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Purpose Hydrocodone, codeine, oxycodone, and tramadol are frequently prescribed to adolescents for moderate pain related to minor trauma or dental, surgical, or medical procedures. Pharmacokinetic and pharmacodynamic differences between these opioids could affect their relative safety. We aimed to compare occurrence of opioid-related adverse events in adolescents without cancer or other severe conditions taking hydrocodone, codeine, oxycodone, and tramadol. Methods Retrospective cohort study of 201 940 Tennessee Medicaid enrollees 12 to 17 years of age without cancer, other severe conditions, or evidence of substance abuse with 529 731 filled prescriptions for study opioids. Adverse events were defined as an emergency department visit, hospital admission, or death related to opioid use, confirmed by medical record review. Serious events had opioid-related escalation of care, hospitalization, or death. Propensity-score adjusted hazard ratios (HRs) were calculated with hydrocodone as the reference category. Results The incidence of opioid-related adverse events per 10 000 person-years of opioid exposure was 97.5 for hydrocodone (127 events/13 026 person-years), 91.2 for codeine (58/6,359), 229.7 for oxycodone (43/1,872), and 317.7 for tramadol (47/1479). The HRs for tramadol in comparison with hydrocodone for all and serious events were 2.98 (2.03-4.39) and 2.94 (1.81-4.75), respectively. Increased risk for tramadol was consistently present when the adverse events were restricted to those with neurologic-respiratory depression/other symptoms of possible overdose. Conclusion In adolescents without cancer or other severe conditions prescribed short-acting opioids, the incidence of both all opioid-related adverse events and more serious events with opioid-related escalation of care, hospitalization, or death was consistently greater for tramadol than for hydrocodone.

BACKGROUND: Polysubstance use is common among opioid-using women, yet its association with pharmacotherapy for neonatal abstinence syndrome (NAS) remains unclear. We hypothesized that benzodiazepine exposure would increase risk of an infant developing pharmacologically treated NAS. METHODS: We conducted a retrospective cohort study of maternal-infant dyads enrolled in Tennessee Medicaid, using individual-level data linkage of vital records and administrative (ie, outpatient, inpatient, and prescription) data from 2009 to 2011. These data underwent chart review from 2013 to 2016 to obtain clinically relevant exposure data (eg, toxicology testing). The association of antenatal exposures with pharmacologically treated NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant factors and clustered by hospital. RESULTS: Among 112 029 maternal-infant dyads, we confirmed 822 cases of NAS, of which 598 (72.7%) were cases of pharmacologically treated NAS. Infants who developed pharmacologically treated NAS were more likely to have been exposed to antenatal benzodiazepines compared with infants with confirmed NAS not treated pharmacologically (40.9% vs 30.8%; P = .008). In adjusted analyses, benzodiazepine exposure was associated with greater risk of developing pharmacologically treated NAS (odds ratio: 1.51; 95% confidence interval: 1.04–2.21). Alternatively, exposure to tobacco, marijuana, cocaine, gabapentin, and selective serotonin reuptake inhibitors were not associated with increased risk of developing pharmacologically treated NAS. CONCLUSIONS: Among a population of infants with intrauterine polysubstance exposure, benzodiazepine exposure was an independent predictor of an infant developing pharmacologically treated NAS. Obtaining history of antenatal benzodiazepine exposure among opioid-exposed infants may allow for risk stratification and development of personalized care plans.

BACKGROUND: Neonatal abstinence syndrome (NAS) is a postnatal opioid withdrawal syndrome. Factors associated with development of the syndrome are poorly understood; however, infant sex may influence the risk of NAS. Our objective was to determine if infant sex was associated with the development or severity of the syndrome in a large population-based cohort. METHODS: This retrospective cohort study used vital statistics and prescription, outpatient, and inpatient administrative data for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. Multivariable logistic regression models were used to evaluate the association between male sex and diagnosis of NAS, accounting for potential demographic and clinical confounders. NAS severity, as evidenced by hospital length of stay, was modeled by using negative binomial regression. RESULTS: Of 102 695 infants, 927 infants were diagnosed with NAS (484 male subjects and 443 female subjects). Adjustments were made for the following: maternal age, race, and education; maternal hepatitis C infection, anxiety, or depression; in utero exposure to selective serotonin reuptake inhibitors and cigarettes; infant birth weight, small for gestational age, and year; and the interaction between opioid type and opioid amount. Male infants were more likely than female infants to be diagnosed with NAS (adjusted odds ratio, 1.18 [95% confidence interval, 1.05–1.33]) and NAS requiring treatment (adjusted odds ratio, 1.24 [95% confidence interval, 1.04–1.47]). However, there was no sex-based difference in severity for those diagnosed with NAS. CONCLUSIONS: Treatment of NAS should be tailored to an infant’s individual risk for the syndrome. Clinicians should be mindful that male sex is an important risk factor in the diagnosis of NAS.

BACKGROUND: Hepatitis C virus (HCV) prevalence doubled among pregnant women from 2009 to 2014, reaching 3.4 per 1000 births nationwide. Infants exposed to HCV may acquire HCV by vertical transmission. National guidelines recommend that infants exposed to HCV be tested; however, it is unclear if these recommendations are being followed. Our objectives were to determine if infants exposed to HCV were tested and to determine hospital- and patient-level factors associated with differences in testing. METHODS: In this retrospective cohort study of infants exposed to HCV who were enrolled in the Tennessee Medicaid program, we used vital statistics–linked administrative data for infants born between January 1, 2005, and December 31, 2014. Infants were followed until 2 years old. Multilevel logistic regression was used to assess the association of HCV testing and hospital- and patient-level characteristics. RESULTS: Only 23% of 4072 infants exposed to HCV were tested. Infants whose mothers were white versus African American (96.6% vs 3.1%; P CONCLUSIONS: Testing occurred in

Objectives To develop and validate clinical risk prediction tools for neonatal abstinence syndrome (NAS). Study design We developed prediction models for NAS based on a set of 30 demographic and antenatal exposure covariates collected during pregnancy. Data (outpatient prescription, vital, and administrative records), were obtained from enrollees in the Tennessee Medicaid Program from 2009 to 2014. Models were created using logistic regression and backward selection based on improvement in the Akaike information criterion, and internally validated using bootstrap cross-validation. Results A total of 218 020 maternal and infant dyads met inclusion criteria, of whom 3208 infants were diagnosed with NAS. The general population model included age, hepatitis C virus infection, days of opioid used by type, number of cigarettes used daily, and the following medications used in the last 30 day of pregnancy: bupropion, antinausea medicines, benzodiazepines, antipsychotics, and gabapentin. Infant characteristics included birthweight, small for gestational age, and infant sex. A high-risk model used a smaller number of predictive variables. Both models discriminated well with an area under the curve of 0.89 and were well-calibrated for low-risk infants. Conclusions We developed 2 predictive models for NAS based on demographics and antenatal exposure during the last 30 days of pregnancy that were able to risk stratify infants at risk of developing the syndrome.

Newborns exposed to opioids before birth can experience withdrawal symptoms known as neonatal abstinence syndrome (NAS). From 2009 to 2015, the average NAS rate per 1,000 hospital births across eight states rose from about six to more than 25.

OBJECTIVES: Neonatal abstinence syndrome (NAS) is a postnatal withdrawal syndrome experienced by some infants with opioid exposure. Hospital administrative data are commonly used for research and surveillance but have not been validated for NAS. Our objectives for this study were to validate the diagnostic codes for NAS and to develop an algorithm to optimize identification. METHODS: Tennessee Medicaid claims from 2009 to 2011 (primary sample) and 2016 (secondary sample; post–International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM]) were obtained. Cases of NAS were identified by using International Classification of Diseases, Ninth Revision, Clinical Modification code (2009–2011) 779.5 and ICD-10-CM code (2016) P96.1. Medical record review cases were then conducted by 2 physicians using a standardized algorithm, and positive predictive value (PPV) was calculated. Algorithms were developed for optimizing the identification of NAS in administrative data. RESULTS: In our primary sample of 112 029 mother-infant dyads, 950 potential NAS cases were identified from Medicaid claims data and reviewed. Among reviewed records, 863 were confirmed as having NAS (including 628 [66.1%] cases identified as NAS requiring pharmacotherapy, 224 [23.5%] as NAS not requiring pharmacotherapy, and 11 [1.2%] as iatrogenic NAS), and 87 (9.2%) did not meet clinical criteria for NAS. The PPV of the International Classification of Diseases, Ninth Revision, Clinical Modification code for NAS in clinically confirmed NAS was 91% (95% confidence interval: 88.8%–92.5%). Similarly, the PPV for the ICD-10-CM code in the secondary sample was 98.2% (95% confidence interval: 95.4%–99.2%). Algorithms using elements from the Medicaid claims and from length of stay improved PPV. CONCLUSIONS: In a large population-based cohort of Medicaid participants, hospital administrative data had a high PPV in identifying cases of clinically diagnosed NAS.

BACKGROUND AND OBJECTIVES: Little is known about opioid prescribing for children without severe conditions. We studied the prevalence of and indications for outpatient opioid prescriptions and the incidence of opioid-related adverse events in this population. METHODS: This retrospective cohort study between 1999 and 2014 included Tennessee Medicaid children and adolescents aged 2 to 17 without major chronic diseases, prolonged hospitalization, institutional residence, or evidence of a substance use disorder. We estimated the annual prevalence of outpatient opioid prescriptions and incidence of opioid-related adverse events, defined as an emergency department visit, hospitalization, or death related to an opioid adverse effect. RESULTS: There were 1 362 503 outpatient opioid prescriptions; the annual mean prevalence of opioid prescriptions was 15.0%. The most common opioid indications were dental procedures (31.1% prescriptions), outpatient procedure and/or surgery (25.1%), trauma (18.1%), and infections (16.5%). There were 437 cases of opioid-related adverse events confirmed by medical record review; 88.6% were related to the child’s prescription and 71.2% had no recorded evidence of deviation from the prescribed regimen. The cumulative incidence of opioid-related adverse events was 38.3 of 100 000 prescriptions. Adverse events increased with age (incidence rate ratio = 2.22; 95% confidence interval, 1.67–2.96; 12–17 vs 2–5 years of age) and higher opioid doses (incidence rate ratio = 1.86 [1.45–2.39]; upper versus lower dose tertiles). CONCLUSIONS: Children without severe conditions enrolled in Tennessee Medicaid frequently filled outpatient opioid prescriptions for acute, self-limited conditions. One of every 2611 study opioid prescriptions was followed by an opioid-related adverse event (71.2% of which were related to therapeutic use of the prescribed opioid).

BACKGROUND AND OBJECTIVES: Although opioid pain relievers are commonly prescribed in pregnancy, their association with neonatal outcomes is poorly described. Our objectives were to identify neonatal complications associated with antenatal opioid pain reliever exposure and to establish predictors of neonatal abstinence syndrome (NAS). METHODS: We used prescription and administrative data linked to vital statistics for mothers and infants enrolled in the Tennessee Medicaid program between 2009 and 2011. A random sample of NAS cases was validated by medical record review. The association of antenatal exposures with NAS was evaluated by using multivariable logistic regression, controlling for maternal and infant characteristics. RESULTS: Of 112 029 pregnant women, 31 354 (28%) filled ≥1 opioid prescription. Women prescribed opioid pain relievers were more likely than those not prescribed opioids (P < .001) to have depression (5.3% vs 2.7%), anxiety disorder (4.3% vs 1.6%) and to smoke tobacco (41.8% vs 25.8%). Infants with NAS and opioid-exposed infants were more likely than unexposed infants to be born at a low birth weight (21.2% vs 11.8% vs 9.9%; P < .001). In a multivariable model, higher cumulative opioid exposure for short-acting preparations (P < .001), opioid type (P < .001), number of daily cigarettes smoked (P < .001), and selective serotonin reuptake inhibitor use (odds ratio: 2.08 [95% confidence interval: 1.67–2.60]) were associated with greater risk of developing NAS. CONCLUSIONS: Prescription opioid use in pregnancy is common and strongly associated with neonatal complications. Antenatal cumulative prescription opioid exposure, opioid type, tobacco use, and selective serotonin reuptake inhibitor use increase the risk of NAS.

More than 3 million human immunodeficiency virus (HIV)-infected women worldwide give birth each year [1], and an increasing number conceive while receiving antiretroviral (ARV) treatment for their own infection or to prevent mother-to-child transmission (MTCT). Yet, the fetal safety of many of the currently approved ARV medications for use in non-pregnant adult populations is largely unknown. ARVs are associated with numerous toxicities in both adults and children [2, 3], and therefore it seems biologically plausible that they would also be toxic to the developing fetus. Until recently, data on the potential teratogenic effect of ARVs had mainly been obtained from animal studies [4], case reports [5, 6], and surveillance data [7]. Nowadays, we do have the results provided by several cohort studies [8–15], but the evidence to date is still limited by differences in the definition and ascertainment of cases across the studies and variations in the selection of control groups. Moreover, some of the studies included a selective sample of relatively healthy participants. Thus, there is a compelling need to have further safety data for the use of ARVs during pregnancy, particularly for disadvantaged populations often neglected by volunteered based research. Large health care utilization databases are an efficient resource for conducting population-based studies with valid reference groups [16–18]. We therefore used data from the Tennessee Medicaid Program (TennCare), linked to vital records and supplemented by in-depth medical chart reviews, to assess the risk of birth defects after in utero exposure to ARVs among infants born to HIV-infected women enrolled in TennCare between 1994 and 2009. Key elements of the database have been validated and these data have been used to conduct several epidemiologic studies of medications in pregnancy [19–22].

PURPOSE: To assess the safety of psychotropic medication use in children and adolescents, it is critical to be able to identify suicidal behaviors from medical claims data and distinguish them from other injuries. The purpose of this study was to develop an algorithm using administrative claims data to identify medically treated suicidal behavior in a cohort of children and adolescents. METHODS: The cohort included 80 183 youth (6-18 years) enrolled in Tennessee's Medicaid program from 1995-2006 who were prescribed antidepressants. Potential episodes of suicidal behavior were identified using external cause-of-injury codes (E-codes) and ICD-9-CM codes corresponding to the potential mechanisms of or injuries resulting from suicidal behavior. For each identified episode, medical records were reviewed to determine if the injury was self-inflicted and if intent to die was explicitly stated or could be inferred. RESULTS: Medical records were reviewed for 2676 episodes of potential self-harm identified through claims data. Among 1162 episodes that were classified as suicidal behavior, 1117 (96%) had a claim for suicide and self-inflicted injury, poisoning by drugs, or both. The positive predictive value of code groups to predict suicidal behavior ranged from 0-88% and improved when there was a concomitant hospitalization but with the limitation of excluding some episodes of confirmed suicidal behavior. CONCLUSIONS: Nearly all episodes of confirmed suicidal behavior in this cohort of youth included an ICD-9-CM code for suicide or poisoning by drugs. An algorithm combining these ICD-9-CM codes and hospital stay greatly improved the positive predictive value for identifying medically treated suicidal behavior. Copyright © 2013 John Wiley & Sons, Ltd. Language: en

Background Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the U.S., 2001-2007.

Background Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-β0-thalassemia (HbSβ0) aged 2–16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence. Procedure A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSβ0 who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan–Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD. Results Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD. Conclusions Publicly insured children with HbSS or HbSβ0 had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines. Pediatr Blood Cancer 2013;60:270–274. © 2012 Wiley Periodicals, Inc.

OBJECTIVE: To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and β-lactams for the treatment of pediatric skin and soft-tissue infections (SSTIs). METHODS: A retrospective cohort of children 0 to 17 years of age who were enrolled in Tennessee Medicaid, experienced an incident SSTI between 2004 and 2007, and received treatment with clindamycin (reference), trimethoprim-sulfamethoxazole, or a β-lactam was created. Outcomes included treatment failure and recurrence, defined as an SSTI within 14 days and between 15 and 365 days after the incident SSTI, respectively. Adjusted models stratified according to drainage status were used to estimate the risk of treatment failure and time to recurrence. RESULTS: Among the 6407 children who underwent drainage, there were 568 treatment failures (8.9%) and 994 recurrences (22.8%). The adjusted odds ratios for treatment failure were 1.92 (95% confidence interval [CI]: 1.49–2.47) for trimethoprim-sulfamethoxazole and 2.23 (95% CI: 1.71–2.90) for β-lactams. The adjusted hazard ratios for recurrence were 1.26 (95% CI: 1.06–1.49) for trimethoprim-sulfamethoxazole and 1.42 (95% CI: 1.19–1.69) for β-lactams. Among the 41 094 children without a drainage procedure, there were 2435 treatment failures (5.9%) and 5436 recurrences (18.2%). The adjusted odds ratios for treatment failure were 1.67 (95% CI: 1.44–1.95) for trimethoprim-sulfamethoxazole and 1.22 (95% CI: 1.06–1.41) for β-lactams; the adjusted hazard ratios for recurrence were 1.30 (95% CI: 1.18–1.44) for trimethoprim-sulfamethoxazole and 1.08 (95% CI: 0.99–1.18) for β-lactams. CONCLUSIONS: Compared with clindamycin, use of trimethoprim-sulfamethoxazole or β-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.

Stool cultures can be important in guiding antimicrobial therapy for diarrhea. From among 11.64 million person-years of Tennessee Medicaid enrollment data collected from 1995 through 2004, 315,828 diarrheal episodes were identified. Stool cultures were performed for only 15,820 episodes (5.0%). Antimicrobials were prescribed for 32,949 episodes (10.4%), 89.4% of which were not accompanied by a stool culture. White race and urban residence were associated with higher rates of stool culture. Frequent use of antimicrobials for diarrhea without stool culture may indicate inappropriate antimicrobial use and has critical implications for public health.

To test the hypothesis that children enrolled in Medicaid managed care health plans that provide asthma-specific communication to providers would be more likely to have adequate asthma medication filling.We conducted a historical cohort study of 4498 children (2-17 years old) with moderate-severe asthma in Washington State and Tennessee Medicaid managed care programs from 2000 to 2002. Interviews with health plans were conducted to identify communication strategies health plans used to improve asthma care by providers in the plan. The main outcome measure was guideline-recommended filling of asthma preventer medications.Children in plans that provided specific feedback to providers about asthma quality and notified providers when children had an asthma-related event had the highest mean days plus or minus SE of filling in the 365-day follow-up period (164.6 +/- 13 days) compared with children in plans with neither (135.3 +/- 10.8 days; P.05). In children with the greatest asthma severity, enrollment in a plan with both features was associated with 27.1 additional days of filling (95% CI, 0.7-53.4 days) during the follow-up period.Health plan communication to providers was associated with increased preventer filling in children with moderate-severe asthma in 2 state Medicaid programs.

Although angiotensin-converting enzyme (ACE) inhibitors are avoided in the second and third trimesters of pregnancy because of an increased risk of fetal pathology, adverse fetal outcomes have not been related to first-trimester exposure. For the most part, however, evidence that exposure early in pregnancy is safe comes from a limited number of animal studies and case report analyses. This cohort study included 29,507 infants enrolled in Medicaid in Tennessee who were born in the years 1985 to 2000 and for whom there was no evidence of maternal diabetes. A total of 411 infants had been exposed to some kind of antihypertensive medication only in the first trimester: 209 infants had been exposed to ACE inhibitors and 202 were exposed to other antihypertensive drugs. Among the 202 infants exposed to other antihypertensive agents in the first trimester, the risk of any major congenital malformation was not increased. Of the 209 infants exposed to ACE inhibitors in the first trimester, 18 had major congenital malformations (8.6%); the adjusted proportion was 7.1%. Seven of these 18 infants had multiple malformations, but 5 of the 7 had been exposed in the second trimester as well and 3 had been exposed in all 3 trimesters. The risk ratio (RR) for first-trimester exposure, compared with children not exposed to any type of antihypertensive drug, was 2.71 (95% confidence interval [CI], 1.72–4.27). This RR was the result of an increased number of cardiovascular malformations (n = 8; RR, 3.72; 95% CI, 1.89–7.30) and central nervous system malformations (n = 3; RR, 4.39; 95% CI, 1.37–14.02). Other malformations included renal dysplasia (n = 2), hypospadius, intestinal and choanal atresia, Hirschsprung disease, and diaphragmatic hernia (n = 1 each). A post hoc analysis revealed a significantly increased risk of renal malformations (RR, 9.32; 95% CI, 1.79–48.5), but the risk of the other malformations was not significantly increased. Women of childbearing age, like other individuals, are increasingly being given ACE inhibitors as the indications for these drugs continue to expand. The present findings strongly suggest that these drugs should not be given to pregnant women during the first trimester.

OBJECTIVES: Recent data showing possible increased risk for suicidal behavior among children and adolescents treated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants have created significant concern among patients, families, and providers, including concerns about the risk of individual antidepressants. This study was designed to compare the risk for medically treated suicide attempts among new users of sertraline, paroxetine, citalopram, escitalopram, and venlafaxine to risk for new users of fluoxetine. METHODS: A retrospective cohort study included 36 842 children aged 6 to 18 years enrolled in Tennessee Medicaid between 1995 and 2006 who were new users of 1 of the antidepressant medications of interest (defined as filling no prescriptions for antidepressants in the preceding 365 days). Medically treated suicide attempts were identified from Medicaid files and vital records and confirmed with medical record review. RESULTS: Four hundred nineteen cohort members had a medically treated suicide attempt with explicit or inferred attempt to die confirmed through medical record review, including 4 who completed suicide. The rate of confirmed suicide attempts for the study drugs ranged from 24.0 per 1000 person-years to 29.1 per 1000 person-years. The adjusted rate of suicide attempts did not differ significantly among current users of SSRI and SNRI antidepressants compared with current users of fluoxetine. Users of multiple antidepressants concomitantly had increased risk for suicide attempt. CONCLUSIONS: In this population-based study of children recently initiating an antidepressant, there was no evidence that risk of suicide attempts differed for commonly prescribed SSRI and SNRI antidepressants.

Objective Guidelines and quality of care measures for the evaluation of adolescent suicidal behavior recommend prompt mental health evaluation, hospitalization of high-risk youth, and specific follow-up plans—all of which may be influenced by sociodemographic factors. The aim of this study was to identify sociodemographic characteristics associated with variations in the evaluation of youth with suicidal behavior. Methods We conducted a large cohort study of youth, aged 7 to 18, enrolled in Tennessee Medicaid from 1995 to 2006, who filled prescriptions for antidepressants and who presented for evaluation of injuries that were determined to be suicidal on the basis of external cause-of-injury codes (E codes) and ICD-9-CM codes and review of individual medical records. Chi-square tests and logistic regression were performed to assess the relationship between sociodemographic characteristics and documentation of mental health evaluation, hospitalization, and discharge instructions. Results Of 929 episodes of suicidal behavior evaluated in an acute setting, rural-residing youth were less likely to be admitted to a psychiatric hospital (adjusted odds ratio [AOR] 0.72; 95% confidence interval [CI] 0.55–0.95) and more likely to be medically hospitalized only (AOR 1.92; 95% CI 1.39–2.65). Female subjects were less likely to be admitted to a psychiatric hospital (AOR 0.55; 95% CI 0.41–0.74) and more likely to be discharged home (AOR 1.44; 95% CI 1.01–2.04). Only 40% of those discharged to home had documentation of discharge instructions with both follow-up provider and date. Conclusions In this statewide cohort of youth with suicidal behavior, there were significant differences in disposition associated with sociodemographic characteristics.

Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-β(0) -thalassemia (HbSβ(0) ) aged 2-16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence.A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSβ(0) who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD.Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD.Publicly insured children with HbSS or HbSβ(0) had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines.

Reversed-phase and ion-exchange HPLC are compared with both slab gel and capillary gel electrophoresis for the separation of antisense phosphorothioate oligomers. The chromatographic separations were found to be markedly inferior to the electrophoretic separations, especially for oligomers greater than 20 bases in length. The potential of gel high-performance capillary electrophoresis for the analysis of phosphorothioate analogues is shown.

OBJECTIVE. The purpose of this work was to estimate the incidence of medically treated thyroid disease in children with Down syndrome enrolled in Tennessee Medicaid (TennCare) during 1995–2005 and to determine whether rates increased after rerelease of American Academy of Pediatrics guidelines in 2001. PATIENTS AND METHODS. We conducted a population-based retrospective cohort study in which we identified children with Down syndrome by using TennCare files and birth certificates. We included 1- to 18-year-olds who were continuously enrolled in TennCare and did not fill a prescription for thyroid medication during a 90-day prestudy period. The rate of medically treated thyroid disease (prescription filled for thyroid medication) was the main outcome. We used Poisson regression to estimate rates of medically treated thyroid disease according to study year, age, gender, race, region of residence, and payer type. RESULTS. During the 11-year study period, 1257 children with Down syndrome (28% black, 72% white) met inclusion criteria. Overall, 10.8% filled a new prescription for thyroid medication. Rates of medically treated thyroid disease per 1000 child-years were 13.25 (1995–1997), 13.34 (1998–1999), 13.62 (2000–2001), 22.37 (2002–2003), and 22.51 (2004–2005). After adjusting for child age and race, there was an increased rate of medically treated thyroid disease in 2002–2003 and 2004–2005 compared with 1995–1997. In a comparison cohort of children without Down syndrome, there was a smaller increase in the rate of medically treated thyroid disease when comparing 2002–2003 and 2004–2005 with 1995–1997. CONCLUSIONS. Over the 11-year period, 10.8% of children with Down syndrome filled a new prescription for a thyroid medication. A 73% increase in the incidence of medically treated thyroid disease occurred after rerelease of American Academy of Pediatrics guidelines, which may have influenced screening.

Purpose To assess the positive predictive value of computerized records in a linked database of vital records and infant claims, with medical record confirmation to detect congenital malformations in a Medicaid population. Methods Study subjects were selected from cases identified for three studies of congenital malformations in the Tennessee Medicaid (TennCare) population including 173 827 (studies 1 and 2) and 519 465 (study 3) mother/infant pairs. Possible malformations were identified from computerized databases of birth certificates linked with maternal and infant claims. Medical records were reviewed for all possible congenital malformations and positive predictive values were calculated for each data source and for each malformation. Results Among 1430 potential congenital malformations identified from either birth certificates or inpatient claims, 67.7% were confirmed by medical record review. The positive predictive value varied considerably depending on the data source and the organ system. For example, cardiac defects had a very low positive predictive value when identified from birth certificates, and somewhat higher positive predictive value when identified from inpatient claims. Orofacial defects had 90.9% positive predictive value from birth certificates and inpatient claims. Requiring evidence of a diagnostic or therapeutic procedure increased the positive predictive value to >90% for specific defects, but substantially reduced the number of included cases. Conclusions Depending on the defect, computerized claims data linked to vital records offer opportunities for identifying birth defects in populations of vulnerable persons. However, for many defects, medical record confirmation is likely to be required to provide valid identification of malformation occurrence. Copyright © 2007 John Wiley & Sons, Ltd.

Objective To determine current diarrhea-associated healthcare usage rates and associated sociodemographic factors. These data can be used to determine the impact of the rotavirus vaccine. Study design Using discharge diagnosis codes, we determined diarrhea-associated visit rates for children aged 0 to 18 years enrolled in Tennessee Medicaid, 1995-2004. Poisson regression compared data across time and within strata. The winter residual excess method estimated the rotavirus burden. Results Analyzing approximately 500 000 person-years annually, outpatient and hospitalization rates remained stable from 1995 to 2004; emergency department (ED) rates approximately doubled, incidence rate ratio (IRR): 1.92 (1.81-2.04). White children used healthcare at greater rates than black children: outpatient IRR 1.90: (1.85-1.95), ED IRR: 1.69 (1.64-1.74), and inpatient IRR: 1.82 (1.73-1.92); and rural children greater than urban: outpatient IRR 1.66 (1.62-1.70), ED IRR 1.14 (1.11-1.17), inpatient IRR 1.88 (1.80-1.97). Children aged 0 to 35 months experienced 1627 outpatient and 792 ED visits, and 148 hospitalizations per 10 000 child-years; rotavirus may have affected up to 40% of these hospitalizations. Conclusions Diarrhea-associated ED visit rates nearly doubled from 1995 to 2004. Future studies could explore factors resulting in increased healthcare usage by white children and those living in rural areas and document the rotavirus vaccine's impact after its release.

Rates of the major congenital abdominal wall defects gastroschisis and omphalocele have been shown to be increasing over the past 10 to 20 years. Although much of the increase was seen in the 1970s and 1980s, there has been conflicting evidence as to whether similar trends exist for more recent years. Clinical observations from the major neonatal referral networks in Tennessee led us to question whether the rates of abdominal wall defects were continuing to increase throughout the 1990s. The purpose of this study was to describe the rates of congenital abdominal wall defects between 1985 and 2002 for the state of Tennessee using 2 independently collected data sources: birth certificates and Medicaid claims. There was nearly a 3-fold increase in congenital abdominal wall defects between 1989 and 2001 identified from birth certificates, and a doubling of these defects was identified from claims. Temporal increases persisted when controlling for maternal age, race, and education. We conclude that the increase in these important birth defects seen in earlier decades has persisted in Tennessee in recent years. Further elucidation of risk factors associated with the increase is warranted.

Background The use of opioids is increasing in children; therefore, opioid toxicity could be a public health problem in this vulnerable population. However, we are not aware of a published algorithm to identify cases of opioid toxicity in children using administrative databases. Objectives We sought to develop an algorithm to identify cases of opioid toxicity in children using administrative databases. Methods After review of literature and de-identified computer profiles, a broad set of ICD-9 CM codes consistent with serious opioid toxicity was selected. Based on these codes, we identified 195 potential cases of opioid toxicity in children enrolled in Tennessee Medicaid. Medical records were independently reviewed by two physicians; episodes considered equivocal were reviewed by an adjudication committee. Cases were adjudicated as definite/probable, possible, or were excluded. Results Of the 195 potential cases, 168 (86.2%) had complete records for review and 85 were confirmed cases. The overall positive predictive value (PPV) for all codes was 50.6%. The PPV for codes indicating: unintentional opioid overdose (25/31) was 80.7%; intentional opioid overdose (15/30) was 50.0%, adverse events (33/58) was 56.9%, the presence of signs or symptoms compatible with opioid toxicity (12/47) was 25.5%, and no cases were confirmed in records from the two deaths. Of the confirmed cases, 65.8% were related to therapeutic opioid use. Conclusions The collective and individual PPV for many ICD-9 CM codes consistent with opioid toxicity is low. For studies utilizing administrative claims, medical record review is to be important to accurately identify episodes of opioid toxicity and optimize case ascertainment. Disclosure of Interest None declared

To evaluate the effect of UK and US warnings placed in response to reports of suicidal thinking in pediatric patients receiving selective serotonin reuptake inhibitor and selective norepinephrine reuptake inhibitor antidepressants on antidepressant prescribing for children and adolescents.Interrupted time-series analysis of antidepressant prescriptions.Tennessee's Medicaid program, January 1, 2002, through September 30, 2005.A mean of 405,000 children and adolescents aged 2 to 17 years qualified each month. Main Exposure Piecewise linear regression models were used to estimate the cumulative effect of the warnings, which were considered the exposure of interest.Monthly proportions of study children and adolescents who were new users of antidepressants, had discontinuity in antidepressant use, or were users of other psychotropic drugs.During the 2 years preceding the UK warning, there was no trend in the monthly proportions of new antidepressant users, with 23 new users per 10 000 persons per month. This proportion subsequently decreased 33% (95% confidence interval, 23% to 41%; P.001) by 21 months following the UK warning. The reduction was most pronounced for the nonfluoxetine selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors, where initiations decreased 54% (95% confidence interval, 46% to 62%; P.001). In contrast, new users of fluoxetine increased 60% (95% confidence interval, 9% to 135%; P = .02). There was no increase in discontinuations of antidepressants, and there was no evidence of substitution of other psychotropic drugs.The regulatory warnings led to decreased use of antidepressants in children and adolescents, but the clinical and public health consequences of this change are unknown.

Nutrient availability has been linked to successional change in the extremely Nlimited coastal heathland ecosystem. A study was conducted on Nantucket Island (Massachusetts) to determine if plants with N-fixing symbioses affect nutrient availability and community succession in coastal heathland ecosystems. N-availability was no different in soils collected beneath N-fixing species than in soils collected away from N-fixing species. Furthermore there was no difference in nitrogen content of grasses and soils found in association with N-fixing species than those located away from N-fixers. The 15N content of soils and plants distributed within and without the canopy of N-fixing species was no different. The annual height and weight increments of pines growing within and away from patches of the N-fixing shrub Myrica pensylvanica were not significantly different, indicating that nitrogen derived from N-fixing symbioses did not contribute to the growth of pines. The lack of noticeable effects of N-fixing species on neighboring plants may be the result of leaching in these sandy soils, which would minimize lateral plant-to-plant N transfers via the soil.

Prescribed burning is being used to manage sandplain grasslands in New England, particularly for rare species habitat enhancement. This study examined the effects of prescribed burning on soil nitrogen availability over time and through the soil profile of sandplain grasslands in addition to short-term primary production estimated as standing crop biomass. Nitrogen availability was increased in the short term in the surface soils of a sandplain grassland ecosystem subjected to spring burning. Mineral nitrogen leached into lower soil horizons following the first large rainstorms after fire, and was eventually significantly depleted throughout the rooting zone. The ecosystem did not return to preburn concentrations of available nitrogen within 3 yr following fire. Production of standing crop biomass over the short term varied among species following fire. There was a significant effect of burning upon standing crop biomass of the graminoids with the highest biomass observed in the unburned reference area. Furthermore, the herbaceous legume, Tephrosia virginiana, increased in aboveground biomass and flowering during the growing season immediately following the spring burn.

Lemna minor L. (strain 6591) and L. turionifera Landolt (strains 6573 and A) respond differently to culture conditions. Turions are produced and the frondsdie in strains grown in Lm medium, while those same strains continue to grow without turion formation when cultured in E medium. Attempts were made to discover possible triggers for turion production in Lm medium. Nutrient limitation, especially of phosphorus and/or nitrogen, does not appear to be the principal cause of turion induction; however, phosphorus addition encouraged turion germination.

Background The use of opioids is increasing in children; therefore, opioid toxicity could be a public health problem in this vulnerable population. However, we are not aware of a published algorithm to identify cases of opioid toxicity in children using administrative databases. We sought to develop an algorithm to identify them. After review of literature and de-identified computer profiles, a broad set of ICD-9 CM codes consistent with serious opioid toxicity was selected. Based on these codes, we identified 195 potential cases of opioid toxicity in children enrolled in Tennessee Medicaid. Medical records were independently reviewed by two physicians; episodes considered equivocal were reviewed by an adjudication committee. Cases were adjudicated as Group 1 (definite/probable), Group 2 (possible), or Group 3 (excluded). Results Of the 195 potential cases, 168 (86.2%) had complete records for review and 85 were confirmed cases. The overall positive predictive value (PPV) for all codes was 50.6%. The PPV for codes indicating: unintentional opioid overdose (25/31) was 80.7%; intentional opioid overdose (15/30) was 50.0%, adverse events (33/58) was 56.9%, the presence of signs or symptoms compatible with opioid toxicity (12/47) was 25.5%, and no cases were confirmed in records from the two deaths. Of the confirmed cases, 65.8% were related to therapeutic opioid use. Conclusion For studies utilizing administrative claims to quantify incidence of opioid toxicity in children, our findings suggest that use of a broad set of screening codes coupled with medical record review is important to increase the completeness of case ascertainment.

Embryology of the ectoproctConopeum tenuissimum was followed from egg extrusion to three days and colony development from settlement to about seven days (20 generations of zooids). The cyphonautes larvae are rare in plankton, perhaps for behavioral reasons. Astogenetic change occurs for about 10 days, but some features reach a state of repetition more rapidly than others. The small colony size, rapid growth and reproduction show that this ectoproct possesses an “opportunist” life strategy, particularly well adapted to estuarine conditions.

Recent work on the taxonomy and biology of three species of membraniporine ectoprocts of the Chesapeake Bay area has necessitated changes in their nomenclature.Acanthodesia tenuis is now known asMembranipora tenuis, Membranipora membranacea must be considered to be as undescribed species ofMembranipora, andElectra crustulenta has been found to beConopeum tenuissimum. Recognition of these changes is particularly important in the case ofConopeum tenuissimum, a very common fouling species over large areas of Chesapeake Bay.