Hepatitis C Testing Among Perinatally Exposed Infants.

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 <.001), used tobacco (78% vs 70%; P <.001), and had HIV (1.3% vs 0.4%; P = .002) were more likely to be tested. Infants exposed to HCV who had a higher median of well-child visits (7 vs 6; P <.001) were more likely to be tested. After accounting for maternal and infant characteristics and health care use patterns, African American infants were less likely to undergo general testing (adjusted odds ratio 0.32; 95% confidence interval, 0.13-0.78). CONCLUSIONS: Testing occurred in <1 in 4 infants exposed to HCV and less frequently among African American infants. Public health systems need to be bolstered to ensure that infants exposed to HCV are tested for seroconversion.

Individual short-acting opioids and the risk of opioid-related adverse events in adolescents.

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.

Increased Severity of Neonatal Abstinence Syndrome Associated With Concomitant Antenatal Opioid and Benzodiazepine Exposure.

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.

Positive Predictive Value of Administrative Data for Neonatal Abstinence Syndrome.

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.

Outpatient Opioid Prescriptions for Children and Opioid-Related Adverse Events.

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).

Development of an algorithm to identify serious opioid toxicity in children.

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.

Evaluation and disposition of Medicaid-insured children and adolescents with suicide attempts.

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.

Antidepressants and suicide attempts in children.

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.

First trimester exposure to antiretroviral therapy and risk of birth defects.

BACKGROUND: Use of antiretroviral (ARV) drugs during pregnancy has been associated with an increased risk of birth defects, but the evidence remains inconclusive. METHODS: We identified infants born to human immunodeficiency virus (HIV)-infected mothers between 1994 and 2009 using Tennessee Medicaid data linked to vital records. Maternal HIV status was based on diagnosis codes, prescriptions for ARVs and HIV-related laboratory testing. ARV exposure was identified from pharmacy claims. Birth defects diagnoses during the first year of life were identified from maternal and infant claims and vital records and were confirmed through medical record review. Multivariate logistic regression models were used to evaluate associations between first trimester ARV dispensing and birth defects. RESULTS: Of 806 infants included in the study, 32 (4.0%) had at least 1 major birth defect, most (44%) in the cardiac system. There was no increased risk for infants exposed in the first trimester to ARVs compared with unexposed infants (odds ratio = 1.07; 95% confidence interval: 0.50-2.31). Of the 20 infants exposed to efavirenz, none had a birth defect (0%; 95% confidence interval: 0.0-13.2). CONCLUSIONS: There was no significant association between first trimester ARV dispensing and the risk of birth defects in this Medicaid cohort of HIV-positive women.

Identifying suicidal behavior among adolescents using administrative claims data.

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.

Adherence to transcranial Doppler screening guidelines among children with sickle cell disease.

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-ß(0) -thalassemia (HbSß(0) ) 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 HbSß(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. 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 HbSß(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.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

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 US, 2001-2007. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Comparative effectiveness of antibiotic treatment strategies for pediatric skin and soft-tissue infections.

OBJECTIVE: To compare the effectiveness of clindamycin, trimethoprim-sulfamethoxazole, and ß-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 ß-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 ß-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 ß-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 ß-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 ß-lactams. CONCLUSIONS: Compared with clindamycin, use of trimethoprim-sulfamethoxazole or ß-lactams was associated with increased risks of treatment failure and recurrence. Associations were stronger for those with a drainage procedure.

Antibiotics potentially used in response to bioterrorism and the risk of major congenital malformations.

This study was designed to assess the association between pregnancy-related exposures to antibiotics recommended for use in the event of a bioterrorism attack and major congenital malformations. A retrospective cohort study included 30 049 infants from Tennessee Medicaid born between 1985 and 2000 identified from computerised state databases. Infants with fetal exposures to ciprofloxacin, azithromycin, doxycycline and amoxicillin (antibiotics recommended for potential bioterrorism attacks) (n = 24 521) and erythromycin (included as a positive control) (n = 2128) were compared with infants with no fetal exposure to any antibiotics (n = 3400). Major congenital malformations identified from computerised records were confirmed through medical record review. Overall, 869 (2.9%) of infants in the cohort had a confirmed major congenital malformation, with major malformations ranging from 2.5% to 3.0% among the antibiotic-specific exposure groups. No increased risk was present in multivariable analyses for any malformations and for malformations of specific organ systems. In conclusion, these data suggest that ciprofloxacin, azithromycin, doxycycline or amoxicillin use by pregnant women should not result in a greater incidence of overall major congenital malformations in infants whose mothers take these medications, though a large increase in risk cannot be ruled out.

Trends in healthcare usage attributable to diarrhea, 1995-2004.

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.

Increase in incidence of medically treated thyroid disease in children with Down Syndrome after rerelease of American Academy of Pediatrics Health Supervision guidelines.

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.

Stool cultures and antimicrobial prescriptions related to infectious diarrhea.

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.

Health plan notification and feedback to providers is associated with increased filling of preventer medications for children with asthma enrolled in Medicaid.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: Health plan communication to providers was associated with increased preventer filling in children with moderate-severe asthma in 2 state Medicaid programs.

Effect of regulatory warnings on antidepressant prescribing for children and adolescents.

OBJECTIVE: 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. DESIGN: Interrupted time-series analysis of antidepressant prescriptions. SETTING: Tennessee's Medicaid program, January 1, 2002, through September 30, 2005. PARTICIPANTS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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.

Major congenital malformations after first-trimester exposure to ACE inhibitors.

BACKGROUND: Use of angiotensin-converting-enzyme (ACE) inhibitors during the second and third trimesters of pregnancy is contraindicated because of their association with an increased risk of fetopathy. In contrast, first-trimester use of ACE inhibitors has not been linked to adverse fetal outcomes. We conducted a study to assess the association between exposure to ACE inhibitors during the first trimester of pregnancy only and the risk of congenital malformations. METHODS: We studied a cohort of 29,507 infants enrolled in Tennessee Medicaid and born between 1985 and 2000 for whom there was no evidence of maternal diabetes. We identified 209 infants with exposure to ACE inhibitors in the first trimester alone, 202 infants with exposure to other antihypertensive medications in the first trimester alone, and 29,096 infants with no exposure to antihypertensive drugs at any time during gestation. Major congenital malformations were identified from linked vital records and hospitalization claims during the first year of life and confirmed by review of medical records. RESULTS: Infants with only first-trimester exposure to ACE inhibitors had an increased risk of major congenital malformations (risk ratio, 2.71; 95 percent confidence interval, 1.72 to 4.27) as compared with infants who had no exposure to antihypertensive medications. In contrast, fetal exposure to other antihypertensive medications during only the first trimester did not confer an increased risk (risk ratio, 0.66; 95 percent confidence interval, 0.25 to 1.75). Infants exposed to ACE inhibitors were at increased risk for malformations of the cardiovascular system (risk ratio, 3.72; 95 percent confidence interval, 1.89 to 7.30) and the central nervous system (risk ratio, 4.39; 95 percent confidence interval, 1.37 to 14.02). CONCLUSIONS: Exposure to ACE inhibitors during the first trimester cannot be considered safe and should be avoided.