The effect of regulatory advisories on maternal antidepressant prescribing, 1995-2007: an interrupted time series study of 228,876 pregnancies.

The purpose of this study was to assess whether antidepressant prescribing during pregnancy decreased following release of U.S. and Canadian public health advisory warnings about the risk of perinatal complications with antidepressants. We analyzed data from 228,876 singleton pregnancies among women (aged 15-44 years) continuously enrolled in Tennessee Medicaid with full pharmacy benefits (1995-2007). Antidepressant prescribing was determined through outpatient pharmacy dispensing files. Information on sociodemographic and clinical factors was obtained from enrollment files and linked birth certificates. An interrupted time series design with segmented regression analysis was used to quantify the impact of the advisory warnings (2002-2005). Antidepressant prescribing rates increased steadily from 1995 to 2001, followed by sharper increases from 2002 to late 2004. Overall antidepressant prescribing prevalence was 34.51 prescriptions [95 % confidence interval (CI) 33.37-35.65] per 1,000 women in January 2002, and increased at a rate of 0.46 (95 % CI 0.41-0.52) prescriptions per 1,000 women per month until the end of the pre-warning period (May 2004). During the post-warning period (October 2004-June 2005), antidepressant prescribing decreased by 1.48 (95 % CI 1.62-1.35) prescriptions per 1,000 women per month. These trends were observed for both selective serotonin reuptake inhibitors (SSRI) and non-SSRI antidepressants, although SSRI prescribing decreased at a greater rate. We conclude that antidepressant prescribing to pregnant women in Tennessee Medicaid increased from 1995 to late 2004. U.S. and Canadian public health advisories about antidepressant-associated perinatal complications were associated with steady decreases in antidepressant prescribing from late 2004 until the end of the study period, suggesting that the advisory warnings were impactful on antidepressant prescribing in pregnancy.

Reporting of Child Maltreatment During the COVID-19 Pandemic in a Southern State in the United States.

OBJECTIVES: COVID-19-related stay-at-home orders (SAHOs) created an immediate physical barrier between children and professionals such as pediatricians and teachers, who are often first to identify and report signs of child maltreatment. Our objective was to determine how the SAHO in a southern state was associated with reports of child maltreatment and whether this association was modified by sociodemographic characteristics. METHODS: We linked data on reports of child maltreatment from a southern state in the United States from October 1, 2018, through September 30, 2020, to data from the US Census Bureau to obtain data on county-level socioeconomic characteristics. We fit a segmented regression model to evaluate changes in reports before and after the SAHO, March 20, 2020. We evaluated potential disparities by child age, case and allegation severity, and socioeconomic characteristics. RESULTS: Of 374 885 hotline calls, 276 878 (73.9%) were made before the SAHO and 98 007 (26.1%) after it. Although an immediate decrease in reports of child maltreatment occurred on the day of the SAHO, the rates of reporting within socioeconomic groups started increasing thereafter. While we found no significant change in the overall rate of change in hotline calls after versus before the SAHO (0.23; 95% CI, -0.11 to 0.58), stratified analyses indicate that the rates at which reporting increased varied by education level, health insurance coverage, median annual household income, and unemployment. CONCLUSIONS: Evaluating these trends is important for policy makers and practitioners to understand how policies enforced during the pandemic influence child maltreatment reporting and how these policies may affect reporting differently across socioeconomic groups.

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

PURPOSE: To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants, and lithium during pregnancy. METHODS: Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. RESULTS: During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies (ß = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. CONCLUSIONS: There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted.

Applying principles from safety science to improve child protection.

Child Protective Services Agencies (CPSAs) share many characteristics with other organizations operating in high-risk, high-profile industries. Over the past 50 years, industries as diverse as aviation, nuclear power, and healthcare have applied principles from safety science to improve practice. The current paper describes the rationale, characteristics, and challenges of applying concepts from the safety culture literature to CPSAs. Preliminary efforts to apply key principles aimed at improving child safety and well-being in two states are also presented.

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.

Changes to the financial responsibility for juvenile court ordered psychiatric evaluations reduce inpatient services utilization: an interrupted time series study.

BACKGROUND: The purpose of the current study was to evaluate the impact of a July 2008 Tennessee Court of Appeals opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County. METHODS: We used de-identified administrative data from the Tennessee Department of Mental Health and mid-year population estimates from the U.S. Census Bureau from July 1, 2006 to June 30, 2010, and an interrupted time series design with segmented regression analysis to quantify the impact of the implementation of the Court opinion. RESULTS: In the study period, there were 2,176 referrals for juvenile court ordered psychiatric evaluations in Tennessee; of these, 74.1% were inpatient evaluations. The Court opinion was associated with a decrease of 9.4 (95% C.I. = 7.9-10.8) inpatient and increase of 1.2 (95% C.I. = 0.4-2.1) outpatient evaluations per 100,000 Tennessee youth aged 12 to 19 years per month. CONCLUSIONS: The Court opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County was associated with a sudden and significant decrease in inpatient psychiatric evaluations, and more modest increase in outpatient evaluations.

Positive predictive value of automated database records for diabetic ketoacidosis (DKA) in children and youth exposed to antipsychotic drugs or control medications: a Tennessee Medicaid Study.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of treatment with some atypical antipsychotic drugs in children and youth. Because drug-associated DKA is rare, large automated health outcomes databases may be a valuable data source for conducting pharmacoepidemiologic studies of DKA associated with exposure to individual antipsychotic drugs. However, no validated computer case definition of DKA exists. We sought to assess the positive predictive value (PPV) of a computer case definition to detect incident cases of DKA, using automated records of Tennessee Medicaid as the data source and medical record confirmation as a "gold standard." METHODS: The computer case definition of DKA was developed from a retrospective cohort study of antipsychotic-related type 2 diabetes mellitus (1996-2007) in Tennessee Medicaid enrollees, aged 6-24 years. Thirty potential cases with any DKA diagnosis (ICD-9 250.1, ICD-10 E1x.1) were identified from inpatient encounter claims. Medical records were reviewed to determine if they met the clinical definition of DKA. RESULTS: Of 30 potential cases, 27 (90%) were successfully abstracted and adjudicated. Of these, 24 cases were confirmed by medical record review (PPV 88.9%, 95% CI 71.9 to 96.1%). Three non-confirmed cases presented acutely with severe hyperglycemia, but had no evidence of acidosis. CONCLUSIONS: Diabetic ketoacidosis in children and youth can be identified in a computerized Medicaid database using our case definition, which could be useful for automated database studies in which drug-associated DKA is the outcome of interest.

Effects of orally disintegrating vs regular olanzapine tablets on body weight, eating behavior, glycemic and lipid indices, and gastrointestinal hormones: a randomized, open comparison in outpatients with bipolar depression.

BACKGROUND: This randomized, open-label trial aimed to compare the metabolic effects of olanzapine orally disintegrating tablets (ODT) and solid oral tablets (SOT) in bipolar depressed and mixed outpatients. METHODS: Participants were openly randomized to receive olanzapine ODT (n = 13) or SOT (n = 10), 10 to 20 mg, once daily. Weight, body mass index (BMI), Food Craving Inventory (FCI), and Three-Factor Eating Questionnaire (3-FEQ) scores were assessed at baseline and at weeks 1, 2, 4, 6, and 8. Fasting glucose and lipid levels were assessed at baseline and at week 8. Insulin and leptin concentrations were measured just prior to olanzapine baseline dosing, 1 and 2 hours following administration of baseline dose, and at weeks 4 and 8. RESULTS: Patients showed significant increases in weight, BMI, and leptin area under the concentration-time curve (AUC), but not in FCI or 3-FEQ scores, over 8 weeks of treatment with olanzapine ODT and SOT. However, no significant differences between olanzapine formulations (ODT vs SOT) were observed in any of the measures assessed, except for a significantly lower triglyceride concentration in the ODT group at week 8. CONCLUSIONS: There was no consistent difference in metabolic profile between olanzapine ODT and SOT formulations during short-term treatment of bipolar depressed patients. Potential differences related to effects on triglyceride concentration warrant further confirmation.

Sleep and school problems among children and adolescents in state custody.

Population-level research into the association between sleep problems and school problems among high-risk youth is limited. This study uses cross-sectional administrative and standardized assessment information for youth entering Tennessee state custody in fiscal year 2009 (n = 4280) to examine whether sleep problems are independently associated with school problems. Sleep problems were identified in 9.8% of the sample. There was no association between sleep and school problems for youth adjudicated delinquent. Among youth adjudicated dependent-neglect/unruly, multivariate logistic regression analysis indicates that youth at risk for sleep problems are 1.78 (95% confidence interval = 1.24-2.55) and youth with actionable sleep problems are 3.30 (95% confidence interval = 1.78-6.14) times more likely than youth without sleep problems to have school problems. Results suggest that the school performance of youth entering state custody adjudicated dependent-neglect/unruly may benefit from systematic screening and intervention for sleep problems.

The constitutional protection of trade secrets and patents under the Biologics Price Competition and Innovation Act of 2009.

The Biologics Price Competition and Innovation Act of 2009 ("Biosimilars Act") is for the field of pharmaceutical products the single most important legislative development since passage of the Drug Price Competition and Patent Term Restoration Act of 1984 ("Hatch-Waxman Act"), on which portions of the Biosimilars Act are clearly patterned. Congress revised section 351 of the Public Health Service Act (PHSA) to create a pathway for FDA approval of "biosimilar" biological products. Each biosimilar applicant is required to cite in its application a "reference product" that was approved on the basis of a full application containing testing data and manufacturing information, which is owned and was submitted by another company and much of which constitutes trade secret information subject to constitutional protection. Because the Biosimilars Act authorizes biosimilar applicants to cite these previously approved applications, the implementation of the new legislative scheme raises critical issues under the Fifth Amendment of the Constitution, pursuant to which private property--trade secrets included--may not be taken for public use, without "just compensation." FDA must confront those issues as it implements the scheme set out in the Biosimilars Act. This article will discuss these issues, after providing a brief overview of the Biosimilars Act and a more detailed examination of the law of trade secrets.

Psychopharmaceutical Prescription Monitoring for Children in the Child Welfare System.

OBJECTIVE: Children in the child welfare system are more likely to receive psychotropic medication prescriptions than children in the general population. The authors used prescription- and administrative-level data to quantify variability in prescribing practices among prescribers for the child welfare population in a southern U.S. state. METHODS: Using administrative- and prescription-level child data and Administration on Children, Youth and Families guidelines, the authors defined the primary outcome, potentially inappropriate psychotropic prescriptions (i.e., red-flagged prescriptions). A hierarchical-logistic regression model was fit to account for case complexity and estimate the adjusted probability of a prescription being red-flagged. A funnel plot was used to visualize standardized prescribing rates for every prescriber and identify outlying prescribers. RESULTS: From May 2016 to September 2017, 506 prescribers issued 64,923 prescriptions for 4,093 children with a median (interquartile range) age of 14 (10-16) years. Most prescribers (76.9%) issued at least one red-flagged prescription, 1,263 (30.9%) children received at least one red-flagged prescription, and 14,806 (22.8%) prescriptions were red-flagged. The standardized prescribing rate for each prescriber was compared with a benchmark of 22.8%, defined a priori as the proportion of red-flagged prescriptions in the overall sample. Forty-seven prescribers (9%) prescribed red-flagged prescriptions between two and three standard deviations above the benchmark, and 72 prescribers (14%) more than three standard deviations above the benchmark. CONCLUSIONS: It is vital to monitor psychotropic prescriptions for children in the child welfare system. Quantifying variability in prescribing practices among prescribers for these children might be used to guide oversight.

Olanzapine monotherapy for acute depression in patients with bipolar I or II disorder: results of an 8-week open label trial.

We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open-label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8 weeks. Assessments of psychopathology (Montgomery-Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS-SR-16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow-up time points (p < or = 0.005). Parallel improvement in QIDS-SR-16 (p < 0.001) and CGI-Severity (p < 0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2 kg, p = 0.001) and body mass index (+1.1 kg/m(2), p = 0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well-tolerated option for treating acute non-psychotic depression across a variety of bipolar disorder subtypes.

Incidence and neighborhood-level determinants of child welfare involvement.

BACKGROUND: Child maltreatment is a global public health issue that has been linked with multiple negative health and life outcomes. OBJECTIVE: This study evaluates the association between children placed in out-of-home care and neighborhood-level factors using eight years of administrative data. PARTICIPANTS AND SETTING: Between 2011-2018, 33,890 unique instances of child welfare involvement were captured in a department of child and family services database in a southern state in the United States. METHODS: Removal addresses were geocoded and linked to the U.S. Census Bureau's American Community Survey to obtain census tract socioeconomic factors. Incidence overall and stratified by individual and neighborhood-level factors was computed. Rate ratios, relative indexes of inequality, and concentration curves quantified disparities in incidence of child welfare involvement by neighborhood-level factors. RESULTS: Incidence of children less than 19 years old placed into out-of-home care was 255 per 100,000 person-years (95 % CI: 252, 258). At the individual level, incidence was highest among children <5 and 15-17 years old, comparable between male and female children, and higher among Black children. At the neighborhood level, incidence was highest in census tracts with lower median household incomes, higher percentages of households below poverty or of female-headed or single-parent households, higher unemployment rates, and fewer residents with some college education or health insurance. CONCLUSIONS: Incidence of children placed into out-of-home care is disproportionally higher for those who live in disadvantaged communities. Understanding neighborhood-level risk factors that may be linked to child welfare involvement can help inform policy and target prevention efforts.

A population-based examination of maltreatment referrals and substantiation for children with autism spectrum disorder.

Children with disabilities experience elevated rates of maltreatment, but little is known about the interaction of children with autism spectrum disorder with child protection systems. A population-based dataset of 24,306 children born in 2008 in Tennessee, which included 387 children with autism spectrum disorder identified through the Autism and Developmental Disabilities Monitoring network, was linked with state child protection records. Rates of maltreatment referrals, screening for further action, and substantiated maltreatment were examined for children with versus without autism spectrum disorder. Significantly more children with autism spectrum disorder (17.3%) than without (7.4%) were referred to the Child Abuse Hotline. Children with autism spectrum disorder were less likely than children without autism spectrum disorder to have referrals screened in for further action (62% vs 91.6%, respectively), but substantiated maltreatment rates were similar across groups (3.9% vs 3.4%, respectively). Girls versus boys with autism spectrum disorder were more likely to have substantiated maltreatment (13.6% vs 1.9%, respectively). The high percentage of children with autism spectrum disorder referred for allegations of maltreatment, the differential pattern of screening referrals in for further action, and the high levels of substantiated maltreatment of girls with autism spectrum disorder highlights the need for enhanced training and knowledge of the complex issues faced by children with autism spectrum disorder, their families, and state welfare agencies.

A systematic review of screening tools in non-young children and adults for autism spectrum disorder.

BACKGROUND: Existing reviews of screening tools for Autism Spectrum Disorder (ASD) focus on young children, and not all screening tools have been examined against validated diagnostic procedures. AIMS: To examine the validity of screening tools for ASD in non-young children and adults to provide clinical recommendations about the use of these tools in a variety of clinical settings. METHODS AND PROCEDURES: Electronic databases, including MEDLINE, EMBASE, PsychINFO, Cochrane Library and CINAHL, were searched through March 2017. Studies examining the validity of ASD screening tools against the Autism Diagnostic Observation Schedule and/or the Autism Diagnostic Interview - Revised in non-young children (age 4 or above) and adults were included. Three authors independently reviewed each article for data extraction and quality assessment. OUTCOMES AND RESULTS: 14 studies met the inclusion criteria, of which 11 studies were with children (4-18 years of age) and 3 studies included adults only (19 years of age and above). Included studies were conducted in a general population/low-risk sample (N = 3) and a clinically referred/high-risk sample (N = 11). In total 11 tools were included. CONCLUSIONS AND IMPLICATIONS: Only three screening tools (the Autism-Spectrum Quotient, the Social Communication Questionnaire, and the Social Responsiveness Scale) were examined in more than 2 studies. These tools may assist in differentiating ASD from other neurodevelopmental and psychiatric disorders or typically developed children. In young adult populations, the paucity of the existing research in this group limits definitive conclusion and recommendations.

AHRQ series on complex intervention systematic reviews-paper 3: adapting frameworks to develop protocols.

BACKGROUND: Once a proposed topic has been identified for a systematic review and has undergone a question formulation stage, a protocol must be developed that specifies the scope and research questions in detail and outlines the methodology for conducting the systematic review. RATIONALE: Framework modifications are often needed to accommodate increased complexity. We describe and give examples of adaptations and alternatives to traditional analytic frameworks. DISCUSSION: This article identifies and describes elements of frameworks and how they can be adapted to inform the protocol and conduct of systematic reviews of complex interventions. Modifications may be needed to adapt the population, intervention, comparators, and outcomes normally used in protocol development to successfully describe complex interventions; in some instances, alternative frameworks may be better suited. Possible approaches to analytic frameworks for complex interventions that illustrate causal and associative linkages are outlined, including time elements, which systematic reviews of complex interventions may need to address. The need for and specifics of the accommodations vary with details of a specific systematic review. This in turn helps determine whether traditional frameworks are sufficient, can be refined, or if alternate frameworks must be adopted.

It did happen here: fear and loathing on the vaccine trail.

Adverse publicity that placed undue emphasis on a possible connection between autism and the measles-mumps-rubella (MMR) vaccine and vaccines containing thimerosal made parents in the United Kingdom reluctant to allow their children to receive the vaccine. The same concerns have played themselves out in the U.S. Food and Drug Administration's decision to recommend removal of thimerosal from other vaccines, even as the individual autism claims have been rejected. That recommendation, based on unsubstantiated safety concerns, reveals a deep-seated institutional overreaction that is more likely to cost lives than to save them.

Treatment of bipolar disorders during pregnancy: maternal and fetal safety and challenges.

Treating pregnant women with bipolar disorder is among the most challenging clinical endeavors. Patients and clinicians are faced with difficult choices at every turn, and no approach is without risk. Stopping effective pharmacotherapy during pregnancy exposes the patient and her baby to potential harms related to bipolar relapses and residual mood symptom-related dysfunction. Continuing effective pharmacotherapy during pregnancy may prevent these occurrences for many; however, some of the most effective pharmacotherapies (such as valproate) have been associated with the occurrence of congenital malformations or other adverse neonatal effects in offspring. Very little is known about the reproductive safety profile and clinical effectiveness of atypical antipsychotic drugs when used to treat bipolar disorder during pregnancy. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated or undertreated maternal bipolar disorder during pregnancy, the effectiveness of interventions for bipolar disorder management during pregnancy, and potential obstetric, fetal, and neonatal risks associated with core foundational pharmacotherapies for bipolar disorder.

Treatment of ankyloglossia for reasons other than breastfeeding: a systematic review.

BACKGROUND AND OBJECTIVE: Children with ankyloglossia, an abnormally short, thickened, or tight lingual frenulum, may have restricted tongue mobility and sequelae, such as speech and feeding difficulties and social concerns. We systematically reviewed literature on feeding, speech, and social outcomes of treatments for infants and children with ankyloglossia. METHODS: Medline, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and Embase were searched. Two reviewers independently assessed studies against predetermined inclusion/exclusion criteria. Two investigators independently extracted data on study populations, interventions, and outcomes and assessed study quality. RESULTS: Two randomized controlled trials, 2 cohort studies, and 11 case series assessed the effects of frenotomy on feeding, speech, and social outcomes. Bottle feeding and social concerns, such as ability to use the tongue to eat ice cream and clean the mouth, improved more in treatment groups in comparative studies. Supplementary bottle feedings decreased over time in case series. Two cohort studies reported improvement in articulation and intelligibility with treatment. Other benefits were unclear. One randomized controlled trial reported improved articulation after Z-frenuloplasty compared with horizontal-to-vertical frenuloplasty. Numerous noncomparative studies reported speech benefits posttreatment; however, studies primarily discussed modalities, with outcomes including safety or feasibility, rather than speech. We included English-language studies, and few studies addressed longer-term speech, social, or feeding outcomes; nonsurgical approaches, such as complementary and alternative medicine; and outcomes beyond infancy, when speech or social concerns may arise. CONCLUSIONS: Data are currently insufficient for assessing the effects of frenotomy on nonbreastfeeding outcomes that may be associated with ankyloglossia.