There was no difference in the ADOS Composite Total Score between baseline and 24 weeks among the 3 treatment groups (P = .400); however, the ADOS Restricted and Repetitive Behavior score showed a time-by-treatment effect (P = .006); the 2.5-mg buspirone group showed significant improvement (P = .003), whereas placebo and 5.0-mg buspirone groups showed no change. Children in the 2.5-mg buspirone group were more likely to improve if they had fewer foci of increased brain tryptophan metabolism on positron emission tomography (P = .018) or if they showed normal levels of blood serotonin (P = .044). Adverse events did not differ significantly among treatment groups. CONCLUSIONS: Treatment with 2.5 mg of buspirone in young children with ASD might be a useful adjunct therapy to target restrictive and repetitive behaviors in conjunction with behavioral interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00873509.

Alcohol, tobacco, cocaine, and marijuana use: relative contributions to preterm delivery and fetal growth restriction.

BACKGROUND: Pregnancy substance use is linked to low birth weight. However, less is known about relative contributions of various substances and whether effects are due to decreased gestational duration, restriction of fetal growth, or both. The study goal was to use causal modeling to evaluate the individual impact of alcohol, tobacco, cocaine, and marijuana on gestational duration and fetal growth. METHODS: Participants were 3164 urban black women recruited at entry to prenatal care and followed to delivery, with all gestational dating ultrasound supported. Pregnancy substance use was assessed via self-report (alcohol, tobacco, cocaine, and marijuana). RESULTS: Alcohol, cigarette, and cocaine use were all individually and negatively related to gestational age at delivery. However, only alcohol, cigarette, and marijuana use predicted fetal growth, with effects for alcohol and cigarette greater and more discrepant for older women. Overall, heavy cigarette smoking had the greatest individual impact on birth weight (up to 431 g). Heavy levels of use of all 4 substances by older women decreased birth weight by 26% (806 g). CONCLUSIONS: For perhaps the first time, reduced birth weight is apportioned both by type of substance and mechanism of effect. The use of alcohol and/or cigarettes was clearly more harmful to fetal growth than cocaine use. Findings demonstrate the need for continued emphasis on intervention efforts to address legal and illicit pregnancy substance use.

Trends in long term exposure to propoxur and pyrethroids in young children in the Philippines.

BACKGROUND/AIM: Pesticides are neurotoxic and can adversely affect children's neurobehavioral outcome. Ongoing pesticide exposure has to be monitored in the study of long term outcome of pesticide adverse effects since changes in the type and amount of exposure can influence outcome. The aim of this paper is to describe the trend in long term pesticide exposure in children through the analysis of pesticides in their hair. PATIENTS AND METHODS: As part of an NIH study on the long term effects of pesticide exposure in young children, ongoing exposure to pesticides was determined by the analysis of children's hair for propoxur and pyrethroids by gas chromatography/mass spectrometry at 2, 4 and 6 years of age. RESULTS: There were significant changes in the prevalence and concentration of propoxur and pyrethroids in children's hair at 2, 4 and 6 years of age. At ages 2 and 4 years, the prevalence of propoxur exposure increased from 12.4% to 24.1% (p<0.001) but dramatically decreased to 1.7% at 6 years (p<0.001). For bioallethrin, the prevalence of exposure steadily increased from 2 years (0.7%, p<0.001) to 4 years (12.4%, p<0.001) and to 6 years (18.4% p<0.001). Exposure to transfluthrin significantly increased from 4 years (1.0%) to 6 years (9.2%, p<0.001). There were also significantly higher median concentrations of bioallethrin at 2 compared to 4 years and for propoxur at 2 years compared to 6 years. Between 4 and 6 years, there was a higher median concentration of propoxur at 4 compared to 6 years and for transfluthrin and bioallethrin, at 6 compared to 4 years. CONCLUSION: Changes in the prevalence and concentration of exposure to propoxur and pyrethroids in children at 2, 4 and 6 years of age are related to the progress in ambulation of young children and to changes in the formulation of home spray pesticides. Thus, periodic monitoring of pesticide exposure is necessary when studying the long term effects of pesticide exposure in the neurodevelopment of young children.

Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age.

OBJECTIVE: Our aim was to determine the effects of fetal exposure to propoxur and pyrethroids, on child neurodevelopment at 2 years of age. PATIENTS AND METHODS: Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin are used. To detect prenatal exposure to these pesticides, maternal hair and blood, infant's hair, cord blood, and meconium were analyzed for the pesticides by gas chromatography/mass spectrometry. Infants were examined at 2 years of age with 95.1% follow up rate and their neurodevelopment outcome was assessed by the Griffiths mental developmental scale (N=754). RESULTS: Meconium analysis was the most sensitive method to detect fetal exposure to pesticides and exposure was highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin, transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed to determine the effects of fetal exposure to propoxur and pyrethroids on the child's neurodevelopment at 24 months of age while controlling for confounders. Only singletons and those with complete data for the path analysis were included (N=696). Using a path analysis model, there was a significant negative (ß=-0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and motor development at 2 years of age after controlling for confounders, e.g., infant gender, socioeconomic status, maternal intelligence, home stimulation (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age. CONCLUSION: At 2 years of age, prenatal exposure to propoxur was associated with poorer motor development in children.

Analysis of House Dust and Children's Hair for Pesticides: A Comparison of Markers of Ongoing Pesticide Exposure in Children.

BACKGROUND/AIM: The long term study of the adverse effects of pesticides on child neuro development requires monitoring not only of initial, but ongoing pesticide exposure. Our aim was to compare house dust and children's hair as environmental and biological markers of ongoing pesticide exposure in children. DESIGN/METHODS: In a continuing NIH study on the adverse effects of prenatal pesticide exposure on child neurodevelopment, ongoing pesticide exposure after birth was measured in swept house dust and hair in the children at 4 years of age for propoxur and pyrethroids (transfluthrin, bioallethrin, cyfluthrin and cypermethrin) by gas chromatography/mass spectrometry. The prevalence and concentration of pesticides in the two matrices were compared. RESULTS: Prevalence of propoxur was higher in hair compared to house dust (p<0.001) whereas prevalence of the pyrethroids was higher (p<0.001) in house dust. The overall concentrations of the pyrethroids were also higher (p<0.007) in house dust compared to hair. There was a significant (p<0.001) correlation between dust and hair for bioallethrin and cypermethrin. CONCLUSIONS: Ongoing exposure of children to environmental pesticides is sensitively detected by analysis of children's hair and house dust. However, prevalence of propoxur was higher in hair compared to swept house dust, but the opposite was found for the pyrethroids. Thus, both matrices should be analyzed. There was a significant (p<0.001) correlation between house dust and hair for bioallethrin and cypermethrin.

Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides.

OBJECTIVE: The aim of this study was to determine optimum biomarkers to detect fetal exposure to environmental pesticides by the simultaneous analysis of maternal (hair and blood) and infant (cord blood, infant hair or meconium) matrices and to determine if a combination of these biomarkers will further increase the detection rate. PATIENTS AND METHODS: Pregnant women were prospectively recruited from an agricultural site in the Philippines with substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Maternal hair and blood were obtained at midgestation and at delivery and infant hair, cord blood and meconium were obtained after birth. All samples were analyzed by gas chromatography/mass spectrometry (GC/MS) for the above pesticides and some of their metabolites. RESULTS: A total of 598 mother/infant dyads were included in this report. The highest rates of pesticide exposure were detected in meconium (23.2% to propoxur, 2.0% to pretilachlor, 1.7% to cypermethrin, 0.8% to cyfluthrin, 0.7% to 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and 0.3% to malathion and bioallethrin) and in maternal hair (21.6% to propoxur, 14.5% to bioallethrin, 1.3% to malathion, 0.8% to DDT, 0.3% to chlorpyrifos and 0.2% to pretilachlor). Combined analysis of maternal hair and meconium increased detection rate further to 38.5% for propoxur and to 16.7% for pyrethroids. Pesticide metabolites were rarely found in any of the analyzed matrices. CONCLUSIONS: There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticides, propoxur and pyrethroids. Analysis of meconium for pesticides was the single most sensitive measure of exposure. However, combined analysis of maternal hair and meconium significantly increased the detection rate. A major advantage of analyzing maternal hair is that prenatal pesticide exposure in the mother can be detected and intervention measures can be initiated to minimize further exposure of the fetus to pesticides.

Effects of mometasone furoate administered via a dry powder inhaler once daily in the evening on nocturnal lung function and sleep parameters in patients with moderate persistent asthma: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND AND OBJECTIVE: Nocturnal symptoms are common in asthma patients and have the potential for considerable clinical effects due to a lack of sleep and persistent daytime symptoms of somnolence and activity impairment. The primary objective of this investigation was to determine the effect of a 14-day course of once-daily evening administration of mometasone furoate 400 microg administered via a dry powder inhaler (MF-DPI 400 microg qd pm) on the overnight decline in pulmonary function observed in patients with nocturnal asthma. METHODS: Eligible enrollees were between the ages of 18 and 60 years and had established mild to moderate asthma, with an improvement in forced expiratory volume in 1 second (FEV(1)) of >15% after administration of inhaled salbutamol (albuterol) 200 microg. All enrolled patients had a history of nocturnal asthma. Enrollees were randomized to receive MF-DPI 400 microg qd pm or placebo administered between 6 pm and 8 pm for 14 days. The primary outcome evaluated in the study was reduction in nocturnal decline in evening (8 pm) to morning (6 am) FEV(1) values. Secondary outcomes included reduction in nocturnal decline in evening to morning peak expiratory flow rate (PEFR), polysomnographic indices of sleep, and psychometric indices (Nocturnal Rhinoconjunctivitis Quality of Life Questionnaire [NRQLQ], 36-item Short Form of the Medical Outcomes Survey [SF-36], and Asthma Quality of Life Questionnaire [AQLQ]). RESULTS: A total of 20 patients were randomized and completed all phases of the study. No significant differences were observed between treatment groups in the primary outcome of nocturnal decline in FEV(1) from pretreatment to end of treatment. Likewise, there was no significant difference between treatment groups in polysomnographic indices of sleep or quality-of-life assessments. However, there was a trend toward improvement in the activity scale of the AQLQ assessment in the MF-DPI 400 microg qd pm treatment group. CONCLUSION: No significant treatment effect on nocturnal pulmonary function, sleep indices or quality of life was observed with 14-day administration of MF-DPI 400 microg qd pm. These findings are limited by the small sample size and the short treatment period evaluated. Future studies are warranted to study the effects of MF-DPI therapy in patients with nocturnal asthma.

A comparison of infant hair, cord blood and meconium analysis to detect fetal exposure to environmental pesticides.

OBJECTIVE: The detection of fetal exposure to environmental pesticides is important because many of the pesticides are neurotoxicants and fetal exposure to these compounds can adversely affect prenatal and subsequent neurodevelopment. The aim of this study was to determine, by the comparative analysis of infant hair, cord blood and meconium, the most sensitive matrix to detect fetal exposure to pesticides. PATIENTS AND METHODS: Pregnant women were prospectively recruited from an agricultural site in the Philippines where a preliminary survey indicated a substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Infant hair, cord blood and meconium were obtained after birth and were analyzed by gas chromatography/mass spectrometry for the above compounds, including lindane and 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and some of their known metabolites. RESULTS: A total of 638 infants were included in the study. The highest exposure rate to pesticides was detected in meconium (23.8% to propoxur, 1.9% to pretilachlor, 1.9% to cypermethrin, 0.8% to cyfluthrin, 0.6% to DDT and 0.3% to malathion and bioallethrin). Cord blood was only positive for propoxur (1.9%) whereas infant hair was only positive for chlorpyrifos (0.2%). The highest exposure was to household pesticide (propoxur). The frequency and concentration of pesticides were compared in the three matrices and there was a significantly higher frequency and concentration of propoxur, pretilachlor, DDT, cyfluthrin and cypermethrin in meconium compared to cord blood and infant hair. Pesticide metabolites were not found in any of the matrices analyzed, except in one meconium sample which was positive for 4,4' dichlorodiphenyldichloro ethylene (DDE), a DDT metabolite. CONCLUSIONS: There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticide, propoxur. Our study has demonstrated that among cord blood, meconium or infant hair, meconium is the most sensitive matrix to analyze for fetal exposure to pesticides. The accumulation of pesticides in meconium, the ease of meconium collection and the large amount of meconium that could be collected are factors that contribute to the increased sensitivity of this matrix.

Changes in REM-sleep percentage over the adult lifespan.

STUDY OBJECTIVES: To resolve inconsistencies in previously reported changes in percentage of rapid eye movement sleep (REM%) over the adult lifespan and to identify gaps in available information about adults' REM sleep. DESIGN: A research synthesis approach specifically designed to detect nonlinear change. Cubic B smoothing splines were fitted to scatterplots generated from reported means and variance for REM%, REM minutes, and total sleep time. PARTICIPANTS: 382 English-language research reports provided REM% values for 4171 subjects; REM minutes values for 2722 subjects; and values of total sleep time for 5037 subjects. Samples were composed of subjects described by authors as normal or healthy. Mean ages of samples ranged from 18.0 to 91.7 years. SETTING: University research center. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Two coders extracted information. Intercoder reliability was above cutoffs for excellent. Authors often failed to describe screening procedures used to determine subjects' health status. Few results were reported separately for women. The functional relationship between age and REM% was essentially linear over much of the adult lifespan, decreasing about 0.6% per decade. The best estimate of when REM% ceased its small linear decline was the mid-70s, after which time a small increase in REM% was observed due to REM minutes increasing while total sleep time declined. CONCLUSIONS: Ability to detect both linear and nonlinear change in REM%, REM minutes, and total sleep time over the lifespan was useful for resolving inconsistent findings about the existence of changes in REM% with aging. This approach to research synthesis also facilitated identification of ages for which little normative information about REM sleep was available.

Extreme prematurity: an alcohol-related birth effect.

BACKGROUND: Rates of preterm delivery, a major proximate cause of perinatal morbidity and mortality, have been increasing. Prenatal alcohol exposure has been implicated in preterm delivery, although results have been inconsistent due to inadequate control for confounding factors, insufficient power, unreliable and inaccurate assessment of both exposure and gestational age, and lack of stratification of prematurity into severity levels. The purpose of this study was to examine the relation between maternal alcohol, cocaine and cigarette use during pregnancy, and extreme and mild preterm birth. METHODS: Three thousand one hundred thirty consecutive gravidas were followed prospectively for antenatal substance use and had ultrasound confirmed pregnancy dating. RESULTS: Alcohol and cocaine, but not cigarette use, were associated with increased risk of extreme preterm delivery after control for potential confounders. For every unit increase in alcohol exposure, risk of extreme preterm delivery increased significantly [odds ratio (OR) 34.8]. Furthermore, in women aged 30+, alcohol exposure was associated with mild prematurity. Abstention from alcohol while continuing to use cocaine and tobacco was related to a decrease in extreme prematurity of 41%. CONCLUSIONS: The risk of extreme preterm delivery associated with alcohol use is substantial and similar in magnitude to other well-recognized risks. Increased accuracy in identifying exposure and the use of ultrasound to confirm gestational age dating likely contributed to the findings of the current study. These findings suggest that eliminating pregnancy alcohol use might substantially reduce the risk of preterm delivery.

Fatty acid ethyl esters in meconium: are they biomarkers of fetal alcohol exposure and effect?

BACKGROUND: Biomarkers of fetal exposure to alcohol are important to establish so that early detection and intervention can be made on these infants to prevent undesirable outcomes. The aim of this study was to analyze long-chain fatty acid ethyl esters (FAEEs) in meconium as potential biomarkers of fetal alcohol exposure and effect. METHODS: Fatty acid ethyl esters were analyzed in the meconium of 124 singleton infants by positive chemical ionization gas chromatography/mass spectrometry (GC/MS) and correlated to maternal ethanol use. RESULTS: A total of 124 mother/infant dyads were enrolled in the study: 31 were in the control group and 93 were in the alcohol-exposed group. The incidence (28% vs 9.7%, p = 0.037) of ethyl linoleate detected in meconium was significantly higher in the alcohol-exposed groups than the control groups. Similarly, when the concentrations of ethyl linoleate in meconium were grouped (trichotomized), there was a significant linear by linear association between alcohol exposure and group concentrations of ethyl linoleate (p = 0.013). Furthermore, only alcohol-exposed infants were found in the group with the highest ethyl linoleate concentration. The sensitivity of ethyl linoleate in detecting prenatal alcohol exposure was only 26.9%, and its specificity and positive predictive value were 96.8 and 96.2%, respectively. There was no significant correlation between the concentration of ethyl linoleate in meconium and absolute alcohol consumed (oz) per drinking day across pregnancy, although a trend toward a positive correlation is seen at lower amounts of alcohol consumed. Among the polyunsaturated, long-chain FAEEs, there was weak evidence that the incidence (21.5% vs 6.5%, p = 0.057) and concentration (p = 0.064) of ethyl arachidonate (AA) were significantly higher in the alcohol-exposed groups than the control groups. Ethyl linolenate and ethyl docosahexanoate (DHA) in meconium were found only in the alcohol group, although not at statistically significant levels. Highly significant correlations were found among the concentrations of ethyl linoleate, ethyl linolenate, ethyl AA, and ethyl DHA in meconium (correlations ranged between rs = 0.203, p = 0.024; and rs = 0.594, p < 0.001). CONCLUSION: We conclude that FAEEs in meconium, particularly ethyl linoleate and ethyl AA, are biomarkers of high specificity for prenatal exposure to alcohol in newborn infants. We also propose that ethyl AA and DHA could be potential biomarkers of fetal alcohol effects on the developing fetal brain and should be investigated further.

Maternal hair--an appropriate matrix for detecting maternal exposure to pesticides during pregnancy.

The detection of exposure of pregnant women to toxicants in the environment is important because these compounds can be harmful to the health of the woman and her fetus. The aim of this study was to analyze for pesticides/herbicides in paired maternal hair and blood samples to determine the most appropriate matrix for detecting maternal exposure to these compounds. A total of 449 pregnant women were prospectively recruited at midgestation from an agricultural site in the Philippines where a preliminary survey indicated significant use at home and on the farm of the following compounds: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon, and transfluthrin. Paired maternal hair and blood samples were obtained from each subject upon recruitment into the study (midgestation) and at birth and were analyzed for the above compounds, as well as lindane and DDT [1,1,1-trichloro-2-2-bis(p-chlorophenyl) ethane], and some of their known metabolites by gas chromatography/mass spectrometry. The highest exposure rate was seen for propoxur and bioallethrin and maternal hair analysis provided the highest detection rate for these two compounds, compared to blood, at both time periods: (1) At midgestation, 10.5% positive for propoxur in hair compared to 0.7% in blood (P<0.001) and for bioallethrin, 11.9% positive in hair compared to 0% in blood (P < or = 0.001), and (2) at birth, 11.8% positive for propoxur in hair compared to 4% in blood (P < or = 0.001) and for bioallethrin, 7.8% in hair compared to 0% in blood (P < or = 0.001). A small number of maternal hair samples were also positive for malathion, chlorpyrifos, pretilachlor, and DDT. Only a few of the pesticide metabolites were detected, principally 3-phenoxybenzoic acid, malathion monocarboxylic acid, and DDE [1,1,dichloro-2-2-bis(p-chlorophenyl)ethylene], and they were mostly found in maternal blood. There was a significant association between the use of the home spray pesticide, Baygon, and propoxur in maternal hair at birth (P=0.001) and between the use of a slow-burning mosquito coil and the presence of bioallethrin in maternal hair at midgestation and at birth (P=0.001, P < or = 0.041, respectively). There is significant exposure of the pregnant woman to pesticides, particularly to pesticides that are used at home. Our study demonstrates the advantages of analyzing maternal hair as a readily available biologic matrix for studying maternal exposure to toxicants in the environment, compared to blood. For propoxur, there was a 3- to 15-fold higher detection rate of the pesticide in maternal hair as compared to blood. As for the other pesticides, bioallethrin, malathion, chlorpyrifos, and DDT were exclusively found in maternal hair compared to blood. On the other hand, pesticide metabolites were infrequently found in maternal hair or maternal blood. Pesticides in blood most likely represent acute exposure, whereas pesticides in hair represent past and/or concurrent exposure. The high sensitivity, wide window of exposure, availability, and ease of hair collection are distinct advantages in using hair to detect exposure to pesticides among pregnant women. However, pesticides in maternal hair may also be secondary to passive exposure and therefore not truly representative of the internal pesticide dose. Finally, the analysis of maternal hair for pesticides as an index of maternal exposure to pesticides in the environment allows the institution of measures to prevent further exposure during pregnancy.

Effects of motivational interviewing training on mental health therapist behavior.

This study examined the effectiveness of training community mental health therapists in motivational interviewing (MI) adapted to treat clients with co-occurring disorders. Ten therapists with high caseloads of culturally diverse clients in two different community mental health settings fulfilled all study requirements. MI training consisted of a two-day didactic and experiential workshop followed by eight biweekly small group supervision (coaching) sessions. Using an interrupted time series design, 156 randomly selected therapy sessions involving 28 clients were coded for assessment of therapist fidelity to MI at multiple points in time, both pre- and post-training. Employing hierarchical linear modeling analysis, significant improvement in MI skill was observed after training on five of six key therapist ratings, and on the sole client rating (client change talk) that was examined. Importantly, the present study demonstrates training-related proficiency in motivational interviewing using: (a) a representative sample of mental health therapists from the community; (b) a protocol emphasizing adherence to a mental health treatment regimen as well as management of substance use behavior for clients with co-occurring disorders; (c) repeated random observations of therapy sessions; (d) measurement of training-related changes in clinician skills and self motivational statements by clients. Findings of this effectiveness study compared favorably with efficacy literature on MI training.

Effect of low-calorie parenteral nutrition on the incidence and severity of hyperglycemia in surgical patients: a randomized, controlled trial.

OBJECTIVE: To determine the effect of a low-calorie parenteral nutrition (PN) regimen on the incidence and severity of hyperglycemia and insulin requirements. DESIGN: Prospective, randomized, clinical trial. SETTING: Urban, university-affiliated, level-I trauma center. PATIENTS: Consecutive surgical patients requiring PN. INTERVENTIONS: Patients were randomized to receive either a low-calorie PN formulation (20 nonprotein kilocalories per kg per day) or a standard PN formulation (30 nonprotein kilocalories per kg per day). Lipid-derived calories were standardized to 1000 kilocalories three times weekly for all patients; consequently, the number of calories varied only by the amount of carbohydrate administered. Protein requirements were individualized on the basis of estimated metabolic stress. Hyperglycemia was defined as a blood glucose level > or = 200 mg/dL. MEASUREMENTS AND MAIN RESULTS: Forty patients were evaluated (low-calorie PN, n = 20; standard PN, n = 20). Demographics of the two groups were similar. The incidence of hyperglycemic events was significantly lower in the low-calorie group (0% [0-0.5] vs. 33.1% [0-58.4]; p = .001]. Additionally, the severity of hyperglycemia was also lower in the low-calorie group (mean glucose area under the curve = 118 +/- 22 [mg x hr]/dL vs. 172 +/- 44 [mg x hr]/dL; p < .001). This resulted in lower average daily insulin requirements (0 [0-0] units vs. 10.9 [0-25.6] units; p < .001.). The only predictor of hyperglycemia was a dextrose administration rate >4 mg/kg/min. CONCLUSIONS: : Administration of a low-calorie PN formulation resulted in fewer and less-severe hyperglycemic events and lower insulin requirements. PN regimens should not exceed a dextrose administration rate of 4 mg/kg/min to avoid hyperglycemic events.

Hospital surveillance of acute stroke treatment in Michigan.

INTRODUCTION: Modern management of acute stroke, including the use of tissue plasminogen activator (t-PA), requires hospitals to be better prepared for rapid diagnosis and treatment. METHODS: Surveillance of practice of acute stroke treatment by Michigan hospitals was performed in 1998. We determined variation in hospital preparedness for treatment by number of emergency department visits. Factors associated with hospital use of t-PA were analyzed using logistic regression. RESULTS: Surveys were returned by 97 (55%) hospitals. Hospitals with a greater number of emergency department visits were significantly more likely to have a clinical pathway, to have given t-PA, and to be better prepared for stroke treatment. After multivariate analysis, greater number of stroke patients per year (P < .001) and availability of skilled intensive care department staff (P = .056) were associated with hospital t-PA use. CONCLUSIONS: Specific hospital characteristics are associated with t-PA use. Consideration of these may be used to devise new strategies for improved delivery of acute stroke treatment.

Tachyphylaxis associated with continuous cisatracurium versus pancuronium therapy.

STUDY OBJECTIVES: To compare dosing requirements over time among patients receiving continuous cisatracurium versus pancuronium therapy, and to identify factors that may account for changes in pancuronium versus cisatracurium infusion requirements over time. DESIGN: Retrospective, comparative cohort analysis. SETTING: A tertiary level 1 trauma center. PATIENTS: Forty-five consecutive adult patients who were admitted to intensive care units at our institution from January 1998-August 2000 and received continuous cisatracurium or pancuronium therapy for at least 48 hours. MEASUREMENTS AND MAIN RESULTS: Dosing requirements of patients treated with pancuronium or cisatracurium were recorded over time throughout the treatment period. Factors that could affect dosing requirements of a neuromuscular blocking agent (NMBA) were stratified as time invariant (admitting service, acute physiology and chronic health evaluation II score, duration of mechanical ventilation, pressure control ventilation, baseline hepatic or renal insufficiency, thermal injury, train-of-four assessment, and concurrent drug administration or disorders affecting neuromuscular transmission) or time variant (concurrent sedation and narcotic analgesia therapy; serum magnesium, potassium, and creatinine concentrations; arterial pH level; temperature; peak airway pressure; and partial pressure of oxygen:fraction of inspired oxygen ratio). Hierarchical linear modeling was used to compare the dosing requirements and to identify confounders affecting the relationship. The infusion rate escalation for the cisatracurium group was greater (0.39 microg/kg/min; 95% confidence interval [CI] 0.22-0.56; 23 patients) than for the pancuronium group (-0.06 microg/kg/min; 95% CI -0.24-0.12; 22 patients; p<0.001) and was associated with an average daily cost/patient significantly higher (p<0.001) with cisatracurium ($258+/-$114) than pancuronium ($11+/-$5). Confounder analysis revealed that only the admitting service and the number of times the NMBA infusion was suspended because no twitch was detected differed between groups. Neither of these confounders significantly affected the temporal relationship between cisatracurium and pancuronium infusion rates. CONCLUSION: Dosing requirements increase over time at a significantly greater rate for cisatracurium than pancuronium infusions. Tachyphylaxis with cisatracurium is associated with substantial drug-related costs and is not accounted for by various disease-, patient-, and therapy-related factors. Further investigation is required to elucidate the mechanisms and risk factors underlying this phenomenon.

Cocaine use and preterm premature rupture of membranes: improvement in neonatal outcome.

OBJECTIVE: Our aim was to determine whether cocaine use increases neonatal morbidity in patients with preterm premature rupture of membranes. STUDY DESIGN: We reviewed records of pregnancies that were complicated with preterm premature rupture of membranes between 24 weeks to 34 weeks of gestation. Clinical characteristics and neonatal outcomes of patients who had positive results for cocaine in the urine were compared with patients with negative test results. RESULTS: During the study period, 16.1% (85/528 patients) had a positive result in a urine screen for cocaine use. Patients who used cocaine were older and of higher gravidity and parity. When major neonatal morbidities were compared, there was improvement in morbidities that were linked to neonatal infection in patients with positive test results for cocaine, including pneumonia (3.5% vs 11.7%; P =.012) and sepsis (5.9% vs 14.7%; P =.016). Jointly, neonatal outcomes were significantly worse in the negative cocaine group (chi(2) = 5.143; P =.023). CONCLUSION: The association of preterm premature rupture of membranes with major neonatal morbidity was unexpectedly and significantly weaker in pregnancies complicated by cocaine use.