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Achieving population behavioral health is urgently needed. The mental health system struggles with enormous challenges of providing access to mental health services, improving quality and equitability of care, and ensuring good health outcomes across subpopulations. Little data exists about increasing access within highly constrained resources, staging/sequencing treatment along care pathways, or personalizing treatments. The conceptual model of the learning healthcare system offers a potential paradigm shift for addressing these challenges. In this article we present an overview of how the three constructs of population health, learning health systems, and measurement-based care are inter-related, and we provide an example of how one academic, community-based, safety net health system is approaching integrating these paradigms into its service delivery system. Implementation outcomes will be described in a subsequent publication. We close by discussing how ultimately, to meaningfully improve population behavioral health, a learning healthcare system could expand into a learning health community in order to target critical points of prevention and intervention. [ABSTRACT FROM AUTHOR]

We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Aβ), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Aβ, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional therapy for aged individuals with VCI. The mechanisms by which RIPostC improves CBF and attenuates tissue damage need to be investigated in the future. [ABSTRACT FROM AUTHOR]

The article presents abstracts on the topic of mental health care for youth which include the research on the causes of mental disorders, development of new and better interventions that incorporate diverse needs of people with mental illness, and the need for earlier preventive and preemptive interventions for mentally ill children.

The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93 520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50 000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios ∼1.8–2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings.Neuropsychopharmacology (2009) 34, 2227–2236; doi:10.1038/npp.2009.50; published online 3 June 2009 [ABSTRACT FROM AUTHOR]

Translational research is urgently needed to turn basic scientific discoveries into widespread health gains and nowhere are these needs greater than in conditions such as schizophrenia and other psychotic disorders. In this article, we discuss one type of translational research—called T1—which is needed to take advantage of developments in the basic neurosciences and translate them into more efficacious diagnostic, preventive, and therapeutic interventions. However, ensuring that interventions from T1 research actually benefit patients will require a second form of translational research—called T2—to turn innovations into everyday clinical practice and health decision-making. Recent examples of T1 and T2 research in schizophrenia and other psychotic disorders as well as strategies for better linking T1 and T2 research agendas are covered.Neuropsychopharmacology (2009) 34, 204–212; doi:10.1038/npp.2008.170; published online 1 October 2008 [ABSTRACT FROM AUTHOR]

Behavioral disturbances associated with dementia are common and burdensome. Although no psychotropic medications are currently approved by the US Food and Drug Administration (FDA) to treat such behavioral symptoms, a variety of drug classes are commonly used for these purposes. Atypical antipsychotic medications may be somewhat effective and are generally considered the pharmacologic treatments of choice; however “black box” warnings have recently been added to their labels by the FDA, warning of significantly increased risks of short-term mortality. Older conventional antipsychotic medications may also be somewhat effective but appear to pose risks that can be at least as great as those of the newer atypical drugs. Although antidepressants, benzodiazepines, mood stabilizers, acetylcholinesterase inhibitors, and N-methyl-D-aspartate (NMDA) receptor antagonists may be considered, particularly in patients with specific types of symptomatology, even less is known about their effectiveness and safety. Also, although various psychotropic medications used for behavioral disturbances in dementia patients may be somewhat effective, they have been increasingly associated with important safety risks. [ABSTRACT FROM AUTHOR]

Appropriate trafficking and targeting of glutamate receptors (GluRs) to the postsynaptic density is crucial for synaptic function. We show that mPins (mammalian homologue of Drosophila melanogaster partner of inscuteable) interacts with SAP102 and PSD-95 (two PDZ proteins present in neurons), and functions in the formation of the NMDAR–MAGUK (N-methyl-D-aspartate receptor–membrane-associated guanylate kinase) complex. mPins enhances trafficking of SAP102 and NMDARs to the plasma membrane in neurons. Expression of dominant–negative constructs and short-interfering RNA (siRNA)-mediated knockdown of mPins decreases SAP102 in dendrites and modifies surface expression of NMDARs. mPins changes the number and morphology of dendritic spines and these effects depend on its Gαi interaction domain, thus implicating G-protein signalling in the regulation of postsynaptic structure and trafficking of GluRs. [ABSTRACT FROM AUTHOR]

Objective: The performance of standard comorbidity scores to control confounding is poorly defined in health care utilization data across elderly populations. We sought to evaluate and rank the performance of comorbidity scores across selected U.S. and Canadian elderly populations using health care utilization databases.Design: Cross-population validation study.Participants: Study participants were residents age 65 years or older who had prescription drug coverage through state-funded programs selected from several large health care utilization databases available to the investigators: British Columbia, BC (N = 141,161), New Jersey, NJ (N = 235,881), and Pennsylvania, PA (N = 230,913).Measurements: We calculated 6 commonly used comorbidity scores for all subjects during the baseline year (1994 for NJ and PA, and 1995 for BC). These included scores based on diagnoses (Romano, Deyo, D'Hoore, Ghali) and prescription drugs (CDS-1, CDS-2). The study outcome was 1-year mortality. The performance of scores was measured by c-statistics derived from multivariate logistic regression that included age and gender.Main Results: Across these 4 large elderly populations, we found the same rank order of performance in predicting 1-year mortality after including age and gender in each model: Romano (c-statistic 0.754 to 0.771), Deyo (c-statistic 0.753 to 0.768), D'Hoore (c-statistic 0.745 to 0.760), Ghali (c-statistic 0.733 to 0.745), CDS-1 (c-statistic 0.689 to 0.738), CDS-2 (c-statistic 0.677 to 0.718), and age and gender alone (c-statistic 0.664 to 0.681). Performance was improved by an average of 6% by adding the number of different prescription drugs received during the past year.Conclusions: Performance ranking of 6 frequently used comorbidity scores was consistent across selected elderly populations. We recommend that investigators use these performance data as one important factor when selecting a comorbidity score for epidemiologic analyses of health care utilization data. [ABSTRACT FROM AUTHOR]

The performance of standard comorbidity scores to control confounding is poorly defined in health care utilization data across elderly populations. We sought to evaluate and rank the performance of comorbidity scores across selected U.S. and Canadian elderly populations using health care utilization databases. Cross-population validation study. Study participants were residents age 65 years or older who had prescription drug coverage through state-funded programs selected from several large health care utilization databases available to the investigators: British Columbia, BC ( N = 141,161), New Jersey, NJ ( N = 235,881), and Pennsylvania, PA ( N = 230,913). We calculated 6 commonly used comorbidity scores for all subjects during the baseline year (1994 for NJ and PA, and 1995 for BC). These included scores based on diagnoses (Romano, Deyo, D’Hoore, Ghali) and prescription drugs (CDS-1, CDS-2). The study outcome was 1-year mortality. The performance of scores was measured by c-statistics derived from multivariate logistic regression that included age and gender. Across these 4 large elderly populations, we found the same rank order of performance in predicting 1-year mortality after including age and gender in each model: Romano (c-statistic 0.754 to 0.771), Deyo (c-statistic 0.753 to 0.768), D’Hoore (c-statistic 0.745 to 0.760), Ghali (c-statistic 0.733 to 0.745), CDS-1 (c-statistic 0.689 to 0.738), CDS-2 (c-statistic 0.677 to 0.718), and age and gender alone (c-statistic 0.664 to 0.681). Performance was improved by an average of 6% by adding the number of different prescription drugs received during the past year. Performance ranking of 6 frequently used comorbidity scores was consistent across selected elderly populations. We recommend that investigators use these performance data as one important factor when selecting a comorbidity score for epidemiologic analyses of health care utilization data. J GEN INTERN MED 2004;19:444– 450. [ABSTRACT FROM AUTHOR]

Objective: Addressing the epidemic of poor compliance with antihypertensive medications will require identifying factors associated with poor adherence, including modifiable psychosocial and behavioral characteristics of patients.Design: Cross-sectional study, comparing measured utilization of antihypertensive prescriptions with patients' responses to a structured interview.Study Population: Four hundred ninety-six treated hypertensive patients drawn from a large HMO and a VA medical center.Data Collection: We developed a survey instrument to assess patients' psychosocial and behavioral characteristics, including health beliefs, knowledge, and social support regarding blood pressure medications, satisfaction with health care, depression symptom severity, alcohol consumption, tobacco use, and internal versus external locus of control. Other information collected included demographic and clinical characteristics and features of antihypertensive medication regimens. All prescriptions filled for antihypertensive medications were used to calculate actual adherence to prescribed regimens in a 365-day study period. MAIN OUTCOME OF INTEREST: Adjusted odds ratios (ORs) of antihypertensive compliance, based on ordinal logistic regression models.Results: After adjusting for the potential confounding effects of demographic, clinical, and other psychosocial variables, we found that depression was significantly associated with noncompliance (adjusted OR per each point increase on a 14-point scale, 0.93; 95% confidence interval [95% CI], 0.87 to 0.99); in unadjusted analyses, the relationship did not reach statistical significance. There was also a trend toward improved compliance for patients perceiving that their health is controlled by external factors (adjusted OR per point increase, 1.14; 95% CI, 0.99 to 1.33). There was no association between compliance and knowledge of hypertension, health beliefs and behaviors, social supports, or satisfaction with care.Conclusions: Depressive symptoms may be an underrecognized but modifiable risk factor for poor compliance with antihypertensive medications. Surprisingly, patient knowledge of hypertension, health beliefs, satisfaction with care, and other psychosocial variables did not appear to consistently affect adherence to prescribed regimens. [ABSTRACT FROM AUTHOR]

Objective: With the increasing availability of automated health-care data, new methods are available to screen large populations for the presence of cancer diagnoses. However, it is crucial to evaluate how completely incident cancer cases can be ascertained using these data sources.Methods: We used capture-recapture techniques to estimate the total number of incident breast cancer cases occurring within one state during a 3-year period. We then compared the ascertainment of these cases by the following two data sources: claims for breast cancer surgery recorded in Medicaid and Medicare data vs a cancer registry in the same state.Results: Medicaid-Medicare breast cancer surgery claims identified 68% of the total estimated number of incident breast cancer cases while cancer registry data identified 78%. Case ascertainment improved markedly to 91% when both registry and Medicare-Medicaid data sources were used together. The sensitivity of ascertainment was lower for Medicaid-Medicare data among those aged under 65 and non-white; ascertainment was lower for the registry among women who were aged under 65, poor, and non-white.Conclusions: Combining health insurance claims data with a population-based cancer registry improved the identification of incident cases of breast cancer, and may be particularly useful among demographic groups found to be at highest risk of under-ascertainment such as younger women, the poor, and racial minorities. [ABSTRACT FROM AUTHOR]

The food intake suppressant effects of three serotonin agonists, m-CPP (a selective 5-HT agonist), 8-OHDPAT (a selective 5-HT agonist) and fenfluramine (a 5-HT releasing agent) were compared in three different rat strains: Wistar, Sprague-Dawley (SD) and Fawn-Hooded (FH) rats. Administration of all three serotonin agonists produced dose-dependent decreases in 1 h food intake in all three strains. FH animals were significantly less sensitive to the food intake suppressant effects of all three serotonin agonists than either Wistar or SD rats. Body weight gain over the 9-week course of the study was also significantly less in FH animals than either Wistar or SD animals. These findings support some other data that Fawn Hooded rats, a strain with a peripheral platelet serotonin storage disorder, also possess altered central nervous system serotonergic function. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is a major viral pathogen responsible for severe respiratory tract infections in infants, young children, and the elderly. The RSV fusion (F) protein is highly conserved among RSV subgroups A and B and is the major protective immunogen. A genetically-engineered version of the RSV F protein was produced in insect cells using the baculovirus expression system. To express a secreted form of this protein, the transmembrane domain was eliminated by removing the region of the gene encoding 48 amino acids at the C-terminus. Production of the truncated RSV F protein (RSV-Fs) was compared in two different insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni (High Five). The yield of RSV-Fs secreted from High Five insect cells was over 7-fold higher than that from Sf9 insect cells. Processing of the RSV-Fs protein was also different in the two insect cell lines. N-terminal sequencing demonstrated that while most of the RSV-Fs protein secreted by High Five cells was correctly processed at the F<$>_2<$>–F<$>_1<$> proteolytic cleavage site, most of the RSV-Fs protein secreted by Sf9 cells was unprocessed or incorrectly processed. Antigenicity of the major RSV F neutralization epitopes was maintained in the RSV-Fs protein secreted from High Five cells. The RSV-specific neutralizing antibody titres in the sera of cotton rats immunized with the RSV-Fs protein were equivalent to those in the sera of animals intranasally inoculated with live RSV. Animals immunized with either live RSV or the immunoaffinity purified RSV-Fs protein from High Five cells were completely protected against live virus challenge. [ABSTRACT FROM AUTHOR]

In this article, the authors discuss the considerations to improve the efficiency of the U.S. National Institute of Mental Health (NIMH) on its pragmatic clinical trials in psychotropic medicine. The authors reveal that the available treatments for mental illness treated some patients although the trials are not accurate. The authors relate the suggestions from the National Mental Health Advisory Council including the development of therapeutics and optimization of the available treatments.

OBJECTIVE: To relate the presence of recent mental disorders to use of mental health services. DESIGN: Cross-sectional survey. STUDY POPULATION: The study population was 3,032 respondents to the Midlife Development in the United States (MIDUS) survey, a nationally representative telephone-and-mail survey conducted in 1996. Twelve-month diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised, Third Edition, of major depressive episode, panic disorder, generalized anxiety disorder, and serious mental illness were made using a structured assessment. Information was obtained on 12-month treatment for mental health problems in the general medical, mental health specialty, human services, and self-help sectors. Definitions of treatments consistent with evidence-based recommendations were developed using available practice guidelines. MEASUREMENTS AND MAIN RESULTS: Crude and adjusted likelihoods of receiving any mental health care and guideline concordant care were measured. Although 53.8% of respondents with at least one 12-month mental disorder received any mental health care in the previous year, only 14.3% received care that could be considered consistent with evidence-based treatment recommendations. Even among those with the most serious and impairing mental illness, only 25% received guideline-concordant treatment. Predictors of receiving guideline-concordant care included being white, female, severely ill, and having mental health insurance coverage. CONCLUSIONS: An epidemic of untreated and poorly treated mental disorders exists in the United States, especially among vulnerable groups such as African Americans and the underinsured. Cost-effective interventions are needed to improve both access to and quality of treatment. [ABSTRACT FROM AUTHOR]