Obsesión de los cuerpos

In order to address the multiple aims of this research project, four samples were constructed. These samples were constructed using inclusion and exclusion criteria based on studies previously conducted in the pediatric bipolar literature, as well as expert-consensus recommendations regarding the design of clinical trials for pediatric bipolar disorder. Details of the study sample inclusion and exclusion criteria are provided below.

The overall study sample included patients in the MarketScan Commercial Claims and Encounters database from January 1, 2005 through December 31, 2007. Patients were included if they were under the age of 18 years at the time of their first recorded bipolar diagnosis and had either one inpatient or two or more outpatient insurance claims with unique service dates for a bipolar spectrum disorder (ICD-9 codes noted in Table 3.1). DSM- IV codes were mapped to the respective ICD-9 codes to provide conservative estimates of the diagnostic prevalence of the spectrum disorders. This mapping was consistent with previous literature in this area.235, 245, 246

Overlapping claims for both inpatient and outpatient services on the same date were counted as inpatient claims. Additionally, because several medical disorders mimic

symptoms of mania, children with any of the following medical disorders were excluded: temporal lobe epilepsy (ICD-9 code 345.4), multiple sclerosis (ICD-9 code 340),

hyperthyroidism (ICD-9 code 242.9), closed or open head injury (ICD-9 codes 800.x - 801.x and 850.x - 854.x) and systemic lupus erythematosus (ICD-9 code 710.0) or if they were

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pregnant (ICD-9 code V22 - V24 and V27 - V29).3, 247 Patients meeting the criteria noted above were included in the initial study sample. Further inclusion and exclusion criteria were added to refine the initial study sample for each aim. These modifications are listed below by aim with corresponding sample flow diagrams provided in Chapter 4.

4Table 3.1 - International Disease Classification, Ninth Edition (ICD-9) and Diagnostic and Statistics Manual for Mental Illness, Text Revision (DSM-IV-TR)

Aim 1 was analyzed in two ways (labeled hereafter as aim 1a and aim 1b to differentiate the study designs). Aim 1a utilized a repeated cross-sectional study design to identify the diagnostic prevalence of bipolar spectrum disorders, along with the treatments and demographic characteristics of children with bipolar disorder. This analytic strategy allowed us to determine the prevalence of diagnosed bipolar disorder by using annual cross- sections. Aim 1b: Restricted the patient population to newly diagnosed patients by including only those patients who had no previous diagnosis or treatment for a bipolar spectrum disorder (an antipsychotic, anticonvulsant or lithium). Using this strategy, patients were

ICD-9 Code ICD-9 Description DSM-IV-TR Code DSM-IV Description 296.0x Manic disorder, single

episode 296 Bipolar disorders

296.1x Manic disorder, recurrent

episode 296 Bipolar disorders

296.4x Bipolar affective disorder,

manic 296.4x

Bipolar I disorder, most recent episode hypomanic

296.5x Bipolar affective disorder,

depressed 296.5x

Bipolar I disorder, most recent episode depressed

296.6x Bipolar affective disorder,

mixed 296.6x

Bipolar I disorder, most recent episode mixed

296.7x Bipolar affective disorder,

unspecified 296.7x

Bipolar I disorder, most recent episode unspecified

296.80 Manic-depressive psychosis,

unspecified 296.80 Bipolar disorder NOS

296.89 Other 296.89 Bipolar II disorder

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followed forward in time to determine if there were changes in their diagnoses or treatments. Using this sample, patient characteristics and physician characteristics were summarized by the child's index bipolar diagnosis subtype.

3.2.1 Aim1a: Repeated cross-sectional design, prevalence study

For aim 1a patients were classified by the bipolar diagnosis code received at their last bipolar-related visit. Because the original study sample required only that patients be under the age of 18 years at the time of their first recorded diagnosis, there may have been patients in the aim 1a sample who were over the age of 17 years by their last bipolar-related visit. Therefore, the age under 18 age limit was re-applied to the aim 1a sample. This sample was used for the prevalence and demographic analyses related to aim 1a.

3.2.2 Aim1a: Repeated cross-sectional design, medication use study

Further criteria were applied to accurately identify the prescription drug eligible sample. In order to identify medication us in the 30 days following the patient's most recent diagnosis, the index diagnosis was modified from the initial sample and above by only considering diagnoses that took place prior to December 1st in each study year. Again, the age less than 18 restriction was applied to this study sample. Only patients who had drug data reported by their insurance provider to MarketScan were included. These patients were identified within the MarketScan claims data as having medication drug information

available (yes/no). This restriction only required that drug records be available, not that patients had a prescription drug claim. Patients were also required to be enrolled in their

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insurance plan at the time of their diagnosis and up to 30 days after their diagnosis in order to correctly classify their use or non-use of medications.

3.2.3 Aim1b: Incident Diagnosis Study Design

Next, additional exclusionary criteria were applied to address Aim 1b. In order to identify patients who were newly diagnosed and to accurately identify their treatments received over time, the initial sample was reduced by restricting the sample to patients whose first diagnosis occurred between July 1, 2005 and December 31, 2006. Patients also were required to have had continuous enrollment over the 18 month study period, and no previous evidence of a bipolar diagnosis or treatment (antipsychotic, anticonvulsant or lithium) for 6 months prior to their index diagnosis. The index diagnosis was the first recorded diagnosis date among patients who met these criteria.248 Similar inclusion criteria have been used previously when analyzing prescription claims data for patients with bipolar disorder.235, 248

Patients were excluded from this cohort if they had a diagnosis of schizophrenia (ICD-9 code 295.x),20, 235, 249, 250 a pervasive developmental disorder (i.e., autism or autism spectrum disorder, ICD-9 code 299.x),20, 250 mental retardation (ICD-9 codes 317 - 319), or a substance abuse disorder (ICD-9 codes 303 - 304)20 in the 6 months prior to their bipolar diagnosis. These criteria are consistent with requirements for clinical trials and with other studies in the area of pediatric bipolar disorder.20 Patients who were identified as substance users (ICD-9 code 305) were not excluded from the current study.

In addition to these criteria, patients whose insurance plans did not provide

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of medications and non-reporting of medications. Characteristics of children in the aim 1b sample were reported for only those children who had medication information available.

3.2.4 Aims 2 and 3 Study Sample

Finally, in order to address Aims 2 and 3 of the research plan, the sample was further reduced by excluding patients who had a bipolar spectrum disorder other than bipolar I disorder (i.e., excluded those with bipolar unspecified, bipolar II and cyclothymic disorder), and children under the age of 6 years at the time of their diagnosis. These exclusions were made because the treatment guidelines were specifically designed for patients with bipolar I disorder and for children ages 6 - 17 years.17 Patients with bipolar I disorder, depressed subtype were included in the analysis but indicator variables were used to identify this subtype since the guidelines were designed specifically for manic or mixed subtypes of the disorder.

Because medication use during hospitalization could not be detected in insurance claims data, children with hospitalizations 60 days prior to or 45 days post initial bipolar diagnosis were excluded. After these exclusions were made, the index treatment date was identified as the date at which the first dispensing of bipolar medications was made post initial diagnosis.