Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM) needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, and mortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17 years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24 months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13 months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

Population-based treated prevalence, risk factors, and outcomes of bicuspid aortic valve in a pediatric Medicaid cohort.

BACKGROUND: We investigated the treated prevalence of bicuspid aortic valve in a pediatric population with congenital heart disease and its incident complications. MATERIALS AND METHODS: A 15-year retrospective data set was analyzed. Selection criteria included age ≤17 years, enrollees in the South Carolina State Medicaid program and diagnosed as having bicuspid aortic valve on one or more service visits. RESULTS: The 15-year-treated prevalence of predominantly isolated bicuspid aortic valve was 2% (20/1000) of pediatric congenital heart disease cases, with a non-African American: African-American ratio of 3.5:1, and a male:female ratio of 1.6:1. Aortic stenosis (28.0%), ventricular septal defect (20.6%), and coarctation of the aorta (20.6%) were the most prevalent coexisting congenital heart lesions. Of the 378 bicuspid aortic valve cases examined, 10.3% received aortic valve repair/replacement, which was significantly more likely to be performed in children with diagnosed aortic stenosis (adjusted odds ratio = 12.90; 95% confidence interval = 5.66-29.44). Cohort outcomes over the study period indicated that 9.5% had diagnosed heart failure, but <1% had diagnosed supraventricular tachycardia, infective endocarditis, aneurysm, dissection, or death. CONCLUSIONS: The majority of isolated bicuspid aortic valve cases without aortic stenosis did not require surgical intervention. Outcomes for cases requiring repair/replacement were relatively benign.

Risk Factors for Heart Failure and Its Costs Among Children with Complex Congenital Heart Disease in a Medicaid Cohort.

Little research attention has been paid to the occurrence of heart failure (HF) in children with complex congenital heart diseases (CHDs). Herein, we describe the prevalence, risk factors, and costs associated with HF in complex CHD. Patients aged ≤17 years and diagnosed with a complex CHD on multiple service visits over a 15-year period in the SC Medicaid dataset (1996-2010) were tracked and analyzed. The cohort included 2999 unduplicated patients; 51.0% were male; 34.4% were African American. HF was diagnosed in 7.6%. Single ventricle lesions, genetic syndromes, and ventricular arrhythmia were significantly associated with an increased likelihood of being diagnosed with HF, controlling for development of comorbid pulmonary hypertension. Patients with HF received significantly more subspecialty care, more surgeries, more hospitalizations, more total days of inpatient care, and more emergency department care than those without HF. Patients with significantly higher total care costs paid by Medicaid had HF, more cardiac surgeries, and more specialized mechanical or other support procedures, controlling for diagnosed single ventricle CHD, a genetic syndrome, and number of non-cardiac surgeries. Complex CHD patients with HF incur significantly higher care costs but require multifaceted, intensive supports for management of incident complications and comorbid conditions.

The Efficacy of Psychostimulants in Major Depressive Episodes: A Systematic Review and Meta-Analysis.

BACKGROUND: Psychostimulants are frequently prescribed off-label for adults with major depressive disorder or bipolar disorder. The frequent and increasing usage of stimulants in mood disorders warrants a careful appraisal of the efficacy of this class of agents. Herein, we aim to estimate the efficacy of psychostimulants in adults with unipolar or bipolar depression. METHODS: The PubMed/Medline database was searched from inception to January 16, 2016 for randomized, placebo-controlled clinical trials investigating the antidepressant efficacy of psychostimulants in the treatment of adults with unipolar or bipolar depression. RESULTS: Psychostimulants were associated with statistically significant improvement in depressive symptoms in major depressive disorder (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.13-1.78; P = 0.003) and bipolar disorder (OR, 1.42; 95% CI, 1.13-1.78; P = 0.003). Efficacy outcomes differed across the psychostimulants evaluated as a function of response rates: ar/modafinil (OR, 1.47; 95% CI, 1.20-1.81; P = 0.0002); dextroamphetamine (OR, 7.11; 95% CI, 1.09-46.44; P = 0.04); lisdexamfetamine dimesylate (OR, 1.21; 95% CI, 0.94-1.56; P = ns); methylphenidate (OR, 1.49; 95% CI, 0.88-2.54; P = ns). Efficacy outcomes also differed between agents used as adjunctive therapy (OR, 1.39; 95% CI, 1.19-1.64) or monotherapy (OR, 2.25; 95% CI, 0.67-7.52). CONCLUSIONS: Psychostimulants are insufficiently studied as adjunctive or monotherapy in adults with mood disorders. Most published studies have significant methodological limitations (eg, heterogeneous samples, dependent measures, type/dose of agent). In addition to improvements in methodological factors, a testable hypothesis is that psychostimulants may be more appropriately tested in select domains of psychopathology (eg, cognitive emotional processing), rather than as "broad-spectrum" antidepressants.

Pharmacotherapy effectiveness for clinical subgroups among children and adolescents with early onset schizophrenia.

OBJECTIVE: This study aims to determine the effectiveness of pharmacotherapies among children and adolescents diagnosed with early onset schizophrenia subgrouped according to their co-occurring psychiatric disorders. METHODS: A retrospective cohort design was employed, using South Carolina's (USA) Medicaid claims dataset covering outpatient and inpatient medical services, between January, 1999 and December, 2013 to identify patients ≤17 years of age. Random effects regression analyses assessed differential changes in acute psychiatric service utilization over time across the 3 subgroups associated with antipsychotic, mood stabilizer, psychostimulant, or antidepressant pharmacotherapy. RESULTS: For patients with schizophrenia and comorbid mood disorders or emotional dysregulation (Cluster 1), or schizophrenia and severe cognitive impairments (Cluster 2), those treated with monotherapy second-generation antipsychotics (SGAs) over time demonstrated consistently lower use of acute psychiatric treatment services as did those coprescribed mood stabilizers, primarily lithium, or anticonvulsants. In all clusters, including the relatively homogenous subgroup of patients with early onset schizophrenia and few comorbid disorders, acute psychiatric service utilization was significantly higher and more variable over time for those prescribed multiple SGAs. CONCLUSIONS: Regardless of the specific constellation of symptoms and comorbid disorders targeted, the coprescription of multiple SGAs was not effective over time in stabilizing children and adolescents outside of acute care settings.

Diagnostic clusters associated with an early onset schizophrenia diagnosis among children and adolescents.

OBJECTIVE: Given the greater severity and chronicity of psychiatric disorders that first declare in individuals under the age of 18, early onset schizophrenia (EOS) and its association with co-occurring psychiatric conditions deserve further investigation. METHODS: Cluster and discriminant analyses were used to examine the heterogeneity of children and adolescents diagnosed with schizophrenia in 1 statewide system of care. A retrospective cohort design was employed, using South Carolina's (USA) Medicaid claims dataset covering outpatient and inpatient medical services between January, 1999 and December, 2013 to identify patients ≤17 years of age. RESULTS: Among the 613 EOS patients selected, 3 main clusters of ICD-9 psychiatric diagnoses were identified: (1) older children with schizophrenia coaggregated with a spectrum of mood/emotional dysregulation conditions; (2) younger children with coaggregated schizophrenia, mental retardation/intellectual disability or autism spectrum disorders; and (3) older children with schizophrenia and significantly fewer diagnosed co-occurring conditions. Externalizing/disruptive behavior disorders (i.e., attention deficit hyperactivity disorder, conduct disorder, and oppositional defiant disorder) were significantly associated with Clusters 1 and 2. CONCLUSION: Symptom patterns plus age of first diagnosis are important differentiators of EOS subgroups in this cohort. Earlier recognition of psychiatric symptom/syndrome patterns that frequently co-occur may enable clinicians to stratify/tailor treatment interventions.

Factors Associated With Musculoskeletal Injuries in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder.

BACKGROUND: Musculoskeletal injuries may be associated with attention-deficit/hyperactivity disorder (ADHD) symptom severity, comorbid psychiatric or medical conditions, and the prescribed psychostimulant. METHODS: A population-based, retrospective cohort design was employed using South Carolina's Medicaid claims data set covering outpatient and inpatient medical services and medication prescriptions over an 11-year period (January 1, 1996, through December 31, 2006) for patients ≤ 17 years of age with ≥ 2 visits for ICD-9-CM diagnostic codes for ADHD. A cohort of 7,725 cases was identified and analyzed using logistic regression to compare risk factors for those who sustained focal musculoskeletal injuries and those who did not. RESULTS: The risk of sustaining sprains, arthropathy and connective tissue disorders, or muscle and joint disorders was significantly related to being diagnosed with comorbid hypertension (adjusted odds ratios [aORs] = 1.60, 2.09, and 1.46, respectively) and a substance use disorder (aORs = 1.58, 1.38, and 1.28). Having a substance use disorder was also related to incident fractures and dorso/spinal injuries (aORs = 1.42 and 1.21). Diagnosed hypertension was related to incident concussions (aOR = 2.00), a diagnosed thyroid disorder was related to an increased risk of sprain and concussion (aORs = 1.44 and 2.05), a diagnosed anxiety disorder was related to an increased risk of dorso/spinal disorders (aOR = 1.71), and diagnosed diabetes was related to incident bone and cartilage disorders (aOR = 1.61). CONCLUSIONS: Comorbid hypertension, substance use disorders, and thyroid disorders deserve increased clinical surveillance in children and adolescents with ADHD because they may be associated with an increased risk of more than one musculoskeletal injury.

Factors Differentiating Childhood-Onset and Adolescent-Onset Schizophrenia:A Claims Database Study.

BACKGROUND: The greater severity and burden of illness in individuals with early onset schizophrenia (ie, before age 18 years) deserves further investigation, specifically regarding its prevalence in community-based treatment and its association with other psychiatric or medical conditions. METHOD: A retrospective cohort design was employed using the South Carolina Medicaid claims database covering outpatient and inpatient medical services from January 1, 1999, through December 31, 2013, to identify patients aged ≤ 17 years with a diagnosis of schizophrenia spectrum disorders (ICD-9-CM). Logistic regression was used to examine the factors differentiating childhood- versus adolescent-onset schizophrenia in a community-based system of care. RESULTS: Early onset schizophrenia was diagnosed in 613 child and adolescent cases during the study epoch or 0.2% of this population-based cohort. The early onset cohort was primarily male (64%) and black (48%). The mean length of time followed in the Medicaid dataset was 12.6 years. Within the early onset cohort, 22.5% were diagnosed at age ≤ 12 years and 77.5% were diagnosed as adolescents. The childhood-onset subgroup was twice as likely to have speech, language, or educational disabilities and an attention-deficit/hyperactivity disorder diagnosis but significantly less likely to have schizophrenia or schizoaffective disorder, an organic brain disorder or mental retardation/intellectual disability, or a substance use disorder (adjusted OR = 2.01, 2.26, 0.38, 0.31, 0.47, and 0.32, respectively) compared to the adolescent-onset subgroup. CONCLUSION: Primary care providers should identify and maintain surveillance of cases of pediatric neurodevelopmental disorders, which appear to be highly comorbid and genetically related, and refer them early and promptly for specialized treatment.

Anhedonia and cognitive function in adults with MDD: results from the International Mood Disorders Collaborative Project.

BACKGROUND: Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia. METHOD: A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations. RESULTS: A total of 369 adults with DSM-IV-TR-defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery-Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007). CONCLUSIONS: These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.

Incidence of primary hypertension in a population-based cohort of HIV-infected compared with non-HIV-infected persons and the effect of combined antiretroviral therapy.

Literature remains scarce on the impact of antiretroviral medications on hypertension in the HIV population. We used the South Carolina Medicaid database linked with the enhanced HIV/AIDS system surveillance database for 1994-2011 to evaluate incident hypertension and the impact of combination antiretroviral therapy (cART) in HIV/AIDS population compared with a propensity- matched non-HIV control group. Multivariable, time-dependent survival analysis suggested no significant difference in incidence of hypertension between the HIV group and the non-HIV control group. However, subgroup analysis suggested that among the HIV-infected group, months of exposure to both non-nucleoside reverse transcriptase inhibitors (adjusted hazard ratio, 1.52; 95% confidence interval, 1.3-1.75) and protease inhibitors (adjusted hazard ratio, 1.26; 95% confidence interval, 1.11-1.44) were associated with an increased risk of incident hypertension after adjusting for traditional demographic and metabolic risk factors. In people with HIV/AIDS, prolonged exposure to both protease inhibitor-based and non-nucleoside reverse transcriptase inhibitor-based cART may increase the risk of incident hypertension.

The impact of cognitive impairment on perceived workforce performance: results from the International Mood Disorders Collaborative Project.

BACKGROUND: Cognitive dysfunction and depression severity are key mediators of workplace adjustment in adults with major depressive disorder (MDD). Herein, we sought to determine the extent to which measures of depression severity and cognitive dysfunction were associated with perceived global disability, workplace performance and quality of life. METHOD: A post hoc analysis was conducted using data from 260 participants with a diagnosis of DSM-IV-TR-defined MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. Measures of workplace function, global disability, depression severity, cognitive function, and quality of life were employed. These data were analyzed using a multiple variable linear regression equations. RESULTS: Perceived global disability was significantly predicted by clinical ratings of depression severity (ß=0.54), and perceived inattention (ß=0.24), accounting for 37% of the variance. In addition, perceived inattention (ß=0.58) and clinical ratings of depression severity (ß=0.18), were also significant predictors of perceived workplace productivity/performance, accounting for 38% of the variance. Finally, both clinical ratings of depression severity (ß=-0.54), and perceived inattention (ß=-0.18) were significant inverse predictors of perceived quality of life, accounting for 34% of the variance. CONCLUSION: The overarching finding in the analysis herein is that workplace performance variability is explained by subjective measures of cognitive dysfunction to a greater extent than total depression symptom severity. Conversely, total depression symptom severity accounts for a greater degree of variability in global measures of disability relative to cognitive measures. Treatment strategies for adults with major depressive disorder should address issues of cognitive dysfunction to improve workforce participation and performance.

Long-Term Neurodevelopmental Outcomes in Children and Adolescents With Congenital Heart Disease.

BACKGROUND: Effective medical and surgical management of pediatric congenital heart disease (CHD) to reduce long-term adverse neurodevelopmental outcomes is an important clinical objective in primary and specialty health care. We identify clinical predictors associated with an increased risk of 6 long-term neurodevelopmental outcomes in children with CHD compared to the general pediatric Medicaid population. METHOD: South Carolina's retrospective, 15-year Medicaid data set (January 1, 1996-December 31, 2010) for 19,947 patients aged ≤ 17 years diagnosed with ≥ 1 CHD lesions (on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes) were compared to 19,948 patients without CHD matched on age at entry into and duration in Medicaid using logistic and Cox proportional hazards regression. RESULTS: The CHD cohort was significantly less likely to have incident neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (adjusted odds ratios [ORs] = 0.34, 0.56, 0.03, 0.01, 0.004, respectively) but was more likely to have incident seizures (OR = 2.00) compared to controls. Exposure to both cardiac and noncardiac surgical intervention was associated with a significantly increased risk of developing neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (cardiac ORs = 1.66, 2.00, 1.67, 1.43, 1.76, respectively) (noncardiac ORs = 2.25, 1.59, 1.48, 1.29, 1.36, 2.46, respectively). Any documented hypoxemia was associated with a significantly increased risk of developing 5 of the neurodevelopmental conditions (neurologic OR = 4.52, psychiatric OR = 1.60, mental retardation OR = 2.90, developmental delay OR = 2.12, seizures OR = 4.23). CONCLUSION: Practitioners should maintain vigilant surveillance of all CHD patients, especially those exposed to surgical procedures or experiencing hypoxemia, to identify any neurodevelopmental issues early and address them promptly.

Risk factors for incident major depressive disorder in children and adolescents with attention-deficit/hyperactivity disorder.

The greater burden of illness in youth with co-occurring attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder (MDD) deserves further investigation, specifically regarding the influence of other psychiatric or medical conditions and the pharmacotherapies prescribed. A retrospective cohort design was employed, using South Carolina's (USA) Medicaid claims' dataset covering outpatient and inpatient medical services, and medication prescriptions between January, 1996 and December, 2006 for patients ≤17 years of age. The cohort included 22,452 cases diagnosed with ADHD at a mean age 7.8 years; 1,259 (5.6 %) cases were diagnosed with MDD at a mean age of 12.1 years. The probability of a child with ADHD developing MDD was significantly associated with a comorbid anxiety disorder (aOR = 3.53), CD/ODD (aOR = 3.45), or a substance use disorder (aOR = 2.31); being female (aOR = 1.77); being treated with pemoline (aOR = 1.69), atomoxetine (aOR = 1.31), or mixed amphetamine salts (aOR = 1.28); a comorbid obesity diagnosis (aOR = 1.29); not being African American (aOR = 1.23), and being older at ADHD diagnosis (aOR = 1.09). Those developing MDD also developed several comorbid disorders later than the ADHD-only cohort, i.e., conduct disorder/oppositional-defiant disorder (CD/ODD), at mean age of 10.8 years, obesity at 11.6 years, generalized anxiety disorder at 12.2 years, and a substance use disorder at 15.7 years of age. Incident MDD was more likely in individuals clustering several demographic, clinical, and treatment factors. The phenotypic progression suggested herein underscores the need for coordinated early detection and intervention to prevent or delay syndromal MDD, or to minimize its severity and associated impairment over time.

Correlates of incident bipolar disorder in children and adolescents diagnosed with attention-deficit/hyperactivity disorder.

BACKGROUND: The greater severity and chronicity of illness in youths with co-occurring attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder deserve further investigation as to the risk imparted by comorbid conditions and the pharmacotherapies employed. METHOD: A retrospective cohort design was employed, using South Carolina's Medicaid claims dataset covering outpatient and inpatient medical and psychiatric service claims with International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses and medication prescriptions between January 1996 and December 2006 for patients ≤ 17 years of age. RESULTS: The cohort included 22,797 cases diagnosed with ADHD at a mean age of 7.8 years; 1,604 (7.0%) were diagnosed with bipolar disorder at a mean age of 12.2 years. The bipolar disorder group developed conduct disorder (CD)/oppositional defiant disorder (ODD), anxiety disorder, and a substance use disorder later than the ADHD-only group. The odds of a child with ADHD developing bipolar disorder were significantly and positively associated with a comorbid diagnosis of CD/ODD (adjusted odds ratio [aOR] = 4.01), anxiety disorder (aOR = 2.39), or substance use disorder (aOR = 1.88); longer treatment with methylphenidate, mixed amphetamine salts, or atomoxetine (aOR = 1.01); not being African American (aOR = 1.61); and being treated with certain antidepressant medications, most notably fluoxetine (aOR = 2.00), sertraline (aOR = 2.29), bupropion (aOR = 2.22), trazodone (aOR = 2.15), or venlafaxine (aOR = 2.37) prior to the first diagnosis of mania. CONCLUSIONS: Controlling for pharmacotherapy differences, incident bipolar disorder was more likely in individuals clustering specific patterns of comorbid psychiatric disorders, suggesting that there are different pathways to bipolarity and providing a clinical impetus for prioritizing prevention and preemptive strategies to reduce their hazardous influence.

Impact of clinical and therapeutic factors on incident cardiovascular and cerebrovascular events in a population-based cohort of HIV-infected and non-HIV-infected adults.

BACKGROUND: Cardiovascular and cerebrovascular (CVD) events/diseases are a common cause of non-acquired immunodeficiency syndrome (AIDS)-related mortality in the aging human immunodeficiency virus (HIV)-infected population. The incidence rate and clinical correlates of CVD in people living with HIV/AIDS compared to the general population warrants further investigation. HYPOTHESIS: HIV/AIDS is associated with increased risk CVD compared to general population. METHODS: CVD events in a matched cohort of HIV-infected and non-HIV-infected adults, ≥18 years old, served through the South Carolina Medicaid program during 1994 to 2011 were examined using time-dependent proportional hazards regression and marginal structural modeling. RESULTS: A retrospective cohort of 13,632 adults was followed longitudinally for an average of 51 months. The adjusted hazard ratio (aHR) of incident CVD events was higher among HIV-infected individuals exposed to combination antiretroviral therapy (cART) (aHR = 1.15) compared to the non-HIV-infected group, but did not differ from the subgroup of cART-naïve HIV-infected adults. A higher aHR of incident CVD was associated with comorbid hypertension (aHR = 2.18), diabetes (aHR = 1.38), obesity (aHR = 1.30), tobacco use (aHR = 1.47), and hepatitis C coinfection (aHR = 1.32), and older age (aHR = 1.26), but with a lower risk among females (aHR = 0.86). A higher risk of incident CVD events was also apparent in HIV-infected individuals with exposure to both protease inhibitors (adjusted risk ratio [aRR] = 1.99) and non-nucleoside reverse transcriptase inhibitors (aRR = 2.19) compared to those with no exposure. Sustained viral load suppression was associated with a lower risk of incident CVD events (aRR = 0.74). CONCLUSIONS: After adjusting for traditional risk factors and sociodemographic differences, there is higher risk of incident cardiovascular events among HIV-infected individuals exposed to combined antiretroviral medications compared to the general population.

Advancing biomarker research: utilizing 'Big Data' approaches for the characterization and prevention of bipolar disorder.

OBJECTIVE: To provide a strategic framework for the prevention of bipolar disorder (BD) that incorporates a 'Big Data' approach to risk assessment for BD. METHODS: Computerized databases (e.g., Pubmed, PsychInfo, and MedlinePlus) were used to access English-language articles published between 1966 and 2012 with the search terms bipolar disorder, prodrome, 'Big Data', and biomarkers cross-referenced with genomics/genetics, transcriptomics, proteomics, metabolomics, inflammation, oxidative stress, neurotrophic factors, cytokines, cognition, neurocognition, and neuroimaging. Papers were selected from the initial search if the primary outcome(s) of interest was (were) categorized in any of the following domains: (i) 'omics' (e.g., genomics), (ii) molecular, (iii) neuroimaging, and (iv) neurocognitive. RESULTS: The current strategic approach to identifying individuals at risk for BD, with an emphasis on phenotypic information and family history, has insufficient predictive validity and is clinically inadequate. The heterogeneous clinical presentation of BD, as well as its pathoetiological complexity, suggests that it is unlikely that a single biomarker (or an exclusive biomarker approach) will sufficiently augment currently inadequate phenotypic-centric prediction models. We propose a 'Big Data'- bioinformatics approach that integrates vast and complex phenotypic, anamnestic, behavioral, family, and personal 'omics' profiling. Bioinformatic processing approaches, utilizing cloud- and grid-enabled computing, are now capable of analyzing data on the order of tera-, peta-, and exabytes, providing hitherto unheard of opportunities to fundamentally revolutionize how psychiatric disorders are predicted, prevented, and treated. High-throughput networks dedicated to research on, and the treatment of, BD, integrating both adult and younger populations, will be essential to sufficiently enroll adequate samples of individuals across the neurodevelopmental trajectory in studies to enable the characterization and prevention of this heterogeneous disorder. CONCLUSIONS: Advances in bioinformatics using a 'Big Data' approach provide an opportunity for novel insights regarding the pathoetiology of BD. The coordinated integration of research centers, inclusive of mixed-age populations, is a promising strategic direction for advancing this line of neuropsychiatric research.

Factors associated with the occurrence and treatment of supraventricular tachycardia in a pediatric congenital heart disease cohort.

In patients with congenital heart disease (CHD), the association between supraventricular tachycardia (SVT), type of pathophysiology, and therapeutic interventions in a population-based cohort warrants further examination. A retrospective, longitudinal 15-year data set (1996-2010) was analyzed. Inclusion criteria included age ≤17 years, enrolled in South Carolina State Medicaid, and diagnosed as having one or more CHDs as well as SVT. SVT was diagnosed in 6.5 % of CHD patients (N = 1,169) during the 15-year epoch investigated. SVT was less likely to occur in African-American (hazard ratio [HR] = 0.76) or male patients (HR = 0.88), but it was significantly more likely to occur in patients age ≤12 months or in adolescents ≥13 years in those undergoing multiple surgeries/medical interventions for their CHD (HR = 1.14), those receiving antiarrhythmic/diuretic/preload-/afterload-reducing medications (HR = 5.46), and those with severe/cyanotic CHDs (HR = 1.52) or chromosomal abnormalities (HR = 1.64). Children who had an atrial septal defect secundum (adjusted odds ratio [aOR] = 3.03) and those treated with diuretic or antiarrhythmic medication (aOR = 1.80) were significantly more likely to undergo SVT ablation, whereas those with late-onset pulmonary hypertension (ages 6-12 years old) were significantly less likely to undergo SVT ablation. SVT recurred in only 14 of 166 patients who underwent SVT ablation. Multiple medical interventions at an early age may increase the risk of SVT occurrence in young CHD patients regardless of the severity/complexity of the CHD.

Association of clinical and therapeutic factors with incident dyslipidemia in a cohort of human immunodeficiency virus-infected and non-infected adults: 1994-2011.

OBJECTIVE: The aim of this study was to determine the incidence rate of dyslipidemia in a retrospective cohort of human immunodeficiency virus (HIV)-infected and non-HIV-infected adults and to evaluate the association of incident dyslipidemia with exposure to combination antiretroviral therapy (cART). METHODS: The study cohort included HIV-infected individuals and a matched group of non-HIV-infected individuals served through the South Carolina Medicaid database in 1994-2011. Linkage with the HIV/AIDS surveillance database provided time-varying viro-immunological status. Time-dependent proportional hazards analysis and marginal structural models were used to assess the demographic, therapeutic, and clinical factors associated with incident dyslipidemia. RESULTS: Among 13,632 adults with a median age of 39 years, the overall incidence rate per 1000 person years of dyslipidemia was higher in cART-treated compared to cART-naïve and matched non-HIV groups (24.55 vs. 14.32 vs. 23.23, respectively). Multivariable results suggested a significantly higher risk of dyslipidemia in the cART-treated HIV-infected group [adjusted hazard ratio (aHR)=1.18; 95% confidence interval (CI)=1.07-1.30] and a significantly lower risk in the cART naïve HIV-infected group (aHR=0.66; CI=0.53-0.82) compared to the control non-HIV-infected group. Marginal structural modeling suggested a significant association between incident dyslipidemia and exposure to both protease inhibitor- [adjusted rate ratio (aRR)=1.27; CI=1.08-1.49] and non-nucleoside reverse transcriptase inhibitor- (aRR=1.78; CI=1.19-2.66) based cART regimens. Pre-existing hypertension, obesity, and diabetes increased the risk of dyslipidemia, whereas hepatitis C virus, lower CD4(+) T cell count, and higher HIV viral load had a protective effect. CONCLUSIONS: Incident dyslipidemia is lower in the early stages of HIV infection, but may significantly increase with cumulative exposure to cART. Viro-immunological status and underlying comorbidities have a strong association with the onset of dyslipidemia.